Heart Failure- Clinical Therapeutics
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Heart Failure, Pharmacology, Clinical Therapeutics Report
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Heart Failure- Clinical Therapeutics
- 1. HYPERTENSION AND CONGESTIVE HEART FAILURE DELA CRUZ, JUSAY, YANG, ZAGADA
- 2. Problem 1 Congestive Heart Failure (in acute exacerbation)
- 3. Basis: Chief Complaint: increased shortness of breath History of Present Illness: swolen legs malaise weakness weight gain paroxysmal nocturnal dyspnea ankle edema PMH: HF (LVEF of 15%) orthopnea HTN for 30 years CAD tachycardia Medications: Digoxin Furosemide Spirinolactone Carvedilol Amiodarone
- 4. Basis: Physical Examination: SOB weight gain of 7 kg hepatomegaly +S1, S2 jugular venous distention edema bibasal rales Laboratory Findings: 2+ protein BUN 32 SCr 1.9
- 5. Treatment Objectives To decrease fluid retention To decrease workload of the heart To increase myocardial contractility
- 6. Pharmacologic intervention 1. Decreasing fluid retention Drug of Choice: Loop Diuretics Action: dec. NaCl and KCl reabsorption in thick ascending limb of the loop of henle in the nephron Indication: antihypertensive, manifestation of fluid overload, swollen legs, edema, weight gain
- 7. Furosemide Drug interactions: Ace inhibitor – can cause hyperkalemia Diuretics – may cause hypokalemia Digoxin – may inc. its effect or may reach toxicity
- 8. Pharmacologic intervention2. To decrease workload of the heart DRUGS EFFICACY SAFETY SUITABILITY COST ACE inhibitor ++++ +++ ++++ ++ ARB +++ +++ +++ +++ Vasodilators ++ + + +
- 9. Drug of Choice: ACE inhibitorPharmacologic intervention Alternative Drug: ARBs ACEIs and ARBs ACTION: Inhibits angiotensin converting enzyme, thus, aldosterone and ADH secretion is inhibited ACE inhibitor will also inhibit the inactivation of bradykinin, thus, prostaglandin synthesis will increase
- 10. Drug of Choice: ACE inhibitorPharmacologic intervention Alternative Drug: ARBs ACE inhibitors: Increase toxicity in patients with renal failure Interaction with : K-sparing diuretics Patient has ACEI-induced cough
- 11. Pharmacologic intervention To increase myocardial contractility DRUGS EFFICACY SAFETY SUITABILITY COST Cardiac Glycoside ++++ + ++ ++ Beta adrenoceptor agonist ++++ ++ ++ +++ Bipyridines ++ ++ ++ +
- 12. Dobutamine ACTION: directly binds to cardiac beta 1 receptors which increase force of contraction Pharmacologic interventionDrug of Choice: Beta Adrenoceptor Agonist
- 13. Pharmacologic intervention IF HEART FAILURE CONTINUES TO WORSEN: Add NITRATES or ALPHA BLOCKERS
- 14. Non - Pharmacologic intervention Diet Daily weight chart Sodium restriction Alcohol restriction Nutritional Supplements (vitamins) Other Smoking cessation Exercise Psychosocial services Intensive follow-up
- 15. Yang, Sheryl Ray B.
