cardiovascular drugs Flashcards by EDGAR JORDAN ESPINOLA

acts as a pump of blood into the circulatory system

Heart

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contractility

inotropy

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rate and rhythm

chronotropy

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conduction velocity

dromotropy

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carry blood to/from the heart/to the tissues

blood vessels

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carry blood away from the heart

arteries

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carry blood toward the heart

veins

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exchange substances between blood and tissues

capillaries

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3 types of circulation

-Pulmonary
-Systemic
-Coronary

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-for oxygenation of blood:
right ventricle to
pulmonary arteries to
lungs to
pulmonary veins to
left atrium

Pulmonary circulation

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for oxygenation of tissues:
left ventricle
aorta
arteries
tissues
veins
superior and inferior vena cava
right atrium

Systemic circulation

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for oxygenation of the heart:
left ventricle
aorta
coronary arteries
cardiac veins
coronary sinus
right atrium

Coronary circulation

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Systolic blood pressure of ≥130 mm Hg or diastolic blood pressure of ≥80 mm Hg on the average of two or more seated blood pressure
readings during each of two or more outpatient visits
the most common cardiovascular disease
increases the risk for coronary heart disease (CHD), congestive heart failure (CHF), ischemic and hemorrhagic stroke, renal failure, and peripheral arterial disease

hypertension

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<120 / <80 bp

normal

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120-129 / <80 bp

elevated

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130-139 / 80-89

stage 1 hypertension

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> 140 / >90

stage 2 hypertension

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BP of 180 mm Hg SBP or 120 mm Hg DBP

Hypertensive crisis

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no end organ damage

hypertensive urgency

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with acute end organ damage

hypertensive emergency

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hypertensive emergency associated w/an abrupt increase of BP in a patient with underlying hypertension or related to the sudden onset of hypertension in a previously normotensive individual

Malignant hypertensive

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“essenytial” hypertension
80-95%
Familial; environmental and genetic factors
No specific cause of hypertension

primary hypertension

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5-20%
Due to other diseases

secondary hypertension

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secondary causes of hypertension

-renal
-renovascular
-adrenal
-aortic coarctation
-obstructive sleep apnea
-preeclampsia/eclampsia
-neurogenic
miscellaneous endocrine
medications

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-parenchymal disease -renal cysts (polycystic kidney disease) -renal tumors (renin-secreting tumors) -obstructive uropathy

renal (secondary cause of hypertension)

-arteriosclerotic -fibromuscular dysplasia

renovascular secondary cause of hypertension

-primary aldosteronism -Cushing's syndrome -17a-hydroxylase deficiency -11b-hydroxylase deficiency -11-hydroxysteroid dehydrogenase deficiency (licorice) -pheochromocytoma

Adrenal secondary cause of hypertension

a narrowing in a part of the body's main artery, called the aorta. The heart must pump more forcefully to send blood through the aorta and on to the rest of the body.

aortic coarctation secondary cause of hypertension

OSA episodes produce surges in systolic and diastolic pressure that keep mean blood pressure levels elevated at night.

obstructive sleep apnea

Early in a pregnancy, new blood vessels develop and evolve to supply oxygen and nutrients to the placenta. In women with preeclampsia, these blood vessels don't seem to develop or work properly

preeclampsia secondary cause of hypertension

determinants of blood pressure

cardia output: stroke volume, heart rate peripheral resistance: vascular structure, vascular function

the greater the heart muscle is stretched during filling, the greater is the force of contraction and the greater the quantity of blood pumped into the aorta

Frank-Starling mechanism

the force required to maintain blood flow from the root of the aorta to the venous exit into the auricles.

