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35 Cards in this Set
- Front
- Back
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What enzyme was methyldopa created to inhibit? What actually happened?
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Aromatic amino acid decarboxylase
Also metabolized by the enzyme that it competitively inhibits, being converted into alpha-methylnorepinephrine |
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What is the MOA of methyldopa?
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Antihypertensive effect is mediated by alpha-methylcatecholamine metabolites that act on alpha-2a adrenoreceptors in the medulla to inhibit the sympathetic outflow to the cardiovascular system
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What kind of sympathetic inhibition does methyldopa cause? Why is that a good thing?
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Sympathetic stimulation of arterial vasoconstriction is inhibited (and blood pressure lowered) in both the supine and standing positions. Some orthostatic hypotension, but much less than drugs that completely block peripheral sympathetic neurotransmission.
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Besides sympathetic inhibition, what 2 effects do the active metabolites of methyldopa have on the CNS?
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Inhibit medullary centers responsible for wakefulness. Produces transitory sedation. Also inhibits centers that control salivation, so can result in dryness of math
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How does methyldopa affect the heart? Why is this a good thing?
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Much less effect on CO than peripheral vasculature, slightly attenuating sympathetic reflexes to the heart with slight reductions in cardiac rate and contractility.
Safe to lower BP in patients with IHD. Does not completely block baroreceptor reflexes, so can be used as an antihypertensive during elective surgery. |
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What are the 4 hemodynamic effects of methyldopa?
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Reduce peripheral vascular resistance
Slight decrease in cardiac rate and contactility Prevents development of LVH and produces regression in LVH Inhibits sympathetic stimulus for renin release |
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Describe the metabolism of methyldopa, aside from the active metabolites?
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Undergoes biotransformation in the liver
Unchanged drug excreted by the kidney |
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Describe the metabolism of active metabolite of methyldopa.
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Accumulates in adrenergic neurons, half life in the CNS is one day.
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What are the non-pharmacologic side effects of methyldopa?
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Drug fever, drug-induced hepatotoxicity
Hemolytic anemia |
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What is the main indication for methyldopa?
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Pregnant patients requiring antihypertensive therapy
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Give a general definition for clonidine.
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Alpha-2a adrenoreceptor agonist that acts in the CNS to lowr blood pressure
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What do the CNS actions of clonidine result in?
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Like methyldopa, produces side effects like sedation, loss of psychic energy, depression, and dry mouth. Extent of postural hypotension is also similar to methyldopa.
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How does clonidine affect other adrenergic receptor?
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Possesses some alpha-1 agonist activity, resulting in some vasoconstrictor activity, causing a pressor response when given IV, and can cause vasoconstriction in the extremities in response to cold (Raynaud's).
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What is the most important 'side effect' for clonidine?
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Clonidine rebound: when discontinued in patients with severe HTN receiving larger doses, a withdrawal phenomenon is seen.
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What causes clonidine rebound? What symptoms does this result in?
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Massive sympathetic discharge in which there are elevated levels of circulating catecholamines.
Tachycardia, nausea, vomiting, HTN, headache |
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Why isn't clonidine good for severe HTN?
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The withdrawal symptoms
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What is the random effect of clonidine?
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Modest reduction in serum cholesterol
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Dexmedetomidine: MOA
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Selective alpha2 agonist
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What is Dexmedetomidine used for?
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Sedative
Intensive care and anesthesiology |
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What is an adverse effect for Dexmedetomidine?
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Bradycardia
Asystole Hypotension (when loading dose infused rapidly) |
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Phenoxybenzamine/phentolamineMOA
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Alpha1 and alpha2 adrenoreceptor antagonists
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When are phenoxybenzamine and phentolamine used? Why?
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Pheochromocytomas, which frequently secrete NE and epi. Epi causes vasoconstriction via alpha1 and 2, so want to block to antagonize the pressor effects of epi.
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What is the major adverse affect of phenoxybenzamine and phentolamine?
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Hypotension
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Differences in use of phenoxybenzamine and phentolamine for pheochromocytoma.
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Phenoxybenzamine: Oral drug for maintenance therapy of pheochromocytoma
Phentolamine: IV for emergent control of HTN in pheochromocytoma |
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What 3 drugs selectively block alpha1 adrenoreceptors?
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Prazosin
Terazosin Doxazosin |
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Prazosin: hemodynamic effects
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Reduce PVR and reduce venous tone
Acutely, reduction in venous tone leads to a drop in right ventricular filling pressure. Baroreceptor response results in tachycardia. |
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Why do you need to be careful with prazosin?
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First dose may elicit a severe hypotension that can lead to syncope.
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How is prazosin typically used?
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In combination with diuretic or a diuretic plus a beta blocker.
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Prazosin: other effects
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Slight favorable effects on plasma lipids: HDL increases and increase in ratio of HDL/LDL.
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Prazosin elimination
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Hepatic
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How is benign prostatic hypertrophy treated? Why isn't this perfect?
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With alpha1 blockers to relax the bladder neck and prostatic smooth muscle to treat the obstructive voiding symptoms. Specific drugs: tamsulosin, alfuzosin
Don't reduce the need for surgical treatment |
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Adverse effects of alpha1 blockers for benign prostatic hypertrophy.
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Floppy iris syndrome during cataract surgery
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What is labetalol?
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Selective alpha1 adrenoreceptor antagonist
Beta1 antagonist Selective partial beta2 adrenoreceptor antagonist |
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What is carvedilol?
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Selective alpha1 adrenoreceptor blockade with nonselective beta adrenoreceptor bloackde
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What is carvedilol used for?
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effective in reducing mortality in select patients with chronic cardiac failure
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