- 16. Hypertension One of the most common worldwide diseases afflicting human and is a major risk factor for stroke, myocardial infarction, vascular disease and CKD HPN is defined as a Systolic Blood Pressure (SBP) of > 140 mmHg, or a Diastolic Blood Pressure (DBP) of >90 mmHg, or taking antihypertensive medication
- 17. Types of HPN Types: 1. Primary (Essential) 90-95% Chronic High blood pressure without a source or associated with any other disease Most common form 2. Secondary 5-10% • Elevation of BP associated with another disease such as kidney disease • Causes include: CKD, D/o of adrenal gland, Pregnancy, Hyperparathyroidism
- 19. Risk factors Family History of High BP Family Hx of Premature CVD Diabetes Race (African American) Lifestyle Risk Factors: Weight (BMI >30) Stress Sedentary lifestyle Diet Smoking Alcohol (F:>1 Drink/day; M: >2 Drinks/day) Birth control pills Can’t be changed Can be changed
- 20. Treatment Goals Use and Maximize nonpharmacologic therapies in combination with pharmacotherapy Individualize all therapies based on compelling indications and comorbid conditions Treat systolic BP to recommended goal as primary focus (esp. patients >50 yrs old) Ultimate treatment goal is the reduction of cardiovascular and renal morbidity & mortality
- 21. Basis of DiagnosisHistory: 59y/o, Male African American Hypertension for 30 years Diabetes Mellitus (DM) type 2 for 5 years Prior cigarette smoker 3-4 packs/week; quit 30 years ago Social drinker; 6 cans of beer/week Medications: Furosemide, 80mg PO QAM Spironolactone, 12.5mg PO QD Carvedilol, 25mg PO QAM, 12.5mg PO QPM Physical Examination: BP 153/91 mmHg BMI of 26.4 = Overweight
- 22. Choice of Anti-HPN drugs depend on: Stage of hypertension Physical factors( cardiac, renal complications) Individualized prescribed on a trial basis
- 23. Diuretics Sympathoplegi c agents Vasodilators Angiotensin antagonists Major Classes of Anti-Hypertensive Drugs
- 24. DRUG CLASSES EFFICACY SAFETY SUITABILITY COST Diuretics ++++ +++ +++ ++++ Vasodilators ++ ++ ++ + Calcium channel blockers ++++ ++ +++ ++ Beta Blockers ++++ ++ ++++ ++ ACE Inhibitor ++++ +++ +++ ++++ Angiotensin Receptor Blocker ++++ ++++ ++++ +++ Major Classes of Anti-Hypertensive Drugs
- 25. Angiotensin-Receptor Blockers Competitive angiotensin II receptor antagonists Effect same as ACEIs Vasodilatation and decreased sodium retention Do not block bradykinin metabolism Same efficacy with ACEIs; more expensive For those unable to tolerate ACEIs Losartan, Valsartan - first marketed AT1 receptor blocker
- 26. Angiotensin Receptor Blockers DRUG EFFICACY SAFETY SUITABILITY COST Losartan (Cozaar) +++ ++++ +++ +++ Valsartan (Diovar) +++ ++++ +++ +++ Olmesartan (Olmetec) ++++ ++++ ++++ +++ Candesartan (Atacand) ++++ ++++ +++ ++ Irbesartan ++++ ++++ +++ ++ Telmisartan (Micardis) ++++ ++++ ++++ ++++
- 27. NONPHARMACOLOGIC THERAPY Appropriate lifestyle modifications are important therapies in both the prevention and treatment of hypertension. The prevalence of hypertension is 50% greater in overweight
- 28. PATIENT EDUCATION Immediate reporting of any adverse side effects, especially slow or irregular heartbeat, dizziness, weakness, breathing difficulty, gastric distress and numbness or swelling of extremities Taking medication on time as prescribed by the physician, not skipping a dose or doubling a dose, NOT discontinuing the medication, even, if the patient is feeling well, without consulting the physician first 29
- 29. PATIENT EDUCATION Rising slowly from reclining position to reduce lightheaded feeling, Taking care in driving a car or operating machinery if medication causes drowsiness. Potentiation of adverse side effects by alcohol, esp dizziness, weakness, sleepiness and confusion, Reduction or cessation of smoking to help lower blood pressure 30 PATIENT EDUCATION
- 30. PATIENT EDUCATION Importance of diet in control of blood pressure , following the physician’s instructions regarding appropriate diet for the individual, which may include a low-salt diet or low sodium or weight reduction diet if indicated. Avoiding hot rubs and hot showers, which may cause weakness or fainting. Mild exercise on a regular basis as approved by the physician. 31 PATIENT EDUCATION
- 31. SHERYL RAY YANG, MD FEU-NRMF MEDICAL CENTER Fairview, Quezon City Tel no. 312-1234 Name:________________ Date: _______________ Age:_____ Sex:_____ Address: __________________ Telmisartan 40 mg tablet # 7 (Micardis) Sig. Take 1 tablet of Telmisartan daily for the control of Hypertension. Follow up after 7 days. Sheryl Ray B. Yang, M.D. Lic. No. 3333_________ PTR no. 101010_______
- 32. JUSAY , ARKEE REYLO P.
