PCOL | Antihypertensives Drugs

* Cardiac output
* Peripheral vascular resistance
* Volume of intravascular fluid (*controlled at the kidney*)

\[**Principles of blood pressure regulation**\]

Blood pressure is regulated by the following:

Baroreflexes

Adjust moment-to-moment blood

pressure?

Carotid baroreceptors

Respond to stretch, and their activation inhibits sympathetic discharge?

Renin–angiotensin system

Provides tonic and longer-term regulation of blood pressure?

Increase

\[***Increase*** or ***Decrease***\]

Reduction in renal perfusion pressure results in ____ reabsorption of salt and water?

Decrease

\[***Increase*** or ***Decrease***\]

______ renal pressure stimulates renin production and leads to enhanced levels of angiotensin II?

Increase

\[***Increase*** or ***Decrease***\]

The renin–angiotensin system, this agent causes resistance vessels to constrict and stimulates aldosterone synthesis, which ultimately ______ the absorption of sodium by the kidney?

ANTI-HYPERTENSIVE DRUGS

**WHAT THERAPEUTIC CLASSIFICATION OF DRUGS?**

* The goal of therapy is to reduce elevated blood pressure, which would ultimately lead to end organ damage, increased risk of stroke, and MI.

ANTI-HYPERTENSIVE DRUGS

**WHAT THERAPEUTIC CLASSIFICATION OF DRUGS?**

* This goal is achieved through the use of various drug classes, and treatment often involves a combination of agents.

Hypertension

**WHAT MEDICATION FOR USE?**

* Thiazide diuretics
* Loop diuretics
* Potassium-sparing diuretics

TRUE

\[***TRUE*** or ***FALSE***\]

Diuretics increase sodium excretion and lower blood volume.

Renin

Decreased renal pressure stimulates _____ production and leads to enhanced levels of angiotensin II.

Sympathetic

Carotid baroreceptors respond to stretch, and their activation inhibits _______ discharge.

Increase

\[***Increase*** or ***Decrease***\]

Diuretics _____ sodium excretion and lower blood volume.

Thiazide diuretics

Are effective in lowering blood pressure 10–15 mm Hg?

Thiazide diuretics

Can provide relief for mild or moderate hypertension when administered alone?

Thiazide diuretics

Used in combination with sympatholytic agents or vasodilators in severe hypertension?

Loop diuretics

Used in combination with sympatholytic agents and vasodilators for hypertension refractory to thiazide treatment?

Potassium-sparing diuretics

Used to avoid potassium depletion, especially when administered with cardiac glycosides?

Propranolol (*Inderal*)

Antagonizes catecholamine action at both b1- and b2-receptors?

Propranolol (*Inderal*)

It produces sustained reduction in peripheral vascular resistance?

b1-adrenoceptors

Blockade of cardiac______ reduces heart rate and contractility?

b2-Adrenoceptor

Blockade increases airway resistance and decreases catecholamine induced glycogenolysis and peripheral vasodilation?

Decrease

\[***Increase*** or ***Decrease***\]

b2-Adrenoceptor blockade increases airway resistance and _____ catecholamine induced glycogenolysis and peripheral vasodilation.

Propranolol (*Inderal*)

Blockade of b-adrenoceptors in the CNS decreases sympathetic activity?

Decrease

\[***Increase*** or ***Decrease***\]

Propranolol (*Inderal*) blockade of b-adrenoceptors in the CNS ______ sympathetic activity?

Propranolol (*Inderal*)

Decreases renin release?

TRUE

\[***TRUE*** or ***FALSE***\]

Propranolol also decreases renin release.

Propranolol (*Inderal*)

Used in mild-to-moderate hypertension.

Sympatholytic agents and Vasodilators

LOOP DIURECTS are used in combination with __*_*__ and ___ for hypertension.

Nadolol (*Corgard*)

Timolol (*Blocadren*)

Carteolol (*Cartrol*)

Pindolol (*Visken*)

Penbutolol (*Levatol*)

These drugs are similar in action to propranolol and block both b1- and b2- adrenoceptors.

TRUE

\[***TRUE*** or ***FALSE***\]

Nadolol has an extended duration of action.

TRUE

\[***TRUE*** or ***FALSE***\]

Pindolol, carteolol, and penbutolol have partial agonist activity (*sympathomimetic*).

Metoprolol (*Lopressor*)

Atenolol (*Tenormin*)

Acebutolol (*Sectral*)

Bisprolol (*Zebeta*)

**ENUMERATE**: These drugs are relatively selective for b1-adrenoceptors.

FALSE (**Acebutolol**)

\[***TRUE*** or ***FALSE***\]

Atenolol has partial agonist activity.

FALSE (a- and b-adrenoceptor antagonist. )

\[***TRUE*** or ***FALSE***\]

Labetalol is an b-adrenoceptor antagonist.

Decrease

\[***Increase*** or ***Decrease***\]

Labetalol reduces heart rate and contractility, slows AV conduction, and _____ peripheral resistance.

