Pharm Exam 1: Section 2

Kidneys hold onto sodium and create thirst which increases volume and smooth muscle contraction Increases BP and increases tissue perfusion in arterioles If local tissue injury, A2 arrives and promotes vascular inflammation Remodeling of cardiac and vascular tissues in myocardium occurs Increased fibrous products in tissues –> hypertrophy Hypertrophy –> CHF

ACEI block Ace enzyme to prevent conversion of A1 to A2 ARBS don’t work on A2, work to block receptors for A2 at tissue level Bradykinin: at high levels in lung –> cough Prostaglandins: ACEI -> angioedema

Black people make less renin than other groups ACEI less effective

Decrease production of A2 and aldosterone Prevent vascular smooth muscle contraction -> decrease afterload (arteries) Decrease Na and H2O retention in kidney -> decrease preload (veins) - less volume in system Reduce vascular inflammation & remodeling bc A2 and its mechanisms are blocked Aldosterone tells kidney to hold onto Na and K -> H2O follows salt - > increased volume. ACEI and ARBS block this mechanism

Well absorbed PO; better on empty stomach. Ok with food Most are prodrugs (not active in own form but when they get to liver, they break down into metabolites that are active form) * Must be used in people with intact hepatic system * lisinopril & captopril not prodrugs Used alone and in combo with diuretics -> tends to improve efficacy

Renal protection: decrease arterial resistance in glomeruli; when blood comes through kidney Mild Insulin sensitization: ACEI & ARBS help cells recognize and use insulin- good for DM Most excreted renal: used in pts w/ early renal failure and microalbuminuria in DM. If pt has more advanced renal failure, start at low dose, check electrolytes in 1 week to ensure no high K Distributed to all tissues except CNS Cross placenta, are in breast milk.

No reflex tachycardia bc no impact on CO Hypotension High K if dose too high Cough: dry; don’t give another ACEI, can try ARB -Cross -sensitivity so can happen with ARBS Angioedema: typically when combined with other drugs like macrolides (zpack) • Occurs in face, mainly lips and mouth, sometimes forehead • If occurs, stop macrolide, stop ACEI for a couple of days • If just on ACEI, stop and start a different BP med; give antihistamine bc its a localized reaction

ARBS excreted fecally more than renal Cause with other BP meds C/I in pregnancy; Category C • avoid K+ sparing diuretics bc ACEI causes changes with Na and K • If K is high in ACEI, double check, if still high -> reduce dose a little bit

HTN (esp w/ DM): 1st line agent 1st line for DM bc of renal protection CHF: A2 and inflammation, remodeling -> cardiac changes; preload reducer, afterload reducer Microalbuminuria: >19 is pathological; reason pts with DM but not HTN might be put on low dose ACEI or ARBS –> decrease arterial deconstruction in kidneys; helps improve perfusion bc less pressure in kidneys Post MI, ACS, LVEF <40%

Potassium: make sure not elevated in first week and check again in 1 month Angioedema esp w. macrolides Don’t prescribe macrolide w/ ACEI if pt has infections Check liver function Check renal function

Most potent class of BP reduction Nondihydropyridines: Type 1 receptors - verapamil and diltiazem Dihydropyridines: Type 2 receptors - pines

Inhibit Ca+ movement at smooth muscle cell membrane • Arterial vasodilation • Decreased contractility • Decreased afterload • No impact on preload (no venous impact) Nondihydropines: slow AV node conduction; verapamil can be given sublingual; monitor BP closely; slow HR Dihydropines: vasodilator; little/no effect on HR; may cause reflex tachycardia if BP drops too low

All absorb well PO, OK with food Nondihydropines - rapid metabolism and bioavailability quickly (verapamil) Dihydropines: varying ,metabolism and absorption - Amlodipine 65-90%: well absorbed; high metabolism (works quickly), long half-life Isradipine 15%: poor absorption and bioavailability

Rarely cross blood brain barrier; don’t have sedative properties All cross placenta Excreted in breast milk, except Nifedipine Hepatic metabolism: broken down in liver Fecal and renal excretion Short 1/2 life if not sustained release formulation; need to be taken multiple times daily Norvasc (amlodipine): long half life; good agent to use for daily dosing

Nondihydropine: chronotropic effect - low HR and arrhythmia related to low HR or alteration in conduction or velocity Peripheral edema: vasodilation lets blood pool -> vascular permeability; elderly more prone Constipation: gut is primarily smooth muscle; effects musculature and contraction of gut; peristalsis slows; elderly more prone Worsen GERD - interferes with muscle contraction of lower esophageal sphincter -> increased reflux Flushing, HA, low BP, edema, reflex tachycardia

Sustained release formulas are most effective; most predictive metabolism and lowest rate of side effects; most predictive bioavailability; long acting prevents BP fluctuations Amlodipine: not sustained release; long acting and stable when crushed (good for pt w/ dysphasia); not excreted quickly; can be given once daily C/I in pt w/ HF!!! Not used immediately post ACS. Can worsen wolf Parkinson white syndrome (conduction disturbance) Category C Amlodipine Category D Check hepatic function before therapy: metabolized almost entirely in liver

Tachycardia dysrhythmias -rate control for SVT, afib, (verapamil & diltiazem) HTN migraine prophylaxis (30% improvement) Vasospastic angina (stable) bc of vasodilation effects Raynauds: peripheral arterial spasms in cold weather; vasodilation Esophageal spasm: lower esophageal sphincter relaxes w/ vasodilation of smooth muscle

Decrease volume decreased preload decreased pressure arterial bed

Inhibit Na, K, Cl, and bicarb reabsorption in distal tubule of nephron. H2O follows electrolytes out of body. Effect is increased Ca and uric acid Electrolyte imbalance: low K Increased glucose bc of dehydration Muscle cramps: due to increased Ca, paresthesias, impotence. Avoid in gout to prevent uric acid buildup

Chlorthalidone (Hygroton): very long 1/2 life (~50 hrs), very effective Hydrochlorothiazide (Microzide, Hyrodiuril) Indapaminde (Lozol) Metolazone (Zaroxolyn): not as effective in pt with renal impairment; with gfr < 25 or low creatinine clearance NOT effective

Work in loop of Henle in kidney; action happens sooner in kidneys than later in tubules where thiazides work. Have more substantial diuretic effect; helpful for pt with kidney function impairment and low gfr Furosemide (lasix) Bumetanide (Bumex) More substantial diuresis 0.5 - 1 hr 1/2 life More K loss; will need to replace K more often than with thiazide Indicated for edema with CHF

Alter Na reabsorption in distal tubules in nephron further than where K is reabsorbed; reason K sparing diuretics let go of Na and not K Triamterene Spironolactone Improve edema in CHF Na depletion: watch for low Na Avoid in ACE or ARB bc they hold onto K –> hyperkalemia

Preload reducers Long term: reduce volume -> decreased SVR and afterload

Triamterene not absorbed as well as others. All effect electrolytes Enter blood AND extracellular spaces Liver metabolizes diuretics; Furosemide is both hepatic and non hepatic All excreted in urine, some feces