- 33. Diabetes Diagnosed as DM type 2 for 5 years. Fasting glucose level of o f 210 mg/ dl (Normal is 126 mg/dL/ 7 mmol/L) HbA1C level of 7.2% (Normal for the patient is less than 7 %)
- 34. Treatment Goals 1. Lower the fasting glucose level less than 130 mg/dL. 2. Lower the HbA1c level to 6.5-6.9 % in 3 months. 3. Follow a versatile diet in relation to patient preference. 4. Maintain the therapeutic glucose level for a long term and educate the patient for glucose monitoring. 5. Develop a routine exercise for the patient.
- 35. Pharmacologic Intervention Management of hyperglycemia in type 2 Diabetes: A patient-centered Approach A position statement of the American Diabetes Association (ADA) and the European association for the study of Diabetes (EASD) PUBLISHED: APRIL 19, 2012
- 37. 1. Classify the patient if its type 1 DM or type 2 -DM type 2 2. FBS level and HbA1c level? - FBS- 210 mg/dL and HbA1c level of 7.2 % 3. Age of the patient and other pertinent data? -59 years old
- 38. DRUG/DRUG CLASS EFFICACY SAFETY SUITABILITY COST METFORMIN +++ + ++ ++++ SULFONYLUR EAS (GLYBURIDE) ++++ +++ +++ ++++ THIAZOLIDINED IONES (PIOGLITAZONE) ++ + + + MEGLITINIDES (REPAGLINIDE) +++ ++ ++ + a- GLUCOSIDASE INHIBITORS ++ +++ ++ ++ DPP-4 INHIBITORS ++++ ++ ++ +
- 39. ARKEE REYLO P. JUSAY, MD FEU-NRMF MEDICAL CENTER Sta Mesa, Manila Tel no. 312-1234 Name:________________ Date: _______________ Age:_____ Sex:_____ Address: __________________ Glyburide 5 mg tablet # 7 (Micardis) Sig. Take 1 tablet of Glyburide daily for the control of Hyperglycemia. Follow up after 7 days. ARKEE REYLO P. JUSAY, M.D. Lic. No. 3333_________ PTR no. 101010_______
- 40. Non-pharmacologic intervention Diet modification. Develop a regular exercise.
- 42. DRUG CLASS MOA EFFECTS CLINICAL APPLICATIO NS Amiodarone Class III antiarrhythmi c • K+ Channel blocker • Beta adrenoreceptor and Ca Blocker • Na channel blockage • Prolongs atrial and ventricular repolarization • slows heart rate and AV node conduction • Slow intraventricula r conduction Ventricular arrhythmias, tachycardia, atrial fibrillation Furosemide Loop Diuretic Inhibition of the Na/K/2Cl transporter in the ascending limb of Henle’s loop Increased excretion of salt and water; reduces cardiac preload and afterload, reduces pulmonary and peripheral edema Acute & chronic heart failure, severe hypertension, edematous conditions
- 43. DRUG CLASS MOA EFFECTS CLINICAL APPLICATIO NS (Avandia) Rosiglitazon e thiazolidinedio ne (TZD) Bind and stimulate the nuclear hormone receptor peroxisome proliferator activated receptor-γ (PPARγ) increasing insulin sensitivity in adipose tissue, liver, and muscle Diabetes Mellitus type 2 Spironolacto ne Aldosterone Antagonist (Potassium sparing) Blocks cytoplasmic aldosterone receptors in collecting tubules of nephron Decreased salt and water retention; reduces cardiac remodeling and mortality Chronic heart failure, aldosteronism , hypertension, adrenal tumor Carvedilol Sympatholytic mixed alpha- and beta-adrenergic blockers Prevents sympathetic cardiac stimulation, reduce renin secretion Hypertension, heart failure
- 44. DRUG CLASS MOA EFFECTS CLINICAL APPLICATIO NS (Coumadi n) Warfarin Oral Anticoagu lant inhibits synthesis of biologically active coagulation factors II, VII, IX, and X and anticoagulant proteins C and S Reduces formation of blood lots Prophylaxis for thrombosis and thrombo- embolism Digoxin Cardiac Glycoside Na+, K+ ATPase inhibition • positive inotropy • increase parasympathetic (vagal) tone • prolong effective refractory period and slow conduction velocity Heart failure, Atrial fibrillation
- 45. DRUG INTERACTIO
- 46. Carvedilol Warfarin Furosemide Amiodarone Management: Additive effects of severe bradycardia, cardiac arrest, ventricular fibrillation Clinical monitoring of patient hemodynamic status and response is recommended. Increased effects of Warfarin 30% to 50% reduction in anticoagulant dosage has been recommended, in addition to frequent monitoring of the patient and the prothrombin time or INR. Additive arrythmogenic potential; Amiodarone causes dose-related prolongation of QT interval Coadministration of amiodarone with medications that can cause potassium and/or magnesium disturbances should generally be avoided
