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109 Cards in this Set
- Front
- Back
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Resistance via what type of blood vessels controls peripheral vascular resistance?
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precapillary arterioles
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What is the hydraulic equation for BP
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BP= CO X PVR
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How does the blood pressure regulation differ in the normotensive patient from the hypertensive patient?
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The baroreceptors and the renal blood-volume-pressure control systems are set higher
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Baroreceptor activation ____ central sympathetic discharge
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inhibits
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what stimulates the carotid baroreceptors?
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they are stimulated by the stretch of the vessel walls brouth about by the internal pressure (arterial pressure)
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In the transition to upright position, what is the function of baroreceptors?
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Disinhibit central sympathetic discharge
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what does happens with the reflex increase in sympathetic outflow?
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constriction of arterioles --> increase in PVR
constriction of capacitance vessels --> increase venous return increase cardiac output --> direct stimulation of the heart |
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what is responsible for long term BP control?
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the kidney by controlling blood volume
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what is responsible for the production of renin?
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decreased renal arteriolar pressure
sympathetic neural activity via B receptors |
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initial treatment with diuretics may_____ PVR
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increase
this is due to the reduction of Blood pressure and cardiac output |
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how long does it take with diuretic therapy for the cardiac output to return to normal and for PVR to decline
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6 - 8 weeks
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how does sodium contribute to PVR?
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it increases vessel stiffness, neural activity, and possible alteration to the sodium-calcium exchange with a resultant increase in intracellular calcium
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how are diuretics still effective even when used with vasodilator and sympathoplegic drugs?
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because the sympathoplegic and vasodilator drugs decrease vascular responsiveness ( blood vessel behaves like a lead pipe) --> the blood pressure becomes very sensitive to fluid
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what class of hypertension is useful for Thiazides
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mild to moderate hypertension
effective in lowering BP by 10 to 15 mmHG |
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what class of diuretics is useful in severe hypertension
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Loop diuretics
also useful when GFR is less than 30 -40 mL, in cardiac failure/liver cirrhosis with marked sodiu retention |
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what is the most common adverse effect of diuretics?
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Hypokalemia
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how can potassium loss be minimized in diuretic use?
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because potassium loss is coupled to sodium reabsorption then
less sodium in the diet then less excretion of potassium |
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can you name some other side effects of Diuretics?
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magnesium depletion,
impaired glucose tolerance increase serum lipid tolerance |
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what is the mechanism of action of methyldopa?
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due to stimulation of central alpha adrenoceptors by alpha-methylnorepinephrine or alpha-methyldopamine
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what is the action of clonidine at the alpha receptors?
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1. there is a brief rise in BP due to the direct stimulation of alpha adrenoreceptors in arterioles
2. the hypotensive effect of clonidine is exerted at alpha adrenoceptors in the medulla of the brain |
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when is methyldopa primarily used?
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in pregnancy
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what are some side effects seen in methyldopa use?
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sedation
lactation in both men and women positive coombs test --> makes it difficult to cross-match blood for transfusion |
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What effect does clonidine have on the body to lower blood pressure?
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blood pressure lowering by clonidine results from reduction of cardiac output due to decreased heart rate and relaxation of capacitance vessels with a reduction in peripheral vascular vessels
there is also reduced renal vascular resistance and maintenance of renal blood flow |
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what is the advantage of transdermal route of administering clonidine?
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causes less sedation
the oral clonidine must be given twice a day for smooth BP control |
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why do people experience withdrawal while on clonidine
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due to increased sympathetic nervous activity
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how many doses can be missed before hypertensive crisis starts?
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patients exhibit nervousness, tachycardia, headache, and sweating after missing one or two doses
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what is the mechanism of action of ganglion blockers
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ganglion blockers competitively block nicotinic cholinoceptors on postganglionic neurons in both sympathetic and parasympathetic
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what are the adverse effects of ganglionic-blocking agents?
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sympatholplegia - excessive orthostatic hypotension and sexual dysfunction
parasympathoplegia- constipation, urinary retention,precipitation of glaucoma, blurred vision, dry mouth |
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what is the mechanism of adrenergic neuron -blocking agents
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by preventing normal physiologic release of norepinephrine from post ganglionic sympathetic neurons
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why is guanethidine rarely used
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can produce marked profound sympathoplegia- marked postural hypotension, diarrhea, and impaired ejaculation
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What are the collective side effects of agents that lower the blood pressure by actions on the CNS?
