* {{Cite web | last=Choudhary | first=Gargi | title=Determination of Acepromazine and its Major Metabolite in Equine Serum by LC-MS/MS using the Finnigan LCQ Deca XP Plus Ion Trap Mass Spectrometer | url=http://tools.thermofisher.com/content/sfs/brochures/App-Note-318-Determination-of-Acepromazine-and-its-Major-Metabolite-in-Equine-Serum.pdf | publisher=Thermo Electron Corporation}}
{{Cite thesis | last=Marroum | first=Patrick John | title=Pharmacokinetic studies of acepromazine in the cat and the horse, studies in lipophilicity, red blood cell partitioning and protein binding | date=1990 | url=http://archive.org/details/pharmacokinetics00marr | publisher=University of Florida | type=PhD }}
{{Cite journal | last1=Wieder | first1=M. E. | last2=Gray | first2=B. P. | last3=Brown | first3=P. R. | last4=Hudson | first4=S. | last5=Pearce | first5=C. M. | last6=Paine | first6=S. W. | last7=Hillyer | first7=L. | title=Identification of Acepromazine and Its Metabolites in Horse Plasma and Urine by LC–MS/MS and Accurate Mass Measurement | journal=Chromatographia | url=http://www.academia.edu/19827532/Identification_of_Acepromazine_and_Its_Metabolites_in_Horse_Plasma_and_Urine_by_LC_MS_MS_and_Accurate_Mass_Measurement | issn=0009-5893 | volume=75 | pages=635-643}}
{{cite book | last1=Ettinger | first1=Stephen J. | last2=Feldman | first2=Edward C. | title=Textbook of Veterinary Internal Medicine - eBook | date=2009-12-24 | publisher=Elsevier Health Sciences | isbn=9781437702828 | url=https://books.google.com/books?id=4Qzau1jagOYC&pg=PA1394-IA32&dq=acepromazine%20cats&pg=PA1394-IA32}}
Boxers & vasovagal syncompe w/ace probably bc combo of bradycardia (due to decreasing sympathetic stimulation) and vasodilation, which causes hypotension
Can be avoided by using Ace with atropine
Hypothermia increased in smaller animals such as cats [from another book] bc larger surface area → more blood in vessels at surface, so more heat lost
{{Cite web | last=Khuly | first=Patty | title=Acepromazine: Why I'm not a big fan when it comes to sedation via 'ace' | work=PetMD | accessdate=2017-06-12 | date=2009-10-22 | url=http://www.petmd.com/blogs/fullyvetted/2009/october/acepromazine-why-im-not-big-fan-when-it-comes-sedation-ace-6937}}
Most common uses in dogs/cats:
Oral sedative before stressful events (travel, storms, grooming, vet visits)
Disagreement on this: since it can make animal more sensitive to noise/other sensory input, shouldn't really be used with aggressive dogs – can sometimes increase aggression (due to dysphoria by phenothiazine)
Inj tranq for aggressive/fractious animal at vet office
W/opiate as a pre-med
Lower dose of other drug needed
Reduce protential for arrhythmias and vomiting
Except boxers – they can get life-threatening arrhythmias
Some minor relaxing
Post-op w/pain releiver to enhance/lower dose of pain reliever neeeded
{{cite journal|last=Kolahian|first=Saeed|title=Efficacy of Different Antiemetics with Different Mechanism of Action on Xylazine Induced Emesis in Cats| journal=Iranian Journal of Veterinary Surgery | year=2014 | volume=9 | number=1 | url=http://www.ivsajournals.com/article_5789_6e9336886fafc7a62f1c710ade9bc1ef.pdf | page=10}}
{{cite book | editor-first=Jill E. |editor-last=Maddison |editor2-first=Stephen W. | editor2-last=Page |editor3-first=David | editor3-last=Church | title=Small Animal Clinical Pharmacology | location=Edinburgh; New York | date=2008 | edition=2 | publisher=Saunders/Elsevier | isbn=9780702028588 | url=https://books.google.com/books?id=RpsROVqemk8C&lpg=PA115}}
p.115
Sedative effect more in dogs, but licensed for both dog and cat use
Antiemetic effects
Mainly ant. at D2; also has ant. action at H1, alpha1, and mAch
Pharmokinetics
Better absorption from IM than SQ sites
Starts 30 min after IM injection (faster if IV)
4-6 hours sedation
Oral dose: not as effective, so need higher dose
Lipophilic and widely distributed
High degree of protein binding
Metabolized by hepatic microsomal enzymes
Oxidized to sulfoxides and glucuronide conjucation
Impaired liver → longer effect
Metabolites excreted in urine
Adverse effects
CNS
BC dopamine, high doses can lead to extrapyramidal signs (restlessness, rigidity, tremor, catalepsy)
Fever, bc modify thermoregulation mechas at hypothalamus
Cardiovascular
Peripheral vasodilation → drop in BP (mainly by anti-alpha1)
Clinical doses don't really affect HR
p.116
Respiratory
Not much
GI
Anti chol: Spasmolytic action on gut → reduce GI motility in dogs; reduced salivation
Other
Quite mild antihistamine effect compared to other phenothiazines
Reduction in hematocrit: liver and spleen sequester/hog RBCs
Can temporarily reduce clotting activity
Contraindications
Hypovolemia/shock
Hx of seizures
Reduced doses:
Hepatic or cardiac problems
Young, old, or weak
Bracycephalic breeds (esp. boxer)
Giant breeds
Known drug interactions
CNS depressant effect makes other drugs' CNS depressant effects stronger as well, so having an opioid, even in nonpainful pt, increases sedation (need to use less)
{{Cite thesis | last=Marroum | first=Patrick John | title=Pharmacokinetic studies of acepromazine in the cat and the horse, studies in lipophilicity, red blood cell partitioning and protein binding | date=1990 | url=http://archive.org/details/pharmacokinetics00marr | publisher=University of Florida | type=PhD }}
p.5
Phenothiazines in general:
Sedation
Decreased anxiety
Decreased spontaneous motor activity
Interruption of intellectual stuff/complex behavior
Antihistaminic and hypotensive
By blocking post-synaptic dopamine receptors
Result: increase in production of dopamine metabolites, which interferes with dopamine action as NT in
p.7
Pre-anesthetic in dog, cat, and horse
Potentiates barbituates
p.13
[Picture of metabolism of ace]
p.116
Erratic absorption in cat, with very high variability from one cat to the next
{{cite web | title=Patient Information Sheet | work=Doctor Foster and Smith Pharmacy | accessdate=2017-07-10 | date=2007-09-14 | url=http://www.drsfostersmith.com/Rx_Info_Sheets/rx_psgag.pdf}}
Injectable polysulfated glycosaminoglycan (PSGAG)
No injectable generics available
Signs of degenerative or traumatic arthritis in dogs & horses
Also has been used in cats and rabbits
IM (intramusc) and sometimes intra-articular (directly into the joint)
Side effects of intra-articular: joint pain, swelling, lameness, rare infection of joint
Side effects (K9): decreased blood clotting → bleeding from nose, blood in stool (or dark stool)
Overdose is rare; signs: joint pain, swelling, lameness
{{cite book | last=Bryant | first=Jennifer O. | title=The USDF Guide to Dressage: The Official Guide of the United States Dressage Foundation | date=2012-12-10 | url=https://books.google.com/books?id=yHp40CJHd_gC&pg=PA285 | publisher=Storey Publishing | isbn=9781612122748}}
One of most widely prescribed joint supplements for horses
{{cite book | last=Fox | first=Steven M. | title=Chronic Pain in Small Animal Medicine | date=2009-12-15 | url=https://books.google.com/books?id=KvY5LR5yHQwC&pg=PA197 | publisher=CRC Press | isbn=9781840765670 | pages=197-200}}
"Chondroprotectant"
Inhibit serine proteinases (play role in IL-1 mediated degradation of cartilage proteoglycans and collagen)
Reportedly inhibits some catabolic enzymes (elastase, stromelysin, metalloproteinases, cathepsin G and B1, hyaluronidases), which degrade collagen, proteoglycans, and hyaluronic acid
Inhibit PGE synthesis, stimulates GAG synthesis
Inhibits aggrecanases, MMPs, NO, PGE2
Potentiating effect on synth of hyaluronic acid by synovial membrane cells
Increase concentration of hyaluronan
Within 2 hours, enters joint and starts its shit
Best to give in early stages of osteoarthritis - once hylaine cartilage is gone, it's gone
{{cite web | last=Khuly | first=Patty | title=Why I Love Adequan for Cats and Dogs | work=PetMD | accessdate=2017-07-10 | date=2010-03-05 | url=http://www.petmd.com/blogs/fullyvetted/2010/march/adequan_cats_dogs-7028}}
Only approved for dogs and hoses
Also used unofficially in cats
Interstitial cystitis
Derived from cow tracheas (WHAT)
Inhibits enzyme that breaks down cartilage, increase thickness of joint fluid
Also reduces bladder swelling and helps repair tracheas
Papich, Mark G. (2007). "Polysulfated Glycosaminoglycan". Saunders Handbook of Veterinary Drugs (2nd ed.). St. Louis, Mo: Saunders/Elsevier. pp. 537–538. ISBN9781416028888.
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{{cite book | last=Papich | first=Mark G. | title=Saunders Handbook of Veterinary Drugs | chapter=Polysulfated Glycosaminoglycan | location=St. Louis, Mo | date=2007 | edition=2nd | publisher=Saunders/Elsevier | isbn=9781416028888 | pages=537–538}}
Dogs/horses to treat/prevent deg. joint disease
IA (aseptic) effective, IM may be too low for some
Effective for acute arthritis, might not be as great for chronic arthropathy
Plumb, Donald C. (2011). "Polysulfated glycosaminoglycan (PSGAG)". Plumb's Veterinary Drug Handbook (7th ed.). Stockholm, Wisconsin; Ames, Iowa: Wiley. pp. 837–839. ISBN9780470959640.
{{cite book | last1=Schulz | first1=Kurt | last2=Beale | first2=Brian | last3=Holsworth | first3=Ian | title=The Pet Lover's Guide to Canine Arthritis & Joint Problems | date=2005 | url=https://books.google.com/books?id=6nS8k6asA6UC&pg=PA192 | publisher=Elsevier Health Sciences | isbn=9781416026143}}
PSGAGs are much larger than chondroitin sulfate (which is also used as a nutritional supplement), so more like the actual molecules in cartilage – once in the joint, it's more likely to stay there
How it works is in theory
Studies show conflicting results, so probably not Adequan alone causing significant healing
Does seem to work in some dogs
Works same way as supplements like glucosamine and chrondroitin
US National Library of Medicine (2016-08-24). "ADEQUAN CANINE". DailyMed. Retrieved 2017-07-10.
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{{cite web | last=US National Library of Medicine | title=ADEQUAN CANINE | work=DailyMed | accessdate=2017-07-10 | date=2016-08-24 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b0fbf2e7-5a2a-4fa2-957c-3d4693a891fe}}
Rx veterinarian
GAG in PSGAG is mostly chondroitin sulfate w/3-4 sulfate esters per disaccharide unit
Molec. weight of PSGAG for Adequan is 3,000-15,000 daltons
Mechanism
Inhibit serine proteases (play a role in Il-L mediated degradation of proteoglycans and collagen)
Inhibit synth of Prostoglandin E2 (which increases loss of proteoglycan)
Stimulate synth of protein, collagen, proteoglycans, hyaluronic acid
IM injection (rabbit): max concentration after 20-40 minutes
Drug distributed to all tissues, inc. cartilage, lungs, eyes, spinal cord, heart, and brain
Binds ot serium proteins in blood at 30-40%
Diffuses from synovial fluid to cartilage (relatively low molecular weight), where it's deposited into cartilage matrix
Metabolism
In rabbits: liver, spleen, bone marrow, may also be in kidneys
If not protein bound, excreted mainly by kidneys (some in feces)
Toxicity
At high concentration (50mg/kg): increased prothrombin time, decreased platelet count, increased ALT and cholesterol, increased weights of liver and kidney (latter 2 also at 15 mg/kg)
Microscopic lesions at liver, kidneys, lymph nodes (at 15 mg/kg and 50 mg/kg)
IM inflammation, hemorrhage, and degeneration dose-related; at 5mg/kg, 15, and 50
Normal dose is 2mg/lb (4.4mg/kg)
Contraindications
Hypersensitivity to PSGAG
Bleeding disorders (PSGAG is synthetic heparinoid)
{{cite journal | last=White | first=Gary W. | title=Adequan: A review for the practicing veterinarian | journal=Journal of Equine Veterinary Science | accessdate=2017-07-10 | date=1988-11-01 | url=http://www.sciencedirect.com/science/article/pii/S0737080688800960 | doi=10.1016/S0737-0806(88)80096-0 | issn=0737-0806 | volume=8 | issue=6 | pages=463-468}}
Cartilage matrix in joints = proteoglycan complexes, collagen, water
Proteoglycan complexes: protein core + glycosaminoglycan side chains (keratin, chondroitin sulfate)
Attached to a strand of hyaluronate
Hyaluronate works as "boundary lubricant" of soft tissue and as barrier btw blood vessels of sonival membrane and synovial cavity
GAG: "polyanionic", adjacent side chains are pushed away → "bottle brush" of side chains
Water is trapped in these complexes → can compress
Exchange of stuff from chondrocytes and synovial fluid due to pumping action, which results from normal movement (when moving your joints)
Under "mechanical load": products of metabolism of chondrocyte are pushed out into fluid
Pressure relieved → fluid goes back into chondrocytes, bringing substrates and shit
Intersperesed with collagen fibers
Degenerative joint disease: start losing proteoglycan, which exposes collagen fibers and chrondrocytes to mechanical stress
Damaged matrix has increased water content, damaging normal nutrient exhange btw chondrocytes and synovial fluid
Which makes it harder for chondrocytes to repair what damage they can
And matrix continues to be lost, and cartilage loses more capacity to withstand stress
Collagen network collapses irreversably, and lose function of joint
Softening/thickening oc cartilage → cartilage bexomes thinner → cartilage fragments and thickness lost → "marginal osteophyte formation" → "sclerosis of the subchondral bone, bone lysis, and lost of joint space"
Quality/quantity of hyaluronate decreased
Lowers viscosity of synovial fluid
Increases friction; WBCs and enzymes enter synovial fluid and reach cartilage
Inflammation
Prostaglandin E2: longer vasodilation, increased blood vessel permeability, reduce threshold of pain receptors, negative effect on PG metabolism
Enzymes released in response to injury destroy parts of cartilage matrix
<ref>{{cite web | title=Albendazole (Albenza) Use During Pregnancy | work=Drugs.com | accessdate=4 August 2017 | url=https://www.drugs.com/pregnancy/albendazole.html}}</ref>
Australia: category D
Contraindicated during pregnancy and 1 month prior to conception
US: category C
Only use during pregnancy if there are no alternatives and benefits outweigh risks
Teratogencicity (embryotoxicity and skeletal malfmormations) in pregnatn rats and rabbit
Alb and metabolites excreted into breast milk
But little was absorbed systemically, WHO says it's ok with breastfeeding
<ref>{{cite web | title=Albendazole Monograph for Professionals | work=Drugs.com | accessdate=24 July 2017 | url=https://www.drugs.com/monograph/albendazole.html}}</ref>
<ref>{{cite web | title=Albenza New FDA Drug Approval | work=CenterWatch | accessdate=8 August 2017 | url=http://www.centerwatch.com/drug-information/fda-approved-drugs/drug/126/albenza-albendazole}}</ref>
FDA approved for hydatid due to Echinococcus granulosis (larva form of dog tapeworm) and neurocysticercosis due to larval form of pork tapeworm, Taenia solium
"Albendazole". Meyler's Side Effects of Drugs (16th\ ed.). Oxford: Elsevier. 2016. pp. 102–110. ISBN978-0-444-53716-4. {{cite book}}: |access-date= requires |url= (help); Unknown parameter |editors= ignored (|editor= suggested) (help)
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<ref>{{cite book | editors=Aronson, J. K. | title=Meyler's Side Effects of Drugs |edition=16th\ | chapter=Albendazole | location=Oxford | accessdate=2 August 2017 | date=2016 | publisher=Elsevier | isbn=978-0-444-53716-4 | pages=102-110}}</ref>
Side effects: abdominal pain, diarrhea, nausea, dizziness, headache
Has been used for cryptosporidiosis, isosporiasis, microsporidiosis
Interactions
Antiepileptics phenytoin, carbamazepine, and phenobarbital all made alb be oxidized, so that reduce concentration of albendazole sulfoxide in plsamsa
<ref>{{cite book | last1=Bennett | first1=John E. | last2=Dolin | first2=Raphael | last3=Blaser | first3=Martin J. | title=Principles and Practice of Infectious Diseases | date=28 August 2014 | page=520 | url=https://books.google.com/books?id=BseNCgAAQBAJ&pg=PA520 | publisher=Elsevier Health Sciences | isbn=978-1-4557-4801-3}}</ref>
CYP3A4 converts to inactive metabolite albendazole sulfone
Diff species produce diff enantiomers; humans mostly produce R(+) enantiomer
R(+) by microsomal flavin monooxidase
S(-) by cytochrome P450 CYP3A and in the gut epithelium
Enzymes (mainly CYP3A4) convert alb sulfoxide to alb sulfone
In pts with neurocyst., albendazole R(+) sulfoxide accumulates more in CSF than S(-)
R(+) more active agasint Taenia solium than S(-)
Pharmakokinetics differ a bit btw men and woman
Oral clearance and volume of distribution lower in women
Serum peak concentration lower in men
Food enhances oral bioavailability
(Presumably) stimulates gastric acid secretion, and alb, absorption is pH-dependent
Alb. sulf crosses BBB and is in CSF at 43% of plasma levels (though differs btw indivs)
Can penetrate CNS, so can treat neurocyst.