- 47. Amiodarone Carvedilol Furosemide Spironolacto ne Digoxin Manage ment may increase serum digoxin concentration s by up to 100% Empirical reduction of digitalis dosage by one-third to one-half should be considered decreases AV nodal conduction; increase the risk of developing bradycardia Serum digoxin levels, heart rate, and blood pressure should be monitored closely. diuretic-induced hypokalemia and hypomagnesemi a may predispose patients on digitalis to arrhythmias. Digoxin, potassium and magnesium levels should be followed closely. Spironolactone may reduce the tubular secretion of digoxin. patient should be monitored for signs and symptoms of digoxin toxicity
- 48. Spironolactone Furosemide Coumadin (Warfarin) Management Spironolactone may cause diuresis and hemoconcentration of clotting factors. The effects of some anticoagulants may be decreased. The INR or PT should be monitored, and oral coagulant dosage should be increased as needed. Loop diuretics may displace warfarin from plasma protein binding sites. Plasma warfarin concentrations and warfarin effects may be increased. Close monitoring of the INR is recommended, particularly if diuretic dosage must be high.
- 50. DRUG CLASS MOA EFFECTS CLINICAL APPLICATIO NS Amiodaron e Class III antiarrhythmi c • K+ Channel blocker • Beta adrenoreceptor and Ca Blocker • Na channel blockage • Prolongs atrial and ventricular repolarization • slows heart rate and AV node conduction • Slow intraventricula r conduction Ventricular arrhythmias, tachycardia, atrial fibrillation Furosemide Loop Diuretic Inhibition of the Na/K/2Cl transporter in the ascending limb of Henle’s loop Increased excretion of salt and water; reduces cardiac preload and afterload, reduces pulmonary and peripheral edema Acute & chronic heart failure, severe hypertension, edematous conditions
- 51. DRUG CLASS MOA EFFECTS CLINICAL APPLICATIO NS (Avandia) Rosiglitazon e thiazolidinedione (TZD) Bind and stimulate the nuclear hormone receptor peroxisome proliferator activated receptor-γ (PPARγ) increasing insulin sensitivity in adipose tissue, liver, and muscle Diabetes Mellitus type 2 Spironolact one Aldosterone Antagonist (Potassium sparing) Blocks cytoplasmic aldosterone receptors in collecting tubules of nephron Decreased salt and water retention; reduces cardiac remodeling and mortality Chronic heart failure, aldosteronism , hypertension, adrenal tumor Carvedilol Sympatholytic mixed alpha- and beta-adrenergic blockers Prevents sympathetic cardiac stimulation, reduce renin secretion Hypertension, heart failure
- 52. DRUG CLASS MOA EFFECTS CLINICAL APPLICATIO NS (Coumadi n) Warfarin Oral Anticoagu lant inhibits synthesis of biologically active coagulation factors II, VII, IX, and X and anticoagulant proteins C and S Reduces formation of blood lots Prophylaxis for thrombosis and thrombo- embolism Digoxin Cardiac Glycoside Na+, K+ ATPase inhibition • positive inotropy • increase parasympathetic (vagal) tone • prolong effective refractory period and slow conduction velocity Heart failure, Atrial fibrillation
- 53. DRUG INTERACTIO
- 54. Amiodarone Carvedilol Furosemide Spironolacto ne Digoxi n Manage ment may increase serum digoxin concentration s by up to 100% Empirical reduction of digitalis dosage by one-third to one-half should be considered decreases AV nodal conduction; increase the risk of developing bradycardia Serum digoxin levels, heart rate, and blood pressure should be monitored closely. diuretic-induced hypokalemia and hypomagnesemi a may predispose patients on digitalis to arrhythmias. Digoxin, potassium and magnesium levels should be followed closely. Spironolactone may reduce the tubular secretion of digoxin. patient should be monitored for signs and symptoms of digoxin toxicity
- 55. Spironolactone Furosemide Coumadin (Warfarin) Management Spironolactone may cause diuresis and hemoconcentration of clotting factors. The effects of some anticoagulants may be decreased. The INR or PT should be monitored, and oral coagulant dosage should be increased as needed. Loop diuretics may displace warfarin from plasma protein binding sites. Plasma warfarin concentrations and warfarin effects may be increased. Close monitoring of the INR is recommended, particularly if diuretic dosage must be high.
