-
chlorothiazide, chlorothalidone, hydrochlorothiazide
- thiazide diuretic - inhibits Na-Cl co-transporter
- most commonly used in HTN treatment alone or in combination
- moderate diuresis
- effects reduced by NSAIDs
- adverse effects: K+ depleting, dec. uric acid and Ca2+ excretion, thiazide and sulfonamide cross reactivity
-
bumetanide, furosemide, torsemide
- loop diuretics - inhibit Na-K-2Cl cotransporter in thick ascending limb of loop of Henle
- used primarily with heart failure and edema
- potent diuresis
- adverse effects: K+ depleting, dec. uric acid excretion, inc. Ca2+ excretion, deafness, allergic rxn (most are sulfonamide derivatives)
-
amiloride and triamterene
- K+ sparing diuretic - Na+ channel blockers
- used in conjunction with other diuretics
- mild diuresis, weak antihypertensive effect so used in conjunction with thiazide
- adverse effects: hyperkalemia
-
eplerenone and spironolactone
- K+ sparing diuretic - aldosterone receptor antagonist blocks aldosterone mediated sodium and water reabsorption
- late distal tubule and collecting duct
- used in conjunction with ACE inhibitors and ARBs
- used for resistant HTN and CHF with HTN
- mild diuresis
- adverse effects: hyperkalemia
-
captopril, enalapril, lisinopril, fosinopril
- RAS - ACE inhibitor
- drug effect doesn't correlate with blood levels due to vascular and cerebral sources of angiotensin II
- block angiotensin II constriction to reduce TPR
- increases Ca+ and water excretion
- Inc. BK levels
- reverse cardiac hypertrophy
- escape phenomenon: loss of angiotensin II feedback inhibition = increased renin and renin activity
- widely used, minimal but common side effect: hypotension, dry cough, hyperkalemia (due to inhibition of aldosterone)
-
candesartan, irbesartan, losartan, valsartan
- RAS - angiotensin receptor blocker (ARB) blocks AT1 receptor
- drug effect doesn't correlate with blood levels due to vascular and cerebral sources of angiotensin II
- block angiotensin II constriction to reduce TPR
- increases Ca+ and water excretion
- reverse cardiac hypertrophy
- escape phenomenon: loss of angiotensin II feedback inhibition = increased renin and renin activity
- used for HTN and HF
- widely used, minimal but common side effect: hypotension, dry cough much less common than in ACE inhibitors, hyperkalemia
-
aliskiren
- RAS - renin inhibitor
- drug effect doesn't correlate with blood levels due to vascular and cerebral sources of angiotensin II
- block angiotensin II constriction to reduce TPR
- increases Ca+ and water excretion
- reverse cardiac hypertrophy
- increases renin levels but not renin activity
- adverse effects: hyperkalemia, hypotension, dry cough (much less than ACEI)
-
diltiazem and verapamil
- Ca2+ channel blockers - cardioselective
- blocks L type Ca2+ channels = reduces CO
- use: HTN, especially in African Americans and older patients with systolic HTN (more effective)
- adverse effects: contraindicated in HF, depresses A-V conduction and contractility, headache, gingival hyperplasia/ inflammation
-
amlodipine, nicardipine, nifedipine
- Ca2+ channel blockers - vascular smooth muscle selective
- dihydropyridines
- relax vascular smooth muscle and decreases TPR
- use: HTN, especially in African Americans and older patients with systolic HTN (more effective)
- adverse effects: contraindicated in HF, depresses A-V conduction and contractility, headache, gingival hyperplasia/ inflammation
-
propranolol
- β-adrenergic receptor antagonist (β blocker)
- prevents effects of NE
- non-selective (first generation)
- reduces heart rate and contractility to reduce CO
- decrease renin release
- blocks both β1 and β2 adrenergic receptors
- withdrawal: rebound HTN
-
metoprolol and atenolol
- β-adrenergic receptor blockers
- prevents effects of NE (selective - β1 receptor blocker) - second generation
- reduces HR and contractility to reduce CO
- decrease renin release
- non-vasodilating β-adrenergic blockers due to unopposed α1 activation
- long term use increased incidence of type 2 diabetes
- withdrawal: rebound HTN
-
prazosin and doxazosin
- α1-adrenergic receptor blockers
- relax vascular smooth muscle
- reduce PVR
- adverse effects: reflex tachycardia, orthostatic hypotension, fluid retention, GI upset,
-
labetalol and carvedilol
- combined α1/β-adrenergic receptor blockers (3rd gen β blockers)
- vasodilating β blockers since prevents α1 mediated smooth muscle constriction
- labetalol approved for HTN only
- carvedilol used in HTN and heart failure
- carvedilol also has additional antioxidant effects and antiproliferative effects
-
nebivolol
- combined β-adrenergic receptor antagonist and NO-mediated dilator (stimulates eNOS)
- reduces PVR
- used for HTN
-
reserpine
- peripheral adrenergic transmission inhibitor
- prevents reuptake of NE in storage terminal
- depletes NE from nerve ending
- low dose reserpine combined with thiazide diuretics
- adverse effects: postural hypotension, sedation, dry mouth, nightmares, sodium and water retention
-
clonidine and α-methyldopa
- central-mediated antihypertensive agent
- α2 adrenergic receptor agonistdecrease sympathetic outflow
- α-methyldopa used in pregnancy-induced HTN (pre-eclampsia)
- limited use due to several central side effects
- try in patients with resistant hypertension
- adverse effects: rebound hypertension, sedation, dry mouth, depression, drowsiness, water and sodium retention,
-
hydralazine
- vasodilator - mechanism unclear
- reduces intracellular Ca2+ and relaxes vascular smooth muscle
- used with β-blockers to prevent reflex increase in CO and HR
- adverse effect: headache, nausea, anorexia, dizziness, sweating, reflex tachycardia, inc. renin and fluid retention, immune response - lupus like syndrome
-
minoxidil
- vasodilator - K+ channel opener
- hyper polarizes and relaxes smooth m
- given with diuretic and β-blockers to prevent reflex increase in CO and HR
- adverse effects: fluid retention, pericardial effusion, reflex tachycardia
- topical form used to treat androgenic alopecia
-
nitroprusside and nitroglycerin
- nitrovasodilator release NO which stimulates guanylyl cyclase
- releases NO and relax smooth m
- nitroglycerin acts preferentially on veins
- used in hypertensive emergencies and during surgery
- rapid onset, short duration of action
- adverse effects: rapid dec. in MAP, cyanide accumulation (nitroprusside)
-
epoprostenol
- vasodilator - prostacyclin stimulated AC generating cAMP
- counteracts thromboxane A2
- used in primary pulmonary HTN
-
bosentan and ambrisentan
- vasodilator - endothelin receptor blockers
- bosentan is non-selective
- ambrisentan is ETA receptor selective
- expression of endothelin receptors high in lung
- used in primary pulmonary hypertension
- adverse effects: edema, HA, spermatogenesis inhibition, resp. tract infection, decreased hematocrit, hepatic effects
-
riociguat
- vasodilator - stimulator of guanylyl cyclase
- used in primary pulmonary HTN
- used in thromboembolic HTN
- adverse effects: HA, dizziness, nausea, diarrhea, hypotension, birth defects
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