Total Peripheral Resistance

the resistance of the arteries to blood flow

peripheral resistance

-blood vessel diameter -blood viscosity -blood vessel length

peripheral resistance

↑ intravascular volume → ↑ preload → ↑ CO → ↑ BP *related to NaCl intake *Na+ - primary ECF cation *↑ Na+ → intravascular volume

Intravascular Volume

* ɑ1 * vasoconstriction → ↑ TPR → ↑ BP * ↑ tubular reabsorption of Na+ * ɑ2 * inhibition of further noradrenergic release → ↓ BP * β1 * ↑ HR and contractility → ↑ CO → ↑ BP * ↑ renin release * β2 * vasodilation → ↓ TPR → ↓ BP

Autonomic Nervous System

* causes a decrease in sympathetic outflow and increase in parasympathetic outflow (via vagus nerve) whenever an increase in blood pressure occurs → decreased HR and inotropy * causes an increase in sympathetic outflow and decrease in parasympathetic outflow (via vagus nerve) whenever a decrease in blood pressure occurs → increased HR and inotropy

Baroreceptor Reflex

* Angiotensin II * Vasoconstriction * NaCl reabsorption * Aldosterone * NaCl reabsorption

RAAS (RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM)

drop in blood pressure drop in fluid volume renin is released from the

kidney

renin acts on the angiotensinogen to form

angiotensin I

ACE release from lungs ACE acts on angiotensin I to form

Angiotensin II

ACE

angiotensin-converting enzyme

Angiotensin acts on the adrenal gland to stimulate the release of

Aldosterone

angiotensin II acts directly on the blood vessels, stimulating

vasoconstriction (narrowing)

aldosterone acts on the kidneys to stimulate

reabsorption of salt and water

* Heart – IHD, heart failure * Brain – stroke * Kidney – chronic kidney disease (CKD), end-stage renal disease (ESRD) * Peripheral arteries – peripheral arterial disease

pathologic consequences of hypertension

treatment of hypertension

-lifestyle modification -pharmacologic therapy

attain and maintain BMI <25kg/m2

weight reduction

<6 g NaCl/day

salt reduction

Decreases heart rate (inhibits)

parasympathetic autonomous nervous system

stimulates heart rate

sympathetic autonomous nervous system

MOA: inhibit Na+ reabsorption Hemodynamics Effects: initial: ↓ CO, maintained/↑ TPR delayed: after 6-8wks: normal, ↓ TPR

Diuretics

* Thiazide Diuretics * Loop Diuretics * K+ -sparing Diuretics

DIURETICS

* Hydrochlorothiazide (HCTZ) – prototype * Chlorothiazide – parent * Chlorthalidone * Indapamide

THIAZIDE DIURETICS

* MOA: block the NCC (Na+-Cl– cotransporter/symporter) in the distal convoluted tubule (DCT)

THIAZIDE DIURETICS

* Uses: mild or moderate hypertension and normal renal and cardiac function * ADR: * hypokalemic metabolic alkalosis * hyperuricemia * hyperglycemia * hyperlipidemia * hyponatremia * hypersensitivity (cross-reactive with sulfonamides)

THIAZIDE DIURETICS

* Furosemide prototype * Ethacrynic Acid prototype * Bumetanide * Torsemide

LOOP DIURETICS

* High-ceiling, most efficacious diuretics * MOA: inhibit NKCC2 (luminal Na+/K+/2Cl−transporter) in the thick ascending limb of loop of Henle

LOOP DIURETICS

* Uses: * severe hypertension * renal insufficiency, when glomerular filtration rate (GFR) <30 mL/min * cardiac failure or cirrhosis * ADR: * hypokalemic metabolic alkalosis * ototoxicity * hyperuricemia * Hypomagnesemia * hypersensitivity (cross reactive with sulfonamides except ethacrynic acid)

LOOP DIURETICS

* Spironolactone * Eplerenone * Amiloride * Triamterene

K+-SPARING DIURETICS

* Spironolactone, Eplerenone (aldosterone antagonists) * Amiloride, Triamterene

K+-SPARING DIURETICS

block aldosterone receptors

Spironolactone, Eplerenone (aldosterone antagonists)

block Na+ entry in the epithelial Na+-channels (ENaC) in the apical membrane of the collecting tubule