Side effects
Most common: transient liver fxn abnormalities (less than 20%) and alopecia (5%)
Bone marrow toxicity is rare but irreversible
Cimetidine: inhibits absorption bc reduces gastric acicidity
But also inhibits metabolism of alb. sulfoxide by interfering with CYP3A4 enz, so prolongs elmination half-life from 7.4 hours to 19 hours
Grapefruit: inhibits metabolism of albendazole in intestinal mucosa
Long-term admin of ritonavir (CYP3A4 inhibitor) decreased AUC and Cmax of alb.
<ref>{{cite book | last1=Briggs | first1=Gerald G. | last2=Freeman | first2=Roger K. | last3=Yaffe | first3=Sumner J. | title=Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk | date=2011 | page=31 | url=https://books.google.com/books?id=OIgTE4aynrMC&pg=PA31 | publisher=Lippincott Williams & Wilkins | isbn=978-1-60831-708-0}}</ref>
If need albendazole during pregnancy, avoid 1st trimester
<ref>{{cite book | last1=Boullata | first1=Joseph I. | last2=Armenti | first2=Vincent T. | title=Handbook of Drug-Nutrient Interactions | date=17 March 2010 | page=306 | url=https://books.google.com/books?id=6MSRviXlDtAC&pg=PA306 | publisher=Springer Science & Business Media | isbn=978-1-60327-362-6}}</ref>
Broad specturm, vs. larva and adults of trematodes and cestodes
If want intestinal parasites, should be given on empty stomach so have intraluminal effects
<ref>{{cite book | last=Bowman | first=Dwight D. | title=Georgis' Parasitology for Veterinarians - E-Book | date=12 March 2014 | page=282 | url=https://books.google.com/books?id=7CFLBAAAQBAJ&pg=PA282 | publisher=Elsevier Health Sciences | isbn=978-1-4557-3988-2}}</ref>
Treats giardia in humans, mice, dogs, cattle
Aplastic anemia/toxic in dogs and cats
Capece, Bettencourt P. S.; Virkel, Guillermo L.; Lanusse, Carlos E. (1 September 2009). "Enantiomeric behaviour of albendazole and fenbendazole sulfoxides in domestic animals: Pharmacological implications". The Veterinary Journal. 181 (3): 241–250. doi:10.1016/j.tvjl.2008.11.010. ISSN1090-0233.
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<ref>{{cite journal | last1=Capece | first1=Bettencourt P. S. | last2=Virkel | first2=Guillermo L. | last3=Lanusse | first3=Carlos E. | title=Enantiomeric behaviour of albendazole and fenbendazole sulfoxides in domestic animals: Pharmacological implications | journal=The Veterinary Journal | date=1 September 2009 | doi=10.1016/j.tvjl.2008.11.010 | issn=1090-0233 | volume=181 | issue=3 | pages=241-250}}</ref>
Most species have more (+) alb sulfoide than (-)
(-) is depleted at faster rate
Alb sulfoxide has an oxidized sulfur that makes the chemical more water-soluble
Alb sulfoxide crosses BBB and placenta in humans
alb sulfoxide is more water soluble due to oxidized sulfur atom
alb → alb sulfoxide
Cytochrome P450 and flavin-monooxygenase
FMO mainly produce +, while cytochrome P450 isoenzymes 2C6 and 2A1 mainly produce - (rat liver)
Ruminants: metabolism on GI tract due to gut microflora
Liver; oxidative metabolism
GI: reduction of foreign compounds, especially those w/nitro and sulfoxide groups (so alb sulfoxide → alb)
(+) version was used up more
(-) alb sulfoxide has lower pharmacological activity, leaves blood faster
Dayan, A. D (1 May 2003). "Albendazole, mebendazole and praziquantel. Review of non-clinical toxicity and pharmacokinetics". Acta Tropica. Preparing to control Schistosomiasis and Soil-transmitted Helminthiasis in the Twenty-First Century. 86 (2): 141–159. doi:10.1016/S0001-706X(03)00031-7. ISSN0001-706X.
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<ref>{{cite journal | last=Dayan | first=A. D | title=Albendazole, mebendazole and praziquantel. Review of non-clinical toxicity and pharmacokinetics | journal=Acta Tropica | series=Preparing to control Schistosomiasis and Soil-transmitted Helminthiasis in the Twenty-First Century | date=1 May 2003| doi=10.1016/S0001-706X(03)00031-7 | issn=0001-706X | volume=86 | issue=2 | pages=141-159}}</ref>
Britain approved for cattle and sheep
Oral absorption: 20–30% in rats, 1–5% in humans, 50% in cattle
Very rapid 1st pass metabolism in all species, so that can't reliably detect unchanged drug in plasma
Eat with fatty food: alb dissolved better in lipids
Metabolism of albendazole by cytochrome P450 oxidases and other flavin-containing oxidases
P450 1A1 and 3A4
P450 enzymes make (-), while flavin enzymes (flavine-adenine-dinucleodtide monooxygenase) make (+)
P450 isozymes then make alb sulfone
First approved for human use in 1982
Not recommended in kids under 6
Approved in Britain for cattle and sheep, inc. pregnant animals and their young
Oral absorption
Rats: 20–30%
Cattle: ~50%
Humans: 1–5%
Very fast 1st pass metabolism in all species, so can't reliably detect unchanged drug in plasma
Plasma levels of sulfoxide and sulfone are much higher
Peak levels of albendazole and of alb sulfoxide is 2–3 hours (in humans, rats, and sheep)
Half life of alb sulfoxide
8–12 hours in humans
Only the metabolites are excreted (since drug is very extensively metabolized); largely in bile
Alb sulfoxide has a chiral center
Cytochrome P450 oxidases makes (-), flavin-containing oxidases (+)
(+) is the main one in human plasma and dogs
Humans: 80:20 ratio of +:-
Dogs: 70:30
Rats is around the same: 59:41
The + is make by oxidation by a flavine-adenine-dinucleotide monooxygenase
The - is makde by P450 enzyme
P450 isoenzymes convert alb sulfoxide to alb sulfone
Fargetton, X.; Galtier, P.; Delatour, P. (1 December 1986). "Sulfoxidation of albendazole by a cytochrome P450-independent monooxygenase from rat liver microsomes". Veterinary Research Communications. 10 (1): 317–324. doi:10.1007/BF02213995. ISSN0165-7380.
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<ref>{{cite journal | last1=Fargetton | first1=X. | last2=Galtier | first2=P. | last3=Delatour | first3=P. | title=Sulfoxidation of albendazole by a cytochrome P450-independent monooxygenase from rat liver microsomes | journal=Veterinary Research Communications | date=1 December 1986 | doi=10.1007/BF02213995 | issn=0165-7380 | volume=10 | issue=1 | pages=317-324}}</ref>
Previously just thought that cytochrome P450 monooxygenase system was only responsible for oxidation of alb, but later found that also due to flavin-containing monooxygenase (EC 1.14.13.8)
<ref>{{cite web | last=Junquera | first=P. | title=Ricobendazole = Albendazole Sulfoxide for Veterinary Use on Cattle, Sheep, Goats, Pig Poultry, Dogs and Cats against roundworms, tapeworms and liver flukes | accessdate=24 July 2017 | url=http://parasitipedia.net/index.php?option=com_content&view=article&id=2518&Itemid=2791}}</ref>
Completely ineffective vs. external parasites
The only benzimidazole than can be injected and also is available for drenching
Used a lot in ruminants in some countries (those in Latin America) but not elsewhere
All benzimidazoles have no residual effect (unless: kill within a few hours, but don't protect much against reinfestation
<ref>{{cite web | last=Junquera | first=P. | title=Trichuris Spp, Parasitic Whipworms of Dogs, Cats and Livestock - Cattle, Sheep, Goats and Pigs; Biology, prevention and control | work=Parasitopedia | accessdate=3 August 2017 | date=12 December 2016 | url=http://parasitipedia.net/index.php?option=com_content&view=article&id=2601&Itemid=2883}}</ref>
Dogs: Trichuris vulpis, Trichuris campanula
Cats: Trichuris serrata, Trichuris campanula
Cattle, sheep, goats and other ruminants: Trichuris discolor, Trichuris globulosa, Trichuris ovis
Pigs: Trichuris suis
Karkhanis, Aneesh; Hong, Yanjun; Chan, Eric Chun Yong (1 July 2017). "Inhibition and inactivation of human CYP2J2: Implications in cardiac pathophysiology and opportunities in cancer therapy". Biochemical Pharmacology. 135: 12–21. doi:10.1016/j.bcp.2017.02.017. ISSN0006-2952.
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<ref>{{cite journal | last1=Karkhanis | first1=Aneesh | last2=Hong | first2=Yanjun | last3=Chan | first3=Eric Chun Yong | title=Inhibition and inactivation of human CYP2J2: Implications in cardiac pathophysiology and opportunities in cancer therapy | journal=Biochemical Pharmacology | date=1 July 2017 | doi=10.1016/j.bcp.2017.02.017 | issn=0006-2952 | volume=135 | pages=12-21}}</ref>
<ref>{{cite book | last1=Maddison | first1=Jill E. | last2=Page | first2=Stephen W. | last3=Church | first3=David | title=Small Animal Clinical Pharmacology | date=2008 | pages=208, 250–280 | url=https://books.google.com/books?id=RpsROVqemk8C&pg=PA208 | publisher=Elsevier Health Sciences | isbn=978-0-7020-2858-8}}</ref>
Developed in 1973
Not actually approved for use in cats and dogs
Broadest spectrum of the benzimidazoles
Dogs and cats
Filaroides hirthi (nematode)
Paragonimus westermani, P. ohirai, P. kellcotti (trematode)
Pneumocystis carinii (w/trimethoprim)
Encephalitozoan cuniculi
Toxacara canis, catis
Trichinella apiralis
Papich, Mark G. (2007). "Albendazole". Saunders Handbook of Veterinary Drugs (2nd ed.). St. Louis, Mo: Saunders/Elsevier. pp. 8–9. ISBN978-1-4160-2888-8.
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<ref>{{cite book | last=Papich | first=Mark G. | title=Saunders Handbook of Veterinary Drugs | chapter=Albendazole | location=St. Louis, Mo | date=2007 | edition=2nd | publisher=Saunders/Elsevier | isbn=978-1-4160-2888-8 | pages=8–9}}</ref>
Associated w/bone marrow suppression/toxicity in dogs and cats at high doses
Other species have high margin of safety
Side effects: anorexia, lethargy, bone marrow toxicity
More likely when longer than 5 days
113.6 mg/mL suspension and 300 mg/mL paste
Don't use in 1st 45 days of pregnancy
27 days cattle withdrawal time for meat
Plumb, Donald C. (2011). "Albendazole". Plumb's Veterinary Drug Handbook (7th ed.). Stockholm, Wisconsin; Ames, Iowa: Wiley. pp. 19–21. ISBN978-0-470-95964-0.
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<ref>{{cite book | last=Plumb | first=Donald C. | title=Plumb's Veterinary Drug Handbook | chapter=Albendazole | location=Stockholm, Wisconsin; Ames, Iowa | date=2011 | edition=7th | publisher=Wiley | isbn=978-0-470-95964-0 | pages=19–21}}</ref>
"Albenza", "Valbluzen"
aka albendazolum
Non-lactating cattle:
Osteragia ostertagi
Haemonchus spp
Trichostrongylus sp
Nematodus sp
Cooperice sp
Bunostomum phlebotomum
Oesphagostum
Dictacaulus vivaparous (adult and stage 4 larva)
Fasciola hepatica (adult)
Moniezia
Sheep
Ostertagia circumcinta
Marshallagia marshalli
Haemonchus contortus
Trichostrongylus
Nematodus
Cooperice
Oesphagostomum
Chibertia ovina
Dictacaulus filaria
Fasciola hepatica
Fascioides magra
Moniezoa expanse
Thysanosoma actinoides
Cats
Paragonimus kellicotti
Capillariasis
Platynosum
opisthorchidoe
Dogs
Filaroides
Capillariasis
Leishmaniases
Rabbits
Encephalitozoon phacoclastic uveitis
E. cumiculi
Chinchilla
Giardia
Birds (ratites): flagellate parasites and tapeworms
Extra-label in small mammals, goats, pigs for endoparasites
Mech
Bind to tubulin and damage, prevent tubulilne polymerization, inhibit microtubule formation
Total: disrcupt intracellular microtubule transport systems
At higher concentrations:
Disrupt metab paths in helminths
Inhibit metabolic enzymes (inc. malate dehydrogenase and fumarate reductase)
Pharmacokin
Better oral absorption than other benzimidazole
Side effects
Dogs: anorexia
Cats: lethargy, depression, anorexia
FDA cat C for pregnancy
Doses @30x normal → cattle dies
Doses @20x normal → sheep dies
Drug interactions
Cimetidine (increase alb in bile and cystic fluid)
Dexamthasone (increase alb in serum)
Praziquantel (increase alb in serum)
Have alb oral 200mg tablets for humans (Rx)
Albendazole suspension/paste both OTC
Rawden, Helen C.; Kokwaro, Gilbert O.; Ward, Stephen A.; Edwards, Geoffrey (1 April 2000). "Relative contribution of cytochromes P-450 and flavin-containing monoxygenases to the metabolism of albendazole by human liver microsomes". British Journal of Clinical Pharmacology. 49 (4): 313–322. doi:10.1046/j.1365-2125.2000.00170.x. ISSN1365-2125.
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<ref>{{cite journal | last1=Rawden | first1=Helen C. | last2=Kokwaro | first2=Gilbert O. | last3=Ward | first3=Stephen A. | last4=Edwards | first4=Geoffrey | title=Relative contribution of cytochromes P-450 and flavin-containing monoxygenases to the metabolism of albendazole by human liver microsomes | journal=British Journal of Clinical Pharmacology | date=1 April 2000 | doi=10.1046/j.1365-2125.2000.00170.x | issn=1365-2125 | volume=49 | issue=4 | pages=313-322}}</ref>
(In humans:)
Alb → alb sulfoxide
Flavin-containing monoxygenase and CYP3A4
Alb sulfoxide → alb sulfone
CYP
Also have alb sulfone → 2-aminosulfone, gamma-hydroxysulfone, and beta-hydroxysulfone
<ref>{{cite book | last1=Riviere | first1=Jim E. | last2=Papich | first2=Mark G. | title=Veterinary Pharmacology and Therapeutics | date=17 March 2009 | pages=1054, 1062 | url=https://books.google.com/books?id=ievLulSqwBAC&pg=PA1054 | publisher=John Wiley & Sons | isbn=978-0-8138-2061-3}}</ref>
Mech
All microtubule functions are inhibited: cell division, maintaining cell shape, cell motility, nutrient absorption, intracellular transport
Binds much better to parasite tubulin than mammalian tubulin (so wide safety margin in mammals(
In ruminants, sulfoxide can be turned back to normal albendazole in GI tract
Preference for turning (+) back over turning (-) back
Absorption depends on lipid solubility and degree of ionization at GI pH levels, since mucus surface of GI tracts acts as lipid barrier agasint absorption
(+) sulfoxide, compared to (-):
Longer in bloodstream
Higher concentration in tissues/fluids where parasites are
<ref>{{cite book | last1=Stipanuk | first1=Martha H. | last2=Caudill | first2=Marie A. | title=Biochemical, Physiological, and Molecular Aspects of Human Nutrition - E-Book | date=13 August 2013 | page=564 | url=https://books.google.com/books?id=XVNPAQAAQBAJ&pg=PA564 | publisher=Elsevier Health Sciences | isbn=978-0-323-26695-6}}</ref>
<ref>{{cite book | last=Tripathi | first=K. D. | title=Essentials of Medical Pharmacology | date=30 September 2013 | page=850 | url=https://books.google.com/books?id=FfG8AQAAQBAJ&pg=PA850 | publisher=JP Medical Ltd | isbn=978-93-5025-937-5}}</ref>
One of drugs of choice
A. lumbricoides
Hookworms:A. duodenale, Necator americanos
Pinworm (E. vermicularis)
Trichinella spiralis
Neurocysticercosis
Hydatid disease (E. granulosus, E. multiocularis)
Alternative
S. stercoralis (alt to ivermectin)
Whipworm T. trichiura: alt to mebendazole
Filaria by W. bancrofit and B. malayi
T. saginata and solium (alts to praziquantel for solium, praziquantel or niclosamide for saginata)
Turner, Arthur; Horton, John (30 December 1987). "Albendazole". Logan Turner's Diseases of the Nose, Throat and Ear (10th ed.). CRC Press. pp. 2228–2239. ISBN978-0-340-92767-0.
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<ref>{{cite book | last1=Turner | first1=Arthur | last2=Horton | first2=John | title=Logan Turner's Diseases of the Nose, Throat and Ear | chapter=Albendazole | date=30 December 1987 | edition=10th | publisher=CRC Press | isbn=978-0-340-92767-0 | pages=2228–2239}}</ref>
Originally made as veterinary antihelmintic
Registered for humans in 1982
Insoluble in water, so haven't developed parenteral preparations
Antimicrobial activity
Very broad spectrum
Works against most human nematode and cestodes species; less against trematode species
Mechanism
Beta tublin
Loss of cytoplasmic microtubules prevents eggs from hatching
Pharmacokin
Drug absorption not needed for intestinal infections
Systemic parasites: albendazole acts as the prodrug, and albendazole sulfoxide is the active drug
A bit of alb sulfoxide (0.09–0.88%) excreted in urine in humans (minor elimination pathway)
Mostly excreted in bile
Liver: flavin monooxygenase and cytochromes P450 (mainly CYP3A4) to S(-)
R(+) by microsomal flavin mixed function oxidases
Some production of S(-) in gut epithelium
Alb sulfoxide oxidized to alb sulfone mainly by CYP2C (in rat livers, but thought to be the same as in humans)
<ref>{{cite web | last=US National Library of Medicine | title=ALBENZA- albendazole tablet, film coated ALBENZA- albendazole tablet, chewable | work=DailyMed | accessdate=24 July 2017 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e8941166-b77d-45aa-a6e8-04f1c0afd845}}</ref>
Drug interactions
Dexamethasone: Trough concentrations of alb. sulfoxide increase by 56%
Praziquantel: increase max plasma concentration of alb. sulfoxide by 50%
Cimetidine: in patients being treated for hydatid cysts, increase alb. sulfoxide concentrations in bile and cystic fluids by 2-fold
Theophylline: Al. induces cyotochrome P450 1A in human hepatoma cells; monitor theophylline plasma concentrations
Warning/precaution
Bone marrow supression
Granulocytopenia or pancyotpenia by alb, can cause bone marrow supression, aplastic anemia, and agranulocytosis
Can be fatal
Increased risk in those with liver disease and those w/hepatic echinococcosis
Teratogenic
In treating neurocysticercosis, can cause neuro symptoms
Should receive steroids and anticonvulsants together w/alb. to prevent things like seizures, increased intracranial pressure, focal signs caused by inflammatory reaction of parasitic death in brain
In treating retina neurocystocercosis, can cause retinal damage
Hepatic effects
Increase hepatic enzyme concentrations in 16% in patients (return to normal when tx is stopped)
Pts w/elevated liver enzymes at increased risk for hepatotoxicity and bone marrow supression
Can unmask undiagnosed neurocysticercosis when treating hydatid patients
Adverse reactions
Can differ in those being treated for hydatid diseae vs. neurocysticercosis
Mechanism
Binds to colchicine-sensitive site of beta-tubulin, inhibiting polymerization
Parasite resistance due to changing amino acids that make up beta-tubuling, decreasing bindinf of alb.
