HSCI 10197 Lecture 11: Diuretics PDF

HSCI 10197: Lecture 11 : DIURETICS Renal Physiology ◼ Renal = kidney ◼ Function: Maintain water, electrolytes, and acid-base balance ◼ Dysfunction: ❑ Nephritis: infection or inflammation ❑ Oliguria: decreased urine production ❑ Anuria: no urine production...

HSCI 10197: Lecture 11 : DIURETICS Renal Physiology ◼ Renal = kidney ◼ Function: Maintain water, electrolytes, and acid-base balance ◼ Dysfunction: ❑ Nephritis: infection or inflammation ❑ Oliguria: decreased urine production ❑ Anuria: no urine production ❑ Uremia: nitrogenous waste buildup due to renal impairment ◼ Diuretics increase flow of urine by inhibiting the tubular reabsorption of sodium ions and water ❑ “water pills” In the process of tubular reabsorption, the renal tubules absorb most of the nutrients filtered at the glomerulus. About 99 percent of the filtered sodium is reabsorbed. Sodium is an important component in extracellular fluid as well as in the renal mechanism of water conservation. Sodium ions are reabsorbed by two mechanisms: cation exchange and chloride ion transport. In the proximal and distal convoluted tubules, sodium ions (Na+) are reabsorbed in exchange for hydrogen ions (H+). Hydrogen ions are produced in the tubular cells through the action of the enzyme carbonic anhydrase (CAH). Carbon dioxide and water combine to form carbonic acid in the presence of the enzyme carbonic anhydrase (CAH), and carbonic acid rapidly breaks down into hydrogen ions and bicarbonate ions. The sodium and bicarbonate ions are transported into the blood at the peritubular capillary. The distal convoluted tubules also secrete potassium ions (K+) in exchange for sodium. The secretion of potassium ions is controlled by the adrenal mineralocorticoid aldosterone. Sodium ions are reabsorbed in the loop of Henle in conjunction with chloride ions (Cl -). When the renal tubules reabsorb sodium ions through these mechanisms, an osmotic gradient is established along the nephron. Classes of Diuretics 1. Carbonic anhydrase inhibitors 2. Organic acids (loop diuretics) 3. Osmotic (luminal) 4. Potassium-sparing 5. Thiazide and thiazide-like ◼ Primarily used in the management of: ❑ anuria, ❑ hypertension, ❑ edema ❑ CHF 1. Carbonic Anhydrase Inhibitors Acetazolamide (Diamox) MOA ◼ Inhibits an enzyme (carbonic anhydrase) that changes the rate of certain reactions, and in turn increases sodium and water excretion ◼ Disadvantage - tolerance develops after 3-4 days of treatment because it’s own action increase its own excretion, due to creating an acid-base imbalance Supplied: Injection, tablets, capsules XR Indications ◼ For the most part, they have been replaced by other diuretics (thiazides) as single drug treatment of edema ◼ May be used in adjunct for most causes of edema ◼ Glaucoma: reduces production of aqueous humor, reduces pressure in eye Adverse Effects (FYI only) ◼ Drowsiness, anorexia, GI distress, headache, depression, allergic rash (sulfonamide-like), hypokalemia, hyperuricemia (gout) 2. Organic Acids (Loop Diuretics) Furosemide (Lasix) Ethacrynic acid (Edecrin) Indications ◼ Patients resistant to thiazide diuretics ◼ Severe edema ◼ Edema associated with CHF ◼ Hypertension ◼ Acute pulmonary edema ◼ Renal disease MOA ◼ Inhibit sodium and chloride transport in loop of Henle ◼ Intense diuresis (loss of Na, Cl, H2O) ◼ Drugs work regardless of acid-base status ( it doesn’t have tolerance) ❑ Do not become refractory like carbonic anhydrase inhibitors Supplied ◼ Injection, tablets, oral liquid Adverse Effects ◼ Hypokalemia*, nausea, hypotension, hyperuricemia 3. Osmotic