AMLODIPINE BESYLATE
Chemistry - Amlodipine besylate, a dihydropyridine calcium channel blocking agent, occurs as awhite crystalline powder that is slightly soluble in water and sparingly soluble in alcohol.
Uses, Indications - Oral amlodipine appears to be a useful agent in the treatment of hypertensionin cats. The drug potentially could be useful in other veterinary species as well, but safety andefficacy data are lacking.
Hypertension in cats is usually secondary to other diseases (often renal failure or cardiac causessuch as thyrotoxic cardiomyopathy or primary hypertrophic cardiomyopathy, etc. ) and is mostoften seen in middle-aged or geriatric cats. These animals often present with acute symptoms suchas blindness, seizures, collapse or paresis. A cat is generally considered hypertensive if systolicblood pressure is >160mmHg. Early reports indicate that if antihypertensive therapy is begunacutely, some vision may be restored in about 50% of cases with blindness secondary tohypertension.
The drug is slowly but almost completely absorbed after oral administration. Peak plasmaconcentrations occur between 6-9 hours post-dose and effects on blood pressure are correspondingly delayed. The drug has very high plasma protein binding characteristics (approximately 93%).
However, drug interactions associated with potential displacement from these sites have not beenelucidated. Amlodipine is slowly, but extensively metabolized to inactive compounds in the liver.
Terminal plasma half-life is approximately 35 hours in healthy humans, but is prolonged in theelderly and in those patients with hypertension or hepatic dysfunction.
Amlodipine is classified as a pregnancy category C drug for humans. While no evidence of impaired fertility was noted in rats given 8X overdoses, amlodipine has been shown to be fetotoxic(intrauterine death rates increased 5 fold) in laboratory animals (rats, rabbits) at very high dosages.
No evidence of teratogenicity or mutagenicity were observed in lab animal studies. In rats, amlodipine prolonged labor. It is unknown whether amlodipine enters maternal milk.
Overdosage - Little information is available. Limited experience with other calcium channelblockers in humans have shown that profound hypotension and bradycardia may result. Whenpossible, massive overdoses should be managed with gut emptying and supportive treatment. Beta-agonists and intravenous calcium may be beneficial.
Storage, Stability, Compatibility
Store amlodipine at room temperature, in tight, light resistantcontainers.Pharmacology - AMLODIPINE BESYLATE
Amlodipine inhibits calcium influx across cel membranes in both cardiac andvascular smooth muscle. It has a greater effect on vascular smooth muscle, thereby acting as aperipheral arteriolar vasodilator and reducing afterload. Amlodipine also depresses impulse formation (automaticity) and conduction velocity in cardiac muscle.Uses, Indications - Oral amlodipine appears to be a useful agent in the treatment of hypertensionin cats. The drug potentially could be useful in other veterinary species as well, but safety andefficacy data are lacking.
Hypertension in cats is usually secondary to other diseases (often renal failure or cardiac causessuch as thyrotoxic cardiomyopathy or primary hypertrophic cardiomyopathy, etc. ) and is mostoften seen in middle-aged or geriatric cats. These animals often present with acute symptoms suchas blindness, seizures, collapse or paresis. A cat is generally considered hypertensive if systolicblood pressure is >160mmHg. Early reports indicate that if antihypertensive therapy is begunacutely, some vision may be restored in about 50% of cases with blindness secondary tohypertension.
Pharmacokinetics - AMLODIPINE BESYLATE
No feline-specific data on the drug's pharmacokinetics was located. In humans amlodipine's bioavailability does not appear to be altered by the presence of food in the gut.The drug is slowly but almost completely absorbed after oral administration. Peak plasmaconcentrations occur between 6-9 hours post-dose and effects on blood pressure are correspondingly delayed. The drug has very high plasma protein binding characteristics (approximately 93%).
However, drug interactions associated with potential displacement from these sites have not beenelucidated. Amlodipine is slowly, but extensively metabolized to inactive compounds in the liver.
Terminal plasma half-life is approximately 35 hours in healthy humans, but is prolonged in theelderly and in those patients with hypertension or hepatic dysfunction.
Contraindications, Precautions, Reproductive Safety
Because amlodipine may have slightnegative inotropic effects, it should be used cautiously in patients with heart failure or cardiogenicshock. It should also be used cautiously in patients with hepatic disease or at risk for developinghypotension. A relative contraindication for amlodipine exists for humans with advanced aorticstenosis.Amlodipine is classified as a pregnancy category C drug for humans. While no evidence of impaired fertility was noted in rats given 8X overdoses, amlodipine has been shown to be fetotoxic(intrauterine death rates increased 5 fold) in laboratory animals (rats, rabbits) at very high dosages.
No evidence of teratogenicity or mutagenicity were observed in lab animal studies. In rats, amlodipine prolonged labor. It is unknown whether amlodipine enters maternal milk.
Adverse Effects, Warnings
Adverse effect profile is not well determined for cats at this time. Inthe limited number of cats treated, amlodipine appears to have minimal adverse effects. In humanstaking amlodipine, headache (7.3%) is the most frequent problem reported.Overdosage - Little information is available. Limited experience with other calcium channelblockers in humans have shown that profound hypotension and bradycardia may result. Whenpossible, massive overdoses should be managed with gut emptying and supportive treatment. Beta-agonists and intravenous calcium may be beneficial.