<ref>{{cite web | last=US National Library of Medicine | title=VALBAZEN- albendazole suspension | work=DailyMed | accessdate=2 August 2017 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=94cf5818-f27d-4374-87ad-54a2d9ce6ef1}}</ref>
Adult liver flukes
Fasciola hepatica (cattle, sheep, goats)
Fascioloides magna (sheep)
Tapeworms
Moniezia benedini (cattle), M. expansa (cattle and sheep), Thysanosoma actinioides (sheep)
Stomach worms
Ostertagia ostertagi (cattle), O. circumcincta (sheep)
Barber pole worm (Haemonchus contortus in both, H. placei in cattle)
Small stomach worm: Trichostrongylus axei
Intestinal worms
Thread-necked Intestinal Worm: Nematodirus spathiger (both), N. helvetianus (cattle), N. filicollis (sheep)
Small intestinal worm/Cooper's worm: Cooperia punctata, (cattle), C. oncophora (both)
<ref>{{cite book | last=Wiebe | first=Valerie J. | title=Drug Therapy for Infectious Diseases of the Dog and Cat | date=11 May 2015 | page=247 | url=https://books.google.com/books?id=jLM_CQAAQBAJ&pg=PA247 | publisher=John Wiley & Sons | isbn=978-1-118-55747-1}}</ref>
Humans: tablets (220mg)
Vet: oral paste, oral suspension
Can penetrate CNS and cystic fluid, so choice for infections of these areas
Dogs
Capillaria plica
P. kellicotti
F. hirth/Oslerus olseri
Giardia
Cats
P. kellicotti
Platynosum/Opisthorchiidae
SE
More than 10%: anorexia/depression in cats and dogs
1-10%: elevated liver enz, nausea, vomiting, diarrhea in cats and dogs
less than 1%" neutropenia and aplastic anemia w/use longer than 5 days in cats and dogs
Alb sulfoxide is excreted into milk (1.5% of maternal dose). Poor oral absorption, so inlukely to have effect on nursing animals
<ref>{{cite book | last1=Yaffe | first1=Sumner J. | last2=Aranda | first2=Jacob V. | title=Neonatal and Pediatric Pharmacology: Therapeutic Principles in Practice | date=2010 | pages=470–472 | url=https://books.google.com/books?id=1e2-yggGeUIC&pg=PA472 | publisher=Lippincott Williams & Wilkins | isbn=978-0-7817-9538-8}}</ref>
Originally introduced in 1977 in Australia for sheep
Licensed for humans in early 1980s
Usually only needs 1 administration for intestinal nematode infections
Not licensed in US to treat intestinal nematode infection
Uses
Nematodes
Ascaris lumbricoides (roundworm) (single dose)
Trichuris trichiura
Hookworm
N. americanus and A. duodenale (single dose)
Cutaneous larva migrans
Taenis solium, T. saginata (beef tapeworm): praziquantel is better, but albendazole used more in endemic countries bc cheaper and broader spectrum
Enterobius vericularis
Capillaria philippensis
Toxocara canis
Trichinella spiralis
Works best when given early; acts on adult worms in intestinal mucosa before they make larva that penetrate the muscle
Give corticosteroids as well to inhibit infl caused by dying larvae
Trichostrongylus (single dose)
Gnathostoma spinigerum
Filarial nematodes (in combo with DEC or ivermectin)
Lymphatic filariasis (W. bancrofti, B. malayi, B. timori)
Loa Loa
Mansonella perstans
In neurocysticercosis
Works best in pts w/viable cysts in cerebral paenchyma OR when cysticercosis is rapidly progressing
Old cysts not affected
Check for ocular cysticeri, since then albendazole can cause changes to existing lesions that can cause permanent blindness
Pharmakocin.
Quickly changed to albendazole sulfoxide in liver, which is metabolized more slowly
Albendazole sulfoxide metabolized to albendazole sulfone (and other oxidative metabolites0
Pediatric
Teratogenic in rats and rabbit, but found that OK in people in 2nd and 3rd timester
Drug interactions
Cimetidine: reduces gastric acid production or inhibits cytochrome P450-mediated metabolism of albendazole to active metabolite, resuling in lower oral bioavailability
Cortcosteroids: increase steady-state plasma concentration of albendazole sulfoxide
Praziquantel
Theophylline: theophylline induces activity of CYP 1A in hepatoma cells, since also a substrate
Side effects
Most common: abdominal pain, nausea, vomiting headache
Much less common: hypersensitiviy (rash, hives), reversible alopecia, leukopenia
Rare: agranulocytosis
If using for a long time (ex. to treat hydatid disease), can increase hepatic enzymes (stops when med stops)
{{cite journal | last1=Bridges | first1=J. W. | last2=Kibby | first2=M. R. | last3=Walker | first3=S. R. | last4=Williams | first4=R. T. | title=Species differences in the metabolism of sulphadimethoxine | journal=Biochemical Journal | accessdate=2017-06-17 | date=October 1968 | url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1187037/ | pmid=4972257 | pmc=PMC1187037 | issn=0264-6021 | volume=109 | issue=5 | pages=851-856}}
Excreted mostly unchanged by dogs
By human: sulfphadimethoxine N1-glucuronide
Papich, Mark G. (2007). Saunders handbook of veterinary drugs (2nd ed.). St. Louis, Mo: Saunders/Elsevier. pp. 617–618. ISBN9781416028888.
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{{cite book | last=Papich | first=Mark G. | title=Saunders handbook of veterinary drugs | location=St. Louis, Mo | date=2007 | edition=2nd | publisher=Saunders/Elsevier | isbn=9781416028888 | pages=617–618 }}
Wide range
But resistance is common unless combined with ormetoprim (Primor)
Dogs are more susceptible to negative effects, since can't acetylate sulfonamides to their metabolites. Doberman pinschers can be especially sensitive.
Plumb, Donald C. (2011). Plumb's veterinary drug handbook (7th ed.). Stockholm, Wisconsin; Ames, Iowa: Wiley. pp. 951, 954. ISBN9780470959640.
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{{cite book | last=Plumb | first=Donald C. | title=Plumb's veterinary drug handbook | location=Stockholm, Wisconsin; Ames, Iowa | date=2011 | edition=7th | publisher=Wiley | isbn=9780470959640 pages=951, 954}}
In liver, is acetylated to acetyl.sulfadimethoxine, and excreted like that in bile
Dogs don't metabolize it in liver: filtered out by kidneys
Has good reabsorption in the renal tubules → longer half-lives
Dobermans susceptible to sulfonamide-induced poly-systemic immune complex disease (contraindicated)
Sulfadimethoxine/ormetoprin
FDA-approved for skin and soft tissue infections in dogs caused by S. aureus or E. coli
Sulfadimethoxine alone would be bacteriostatic; together with ormetoprin is bacteriocidal
Sympathomimetics → cardiovascular system side effects
Metabolism
Metabolized by intestinal wall and liver to inactive metabolites
But most is excreted by kidneys unchanged (over 70% oral dose within 24 hours)
"Albluterol". National Library of Medicine HSDB Database. Retrieved 2017-06-26.
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{{Cite web | title=Albluterol | work=National Library of Medicine HSDB Database | accessdate=2017-06-26 | url=https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+7206}}
Overdose s/s: exaggerated common adverse reactions, esp. angina, hypertention, hypokalemia
Albuterol prefers Beta2-adrenergic receptors, which are predominant receptors on bronchial smooth muscles
Activation of these receptors → activation of adenylcyclase → increase in intracellular cAMP → protein kinase A activation → inhibit phosphorylation of myosin and lowers intracellular Ca+ concentration
Increase in cAMP also → inhibit release of mediators by mast cells in the airway
Relaces all muscles of airway, from trachea down to terminal bronchioles
Unlike other betaadrenergic agonists, can have significant cardiovascular effect
{{Cite book | last1=Briggs | first1=Gerald G. | last2=Freeman | first2=Roger K. | last3=Yaffe | first3=Sumner J. | title=Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk | year=2011 | publisher=Lippincott Williams & Wilkins | isbn=9781608317080 | url=https://books.google.ca/books?id=OIgTE4aynrMC&pg=PA33 | pages=33–34}}
Can cause maternal and fecal tachycardia
Major decreases in maternal BP (dropping by 30)
Maternal adverse effects inc. acute congestive heart failure, pulmonary edema, death
Can cause temporary hyperglycemia, then increase in serum insulin in both mother and fetus (like all B-mimetics)
Insulin in cord blood are 2x if get albuterol
More pronounced in diabetes pts
Again, like all B-mimetics, increases chance of neonatal respiratory distress syndrome
Long term in utero exposure assoc. w increased chance of: autism, psychiatric disorders, poor cognitive function, poor motor function, poor performance in school, elevated HR, hypertension
{{Cite book | last=Cote | first=Etienne | title=Clinical Veterinary Advisor - E-Book: Dogs and Cats | chapter=Albuterol Toxicosis | date=2014-12-09 | publisher=Elsevier Health Sciences | isbn=9780323240741 | pages=45–46 | url=https://books.google.com/books?id=NmziBQAAQBAJ&pg=PR120}}
Toxic via inappropriate dosing or pets biting into inhalers or vials for nebulizers
Brand names: Proventil, Ventolin, Combivent (when combined with ipratropium)
Dogs more common in overdosing (again, inhaler chewing)
Greyhounds possibly more susceptible to severe cardia arrhytmias
Acute onset of panting, vomiting, anxiety, tremor, weakness, leghargy
At overdose levels, not very selective for beta-2, so has excessive beta-1 and beta-2 actividy
Beta-2 toxic effects: "hypotension, reflex sinus tachycardia, arrhythmias; tremors from stimulation of receptors in skeletal muscles; vomiting; intracellular shifting of Ka and P secondary to increased ATP enzymes, and respiratory alkalosis from panting
Beta-1 toxic effects: "positive inotropic effects on the heart, tachychardia, hypertension, restlessness, anxiety"
Secondary myocardial damage and hypokalemia can also → arrhythmia
Aerosilized inhalers often have hydrocarbons as propellant → sensitive myocardium and increase risk for arrhythmias
Weakness due to hypokalemia and prolonged tachycardia
Treatment
Beta blockers for tachycardia
Possibly K, but can have rebound hyperkalemia if give too much
Benzos for tremors/stimulation
Can't have induced emesis or activated charcoal if in liquid or syrup form (or inhaled), bc absorbed too fast (can still do for tablets)
Muscle weakness → collapse in dogs after a few hours, due to severe hypokalemia
{{Cite book | last=Eghianruwa | first=Kingsley | title=Essential Drug Data for Rational Therapy in Veterinary Practice | date=2014-01-29 | publisher=AuthorHouse | isbn=9781491800102 | url=https://books.google.com/books?id=CtfIAgAAQBAJ&pg=PA13|pages=13–14}}
"Ventolin"
Relaxes uterine and vascular smooth muscles
Potassium effect by stimulating Na-K-ATPase
For cats and dogs: bronchospasm relief; for horses: bronchodilation
Crosses placenta
Can enter CNS, with 5% concentration in brain as of that in plasma
Metabolized in liver to inactive 4'-O-sulfate
Contraindicated by hypersensitivity to albuterol.
Use caution with inhalatant anesthetics, during pregnancy, and in ps w/diabetes, hypertheyroidism, and heart disorders
Drug interactions
Can develop tolerance, so bronchodilation effects can be increased by giving methylxanthine such as aminophylline
Antagonizes dinoprost and oxytocin
Use with other sympathomimetic drugs → more likely to have cardiovascular side effects
Betra-adrenergic blockers inhibit action of albuterol
MAOIs and tricyclic antideprresants can incraese pressor effects
Use w/digitalis can cause cardiac arrthymia
Use with inhaled anesthesia (that's halogenated hydrocarbon) can increase cardiac arrhythmia
{{Cite web | last=Peacock | first=Rachel | title=Salbutamol Toxicosis in Dogs | work=AEC: Animal Emergency Centre | accessdate=2017-06-23 | date=2014-08-26 | url=http://www.aecvets.com.au/News/?id=68}}
B1 effects at high doses can → tachyarrhytmia
Hypokalemia
B2-adrenergic stimulation of Na-K-ATPase pumps in RBCs, liver cells, and muscle cells → intracellular translocation of K ions
Hypokalemia → delayed ventricular reporlarization, prolonged action potential duragion, increased automaticity → can contribute to cardiac arrhythmia
Plumb, Donald C. (2011). ""Albuterol Sulfate"". Plumb's Veterinary Drug Handbook (7th ed.). Stockholm, Wisconsin; Ames, Iowa: Wiley. pp. 24–25. ISBN9780470959640.
{{Cite book | last1=Riviere | first1=Jim E. | last2=Papich | first2=Mark G. | title=Veterinary Pharmacology and Therapeutics | date=2009-03-17 | publisher=John Wiley & Sons | isbn=9780813820613 | url=https://books.google.com/books?id=ievLulSqwBAC&pg=1299 | page=1299–1300}}
Dose in small animals is much smaller than in humans - 20–50 micrograms per kg up to QID vs. 100–200 micrograms per kg up to QID
Cardiac affects include tachycardia, palpitations, and tremors - more w/B1 agonists, but can be caused by B2 agonists at higher doses
Starkey, E. S.; Mulla, H.; Sammons, H. M.; Pandya, H. C. (September 2014). "Intravenous salbutamol for childhood asthma: evidence-based medicine?". Archives of Disease in Childhood. 99 (9): 873–877. doi:10.1136/archdischild-2013-304467. ISSN1468-2044. PMID24938536.
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{{Cite journal | last1=Starkey | first1=E. S. | last2=Mulla | first2=H. | last3=Sammons | first3=H. M. | last4=Pandya | first4=H. C. | title=Intravenous salbutamol for childhood asthma: evidence-based medicine? | journal=Archives of Disease in Childhood | date=September 2014 | pmid=24938536 | doi=10.1136/archdischild-2013-304467 | issn=1468-2044 | volume=99 | issue=9 | pages=873-877}}
Alveolar epithelium → absorbed and enters pulmonary circulation
Toxicity due to B1 and B2 adrenoreceptors outside lungs
Either
Filtered out by kidneys
Metabolized into 4'-O-sulphate → urine
Half-life: 4-6 hours
US Department of Health and Human Services (2017-04-28). "Albuterol". CHEMM. Retrieved 2017-06-23.
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{{Cite web | last=US Department of Health and Human Services | title=Albuterol | work=CHEMM | accessdate=2017-06-23 | date=2017-04-28 | url=https://chemm.nlm.nih.gov/countermeasure_albuterol.htm}}
Albuterol and other B2-adrenergic receptor agonists increase conductance of Ca2+ sensitive and K+ sensitive channels in airway smooth muscle → hyperpolarization → relaxation (independent of cAMP and shit)
Stimulating B2-adrenergic receptors inhibits function of mast cells, basophils, eosinophils, neutrophils, and lymphocytes
Increase intracellular cAMP → signalling cascade to inhibit release of inflammatory mediators & cytokines
Possible in use of chemical defense as "anditode" (mitigate damage) from chlorine gas, mustard gas, phosgene, sarin, soman
Wiley, J. F.; Spiller, H. A.; Krenzelok, E. P.; Borys, D. J. (August 1948). "Unintentional albuterol ingestion in children". Pediatric Emergency Care. 10 (4): 193–196. ISSN0749-5161. PMID7937293.
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{{Cite journal | last1=Wiley | first1=J. F. | last2=Spiller | first2=H. A. | last3=Krenzelok | first3=E. P. | last4=Borys | first4=D. J. | title=Unintentional albuterol ingestion in children | journal=Pediatric Emergency Care | date=August 1994 | pmid=7937293 | issn=0749-5161 | volume=10 | issue=4 | pages=193-196}}
Most common toxicology signs: tachycardia, widened pulse pressure, hyperglycemia, agistation, low serum CO2, vomiting, hypokelemia
Threshold dose was 1 mg/kg (three to ten times normal daily dose
2-hydroxylproplyl-beta-cyclodextrin is toxic to ppl
Phaxan, w/alfaxalone dissolved in 7-sulfo-butyl-ether-beta-cyclodextrin - low toxicty in ppl
Clarke, K. W.; Trim, C. M.; Hall, L. W., eds. (2014). "Chapter 6: General pharmacology of the injectable agents used in anaesthesia". Veterinary Anaesthesia (11th ed.). Oxford: W.B. Saunders. pp. 135–153. doi:10.1016/B978-0-7020-2793-2.00006-2. ISBN9780702027932.
