Hypertension Drugs Flashcards
First Line Drug agents for Hypertension?
• ACE-inhibitors, ARBs, calcium channel blockers,
thiazide diuretics
Second line Drug agents for hypertension?
• b-blockers, aldosterone antagonists
Other Agents used to treat for hypertension aside from first and second line?
• Loop diuretics, a-blockers, direct vasodilators,
central a2-agonists, renin inhibitors
List the Ace inhibitors and their MOA?
Captopril / Enalapril / Lisinopril
MOA: • BP by peripheral vascular resistance
• INHIBIT ACE (angiotensin converting enzyme) that
cleaves angiotensin I to form angiotensin II
• DECREASE Na+ & H20 retention
• INCREASE BRADYKININ levels
• DO NOT reflexively increase cardiac output, rate or
contractility
Clinical Application of Ace inhibitors?
• Hypertension (most effective in white and/or young
patients)
+ diuretic = effectiveness similar in non-black and black
patients
• Preserve renal function in patients with either diabetic
or non-diabetic nephropathy
• Effective in treatment of chronic HF
• Standard of care for patients following MI (started 24h
after end of infarction)
ACE inhibitors AE?
• Dry hacking cough • Hyperkalemia • Hypotension • Angioedema (rare but life-threatening) • Acute renal failure (patients with bilateral renal artery stenosis) • Rash, fever, altered taste
Ace inhibitor contraindications?
• Pregnancy
During 1st trimester due to risk of congenital
malformations and during 2nd and 3rd trimesters
because of risk of fetal hypotension, anuria & renal
failure
• Patients with bilateral renal artery stenosis
• Patients with a history of angioedema related to previous
treatment with an ACEI and in patients with hereditary or
idiopathic angioedema.
Name ARBS for htn and MOA?
ARBS: Losartan / Valsartan
MOA:
• Angiotension receptor blockers (ARB’s)
• First-line agents
• Alternatives to ACEI’s (in intolerant patients)
• Block angiotensin-2 type 1 receptors
• BP by causing arteriolar & venous dilation
• Block aldosterone secretion à decrease Na+ & H20
retention
• diabetic nephrotoxicity
• DO NOT INCREASE BRADYKININ levels
ARB AE?
• Similar to those of ACE inhibitors( Hyperkalemia
• Hypotension
• Acute renal failure (patients with bilateral renal artery
stenosis)
• Rash, fever, altered taste)
• Dry cough does not occur (due to no effect on
bradykinin levels)
• Angioedema risk is significantly lower than with
ACEI’s
• Losartan reduces plasma uric acid levels by inhibiting
URAT1 transporter – can be useful in patients with
gout
ARB contraindications?
- Pregnancy
* Patients with bilateral renal artery stenosis
Renin inhibitor name, MOA and AE?
Aliskiren
MOA: • Inhibits enzyme activity of renin and prevents
conversion of angiotensinogen into angiotensin I
End result:
• Inhibits production of both angiotensin II and
aldosterone
AE:• Similar to those of ACE inhibitors
• Dry cough does not occur (due to no effect on
bradykinin levels)
• Angioedema risk is significantly lower than with
ACEI’s
Name calcium channel blockers?
Ca2+ CHANNEL CLASSES • Non-dihydropyridines • Verapamil • Diltiazem • Dihydropyridines • Nifedipine, amlodipine
Verapamil selectivity and use?
• Least selective of any Ca2+-blocker
• Significant effects in cardiac & vascular smooth muscle
• Used to treat angina, supraventricular
tachyarrhythmias, hypertension, migraine & cerebral
vasospasm
Diltiazem selectivity and use?
• Effects in both cardiac & vascular smooth muscle (less
pronounced effect on heart than verapamil)
• Good side-effect profile
• Used to treat angina, hypertension, supraventricular
tachyarrhythmias & cerebral vasospasm
Dihydropyridines selectivity and use?
Amlodipine, nifedipine
• Greater affinity for vascular Ca2+-channels than for cardiac
Ca2+-channels
• Reduce Ca2+ entry into smooth muscles to cause
coronary & peripheral vasodilatation & lower BP
• Primarily used in treating hypertension.
Calcium channel blocker clinical applications?
