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Pharm Hypertension

2 things arterial pressure is determined by cardiac output and peripheral resistance
cardiac output heart rate x stroke volume. Usually 5L/min. Treatment of HTN aims at heart rate, contractility, blood volume, and venous return of blood to heart
peripheral resistance tx of HTN aims at vasodilation
3 regulatory mechanisms of BP control autonomic nervous system, RAA system, kidneys
Autonomic nervous system (baroreceptor reflex) rapid(sec-min)baroreceptors sense drop in BP relay signal to brainstem, brainstem sends impulses along SNS to stimulate heart and vessels, BP is elevate by acitvation of B1 receptors in heart(inc CO) and activation of alpha1 receptors (vasoconstriciton)
Renin Angiotensin Aldosterone slow(hours-days),Renin released from kidney bc of reduced renal flow,blood volume, reduced BP. Renin turns Angiotensinogen to angiotensin I. ACE converts angiotensin I to angiotensin II - constricts vessels, causes release of aldosterone (inc blood vol)
Kidneys (BP control) long term control (days-weeks). When BP falls, GFR falls causing retention of sodium, Cl, water
non drug lifestyle changes for HTN weight loss, sodium restriction, DASH diet, alcohol restriction, aerobic exercise, smoking cessation, maintenance of potassium and calcium intake
Classes of antihypertension drugs (9) Diuretics, ACE inhibitors, Angiotensin II Receptor Blockers (ARBs), Renin Inhibitors, Calcium channel blockers, Beta 1 Receptor Antagonists, Alpha 1 blcokers, Alpha 2 agonists, direct arteriolar vasodilators
3 types of diuretics thiazide diuretics, high ceiling (loop) diuretics, Potassium sparing diuretics
Thiazide Diuretics- MOA increase excretion of Na+ and water by blocking Na+ reabsorption; reduce BP by reducing blood volume and arterial resistance
Name 2 Thiazide Diuretics Hydrochlorothiazide (HCTZ) and chlorothalidone (Hygrotonl)
adverse effets of thiazide diuretics hyponatremia, dehydration, HYPOKALEMIA, hyperuricemia, hyperglycemia, hyperlipidemia
High Ceiling (Loop) diuretics- MOA produce a lot more diuresis than thiazides, not used routinely for chronic HTN. Inhibit cotransport of Na+/K+/2Cl- in the ascending loop of henle = increased Na+ and K+ excretion
High Ceiling (Loop) diuretics- drugs Furosemide (Lasix), Bumetanide (Bumex)
Adverse Effects of High Ceiling (Loop) diuretics electrolyte imbalance (hyponatremia, dehydration), HYPOKALEMIA, hyperuricemia, hypotension, ototoxicity
Potassium Sparing Diuretics less potent than thiazides and loop diuretics, modest Hypotensive effects (can conserve K+ when using thiazides or loops- used in combo to reduce hypokalemia)
Amiloride (Midamar) - MOA Potassium Sparing Diuretic. Blocks Na+/K+ pump; prevents Na+ reabsorption and K+ secretion in collecting tubule
Spironolactone (aldactone)/Eplerenone (Inspra) Potassium Sparing Diuretics; aldosterone antagonist to work in collecting duct and excrete Na+ and reabsorb K+
Adverse Effects of Potassium Sparing Diuretics hyperkalemia, avoid in patients with CKD or diabetes, gynecomastia (eplerenone), abnormal vaginal bleeding in females
Therapeutic uses of Diuretics essential hypertension, more potent in African Americans, Obese, Elderly, smokers
Angiotensin Converting Enzyme (ACE) Inhibitors- MOA inhibtion of angiotensin converting enzyme- blocks transformation of Angiotensin I to Angiotensin II (lowers levels of Angiotensin II), also inhibits bradykinin degradation (inc bradykinin= potent vasodilator).Dilates blood vessels and lowers blood volume
ACE Inhibitors (2) Captopril and Lisinopril
Indications of ACE Inhibitors hypertension, MI, prevention of MI, stroke, death in patients at high risk of CVD, heart failure. Single therapy (control in 40-50% patients), potent in combo therapy, more effective in caucasians
adverse effects hypotension,dry cough, hyperkalemia, angioedema
Warnings of ACE inhibitors lower starting dose d/t hypotension risk, may cause hyperkalemia (CKD and patients taking other K+ sparing meds), contraindicated in pregnancy
Angiotensin II Receptor Blockers (ARBs)- MOA bind competitively and selectively to angiotensin II receptor subtype and blocks actions of angiotensin II (relaxes smooth muscle/vasodilation and decreases aldosterone release)
Angiotensin II Receptor Blockers- Drugs Losartan (Cozaar) and Candesartan
Indications of ARBs hypertension, MI, heart failure, prevention of stroke in paitnets wiht high risk of CVD. High cost- reserved for patients who develop cough with ACE inhibitors
Adverse Effects of ARBs hypotension, well tolerated (no coughing), angioedema (rare), renal failure, hyperkalemia, additive effects with other hypotensive drigs
Warnings for ARBs low starting dose due to hypotension risk (patients also taking diuretic, elderly), may cause hyperkalemia in CKD patients and patients on other K+ sparing meds, contraindicated in pregnancy
Renin Inhibitors- MOA inhibits angiotensinogen to angiotensin I conversion
Renin Inhibitor- drug Aliskiren (Tekturna)
Renin Inhibitors- Uses monotherapy and combo therapy with other antihypertensive, efficacy demonstrated with other antihypertensives, does not block bradykinin breakdown (less cough than ACE)
Adverse Effects of Renin Inhibitors (Aliskiren) orthostatic hypotension, hyperkalemia, contraindicated in pregnancy