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<ref>{{cite book | editor-last1=Clarke | editor-first1=K. W. | editor-last2=Trim | editor-first2=C. M. | editor-last3=Hall | editor-first3=L. W. | title=Veterinary Anaesthesia | chapter=Chapter 6: General pharmacology of the injectable agents used in anaesthesia | location=Oxford | date=2014 | edition=11th | publisher=W.B. Saunders | isbn=9780702027932 | pages=135-153 | doi=10.1016/B978-0-7020-2793-2.00006-2}}</ref>
Althesin (alfaxalone + alfadone, human version) removed from market in 1984; Saffan (for cats) stayed until alfaxalone
Saffan
Vasodilation → lower BP
Kept "cardiac index"
histamine release lead to the death of some cats, but Saffan was still less mortal than other anesth, most likely bc less cardiac depression
Was used in cats and other domestics and exotics (just not dogs)
Alfaxalone
Smooth and rapid
Recovery better when premedicated
Pre-med certain med + alfaxalone, then anesthesia via CRI alfaxalone:
Buprenorphine + Acepromazine
Buprenorphine + Dexmedetomidine
2nd required much less alfaxan as CRI
Alf can use IM: was done routinely w/cats
Used in exotics: red-eared turtles, axolotl, green iguana, marmosets
Larger animals: horses, sheep
Clarke, K. W.; Trim, C. M.; Hall, L. W., eds. (2014). "Chapter 15: Anaesthesia of the dog". Veterinary Anaesthesia (11th ed.). Oxford: W.B. Saunders. pp. 135–153. doi:10.1016/B978-0-7020-2793-2.00015-3. ISBN9780702027932.
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<ref>{{cite book | editor-last1=Clarke | editor-first1=K. W. | editor-last2=Trim | editor-first2=C. M. | editor-last3=Hall | editor-first3=L. W. | title=Veterinary Anaesthesia | chapter=Chapter 15: Anaesthesia of the dog | location=Oxford | date=2014 | edition=11th | publisher=W.B. Saunders | isbn=9780702027932 | pages=135-153 | doi=10.1016/B978-0-7020-2793-2.00015-3}}</ref>
Useful as anasth agent if have ventricular arrhythmia (this was for dog)
Clarke, K. W.; Trim, C. M.; Hall, L. W., eds. (2014). "Chapter 16: Anaesthesia of the cat". Veterinary Anaesthesia (11th ed.). Oxford: W.B. Saunders. pp. 499–534. doi:10.1016/B978-0-7020-2793-2.00016-5. ISBN9780702027932.
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<ref>{{cite book | editor-last1=Clarke | editor-first1=K. W. | editor-last2=Trim | editor-first2=C. M. | editor-last3=Hall | editor-first3=L. W. | title=Veterinary Anaesthesia | chapter=Chapter 16: Anaesthesia of the cat | location=Oxford | date=2014 | edition=11th | publisher=W.B. Saunders | isbn=9780702027932 | pages=499–534| doi=10.1016/B978-0-7020-2793-2.00016-5}}</ref>
Alfaxalone doesn't provide analgesia, so required additional stuff to be on board (usually opioids, NSAIDs, nerve blocks, and/or NMDAR-antagonist)
Sx less than 30 min can use only injectable anesth
Common anesth combos for general anesth in cats:
Premed: acepromazine + opioid, induce: alfaxalone + diazepam, maintain: iso or sevo
Premed: medetomidine or dexmedetomidine + opioid, induce: alfaxalone, maintain: iso or sevo
Saffan caused histamine release, but was still 3 times less likely to kil cat than any other anesth method at the time
Need less alfaxalone for induction if dilute with sterile water, possibly by being able to administer more slowly
Clarke, K. W.; Trim, C. M.; Hall, L. W., eds. (2014). "Chapter 19: Anaesthesia for obstetrics". Veterinary Anaesthesia (11th ed.). Oxford: W.B. Saunders. pp. 587–598. doi:10.1016/B978-0-7020-2793-2.00019-0. ISBN9780702027932.
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<ref>{{cite book | editor-last1=Clarke | editor-first1=K. W. | editor-last2=Trim | editor-first2=C. M. | editor-last3=Hall | editor-first3=L. W. | title=Veterinary Anaesthesia | chapter=Chapter 19: Anaesthesia for obstetrics | location=Oxford | date=2014 | edition=11th | publisher=W.B. Saunders | isbn=9780702027932 | pages=587–598 | doi=10.1016/B978-0-7020-2793-2.00019-0}}</ref>
Cesareans: crossed placental barrier and affects the kittens, but doesn't cause decrease in RR (Saffan)
<ref>{{cite book | editor-last1=Maddison | editor-first1=Jill E. | editor-last2=Page | editor-first2=Stephen W. | editor-last3=Church | editor-first3=David | title=Small Animal Clinical Pharmacology | chapter=Alphaxalone (±alphadolone) | date=2008 | publisher=Elsevier Health Sciences | isbn=9780702028588 | pages=101–103 | url=https://books.google.com/books?id=RpsROVqemk8C&pg=PA101}}</ref>
Protein binding: 30-50%
Precaution in pts w/hypovolemia, low BP, or pts w/heart disease
Martinez-Botella, Gabriel; Ackley, Michael A.; Salituro, Francesco G.; Doherty, James J. (January 1, 2014). "Natural and Synthetic Neuroactive Steroid Modulators of GABAA and NMDA Receptors". Annual Reports in Medicinal Chemistry. 49: 27–42. doi:10.1016/B978-0-12-800167-7.00003-1. ISSN0065-7743.
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<ref>{{cite journal | last1=Martinez-Botella | first1=Gabriel | last2=Ackley | first2=Michael A. | last3=Salituro | first3=Francesco G. | last4=Doherty | first4=James J. | title=Natural and Synthetic Neuroactive Steroid Modulators of GABAA and NMDA Receptors | journal=Annual Reports in Medicinal Chemistry | date=January 1, 2014 | doi=10.1016/B978-0-12-800167-7.00003-1 | issn=0065-7743 | volume=49 | pages=27-42}}{{closed access}}</ref>
Neuroactive steroids
Target different GABA A receptors than benzodiazepenes
Low concentrations: bind to M3/M4 in alpha subunit - allosteric modification of current
High concentrations: "direct gating of GabaA currents", binds to alpha/beta interface near GABA binding site
Possibly affect expression levels of GABAa
Enhance tonic current but have little effect on phasic currents even after prolonged exposure
Research suggests that neuroactive steroids increase GABAa receptors (so harder to build a tolerance, unlike w/benzos)
Every since progesterone and 5beta-pregnance-3,2-dione reported to have depressant effect on CNS in rodents in 1941, multiple groups searched for synthetic to use as anasthetic
Mainly focused on increasing water solubility
1971: Althesin (withdrawn from market in 1984 bc anaphylactic reactions)
Phaxan being developed for use in ppl (alfaxalone in cyclodextrin)
Dogs and cats that got only midazolam as premed needed MORE alfax than normal for induction
Varga, Molly (2014). "Chapter 4: Anaesthesia and Analgesia". Textbook of Rabbit Medicine (2nd ed.). Butterworth-Heinemann. pp. 178–202. ISBN9780702049798.
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<ref>{{cite book | last=Varga | first=Molly | title=Textbook of Rabbit Medicine | chapter=Chapter 4: Anaesthesia and Analgesia | date=2014 | edition=2nd | publisher=Butterworth-Heinemann | isbn=9780702049798 | pages=178-202}}</ref>
<ref>{{cite journal | last1=Visser | first1=S. a. G. | last2=Smulders | first2=C. J. G. M. | last3=Reijers | first3=B. P. R. | last4=Graaf | first4=P. H. van der | last5=Peletier | first5=L. A. | last6=Danhof | first6=M. | title=Mechanism-Based Pharmacokinetic-Pharmacodynamic Modeling of Concentration-Dependent Hysteresis and Biphasic Electroencephalogram Effects of Alphaxalone in Rats | journal=Journal of Pharmacology and Experimental Therapeutics | accessdate=July 15, 2017 | date=September 1, 2002 | url=http://jpet.aspetjournals.org/content/jpet/302/3/1158.full.pdf | pmid=12183676 | doi=10.1124/jpet.302.3.1158 | issn=0022-3565 | volume=302 | issue=3 | pages=1158-1167}}</ref>
Alfaxan at higher concentrations acts on GABA R as agonist, "higher concentrations' being at least 1 microM
Ahmad, Suhail; Mokaddas, Eiman (1 March 2014). "Current status and future trends in the diagnosis and treatment of drug-susceptible and multidrug-resistant tuberculosis". Journal of Infection and Public Health. 7 (2): 75–91. doi:10.1016/j.jiph.2013.09.001. ISSN1876-0341. {{cite journal}}: Invalid |ref=harv (help)
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<ref>{{cite journal | last1=Ahmad | first1=Suhail | last2=Mokaddas | first2=Eiman | title=Current status and future trends in the diagnosis and treatment of drug-susceptible and multidrug-resistant tuberculosis | journal=Journal of Infection and Public Health | date=1 March 2014 | pages=75-91 | doi=10.1016/j.jiph.2013.09.001 | issn=1876-0341 | volume=7 | issue=2 | ref=harv }}</ref>
Resistance to amikacin and kanamycin in TB due to mutation in rrs gene, which codes for a 16S rRNA that is different at the 3' end
In 80–85% of strains resistant to kanamycin/amikacin
Risk of hearing loss (increases w/increasing peak concentration)
No symptom of cochlear damage (due to 8th nerve toxicity) during treatment
So can be partially or fully deaf after finish drug
Neuromuscular blockade and respiratory paralysis (inc. acute muscular paralysis and apnea) from topical or oral use of aminoglycosides
Ca salts can reverse neuromusc blockade
Increased risk for pts getting anesthetics or neuromuscular blocking agents (ex. tubocurarine, succinylcholine) or getting large transfusions of citrated-anticoagulated blood
Don't use with or sequentally with other neurotoxic/nephrotoxic drugs
Dehydration and being old increase risk of tox
Avoid using w/potent diuretics bc diuretics can cause ototox, and can change aminoglycoside concentrations, which would also enhance tox
Aminoglycoside derived from kanamycin
Uses:
Bone and joint infections (serious inf by susceptible gram -)
Intra-abdominal infections (serious inf by susceptible gram -)
Inc. peritonitis
Use as adjunct to clindamycin, metronidazole, piperacillin + tazobactam, ampicillin + sulbactam
Meningitis (by gram - bact) as adjunct in initial treatment
With ampicillin for neonatal S. agalactiae or Listeria monocytogenes
With 3rd generation cephalosporin for neonatal gram- bact meningitis, inc. by E. coli
With imipenem in adults for menin by E. coli
With meropenem in menin by Pseudomonas
With impimenem or colistin for menin by Acinetobacter
Resp tract inf (serious, by gram -)
As adjunct ot Beta-lactam or carbapenem for treating nosocomial pneumonia
Septicemia (by gram -)
As adjunct to betalactam or carbapenem
Skin and skin suture infections (serious inf, by susc. gram -)
UTIs (serious, complicated by susc. gram-)
Inc. by Enterobacteriaceae or Pseudomonas aeruginosa
Possibly as adjunct to another tx
Only use if causing organism is resistant to less toxic drugs
Mycobacterial
2nd line agent in multiple-drug regiments for treating active TB (if have relapse or tx failure) or TB resistant to isoniazid and/or rifampin or when 1st-line drugs can't be tolerated
Use as alernative in multiple-drug regiments for treating M. avium
Use for nonpulmonary M. abscessus, M. chelonae, M. fortiuitum
Infections by Nocardia
(Usually) As adjunct to sulfonamide if inf is severe or disseminated
If can't use sufonamide, use amikacin + carbapenem or 3rd gen cephalosporin or tetraxycline or amoxiclav or clarithromycin or cycloserine or linezolid
Inf by Rhodococcus equi
Inf in febrile neutropenic patients
(Empiric therapy)
Use w/anti-psuedomonal cephalosporin or extended-spectrum penicillin or carbapenem
Administration
IV or IM
Can be given intrathecally or intraventricularly for meningitit or other CNS infection
If giving IV with a beta-lactam, don't admix them; administer separately
IV and IM dosage is the same
Special populations
Old people: age-related decrease in kidney fxn
PPl w/muscular disorder like myasthenia gravis or parkinsons since amikacin has strong curare-like effect on neuromusc junctions and can make muscle weakness worse
Pregnancy category D
Possible harm to fetus
W/comcurrent aminoglycoside, can cause bilateral congentical deafness
Low concentration in lactated milk
Pediatric: immature renal system (→ prolonged serum half-lif)
Contraindications
Sensitivity to aminoglycosides (cross-allergenic)
Sensitivity to sulfite, since amikacin has sodium metabisulfite and can cause allergic-type reactions
Possibility of additive toxicity, so avoid concurrent or sequential use of other neurotoxic/nephrotoxic drugs, esp. bacitration ,cisplatin, ampotericin B, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, vancomycin, or other aminoglyc.
Diuretics: increased risk of ototox (since diuretics can cause them); increase SE of aminoglycosides, since can change their concentration in serum or tissue
Nuromuscular blocking agents (see above)
Indomethacin: possibly increase serum aminoglycosides in premature babies
Pharmacokin
Not absorbed orally
Peak serum concentration within 0.5–2 hours after IM
Needs long duration of tdx and repeated courses or high cumulative dose
Cause high-frequency hearing loss (beyond range of normal speech)
Hearing loss of 15 decible at 2 or more frequencies, or 20 decibels at at least 1 freuency: 18%
Nephrotox w/amikacin: 8.5%
Bauman, Robert W. (2015). Microbiology: With Diseases by Body System (4th ed.). Boston: Pearson. p. 294. ISBN978-0-321-91855-0. {{cite book}}: Invalid |ref=harv (help)
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<ref>{{cite book | last=Bauman | first=Robert W. | title=Microbiology: With Diseases by Body System | location=Boston | year=2015 | page=294 | edition=4th | publisher=Pearson | isbn=978-0-321-91855-0 | ref=harv }}</ref>
Type of aminoglycoside that binds to 30S of ribosome and changes its shape so that can't read mRNA codons correctly
Treating MDR tuberculosis, use several different drugs
Regimen includes capreomycin; if that doesn't work, trade out for kanamycin; if that doesn't work, trade out for amikacin
Although capreomycin is often skipped out on - not available everywhere, and more expensive than kanamycin
Cross-resistance
Resistance to streptomycin usually still susc to amikacin
Resistance to capreomycin usually still susc to amikacin
Resistance to amikacin also resistant to kanamcin and capreomycin
Resistant to kanamycin: diff levels of resistance to amikacin
Never use amikacin 1st, bc will confer cross-resistance to other drugs
Corti, Natascia; Taegtmeyer, Anne; Imhof, Alexander (1 January 2011). "Miscellaneous antibacterial drugs". Side Effects of Drugs Annual. A worldwide yearly survey of new data in adverse drug reactions. 33: 509–540. doi:10.1016/B978-0-444-53741-6.00026-X. ISSN0378-6080. {{cite journal}}: Invalid |ref=harv (help)
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<ref>{{cite journal | last1=Corti | first1=Natascia | last2=Taegtmeyer | first2=Anne | last3=Imhof | first3=Alexander | title=Miscellaneous antibacterial drugs | journal=Side Effects of Drugs Annual | series=A worldwide yearly survey of new data in adverse drug reactions | date=1 January 2011 | pages=509-540 | doi=10.1016/B978-0-444-53741-6.00026-X | issn=0378-6080 | volume=33 | ref=harv }}</ref>
Causes vestibular toxicity at 7.4%
(Most likely) By creating excessive oxidative free radicals (time-dependent, but not dose-dependent)
Reduce risk by minimizing duration of exposure
Electrolyte imbalance (aminoglyc in general)
Change renal tubular function → changes in fluid/electrolyte/acid-base → hypokalemia and acidosis or alkalosis
UTI (aminoglyc in general): nephrotox more common in those w/glomerular filtration rate under 60mL/min/1,73 m3, diabetes mellitus, treatment with other nephrotox drugs or iodinated contrast agents, hypotension
Amikacin damages vestibular organ in infants more often than damages the cochlea
Amikacin attributed to Type 5 Barter-like syndrome w/severe hypocalcemia
Susceptibility factors
Correlation btw lower gestational age and/or birth weight percentile and lower amikacin clearance
Cote, Etienne (2010). Clinical Veterinary Advisor - E-Book: Dogs and Cats. Elsevier Health Sciences. p. 27. ISBN978-0-323-06876-5. {{cite book}}: Invalid |ref=harv (help)
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<ref>{{cite book | last=Cote | first=Etienne | title=Clinical Veterinary Advisor - E-Book: Dogs and Cats | year=2010 | page=27 | publisher=Elsevier Health Sciences | isbn=978-0-323-06876-5 | ref=harv }}</ref>
Nocardiosis: sulfonamides are drugs of choice; might end up needeing amikacin or imipenem
Cunha, Burke A. (1 November 2006). "New Uses for Older Antibiotics: Nitrofurantoin, Amikacin, Colistin, Polymyxin B, Doxycycline, and Minocycline Revisited". Medical Clinics of North America. Antimicrobial Therapy. 90 (6): 1089–1107. doi:10.1016/j.mcna.2006.07.006. ISSN0025-7125. {{cite journal}}: Invalid |ref=harv (help)
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<ref>{{cite journal | last=Cunha | first=Burke A. | title=New Uses for Older Antibiotics: Nitrofurantoin, Amikacin, Colistin, Polymyxin B, Doxycycline, and Minocycline Revisited | journal=Medical Clinics of North America | series=Antimicrobial Therapy | date=1 November 2006 | pages=1089-1107 | doi=10.1016/j.mcna.2006.07.006 | issn=0025-7125 | volume=90 | issue=6 | ref=harv }}</ref>
Amikacin stx makes it immune to aminogly-inactivating enzymes
Only one location on stx makes it vulnerable – ginteamicin and tobramycin have 6
Aminogly w/"greatest degree" of activity against P. aeruginosa and the one least likely to cause resistance
Mostly against aeribic gram- bacilli
Rarely used as monotherapy
Pharmacokin
Plasma protein binding: less than 5%
95% excreted unchanged
2 hr serum half life normally; 50 hrs in end-stage renal disease
volume of distribution 0.25 L/kg
Single daily dose "virtually eliminates" nephrotox/ototox potential
CSF penetation: 15% (w/inflamed meninges, is 20%)
Traditional uses
Combo therapy for P. aeruginosa and aerobic G- bacilli
Increased/new uses; combo therapy for:
MDR P. aeruginosa
MDR Klebsiella pneumoniae
MDR Acenitobacter baumannii
MDR M. tuberculosis
DrugBank (2 August 2017). "Amikacin". DrugBank. Retrieved 10 August 2017.