- 56. Warfarin Glyburide Management sulfonylureas may enhance or reduce the hypoprothrombinemic response to oral anticoagulants The patient should be monitored for altered anticoagulation (PT/INR) and altered glycemic effect spironolactone Telmisartan Management may increase the risk of hyperkalemia Caution is advised if angiotensin II receptor blockers must be used concurrently with potassium-sparing diuretics
Notes de l'éditeur
- Orthopnea is shortness of breath (dyspnea) which occurs when lying flat,causing the person to have to sleep propped up in bed or sitting in a chair. It is the opposite of platypnea.
- Orthopnea is shortness of breath (dyspnea) which occurs when lying flat,causing the person to have to sleep propped up in bed or sitting in a chair. It is the opposite of platypnea.
- Bec. Of signs of congestion of the patient. dyspnea, Orthopnea, edemaWHY WAS THERE CONGESTION?Bec. Lisinopril is discontinued, therefore angiotensin II is produced forming aldosterone-w/c is resp. for Na and water retention.
- Loop (furosemide)– 2-4hrs duration of action (shorter), IVMOA-dec. Nacl and KCl reabsorption in thick ascending limb of the loop of henle in the nephron.efficaceous for acute CHF bec. Of rapid onset of action, and can maximally reduce fluid (good for severe HPN).not for maintenance bec. Of shorter duration of actionThiazide – inhibits Na/Cl transporter in the distal convoluted tubule, 25mg/day PO, 8-12hrs Doa (longer)
- Loop (furosemide)– 2-4hrs duration of action (shorter), 80 mg/day BID, POMOA- dec. Nacl and KCl reabsorption in thick ascending limb of the loop of henle in the nephron.efficaceous for acute CHF bec. Of rapid onset of action, and can maximally reduce fluid (good for severe HPN).not for maintenance bec. Of shorter duration of actionAdministration of drugs – may be taken with meals to reduce GI discomportToxicity: hypovolemia, hypokalemia, orthostatic hypotension, ototoxicity, allergic reaction,
- Effect of diuretics to potassium:-decrease or hypokalemiaDigoxin – binds with Na K ATPase binding site (phosphorilated – binding will be greater), potassium dephosphorilates the binding site of Na k ATPase so if hypokalemic, Na K ATPase is more phosphorilated w/c has more higher affinity to digoxin – increase digoxin effect or may reach toxicity
- VasodilatorsWhy more efficaceous? – bec. Arterioles – for afterload and veins – for preloadThe fastest way to reduce the afterload and preload is to reduce blood going back to the heart. So that the pressure will be reduced. Ace inhibitor – reduce peripheral resistance thereby reduce afterload and preload( reduce salt and water retention), 12-24hrs duration of action, 5 mg/ OD oral, toxicity – hyperkalemia, cough, edema, Cardiac glycosides – inhibits sodium pump, increase cardiac contractility,. 0.25mgx500 oral, 36-40hrs duration, toxicity-nausea and vomiting, diarrhea, cardiac arrhythmias (choice for chronic heart failure)
- For maintenance – oral nitratesAdvantage-longer duration of action compare to nitroglycerine
- For maintenance – oral nitratesAdvantage-longer duration of action compare to nitroglycerine
- Symptoms of diabetes plus casual plasma glucoseconcentration 200 mg/dL (11.1 mmol/L). Casual isdefined as any time of day without regard to time sincelast meal.The classic symptoms of diabetes include polyuria, polydipsia,and unexplained weight loss.OrFasting plasma glucose 126 mg/dL (7.0 mmol/L). Fastingis defined as no caloric intake for at least 8 hours.OrTwo-hour plasma glucose 200 mg/dL during an oralglucose tolerance test. A 75-g glucose load or equivalent isrecommended when performing this test.(From Expert Committee on the Diagnosis and Classification ofDiabetes Mellitus. Report of the expert committee on the diagnosisand classification of diabetes mellitus. Diabetes Care20:1183–1197, 1997; and Expert Committee on the Diagnosis andClassification of Diabetes Mellitus. Follow-up report on the diagnosisof diabetes mellitus. Diabetes Care 26:3160–3167, 2003.)