Labetalol

Is useful for treating hypertensive emergencies.

Labetalol

Does not cause reflex tachycardia?

TRUE

\[***TRUE*** or ***FALSE***\]

Carvedilol has a significantly greater ratio of b to a antagonist activity than labetalol.

a-Adrenoceptor antagonists

Lower total peripheral resistance by preventing stimulation, which are located predominantly in resistance vessels of the skin, mucosa, intestine, and kidney?

a-Adrenoceptor antagonists

These drugs reduce pressure by dilating resistance and conductance vessels.

Labetalol

Treatment of hypertension of pheochromocytoma?

Prazosin (*Minipress*)

Terazosin (*Hytrin*)

Doxazosin (*Cardura*)

These drugs are a1-selective antagonists?

TRUE

\[***TRUE*** or ***FALSE***\]

Prazosin (*Minipress*), Terazosin (*Hytrin*) and Doxazosin (*Cardura*) are used in treating hypertension, especially in the presence of Congested Heart Failure (CHF) but use has diminished because no evidence of reduced cardiovascular events with doxazosin was found in a large clinical trial.

Prazosin (*Minipress*)

Terazosin (*Hytrin*)

Doxazosin (*Cardura*)

Are often administered with a diuretic and b-adrenoceptor antagonist?

Prazosin (*Minipress*)

Terazosin (*Hytrin*)

Doxazosin (*Cardura*)

These drugs may produce initial orthostatic hypotension?

Phentolamine (*Regitine*)

Phenoxybenzamine (*Dibenzyline*)

Antagonize a1- and a2-adrenoceptors?

Phentolamine (*Regitine*)

Phenoxybenzamine (*Dibenzyline*)

Treating hypertension in the presence of pheochromocytoma?

FALSE

(__Phentolamine__ is administered parenterally; __phenoxybenzamine__ is administered orally)

\[***TRUE*** or ***FALSE***\]

Phentolamine is administered orally; phenoxybenzamine is administered parenterally.

Decrease

\[***Increase*** or ***Decrease***\]

ACE inhibitors reduce vascular resistance and blood volume; they lower blood pressure by ______ total peripheral resistance.

ACE Inhibitors

A drugs include **captopril** (*Capoten*), **enalapril** (Vasotec), **lisinopril** (*Prinivil*, *Zestril*), **ramipril** (*Altace*), **fosinopril** (*Monopril*), **benazepril** (*Lotensin*), **moexipril** (*Univasc*), **quinapril** (*Accupril*), **perindopril** (*Aceon*), and **trandolapril** (*Mavik*).

ACE Inhibitor DRUGS (-pril)

These drugs are useful in treating mild-to-severe hypertension.

TRUE

\[***TRUE*** or ***FALSE***\]

ACE inhibitors may be less effective in African Americans than in Caucasians.

Angiotensin II receptor antagonists,

Losartan potassium (*Cozaar*)

These drugs block angiotensin II type-1 (AT-1) receptors?

FALSE

\[Losartan potassium (*Cozaar*)\]

\[***TRUE*** or ***FALSE***\]

Inhibitors of renin activity, aliskiren (Tekturna) the effects of these drugs are similar to those seen with ACE inhibitors.

Aliskiren

inhibits renin and thereby reduces the production of all angiotensins?

Calcium channel-blocking (CCB) agents

Inhibit the entry of calcium into cardiac and smooth muscle cells by blocking the L-type Ca2+-channel; they lower blood pressure by reducing peripheral resistance?

Calcium channel blockers

Used for treatment of hypertension include verapamil, nifedipine, nicardipine, nisoldipine (*Sular*), isradipine (*DynaCirc*), amlodipine (*Norvasc*), felodipine (*Plendil*), and diltiazem.

Calcium channel blockers

Are effective in the treatment of mild-to-moderate hypertension.

\[**same with propranolol**\]

Nifedipine

* have been associated with an increase in cardiovascular mortality and events, including MI and increased anginal attacks.

Short-acting preparations of the dihydropyridines?

Methyldopa (*Aldomet*)

Has an active metabolite, a-methylnorepinephrine, a potent false neurotransmitter?

Methyldopa (*Aldomet*)

Activates presynaptic inhibitory a-adrenoceptors and postsynaptic a2- receptors in the CNS and reduces sympathetic outflow. It decreases total peripheral resistance.

Methyldopa (*Aldomet*)

Reduces pressure in standing and supine positions?

Methyldopa (*Aldomet*)

Used to treat mild-to-moderate hypertension; it can be added to the regimen when a diuretic alone is not successful?

Methyldopa (*Aldomet*)

Produces adverse effects that include drowsiness, dry mouth, and GI upset?

Clonidine (*Catapres*)

Stimulates postsynaptic a2-adrenoceptors in the central nervous system (CNS) and causes reduction in total peripheral resistance.

Clonidine (*Catapres*)

Commonly produces drowsiness and lethargy, dry mouth, and constipation?

