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Pharm Hypertension
| Question | Answer |
|---|---|
| 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
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