<ref>{{cite book | last=Eghianruwa | first=Kingsley | title=Essential Drug Data for Rational Therapy in Veterinary Practice | year=2014 | url=https://books.google.com/books?id=h4zCAgAAQBAJ&pg=PA16 | pages=16–17 | publisher=Author House | isbn=978-1-4918-0000-3 | ref=harv }}</ref>
Amikin (human), Amiglyde (vet)
Aminocyclitol
Sparingly soluble in water; works best in alkaline environment; heat resistant
Rapidly bacateriocidal to most G-
Resistant to aminoglyc-inactivating enzymes
Binds to 30S and 50S subunits
Abnormal initiation complexes accumulate
Misread mRNA and add incorrect amino acid
Uses
Treating aerobic G- resistant to gentamicin and tobramycin
Treating G- eye infections (esp. by P. aeuroginosa)
Uterine absorption poor
Ocular absorption has been found (when have conjunctivitis(
Bioavilability: >90% from IM or SQ injections
Distribution
Sequestered in the inner ear and kidneys
Vd = 0.27 L/kg in humans (lower in obesity, higher in newborns)
0.15–0.3 in cats and dogs
0.26–0.58 in horses
Clearance higher in those w/cystic fibrosis
Interactions; indomethacin, enflurane, and methoxyflurane increase tox potential
Esposito, Susanna; Canevini, Maria Paola; Principi, Nicola (1 July 2017). "Complications associated with antibiotic administration: neurological adverse events and interference with antiepileptic drugs". International Journal of Antimicrobial Agents. 50 (1): 1–8. doi:10.1016/j.ijantimicag.2017.01.027. ISSN0924-8579. {{cite journal}}: Invalid |ref=harv (help)
Factors that increase risk of tox: prolonged use (more than 5 days), high trough levels (>5 microg/mL), pre-existing renal disease, dehydration, hypokalemia, hypocalcemia, hypomagnesemia, metabolic acidosis, age, concurrent nephrotox drug admin, diureitcs, antiprostaglandins
Tox can be reduced by less frequent dosing
Efficacy of aminoglycs is assessed by peak concentrations, but toxicity correlated more to trough concentrations (so dosing every 24 hrs instead of every 8 hours)
Severe, unstable bacterial pneumonia p1103
As pat of combo therapy w/a beta-lactam
Avoid in neonates p523
2nd line tx for Mycobacteriam avium-intracellular complex and non-TB mycobacteria in dogs and cats p879
Pus and necrotic debris bind and inactivate vancomycin and aminoglycs → they become ineffective p591
<ref>{{cite book | last1=Mader | first1=Douglas R. | last2=Divers | first2=Stephen J. | title=Current Therapy in Reptile Medicine and Surgery - E-Book | year=2013 | url=https://books.google.com/books?id=2phWAgAAQBAJ&pg=PA382| pages=41, 382 | publisher=Elsevier Health Sciences | isbn=978-0-323-24293-6 | ref=harv }}</ref>
Maire, P.; Bourguignon, L.; Goutelle, S.; Ducher, M.; Jelliffe, R. (2017). "Chapter 20 - Individualizing Drug Therapy in the Elderly". Individualized Drug Therapy for Patients. Boston: Academic Press. pp. 373–382. doi:10.1016/B978. ISBN978-0-12-803348-7. {{cite book}}: External link in |chapterurl= (help); Invalid |ref=harv (help); Unknown parameter |chapterurl= ignored (|chapter-url= suggested) (help)
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<ref>{{cite book | last1=Maire | first1=P. | last2=Bourguignon | first2=L. | last3=Goutelle | first3=S. | last4=Ducher | first4=M. | last5=Jelliffe | first5=R. | title=Individualized Drug Therapy for Patients | chapter=Chapter 20 - Individualizing Drug Therapy in the Elderly | location=Boston | year=2017 | chapterurl=http://www.sciencedirect.com/science/article/pii/B9780128033487000204 | pages=373-382 | doi=10.1016/B978 | publisher=Academic Press | isbn=978-0-12-803348-7 | ref=harv }}</ref>
Average clearance at age 20 is 6 L/hr
Average clearance at age 80 is 3 L/h (with larger standard deviation)
Monteleone, Peter M.; Muhammad, Naseem; Brown, Robert D.; McGrory, John P.; Hanna, Samir A. (1 January 1983). "Amikacin Sulfate". Analytical Profiles of Drug Substances. 12: 37–71. doi:10.1016/S0099-5428(08)60163-X. ISSN0099-5428. {{cite journal}}: Invalid |ref=harv (help)
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<ref>{{cite journal | last1=Monteleone | first1=Peter M. | last2=Muhammad | first2=Naseem | last3=Brown | first3=Robert D. | last4=McGrory | first4=John P. | last5=Hanna | first5=Samir A. | title=Amikacin Sulfate | journal=Analytical Profiles of Drug Substances | date=1 January 1983 | pages=37-71 | doi=10.1016/S0099-5428(08)60163-X | issn=0099-5428 | volume=12 | ref=harv }}</ref>
Alteration of kanamycin A, bc resistant bacteria were speading\
<ref>{{cite book | last1=Morris | first1=Daniel O. | last2=Kennis | first2=Robert A. | title=Clinical Dermatology, an Issue of Veterinary Clinics: Small Animal Practice, E-Book | year=2012 | url=https://books.google.com/books?id=TsKQVAWxHg4C&pg=PA29 | page=29 | publisher=Elsevier Health Sciences | isbn=978-1-4557-7377-0 | ref=harv }}</ref>
Can give SQ at home for pyoderma
Nephrotox: renal proximal tubular necrosis
Still might be less nephrotox than other aminoglycs, inc. gentamicin
Signs: decreased specific gravity, cats, proteinuria, glycoosuria, finally azotemia
Renal tox is usually reversible with early drug withdrawal
Ototox
Causes apoptosis in inner ear hair cells
Orsini, James A. (1 August 2017). "Update on Managing Serious Wound Infections in Horses: Wounds Involving Joints and Other Synovial Structures". Journal of Equine Veterinary Science. 55: 115–122. doi:10.1016/j.jevs.2017.01.016. ISSN0737-0806. {{cite journal}}: Invalid |ref=harv (help)
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<ref>{{cite journal | last=Orsini | first=James A. | title=Update on Managing Serious Wound Infections in Horses: Wounds Involving Joints and Other Synovial Structures | journal=Journal of Equine Veterinary Science | date=1 August 2017 | pages=115-122 | doi=10.1016/j.jevs.2017.01.016 | issn=0737-0806 | volume=55 | ref=harv }}</ref>
For subcutis infections in horses (cellulitis, ulcerative lymphangitis), usually caused by Staphylococcus
In combo with cephalosporin
Inf of synovial stx (joint, tendon sheath, bursa), either traumatic or surgical
Cephalosporin + amikacin; add metronidazole for wounds on distal limb or anywhere likely to have fecal contamination
Staphylococcus infections
Amikacin more likely than gentamicin to work, but susceptibility to amikacin in equine MRSA is variable
Less effective agasint Streptococcus than gentamicin
Enterobacter: better than gentamicin
E. coli and other enterobacteria: amikacin better than gentamicin
Pasteurella: gentamicin better than amikacin
Choice abx against Pseudomonas
Papich, Mark G. (2015). "Amikacin". Saunders Handbook of Veterinary Drugs: Small and Large Animal (4th ed.). Elsevier Health Sciences. pp. 25–27. ISBN978-0-323-24485-5. {{cite book}}: External link in |chapterurl= (help); Invalid |ref=harv (help); Unknown parameter |chapterurl= ignored (|chapter-url= suggested) (help)
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<ref>{{cite book | last=Papich | first=Mark G. | title=Saunders Handbook of Veterinary Drugs: Small and Large Animal | chapter=Amikacin | year=2015 | chapterurl=https://books.google.com/books?id=ip8_CwAAQBAJ&pg=PA25 | pages=25–27 | edition=4th | publisher=Elsevier Health Sciences | isbn=978-0-323-24485-5 | ref=harv }}</ref>
"Amiglyde-V" (vet version)
More active than gentamicin against many Gram-
1/2 life short in most animals (1-2 hours)
Horses;
Local administration as an intrauterine lavage to treat metritis
Regional limb perfusion
Dogs, cats, horses, cattle
Park, Je Won; Ban, Yeon Hee; Nam, Sang-Jip; Cha, Sun-Shin; Yoon, Yeo Joon (1 December 2017). "Biosynthetic pathways of aminoglycosides and their engineering". Current Opinion in Biotechnology. Chemical biotechnology • Pharmaceutical biotechnology. 48: 33–41. doi:10.1016/j.copbio.2017.03.019. ISSN0958-1669. {{cite journal}}: Invalid |ref=harv (help)
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<ref>{{cite journal | last1=Park | first1=Je Won | last2=Ban | first2=Yeon Hee | last3=Nam | first3=Sang-Jip | last4=Cha | first4=Sun-Shin | last5=Yoon | first5=Yeo Joon | title=Biosynthetic pathways of aminoglycosides and their engineering | journal=Current Opinion in Biotechnology | series=Chemical biotechnology • Pharmaceutical biotechnology | date=1 December 2017 | pages=33-41 | doi=10.1016/j.copbio.2017.03.019 | issn=0958-1669 | volume=48 | ref=harv }}</ref>
Amikacin = has 4-amino-2-hydroxybutyrate group instead of an H that kanamycin A has
Plumb, Donald C. (2011). "Amikacin Sulfate". Plumb's Veterinary Drug Handbook (7th ed.). Stockholm, Wisconsin: Wiley. pp. 39–43. ISBN978-0-470-95964-0. {{cite book}}: Invalid |ref=harv (help)
US National Library of Medicine. "amikacin". Pubchem. Retrieved 11 August 2017.
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<ref>{{cite web | last=US National Library of Medicine | title=amikacin | work=Pubchem | accessdate=11 August 2017 | url=https://pubchem.ncbi.nlm.nih.gov/compound/37768 }}</ref>
Binds to 30S ribosome subunit: locks 16S rRNA and S12 protein within 30S
<ref>{{cite web | last=US National Library of Medicine | title=AMIKACIN SULFATE- amikacin sulfate injection | work=DailyMed | accessdate=8 August 2017 | date=17 August 2016 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0b56f6df-a05d-4520-8bf0-d7cefe20f6ad }}</ref>
Pharmacokin
Volume of distribution: 24 liters
Excreted via glomerular filtration
Spinal fluids in infants: 10-20% (can reach 50% in meningitis)
Crosses placenta at 16% peak maternal serum concentration
1/2 life in mom is 2 hours, 1/3 life in fetus is 3.7 hours
Mechanism
Binds to prokaryotic ribosome and inhibits protein synth
Vs. gram+ and gram-
Resistance
Salmonella, Shigella
Some aminoglycoside inactivating enzymes that work against gentamicin, tobramycin, or kanamycin don't work agasint amikacin
Activity
Lower activity against Gram+ other than Straphylococcus
Gram-
Pseudominas
E. coli
Proteus
Klebsiella
Enterobacter
Serratia
Acinetobacter
Citrobacter freundii (in vitro)
Uses
Short-term of serious infections by susceptible gram-, inc. Pseudomonas, E. coli, Proteus, Klebsiella, Enterobacter, Serratia, Acinetobacter
Effective against: Bacterial septicemia (inc. neonatal), serious inf of repiratory tract, bones and joints, CNS, skin and soft tissue, intra-abdominal, burns, post-op infections, complicated UTIs
Some severe inf (ex. neonatal sepsis), use w/penicillin-type to cover any Gram+ bact
Pregnancy
Aminoglyc.: deafness to fetuses (no serious effect by other aminogl.)
No harm to fetuses in rat/mice studies
Sulfite sensitivity (seen more in people w/asthma)
Can lead to C. difficile-associated diarrhea
Adverse effects
Neurotox-ototox
Toxic effect on 8th cranial nerve → hearing loss, loss or balance
Cochlear damage (inc. losing high frequency hearing) happens before clinical hearing loss can be detected
<ref>{{cite web | last=US National Library of Medicine | title=AMIGLYDE-V- amikacin sulfate injection | work=DailyMed | accessdate=8 August 2017 | date=9 March 2017 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e2abecaf-9532-45a0-a284-5697b2aa38f1 }}</ref>
"AMIGLYDE-V": by vet Rx only
For intrauterine use in horse
Uterine infections (endometritis, metritis, poyometra) by susc. bacteria (inc. E. voli, Pseudomonas, Klebsiella)
Vardanyan, Ruben; Hruby, Victor (2016). "Chapter 32 - Antimicobacterial Drugs". Synthesis of Best-Seller Drugs. Boston: Academic Press. pp. 669–675. doi:10.1016/B978. ISBN978-0-12-411492-0. {{cite book}}: External link in |chapterurl= (help); Invalid |ref=harv (help); Unknown parameter |chapterurl= ignored (|chapter-url= suggested) (help)
<ref>{{cite book | last1=Bowen | first1=Jon | last2=Heath | first2=Sarah | title=Behaviour Problems in Small Animals: Practical Advice for the Veterinary Team | date=2005 | page=52 | publisher=Elsevier Health Sciences | isbn=978-0-7020-2767-3 | url=https://books.google.com/books?id=aRpgViLvf1oC&pg=PA52}}</ref>
2 most common benzos in vet med are diazepam and alprazolam
Benzos: limit depth perception, so don't allow cats outside
{{cite web | last=Lambert Vet Supply | title=Use of Aluminum Hydroxide Helps Stabilize Pet Renal Failure Issues | work=General Pet Health Articles | accessdate=2017-06-30 | url=http://www.lambertvetsupply.com/Aluminum-Hydroxide-and-Renal-Failure}}
As adjuvant in human and pet vaccines
Powder is most popular form
Cheap, OTC
Doesn't accumulate in body, so no toxicity
No serious side effects (some constipation in small animals)
OTHER USES
Horses with chronic renal failure
Adjuvant for vax for livestock
Lifelearn Inc (2010-11-01). [vcahospitals.com/know-your-pet/aluminum-hydroxide "Aluminum Hydroxide"]. Know Your Pet. Retrieved 2017-06-30. {{cite web}}: Check |url= value (help)
copy
{{cite web | last=Lifelearn Inc | title=Aluminum Hydroxide | work=Know Your Pet | accessdate=2017-06-30 | date=2010-11-01 | url=vcahospitals.com/know-your-pet/aluminum-hydroxide}}
Reduce hyper-P in pts w/renal failure
Binding to dietary P, reducing amount that's absorbed from intestines
Kidneys normally filter excess P out, but P accumulates if kidneys failing
High P → lethargy, poor appetite
Al. hydroxide used when dietary restriction/renal diet not enough
Powder that you mix into food, or capsules or liquid
Most likely side effect in small animals is constipation
Papich, Mark G. (2007). "Aluminum Hydroxide and Aluminum Carbonate". Saunders Handbook of Veterinary Drugs (2nd ed.). St. Louis, Mo: Saunders/Elsevier. pp. 15–16. ISBN9781416028888.
copy
{{cite book | last=Papich | first=Mark G. | title=Saunders Handbook of Veterinary Drugs | chapter=Aluminum Hydroxide and Aluminum Carbonate | location=St. Louis, Mo | date=2007 | edition=2nd | publisher=Saunders/Elsevier | isbn=9781416028888 | pages=15–16}}
Cats, dogs, and horses
As a gel: Amphogel
In combo with diets that reduce phosphorous
Antacid action (neutralizes stomach acid) is short
Often substituted with Ca carbonate or Ca citrate, since not available everywhere/from many sources (bc has Al)
Plumb, Donald C. (2011). "Aluminum Hydroxide". Plumb's Veterinary Drug Handbook (7th ed.). Stockholm, Wisconsin; Ames, Iowa: Wiley. pp. 36–37. ISBN9780470959640.
copy
{{cite book | last=Plumb | first=Donald C. | title=Plumb's Veterinary Drug Handbook | chapter=Aluminum Hydroxide | location=Stockholm, Wisconsin; Ames, Iowa | date=2011 | edition=7th | publisher=Wiley | isbn=9780470959640 | pages=36–37}}
"Amphogel"
Oral antacid/phosphate binder
Decreases hyperphosphatemia in patients w/renal failure if diet changes don't work
Al salts bind to dietary P, reducing amount of P absorbed from intestine
Small animals; can cause constipation
Class A for pregnancy
Hard to OD orally
Dogs & foals: also used as adj. therapy for gastric ulcers
Ca-channel blockers preferred for high BP in patients with certain preexisting conditions (ex. ischemic heart disease) and old people, and black people (respond better)
Don't use for acute crises
Amlodopine-associated edema risk can go down if add ACE inhibitor or angiotensin II
Combo therapy (NOT in order of strength)
Amlodopine/atorvastatin for hypertension (former) and dyslipidemias and preventing cardiovascular events (latter)
Or for CAD (former) and same for latter
Amlodopine/aliskiren if need more than one agent for BP control (can give individually or as combo)
Amlodopine/aliskiren/hydrochlorothiazide combo tablet if BP still not decreasing
Amlodopine/benazepril combo if either has failed indivi
Or if amlodopine alone gave edema
Amlodopine/olmesartan for ppl who need more for BP
Amlodopine/olmesartan/hydrohclorothiazide
Amlodipine/Perindopril
Or if amlodipine alone gave edema
Amlodipine/telmisartan
Amdlodipine/valsartan
Amlodipine/valsartan/hydrochlorothiazide
Use for Prinzmetal variant angina and chronic stable angina pectoris
Can be taken orally
Side effects: edema, dizziness, flushing, palpitations, fatigue, nausea, abd pain (flushing, palpitations, and sleepiness more common in women)
Treatment for glaucoma reduces intraocular pressure → blood flow to optic nerve increases → sudden release of Ca from mitochondria, which can damage optic nerve
Ca channel blockers like amlodipine can prevent this/protect optic nerve from damage
Papich, Mark G. (2007). "Amlodipine Besylate". Saunders Handbook of Veterinary Drugs (2nd ed.). St. Louis, Mo: Saunders/Elsevier. pp. 26–27. ISBN9781416028888.
copy
Papich, Mark G. (2007). "Amlodipine Besylate". Saunders Handbook of Veterinary Drugs (2nd ed.). St. Louis, Mo: Saunders/Elsevier. pp. 26–27. ISBN9781416028888.
