Title: Pharmacology CVS Final / Drugs for HF 2

Q: Positive inotropic agents: (3)
A: 1. Logically will improve cardiac function
2. These drugs increase the force of contraction by increasing intracellular cardiac Ca++ concentration
3. It can cAMP dependent or independent

Q: cAMP independent agent:
A: Digitalis

Q: cAMP dependent agent: (2)
A: 1. Beta- adrenergic agonist
2. Phosphodiesterase inhibitors

Q: Types of digitalis glycosides: (3)
A: 1. Digitalis purpura
2. Digitalis lanata
3. Strophanthus

Q: MOA of Digitalis Glycosides:
A: Inhibits Na+/K+ ATPase

Q: Actions of Digitalis glycosides: (4)
A: • Positive Inotropic Effect
• Vascular Muscle Contraction
• Vagal Stimulation
• Effects on Electrical Properties of Cardiac Tissues.

Q: The effect of digitalis on the contractility of the heart and vascular muscle (normal vs. failure): (2)
A: 1. In a normal heart, it leads to decreased cardiac output and increased peripheral vascular resistance
2. In heart failure, it leads to increased cardiac output and decreased peripheral vascular resistance

Q: Types of digitalis toxicity: (4)
A: 1. GIT
2. Visual
3. Neurologic
4. Cardiac

Q: GIT Digitalis toxicity:
A: 1. Anorexia
2. Nausea
3. Intestinal cramping
4. Diarrhea

Q: Visual digitalis toxicity: (2)
A: 1. Xanthopsia (predominance of yellow color in vision)
2. Abnormalities of color vision

Q: Neurologic Digitalis toxicity: (4)
A: 1. Malaise
2. Confusion
3. Depression
4. Vertigo

Q: Cardiac digitalis toxicity: (6)
A: 1. Bradycardia
2. Palpatations
3. Syncope
4. Arrythmias
5. AV node block
6. Ventricular tachycardia

Q: Interactions of digitalis: (2)
A: • Pharmacological and toxic effects are greater in hypokalemic patients.
• K+-depleting diuretics are a major contributing factor to digoxin toxicity.

Q: Treatment of digitalis toxicity: (5)
A: 1. Reduce or stop the drug.
2. Cardiac pacemaker for heart block.
3. Digitalis antibodies (Digoxin Immune Fab).
4. Arrhythmias may be converted to normal sinus rhythm by K+ when the plasma K+ conc. is low or within the normal range.
5. When the plasma K+ conc is high, antiarrhythmic drugs, such as lidocaine, phenytoin*, procainamide, or propranolol, can be used.

Q: Therapeutics benefits: (4)
A: Was widely used in the treatment of heart failure.
1. Nowadays, use is restricted only  to CCHF with supraventricular arrhythmia.
2. Might decrease  morbidity and improve quality of life.
3. Withdrawal might be hazardous.
4. Does not improve mortality

Q: MOA of beta adrenergic agonists as an positive inotropic agent:
A: All increase myocardial oxygen consumption, so not helpful for chronic use, may be used (IV) for short term or in acute heart failure.

Q: Use of NE as a positive inotropic agent:
A: Used in acute heart failure (cardiogenic shock) but can cause severe vasospasm and gangrene.

Q: Use of EP as a positive inotropic agent:
A: Used
in cardiac arrest, and it is first line in anaphylactic shock

Q: Dopamine and its dosage: (5)
A: 1. Was widely used in cardiogenic shock but caused cardiac arrhythmias.
2. Low doses: stimulate DA1 receptors leading to renal vasodilation and improved renal perfusion.
3. Intermediate doses:  stimulate β1 receptors leading to positive inotropic actions.
4. High doses: stimulate α receptors leading to vasoconstriction and elevation of blood pressure.
5. Can cause arrhythmias and ischemic changes.

Q: Dobutamine: (3)
A: 1. Nonselective β and α1 agonist, used intermittently (IV) in CCHF.
2. Produces mild vasodilation.
3. Has more inotropic than chronotropic actions.

