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Questions and Answers
What is a significant contraindication for the use of phentolamine?
Which therapeutic indication is NOT associated with phentolamine?
What is the primary receptor blocked by prazosin?
Which statement about prazosin is accurate?
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Which agent is noted to be less potent than phentolamine?
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What is a major potential adverse effect of certain antihypertensive agents?
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Which condition is NOT an established therapeutic indication for prazosin?
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Which of the following is a clinical application of selective α2-AR blockers?
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What type of drug are all clinically available β-blockers classified as?
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What effect can occur 30 to 90 minutes after the first dose of certain antihypertensive agents?
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Which of the following statements about labetalol is true?
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What is the mechanism of action of reserpine?
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Which adverse effect is associated with the use of alpha-1 blockers like labetalol?
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How does guanethidine lower blood pressure?
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Which of the following is NOT a characteristic of labetalol?
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What is the primary action of α-adrenergic blockers on blood pressure?
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What is a characteristic of phenoxybenzamine as an adrenergic antagonist?
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Which of the following drugs is considered a reversible α-adrenergic antagonist?
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What occurs as a reflex action due to reduced blood pressure from α-adrenergic blockade?
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What is the effect of α-adrenergic antagonists on the sympathetic nervous system?
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How long do the actions of phenoxybenzamine typically last after a single dose?
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Which type of adrenergic antagonist targets only β1-adrenoreceptors?
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What physiological effect results from using α-adrenergic blockers in cardiovascular medicine?
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What is the primary therapeutic use of phenoxybenzamine?
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What adverse effect may be caused by phenoxybenzamine due to impaired smooth muscle contraction?
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Which condition is phenoxybenzamine used to preempt during surgical removal of a tumor?
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What is a common adverse effect of both phenoxybenzamine and phentolamine?
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Which of the following is true regarding phentolamine's action?
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What is one of the physiological effects of decreased peripheral resistance due to phenoxybenzamine?
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For which condition is phenoxybenzamine NOT typically indicated?
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What effect can phenoxybenzamine have on the heart rate and cardiac output?
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Study Notes
Adrenergic Antagonists:
- Adrenergic antagonists, also known as adrenergic blockers or sympatholytic agents, bind to adrenoreceptors without triggering their usual effects.
- These drugs can bind reversibly or irreversibly, preventing activation by catecholamines like adrenaline, noradrenaline, and dopamine.
- They are categorized based on their affinity for α or β-adrenoreceptors in the periphery.
- They interfere with functions of the sympathetic nervous system, affecting organs innervated by it.
- Many of these agents are crucial in clinical medicine, particularly for treating cardiovascular diseases.
α-adrenergic Blockers:
- α-AR blockers are either reversible (competitive) or irreversible (non-competitive) in their interaction with receptors.
- They significantly affect blood pressure by lowering peripheral vascular resistance due to α1-AR blockade.
- This can trigger reflex tachycardia caused by the lowered BP because β-ARs, especially β1-ARs on the heart, are unaffected by α blockade.
Phenoxybenzamine:
- Phenoxybenzamine, a haloalkylamine drug, is nonselective, binding to both postsynaptic α1-ARs and presynaptic α2-ARs irreversibly.
- The block is noncompetitive, requiring synthesis of new ARs, which takes at least a day, meaning the effects last about 24 hours after a single dose.
- It is a pro-drug, activated via biotransformation, leading to a delayed onset of blockade.
- Cardiovascular effects: Phenoxybenzamine prevents vasoconstriction of peripheral blood vessels by blocking α1-ARs. The decreased peripheral resistance leads to reflex tachycardia. It also affects presynaptic α2-ARs, increasing cardiac output.
- It is less effective in maintaining lowered BP in hypertension.
Therapeutic Uses of Phenoxybenzamine:
- Long-term treatment of hypertension in patients with pheochromocytoma (tumor of the adrenal medulla).
- Used prior to surgical removal of the tumor to prevent hypertensive crises.
- Also used for chronic management, especially if the tumor is inoperable.
- Treatment of Raynaud's disease (spasm of arteries causing finger & toe pallor).
- Used for benign prostatic hyperplasia (enlarged prostate causing urination difficulty) to decrease obstructive symptoms and urinary frequency.
Adverse Effects of Phenoxybenzamine:
- Postural hypotension (low BP upon standing) often accompanied by reflex tachycardia and other arrhythmias.
- Inhibition of ejaculation due to impaired smooth muscle contraction of the vas deferens and ejaculatory duct.
- Nasal stuffiness, nausea, and vomiting.
Phentolamine and Tolazoline:
- Phentolamine produces a competitive block of α1- and α2-ARs.
- Cardiovascular effects are similar to those of phenoxybenzamine, referred to as "classical" α-AR blockers.
- Single administration lasts approximately 4 hours, also producing postural hypotension and adrenaline reversal.
