Pharm 118 (Week 3) - Ch 24 Part 2

Adrenergic Drugs: Sympathetic Nervous system blockers :Adrenergic Drugs: Sympathetic Nervous system blockers Five Subcategories Centrally and peripherally acting adrenergic neuron blockers Centrally acting a2-receptor agonists Peripherally acting a1-receptor blockers Peripherally acting b-receptor blockers (b-blockers)—both cardioselective (b1 receptors) and nonselective (both b1 and b2 receptors) Peripherally acting dual a1- and b-receptor blockers 1


Adrenergic Drugs:Mechanism of Action :Adrenergic Drugs:Mechanism of Action b-blockers Reduce BP by reducing heart rate through b1-blockade Cause reduced secretion of renin Long-term use causes reduced peripheral vascular resistance Propranolol, atenolol, others Result: decreased blood pressure Dual-action a1- and b-receptor blockers Block the a1-adrenergic receptors Reduction of heart rate (b1-receptor blockade) Vasodilation (a1-receptor blockade) labetalol and carvedilol Result: decreased blood pressure 2


Adrenergic Drugs:Mechanism of Action :Adrenergic Drugs:Mechanism of Action Dual-action a1- and b-receptor blockers Block the a1-adrenergic receptors Reduction of heart rate (b1-receptor blockade) Vasodilation (a1-receptor blockade) labetalol and carvedilol Result: decreased blood pressure 3


Indications for Adrenergic Drugs :Indications for Adrenergic Drugs Peripherally acting a1-receptor agonists  Treatment of hypertension Relief of symptoms of BPH Management of severe HF when used with cardiac glycosides and diuretics 4


Centrally Acting Alpha-Receptor Agonist :Centrally Acting Alpha-Receptor Agonist Adrenergic Drugs:Mechanism of Action Centrally acting a2-receptor agonists Stimulate a2-adrenergic receptors in the brain Sympathetic outflow from the CNS is decreased Norepinephrine production is decreased Stimulation of the a2-adrenergic receptors reduces renin activity in the kidneys Result: decreased blood pressure Adrenergic Drugs:Centrally Acting a2-Receptor Agonists clonidine (Catapres) guanfacine (Tenex) methyldopa (Aldomet) Drug of choice for hypertension in pregnancy 5


Indications for Adrenergic Drugs :Indications for Adrenergic Drugs Centrally acting a2-receptor agonists Treatment of hypertension, either alone or with other drugs Usually used after other drugs have failed due to adverse effects Also may be used for treatment of severe dysmenorrhea, menopausal flushing, glaucoma Clonidine is useful in the management of withdrawal symptoms in opioid- or nicotine-dependent persons 6


Adrenergic Drugs :Adrenergic Drugs Adverse Effects Most common: Dry mouth Drowsiness Sedation Constipation Other: Headaches Sleep disturbances: Nausea Rash Cardiac disturbances (palpitations), others HIGH INCIDENCE OF ORTHOSTATIC HYPOTENSION 7


Angiotensin Converting Enzyme Inhibitors :Angiotensin Converting Enzyme Inhibitors (ACE inhibitors, or ACEIs) Large group of safe and effective drugs Often used as first-line drugs for HF and hypertension May be combined with a thiazide diuretic or calcium channel blocker Mechanism of Action Renin-Angiotensin-Aldosterone System Inhibit angiotensin-converting enzyme, which is responsible for converting angiotensin I (through the action of renin) to angiotensin II Angiotensin II is a potent vasoconstrictor and causes aldosterone secretion from the adrenals 8


ACE Inhibitors Mechanism of Action :ACE Inhibitors Mechanism of Action Aldosterone stimulates water and sodium resorption Result: increased blood volume, increased preload, and increased BP ACE inhibitors block the angiotensin converting enzyme, thus preventing the formation of angiotensin II Also prevent the breakdown of the vasodilating substance, bradykinin Result: decreased systemic vascular resistance (afterload), vasodilation, and therefore decreased blood pressure 9


ACE Inhibitors:Indications :ACE Inhibitors:Indications Hypertension HF (either alone or in combination with diuretics or other drugs) To slow progression of left ventricular hypertrophy after an MI (cardioprotective) Renal protective effects in patients with diabetes Drugs of choice in hypertensive patients with HF Drugs of choice for diabetic patients 10


Ace Inhibitors :Ace Inhibitors captopril (Capoten) Very short half-life enalapril (Vasotec) Available in oral and parenteral forms lisinopril (Prinivil and Zestril) and quinapril (Accupril), others Newer drugs, long half-lives, once-a-day dosing Several other drugs available Captopril and lisinopril are NOT prodrugs Prodrugs are inactive in their administered form and must be metabolized in the liver to an active form in order to be effective Captorpril and lisinopril can be used if a patient has liver dysfunction, unlike other ACE inhibitors that are prodrugs 11


ACE Inhibitors:Adverse Effects :ACE Inhibitors:Adverse Effects Fatigue Dizziness Headache Reflex tachycardia, chest pain, CHF, arrhythmias Mood changes Impaired taste Possible hyperkalemia constipation Dry, nonproductive cough, which reverses when therapy is stopped Angioedema: rare but potentially fatal NOTE: first-dose hypotensive effect may occur! 12