• Hypertension (particularly black and/or elderly
patients)
• Have intrinsic natriuretic effect (no need for diuretic)
• Useful in patients with asthma, diabetes, peripheral
vascular disease
Calcium channel blockers can and can’t be used for what clinical use?
Hypertension, angina, and cardiac arrythmias(except Dihydropyridines(amlodipine, nifedipine), these can’t be used for arrythmias).
Calcium channel PK?
• High-doses of short-acting dihydropyridine Ca2+-
channel blockers can increase risk of MI (excessive
vasodilation & reflex cardiac stimulation)
• Sustained release preparations are preferred
AE of Calcium Channel blockers
• Verapamil
Constipation (~7%), negative inotropic effects, gingival
hyperplasia
• Dihydropyridines
Hypotension, peripheral edema (esp. feet & ankles),
dizziness, headache, fatigue, gingival hyperplasia,
flushing, reflex tachycardia can occur (especially in
short-acting preparations)
• Non-dihydropyridines (verapamil & diltiazem)
Relatively contraindicated in patients taking b-blockers,
or who have 2nd or 3rd degree AV block, or severe left
ventricular systolic dysfunction
Thiazides MOA and Clinical applications with regard to hypertension?
• First-line agents (particularly black and/or elderly
patients)
MOA
• Lower BP by Na+ and H20 excretion à in extracellular
volume à in cardiac output & renal blood flow.
• Long-term treatment = normal plasma volume but
sustained decreased peripheral resistance
Thiazides
• Counteract Na+ & H20 retention caused by other
antihypertensive drugs
• Particularly useful in black & elderly (with normal renal
& cardiac function)
Thiazide AE?
- Hypokalemia
- Hyperuricemia
- Hyperglycemia
- Hypomagnesemia
- Hypercholesterolemia
- Sexual dysfunction
Loop diuretic role in Hypertension. Potassium sparing diertics role in hypertension?
Loop: • Act promptly in patients with poor renal function or heart failure
• More potent at inducing diuresis & can cause more side effects
• Used primarily in patients who do not respond to
thiazide therapy adequately
• Cause renal vascular resistance & renal blood flow
Potassium sparing:
• K+ loss in urine caused by thiazide or loop diuretics
• Used in combination with other diuretics
Aldosterone antagonist MOA and clinical use in hypertension?
Spirnolactone
Antagonism of aldosterone receptor à inhibition of Na+
and H20 retention à inhibition of vasoconstriction
• Reduces K+ excretion à risk of hyperkalemia (more
prominent in patients with chronic kidney disease or in
patients taking concurrent ACEI, ARB or other K+-sparing
diuretics)
• Used in the treatment of hypertension & heart failure
• Can be used as part of first-line therapy in patients
with hypertension & severe left ventricular
dysfunction
Name Beta blockers used for hypertension and when are beta blockers added used for hypertension?
Propranolol / Metoprolol / Atenolol / Pindolol
• Used only as add-on therapy to first line agents in
primary prevention patients
• First-line therapy only for patients with coronary
artery disease, heart failure or post-MI
Propranolol / Metoprolol / Atenolol / Pindolol selectivity?
• Propranolol
Non-selective b1 & b2 receptor antagonist
• Metoprolol & atenolol (most widely used)
Selective b1 receptor antagonists
• Pindolol
Non-selective b1 & b2 partial agonist with intrinsic
sympathomimetic activity (preferred b-blocker in
pregnancy)
Beta blockers MOA and PK?
MOA
• Reduce BP by cardiac output, contractility & heart rate
• Blunt sympathetic reflex with exercise
• Inhibit both release of norepinephrine and renin (b1 R) (à
decrease in angiotensin II & aldosterone secretion)
Pharmacokinetics
• May take several weeks to develop full effects
Beta blocker AE?
• Bradycardia, CNS effects (fatigue, lethargy, insomnia,
hallucinations), hypotension, decreased libido &
impotence
• Disturb lipid metabolism ( HDL & TAGs)
• Hypoglycemia (via b2 blockade)
• Drug withdrawal (abrupt withdrawal may induce angina,
MI or sudden death in patients with heart disease) à
taper off dose in these patients
• Propranolol is contraindicated in asthmatics and COPD
patients
List Alpha 1 blockers and MOA?
