B: 14-16 Flashcards
Pharmacotheraputic aims of Manangement of HF
↓ Preload
↓ Afterload
↓ Cardiac muscle remodeling
↑ Contractility (Ionotropic)
What is Preload?
Volume of blood in the ventricles at the end of diastole
Stretch
What is Afterload?
Resistance left ventricle must ovrcome to pump blood
Squeeze
Which drugs can help lower preload?
Diuretics
ACEI
ARB’s
Venodilators
Less blood in the heart system
Which drugs can help lower afterload?
ACEI
ARB’s
Arteriodilators
Which drugs can help increase contractility?
Digoxin
B agonists
PDE-III inhibitors
Which drugs can help lower cardiac muscle remodeling?
ACEI
ARB’s
Spironolactone
B blockers
Help improve survival!
Digoxin is for Acute/chronic management of HF?
Chronic
systolic failure!!
Which diuretics are given in case of HF?
Thiazides: Hydrochlorothiazides
Loop diuretics: Furosemide
K+ sparing agents: Spironolactone
ACE inhibitors which are given in case of HF?
Captopril
Enalapril
Perindopril
ramipril
אפריל מהאופיס קצת דומה לאייס
ARB’s which are given in case of HF?
Losartan
Valsartan
Irbesartan
B blockers which are given in case of HF?
Metoprolol (B1 selective antag.)
Carvedilol (B and a)
Positive iontropic agents
Cardiac glycosides: Digoxin, Digitoxin
Sympathomimetics: Dobutamine
PDE-inhibitor: Milrinone
Cardiac glycosides MOA
Inibition of cadiac Na/K ATPase → Na/Ca exchanger wont work as well → I.C Ca2+ conc. ↑ → increased Ca release from SR → Increased actin-myosin interaction → positive ionotropic (contractility)
Inhibition of neuronal Na/K ATPase → vagal activity ↑ → Negative chronotropic (HR)
AV conduction ↓ → Negative dromotropic (AV conduction)
Digoxin drug properties
Oral: bioavailability 75% Narroe theraputic index Onset of action 0.5-1 h Elimination half life 30-40 h: requires loading dose Renal elimination
Digoxin displacement by which other drugs?
Quinidine
Amiodarone
Verapamil
Digoxin indications
Chronic HF (positive inotropic) systolic failure
Arrhythmias: SVT, A.Fib, A.Flutter ( decreases AV conduction, increases AV refractory period)
Digoxin adverse effects
Hyperkalemia GI ECG changes Conduction blocks Arrhythmias
Predisposing factors for Digoxin toxicity
Renal impairment
Hypokalemia
Hypomangesemia
Hypercalcemia
Treatment for Digoxin toxicity
Correcting electrolyte (Mg , K )
Class Ib: Lidocaine, Phenytoin
digoxin Antibodies (Fab fragment)
Digoxin contraindications
Hypertrophic cardiomyopathy
AV block
Diastolic HF
WPW syndrome
Digitoxin drug properties
Oral: bioavailability 90%
Onset of action 3-6 h
Elimination half life 5-7 h: requires loading dose
Hepatic metabolism
Digitoxin indications
CHF
Arrhythmias: SVT, A.Fib, A.Flutter
Dobutamin
Tell me about it
B1 selective agonist
Parenteral
Duration is minutes
Dobutamine indications and CI
Acute HF: Systolic function ↑
CI : in chronic treatment due to tolerance, low oral bioava, arrythmogenic effect
PDE inhibitor for the management of AHF?
Milrinone
Milrinone MOA
PDE-inhibitor
↑ cAMP in heart muscle: Positive ionotropic (Contractility)
↑ cAMP in vascular smooth muscle: TPR ↓
How to give Milrinone?
IV
Milrinone indication and contra
AHF
Contra. in chronic treatment due to increased morbidity, mortality)
Levosimenadan MOA
Ca2+ sensitizing agent:
- Sensitize troponin to Ca –> (Positive ionotropic)
- Inhibits PDE (Vasodilation)
- Open ATP-sensitive K ch (Vasodilation)
Ca2+ sensitizing agent
Levosimenadan
Levosimenadan indications
Acute decompensated HF`
Levosimenadan contra.