Q: Types of phosphodiesterase inhibitors: (3)
A: 1. Inamrinone (PDE-3)
2. Milrinone (PDE-3)
3. Vesanirone (PDE-3)

Q: MOA of vasodilators: (5)
A: • Affect preload and/or afterload without directly affecting contractility.
• Consequently, can decrease myocardial ischemia, enhance coronary blood flow and decrease MVO2.
• Can be used in acute heart failure and for short periods in CCHF.
• Hydralazine-Isosorbide dinitrate combination was documented to decrease mortality in African americans, maybe by reducing remodeling of the heart.
• Can be combined with ACEI, diuretics and digitalis.

Q: The effect of venous dilators on left ventricular diastolic volume (LVEDV), and myocardial oxygen consumption (MVO2) and cardiac output (CO): (3)
A: They cause:
1. Decrease in the LVEDV
2. Decrease in the MVO2
3. No effect on the cardiac output

Q: The effect of vasodilators with mixed action on the LVEDV and MVO2 and CO:
A: They cause:
1. Decrease in the LVEDV
2. Decrease in the MVO2
3. Increase in the cardiac output

Q: The effect of arterial dilators on LVEDV and MVO2 and CO:
A: They cause:
1. No eefect on the LVEDV
2. Decrease in the MVO2
3. Increase in the cardiac output

Q: Inotropes are used for treatment of heart failure in the case of:
A: Reduced cardiac output

Q: Venodilators are used for treatment of heart failure in the case of: (2)
A: 1. Fluid retention
2. Increased Preload

Q: Arteriolar vasodilators are used for treatment of heart failure in the case of:
A: Peripheral vasoconstriction

Q: BNP- Niseritide: (5)
A: • Brain natriuretic peptide (BNP) is secreted constitutively by ventricular myocytes in response to stretch.
• BNP increases levels of cGMP.
• BNP is released under atrial and ventricular stress leading to vasodilation, natriuresis (loss of sodium) and diuresis.
• Niseritide: a recombinant human BNP was used for treatment of acute decompensated CHF.
• BNP is cleaved by Neprilysin which is inhibited by Sacubitril

Q: Hemodynamic pharmalogical action of Human BNP:
A: Balanced vasodilation of veins, arteries and coronary arteries

Q: Neurohumoral pharmalogical action of Human BNP: (3)
A: 1. Decreased aldosterone
2. Decreased endothelin
3. Decreased NE

Q: Renal pharmalogical action of Human BNP: (2)
A: 1. Increased diuresis
2. Increased natriuresis

Q: Cardiac pharmalogical action of Human BNP: (3)
A: 1. Lusiotropic (increased myocardial relaxation)
2. Anti-fibrotic
3. Anti-remodelling

Q: Sacubitril: (2)
A: Neprilysin inhibitor used in combination with valsartan (Entresto) to reduce the risk of cardiovascular events in patients with chronic heart failure.
• Also breaks down angiotensin I and II, endothelin-1 and peptide amyloid beta-protein.

Q: Errors in management of heart failure: (7)
A: • Missed diagnosis.
• Improper dosage of diuretics.
• Failure to assess quality of life.
• Failure to consider long term therapeutic goals.
• Underprescribing of ACEI.
• Use of potentially harmful drugs.
• Failure to use hydralazine-isosorbide combination which has proved evidence of benefit.

Q: Stage A in the management of heart failure: (3)
A: 1. Risk factor reduction
2. Patient and family education
3. Treat hypertension, diabetes, dyslipidemia; ACE inhibitors or AT_1 blockers in some patients

Q: Stage B in the management of heart failure:
A: ACE inhibitors or AT1 blockers in all patients; beta blockers in selected patients

Q: Stage C in the management of heart failure: (6)
A: 1. ACE inhibitors and beta blockers in all patients
2. Dietray Na+ restriction, diuretics, and digoxin
3. Cardiac resynchronization of bundle-branch block present
4. Revascularization, mitral-valve surgery
5. Consider multidisciplinary team
6. Aldosterone antagonist, nesinitide

Q: Stage D in the management of heart failure: (3)
A: 1. Inotropes
2. VAD (ventricular assist device); transplantation
3. Hospice (caring for terminally ill patients)