- Safety: adverseSuitability: interactionEfficacy: moa & therapeutic goal
- 1. AF occurs if rapid, disorganized electrical signals cause the heart's two upper chambers—called the atria (AY-tree-uh)—to fibrillate. The term "fibrillate" means to contract very fast and irregularly.2. The high sodium reabsorption capacity of the TAL makes loop diuretics a front-line therapy for acute relief of pulmonary and peripheral edema in the context of heart failure
- 3.binding to the β1- and β2-adrenergic receptors. Carvedilol blocks the binding to those receptors,which both slows the heart rhythm and reduces the force of the heart's pumping. This lowers blood pressure thus reducing the workload of the heartbinds to the α1-adrenergic receptors on blood vessels, causing them to constrict and raise blood pressure. Carvedilol blocks this binding to the α1-adrenergic receptors too,which also lowers blood pressure.
- Coumarin anticoagulants block the γ-carboxylation of several glutamate residues in prothrombin and factors VII, IX, and X as well as the endogenous anticoagulant proteins C and S. The blockade results in incomplete coagulation factor molecules that are biologically inactive. The protein carboxylation reaction is coupled to the oxidation of vitamin K. The vitamin must then be reduced to reactivate it. Warfarin prevents reductive metabolism of the inactive vitaminK epoxide back to its active hydroquinone form1) In myocardium, inhibit plasma membrane Na+/K+-ATPase, leading to increased cytoplasmic Ca2+ concentration, which results in positive inotropy; 2) in autonomic nervous system, inhibit sympathetic outflow and increase parasympathetic (vagal) tone; 3) at AV node, prolong effective refractory period and slow conduction velocity
- 1. (moderate) Amiodarone enhances the B-blocking effects of carvedilol since it is an inhibitor of hepatic CYP2C9 and P-glycoprotein which increases carvedilol’s concentration by inhibiting 1st pass metabolism. 2. (major) Amiodarone inhibition of CYP450 2C9, preventing Warfarin’s metabolism; may lead to significant hypoprothombinemia and bleeding; resulting to life-threatening bleeding complications.3. (major) Theoretically, coadministration with agents that can produce hypokalemia and/or hypomagnesemia (e.g., potassium-wasting diuretics, amphotericin B, cation exchange resins, stimulant laxatives) may result in elevated risk of ventricular arrhythmias, including ventricular tachycardia and torsades de pointes, because of additive arrhythmogenic potential.
