PRAZOSIN HCL
Chemistry - A quinazoline-derivative postsynaptic alpha1-adrenergic blocker, prazosin HCl occursas a white to tan powder. It is slightly soluble in water and very slightly soluble in alcohol. Prazosinmay also be known as Furazosin.
Prazosin significantly reduces systemic and venous pressures, right atrial pressure and increasescardiac output in patients with CHF. Moderate reductions in blood pressure, pulmonary vascularresistance and systemic vascular resistance are seen in these patients. Heart rates can be moderatelydecreased or unchanged. Unlike hydralazine, prazosin does not seem to increase renin release sodiuretic therapy is not mandatory with this agent (but is usually beneficial in CHF).
Uses, Indications - Prazosin is less well studied in dogs than is hydralazine, and its capsule dosageform makes it less convenient for dosing. Prazosin, however, appears to have less problems withcausing tachycardia, and its venous dilation effects may be an advantage over hydralazine whenpreload reduction is desired. It could be considered for therapy for the adjunctive treatment of CHF, particularly when secondary to mitral or aortic valve insufficiency when hydralazine is ineffective ornot tolerated. Prazosin may also be used for the treatment of systemic hypertension or pulmonaryhypertension in the dog.
Prazosin is widely distributed throughout the body and is approximately 97% bound to plasmaproteins. Prazosin is minimally distributed into milk. It is unknown if it crosses the placenta.
Prazosin is metabolized in the liver and some metabolites have activity. Metabolites and someunchanged drug (5-10%) are primarily eliminated in feces via the bile.
Contraindications/Precautions - Prazosin should be used with caution in patients with chronicrenal failure or preexisting hypotensive conditions.
Overdosage - Evacuate gastric contents and administer activated charcoal using standard precautionary measures if the ingestion was recent and if cardiovascular status has been stabilized.
Treat shock using volume expanders and pressor agents if necessary. Monitor and support renalfunction.
Verapamil or nifedipine may cause synergistic hypotensive effects when used concomitantlywith prazosin.
Beta-blocking agents (e.g., propranolol) may enhance the postural hypotensive effects seen afterthe first dose of prazosin. Other antihypertensive agents can also cause additive hypotension.
Storage, Stability, Compatibility
Prazosin capsules should be stored in well-closed containersat room temperature.Pharmacology - PRAZOSIN HCL
Prazosin's effects are a result of its selective, competitive inhibition of alpha1-adrenergic receptors. It reduces blood pressure and peripheral vascular resistance and unlike hydralazine, has dilatory effects on both the arterial and venous side.Prazosin significantly reduces systemic and venous pressures, right atrial pressure and increasescardiac output in patients with CHF. Moderate reductions in blood pressure, pulmonary vascularresistance and systemic vascular resistance are seen in these patients. Heart rates can be moderatelydecreased or unchanged. Unlike hydralazine, prazosin does not seem to increase renin release sodiuretic therapy is not mandatory with this agent (but is usually beneficial in CHF).
Uses, Indications - Prazosin is less well studied in dogs than is hydralazine, and its capsule dosageform makes it less convenient for dosing. Prazosin, however, appears to have less problems withcausing tachycardia, and its venous dilation effects may be an advantage over hydralazine whenpreload reduction is desired. It could be considered for therapy for the adjunctive treatment of CHF, particularly when secondary to mitral or aortic valve insufficiency when hydralazine is ineffective ornot tolerated. Prazosin may also be used for the treatment of systemic hypertension or pulmonaryhypertension in the dog.
Pharmacokinetics - PRAZOSIN HCL
The pharmacokinetic parameters for this agent were not located for veterinaryspecies. In humans, prazosin is variably absorbed after oral administration. Peak levels occur in 2-3hours.Prazosin is widely distributed throughout the body and is approximately 97% bound to plasmaproteins. Prazosin is minimally distributed into milk. It is unknown if it crosses the placenta.
Prazosin is metabolized in the liver and some metabolites have activity. Metabolites and someunchanged drug (5-10%) are primarily eliminated in feces via the bile.
Contraindications/Precautions - Prazosin should be used with caution in patients with chronicrenal failure or preexisting hypotensive conditions.
Adverse Effects, Warnings
Syncope secondary to orthostatic hypotension has been reported inpeople after the first dose of the drug. This effect may persist if the dosage is too high for the patient. CNS effects (lethargy, dizziness, etc.) may occur, but are usually transient in nature. GI effects(nausea, vomiting, diarrhea, constipation, etc) have been reported. Tachyphylaxis (drug tolerance)has been reported in man, but dosage adjustment, temporarily withdrawing the drug &/or adding analdosterone antagonist (e.g., spironolactone) usually corrects this.Overdosage - Evacuate gastric contents and administer activated charcoal using standard precautionary measures if the ingestion was recent and if cardiovascular status has been stabilized.
Treat shock using volume expanders and pressor agents if necessary. Monitor and support renalfunction.
Drug Interactions
As prazosin is highly bound to plasma proteins, it may displace or be displaced by other highly protein bound drugs (e.g., sulfonamides, phenylbutazone, warfarin, etc.).Verapamil or nifedipine may cause synergistic hypotensive effects when used concomitantlywith prazosin.
Beta-blocking agents (e.g., propranolol) may enhance the postural hypotensive effects seen afterthe first dose of prazosin. Other antihypertensive agents can also cause additive hypotension.