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They cause sedation and mental depression; disturbances of sleep, including nightmares
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Is postural hypotension commonly seen with centrally acting sympathoplegic drugs?
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NO
They reduce sympathetic outflow from vasomotor centers in the brain stem but allow these centers to retain their sensitivity to baroreceptor control |
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What is the effect of clonidine on the vasculature?
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It reduces sympathetic and increases parasympathetic tone, resulting in lowered BP and bradycardia
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Why is methyldopa associated with increased prolactin secretion?
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It is mediated by inhibition of dopaminergic mechanisms in the hypothalamus
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What drugs can block the antihypertensive effects of clonidine?
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TCAs
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What are the common side effects in Centrally acting sympathoplegic drugs?
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dry mouth and sedation
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How does guanethidine prevent the release of of norepinephrine?
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Guanethidine is transported across the sympathetic nerve membrane by NET. Once it has entered the nerve it is concentrated in the transmitter vesicles where is replaces norepi. This leads to a gradual depletion of norepinephrine stores in the nerve ending.
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How long does it take for guanethidine's sympatholplegia to take effect?
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the onset is gradual (max effect in 1-2 weeks)
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How does reserpine prevent norepinephrine from being released?
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It blocks the ability of vesicles to take up and store amines by interfering with VMAT
This affects norepi, dopamine, serotonin in both central and peripheral neurons and also the chromaffin granules in the adrenal medulla |
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What are the side effects of reserpine?
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It enters the CNS and causes sedation, mental depression, and parkinsonism symptoms.
At high doses, it can cause nightmares. It also causes mild diarrhea and GI cramps and increases gastric acid secretion |
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How does reserpine lower BP?
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It decreases cardiac output and PVR
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What is propanolol?
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nonselective beta blocker
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How does propanolol reduce BP?
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It mainly decreases cardiac output
It also inhibits renin production by catecholamines by the beta 1 receptor |
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How can you tell propanolol is working?
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by the resting bradycardia and a reduction in the heart rate during exercise
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What is the withdrawal syndrome seen with propanalol discontinuation?
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Nervousness, tachycardia, increased intensity of angina and increase of BP
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Metoprolol and Atenolol are cardioselective. Which means they prefer the ____ receptor.
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beta 1
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What cardiac conditions are metoprolol indicated for?
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It is effective in reducing mortality in patients with heart failure and hypertension
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What is unique about nadolol and cartelol?
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They are both nonselective beta- receptor anatagonists that have a long half life (they can be dosed once a day)
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What is unique about betaxolol and bisoprolol?
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They are selective beta1 antagonists that have a long half (they can be dosed once a day)
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What disease states are useful for pinodol, acebutolol and penbutolol?
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Because they decrease the cardiac output and heart rate less than other beta blockers--> this is useful in patients with bradyarrhythmia or PVD
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What is unique about pinodol, acebutolol and penbutolol?
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They are partial beta agonists with some intrinsic sympathomimetic activity. This means that they lower BP by decreasing vascular resistance but depress the cardiac output and heart rate less than other beta blockers
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Why does the half life of Esmolol last only 9-10 minutes?
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It is a beta1 selective blocker that is rapidly metabolized via hydrolysis by RBC esterases
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What is the clinical indication for Esmolol?
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It is used for management of intraoperative and postoperative HTN
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Name the betablockers that have both beta blocking and vasodilating effects
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Labetalol, Carvedilol, and Nebivolol
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How does Labetalol achieve both beta blocking and vasodilating effects
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Labetalol is a racemic mixture of four isomers. Two are inactive and two are active. One of the active (S,R) isomers is a potent alpha blocker and the other (R,R) isomers is a potent beta blocker. It has a ratio of 3:1 of beta:alpha (decreases PVR)
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How does Carvedilol achieve both beta blocking and vasodilating effects?
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It is a racemic mixture that has a S isomer that has both alpha blocking and nonselective beta blocking potency and a R isomer that has the same alpha blocking potency
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How does Nebivolol achieve both beta blocking and vasodilating effects?