- This increase occurs because of the inhibition of digoxin secretion from renal tubules and the inhibition of the P-glycoprotein membrane transporter system.(major) Amiodarone has been suggested to increase intestinal transit time, reduce renal clearance and volume of distribution, displace digoxin from protein binding sites, as well as induce hypothyroidism, all of which may contribute to increased serum digoxin levels. In addition, both drugs may have additive bradycardic effects. Management: continued digitalis therapy should be evaluated if amiodarone is prescribed to patients treated with digitalis. Empirical reduction of digitalis dosage by one-third to one-half should be considered in patients who require concomitant treatment with these drugs.(moderate) Concomitant use of digitalis glycosides and beta-blockers including carvedilol may increase the risk of bradycardia. These agents slow atrioventricular conduction and decrease heart rate, hence they may have additive cardiac effects during coadministration. Pharmacokinetically, carvedilol has been shown to modestly increase the systemic bioavailability of digoxin. The mechanism may involve enhanced absorption as well as reduced renal excretion of digoxin due to inhibition of intestinal and renal P-glycoprotein efflux transporter by carvedilol. Management: monitored closely, particularly during the first few weeks of concomitant therapy(moderate) decreases plasma potassium concentration, which can increase the affinity of digoxin for the Na/K- ATPase predisposing to Digoxin toxicity; diuretic-induced hypokalemia and hypomagnesaemia may predispose patients to arrhythmias.(minor) Plasma clearance of digoxin may be decreased, and plasma levels may increase. Reduces tubular secretion of digoxin; Increased plasma digoxin levels
- (minor) (minor)
- 1. Extracardiac effect: Peripheral vasodilation- Hypotension. Block thyroid conversion of T3-T4. AF occurs if rapid, disorganized electrical signals cause the heart's two upper chambers—called the atria (AY-tree-uh)—to fibrillate. The term "fibrillate" means to contract very fast and irregularly.2. The high sodium reabsorption capacity of the TAL makes loop diuretics a front-line therapy for acute relief of pulmonary and peripheral edema in the context of heart failure
- The TZDs do not affect insulin secretion, but rather enhance the action of insulin at target tissues. TZDs are agonists for the nuclear hormone receptor peroxisome proliferator activated receptor-γ (PPARγ).Mineralocorticoid receptor antagonists such as spironolactone competitively inhibit the interaction of aldosterone with the mineralocorticoid receptor, and thereby decrease expression of ENaC(apical membrane sodium channel).binding to the β1- and β2-adrenergic receptors. Carvedilol blocks the binding to those receptors,which both slows the heart rhythm and reduces the force of the heart's pumping. This lowers blood pressure thus reducing the workload of the heartbinds to the α1-adrenergic receptors on blood vessels, causing them to constrict and raise blood pressure. Carvedilol blocks this binding to the α1-adrenergic receptors too,which also lowers blood pressure.
- 1. Warfarin acts on the carboxylation pathway, not by inhibiting the carboxylase directly, but by blocking the epoxide reductase that mediates the regeneration of reduced vitamin K.Coumarinanticoagulants block the γ-carboxylation of several glutamate residues in prothrombin and factors VII, IX, and X as well as the endogenous anticoagulant proteins C and S. The blockade results in incomplete coagulation factor molecules that are biologically inactive. The protein carboxylation reaction is coupled to the oxidation of vitamin K. The vitamin must then be reduced to reactivate it. Warfarin prevents reductive metabolism of the inactive vitamin K epoxide back to its active hydroquinone form2. 1) In myocardium, inhibit plasma membrane Na+/K+-ATPase, leading to increased cytoplasmic Ca2+ concentration, which results in positive inotropy; 2) in autonomic nervous system, inhibit sympathetic outflow and increase parasympathetic (vagal) tone; 3) at AV node, prolong effective refractory period and slow conduction velocitydigoxin exerts autonomic effects through its binding to sodium pumps in the plasma membranes of neurons in the central and peripheral nervous systems. These effects include inhibition of sympathetic nervous outflow, sensitization of baroreceptors, and increased parasympathetic (vagal) tone. Digoxin also alters the electrophysiologic properties of the heart by a direct action on the cardiac conduction system. At therapeutic doses, digoxin decreases automaticity at the AV node, prolonging the effective refractory period of AV nodal tissue and slowing conduction velocity through the node.
