Drugs Used To Treat Congestive HF

Question 1

Factors determining cardiac working capacity

Answer 1

Preload (determined by venous return Frank Starling)
After load
Intrincic Myocardial Contractility
IC Ca conc. O2 conc. Gluc conc. ATP avail.

Question 2

Positive Inotropic Drugs: Cardiac Glycoside

Mechanism of Action

Answer 2

Na/K ATPase Inhibition
bind to same site as K+

Inhibition of ATPase –> no Na outflow—> no Na/Ca exchange–> increased IC Ca–> Ca release from sarcoplasmic reticulum–> IC Ca increase–>
contraction

Question 3

Positive Inotropic Drugs: Cardiac Glycoside

Pharmacokinetics

Answer 3

Orally administered
Widely distributed, predominantly acts in heart
PPB: almost complete for digitoxin
Digitoxin: metabolized in liver, biliary excretion, enterohepatic circulation–> accumulation

Digoxin: mostly excreted unchanged renally (careful in renal failure)

Question 4

Positive Inotropic Drugs: Cardiac Glycoside

Pharmacodynamics

Answer 4

Positive Inotropic
Positive Bathmotropic
Nevative Chronotropic
Negative Dromotropic (decrease velocity AV conduction)

Negative Mechanisms via vagal tone (presence of Na/K ATPase in vagal nuclei)–> acetylcholine acts on M2 R of pacemaker cells

Kidney: decrease renin release
GIT: nausea, vomiting via stimulation of vagal and CTZ
CNS: disorientation

Question 5

Positive Inotropic Drugs: Cardiac Glycoside

Side Effects

Answer 5

Toxicity due to narrow therapeutic window
Bradycardia, slow AV conduction, ventricular ES

Glycoside intoxication induced bradycardia
—> atropine a good remedy

Question 6

Positive Inotropic Drugs: Cardiac Glycoside

Dosing

Answer 6

Oral or Parenteral (acute case)
Loading dose and maintenance dose

Digitoxin T1/2: 4-5 days
Digoxin T1/2: 36 hrs

Question 7

Positive Inotropic Drugs: Cardiac Glycoside

Drug Interactions

Answer 7

Verapamil/Amlodipine/NSAIDs
displacement from PP

Ca: potentiation
K: antagonism ( same binding site)

Question 8

Positive Inotropic Drugs: Cardiac Glycoside

Contraindications

Answer 8

only for end stage HF

not:
slow AV conduction
sinus bradycardia
ventricular ES/ WPW
renal failure

Question 9

Positive Inotropic Drugs: Beta 1 Agonist

Answer 9

Dobutamine
Dopamine

Gs–> PKA–> Phosphorylation L type Ca Channels

Question 10

Positive Inotropic Drugs: Phosphodiesterase Inhibitor

Answer 10

Aminophylline
Amrinone
Milrinone

inhibit cAMP degradation–> IP3–> increase IC Ca

danger of increased cAMP: vasodilation–> decreased after load –> hypotension

Question 11

Positive Inotropic Drugs: Ca sensitisers

Answer 11

Pimobendane: Ca sensitiser and Phosphodiesterase Inhibitor
Narrow th range

bind to TropC and increase it’s Ca sensitivity without increasing IC Ca.
Non arrythmogenic