2: Lecture 3 Drugs Flashcards
Why use Positive Inotropic drugs
Cardiac glycosides
ex. Digoxin
Treat heart failure and atrial fibrillation
VERY TOXIC
Side effects: cardiac arrhythmias, upset GIT, rarely neuroendocrine effects
Mechanism of action of Positive ionotropic drugs (cardiac glycosides)
ex. Digoxin
Blocks the Na+/K+ ATPase allowing sodium accumulation within the cell
Action of Na+/Ca2+ antiporter is reduced (as there is less sodium to pump into the cell)–>resulting in an accumulation of calcium in the intracellular space
Calcium acts as a second messenger to activate Ryanodine receptors and release calcium from sarcoplasmic reticulum to trigger muscle contraction–>increase contractility of heart
No change in excitability of heart muscle
What is enhanced calcium-induced calcium release
Amplification of calcium release and muscle contraction by greater calcium concentration within the cell
First line agents in Heart failure
Diuretics
Angiotensin Antagonists
Types of Angiotensin Antagonists
ACE inhibitors–>Captopril
AT1 type receptor antagonists–>Losartan (used in ACE inhibitors are not well tolerated)
Effect of ACE inhibitors (angiotensin antagonist)
ex. Captopril
Reduce preload, afterload, remodeling, and apoptosis by inhibiting angiotensin II synthesis
Effect of AT1 type receptor antagonists (angiotensin antagonist)
Prevent action of angiotensin II to reduce remodeling, preload, afterload, and apoptosis by angiotensin receptor inhibitors blocking AT1 type receptors
Side effects of Angiotensin antagonists
Renal damage–>ACE inhibitors
Avoided during pregnancy–>AT1 antagonists
Effect of Beta blockers
ex. Metoprolol
Reduce afterload, remodeling, and apoptosis
Effect of Beta receptor agonist
ex. Dobutamide for SEVERE heart failure
Directly causes an increase in the contractility of the heart (increasing cardiac output)
Mechanism of Phosphodiesterase inhibitors
ex. Theophylline
Prevent breakdown of cAMP by phosphodiesterase in heart tissue (increasing cAMP concentration in the heart)–>increase heart contractility
Effect of Vasodilators
ex. Nitroglycerin
Reduction of afterload by increasing ejection fraction and reduction of preload by reducing myocardial oxygen requirement
What is fibrosis
Accumulation of non-muscle tissue which prevents proper contraction of heart as fibrous tissue does not stretch/contract
Only in pathological hypertrophy NOT physiological hypertrophy