ACE inhibitors less effective in cats
2.5, 5, 10mg tablets
[Cats and dogs only]
Plumb, Donald C. (2011). "Amlodipine Besylate". Plumb's Veterinary Drug Handbook (7th ed.). Stockholm, Wisconsin; Ames, Iowa: Wiley. pp. 53–54. ISBN9780470959640.
copy
Plumb, Donald C. (2011). "Amlodipine Besylate". Plumb's Veterinary Drug Handbook (7th ed.). Stockholm, Wisconsin; Ames, Iowa: Wiley. pp. 53–54. ISBN9780470959640.
"Norvasc"
High BP in cats (often 1st choice)
Decrease BP in dogs w/chronic renal failure, but otherwise meh
Activates renin-angiotensin aldosterone system (RAAS) in healthy dogs at higher doses except with ACE inhibitor
Cat: high BP often sign of other disease (renal failure, thryotoxic cardiomyopathy, etc.)
Mech: decrease impulse formation and conduction velocity in cardiac cells
Diuretic in dogs
Concerns
Renal disease in cats with high BP
Local increase in RAAS activity higher pressure bc of efferent arteriolar constriction
Infrequent, bug in cats; azotemia, lethargy, hypokalemia, reflex tachychardia, weight loss
Dogs: possible gingival hyperplasia with chronic use
<ref>{{cite web | title=Ampicillin Monograph for Professionals | work=Drugs.com | accessdate=18 August 2017 | url=https://www.drugs.com/monograph/ampicillin.html }}</ref>
Uses
Endocarditis
Enterococcal endocarditis, w/aminoglycoside
Endo by slow-growing fastidious gram-negative bacilli (HACEK group: Haemophilus parainfluenzae, H. aphrphilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae)
W/gentamicin
By susceptible staphylococci, streptococci, E. coli, P. mirabilis, or Salmonella
Prevention of endocarditis in those w/cardiac conditions undergoing dental, oral, respiratory tract, or esophageal procedures, or GU and GI procedures
Meningitis/other CNS
By Neisseria mengingitisis, S. agalactiae, Listeria monocytogenes, E. coli, H. influenzae, S. pneumoniae
Drug of choice for neonatal S. agalactiae meningitis and L. monocytogenes; use w/aminoglycoside
For Haemophilus influenzae, used w/chloramphenicol
Respiratory tract infections
By S. aureus (inc strains resistant to penicillin), Streptococcus, S. pyogenes, H. influenzae (non-penicillinase strains only)
Don't use for strept or staph rep infections if penicillin works
Septicemia
Susc. staph, strept, enterococci, E. coli, P. mirabilis, Salmonella
UTIs
Susc. enterococci (drug of choice), E. coli, P. mirabilis
Infections by Eikenella corrodens (drug of choice)
Used to be used for gonorrhea and associated infections, but too many penicillin-resistant strains now
Listeria monocytogenes, alone or w/aminoglycoside
Drug of choice for tx during pregnancy, granulomatosis infantiseptica, sepsis, endocarditis, meningitis, foodborne infections
Whooping cough (prevent and treat 2ndary infections)
Salmonella infections, inc. typhoid fever, and inc. chronic carriers of T. typhi
Shigella infections
Previously a drug of choice before resistance strains of S. flexneri and S. sonnei started popping up more
Prevent early-onset neonatal group B streptococcal disease
Amp given to pregnant women identified as GBS carriers in prenatal screenings
Perioperative prophylaxis for vaginal hysterectomy or C-sections
Administration
Orally
But not as initial treatment for severe infections; can be follow-up to IV or IM ampicillin
Slow IV injection/infusion
IM injection
Contraindications: hypersensitivity to any penicillin
Warning
Can cause C. diff-associated colitis
Hypersensitivity reactions
Higher risk of rash in patients w/mono
Pregnancy category B
Distributed into maternal milk
Renal clearance delayed in young infants bc renal function not fully matured
Common side effects: diarrhea, nausea, rash
Interactions
Allopurinol: increase risk of rash, though unclear if bc allopurinol or bc of hyperuricemia in those patients
Aminoglycosied: synergistic effects
Chloramphenicol: evidence of antagonism
Hormonal contraceptives: possible decrease of efficacy of oral contraceptives w/estrogen and increased probability of breakthrough bleeding
Methotrexate: possible decrease in renal clearance of both drugs
Probenecid: decreased renal tubular secretoin
Sulbactam: synergistic bactericidal effect against bact that make beta-lactamase
Sulfonamides: antagonism
Glucose test: possible false-positives in urine glucose tests that use Clinitest, Benedict's solution, or Fehling's solution. Use glucose tests that are based on enzymatic glucose oxidase reactions instead
Uric acid test: possible false increased serum concentration of uric acid if use copper-chelate method; use phosphotungstate or uricase method
Pharmacokinetics
Bioavailability
30–55% oral dose absorbed in GI tract of fasting adults
Peak concentration in serum in 1–2 hours
IM: peak concentrations faster and higher
IV: peak concentrations immediately after infusion
<ref>{{cite web | title=Drug interactions between amikacin and ampicillin | work=Drugs.com | accessdate=22 February 2018 | url=https://www.drugs.com/drug-interactions/amikacin-with-ampicillin-153-0-196-0.html }}</ref>
Can inactivate aminglycosides by forming a complex with them. can be avoided by administering them separately instead of in combined IV container or line
<ref>{{cite web | title=Drug interactions between ampicillin and anisindione | work=Drugs.com | accessdate=22 February 2018 | url=https://www.drugs.com/drug-interactions/ampicillin-with-anisindione-196-0-210-0.html }}</ref>
Can inactivate aminglycosides by forming a complex with them. can be avoided by administering them separately instead of in combined IV container or line
<ref>{{cite web | title=Drug interactions between ampicillin and cholera vaccine, live | work=Drugs.com | accessdate=22 February 2018 | url=https://www.drugs.com/drug-interactions/ampicillin-with-cholera-vaccine-live-196-0-3772-0.html }}</ref>
Can lower immunological response to live cholera vaccine enough to prevent if from being effective
<ref>{{cite web | title=Drug interactions between ampicillin and Folex PFS | work=Drugs.com | accessdate=22 February 2018 | url=https://www.drugs.com/drug-interactions/ampicillin-with-folex-pfs-196-0-1590-3015.html }}</ref>
Large doses of penicillins can elevate serum concentrations of methotrexate (inhibit renal tubular secretion)0
<ref>{{cite web | title=Drug interactions between ampicillin and typhoid vaccine, live | work=Drugs.com | accessdate=22 February 2018 | url=https://www.drugs.com/drug-interactions/ampicillin-with-typhoid-vaccine-live-196-0-2271-0.html?professional=1 }}</ref>
Typhoid vaccine (same interaction as cholera vaccine)
Esp. bc amp is used to treat Salmonella, and typhoid vax is vs, Salmonella typhi (so can't mount an immune response)
Boothe, Dawn. "Penicillins". Merck Veterinary Manual. Retrieved 22 August 2017.
copy
<ref>{{cite web | last=Boothe | first=Dawn | title=Penicillins | work=Merck Veterinary Manual | accessdate=22 August 2017 | url=http://www.merckvetmanual.com/pharmacology/antibacterial-agents/penicillins }}</ref>
Broad-spectrum, semisynth
Destroyed by beta-lactamase
Aminopenicillin (amoxicillin is also)
Susceptible genera include Staph, Strept, Trueperella, Clostridium, Eschericia, Klebsiella, Shigella, Salmonella, Proteus, Pasteurella
Sulbactam given w/ampicilin to protext agasint beta-lactamase
<ref>{{cite book | last=Eghianruwa | first=Kingsley | title=Essential Drug Data for Rational Therapy in Veterinary Practice | year=2014 | url=https://books.google.com/books?id=CtfIAgAAQBAJ&pg=PA26 | pages=26–27 | publisher=AuthorHouse | isbn=978-1-4918-0010-2 | ref=harv }}</ref>
aka aminobenzylpenicillin
Inhibits transpeptidase enzyme, blocking synth of peptidoglycan
Can go intra mammary in animals
Well-absorbed from GI tract
Bioavailability: 62% (plus-minus 17%) in humans
Distribution: through most tissues, concentrated in liver and kidneys
In CSF only when meninges are inflamed, and then at 5–10%
15–20% plasma protein binding (lower in neonates)
Small portion is metabolized by hydrolysis to inactive penicilloic acid
Half-life
1.3 +/- 0.2 hours in humans
Higher w/uremia or hepatic cirrhosis, or in neonates
12 hours in animals
Side effects
10%: skin rash, diarrhea, vomiting
rare: Severe abdominal cramp, encephalopathy, seizure, lymphocytic leukemia
<ref>{{cite book | last1=Giguère | first1=S. | last2=Prescott | first2=John F. | last3=Dowling | first3=Patricia M. | title=Antimicrobial Therapy in Veterinary Medicine | year=2013 | url=https://books.google.com/books?id=ybA2AAAAQBAJ&pg=RA2-PT166 | pages=167–170 | publisher=John Wiley & Sons | isbn=978-1-118-67507-6 | ref=harv }}</ref>
1/2 systemic availability of amoxicillin (20–40% vs. 60–70%)
Hetacillin and pivampicillin are ampicillin esters developed to increase systemic availability
Forms
Sodium salt
Trihydrate salts (less soluble and thus absorbed less intestinally, but ok in aq preparations for inj)
Aq forms reconstituted are unstable after several hours
Inj forms should be given within 6 hour intervals (bc short half-life) to maintain
Toxicities/adverse effects
Don't give to small rodents or rabbis bc can produce clostridial colitis (C. dif; in rabbits, C. spiroforme)
Uses
Cattle, sheep, and goats, oral ampicillin has been used to treat E. coli and Salmonella (but resistance more common so now not as effective)
Bovine respiratory disease (but no advantage over penicillin G)
Don't use much in horses bc don't have much advantage over benzyl penicilins, largely due to acquired resistance in G- bact
For mixed aerobic-anaerobic infections, such as from cat bites
Canine urinary tract infections (over 90% of S. aureus, streptococci, and P. mirabilis, almost 90% of E. coli, and 65% of Klebsiella are susceptible to ampicillin at concentrations used to treat UTIs)
Oral in poultry to prevent or treat salmonellosis, E. coli sepsis, S. aureus sepsis
<ref>{{cite book | last=Hauser | first=Alan R. | title=Antibiotic Basics for Clinicians: The ABCs of Choosing the Right Antibacterial Agent | year=2012 | url=https://books.google.com/books?id=17pMk0v3_bYC&pg=PA25 | page=25 | publisher=Lippincott Williams & Wilkins | isbn=978-1-4511-1221-4 | ref=harv }}</ref>
Additional amino group in side chains of ampicillin and amoxicillin make them more hydrophilic and lets them enter porins of outer membranes of some G– rods (ex. E. coli, P. mirabilis. S. enterica, Shigella)
Powder reconstituted with sterile water or bacteriostatic water
Lasts longest with reconstituted with sterile water, saline, or LRS (8 hours in fridge, 24hrs - 72 hours in fridge depending on choice of reconstitution and concentration, with low concentration lasting longer)
Sterile water: 48–72 hours
Saline: 24–48 hours
LRS: 24 hours
Can also be reconstituted in 5% dextrose, but stable for only 1 or two hours (in or out of fridge)
<ref>{{cite book | last=Papich | first=Mark G. | title=Saunders Handbook of Veterinary Drugs: Small and Large Animal | year=2015 | url=https://books.google.com/books?id=ip8_CwAAQBAJ&pg=PA43 | pages=43–47 | publisher=Elsevier Health Sciences | isbn=978-0-323-24485-5 | ref=harv }}</ref>
Narrow spectrum, similar to that of amoxicillin
Streptococci, non-beta-lactamase producing staphpylococci, other gram +
Many staphylococci resistant due to beta-lactamase production
Most enteric gram- bacilli of Enterobacteriaceae are resistant
<ref>{{cite book | last1=Rello | first1=Jordi | last2=Kollef | first2=Martin H. | last3=Díaz | first3=Emilio | last4=Rodríguez | first4=Alejandro | title=Infectious Diseases in Critical Care | year=2010 | url=https://books.google.com/books?id=wysQmU5bYAAC&pg=PA172 | pages=172 | publisher=Springer Science & Business Media | isbn=978-3-540-34406-3 | ref=harv }}</ref>
Poorly bound penicillins like amp cross placental barrier better
Get concentration in amniotic fluid that is 0.5–1 times that of in maternal plasma; can lead to high concentration of drug in newborn
bc increased blood volume and renal clearance, ampicillin concentrations can be reduced by up to 50% in pregnant women, so need higher doses for same abx effect
No evidence of embryotoxic, fetotoxic, or teratogenic effects
<ref>{{cite web | last=US National Library of Medicine | title=AMPICILLIN- ampicillin injection, powder, for suspension | work=DailyMed | accessdate=21 August 2017 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=af6eb56d-698f-43aa-bb3b-a0a69732a7ae }}</ref>
[Vet version]
Pharmacology
Peak serum levels in cats and dogs in 30 min. after SQ or IM injections; 1-2 hours in cattle after IM injections
Uses
Upper resp infections, tonsilitis, and bronchopneumonia by hemolytic streptococci, S. aureus, E. coli, P. mirabilis, Pasteurella
UTIs due to P. mirabilis, E. coli, Staph, hemolytic streptococci, Enterococcus
GI inf due to Enterococc, Staph, E. coli
Abscesses, pustular dermatitis, cellulitis, anal gland infections due to E. coli, P. mirabilis, hemolytic strept, Staph, Pasteurella
<ref>{{cite web | last=US National Library of Medicine | title=AMPICILLIN- ampicillin sodium injection, powder, for solution | work=DailyMed | accessdate=21 August 2017 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0642ef5e-7eff-4117-a0df-4bd15d7b7d63 }}</ref>
Pharmacology
Into CSF and brain only when meninges are inflamed
Excreted largely unchanged in urine; can be delayed if also getting probenecid at same time
Active form more in bile than in serum
Is least serum-bound of all the penicillins (average of 20% vs. 60–90%)
Well-tolerated by most patients
Use
Resp tract infections by: S. pneumoniae, S. aureus, H. influenzae, Group A beta-hemolytic streptococci
Meningitis by: E. coli, Group B streptococci, other Gram - (ex. Listeria monocytogenes, N. meningitidis)
Add aminolgycoside for more effectiveness vs. Gram-
Septicemia and endocarditis by Streptococcus, susc. Staphylococcus, enterococci
Gram- sepsis by E. coli, Proteus mirabilis, Salmonella
Endocarditis by enterococcal strains
Add aminoglycoside for better effectiveness vs. streptococcal endocarditis
UTIs by: E. coli and P. mirabilis
GI infections by: Salmonella (inc. typhoid fever)
Contraindications: hypersensitivity to any penicillin (can → fatal anaphylactoid reactions; more common in parenteral therapy, though also happens w/oral admin)
Warnings
C. diff diarrhea (from mild diarrhea to fatal colitis)
43–100% of pts w/mononucleosis get skin rash w/apmicillin (7 to 10 days after oral amp is started; goes away a few days to a week after ended)
Usually maculopapular, pruritic, and generalized
Interactions:
Transient elevation of transaminase in serum after ampicillin
Skin rashes more common if given w/allopurinol
High concentrations of ampicillin: false positive for glucose reaction tests
Side effects
More likely in those w/sensitivity to penicillins and those w/history of allergy, asthma, hay fever, or hives
GI (most often w/oral form): glossitis, stomatitis, black "hairy" tongue, nausea, vomiting, entercolitis, pseudomembraneous colitis, diarrhea
Hypersens.
Frequent: skin rashes and hives
Some: exfoliative dermatitis and erythema multiforme
Liver: moderate rise in serum glutamic oxaloacetic transaminase (esp. in infants)
Hemic/lymphatic: anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, agranylocytis (all reversible and thought to be caused by hypersens.)
<ref>{{cite web | last=WebMD | title=Principen (ampicillin) Drug Side Effects, Interactions, and Medication Information | work=eMedicineHealth | accessdate=23 February 2018 | url=https://www.emedicinehealth.com/drug-ampicillin/article_em.htm }}</ref>
Overdose inc. behavioral changes, confusion, black outs, convulsions
<ref>{{cite book | last1=Weiner | first1=Carl P. | last2=Rope | first2=Kate | title=The Complete Guide to Medications During Pregnancy and Breastfeeding: Everything You Need to Know to Make the Best Choices for You and Your Baby | year=2013 | url=https://books.google.com/books?id=apoTV0TZHRQC&pg=PT47 | pages=47–49 | publisher=St. Martin's Press | isbn=978-1-250-03720-6 | ref=harv }}</ref>
One of most commonly used drugs in pregnancy
Reduces risk of post-op fever in c-section
Pregnancy increases clearance
Ampicillin/sulbactam prolongs period of time btw water breaking to delivery in women where water breaks before 37 weeks
No evidence of birth defects in humans or rodents
Some amounts (minimal) secreted in breast milk; considered OK
{{cite book | publisher = Lippincott Williams & Wilkins | isbn = 978-1-58255-455-6 | title = Portable Pathophysiology | date = 28 January 2006 | url=https://books.google.com/books?id=w7O9c78uQU0C&pg=PA262}}
Antiemetics decrease nausea → reduce urge to vomit (262)
Antihistamines
Block dopamine receptors in "chemoreceptor trigger zone of brain"/may "directly depress vomiting center"
For severe nausea and vomiting
Used for chemo or radiotherapy
Serotonin-receptor antagonists
ex. Dolasteron, ganisteron, ondansetron
Block serotonin receptors in "chemoreceptor trigger zone" and vagal nerve terminals (so work in both CNS and peripheral nervous system)
Used for chemo or radiotherapy
Diemunsch, Pierre; Grélot, Laurent (2003). "Potential of Substances P Antagonists as Antiemetics". In Donnerer, Josef (ed.). Antiemetic Therapy. Karger Medical and Scientific Publishers. pp. 78–97. ISBN978-3-8055-7547-8.
