Antihypertensive Drugs Flashcards
Major groups of antihypertensive drugs
Diuretics (thiazide, loop, potassium-sparing), sympatholytic, angiotensin inhibitors and vasodilators
Thiazide and related diuretics - MoA
Mechanism of decrease BP stems from their ability to increase sodium and water excretion.
When they are first administrated, the drug decreases blood volume and thereby decreases cardiac output. When adm is continued over weeks and months they also decrease peripheral vascular resistance (PVR), and this appear to account for much of their long term antihypertensive effect. The decrease PVR may result from a reduction in the sodium content of arteriolar smooth muscle cells, which decrease muscle contraction in response to vasopressor agents such as norepinephrine and angiotensin.
Thiazide and related diuretics - Adverse effects
Hypokalemia –> cardiac arrhythmias and muscle weakness.
Elevate plasma levels of: glucose, uric acid and lipids in some pat.
Hematologic toxicity
Aggravate hepatic disease and diabetes
Compensatory increase in renin secretion
Blood cell deficiencies
Thiazide and related diuretics - Interactions
Increase serum levels of lithium. Hypotensive effect decreased by NSAIDs and augmented by ACE inh.
Thiazide diuretics
Hydrochlorothiazide
Indapamide
Chlorthalidone
Hydrochlorothiazide - Indication
Initial treatment of persons with mild to moderate hypertension.
Thiazide diuretic most often used to treat hypertension.
Indapamide - Indication and benefit
Hypertension and the risk of stroke and MI.
Causes vasodilation via calcium channel blockade
Loop diuretics - MoA
Greater natriuretic effect.
Less effective than thiazide, they are reserved for use in hypertensive pat who have poor renal function and serum creatinine level greater than 2,3mg/dL.
Potassium - sparing diuretics - MoA
Mild natriuretic effect and they reduce renal potassium excretion –> prevent hypokalemia by thiazide drugs/ loop diuretics
Potassium - sparing diuretics - Adverse effects
Hyperkalemia
Potassium - sparing diuretics - Interactions
Hyperkalemic effect increased by ACE inh and potassium supplements.
Potassium - sparing diuretics
Amiloride
Spironolactone
Eplerenone
Triamterene
Spironolactone and Eplerenone - Indication
Hypertension that cannot be controlled with combinations of three or more other agents.
Alpha-adrenoceptor antagonists
Doxazosin
Prazosin
Terazosin
Alpha-adrenoceptor antagonists - MoA
Effectively inhibit sympathetic stimulation of arteriolar contraction –> vasodilation and decrease vascular resistance, BUT several disadvantages.
Alpha-adrenoceptor antagonists - Indication
Not recommended for the initials treatment of hypertension, but can be added with other drugs when BP is not adequately controlled.
Alpha-adrenoceptor antagonists - Adverse effect
Reflex activation of SNS: increased HR, contractile force, circulating NE --> increased myocardial oxygen requirements Orthostatic hypotension “first dose” syncope Dizziness Fluid retention
Alpha-adrenoceptor antagonists - Interactions
Hypotensive effect increased by beta-blockers and potassium supplements.
Beta-Adrenoceptor antagonists
Nonselective: Nadolol Pindolol Propranolol Timolol Selective: Atenolol Esmolol Nebivolol Mixed alpha and beta: Carvedilol and labetalol
Beta-Adrenoceptor antagonists - MoA
Blockade of beta1 receptors reduces cardiac output by decreasing the heart rate and contractility. Block of these receptors in renal juxtaglomerular cells inhibit renin secretion –> reduces the formation of Angiotensin II and the release of Aldosterone.
The drugs also appear to reduce sympathetic outflow from the central nervous system.
Beta-Adrenoceptor antagonists - Indication
Beneficial in hypertensive persons with other cardiovascular diseases. In coronary heart disease- reduce myocardial ischemia and lower risk of MI.
In persons with previous MI they are cardioprotective- prevent sudden death, by decreasing HR and the risk of ventricular arrhythmias.
In heart failure: improves symptoms and survival.
