Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

ASPIRIN

Chemistry - Aspirin, sometimes known as acetylsalicylic acid or ASA, is the salicylate ester ofacetic acid. The compound occurs as a white, crystalline powder or tabular or needle-like crystals. Itis a weak acid with a pKa of 3.5. Aspirin is slightly soluble in water and is freely soluble in alcohol.
Each gram of aspirin contains approximately 760 mg of salicylate.

Storage, Stability, Compatibility

Aspirin tablets should be stored in tight, moisture resistantcontainers. Do not use products past the expiration date or if a strong vinegar-like odor is notedemitting from the bottle.
Aspirin is stable in dry air, but readily hydrolyzes to acetate and salicylate when exposed to wateror moist air. It will then exude a strong vinegar-like odor. The addition of heat will speed the rate ofhydrolysis. In aqueous solutions, aspirin is most stable at pH's of 2-3 and least stable at pH'sbelow 2 or greater than 8. Should an aqueous solution be desirable as a dosage form, thecommercial product Alka-Seltzer® will remain stable for 10 hours at room temperature in solution.

Pharmacology - ASPIRIN

Aspirin inhibits cyclooxygenase (prostaglandin synthetase) thereby reducing thesynthesis of prostaglandins and thromboxanes. These effects are thought to be how aspirinproduces analgesia, antipyrexia, and reduces platelet aggregation and inflammation. Most cells cansynthesize new cyclooxygenase, but platelets cannot. Therefore, aspirin causes an irreversible effecton platelet aggregation. Aspirin has been shown to decrease the clinical symptoms ofexperimentally induced anaphylaxis in calves and ponies.

Pharmacokinetics - ASPIRIN

Aspirin is rapidly absorbed from the stomach and proximal small intestine inmonogastric animals. The rate of absorption is dependent upon factors as stomach content, gastricemptying times, tablet disintegration rates and gastric pH. Absorption is slow from the GI tract incattle, but approximately 70% of an oral dose will be absorbed.
During absorption, aspirin is partially hydrolyzed to salicylic acid where it is distributed widelythroughout the body. Highest levels may be found in the liver, heart, lungs, renal cortex, and plasma.
The amount of plasma protein binding is variable, depending on species, serum salicylate andalbumin concentrations. At lower salicylate concentrations, it is 90% protein bound, but only 70%protein bound at higher concentrations. Salicylate is excreted into milk, but levels appear to be verylow. Salicylate will cross the placenta, and fetal levels may actually exceed those found in themother.
Salicylate is metabolized in the liver primarily by conjugation with glycine and glucuronic acid viaglucuronyl transferase. Because cats are deficient in this enzymatic pathway, they have prolongedhalf-lives and are susceptible to accumulating the drug. Minor metabolites formed include gentisicacid and 2, 3-dihydroxybenzoic acid, and 2, 3, 5-trihydroxybenzoic acid. Gentisic acid appears to bethe only active metabolite, but because of its small concentrations, it appears to play an insignificantrole therapeutically. The rate of metabolism is determined by both first order kinetics and dose-dependent kinetics depending on which metabolic pathway is looked at. Generally, steady-stateserum levels will increase to levels higher (proportionally) than expected with dosage increases.
These effects have not been well studied in domestic animals, however.
Salicylate and its metabolites are rapidly excreted by the kidneys by both filtration and renaltubular secretion. Significant tubular reabsorption occurs which is highly pH dependent. Salicylateexcretion can be significantly increased by raising urine pH to 5-8. Salicylate and metabolites maybe removed using peritoneal dialysis or more rapidly using hemodialysis.
Uses, Indications - Aspirin is used in all species for its analgesic and antipyretic effects. It is theone nonsteroidal anti-inflammatory agent that is relatively safe to use in both dogs and cats. Besidesits analgesic, anti-inflammatory and antipyretic effects, aspirin is used therapeutically for its effectson platelet aggregation in the treatment of DIC and pulmonary artery disease secondary toheartworm infestation in dogs. It is also used in cats with cardiomyopathy.
Contraindications/Precautions - Aspirin is contraindicated in patients demonstrating previoushypersensitivity reactions to it. It is also contraindicated in patients with bleeding ulcers. It is relatively contraindicated in patients with hemorrhagic disorders, asthma, or renal insufficiency.
Because aspirin is highly protein bound to plasma albumin, patients with hypoalbuminemia mayrequire lower dosages to prevent symptoms of toxicity. Aspirin should be used cautiously, withenhanced monitoring, in patients with severe hepatic failure or diminished renal function. Becauseof its effects on platelets, aspirin therapy should be halted, if possible, one week prior to surgicalprocedures. Aspirin has been shown to delay parturition and therefore should be avoided during thelast stages of pregnancy.
Aspirin must be used cautiously in cats because of their inability to rapidly metabolize and excretesalicylates. Symptoms of toxicity may occur if dosed recklessly or without stringent monitoring.
Aspirin should be used cautiously in neonatal animals; adult doses may lead to toxicity.