Diuretics (Mannitol) MOA ◼ Drug is filtered by kidney and not reabsorbed creating an osmotic gradient ❑ Which draws fluid from edematous tissue and water is excreted with diuretic Indications ◼ Used to stimulate urine flow in treatment of oliguria and anuria ◼ Acute renal failure ◼ Used to reduce intracranial or intraocular pressure ◼ Serious edema Supplied ◼ IV Adverse Effects ◼ Nausea, dizziness, headache, chills ◼ Increase in plasma volume, may be problem in patients with CHF or cardiac compromise ◼ Typically, not drug of choice 4. Potassium-Sparing Diuretics ◼ Spironolactone (Aldactone) ❑ Spironolactone/hydrochlorothiazide (Aldactazide) ◼ Amiloride (Midamor) ❑ Amiloride/hydrochlorothiazide (Moduret) ◼ Triamterene (Dyrenium) ❑ Triamterene/hydrochlorothiazide (Dyazide) MOA ◼ Produces mild diuresis without electrolyte changes and acid-base disturbances ❑ Inhibit potassium secretion in the distal convoluting tubules ◼ Holds K+ in regular blood flow ◼ Spironolactone – blocks aldosterone receptors ◼ Triamterene/amiloride – membrane alteration so potassium can not be secreted Indications ◼ Hypertension ◼ Hyperaldosteronism (adrenal condition) ◼ Edema when combined with thiazide and loop diuretics ◼ Use to control potassium depletion Adverse Effects ◼ Hyperkalemia, nausea, diarrhea Supplied ◼ Tablets (often combined with thiazide diuretic 5. Thiazide and Related Drugs Hydrochlorothiazide (HCTZ)**** Indapamide (Lozide) Metolazone (Zaroxolyn) Indications ◼ Edema (all types) ◼ Hypertension MOA ◼ Inhibit sodium transport in the distal portion of nephron – loss of Na and H2O ◼ Increased chloride and potassium excretion ◼ This results in hyperchloremic alkalosis & hypokalemia Supplied ❑ Tablets Adverse Effects ❑ Orthostatic hypotension (dizzy, faint, lightheaded) ❑ Hypokalemia, hyperuricemia, and hyperglycemia ❑ Muscle cramps or muscle spasms ❑ Hypersensitivity reactions – skin sensitivities ❑ Nausea, diarrhea, headache Counseling Tips ❑ Take dose with orange juice or banana (supplement K+) ❑ Take in morning…why? Because it causes you to go to the washroom. ❑ Get up slowly…why? Because the medication causes headache and dizziness. ❑ What auxiliary labels should be included? Thiazides reduce the clearance of uric acid since they compete for the same transporter, and therefore raise the levels of uric acid in the blood. Hence, they are prescribed with caution in patients with gout or hyperuricemia.  Antihypertensive Drugs Hypertension ◼ When blood pressure (BP) in the arterial system is abnormally high ◼ Occurs in about 10% of general population (US) ◼ 90% of these have no underlying disease which accounts for the disease = essential hypertension ◼ Secondary hypertension is most often associated with kidney disease, thyroid disease, and lifestyle factors ◼ Hypertension is a risk factor leading to other conditions: ❑ Stroke, myocardial infarction, kidney disease, congestive heart failure, coronary artery disease Blood Pressure Blood Pressure is determined by two factors: 1. Cardiac Output ❑ Determined by stroke volume and heart rate 2. Peripheral Resistance ( you start to see more problematic hypertension) ❑ Degree of vasoconstriction in blood vessels (arterioles) produced by increase in sympathetic tone or angiotensin levels ◼ Factors in BP control: - Weight (Obesity) - Physical Exercise - Smoking - Stress Levels - Sodium Intake - Cholesterol ◼ Often referred to as a silent disease because the condition has no readily identifiable symptoms ◼ Patients “feel” well – which may affect medication compliance and willingness to change lifestyle factors Role of Kidneys in Hypertension ◼ Increased peripheral resistance – reduced blood flow to kidney ◼ Kidney then reacts and increases secretion of renin ◼ Renin stimulates formation of angiotensin ◼ Angiotensin is an extremely potent vasoconstrictor and stimulates release of aldosterone from adrenal cortex ◼ Aldosterone causes the kidney to reabsorb more sodium and water – this exacerbates hypertension Categories of Hypertension Classification Diastolic SystolicTreatment Normal 75-84 120-129 None Borderline 85-89 130-139 Lifestyle changes Mild 90-99 140-159 Single Drug Moderate 100-109 160-179 Combined Drugs Severe 110-119 180-209 Combined Drugs Very Severe > 120 > 210 Combined Drugs Treating Hypertension ◼ Decision to treat mild hypertension may be influenced by risk factors – diabetes, cardiovascular disease (personal or famliy history), high cholesterol, target organ complications ◼ Only 50% of treated patients have optimally controlled Blood Pressure. ❑ Why? ❑ Where/how can Techs make a difference? Gathering information, how are they taking it , how compliance are they with their medication. Denial, no symptoms Non-compliance Poor follow-up by health professionals Failure to adjust doses over time Failure to minimize side effects Failure to set treatment goals in collaboration with patient Antihypertensive Drug Classes 1. Diuretics 2. Beta Blockers 3. Calcium Channel Blockers 4. Direct Vasodilators 5. Angiotensin Converting Enzyme Inhibitors 6. Angiotensin Receptor Blockers 7. Alpha Adrenergic Blockers 8. Central Adrenergic Inhibitors 1. Diuretics ◼ Often the first class of agents used in management of hypertension (depends on underlying disease) ◼ Thiazide or thiazide-like agents most common ◼ Low dosages are effective ◼ MOA: ❑ Reduces blood volume, reducing peripheral resistance and creates mild vasodilation ◼ Hydrochlorothiazide ◼ Indapamide ◼ Metolazone Indications ◼ Used alone in mild hypertension ◼ Used in combination with other medications in moderate to severe hypertension ◼ Many other indications as earlier seen Supplied Tablets (sometimes w/ potassium sparing diuretic) Note potassium sparing diuretics rarely used alone for CHF, edema, or HTN – used to help maintain K when on other drugs 1. Diuretics - Thiazides Adverse Effects ◼ Increase urination ◼ Hypokalemia ◼ Hypotension ( adjust the dose) ◼ Dehydration ( water, electrolytes) ◼ Muscle weakness, fatigue ◼ Hyperuricemia – may cause gout attack ( look for alternative) ◼ Hyperglycemia – interfere with action of insulin 1. Diuretics - Loop Diuretics ◼ Furosemide Indications ◼ May be used in hypertension in patients where thiazide or related drug is not able to reduce BP or is contraindicated – ie renal failure patient  2. Beta Blockers ◼ Acebutolol Monitan, Sectral S ◼ Atenolol Tenormin S ◼ Propranolol Inderal NS ◼ Nadolol Corgard NS ◼ Metoprolol Betaloc, Lopressor S ◼ Timolol NS ◼ Oxprenolol Slow-Trasicor, Trasicor NS ◼ Pindolol Visken NS ◼ Labetalol Trandate NS ◼ Bisoprolol Monocor S MOA ❑ Beta-blockade reduces heart rate ❑ Also reduces blood pressure by reducing cardiac output ❑ Blocks the release of renin (which causes vasoconstriction) Supplied ❑ Tablets, SR capsules/tablets (Why?) Adverse Effects ❑ Nausea, vomiting, diarrhea ❑ Bradycardia ❑ Vasodilation, hypotension, dizzy, faint, light headed ❑ Drowsiness, depression 3. Calcium Channel Blocking Agents ◼ Nifedipine Adalat ◼ Amlodipine Norvasc ◼ Felodipine Renedil, Plendil ◼ Diltiazem Cardizem ◼ Verapamil Isoptin MOA ◼ Interfere with the influx of calcium in vascular smooth muscle resulting in vasodilation Supplied ◼ Tablets, capsules, SR dosage forms Adverse Effects ◼ Hypotension, bradycardia ❑ Headache, fatigue, dizzy, lightheaded Other SE’s specific to agent 4. Direct Vasodilators ❑ Hydralazine (Apresoline) ❑ Minoxidil (Loniten) MOA ❑ Acts directly to relax vascular smooth muscle causing vasodilation ❑ Greater on arterioles than veins Supplied ❑ Hydralazine – tablets, injection ❑ Minoxidil – tablets What is minoxidil also used for?? Minoxidil affects the potassium channels present in vascular smooth muscles and hair follicles. This potassium channel activity may induce the following effects: Stimulation of the microcirculation around the hair follicles induces arteriolar vasodilation, thereby encouraging conditions conducive to hair growth. Indication ❑ Used in combination with beta blockers and diuretics to reduce blood pressure ❑ These agents are only used in combination with other agents in severe hypertensives Adverse Effects ❑ Hypotension ❑ Reflex Tachycardia ❑ N/V ❑ Headache 5. Angiotensin Converting Enzyme Inhibitors (ACE-Inhibitors) ◼ Benazepril Lotensin ◼ Captopril Capoten ◼ Enalaril Vasotec ◼ Ramipril Altace* ◼ Lisinopril Prinivil, Zestril ◼ Fosinopril Monopril ◼ Cilazapril Inhibace ◼ Perindopril Coversyl ◼ Quinapril Accupril MOA ◼ Inhibit ACE which is an enzyme involved in the conversion of angiotensin 1 to angiotensin 2 (a vasoconstrictor) ◼ Angiotensin 2 leads to production of aldosterone and increased salt and water retention Supplied ◼ Oral solids (tablets, capsules) – Why PO? ◼ One Injection – enalapril (Vasotec) Adverse Effects ◼ Headache, dizziness…why? ◼ GI disturbances ◼ Nonproductive Cough ◼ may be related to increase in bradykinin concentration ◼ occurs in about 10% of treated patients, affects compliance (prescriber may switch within class or switch to new class to avoid) ◼ Rare: ❑ Angioedema ❑ Rash 5. ACE Inhibitors ◼ ACE-inhibitors are often combined with hydrochlorothiazide…Why? Quinapril + HCTZ Accuretic Enalapril + HCTZ Vaseretic Lisinopril + HCTZ Zestoretic, Prinzide Cilazapril + HCTZ inhibace Plus Reduces action of aldosterone which causes retention of K+ and possible hyperkalemia therefore give HCTZ to reduce risk 6. Angiotensin Receptor Blockers ◼ Irbesartan Avapro ◼ Losartan Cozaar ◼ Valsartan Diovan ◼ Candesartan Atacand ◼ Telmisartan Micardis ◼ Eprosartan Teveten 6. ARB’s Indications ◼ Mild to moderate essential hypertension ◼ Alone or with thiazide diuretics MOA ◼ Blocks the Angiotensin receptor, preventing angiotensin from producing vasoconstrictor effects Supplied ◼ Tablets and capsules (all po forms…why?) Drugs available in combination with a diuretic: ◼ Irbesartan + HCTZ Avalide ◼ Candesartan + HCTZ Atacand Plus ◼ Losartan + HCTZ Hyzaar, Hyzaar DS ◼ Telmisartan + HCTZ Micardis Plus ◼ Valsartan + HCTZ Diovan-HCT 7. Alpha Adrenergic Blockers ◼ Prazosin Minipress ◼ Terazosin Hytrin ◼ Doxazosin Cardura Indications ◼ Treatment of mild to moderate essential HTN ◼ Also Benign Prostatic Hypertrophy (BPH) Adverse Effects ◼ Hypotension ❑ Dizziness, fainting, light-headedness 8. Central Adrenergic Inhibitors ◼ Methyldopa Aldomet ◼ Clonidine Catapres ◼ Used in severe hypertensives or if patient refractory to first line treatments ◼ Many other unrelated uses Methyldopa also use in Parkinson disease and high blood pressure. Choice of AntiHx drug… ◼ Dependent on patient factors, other meds, and other underlying diseases ◼ Typically: 1. Diuretic 2. Then add ACE or ARB 3. Then add Beta or Ca Blocker 4. Direct Vasodilators and Alpha Blockers typically only used in severe hypertensives Note potassium sparing diuretics rarely used alone for CHF, edema, or HTN – used to help maintain K when on other drugs