Amiloride, Triamterene

* Use: * to avoid excessive potassium depletion * to enhance the natriuretic effects of other diuretics * Hyperaldosteronism * ADR: * hyperkalemia * hyperchloremic metabolic acidosis * gynecomastia (spironolactone) * kidney stones (triamterene) * CI: hyperkalemia

K+-SPARING DIURETICS

* Aliskiren * Angiotensin Converting Enzyme (ACE) Inhibitors * Angiotension II Receptor Blockers (ARBs)

RAAS INHIBITORS

* MOA: blocks binding site of renin in angiotensinogen * Hemodynamic Effect: decreased TPR * Use: primary hypertension (in combination) * ADR: angioedema, hyperkalemia

ALISKIREN

* All are prodrugs except captopril and lisinopril. * MOA: inhibit ACE * Hemodynamic Effect: decreased TPR

ACE INHIBITORS

* Uses: * hypertension with CKD, diabetes, and heart failure * hypertensive emergency (IV enalaprilat) * ADR: * acute renal failure in renal artery stenosis * hyperkalemia * dry cough and angioedema (due to increased bradykinins) * CI: pregnancy

ACE INHIBITORS

* MOA: block AT1 receptor * Hemodynamic Effect: decreased TPR * Uses: same as ACE inhibitors * ADR: same as ACE inhibitors but less common cough and angioedema

ARBs

Azilsartan Candesartan Eprosartan Irbesartan Losartan Olmesartan Telmisartan Valsartan

ARBs Angiotensin Receptor Blockers

*dihydropyridine *non-dihydropyridine

CCBs Calcium Channel Blockers

* Amlodipine * Felodipine * Isradipine * Nicardipine * Nifedipine * Nisoldipine * Clevidipine (IV)

DIHYDROPYRIDINE CCBs

* Verapamil * Diltiazem

NON-DIHYDROPYRIDINE CCBs

* MOA: block voltage-gated L-type calcium channel and thereby block Ca2+ influx into the cardiac and arterial smooth muscles * ADR: cardiac depression, peripheral edema

Ca2+ -CHANNEL BLOCKERS (CCBs)

vascular effect only – vasodilation; decreased TPR and maintained/increased CO

Dihydropyridines CCBs

vascular and cardiac effects – vasodilation and decreased heart rate; decreased TPR and CO

Nondihydropyridines CCBs

* β-blockers * ɑ-blockers * Centrally Acting Sympatholytics * Adrenergic Neuron Blockers

SYMPATHOLYTICS

* MOA: competitively block β receptors; decrease renin * Uses: mild to moderate hypertension

β-BLOCKERS

Propranolol, Nadolol, Pindolol, Penbutolol, Timolol, Labetalol, Carvedilol, Carteolol

Nonselective: β-BLOCKERS

Bisoprolol, Metoprolol, Atenolol, Acebutolol, Nebivolol, Esmolol, Betaxolol, Celiprolol

Cardioselective: β-BLOCKERS

Pindolol, Acebutolol, Carteolol, Celiprolol, Penbutolol, Labetalol

with ISA (Intrinsic Sympathomimetic Activity) β-BLOCKERS

β-BLOCKERS Hemodynamic Effects Without ISA:

decreased HR, CO and TPR

β-BLOCKERS Hemodynamic Effects With ISA:

decreased TPR

* Carvedilol, Labetalol * Hemodynamic Effect: decreased TPR but normal CO * Uses: pheochromocytoma, hypertensive emergencies

β-BLOCKERS WITH ɑ1 -ANTAGONIST ACTIVITY

* Celiprolol, Nebivolol, Carteolol * Hemodynamic Effect: decreased TPR but normal CO

β-BLOCKERS WITH NO PRODUCTION

DOXAZOSIN PRAZOSIN TERAZOSIN

ɑ-BLOCKERS

* MOA: block all ɑ-receptors * Hemodynamic Effect: decreased TPR but increased HR & CO * Uses: diagnosis and treatment of pheochromocytoma