Beta-Adrenoceptor antagonists - Adverse effects
Fatigue, depression, vivid dreams, decreased exercise capacity
Bradycardia
Bronchoconstriction
Impaired glycogenolysis
Beta-Adrenoceptor antagonists - Contraindications and Interactions
Contraindications:
Nonselective: Contraindicated in pt with asthma or COPD
In diabetics, delay recovery from hypoglycemia by blocking glycogenolysis and mask symptoms of hypoglycemia.
Interactions:
Cardiac depression increased by diltiazem and verapamil.
Hypotensive effect decreased by NSAID
Labetalol - Indication
Treats both chronic hypertension and hypertensive emergencies.
Carvedilol and Labetalol - Adverse effects
Orthostatic hypotension
Esmolol - Indications
Treat hypertension in surgical procedures and in persons with hypertensive emergencies.
Nebivolol - Indications
Hypertension in pat with heart failure, diabetes and cardiac arrhythmias.
Centrally acting drugs
Clonidine
Guanfacine
Methyldopa
Centrally acting drugs - MoA
Reduce sympathetic outflow from the central vasomotor center to the circulation primarily through the activation of alpha2 adrenoceptors in the brain stem medulla
Lower BP by reducing vascular resistance, while having little effect on HR and CO
Centrally acting drugs - Adverse effects
Sedation
Dry mouth
Impaired mental acuity
Severe rebound hypertension can occur if they are discontinued abruptly
Centrally acting drugs - Interactions
Hypotensive effect decreased by tricyclic antidepressants
Sedative effect increased by CNS depressants
Clonidine - Indication
Hypertensive urgencies in the outpatient setting (slowly reduced BP with one single oral dose)
Reduce SNS symptoms of alcohol, opioid or nicotine withdrawal.
Methyldopa - MoA
Has to be converted to an active metabolite (methyl norepinephrine) by central neurons, which then activates alpha2.
Methyldopa - Indication
Hypertension in pregnant women.
Methyldopa - Adverse effects
Immunologic effects including:
Coombs positive hemolytic anemia
Autoimmune hepatitis
Lupus-like syndrome
Methyldopa - Interactions
Hypotensive effect increased by levodopa
Angiotensin-Converting enzyme inhibitors
Benazepril Captopril Enalapril Fosinopril Lisinopril Quinapril Ramipril
Angiotensin-Converting enzyme inhibitors - MoA
Act by binding to zinc atom at the enzyme’s active site. Lower BP by reducing vascular resistance. Decrease both arterial and venous pressure --> reduced CO and cardiac preload. By reducing angiotensin-stimulated aldosterone secretion: ACE inhibitors prevent the compensatory increase in sodium retention and plasma V that can occur with some other antihypertensive drugs. Inactivated bradykinin (vasodilator) --> act partly by inhibiting its degradation Decreases stimulation of growth factors of cells --> decreases cardiac remodeling
Angiotensin-Converting enzyme inhibitors - Indication
Mild to severe hypertension
Protect against stroke and MI
Hypertension in pat with coexisting heart failure, MI, chronic kidney disease or diabetes mellitus.
They increase cardiac output and survival in persons with heart failure.
Reduce incidence of overt heart failure and increase survival in pt with MI and significant left ventricular dysfunction
Renoprotective effect in diabetic pt who exhbit early signs of renal impairment (albuminuria, increaser serum creatinine).
Reduce risk of primary and secondary stroke
Angiotensin-Converting enzyme inhibitors - Adverse effect
Hyperkalemia
Hyponatremia
Dry cough (due to increase of bradykinin)
Angioedema (swollen lips, face and throat)
Rash
Abnormal taste sensation
Neutropenia
Fetal and neonatal injury
Renal failure in patients with bilateral renal artery stenosis(due to their dependency on angiotensin II to maintain renal blood flow and glomerular filtration)
Angiotensin-Converting enzyme inhibitors - Interaction and Contraindications
Interactions
Augmented by diuretics and CCB.
Can interact with potassium sparing diuretics and supplement to increase potassium levels –>hyperkalemia
They also increase lithium levels –> lithium toxicity
NSAIDs (esp Ibuprofen) can impede the effect of ACE inh.
Contraindications:
Pregnancy because of fetal and neonatal injury
Bilateral renal artey stenosis because it can cause renal failure due to the dependency on angiotensin II to maintain renal blood flow and glomerular filtration
Enalapril - Indication
Pt with left ventricular failure
Angiotensin receptor blockers - MoA
These drugs selectively block AT1 receptors in various tissues and thereby reduce vasoconstriction, aldosterone secretion, sodium reabsorption by the proximal tubule and norepinephrine release from sympathetic nerve terminals.