Prazosin / Doxazosin
MOA:
• Competitively block a1-adrenoceptors
• peripheral vascular resistance & arterial BP by
relaxing both arterial & venous smooth muscle
• Cause minimal changes in cardiac output, renal blood
flow & GFR -> no long-term tachycardia
• Na+ & H20 retention does occur
• Effective in lowering BP but more side effects than
other antihypertensives
Clinical applications of alpha 1 blockers?
• Hypertension (due to side-effect profile, development
of tolerance & advent of safer antihypertensives, ablockers are seldom used in treatment of
hypertension)
• Reserved as alternative agents for unique situations, such as men with benign prostatic hyperplasia
• Have been used in heart failure (but not commonly)
alpha 1 blocker AE?
• Orthostatic hypotension (which may lead to syncope)
upon first-dose or large increases in dose
• Concomitant use of a b-blocker may be necessary to blunt short-term effect of reflex tachycardia
• Dizziness, drowsiness, headache, lack of energy, nausea, and palpitations,
• Doxazosin shown to rate of congestive HF
Mixed Alpha and Beta blocker name, PK, advantages, and AE?
Labetalol
• Oral & parenteral admin.
• Used in hypertension management (safe in pregnancy)
• IV labetalol = rapid reduction in BP à useful in
hypertensive emergencies
Advantages
• in BP associated with a1-blockade is not
associated with reflex increase in HR or cardiac
output
AE:
• Orthostatic hypotension may be a problem (first use or
high doses)
Clonidine MOA, use, and AE?
Central alpha 2 agonist
• Reduces sympathetic outflow by acting on presynaptic a2
adrenergic autoreceptors
• Resultant decrease in peripheral vascular resistance &
cardiac output à BP
• DOES NOT renal blood flow or GFR
• Used in hypertension management, including
hypertensive crises (other drugs with fewer side effects
are now generally preferred)
• Drowsiness, dry mouth, dizziness, headache & sexual
dysfunction occur commonly
• Rebound hypertension may occur following abrupt
withdrawal (avoid concomitant use with b-blockers)
AE of methyldopa?
• Sedation, drowsiness, dizziness, nausea, headache,
weakness, fatigue, sexual dysfunction
• Nightmares, mental depression, vertigo (infrequent)
• Development of positive Coombs test (10-20% patients
on long-term treatment (>1 year)). Can result in hemolytic
anemia, hepatitis & drug fever
MOA and Clinical use of methyl dopa?
Central alpha 2 agonist
• a2-agonist converted to a-methyldopamine and amethylnorepinephrine
centrally to diminish sympathetic
outflow in CNS
• à peripheral resistance & BP (cardiac output NOT )
• DOES NOT renal blood flow or GFR
• Usually treatment of choice for pregnancy-induced
hypertension
• Used in hypertension management (other drugs with
fewer side effects are now generally preferred)
Direct vasodilators name and moa?
Hydralazine / Minoxidil
• Not used as first-line antihypertensives
• Direct acting smooth muscle relaxants
• Produce reflex tachycardia, increase plasma renin à Na+ & H20 retention
• Major side effects can be blocked if combined with diuretic & b-blocker
Hydralazine pk and use?
- Can be given oral or IV
- Acts mainly on arterioles
- Used to treat pregnancy induced hypertension / preeclampsia
- Used in management of hypertension as last-line therapy
Hydralazine AE?
- Fluid retention & reflex tachycardia are common
- Reversible lupus-like syndrome
- Headache, nausea, sweating, flushing
- Usually administered with b-blocker & thiazide
Minoxidil AE and use?
• Causes direct peripheral vasodilatation of arterioles
• Oral treatment for severe-malignant hypertension
(refractory to other treatments)
AE:
• Reflex tachycardia & fluid retention may be severe
(combine with loop diuretic & b-blocker)
• Causes hypertrichosis (also used topically to treat
male pattern baldness)
Treatments for pulmonary hypertension?
• Prostaglandins (epoprostenol)
• Inhibitors of endothelin synthesis and action
(bosentan)
• Vasodilators (sildenafil)
Epoprostenol PK, AE, and use?