NONSELECTIVE: PHENTOLAMINE, PHENOXYBENZAMINE

* MOA: block ɑ1-receptors in arterioles and venules * Hemodynamic Effect: decreased TPR * Use: combined with β-blockers or diuretics in hypertension * ADR: first-dose phenomenon (orthostatic hypotension)

SELECTIVE ɑ1: PRAZOSIN, TERAZOSIN, DOXAZOSIN

refers to a sudden drop in blood pressure (orthostatic hypotension) that occurs after taking the first dose of certain medications, particularly alpha-blockers. This can cause dizziness, fainting, or even falls when a person stands up suddenly.

first-dose phenomenon (orthostatic hypotension)

CLONIDINE GUANABENZ GUANFACINE METHYLDOPA

CENTRALLY ACTING SYMPATHOLYTICS

* an analog of L-dopa * PK: metabolized to ɑ-methyldopamine, then ɑ- methylnorepinephrine * MOA: ɑ-methylnorepinephrine inhibits adrenergic neuronal outflow from the brainstem (acts as agonist at presynaptic ɑ2 -receptors in the brainstem) * Hemodynamic Effect: decreased TPR w/ or w/o decreased HR and CO * Use: hypertension in pregnancy * ADR: sedation, (+) Coombs test

METHYLDOPA

* MOA: agonists at ɑ2 -receptors in the medulla * Hemodynamic Effect: decreased HR, CO, and TPR * ADR: sedation, xerostomia, abrupt withdrawal can cause hypertensive crisis

CLONIDINE (PO, IV, TRANSDERMAL), GUANFACINE, GUANABENZ

GUANADREL GUANETHIDINE RESERPINE

ADRENERGIC NEURON BLOCKING AGENTS

* MOA: interferes with vesicular membrane-associated transporter (VMAT) and thereby inhibiting storage of biogenic amines in vesicles * ADR: sedation, lassitude, nightmares, severe mental depression, EPS

RESERPINE

* MOA: block release of NE from sympathetic nerve endings * ADR: postural hypotension, delayed or retrograde ejaculation, diarrhea

GUANATHIDINE, GUANADREL

DIAZOXIDE FENOLDOPAM HYDRALAZINE MINOXIDIL NITROPRUSSIDE

DIRECT VASODILATORS

* Hydralazine * Minoxidil * Diazoxide * Fenoldopam

ARTERIAL VASODILATORS

* Nitroprusside

ARTERIAL & VENOUS VASODILATORS

release of NO (nitric oxide) from drug or endothelium

DIRECT VASODILATORS Nitroprusside Hydralazine Nitrates Histamine Acetylcholine

reduction of Calcium influx

DIRECT VASODILATORS Verapamil Diltiazem Nifedipine

hyperpolarization of cell membranes through opening of potassium channels

DIRECT VASODILATORS Minoxidil Diazoxide

activation of dopamine receptors

DIRECT VASODILATORS Fenoldopam

* MOA: relaxation of vascular smooth muscles * Hemodynamic Effect: decreased TPR with increased HR & CO * Uses: oral forms used in combination with other antihypertensive drugs; parenteral forms for hypertensive emergencies

DIRECT VASODILATORS

* MOA: unknown * Uses: in combination with ACEI or ARB for CHF; preeclampsia * ADR: headache, nausea, flushing, hypotension, palpitations, tachycardia, dizziness, angina pectoris, SLE-like syndrome (malar rash, arthralgia, myalgia)

HYDRALAZINE (PO)

* MOA: activates the ATP-modulated K+ channel in smooth muscle, causing hyperpolarization and relaxation of arteriolar smooth muscle * Uses: for severe hypertension that responds poorly to other antihypertensives; hair regrowth (topical) * ADR: fluid and salt retention, cardiovascular effects (tachycardia, angina), hypertrichosis

MINOXIDIL (PO)

* MOA: activates the ATP-modulated K+ channel in smooth muscle, causing hyperpolarization and relaxation of arteriolar smooth muscle * Uses: hypertensive emergency; hypoglycemia secondary to insulinoma (inhibits insulin release from the pancreas) * ADR: hypotension, angina

DIAZOXIDE (IV)