Adverse Effects, Warnings

The most common adverse effect of aspirin at therapeutic doses isgastric or intestinal irritation with varying degrees of occult GI blood loss occurring. The resultantirritation may result in vomiting and/or anorexia. Severe blood loss may result in a secondaryanemia or hypoproteinemia. In dogs, plain uncoated aspirin may be more irritating to the gastricmucosa than either buffered aspirin or enteric coated tablets. Hypersensitivity reactions have beenreported in dogs, although they are thought to occur rarely.
Salicylates are possible teratogens and their use should be avoided during pregnancy, particularlyduring the later stages.
Overdosage - Symptoms of acute overdosage in dogs and cats include: depression, vomiting (maybe blood tinged), anorexia, hyperthermia, and increased respiratory rate. Initially, a respiratoryalkalosis occurs with a compensatory hyperventilation response. A profound metabolic acidosisfollows. If treatment is not provided, muscular weakness, pulmonary and cerebral edema, hypernatremia, hypokalemia, ataxia and seizures, may all develop with eventual coma and death.
Treatment of acute overdosage initially consists of emptying the gut if ingestion has occurredwithin 12 hours, giving activated charcoal and an oral cathartic, placing an intravenous line, beginning fluids and drawing appropriate lab work (e.g., blood gases). Some clinicians suggest performing gastric lavage with a 3-5% solution of sodium bicarbonate to delay the absorption of aspirin. A reasonable choice for an intravenous solution to correct dehydration would be dextrose 5%in water. Acidosis treatment and forced alkaline diuresis with sodium bicarbonate should beperformed for serious ingestions. Diuresis may be enhanced by the administration of mannitol (1-2gm/kg/hr). Seizures may be controlled with IV diazepam. Treatment of hypoprothrombinemia maybe attempted by using phytonadione (2.5 mg/kg divided q8-12h) and ascorbic acid (25 mgparenterally), but ascorbic acid may negate some of the urinary alkalinization effects of bicarbonate.
Peritoneal dialysis or exchange transfusions may be attempted in very severe ingestions whenheroic measures are desired.

Drug Interactions

Drugs that alkalinize the urine (e.g., acetazolamide, sodium bicarbonate)significantly increase the renal excretion of salicylates. Because carbonic anhydrase inhibitors (e.g., acetazolamide, dichlorphenamide) may cause systemic acidosis and increase CNS levels ofsalicylates, toxicity may occur.
Urinary acidifying drugs (methionine, ammonium chloride, ascorbic acid) will decrease theurinary excretion of salicylates.
Furosemide may compete with the renal excretion of aspirin and delay its excretion. This maycause symptoms of toxicity in animals receiving high aspirin doses.
Phenobarbital may increase the rate of metabolism of aspirin by inducing hepatic enzymes.
Corticosteroids may increase the clearance of salicylates and decrease serum levels.
Increased chances of developing GI ulceration exist if administering aspirin with corticosteroidsor phenylbutazone or other non-steroidal agents concurrently. Aspirin may increase the risksof bleeding associated with heparin or oral anticoagulant therapy.
At usual doses, aspirin may antagonize the uricosuric effects of probenicid or sulfinpyrazone.
Aspirin may inhibit the diuretic activity of spironolactone.
Aspirin may displace highly protein bound drugs from plasma proteins thus increasing free druglevels and pharmacologic effect. The following drugs may be affected by this mechanism (clinicalsignificance is unknown, but increased monitoring should be performed if adding aspirin):methotrexate, valproic acid, phenytoin, oral anticoagulants, penicillins, and sulfonamides.
The antacids in buffered aspirin may chelate tetracycline products if given simultaneously, spacedoses apart by at least one hour.
In dogs, aspirin has been demonstrated to increase the plasma levels of digoxin by decreasing theclearance of the drug.
Some clinicians feel that aspirin should not be given concomitantly with aminoglycoside antibiotics because of an increased likelihood of nephrotoxicity developing. The actual clinicalsignificance of this interaction is not entirely clear, and the risk versus benefits should be weighedwhen contemplating therapy.
Laboratory Test Interference - At high doses, aspirin may cause false-positive results for urinary glucose if using the cupric sulfate method (Clinitest® , Benedict's solution) and false-negative results if using the glucose oxidase method (Clinistix® or Tes-Tape® ).
Urinary ketones measured by the ferric chloride method (Gerhardt) may be affected if salicylatesare in the urine (reddish-color produced). 5-HIAA determinations by the fluoremetric method maybe interfered by salicylates in the urine. Falsely elevated VMA (vanillylmandelic acid) may be seenwith most methods used if salicylates are in the urine. Falsely lowered VMA levels may be seen ifusing the Pisano method.
Urinary excretion of xylose may be decreased if aspirin is given concurrently. Falsely elevatedserum uric acid values may be measured if using colorimetric methods.
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