• Synthetic PGI2
• Lowers peripheral, pulmonary, and coronary resistance
• Given via continuous infusion
• Adverse effects include flushing, headache, jaw pain,
diarrhea and arthralgias
Bosentan moa and contraindication?
• Nonselective endothelin receptor blocker
• Blocks both the initial transient depressor (ETA) and the
prolonged pressor (ETB) responses to endothelin
• Pregnancy category X
Sildenafil
• Inhibitor of phosphodiesterase 5 (PDE5)
• Increased cGMP à smooth muscle relaxation
• Adverse Effects: headache, flushing, dyspepsia,
cyanopsia
• Contraindications: Nitrates
First and second line treatment for CKD, Diabetes, and prior ischemic stroke when treating hypertension?
1st line b-blocker + ACEI or ARB 2nd Line: Thiazide diuretic (BP control), CCB (ischemia control)
Drugs used for hypertensive emergency?
• Sodium nitroprusside • Labetalol • Fenoldopam • Nicardipine • Nitroglycerin • Diazoxide • Phentolamine • Esmolol • Hydralazine
Hypertension treatment for patient with previous HF?
1st Line ACEI or ARB + thiazide (or loop) diuretic + b-blocker 2nd line: Aldosterone antagonist (if severe), hydralazine/isosorbide dinitrate ( if black)
Hypertension treatment with Chronic or Acute
CAD?
1st line b-blocker + ACEI or ARB 2nd line Thiazide diuretic (BP control), CCB (ischemia control)
Hypertension with previous MI?
1st line:
b-blocker then add ACEI / ARB
2nd line:
Aldosterone antagonist
Sodium nitroprusside pk and MOA?
• Always given IV (poisonous if given orally)
• t1/2 = 1-2 min à requires continuous infusion
• Prompt vasodilation & reflex tachycardia
• Causes peripheral vasodilation by direct effects on
arterial & venous smooth muscle
Sodium Nitroprusside AE?
• Hypotension (overdose), goose bumps, abdominal
cramping, nausea, vomiting, headache
• Cyanide toxicity (rare)
Nitroprusside metabolism à cyanide ion
Can be treated with sodium thiosulfate infusion à
nontoxic thiocyanate
Significance of Labetalol use in hypertensive emergencies?
• Combined a and b blocker
• IV bolus or infusion for hypertensive emergency
• t1/2 = 3-6 h
• DOES NOT cause reflex tachycardia
Contraindications
Asthma, COPD, patients with 2nd or 3rd-degree AV
block or bradycardia
Fenoldopam moa, ,pk, ae, and contraindications?
• Peripheral dopamine-1 (D1) receptor agonist
• Evokes arteriolar dilation
• IV infusion for hypertensive emergency
• t1/2 = 30 min
• Maintains or increases renal perfusion as lowers BP
• Promotes naturesis
• Safe to use in all hypertensive emergencies (particularly
beneficial in patients with renal insufficiency)
Contraindications
Glaucoma
Nicardipine significance as a calcium channel blocker?
- Calcium-channel blocker
- IV infusion for hypertensive emergency
- t1/2 = 30 min
- Evokes reflex tachycardia
Nitroglycerin use in hypertensive emergencies?
• Vasodilator (more effect on veins than arteries)
• Drug of choice for hypertensive emergencies in
patients with cardiac ischemia or angina, or after
cardiac bypass surgery
• t1/2 = 2-5 min
• Hypotension = most serious side effect
Diazoxide use in hypertensive emergencies?
• Arteriolar dilator
• Prevents vascular smooth muscle contraction by opening
K+ channels and stabilizing membrane potential
• t1/2 = ~ 24 h
Adverse Effects
Hypotension, reflex tachycardia, Na+ & H20
retention
• Inhibits insulin release and can be used to treat
hypoglycemia secondary to insulinoma
Phentolamine, Esmolol, and hydralazine use in hypertensive emergencies?
Phentolamine
Drug of choice for patients with catecholaminerelated
emergencies
Esmolol
Often used for aortic dissection or postoperative
hypertension
Hydralazine
Drug of choice in treating hypertensive emergencies
in pregnancy related to eclampsia