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It is a beta 1 selective blocker via its D-Nebivolol isomer and its L-Nebivolol isomer cause vasodilation via an increase in endothelial release of nitric oxide via eNOS induction
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What is the clinical use for Labetalol?
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Pheochromocytoma because of its combined alpha and beta blocking
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What is the clinical use for Carvedilol?
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It reduces morality in patients with heart failure and hypertension
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How do prazosin, terazosin, and doxazosin cause less reflex tachycardia than phentolamine?
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Phentolamine is an nonselective alpha blocker that blocks both presynaptic and postsynaptic alpha receptors that cause reflex tachycardia because of greater release of transmitter.
Prazosin, terazosin, and doxazosin are alpha1 receptor selective that allows norepi to exert unopposed negative feedback on its own release. |
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How do prazosin, terazosin, and doxazosin lower blood pressure?
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They selectively block alpha 1 receptors in arterioles and venules. They dilate both resistance and capacitance vessels
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What is an expected side effect of prazosin, terazosin, and doxazosin when used alone?
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The retention of salt and water.
First dose precipitous drop in standing BP |
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What is the clinical indication of prazosin, terazosin, and doxazosin?
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It is beneficial in hypertensive men with prostatic hyperplasia and bladder obstruction symptoms
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Name the nonselective alpha blockers?
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Phentolamine and phenoxybenzamine
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Name the oral vasodilators used for long term HTN management.
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Hydralazine
Minoxidil |
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Name the parental vasodilators that are used for HTN emergencies.
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Nitroprusside
Diazoxide Fenoldopam |
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What are the antihypertensives that lower BP by hyperpolarization of smooth muscle membrane through opening K channels causing vasodilation?
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Minoxidil
Diazoxide |
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What are the antihypertensives that lower BP by release of nitric oxide from either the drug or endothelium?
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nitroprusside
Hydralazine Nitrates |
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Why do diuretics work well with vasodilators?
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When vasodilators decrease arterial pressure via vasodilation of arterioles it leads to decreased renal sodium excretion.
Diuretics work to increase renal sodium excretion and decrease aldosterone |
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Why do beta blockers work well with vasodilators?
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When vasodilators decrease arterial pressure via vasodilation of arterioles it leads to increased sympathetic nervous system outflow.
Beta blockers work to decrease the HR, cardiac contractility, venous capacitance and renin release |
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Describe what happens in persons who slowly acetylate the hydralazine.
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With dosages greater than 400mg/ day- A syndrome characterized by arthralgia, myalgia, skin rashes, and fever --> resembles lupus erythematosus
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Why should hydralazine be used in caution with patients with ischemic heart disease?
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The reflex tachycardia and sympathetic stimulation may provoke angina or ischemic arrhythmia
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What is the mechanism of action for hydralazine?
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It dilates arterioles but NOT veins
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What is the clinical indication of hydralazine?
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The COMBO with nitrates is effective in patients with heart failure, especially in African- American patients
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What are the vasodilators that ONLY dilate arterioles?
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Hydralazine
Minoxidil Diazoxide Fenoldopam Calcium Channels blockers |
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What is the mechanism of action for minoxidil?
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Minoxidil opens K channels in smooth muscle membranes; the increased K permeability stabilizes the membrane its resting potential and makes contraction less likely
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What HAS to be combined with minoxidil to counteract the reflex tachycardia and salt water retention?
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A loop diuretic and beta blocker
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What are the side effects of Minoxidil?
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HA, sweating, and hypertrichosis
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What is clinical indication of sodium nitroprusside?
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It is used in treating hypertensive emergencies as well as severe heart failure.
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How does nitroprusside lower blood pressure?
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It dilates arterial and venous vessels which decreases venous return and PVR via activation of guanylyl cyclase which increases intracellular cGMP
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How is nitroprusside metabolized?
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It is metabolized rapidly by RBCs with liberation of cyanide. Cyanide is metabolized by the mitochondrial enzyme rhodanse, in the presence of a sulfur donor to thiocyanate. Thiocyanate is slowly excreted by the kidney
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What is the treatment of cyanide poisoning via nitroprusside administration?
