Lecture 4 Anti-hypertensive Drugs PDF

Lecture: 4 Anti-hypertensive Drugs [email protected] Hypertension Consistent elevation of systemic arterial blood pressure – High blood pressure – “Normal” BP varies with age; abnormal as we age Hypertension is most common form of cardiovascular disease...

Lecture: 4 Anti-hypertensive Drugs [email protected] Hypertension Consistent elevation of systemic arterial blood pressure – High blood pressure – “Normal” BP varies with age; abnormal as we age Hypertension is most common form of cardiovascular disease Associated with more than 348,000 deaths in United States per year Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Three Factors Responsible for Blood Pressure Cardiac output Peripheral resistance Blood volume MAP = CO x TPR (Resistance = R=ηL/r4) η = viscosity L = length r = radius Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Cardiac Output Volume of blood pumped per minute Determined by: – Stroke volume – Heart rate Medications that affect cardiac output, stroke volume, heart rate will affect blood pressure Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Peripheral Resistance Friction in arteries as blood flows through vascular system Greater resistance in arteries yields higher blood pressure Medications that affect vascular smooth muscles may lower or raise BP Autonomic nervous system plays role in regulating peripheral resistance Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Blood Volume Total amount of blood in vascular system Increased blood volume increases blood pressure Medications that affect blood volume may lower or raise BP – Diuretics Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Primary factors affecting blood pressure Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Emotions Affect Blood Pressure Stress and anger increase Depression and lethargy decrease Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Hormones Affect blood pressure Natural hormones affect blood pressure daily – Epinephrine and norepinephrine injections raise BP – Antidiuretic hormone (ADH) raises BP by raising blood volume Renin–angiotensin–aldosterone system is a primary homeostatic mechanism for controlling blood pressure Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Hormonal and nervous factors influencing blood pressure Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Types of Hypertension Primary hypertension—no identifiable cause Secondary hypertension—cause identified – Cushing’s syndrome – Hyperthyroidism – Chronic renal disease – Certain drugs Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Target Organs Affected by Untreated Hypertension Heart Brain Kidneys Retina Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Disease Progression Related to Organs Heart failure TIA or cerebral vascular accident Renal failure Visual impairment and blindness Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Nonpharmacologic Methods to Control Hypertension Limit alcohol intake Restrict sodium consumption Reduce saturated fat and cholesterol; increase fresh fruit and vegetable intake Increase aerobic physical activity Discontinue tobacco use Reduce stress Maintain optimum weight Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Pharmacologic Management of Hypertension Individualized to patient's risk factors, medical conditions, degree of blood pressure elevation Healthcare provider experience plays role in choice of therapy Monotherapy: Its useful mainly in stage 1 hypertension. Combination Therapy: which is double or triple antihypertensive drugs used in stage 2 HTN. Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved First-Line Antihypertensive Drugs Primary Antihypertensive Agents – Diuretics (especially thiazide and thiazide-like diuretics, potassium-sparing diuretics) – Angiotensin-converting enzyme (ACE) inhibitors – Angiotensin receptor blockers (ARBs) – Direct renin inhibitors – Calcium channel blockers (CCBs) Prescribing two antihypertensives results in additive or synergistic blood pressure reduction Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Second-Line Antihypertensive Drugs Beta-adrenergic receptor blockers (in heart) Alpha1-adrenergic receptor blockers (in arterioles) Alpha2-adrenergic agonists Direct-acting vasodilators Peripherally acting adrenergic neuron blockers Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Assessment of Patient’s Lifestyle Dietary habits Exercise or activity regimen Use of medication Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Factors That Can Help Control Blood Pressure Losing weight Limiting foods high in fat and sodium Limiting use of tobacco and alcohol Beginning an exercise program Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Role of Nurse Obtain complete health history Obtain vital signs Do physical examination Obtain blood and urine specimens for analysis Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved 1- Diuretics Increase urinary excretion of water and electrolytes, thereby reducing blood volume ↓ BP by ↓ Na store ( increase Na excretion ) ↓ blood volume (by increase urine output) ↓ CO ↑ H2O excretion Used for mild to moderate hypertension There site of actions in the Nephron. In sever case: combination( sympathoplegic, Angiotensin antagonist & vasodilator drugs) Cause electrolyte imbalance Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Diuretics divided into 3 classes 1. Thiazide (Hydrochlorothiazide) – Used for long treatment – The 1st line antihypertensive drugs particularly in elderly and diabetics. – The most commonly used (it's extremely cheap) – Also it has vasodilator effect, so reduce peripheral resistance – Side effects: hyperglycemia Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Diuretics divided into 3 classes 2. Loop diuretics (furosemide) – Used in emergency(IV) very effective – The first line in heart failure and renal failure patients – Strongest diuretics – Side effects :ototoxicity (they cause some defect in hearing) 3. Potassium sparing diuretics (spironolactone) – Weakest diuretics. – Used in combination Not alone – Aldosterone antagonist. – Side effects: hyperkalemia Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved NSAIDs interfere with response to diuretics NSAIDs inhibit the prostaglandins synthesis and particularly in the chronic use of diuretics, NSAIDs will reduce the effect of diuretics. Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved 2- Saympathoplagics 1. Alpha-blockers: the major function is on the blood vessels. 2. Beta-blocker: effect on both B1 & B2 3. Central sympatholytics : which affect both of them and cause reduction in sympathetic activity. Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Alpha-1-blockers Ex. Prazosin Are the major regulator of sympathetic tone in the blood vessels. block the sympathetic nerve supply to the small arteries and arterioles by Blocking Alpha-receptors on vascular smooth muscle allows muscle relaxation, dilation of vessel, and reduced resistance. Adverse effects:- postural hypotension; reflex tachycardia 1st dose syncope. Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Beta Blockers Non-selective (β1, β2):- Propranolol (prototype) Selective(β1) :- Atenolol Non selective ( β & α1 ):- labetalol,carvedilol. Mechanism of Action:- Block cardiac β1 receptors ↓HR ,↓ contractility,↓ CO reduce BP. Block renal β1 receptors (on chronic use) ↓ renin secretion ↓ PVR reduce BP Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Beta Blockers Therapeutic use Adverse Effects Hypertension Bradycardia. Angina Hypotension. MI Bronchoconstriction (non-selective). Arrhythmias Withdrawal syndrome. Hyperthyroidism Cold extremities. Heart failure (selective drug for selective pts) Contraindications Glaucoma Asthma (due toβ2 antagonist). migraine Diabetes. Bradycardia. Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Centrally acting sympatholytics Alpha-2 Agonists Mechanism of Action: CNS Alpha-2 adrenergic stimulation in the medulla decreases peripheral sympathetic activity reduces tone vasodilation and decreases Total Peripheral Resistance Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved 3- Direct Vasodilators Dilate(relax) blood vessels by acting directly on the smooth muscle of arterioles some them on veins ↓ PVR. Example: - Hydralazine - Minoxidil - Nitroprusside Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved 3- Direct Vasodilators Primary acting on arteries and arterioles not veins (Hydralazine Minoxidil) Hydralazine – safe for pregnancy – given IV & oral. Adverse Effects – Fall in BP Reflex tachycardia. – Fall in BP renin release Na/water retention. – Systemic lupus-Like syndrome – Hypertrichosis (growth body hair) Minoxidil Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved 3- Direct Vasodilators Nitroprusside dilates both arterial and venous vessels. its powerful reduced BP reduced Peripheral resistance & venous return used in hypertensive emergencies we have another drug which is Labetalol (used in emergency hypertensive control hypertensive crisis) and it is a combined alpha1 & beta blocker. The onset of action for Nitroprusside is immediate while it takes 5-10 minutes with labetalol Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved 4- Calcium Channel Blockers They block the inward movement of calcium by binding to L-type calcium channels in the heart and in smooth muscle of the coronary and peripheral vasculature. This causes vascular smooth muscle to relax, dilating mainly arterioles Used to treat hypertension and other cardiovascular diseases Block calcium ion channels; cause vasodilation, decreasing BP Adverse effects include dizziness, headache, flushing Some selectively target calcium channels in arterioles; others also affect cardiac muscle Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Calcium Channel Blockers Amlodipine Verapamil Diltiazem Dihydropyridine Non-dihydropyridine Non-dihydropyridine Selective act on vascular Act on cardiac muscle smooth muscle or blood vessel (arterial side) both cardiac and vascular smooth muscle reduce peripheral Inhibit lead to slow heart resistance (reduce after rate & delay of conduction. load) cause relaxation (-ve inotropic & dromotropic) thus decrease in BP Cause reflex tachycardia Cause bradycardia Bradycardia due to hypotension Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Calcium Channel Blockers Therapeutic use Cardiac Effects Hypertension Decrease Heart rate Angina Decrease Conduction velocity Arrhythmias Decrease Contractility Vascular effects Adverse Effects Smooth muscle relaxation Amlodipine Postural hypotension vertigo reflex tachycardia. ankle edema Verapamil , Diltiazem bradycardia Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved  Prototype Drug: Nifedipine (Adalat CC, Procardia XL) Therapeutic Class: Drug for hypertension and angina Pharmacologic Class: Calcium channel blocker Actions and Uses – Nifedipine is a CC B generally prescribed for HTN and variant or vasospastic angina. – Nifedipine acts by selectively blocking calcium channels in myocardial and vascular smooth muscle, including those in the coronary arteries. – This results in coronary artery dilation, less oxygen utilization by the heart, an increase in cardiac output, and a fall in blood pressure. Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved 5- Renin–Angiotensin System Inhibitors (RAS inhibitor) Prevent the synthesis of angiotensin II Angiotensin Converting Enzyme Angiotensin II Receptor Antagonists Inhibitors (ACEI) (ARB) Enalopril Losartan Captopril Candesartan Valsartan Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved The renin-angiotensin-aldosterone pathway Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Angiotensin Converting Enzyme Inhibitors (ACEI) Indications Adverse Effects Dry cough, angioedema (due to Hypertension bradykinin) chronic Heart Failure hyperkalemia Drug of choice In first dose syncope (hypotension) progressive renal insufficiency, diabetic nephropathy. Contraindication Pregnant women (they are fetotoxic drugs) bilateral renal stenosis Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved Angiotensin II Receptor Antagonists (ARB) Block the AT1 receptors. They carry NO advantage over ACE inhibitors, they actually much more expensive, EXCEPT for one advantage : they don`t produce dry cough, because it won`t cause accumulation of bradykinin, and this is important for the patients who are complaining of dry cough to consider switch them to AT2 receptor blockers but they have to have insurance or enough money. Copyright © 2020, 2017, 2014 Pearson Education, Inc. All Rights Reserved