Antihypertensive DrugsBlood Pressure- Blood pressure = CO × SVR o CO = cardiac outputo SVR = systemic vascular resistance- Hypertension = high blood pressureFour stages, based on BP measurements1. Normal <120/<802. Prehypertension 120-139/80-893. Stage 1 hypertension 140-159/90-994. Stage 2 hypertension >160/>100Classification of BP- Hypertension can also be defined by its cause- Unknown causeo Essential, idiopathic, or primary hypertensiono 90% of cases- Known causeo Secondary hypertensiono 10% of casesAutonomic Nervous System- Parasympathetic nervous system – Stimulates smooth muscle, cardiac muscle, glands- Sympathetic nervous system – Stimulates the heart, blood vessels, skeletal muscleDecreased volume - Renin released - Stim Angie I- Convert to Angie II- Vessel constriction o Increased BP- Angie II stim secrete o Aldosterone = Reabsorb Na and Water o Increased BPAntihypertensive Drugs- Medications used to treat hypertension- Categorieso Adrenergic drugso Angiotensin-converting enzyme (ACE) inhibitorso Angiotensin II receptor blockers (ARBs)o Calcium channel blockers (CCBs)o Diureticso Vasodilatorso Direct renin inhibitorsAdrenergic Drugs: Five Subcategories- Centrally and peripherally acting adrenergic neuron blockers- Centrally acting alpha2 receptor agonists- Peripherally acting alpha1 receptor blockers- Peripherally acting beta receptor blockers (beta blockers)o Cardioselective (beta1 receptors)o Nonselective (both beta1 and beta2 receptors)- Peripherally acting dual alpha1 and beta receptor blockers- “lol” drugs are beta blockersAdrenergic Drugs- Centrally acting alpha2 receptor agonists o Stimulate alpha2-adrenergic receptors in the braino Decrease sympathetic outflow from the CNSo Decrease norepinephrine productiono Stimulate alpha2-adrenergic receptors, thus reducing renin activity in the kidneyso Result in decreased blood pressureo Clonidine- Centrally acting alpha2 receptor agonists (cont’d)o clonidine (Catapres) – good emergency medication, brings bp down very fast. Doesn’t last long Few side effects – makes patient *sleepy*- Peripheral alpha1 blockers/antagonists- Decreases peripheral-vascular resistance - All alpha1 blockers end in “zosin” o Block alpha1-adrenergic receptorso doxazosin (Cardura)o terazosin (Hytrin) – also reduces size of the prostate  Generally in older men, lower bp and make them void less o prazosin (Minipress) - Beta blockerso Reduce BP by reducing heart rate through beta1 blockade Slows heart rate o Cause reduced secretion of rennino Long-term use causes reduced peripheral vascular resistanceo Examples: nebivolol (Bystolic), propranolol (Inderal), atenolol (Tenormin), otherso “lol” drugs- Dual-action alpha1 and beta receptor blockerso Reduce heart rate (beta1 receptor blockade)o Cause vasodilation (alpha1 receptor blockade)o carvedilol (Coreg) and labetalol Especially good for heart failure patients because it is cardioselective  Good for patients with withdraw symptoms - Slows them down o Result in decreased blood pressure- Indications o All used to treat hypertensiono Centrally acting alpha2 receptor agonists  Treatment of hypertension, either alone or with other drugs Usually used after other drugs have failed because of adverse effects Clonidine is useful in the management of withdrawal symptoms in opioid-dependent persons- Peripherally acting alpha1 receptor agonists o Treatment of hypertensiono Some used to relieve symptoms of BPHo Management of severe heart failure (HF) when used with cardiac glycosides and diuretics- Adverse Effectso High incidence of orthostatic hypotension Especially if given IV and used to lower cardiac output  Fall precaution o Most common Bradycardia (slowing heart rate) with reflex tachycardia, dry mouth, drowsiness, sedation, constipation, depression, edema, and sexual dysfunction- All “lol” drugs o Other: Headaches, sleep disturbances, nausea, rash, cardiac disturbances (palpitationsAngiotensin-Converting Enzyme (ACE) Inhibitors- 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- Created from venom of South American viper- First line - Can be combined with other medications Lowering BP- First drug of choice: HCTZ (Hydrocholrathyazoid)o Diuretics to reduce water volume - Second drug of choice: Furosemide - ACE inhibitors – “pril” drugs ACE Inhibitors - captopril (Capoten), benazepril (Lotensin), enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil), moexipril (Univasc), quinapril (Accupril), and others- Mechanism of Actiono Inhibit angiotensin-converting enzyme, which is responsible for converting angiotensin I (through the action of renin) to angiotensin IIo Angiotensin II is a potent vasoconstrictor and causes aldosterone secretion from the adrenal glandso Block angiotensin-converting enzyme, thus preventing the formation of angiotensin IIo Prevent the breakdown of the vasodilating substance bradykinino Result in decreased systemic vascular resistance (afterload), vasodilation, and therefore decreased blood pressure- Indicationso Hypertensiono Heart Failure (either alone or in combination with diuretics or other drugs)o Slow progression of left ventricular hypertrophy after MI (cardioprotective) Slow enlargement of the hearto Renal protective effects in patients with diabetes Type II Diabetes patients will all be on an antihypertensive because it is renal-protectiveo Drugs of choice in hypertensive patients with HFo Drugs of choice for diabetic patientso Captopril and lisinopril (number one and least costly) are NOT prodrugs Prodrugs are inactive in their administered form and must be metabolized in the liver to an active form so as to be effective Captopril and lisinopril can be used if a patient has liver dysfunction, unlike other ACE inhibitors that are prodrugs- Adverse Effectso Fatigue (initial), Dizziness, Headache, Mood changes, Impaired taste, and Possible hyperkalemia (Retain more potassium)o Dry, nonproductive cough, which reverses when therapy is stopped – 18-20% of patients o Angioedema: rare but potentially fatalo ***ACE inhibitor will be less affective if the patient is on NSAIDS o First-dose hypotensive effect may occurAngiotensin II Receptor Blockers - Also referred to as angiotensin II blockers or ARBs- Well tolerated- Do not cause a dry cougho Created last o If ACE inhibitor