* MOA: an agonist of dopamine D1 -receptors, resulting in dilation of peripheral arteries and natriuresis * Use: hypertensive emergency, postoperative hypertension * ADR: tachycardia, headache, flushing, increased intraocular pressure (IOP)

FENOLDOPAM (IV)

* MOA: activates guanylyl cyclase, either via release of nitric oxide or by direct stimulation of the enzyme * Use: hypertensive emergency * ADR: accumulation of cyanide; metabolic acidosis, arrhythmias, excessive hypotension, death

Na NITROPRUSSIDE (IV)

hemodynamic effects summary *diuretics *arteriolar vasodilators *ca+ channel blockers *ACEIs (ACE inhibitors) *AT1, receptor blockers *renin inhibitors

decreased TPR except No ISA (↓ or no change)

sympathetic nerve terminals

Guanadrel Guanethidine Reserpine

Vasomotor center

Methyldopa Clonidine Guanabenz Guanfacine

Beta- receptors of the heart

Propranolol and other beta blockers

Sympathetic ganglia

Trimethaphan

* thiazide diuretic * calcium channel blocker * ACE inhibitor * ARB

General Nonblack Population:

* thiazide diuretic * calcium channel blocker

General Black Population:

If target BP is not reached w/n 1 month,

increase dose of initial medication or add a second medication.

direct sequelae of hypertension

(HF, IHD, chronic kidney disease, recurrent stroke)

commonly associated with hypertension

(diabetes, high coronary disease risk)

Therapeutic decisions in such individuals should be

directed at both the compelling indication and BP lowering.

recommended drugs for compelling indication: Heart Failure

*diuretic *beta blockers *ACE inhibitors * ARBs Angiotensin II receptor blockers *aldosterone antagonist

recommended drugs for compelling indication: Post Myocardial Infarction

*beta blockers *ACE inhibitors *aldosterone antagonist

recommended drugs for compelling indication: High Coronary Heart Disease

*diuretic *beta blockers *ACE inhibitors *calcium channel blockers

recommended drugs for compelling indication: Diabetes

*diuretic *beta blockers *ACE inhibitors * ARBs Angiotensin II receptor blockers *calcium channel blockers

recommended drugs for compelling indication: Chronic Kidney Disease

*ACE inhibitors * ARBs Angiotensin II receptor blockers

recommended drugs for compelling indication: Recurrent Stroke Prevention

*diuretic *ACE inhibitors

ANTIHYPERTENSIVES IN PREGNANCY

* Methyldopa * Nifedipine * Hydralazine * Labetalol

ANTIHYPERTENSIVES IN HYPERTENSIVE EMERGENCY Hypertensive encephalopathy

nitroprusside nicardipine labetalol

ANTIHYPERTENSIVES IN HYPERTENSIVE EMERGENCY malignant hypertension (when IV therapy is indicated)

labetalol nicardipine nitroprusside enalaprilat

ANTIHYPERTENSIVES IN HYPERTENSIVE EMERGENCY stroke

nicardipine labetalol nitroprusside

ANTIHYPERTENSIVES IN HYPERTENSIVE EMERGENCY myocardial infarction/unstable angina

nitroglycerin nicardipine labetalol esmolol

ANTIHYPERTENSIVES IN HYPERTENSIVE EMERGENCY acute left ventricular failure

nitroglycerin enalaprilat loop diuretics

ANTIHYPERTENSIVES IN HYPERTENSIVE EMERGENCY aortic dissection

nitroprusside esmolol labetalol

ANTIHYPERTENSIVES IN HYPERTENSIVE EMERGENCY adrenergic crisis

phentolamine nitroprusside

ANTIHYPERTENSIVES IN HYPERTENSIVE EMERGENCY postoperative hypertension

nitroglycerin nitroprusside labetalol nicardipine

ANTIHYPERTENSIVES IN HYPERTENSIVE EMERGENCY preeclampsia/eclampsia of pregnancy

hydralazine labetalol nicardipine

cardiovascular drugs Flashcards

midterm