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1. Sodium thiosulfate- acts as a sulfur donor that helps with metabolism
2. Hydroxocobalamin- combines with cyanide to form nontoxic cyanocobalamin |
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What are the symptoms of thiocyanate toxicity (excessive nitroprusside)?
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Thiocyanate toxicity- weakness, disorientation, psychosis, muscle spasms, and convulsions
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What is a delayed side effect of nitroprusside administration?
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Delayed hypothyroidism- thiocyanate inhibits iodide uptake by the thyroid
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How does diazoxide lower BP?
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It prevents vascular smooth muscle contraction by opening K channels and stabilizing the membrane potential at resting level.
It causes rapid fall in systemic vascular resistance (dilates arterioles) and mean arterial BP associated with tachycardia and increase in cardiac output |
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Why is diazoxide used to treat hypoglycemia secondary to insulinoma?
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It inhibits insulin release from the pancreas - it opens K channels in the beta cell membrane
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In which patients is Fenoldopam contraindicated?
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Glaucoma patients
It increases intraocular pressure |
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How does Fenoldopam lower blood pressure?
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It is peripheral arterial arteriolar dilator due to acting as an agonist of dopamine D1 receptors.
It causes dilation of peripheral arteries and natriuriesis |
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How do calcium channel blockers work to primarily lower BP?
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It inhibits calcium influx into arterial smooth muscle cells causing vasodilation
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Which of the calcium channel blockers has the least effect on the cardiac output and heart rate?
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Nifedipine and the other dihydropyridine agents
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Which of the calcium channel blockers lower the heart rate and cardiac output the most?
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Verapamil
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Which of the calcium channel blockers should NOT be used for HTN? Why?
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Short acting oral dihydropyridines
There is increased risk of MI or mortality |
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Where is renin released from?
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kidney cortex
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What are the factors that stimulate renin release?
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1. Reduced renal arterial pressure
2. Sympathetic neural stimulation 3. reduced sodium delivery 4. increased sodium concentration at the distal renal tubule |
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What is the renin antagonist?
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Aliskiren
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How do ACE inhibitors lower BP?
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1. It inhibts the converting enzyme peptidyl dipeptidase that breaks down angiotensin I to angiotensin II- decreases PVR
2. It blocks the breakdown of Bradykinin - this leads to vasodilation via increased prostaglandin synthesis and the release of nitric oxide |
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Do ACE inhibitors cause reflex tachycardia?
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NO
They decease PVR without decreasing CO and HR |
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What is the role of ACE inhibitors in treating patients with CKD?
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They diminish proteinuria and stabilize renal function.
This is due to decreased glomerular efferent arteriolar resistance --> reducing intraglomerular capillary pressure |
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When is ACE inhibitors contraindicated in pregnancy?
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2nd and 3rd trimester
There is a risk of fetal hypotension, anuria, and renal failure |
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What over the counter drugs have an important interaction with ACE inhibitors?
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NSAIDs impair the hypotensive effects of ACE inhibitors by blocking bradykinin mediated vasodilation
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What are the common side effects to all ACE inhibitors?
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ARF (esp in bilaterally renal artery stenosis)
Hyperkalemia (more likely in DM and renal insufficiency) dry cough angioedema |
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What is malignant hypertension?
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HTN associated with hemodynamic complications such as HF, CVA, or dissectin aortic aneurysm
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What is the underlying cause of malignant HTN?
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progressive arteriopathy with inflammation and necrosis of arterioles.
The vascular lesions in the kidney releases renin-aldosterone pathway that further increases BP |
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What is Hypertensive encephalopathy?
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A classic feature of maligant HTN.
Its clinical presentation includes severe HA, mental confusion, apprehension, blurred vision, N/V, and focal neuro deficits |
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How should malignant hypertension be treated?
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BP should be lowered by about 25% maintaining diastolic BP no less than 100-110
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Which antiHTN do blacks respond?
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diuretics
CCB |
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Which antiHTN are suggested for hypertensive diabetics or for those with CKD and proteinuria?
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ACE inhibitors
ARBs Renin antagonists |
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Which antiHTN are suggested for those who have angina?
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beta blockers
CCBs |
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Which antiHTN are suggested for those who have HF?
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Diuretics; ACE inhibitors, ARBs, beta blockers or hydralazine in combo with nitrates
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