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What is a common adverse effect of methyldopa, especially at the beginning of treatment?
Which of the following indicates a potential long-term effect of methyldopa treatment?
What primary mechanism does clonidine utilize to decrease noradrenaline release?
Which symptom is commonly associated with clonidine and is centrally mediated?
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What should be done if a patient on clonidine therapy develops mental depression?
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What distinguishes labetalol from other β-blockers?
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Which of the following statements about carvedilol is true?
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What is a unique feature of nebivolol compared to traditional β-blockers?
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How does the mechanism of action of pindolol, acebutolol, and penbutolol differ from traditional β-blockers?
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What is the primary reason labetalol is used in treating hypertensive emergencies?
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Which statement is true regarding the stereoselective metabolism of carvedilol?
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Which β-blocker is specifically noted for its effectiveness in patients with both heart failure and hypertension?
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What is a potential side effect of nebivolol noted in studies compared to older β-blockers?
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What effect may tricyclic antidepressants have when used with clonidine?
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What can occur after suddenly omitting one or two doses of clonidine?
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What primary effect does sodium nitroprusside have on vascular resistance and venous return?
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What is a significant adverse effect of ganglion blocking agents?
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Which mechanism does sodium nitroprusside use to relax vascular smooth muscle?
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Which of the following describes the mechanism of action of reserpine?
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What is a potential risk associated with prolonged administration of sodium nitroprusside?
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Why have adrenergic neuron blocking agents become rarely used?
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What is a major reason for discontinuing ganglion blockers in the treatment of hypertension?
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What adverse effect can sodium nitroprusside cause due to cyanide accumulation?
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What role does sodium thiosulfate play in the context of sodium nitroprusside infusion?
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What is the action of guanethidine as an adrenergic neuron blocking agent?
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Which of the following best describes sympathoplegia as it relates to ganglion blocking agents?
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What dosage range is typically recommended for sodium nitroprusside infusion?
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Which of the following is a reported adverse effect from the infusion of sodium nitroprusside?
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What is the main classification of diazoxide?
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What is a significant characteristic of esmolol that makes it suitable for intra-operative management?
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Which of the following is a main usage of alpha-1 blockers?
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Why should the first dose of an alpha-1 blocker be small and administered at bedtime?
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What is a key difference between α1 blockers and non-selective α-antagonists?
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Which of the following statements is true regarding terazosin?
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What is the primary mechanism by which alpha-1 blockers reduce blood pressure?
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In which position is blood pressure reduced more significantly when using alpha-1 blockers?
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What should be a consideration when administering alpha-1 blockers without diuretics?
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Study Notes
Sodium Nitroprusside
- Powerful parenteral vasodilator used for hypertensive emergencies and severe heart failure.
- Dilates arteries and veins, lowering peripheral vascular resistance and venous return.
- Activates guanylyl cyclase through nitric oxide release or direct stimulation, leading to increased cGMP and vascular smooth muscle relaxation.
- In the absence of heart failure, reduces BP due to decreased vascular resistance, without impacting or slightly reducing cardiac output.
- In patients with heart failure and low cardiac output, output often increases due to afterload reduction.
- Rapidly metabolized by red blood cells, releasing nitric oxide and cyanide.
- Cyanide is metabolized to thiocyanate by mitochondrial enzyme rhodanese.
- Thiocyanate is slowly eliminated by the kidneys.
- Quickly lowers BP, but effects disappear within 1-10 minutes after discontinuation.
- Infused intravenously as an aqueous solution, sensitive to light.
- Dosage usually starts at 0.5 mcg/kg/min and can be increased up to 10 mcg/kg/min to control blood pressure.
- High infusion rates sustained for over an hour can lead to toxicity.
- Requires continuous monitoring of arterial BP due to its efficacy and rapid onset.
Sodium Nitroprusside: Adverse Effects
- Cyanide accumulation can lead to metabolic acidosis, arrhythmias, excessive hypotension, and death.
- Sodium thiosulfate, a sulfur donor, facilitates cyanide metabolism.
- Hydroxocobalamin combines with cyanide to form non-toxic cyanocobalamin.
- Sodium thiosulfate and hydroxocobalamin are used for prophylaxis or treatment of cyanide poisoning during nitroprusside infusion.
- Thiocyanate may accumulate over prolonged administration, especially in renal insufficiency.
- Thiocyanate toxicity can cause weakness, disorientation, psychosis, muscle spasms, and convulsions.
- Rare cases of delayed hypothyroidism due to thiocyanate inhibition of iodide uptake by the thyroid.
- Methemoglobinemia can develop during nitroprusside infusion.
Diazoxide
- Potassium channel opener that hyperpolarizes smooth muscle and pancreatic β cells.
Clonidine
- Partial agonist at α receptors.
- Stimulates pre-synaptic α-2-adrenoceptors, decreasing norepinephrine release from both central and peripheral sympathetic nerve terminals.
- May also act on postsynaptic α-2 adrenoceptors to inhibit activity.
- Binds to imidazoline receptor, which may also mediate antihypertensive effects.
- Lowers BP by reducing cardiac output due to decreased heart rate, relaxation of capacitance vessels, and decreased peripheral vascular resistance.
- Reduces arterial BP while maintaining renal blood flow by decreasing renal vascular resistance.
- Lipid soluble and rapidly enters the brain from the circulation.
- Relatively short half-life, requiring twice daily administration.
Clonidine: Adverse Effects
- Common side effects include dry mouth and sedation.
- Central mediation and dose-dependent.
- Should not be given to patients at risk for mental depression and should be withdrawn if depression develops during therapy.
- Concomitant use of tricyclic antidepressants can block clonidine's antihypertensive effect due to the tricyclic's α-adrenoceptor blocking action.
- Rare side effects can include postural hypotension.