Guanabenz acetate (*Wytensin*)

Activates central a2-adrenoceptors and inhibits sympathetic outflow from the brain,

Guanabenz acetate (*Wytensin*)

This drug is used in mild-to-moderate hypertension, most commonly in combination with a diuretic?

Guanabenz acetate (*Wytensin*)

Most commonly produces sedation and dry mouth as adverse effects but with reduced frequency compared to clonidine?

Reserpine

Eliminates norepinephrine release in response to nerve impulse by preventing vesicular uptake. It depletes norepinephrine from sympathetic nerve terminals in the periphery and in the adrenal medulla?

Reserpine

Used in mild-to-moderate hypertension?

\[**same with propranolol**\]

Reserpine

Most commonly produces GI disturbances. Mental depression, sometimes severe, may result, especially with high doses; use of reserpine is contraindicated in patients with a history of depression?

Vasodilators

Relax smooth muscle and lower total peripheral resistance, thereby lowering blood pressure?

ACE inhibitors and calcium channel-blocking agents

The use of vasodilators is declining as a result of newer modalities, such as ___ and ___, which are more effective with fewer adverse effects.

Hydralazine (*Apresoline*)

Reduces blood pressure directly by relaxing arteriolar muscle. This effect is probably mediated by increasing K+ efflux and decreasing Ca2+ influx, and increasing the production of nitric oxide?

Increasing K+ efflux and decreasing Ca2+ influx

\[***Increase*** or ***Decrease***\]

The effect is probably mediated by ___ K+ efflux and ___Ca2+ influx, and increasing the production of nitric oxide?

Hydralazine (*Apresoline*)

Elicits the baroreceptor reflex, necessitating coadministration with a diuretic to counteract sodium and water retention and a b-blocker to prevent tachycardia?

Hydralazine (*Apresoline*)

This drug is used to treat chronic hypertension and in hypertensive crises accompanying acute glomerular nephritis or eclampsia?

Hydralazine (*Apresoline*)

May cause a “lupuslike syndrome”?

Minoxidil (*Loniten*)

Has effects similar to hydralazine. Minoxidil acts to increase K+ efflux, which hyperpolarizes cells and reduces the activity of L-type (voltage-sensitive) calcium channels. Vasodilates predominantly arteriolar vessels?

Minoxidil (*Loniten*)

Elicits the baroreceptor reflex, necessitating use of a b-adrenoceptor antagonist and a diuretic?

Minoxidil (*Loniten*)

Useful for long-term therapy of refractory hypertension?

Minoxidil (*Loniten*)

Produces hirsutism, an advantage in formulations that are now used to reduce hair loss in both males and females?

Sodium nitroprusside (*Nipride*, *Nitropress*)

Dilates both resistance and capacitance vessels; it increases heart rate but NOT output?

Sodium nitroprusside (*Nipride*, *Nitropress*)

This drug is frequently used in hypertensive emergencies because of its rapid action?

Furosemide

Sodium nitroprusside is usually administered with ____.

Sodium nitroprusside (*Nipride*, *Nitropress*)

Converted to cyanide and thiocyanate?

* The accumulation of cyanide and risk of toxicity are minimized by concomitant administration of sodium thiosulfate or hydroxocobalamin.

Diazoxide (*Hyperstat*)

Used intravenously to reduce blood pressure rapidly, usually in an emergency situation?

TRUE

\[***TRUE*** or ***FALSE***\]

Diazoxide is administered with furosemide to prevent fluid overload.

Diazoxide (*Hyperstat*)

Declining in use because of its unpredictable action and adverse effects?

Fenoldopam (*Corlopam*)

Selective agonist at dopamine DA1 receptors that increases renal blood flow while reducing blood pressure?

Ambrisentan (*Letaris*)

Selective endothelin A receptor antagonist used to treat pulmonary hypertension. Plasma endothelin-1 is elevated in patients with pulmonary hyper tension?

Bosentan

Antagonizes both endothelin A and B receptors and reduces pulmonary hypertension. Headache and edema are common side effects?

Drugs used to treat erectile dysfunction

Drugs in this class include sildenafil citrate (*Viagra, Revatio*), tadalafil (*Cialis*), and vardenafil hydrochloride (*Levitra*). (2) Viagra was originally developed as an antianginal and antihypertensive agent?

Viagra

Was originally developed as an antianginal and antihypertensive agent but proved very effective in treating erectile dysfunction.

Drugs used to treat erectile dysfunction

These agents specifically inhibit phosphodiesterase type V, the class of enzymes that are responsible for the breakdown of cGMP?

Drugs used to treat erectile dysfunction

These drugs are contraindicated in patients taking nitrates, because of exacerbation of the effects of these drugs, or in patients taking a1-adrenoceptor antagonists such as doxazosi?

Doxazosi

in patients taking a1-adrenoceptor antagonists such as ____ drug that contraindicated when taking nitrates because of exacerbation of the effects of this drugs.