- This increase occurs because of the inhibition of digoxin secretion from renal tubules and the inhibition of the P-glycoprotein membrane transporter system.(major) Amiodarone has been suggested to increase intestinal transit time, reduce renal clearance and volume of distribution, displace digoxin from protein binding sites, as well as induce hypothyroidism, all of which may contribute to increased serum digoxin levels. In addition, both drugs may have additive bradycardic effects. Management: continued digitalis therapy should be evaluated if amiodarone is prescribed to patients treated with digitalis. Empirical reduction of digitalis dosage by one-third to one-half should be considered in patients who require concomitant treatment with these drugs.(moderate) Concomitant use of digitalis glycosides and beta-blockers including carvedilol may increase the risk of bradycardia. These agents slow atrioventricular conduction and decrease heart rate, hence they may have additive cardiac effects during coadministration. Pharmacokinetically, carvedilol has been shown to modestly increase the systemic bioavailability of digoxin. The mechanism may involve enhanced absorption as well as reduced renal excretion of digoxin due to inhibition of intestinal and renal P-glycoprotein efflux transporter by carvedilol. Management: monitored closely, particularly during the first few weeks of concomitant therapy(moderate) decreases plasma potassium concentration, which can increase the affinity of digoxin for the Na/K- ATPase (since digoxin normally competes with K+ ions for the same binding site on the Na+/K+ ATPase pump.) predisposing to Digoxin toxicity; diuretic-induced hypokalemia and hypomagnesaemia may predispose patients to arrhythmias.(minor) Plasma clearance of digoxin may be decreased, and plasma levels may increase. Reduces tubular secretion of digoxin; Increased plasma digoxin levels
- (minor) (minor)
- Oral sulfonylureas may enhance or reduce the hypoprothrombinemic response to oral anticoagulants. The mechanism may be related to displacement from plasma protein binding sites. In addition, coumarin anticoagulants may cause an increase in blood levels of hypoglycemic agents, possibly by inhibiting their hepatic metabolism. Clinical data have been highly variable. MANAGEMENT: The patient should be monitored for altered anticoagulation (PT/INR) and altered glycemic effect when either of these drugs is added to or removed from a patient's regimen. Patients should be advised to regularly monitor their blood sugar, counseled on how to recognize and treat hypoglycemia (e.g., headache, dizziness, drowsiness, nausea, tremor, hunger, weakness, or palpitations), and to promptly report any signs of bleeding 2. Concomitant use of angiotensin II receptor blockers (ARBs) and potassium-sparing diuretics may increase the risk of hyperkalemia. Inhibition of angiotensin II results in decreased aldosterone secretion, which can lead to increases in serum potassium that may be additive with that induced by potassium-sparing diuretics. Life-threatening and fatal hyperkalemia can occur, especially when the combination is used in patients with risk factors such as renal impairment, diabetes, old age, severe or worsening heart failure, dehydration, and concomitant use of other agents that block the renin-angiotensin-aldosterone system or otherwise increase serum potassium levels. Individually, both ARBs and potassium-sparing diuretics have been associated with hyperkalemia in patients with renal impairment. ARBs may also cause deterioration of renal function in patients with chronic heart failure, and the risk is increased if they are sodium-depleted or dehydrated secondary to excessive diuresis. A retrospective analysis of the incidence of hyperkalemia in the CHARM study (Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity) found that the addition of candesartan to standard medical therapy for heart failure was associated with a 2- to 3-fold increase in risk of hyperkalemia, which was further amplified by cotreatment with spironolactone or ACE inhibitors.MANAGEMENT: Caution is advised if angiotensin II receptor blockers must be used concurrently with potassium-sparing diuretics, particularly in patients with renal impairment, diabetes, old age, severe or worsening heart failure, dehydration, or concomitant therapy with other agents that increase serum potassium such as nonsteroidal anti-inflammatory drugs, beta-blockers, cyclosporine, heparin, tacrolimus, and trimethoprim. Serum potassium and renal function should be checked prior to initiating therapy and regularly thereafter, and potassium supplementation as well as the use of potassium-containing salt substitutes should be avoided unless absolutely necessary and the benefits outweigh the potential risks. Patients should be given counseling on the appropriate levels of potassium and fluid intake, and advised to seek medical attention if they experience signs and symptoms of hyperkalemia such as nausea, vomiting, weakness, listlessness, tingling of the extremities, paralysis, confusion, weak pulse, and a slow or irregular heartbeat. If spironolactone is prescribed with an ARB, some investigators recommend that its dosage not exceed 25 mg/day in high-risk patients.