- Sudden withdrawal after prolonged use can lead to a potentially dangerous hypertensive crisis.
- Hypertensive crises are characterized by increased sympathetic nervous activity, manifested as nervousness, tachycardia, headache, and sweating.
- Gradual discontinuation of clonidine is necessary to avoid crises.
Ganglion Blocking Agents
- Historically among the first agents used to treat hypertension.
- Competitively block nicotinic cholinoceptors on postganglionic neurons in both sympathetic and parasympathetic ganglia.
- May also directly block the nicotinic acetylcholine channel.
- Adverse effects include sympathoplegia (excessive orthostatic hypotension, sexual dysfunction) and parasympathoplegia (constipation, urinary retention, glaucoma precipitation, blurred vision, dry mouth).
- Severe toxicities led to the discontinuation of ganglion blockers for hypertension treatment.
Adrenergic Neuron Blocking Agents
- Lower BP by inhibiting the release of norepinephrine from postganglionic sympathetic neurons.
- Significant toxicity limits their use, and they are rarely used today.
- Guanethidine can cause profound sympathoplegia (marked postural hypotension, diarrhea, and impaired ejaculation).
- Too polar to enter the CNS, lacking central effects seen in other antihypertensive agents.
- Guanadrel, bethanidine, and debrisoquin are similar agents no longer in clinical use.
Reserpine
- An alkaloid extracted from the roots of the Rauwolfia serpentine plant.
- Rarely used, considered as a fourth-line treatment for hypertension in some regions.
- Mechanism of action involves blocking the ability of aminergic transmitter vesicles to take up and store biogenic amines by interfering with the vesicular membrane associated transporter (VMAT).
- Affects the entire body, leading to depletion of norepinephrine, dopamine, and serotonin in both central and peripheral neurons.
- Peripheral amine depletion provides the beneficial antihypertensive effect, but a central component cannot be ruled out.
- Lowers BP by reducing cardiac output and peripheral vascular resistance.
Pindolol, Acebutolol, & Penbutolol
- Partial agonists with β-blocking properties and some intrinsic sympathomimetic activity.
- Lower BP but are rarely used in hypertension treatment.
Labetalol, Carvedilol, & Nebivolol
- Possess both β-blocking and vasodilating properties.
- Labetalol is a racemic mixture of four isomers, with two being inactive, one a potent α blocker, and one a potent β blocker.
- Labetalol has a 3:1 ratio of β:α antagonism following oral administration.
- Lowers BP by reducing systemic vascular resistance via α blockade, without significantly affecting heart rate or cardiac output.
- Useful for treating hypertension in pheochromocytoma and hypertensive emergencies due to its combined α and β-blocking activity.
Carvedilol
- Administrated as a racemic mixture.
- The S(-) isomer is a non-selective β-adrenoceptor blocker.
- Both S(-) and R(+) isomers have similar α1-blocking potency.
- Stereoselectively metabolized in the liver, leading to different elimination half-lives.
- Average half-life of 7-10 hours.
- Reduces mortality in patients with heart failure, particularly beneficial for patients with both heart failure and hypertension.
Nebivolol
- β1-selective blocker with vasodilating properties.
- Marketed as a racemic mixture.
- Vasodilation is attributed to the L-isomer.
- Vasodilating effects may be due to increased endothelial release of nitric oxide through induction of endothelial nitric oxide synthase.
- Hemodynamic effects differ from pure β-blockers, as peripheral vascular resistance is reduced acutely by nebivolol, unlike the older agents that increase it acutely.
- Extensive metabolism with active metabolites.
- Half-life of 10-12 hours, allowing once-daily administration.
- Efficacy similar to other antihypertensive agents, but studies report fewer adverse effects.
Esmolol
- β1-selective blocker.
- Rapidly metabolized via hydrolysis by red blood cell esterases.
- Short half-life of 9-10 minutes, administered by IV infusion.
- Used for managing intra-operative and post-operative hypertension.
- Sometimes used for hypertensive emergencies, especially when hypertension is accompanied by tachycardia or concern exists for toxicity such as aggravation of severe heart failure.
- Short duration of action allows for quick discontinuation.
Alpha-1 Blockers
- Prazosin, terazosin, and doxazosin selectively block α1 receptors in arterioles and venules.
- Induce less reflex tachycardia when reducing BP compared to non-selective α-antagonists like phentolamine.
- Alpha-1 receptor selectivity allows norepinephrine to exert unopposed negative feedback (mediated by presynaptic α2 receptors) on its own release.
- Reduce arterial pressure by dilating both resistance and capacitance vessels.
- BP reduction is greater in the upright position compared to the supine position.
- Salt and water retention can occur when these drugs are administered without a diuretic.
- More effective when combined with other agents like a β blocker and a diuretic.
- Beneficial effects in males with prostatic hyperplasia and bladder obstruction symptoms, primarily used in men with concurrent hypertension and benign prostatic hyperplasia.
Terazosin
- Extensively metabolized with minimal first-pass metabolism.
- Half-life of 12 hours, often given once daily.
Doxazosin
- Intermediate bioavailability with a half-life of 22 hours.
- Typically given once daily.
Alpha-1 Blockers: Adverse Effects
- While long-term treatment with these α-blockers causes relatively little postural hypotension, some patients experience a significant drop in standing BP shortly after the first dose is absorbed.
- First dose should be small and administered at bedtime to minimize this effect.
- The mechanism of this first-dose phenomenon is unclear, but it occurs more frequently in patients who are salt and volume depleted.
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Description
This quiz covers Sodium Nitroprusside, a potent vasodilator utilized in hypertensive emergencies and heart failure. Learn about its mechanism of action, effects on blood pressure, metabolism, and administration. Test your understanding of its pharmacology and clinical applications.