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{{cite book | publisher = Karger Medical and Scientific Publishers | isbn = 978-3-8055-7547-8 | pages = 78–97| editor1-last = Donnerer| editor1-first = Josef | last1 = Diemunsch| first1 = Pierre| last2 = Grélot| first2 = Laurent | title = Antiemetic Therapy | chapter = Potential of Substances P Antagonists as Antiemetics | date = 2003 | url=https://books.google.com/books?id=CmK8jEjUujIC&pg=PA79}}
Triggers for vomiting (79)
"Emetic coordinating circuitry" is in medulla oblongata
Area postrema though to have chemoreceptor for triggering vomiting
5-HT3 receptor antagonists fail against emetogens like opioid or dopaminergic agonists, copper sulfate, or motion (80)
(continue)
Gralla, Richard J.; Osoba, David; Kris, Mark G.; Kirkbride, Peter; Hesketh, Paul J.; Chinnery, Lawrence W.; Clark-Snow, Rebecca; Gill, David P.; Groshen, Susan; Grunberg, Steven; Koeller, James M.; Morrow, Gary R.; Perez, Edith A.; Silber, Jeffrey H.; Pfister, David G. (1 August 1999). "Recommendations for the Use of Antiemetics: Evidence-Based, Clinical Practice Guidelines". Journal of Clinical Oncology. 17 (9): 2971–2971. ISSN0732-183X. PMID10561376. Retrieved 2015-10-08.
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{{cite journal | issn = 0732-183X | volume = 17 | issue = 9 | pages = 2971–2971| last1 = Gralla| first1 = Richard J.| last2 = Osoba| first2 = David| last3 = Kris| first3 = Mark G.| last4 = Kirkbride| first4 = Peter| last5 = Hesketh| first5 = Paul J.| last6 = Chinnery| first6 = Lawrence W.| last7 = Clark-Snow| first7 = Rebecca| last8 = Gill| first8 = David P.| last9 = Groshen| first9 = Susan| last10 = Grunberg| first10 = Steven| last11 = Koeller| first11 = James M.| last12 = Morrow| first12 = Gary R.| last13 = Perez| first13 = Edith A.| last14 = Silber| first14 = Jeffrey H.| last15 = Pfister| first15 = David G. | title = Recommendations for the Use of Antiemetics: Evidence-Based, Clinical Practice Guidelines | journal = Journal of Clinical Oncology | accessdate = 2015-10-08 | date = 1 August 1999 | url = http://jco.ascopubs.org/content/17/9/2971 | pmid = 10561376}}
<ref name=camello>{{cite web | publisher = Camello Safari | title = The amazing characteristics of the camels | aaccessdate = 26 November 2012 | url = http://www.camellosafari.com/?page_id=251 }}</ref>
"A fully-grown adult camel stands 1.85m/6 feet at the shoulder and 2.15m/7 feet at the hump."
Meat
Delicacy in Arabian diet
Tastes like beef
Tough to chew
Milk
More nutritious than cow milk
Lower in fat and lactose, higher in potassium, iron, and Vit. C
Mukasa-Mugerwa, E. (1981). The Camel (Camelus Dromedarius): A Bibliographical Review. International Livestock Centre for Africa Monograph. Vol. 5. Ethiopia: International Livestock Centre for Africa.
copy
<ref name=mukasa81>{{cite book | publisher = International Livestock Centre for Africa | volume = 5 | last = Mukasa-Mugerwa | first = E. | title = The Camel (Camelus Dromedarius): A Bibliographical Review | location = Ethiopia | series = International Livestock Centre for Africa Monograph | year = 1981 }}</ref>
Origins and Distribution p. 1–10
Genus Camelus has 2 species: dromedary (C. dromedarius) and Bactrian (C. bactrianus)
Origin traced to Protylopus (1)
Was in N. America in Eocene (1)
Camelidae disappeared from N. America (unknown why)
Camelidae Migrated across Bering Straits to Asia (late Pliocene/early Glacial epochs" (1)
Camels and llama evolved over 1mya from common N. American ancestor
Dromadary evolved from 2-humped version
Domesticated Bactrian earlier than 2500 BC
Domesticated dromedary around 3000 BC in s. Arabia (3)
Somalia
Has largest herd in world
Sudan
2nd largest in world – almost 3 million
Reproductive Performance p. 11–32 [DROMEDARY]
Anatomy
Male
Testes look similar to that of horse (11)
Right testicle is often a bit smaller than left one (11)
Diameter of seminiferous tubules smallest in summer and largest in winter (12)
Breeding season: larger testes, more spermatogenesis (12)
Has prostate gland, no seminal vesicles (12)
Point of penile sheath points posteriorly, so when camels pee, urine goes backwards (13)
Large casing: non-erect penis is hidden inside (like horse) (13)
Average length of camel penis is 60cm (13)
Female
Reproductive tract is like that of a horse (13)
Size and weights of gonads vary with ovarian activiy (14)
Gonads = "Fairly flattened with numerous ovisacs, giving them the appearance of a bunch of grapes (14)
Left ovary's Graffian follicles usually slightly larger than those of the right (14)
Follicular activity decreases when get farther into pregnancy (14)
More ovulation from left ovary than right
Ovulation needs copulation to occur (15) ("induced ovulator")
Castration
Domestic males not reserved for breeding often castrated (18)
Camels become more maneagable
Mating
From behind (20)
Single mating session → ejaculate 3 or 4 times (21)
Production and Utilization 59–80
Camel slaughter for meat: Kenya, Ethiopia, Sudan, Somalia (65)
Average carcass weight: 300–400 kg for dromedary male, 250–300 kg for dromedary female, 650 kg (estimate) for Bactrian male (67)
Best time for meat is 2.5 years: as get older, meat → tougher and less tasty (68)
<ref note=bigfacts>{{Cite web | title = How Fast Can Camels Run and How Long Can They Run For? | work = Big Site of Amazing Facts | accessdate = 29 November 2012 | url = http://www.bigsiteofamazingfacts.com/how-fast-can-camels-run-and-how-long-can-they-run-for/ }}</ref>
Start of race: 40mph
Pace slows; average speed of racing camel is 25mph
<ref name=netindustries>{{cite web | publisher = Net Industries | title = Camels - Old World Camels | work = Science Encyclopedia | accessdate = 29 November 2012 | url = http://science.jrank.org/pages/1151/Camels-Old-world-camels.html }}</ref>
Bactrian named after Baktria region of Persia
Can carry twice as much in weight as dromedary camels can
Can carry up to 1000 lbs
Racing (dromedary) camels can run up to 100mi in a day
1- and 2-humped camels can interbreed
Child has 2 humps, called "tulu"
Has 3rd eyelid (transparent) that dislodges sand from eye
<ref name=fahmy02>{{cite web|title='Cama' camel/llama hybrids born in UAE research centre|url=http://www.royalsociety.org.nz/2002/03/21/emirates-cama/|first=Miral|last=Fahmy|date=21 March 2002|accessdate=28 November 2012|work=Science in the News|publisher=The Royal Society of New Zealand}}</ref>
In UAE
Rama, male born 1998
Kamilah, female, born February 2002
Camels and llamas don't mate in wild, but have same number of chromosomes
Camelids only ovulate in intercourse, so have to inject female llamas with gonadotorphin to start ovulation
Then inseminate llama with "fresh camel semen" collected with artifical vagina
<ref name=metrouk>{{cite web | title = Joy for world’s first camel and llama cross | work = Metro UK | accessdate = 29 November 2012 | url = http://www.metro.co.uk/news/136134-joy-for-world-s-first-camel-and-llama-cross |date=6 April 2008}}<ref>
Camas:
No hump
Llama coat
Ears are 1/2-way in length btw camel's and llamas
"Strong, desert-ready legs of a camel"
Partially cloven feet (like mix of camel's foot pad and llama's cloven feet)
<ref name=potts>{{cite journal|url=http://www.silkroadfoundation.org/newsletter/vol3num1/7_bactrian.php|title=Bactrian Camels and Bactrian-Dromedary Hybrids|last=Potts|first=Danel|journal=Silkroad|volume=3|issue=1}}</ref>
Hybrids of dromedary and Bactrian have one hump, but is asymmetrical and has indentation (4–12cm deep) dividing back from front
Or can look flat
Animal is 2.32m tall at hump; 2.15m tall at shoulder
Legs are long
Weight average is 650kg
Can carry ~400–450kg, more than dromedary or Bactrian
"Indeed Herodotus says that camels carried provisions for the advancing Persians, marvelling that Xerxes' camel train was attacked by lions while marching between Acanthus and Therma, even though the lions had never seen that beast before, nor had any experience of it. We do not know whether these were dromedaries, like those used by Cyrus against Croesus of Lydia."
<ref name=junglestore>{{cite web | title = Fun facts about the Camel | work = The Jungle Store | accessdate = 3 December 2012 | url = http://www.thejunglestore.com/Camels }}</ref>
"A camel's poop is so dry you can use it immediately to start a fire"
Camels sometimes cluster to keep cool - when body temp is lower than env temp
3rd eyelid moves sideways like windshield wiper
Can still see if that eyelid is closed, so can travel in sandstorms
Nose traps moisture from exhalations
Normally herbivore, but becomes omnivore when food is scarce (will eat owners' tents)
Drink brackish water
Sharp teeth
Camel can be fully trained and be able to carry full load by age 5
"Kidneys and Concentrated Urine". Temperature and Water Relations in Dromedary Camels (Camelus dromedarius). Davidson College. {{cite web}}: |access-date= requires |url= (help); Italic or bold markup not allowed in: |work= (help); Missing or empty |url= (help)
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<ref name=davidson-kidney>{{cite web | publisher = Davidson College | title = Kidneys and Concentrated Urine | work = Temperature and Water Relations in Dromedary Camels (''Camelus dromedarius'')|accessdate=3 December 2012}}</ref>
"A concentrated urine with a syrupy consistency was noted to change to a watery and colorless urine after only a short time of drinking"
Bernstein, William J. (6 May 2009). A Splendid Exchange: How Trade Shaped the World. Grove Press. pp. 54–55. ISBN9780802144164.
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<ref name=bernstein09>{{cite book | publisher = Grove Press | isbn = 9780802144164 | last = Bernstein | first = William J. | title = A Splendid Exchange: How Trade Shaped the World | date = 6 May 2009 |pages=54–55 }}</ref>
p. 54
Protolypus of N. America around size of rabbit
Beginning of Pleistocene (3mya), Isthmus of Panama formed and Protolypus migrated to S. America
p. 55
Camel gained water-storing abilities in Arabia
Harington, C. R. (June 1997). "Ice Age Yukon and Alaskan Camels". Yukon Beringia Interpretive Centre. Government of Yukon, Department of Tourism and Culture, Museums Unit. Retrieved 3 December 2012.
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<ref name=harington97>{{cite web | last = Harington | first = C. R. | title = Ice Age Yukon and Alaskan Camels | work = Yukon Beringia Interpretive Centre | accessdate = 3 December 2012 | date = June 1997 | url = http://www.beringia.com/research/camels.html | publisher=Government of Yukon, Department of Tourism and Culture, Museums Unit}}</ref>
Protylopus common in open woodlands of what is now S. Dakota (earliest known camelids, 24–25 mya)
Early Pliocone (~5mya), spread to S. America and Old World (Bering Isthmus)
S. America line → llamas, etc.
North Dakota Industrial Commission Department of Mineral Resources. "Poebrotherium" (Document). North Dakota State Government. {{cite document}}: Unknown parameter |accessdate= ignored (help); Unknown parameter |url= ignored (help)
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<ref name=northdakota>{{cite document | publisher = North Dakota State Government | author = North Dakota Industrial Commission Department of Mineral Resources | title = Poebrotherium | url = https://www.dmr.nd.gov/ndfossil/poster/PDF/Poebrotherium.pdf | accessdate= 3 December 2012}}</ref>
Poebrotherium was early camel in open-woodland area of N. Dakota, ~30mya
<ref name=scibuzz04>{{cite web | publisher = Science Museum of Minnesota | title = Fossil camel skull (Poebrotherium sp.) | work = Science Buzz | accessdate = 3 December 2012 |date=January 2004 | url = http://www.sciencebuzz.org/museum/object/2004_01_fossil_camel_skull_poebrotherium }}</ref>
~35mya fossil
Similar chars to camels: teeth, limbs
Prob. look more like llamas than camels (no evidence of humps)
Kindersley, Dorling (2 June 2008). "Camels". Encyclopedia of Dinosaurs and Prehistoric Life. Penguin. pp. 266–7. ISBN9780756682415.
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<ref name=kindersley08>{{cite encyclopedia | publisher = Penguin | isbn = 9780756682415 | last = Kindersley | first = Dorling | encyclopedia = Encyclopedia of Dinosaurs and Prehistoric Life |title=Camels |pages=266–7 | date = 2 June 2008 }}</ref>
Aepycamelus: 2m tall at shoulder, ate leaves from trees
Open woodland/grassland with trees
N. America in Miocene
"High camel"
Long leg and neck bones
Like camels, had (probably): divided upper lip, long and curved neck, two-towed feet
Stenomylus from Oligocene (~30mya), small early camel with huge teeth
Pointed hooves and walked on tippytoes
Singh; Tomar. Evolutionary Biology (8th revised ed.). New Delhi: Rastogi Publications. p. 334. ISBN9788171336395.
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<ref name=singh-tomar>{{cite book | edition = 8th revised | publisher = Rastogi Publications | isbn = 9788171336395 | author1 = Singh | author2 = Tomar | title = Evolutionary Biology | location = New Delhi |page=334}}</ref>
In upper Miocene/lower Pliocene, Procamelus → main ancestor of modern camel
Main divergence had begun in Oligocene
Worboys, Graeme L.; Francis, Wendy L.; Lockwood, Michael (30 March 2010). Connectivity Conservation Management: A Global Guide. Earthscan. p. 142. ISBN9781844076048.
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<ref name=worboys10>{{cite book | publisher = Earthscan | isbn = 9781844076048 | last = Worboys | first = Graeme L. | first2 = Wendy L.|last2= Francis|first3= Michael |last3=Lockwood | title = Connectivity Conservation Management: A Global Guide | date = 30 March 2010 |page=142}}</ref>
End of Pleistocene: evidence that early Native Americans hunted N. American mega fauna: Camelops hesternus, mammoths (Mammuthus imperator), mastodon (Mammut americanum), horses (dinohippus sp.)
Some also claim N. American overhunting → these species' extinction, but has been disputed
MacPhee, Ross D. E.; Sues, Hans-Dieter (30 June 1999). Extinctions in Near Time: Causes, Contexts, and Consequences. Springer. pp. 18, 20, 26. ISBN9780306460920.
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<ref name=macphee99>{{cite book | publisher = Springer | isbn = 9780306460920 | last1 = MacPhee | first1 = Ross D. E. | first2 = Hans-Dieter |last2=Sues | title = Extinctions in Near Time: Causes, Contexts, and Consequences | date = 30 June 1999 |pages=18, 20, 26}}</ref>
p. 18
FC: "First contact" with humans
p. 20
N. America extinctions: Camelops hestrnus, mammoth, mastodon, horse, ground sloth, saber-tooth, short-faced bear
12,000 to 10,000 years ago
p. 26
N. America: FC → megafauna extinctions
Fedewa, Jennifer L. (2000). "Camelus bactrianus". Animal Diversity Web. University of Michigan Museum of Zoology. Retrieved 4 December 2012.
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<ref name=fedewa00>{{cite web | last = Fedewa | first = Jennifer L. | title = Camelus bactrianus | work = Animal Diversity Web | accessdate = 4 December 2012 | year = 2000 | url = http://animaldiversity.ummz.umich.edu/accounts/Camelus_bactrianus/ |publisher=University of Michigan Museum of Zoology}}</ref>
Almost all camels are now domestic
Carry packages, transportation
Can take vocal commands from age 1
Humans use camel meat and milk
Fat from humps is melted and served in cooking
Poop is uses as fuel for heating
Loose hair → clothes, blankets, carpets, tents
Tanned hide → shoes, sandals, other leather stuff
Some countries: camels show wealth
When hungry, camels can eat people's tents, sandals, or blanks
<ref name=sandiegozoo>{{cite web | publisher = San Diego Zoo Global Library | title = Bactrian & Dromedary Camels | work = Factsheets | accessdate = 4 December 2012 | date = March 2009| url = http://library.sandiegozoo.org/factsheets/camel/camel.htm }}</ref>
Domestication ~4000–2000 BC
Wild camels, not domestic, can drink salt water slush if no fresh water available
Domestic camels maintained in semi-wild state: watered by man, but get food from wild vegetation
If unguarded, will still return to a familiar well
Wild camels are super shy and can spot danger from 2–3 miles away
Integral part of nomad culture
Females can produce milk several years after birth
<ref name=walker09>{{cite news | last = Walker | first = Matt | title = Wild camels 'genetically unique' | newspaper =Earth News |publisher=BBC| accessdate = 4 December 2012 | date = 22 July 2009 | url = http://news.bbc.co.uk/earth/hi/earth_news/newsid_8151000/8151804.stm }}</ref>
Few hundred wild Bactrians remain, and are distinct from domestic ones
Bactrians are last remaining wild camels
Bulliet, Richard W.; Crossley, Pamela Kyle; Headrick, Daniel R.; Hirsch, Steven W.; Johnson, Lyman L. (1 January 2010). The Earth and Its Peoples: A Global History: To 1550. Cengage Learning. p. 220. ISBN9781439084748.