Angiotensin receptor blockers - Adverse effects and contraindication
Hyperkalemia, neutropenia, elevated serum levels of hepatic aminotransferase
Fetal injury and death
Contraindication: pregnancy
Rarely cause dry cough that occurs with ACE inh.
Angiotensin receptor blockers - Interactions
Serum levels increased by cimetidine and decreased by phenobarbital
Angiotensin receptor blockers
Candesartan Irbesartan Losartan Telmisartan Valsartan
Losartan - Indication
Greater reduction of left ventricular hypertrophy and risk of stroke and new-onset diabetes
Telmisartan - MoA
Increase insulin sensitivity by activating peroxisome proliferator-activated receptor-gamma.
Direct renin inhibitor
Aliskiren
Aliskiren - MoA
Binds to the active site of renin, preventing cleavage of angiotensinogen and formation of angiotensin I.
Lowers plasma renin activity and levels of angiotensin I and angiotensin II.
Can protect against compensatory increases in angiotensin II evoked by other drugs.
Equal or superior BP-lowering ability compared with other drugs and a placebo-like side effect profile.
Aliskiren - Indication and adverse effects
High blood pressure
Hyperkalemia
Aliskiren - Interactions
Reduces serum levels of furosemide
Cyclosporine increases levels of aliskerin
Calcium channel blockers - MoA
By blocking calcium ion channels in the plasma membranes of smooth muscle, the ccbs relax vascular smooth muscle and causes vasodilation. They have greater effect on arteriolar smooth muscle then venous, effect on BP is mainly because a reduction in PVR.
Calcium channel blockers - Indication
Hypertension Angina pectoris Peripheral vascular disorders Cardiac arrhythmias Hypertension in Asthma Protect against: stroke, coronary heart disease, kidney disease.
Hypertensive pt who have asthma or are of African heritage
Calcium channel blockers - Adverse effects
Dihydropyridine CCB: Reflex tachycardia
Gingival hyperplasia in persons with poor dental care
Dizziness, edema, headache
Calcium channel blockers - Interaction
Serum levels increased by azole antifungal agents, cimetidine and grapefruit juice
Calcium channel blockers
Diltiazem Verapamil Amlodipine Felodipine Isradipine Nicardipine Nifedipine
Diltiazem and Verapamil - MoA and Indication
Significant effect on cardiac tissue and can reduce heart rate and cardiac output.
Reduce protein excretion in patients with kidney disease and may be used with ACE inh or ARB for this purpose.
Diltiazem and Verapamil - Adverse effects
AV block, bradycardia, constipation, dizziness, edema, gingival hyperplasia, headache, heart failure
Diltiazem and Verapamil - Interactions
Increases serum levels of carbamazepine, digoxin, theophylline. Decreases serum levels of lithium
Nicardipine - Indications
Hypertensive emergencies
Vasodilators
Hydralazine
Minoxidil
Nitroprusside
Fenoldopam
Hydralazine
Minoxidil - Indication
Moderate to severe hypertension resistant to other drugs, in combo with other antihypertensive drugs.
Minoxidil: alopecia
Hydralazine
Minoxidil - Adverse effects
Reflex tachycardia
Fluid retention
Precipitate angina in susceptible patients. –> these side effects when given alone, therefor given with diuretics and beta blockers.
Hydralazine- lupus like syndrome
Minoxidil- hypertrichosis(excessive hair growth)- given topical for alopecia.
Hydralazine
Minoxidil - Interactions
Hypotensive effect decreased by NSAIDs
Nitroprusside - Indications
Management of Hypertensive emergencies
Nitroprusside - Adverse effect
Dizziness Headache Increased intracranial pressure Methemoglobinemia Thiocyanate and cyanide toxicity
Fenoldopam - MoA and Indication
Activates vascular dopamine D1 receptors and produces vasodilation in systemic vascular beds including coronary, renal and mesenteric vessels.
Hypertensive emergencies
Fenoldopam - Adverse effects
Hypokalemia
Headache
Nausea