Calcium Channel Blockers- MOA inhibit the influx of calcium through the voltage dependent calcium channels in vascular smooth muscle (coronary and peripheral vasculature)- peripheral vasodilation
2 categories of calcium channel blockers dihydropyridines and non dihydropyridines
Dihydropyridines Nifedipine(Procardia) and Amlodipine (Norvasc) Act primarily on arterioles (inhibit influx of calcium in coronary and peripheral vasculature only)
Non-dihydropyridines Verapamil (Calan, Isoptin) and Diltiazem (Cardizem) Act on arterioles AND heart (inhibit influx of calcium in vessels and heart- lowers HR, decreases AV conduction, decreases force of contraction)
Adverse Effects of Dihydropyridines (Nifedipine, Amlodipine) dizziness, headache, flushing, reflex tachycardia (use beta blocker too)
Adverse Effects of Verapamil bradycardia, AV block, decreases myocardial contractility (exacerbates HF), constipation, dizziness, headache, fatigue
Indications of Calcium Channel Blockers hypertension, cardiac dysrhythmias, angina. Effective montherapy, effective in all demographics and grades of HTN, preferable to beta blockers and ACe inhibitors in African Americans and Elderly, long acting CCB- reduce stroke and CV morbidity/mortality
Beta 1 Adrenergis receptor Antagonists (Beta blockers)- MOA competitively antagonize the response to catecholamines mediated by beta receptors- decreased heart contractility and HR (dec. CO), less peripheral resistance, less renin release. Most effective in young, caucasians
nonselective B1 and B2 blockers propranolol (Inderal)
Selective B1 blocker (cardioselective) atenolol, metoprolol
Patrial Beta agonists Acebutolol (depresses heart rate less than other beta blockers)
Nonselective Beta blockade with alpha blockade Carvedilol (Coreg)- a1 blockade produces vasodilation and b1 blockade lowers HR/contractility, also decreases renin release
Adverse Effects of Beta Blockers bradycardia, AV block, bronchospasm, can precipitate heart failure, sexual impairment, CNS symptoms, increased glucose/triglycerides, dec. HDL, severe allergy, rebound hypertension on discontinuation
Alpha1 Blockers- MOA blocks alpha1 receptors (competitive inhibition)- compete with norepinephrine and epinephrine on vascular smooth muscle and prevent vasoconstriction. Dilates arterioles and veins, reduce prostatic symptoms in men
Alpha 1 Blockers- drugs Prazosin (Minipres), Terazosin (Hytrin) Tamsulosin (Flomax)
Indications of Alpha 1 blockers hypertension, BPH
Adverse Effects of alpha 1 blockers reflex tachycardia, orthostatic hypotension, salt and water retention, blurred vision, nasal congestion, erectile dysfunction
Centrally Acting Agents (Alpha 2 agonists)- MOA selective activation of alpha2 receptors in CNS (brainstem)= vasodilation, reduce HR and CO
Centrally Acting Agents (Alpha 2 agonists)- drugs Methyldopa and Clonidina (Catapres)
Indications of Centrally Acting Agents (Alpha2 agonists) hypertension (methyldopa first line agent for pregnancy induced HTN), clonidine used in resistant HTN. Second and Third line agents. Pain (clonidine), more effective with diuretic, use caution in elderly
clonidine transdermal patch placed weekly, may result in fewer adverse effects, avoids high peak serum drug concentrations, delayed onset (2-3 days)
Adverse Effects of centrally acting Agents (Alpha 2 agonists) CNS depression (drowsiness), dry mouth, rebound HTN (upon abrupt clonidine withdrawal)- can be avoided by withdrawing slowly
Direct Arteriolar Vasodilators- MOA selective dilation of arteriole, little or no effects on veins. Direct action on vascular smooth muscle- produce peripheral vasodilation. Decreased peripheral resistance + increased HR and myocardial contractility by baroreceptor reflex
Direct Arteriolar Vasodilators- Drugs Hydralazine (Apresoline) and Minoxidil (Loniten)
Indications of Direct Arteriolar Vasodilators refractory patients
Adverse Effects of direct arteriolar vasodilators slat and water retention, reflex tachycardia, vascular headache, lupus like syndrome, hirsutism
Categories that inhibit effects of angiotensin ACE Inhibitors, Angiotensin Receptor Blockers (ARBs), Renin Inhibitors
All vasodilators ACE inhibitors, ARBs, CCB, alpha1 blockers, alpha2 agonist, direct arteriolar vasodilators
Preeclampsia (definition) BP >140/90 mmHg after 20 weeks gestation with proteinuria.
Preeclampsia treatment IV hydralazine, IV labetolol
Treatment for Chronic hypertension in pregnancy methyldopa
teratogenic antihypertesive drugs ACE INHIBITORS/ARBs (fetal toxicity ad death) beta blockers (generally safe, but intrauterine growth retardation) diuretics (probably safe in low doses)
Antihypertensive drugs for patients with Diabetes Type II ACE Inhibitor or ARB add on: diuretic (low doses), betablocker, calcium channel blocker
Antihypertensive drugs for patients Post MI Beta Blocker + ACE inhibitor/ARB add on: aldosterone antagonist
Antihypertensives for Young Caucsians Beta blockers and ACE inhibitors
Antihypertensives for Elderly/African Americans diuretics
Antihypertensives to avoid in patients with asthma beta blockers
Antihypertensives to avoid in patients with diabetes avoid thiazides, furosemide, and beta blockers promote hyperglycemia
Created by: alexadianna