- It can trigger arrhythmias & anginal pain and is contraindicated in patients with decreased coronary perfusion.
- It blocks 5-HT receptors, triggers histamine release from mast cells, and blocks K+ conductance
- Tolazoline is less potent than phentolamine, not marketed but stimulates secretions by salivary, lacrimal, and sweat glands.
Therapeutic Indications of Phentolamine:
- Short-term control of hypertension in patients with pheochromocytoma.
- Treatment of hypertensive crisis induced by sudden clonidine withdrawal or tyramine-containing food ingestion during non-selective MAO inhibitor use.
- Direct intracavernous injection of phentolamine is investigated for male sexual dysfunction.
Prazosin, Terazosin, Doxazosin, Tamsulosin, and Alfuzosin:
- Prazosin is the prototype, containing the piperazinyl quinazoline nucleus.
- It is a potent, selective, and competitive α1-AR antagonist with over 1000 times more affinity for these receptors than α2-ARs.
- These agents are more clinically useful and have replaced nonselective α-AR antagonists like phenoxybenzamine and phentolamine.
Prazosin:
- The main effects of prazosin result from α1-AR blockade in arterioles and veins, causing decreased peripheral resistance and venous return to the heart.
- Unlike other vasodilating drugs, prazosin does not increase heart rate or promote NA release (has little α2-AR-blocking effects).
- It is well absorbed orally with bioavailability between 50-70%.
- Plasma half-life is approximately 2-3 hours and the duration of action is 7-10 hours for hypertension treatment.
- It is extensively metabolized and has a half-life of 3-5 hours.
Therapeutic Indications of Prazosin:
- Essential hypertension.
- Congestive heart failure (ACE inhibitors are the preferred treatment).
- BPH.
- Other indications with inconclusive evidence:
- Variant angina due to coronary vasospasms.
- Aortic valvular insufficiency.
- Vasospasms in patients with Raynaud’s disease.
Adverse Effects of Prazosin:
- The major adverse effect is the first-dose effect: marked postural hypotension, and first-dose syncope, occurring 30 to 90 minutes after the initial dose.
- Syncope can also occur with a rapid increase in dosage or with the addition of another antihypertensive drug.
- Non-specific adverse effects include headache, dizziness, and asthenia, which rarely limit treatment.
- Tamsulosin impairs ejaculation.
Selective α2-AR blockers:
- Examples include rauwolscine, yohimbine, idazoxan, and tolazoline.
- Their clinical role is not established, mostly used in experimental pharmacology like treating type-2 diabetes (α2-AR stimulation inhibits insulin release).
- Theoretically, they could be useful in autonomic insufficiency by blocking presynaptic α2-ARs.
- Yohimbine is suggested to improve male sexual function (insufficient data), but PDE5 inhibitors (sildenafil) are preferred.
- Yohimbine readily crosses the BBB, where it acts to increase BP and heart rate, opposing the actions of clonidine.
β-Adrenergic Blocking Agents:
- All clinically available β-blockers are competitive antagonists.
- Divided into selective and non-selective blockers.
- Nonselective β-blockers act at both β1- and β2-ARs, while cardioselective blockers primarily block β1-ARs.
- Valuable in diabetics because carbohydrate metabolism is less affected.
Labetalol, Bucindolol, Nebivolol, Celiprolol, and Carvedilol:
- Antagonists of both α- and β-ARs.
- They reversibly block β- and α1-ARs, producing peripheral vasodilation and lowering BP.
- Unlike other β-blockers (which cause peripheral vasoconstriction), they are useful in treating hypertensive patients where increased peripheral vascular resistance is undesirable.
- They do not alter serum lipid or blood glucose levels.
Clinical Uses of Labetalol:
- Treating elderly or Black hypertensive patients with undesirable increased peripheral vascular resistance.
- Alternative to hydralazine for pregnancy-induced hypertension treatment.
- Used to treat hypertensive emergencies due to its rapid blood pressure reduction.
Adverse Effects of Labetalol:
- Orthostatic hypotension and dizziness (associated with α1-blockade).
Drugs Affecting Neurotransmitter Release or Uptake:
Reserpine:
- It blocks the Mg2+/ATP-dependent transport of biogenic amines (NA, D, and serotonin) from the cytoplasm into storage vesicles.
- This depletes NA levels in the adrenergic neuron because MAO degrades NA in the cytoplasm.
- Has a slow onset and long duration of action, lasting many days after discontinuation.
- It is only used for hypertension that doesn’t respond to other treatments.
Guanethidine:
- It blocks the release of stored NA, leading to gradual lowering of BP in hypertensive patients and a decrease in cardiac rate.
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Description
Explore the role of adrenergic antagonists, also known as adrenergic blockers or sympatholytic agents. This quiz covers the mechanisms of action, classification, and clinical relevance, particularly in treating cardiovascular diseases. Understand how these drugs interact with adrenoreceptors and their effects on blood pressure.