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<ref name=bulliet10>{{cite book | publisher = Cengage Learning | isbn = 9781439084748 | last1 = Bulliet | first1 = Richard W. | first2 = Pamela Kyle |last2= Crossley|first3= Daniel R.|last3= Headrick|first4= Steven W. |last4=Hirsch|first5=Lyman L.|last5= Johnson | title = The Earth and Its Peoples: A Global History: To 1550 | date = 1 January 2010 |page=220}}</ref>
S. Arabian saddle: good for riding
Baggage can be tied to wooden arches at front
Militarily inefficient: rider kneels on cushion behind hump, so hard to hold weapons
North Arabian saddle
1st centuries BC
Solid wooden frame, can attach loads
Warriors had solid loads and height advtg.s
s. Sahara saddles
Lightest and most efficient
Sahara trade → camel domestication
Bulliet, Richard W. (1975). The Camel and the Wheel. Columbia University Press. pp. 23, 25, 28, 35–36, 38–40. ISBN9780231072359.
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<ref name=bulliet75>{{cite book | publisher = Columbia University Press | isbn = 9780231072359 | last = Bulliet | first = Richard W. | title = The Camel and the Wheel | year = 1975 |pages=23, 25, 28, 35–36, 38–40}}</ref>
p. 23
Camel > ox + wagon transport because:
Can carry/draw twice as much
Faster and can cover more ground
20–25 mi in one stretch
More journeys per year and per lifetime
Live and work 4x as long
Can survive for stretches without food/water
Tenacity/endurance
Can cover ground a wagon would stick in
Can cross shallow rivers where would have to unload wagon
Wagon liable to breaking down
Wagon adds on a dead weight
p. 25
Wagon: 1 person per 2 animals
Camel: 1 person per string of 3–6 camels
Chariot had been main military transport
In 700s BC, started to be overtaken by cavalry (on camels) as main force of Assyria
Increased camel traffic → decreased road maintenance in that area
p. 28
1st rabbit-sized ancestor of camel
p. 35–36
Camel domestication in book of Genesis
Abraham got bribes from Egypt Pharaoh to have Sarah in haram: sheep, oxen, asses, camels
W. F. Albright: scholar of Biblical history and Palestinian archaeology
Mentions of camels in Abraham period: priests tampering with earlier texts
Wanted to make it fit in more with social conditions
Semites of Abraham time herded sheep, goats, and donkeys; not camels
p. 38–40
Somalia has ~4 million camels
Horn of Africa: "one of the largest and most abundant camel territories in the word"
Somalis, unlike other camel people, never ride their camels (said it made them easy targets)
Milk was dietary staple, esp. in wet seasons
Don't really use camels to carry shit
Gabriel, Richard A. (2007). Soldiers' Lives Through History: The Ancient World. Greenwood Publishing Group. p. xvi. ISBN9780313333484.
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<ref name=gabriel07>{{cite book | publisher = Greenwood Publishing Group | isbn = 9780313333484 | last = Gabriel | first = Richard A. | title = Soldiers' Lives Through History: The Ancient World | year = 2007 |page=xvi }}</ref>
853 BC: Battle of Qarqar, first use of camel cavalry (by Gingibu the Arab)
<ref name=bhatia12>{{cite news | last = Bhatia | first = Vimal | title = BSF to ditch camels to ride sand scooters | work = The Times of India | accessdate = 4 December 2012 | date = 23 July 2012 | url = http://timesofindia.indiatimes.com/india/BSF-to-ditch-camels-to-ride-sand-scooters/articleshow/15099086.cms }}</ref>
...They have camels
Gann, Lewis Henry; Duignan, Peter (1972). Africa and the World: An Introduction to the History of Sub-Saharan Africa from Antiquity to 1840. University Press of America. ISBN9780761815204.
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<ref name=gann72>{{cite book | publisher = University Press of America | isbn = 9780761815204 | last1 = Gann | first1 = Lewis Henry | first2 = Peter |last2=Duignan | title = Africa and the World: An Introduction to the History of Sub-Saharan Africa from Antiquity to 1840 | year = 1972 |page=156|quote=The camel was acclimatized in Egypt long before the time of Christ and was subsequently adopted by the Berbers of the desert, who used camel cavalry to fight the Romans. The Berbers spread the use of the camel across the Sahara.}}</ref>
"The camel was acclimatized in Egypt long before the time of Christ and was subsequently adopted by the Berbers of the desert, who used camel cavalry to fight the Romans. The Berbers spread the use of the camel across the Sahara."
Southern, Pat (1 October 2007). The Roman Army: A Social and Institutional History. Oxford University Press. p. 123. ISBN9780195328783.
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<ref name=southern07>{{cite book | publisher = Oxford University Press | isbn = 9780195328783 | last = Southern | first = Pat | title = The Roman Army: A Social and Institutional History | date = 1 October 2007 |page=123 }}</ref>
Camel Riders (Dromedarii) [in TOC, listed under auxiliary units]
Eastern provinces: Roman army unites often had some camel riders
Btw. 32 and 36 dromedarii listed in an early roster
A 1000-camel unit, ala I Ulpia adromedariorum milliaria was raised by Trajan and stationed in Syria
No consistency in whether organized as infantry or cavalry – depended on province
<ref name=fleming09>{{cite news | issn = 0161-7370 | volume = 74 | issue = 8 | publisher = Bonnier Corporation | first = Walter L. |last= Fleming | title = Jefferson Davis's Camel Experiment | work = The Popular Science Monthly | date = February 1909 |page=150 |url=http://books.google.com/books?id=DyADAAAAMBAJ&pg=PA150 | quote = Other trials of the camel were made in 1859 by Major D. H. Vinton, who used twenty-four of them in carrying burdens for a surveying party...All in all, he concluded, the camel was much superior to the mule.}}</ref>
"Other trials of the camel were made in 1859 by Major D. H. Vinton, who used twenty-four of them in carrying burdens for a surveying party...All in all, he concluded, the camel was much superior to the mule."
<ref name=mantz06>{{cite book | publisher = Heritage House Publishing Co | isbn = 9781894384018 | pages = 51–54 | editor-first = Garnet | editor-last= Basque | last = Mantz | first = John | title = Frontier Days in British Columbia | chapter = Camels in the Cariboo | date = 20 April 2006 |url=http://books.google.com/books?id=fecJGyNKtwoC&pg=PA51}}</ref>
Camels have been used by US Army
US Army Camel Corps established early 1856
70 camels shipped to Texas from Arabia
Tested them out – rode 4000 miles without incident
US Secretary of War recommended in 1858 that funds → 1000 more camels
Recommendation repeated twice after, but Congress didn't grant it bc worried about upcoming Civil War
Camels stationed at Camp Verde near San Antonio, Texas
Western terminal of Camel Corps was Fort Tejon, near present-day Bakersfield, California
Lt. Beale: one good camel worth 4 army mules
Could carry more than 5 times normal mule load
Bought dromedaries and Bactrians
"The outbreak of the American Civil War doomed the U.S. Army Camel Corps"
Texas → Confederacy
Most camels just wandered away into the desert
Some dude from Cariboo bought 25 → gold rush in Canada
Nicolle, David (26 March 1991). The Desert Frontier. Rome's Enemies. Vol. 5 (illustrated, reprint ed.). Osprey Publishing. p. 4. ISBN9781855321663.
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<ref name=nicolle91>{{cite book | edition = illustrated, reprint | publisher = Osprey Publishing | isbn = 9781855321663 | volume = 5 | last = Nicolle | first = David | title = The Desert Frontier | series = Rome's Enemies | date = 26 March 1991 |page=4 |quote=Nevertheless the military prowess of desert peoples impressed the Romans, who recruited large numbers as auxiliary cavalry and archers. In addition to providing the Roman Army with its best archers, the Easterners (largely Arabs but generally known as 'Syrians') served as Rome's most effective ''dromedarii'' or camel-mounted troops.}}</ref>
"Nevertheless the military prowess of desert peoples impressed the Romans, who recruited large numbers as auxiliary cavalry and archers. In addition to providing the Roman Army with its best archers, the Easterners (largely Arabs but generally known as 'Syrians') served as Rome's most effective dromedarii or camel-mounted troops." (4)
<ref name=herodotus>{{cite book | author = Herodotus | title = The History of Herodotus | accessdate = 4 December 2012 | date = 440 BC | url = http://classics.mit.edu/Herodotus/history.html|quote=He collected together all the camels that had come in the train of his army to carry the provisions and the baggage, and taking off their loads, he mounted riders upon them accoutred as horsemen. These he commanded to advance in front of his other troops against the Lydian horse; behind them were to follow the foot soldiers, and last of all the cavalry. When his arrangements were complete, he gave his troops orders to slay all the other Lydians who came in their way without mercy, but to spare Croesus and not kill him, even if he should be seized and offer resistance. The reason why Cyrus opposed his camels to the enemy's horse was because the horse has a natural dread of the camel, and cannot abide either the sight or the smell of that animal. By this stratagem he hoped to make Croesus's horse useless to him, the horse being what he chiefly depended on for victory. The two armies then joined battle, and immediately the Lydian war-horses, seeing and smelling the camels, turned round and galloped off; and so it came to pass that all Croesus's hopes withered away.}}</ref>
"He collected together all the camels that had come in the train of his army to carry the provisions and the baggage, and taking off their loads, he mounted riders upon them accoutred as horsemen. These he commanded to advance in front of his other troops against the Lydian horse; behind them were to follow the foot soldiers, and last of all the cavalry. When his arrangements were complete, he gave his troops orders to slay all the other Lydians who came in their way without mercy, but to spare Croesus and not kill him, even if he should be seized and offer resistance. The reason why Cyrus opposed his camels to the enemy's horse was because the horse has a natural dread of the camel, and cannot abide either the sight or the smell of that animal. By this stratagem he hoped to make Croesus's horse useless to him, the horse being what he chiefly depended on for victory. The two armies then joined battle, and immediately the Lydian war-horses, seeing and smelling the camels, turned round and galloped off; and so it came to pass that all Croesus's hopes withered away."
"The Posts at Benicia". The California State Military Museum. Retrieved 4 December 2012.
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<ref name=military-museum>{{cite web | publisher = The California State Military Museum | title = The Posts at Benicia | accessdate = 4 December 2012 | url = http://www.militarymuseum.org/Benicia.html }}</ref>
"The grounds of the Benicia Arsenal are also famous for stabling the Army's one and only Camel Corps. The short-lived Camel Corps was disbanded in 1863, but the Camel Barns, built in 1855, remain and are now the Benicia Historical Museum."
Heinrich, Bernd (7 May 2002). Why We Run: A Natural History. HarperCollins. ISBN9780060958701.
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<ref name=bernd02>{{cite book | publisher = HarperCollins | isbn = 9780060958701 | last = Heinrich | first = Bernd | title = Why We Run: A Natural History | date = 7 May 2002}}</ref>
[page not shown in Google preview]
French in Egyptian Sudan in 1883 created camel corps – took part in all military ops till 1921
1900: 20,000 of 34,000 camels died from overwork and lack of proper care
Later, French employed desert nomads as camel men → méhariste
Were better with camels
Méharistes always had two camels: worked one at a time, let other rest
<ref name=guillaume12>{{cite news | last = Guillaume | first = Philippe | title = L’incroyable épopée des méharistes français |trans_title=The incredible epic of the French méharistes| newspaper = BDSphère | accessdate = 5 December 2012 | date = 16 June 2012 | url = http://www.bdsphere.fr/2012/06/16/lincroyable-epopee-des-meharistes-francais/ | lang = French}}</ref>
French colonies in Algeria
Méharistes helped with conquest in Sahara
December 1894: created Saharan troops from "spahis" and "tirailleurs"
Vehicles began replacing camels
Participated in campaigns in WWII under General Leclerc
Were disbanded at end of France's colonial possession of Algeria
Bimberg, Edward L. (January/February 2006). "Faceless Warriors of the Sahara"(PDF). Military History. Primedia Special Interest Publications. p. 27. {{cite news}}: Check date values in: |date= (help)
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<ref name=bimberg06>{{cite news | page = 27 | last = Bimberg | first = Edward L. | publisher = Primedia Special Interest Publications | title = Faceless Warriors of the Sahara | work = Military History | date = January/February 2006 |url=http://www.wwcc.wy.edu/library/pdf/Faceless%20Warriors%20of%20the%20Sahara.pdf }}</ref>
Some tirailleurs were Algerian
Spahis were native Algerian cavalrymen
Hall, Bruce S. (6 June 2011). A History of Race in Muslim West Africa, 1600-1960. Cambridge University Press. p. 143. ISBN9781107002876.
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<ref name=brucehall>{{cite book | publisher = Cambridge University Press | isbn = 9781107002876 | last = Hall | first = Bruce S. | title = A History of Race in Muslim West Africa, 1600-1960 | date = 6 June 2011 |page = 143}}</ref>
French wanted to defeat insurgents, but they rode camels and so where twice as fast
Created méhariste (on camels) colonial regiments to exercise control over dispersed Tuareg and Arab population
"Cameliers and camels at war". New Zealand History online. History Group of the New Zealand Ministry for Culture and Heritage. 30 August 2009. Retrieved 5 December 2012.
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<ref name=historygroup-nz>{{cite web | publisher = History Group of the New Zealand Ministry for Culture and Heritage | title = Cameliers and camels at war | work = New Zealand History online | accessdate = 5 December 2012 | date = 30 August 2009 | url = http://www.nzhistory.net.nz/war/camel-corps |pages=1, 2, 4, 5}}</ref>
p. 1
Imp. Camel Corps had vital roles in Sinai and Palestine campaigns
"Cameliers": soldiers of Imp. Camel Corps
Rode camels to battle, then fought on foot
p. 2
First recorded use of camels in battle: Cyrus the Great vs. Lydia at Battle of Thymbra in 547 BC
Sinai and Palestine campaigns in WWI
Imp. CC formed in Jan 1916 to help with fighting Senussi (Islamist movements supported by many Arab and Berber tribes on Libya–Egypt border)
p. 4
After July 1918, began to become run down, got no new reinforcements
Disbanded in 1919
p. 5
First Imperial Camel Corps used Bikanir camels from India
Later, got lighter Egyptian camels for mounts (Bikanirs still used for carrying supplies + heavy equip)
Only used un-neutered male camels (in accordance with local Egyptian practice)
This often made them hard to control
p. 6
In brigade-level structure
Woodward, David R. (2006). Hell in the Holy Land: World War I in the Middle East. University Press of Kentucky. ISBN9780813123837.
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<ref name=woodward06>{{cite book | publisher = University Press of Kentucky | isbn = 9780813123837 | last = Woodward | first = David R. | title = Hell in the Holy Land: World War I in the Middle East | year = 2006 | pages=36, 39, 43, 56, 133}}</ref>
p. 36
British employed/created → Egyptian Labour Corps (ELC) -gave rise to→ Camel Transport Corps (CTC)
→ Essential in war against Turks
Camel drivers
Best workers from s. provinces of Egypt
Initially, 1 company in CTC: 1,168 Egyptians, 2020 camels, 20 horses
p. 39
CTC in Sinai (gave water to troops)
p. 43
Assistant director of transport for EEF (Egyptian Expeditionary Force) [245]: "Tried by extremes of heat and cold, always his own worst enemy, not accounting bravery a virtue or cowardice a crime, scourged by fever, cheerful, miserable, quarrelsome, useless, wonderful men, their name is for ever written honoris causa in the records of the War."
p. 56
A. V. Benbow of Imperial Camel Corps Brigade of the way to Gaza: "On the left a column of cavalry, in the center the Camel Corps and on the right the Transport Corps, with their loads of stores and blue-gowned camel-drivers, the Red Cross Unit with their dozens of white hooded red crossed wagons drawn by six or eight mules a piece, and all the camels, each carrying a stretcher, better known as cacolets, slung on either side of their backs."
p. 133
Army depended on CTC for water when advancing into Jerusalem
<ref murray20>{{cite book | publisher = J.M. Dent | last = Murray | first = Archibald James | title = Sir Archibald Murray's despatches (June 1916–June 1917) | year = 1920 |url=http://books.google.com/books?id=TgHIAAAAMAAJ&pg=PA123 |page=123 |quote=A great deal of the work of supplying the troops on both fronts has been done by the Camel Transport Corps}}</ref>
Camel Transport Corps did a lot of supplying of troops ("A great deal of the work of supplying the troops on both fronts has been done by the Camel Transport Corps..."
McGregor, Andrew James (30 May 2006). A Military History of Modern Egypt: From the Ottoman Conquest to the Ramadan War. Greenwood Publishing Group. ISBN9780275986018.
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<ref name=mcgregor06>{{cite book | publisher = Greenwood Publishing Group | isbn = 9780275986018 | last = McGregor | first = Andrew James | title = A Military History of Modern Egypt: From the Ottoman Conquest to the Ramadan War | date = 30 May 2006 |page=215 }}</ref>
p. 215
"Much of the success of the British campaign in Palestine and Syria can be credited to the performance of the Camel Transport Corps."
Egyptian recruits
Lead by 1 Brit soldier per 100 Egyptians
Federal Research Division (30 June 2004). Somalia a Country Study. Area handbook series (3rd ed.). Kessinger Publishing. ISBN9781419147999.
copy
<ref name=fedresearchdiv04>{{cite book| edition = 3rd| publisher = Kessinger Publishing| isbn = 9781419147999| author = Federal Research Division| title = Somalia a Country Study| series = Area handbook series| date = 30 June 2004 | pages = 230–231}}</ref>
p. 230
1912: Brit gov approved creation of Camel Corps
Just before WWI, Camel Corps → Somaliland Camel Corps after reorganization
p. 231
1943: colonial authorities changed Somaliland Camel Corps → armored car regiment
Following year had mutinies; Brits permanently disbanded the Camel Corps
{{/Template
|citation={{cite web| last = Jupiter Infomedia Ltd| title = Bikaner Camel Corps, Presidency Armies in British India| work = IndiaNetzone| accessdate = 6 December 2012| date = 28 November 2012