Hypotension
What each class I AA do to the Action potential?
Ia (procainamide) : Prolonged AP
Ib (lidocaine, phenytoin) : Shorten AP in some cardiac tissue esp. purkinje
Ic (flecainide) : No effect on AP
Class Ia MOA and names
- Blocks open/inactive FAST Na+ ch “state dependent blockade”
- tissues undergoing Frequent depol are more susceptible to inhibition
- Blocks K+ ch so prolonged repol.
- increased AP duration, Effective refractory period
Procainamide
Quinidine
disopyramide
Class Ib MOA and names
- Blocks inactivated Na ch.
(minimal effect on normal tissue bcz selectively affect ischemic or depolarized purkinje & ventricle)
little effect on atria
shorten AP & refractory period
Lidocaine
mexiletine
phenytoin
Lidocaine indications
Ventricular arrhythmias
Post MI
Digoxin toxicity
Lidocaine side effects
Seizures
Least cardiotoxic!
Class Ic MOA and names
- Block fast Na ch.
- His-Purkinje tissue
- No ANS effects
Propafenone
flecainide
flecainide, Propafenone is given
Oral
Class II AA
Esmolol
(Propranolol)
metoprolol
Esmolol AA indications
Perioperative
thyrotoxicosis arrhythmias
emergency acute arrythmias
Class III AA MOA
K+ ch. blockrs (prolongs AP, RP)
Rhythm control
amiodarone
Dronedarone
sotalol (BB + K-blocker)
Class III AA drugs
Amiodarone
Sotalol
Amiodarone drug properties
Blocks Na, B-adrenoreceptor, K, Ca, ( has group 1, 2, 4 AA actions)
greatest AP prolonging effect
HR ↓
AV node conduction ↓
Elimination half life 1-10 weeks
Binds to tissues
Inhibits CYP450 (Careful with Warfarin, Statins)
oral, parenteral
Amiodarone side effects
Thyroid abnormalities
Skin and cornea deposition
Pulmonary fibrosis
optic neuritis
Sotalol MOA
Blocks K+ ch.
Non selective B blocker
Sotalol
How to give? Duration?
Oral
7 h
Sotalol indications
Ventricular arrhythmias
A.Fib
(May cause Dose dependent TdP)
Class IV AA MOA
Blocks L type Ca2+ ch.
Non-dihydropyridines more selective for myocardium!!
Class IV AA drugs
How to give?
Verapamil
Oral, parenteral D= 7hrs
Diltiazem oral, parenteral
D= 6hrs
Verapamil indications
Diltiazem indic
Verapamil : AV nodal arrhythmias esp in prophylaxis
Diltiazem : Rate control in atrial fibrillation
Verapamil, diltiazem side effects
- Cardiac depression
- Constipation
- Hypotension
Class V AA drugs
Adenosine
Mg2+
Digoxin
Adenosine R and their G protein
A1-R-(Gi): K+ current ↑, Ca2+ current ↓, hyperopolariz.
-increase in diastolic K current –> hyperpolar –> conduction block
A2-R-(Gs) : Vasodilation
Adenosine
How to give? Duration?
IV
10-15 seconds!
Adenosine indications
-Acute nodal tachycardia (book)
AV arrhythmias
Paroxysmal SVT
Adenosine side effects
- bronchospasm
- chest pain
- Flushing
- headache
Adenosine can be antagonized with
Theophylline
Mg++ as an AA
- possibly increase in Na/K ATPase
Mg++ is given how
IV
Mg++ indications
TdP
Long QT syndrome
Digitalis induced arrhythmias
arrythmias if serum K is low
Digoxin as an AA
Inhibition of neuronal Na/K ATPase → Vagal tone ↑ → negative chronotropic
AV conduction ↓ → negative dromotropic
inhibits Na/K ATPase –> interfere with Ca/Na exchanger–> increased IC Ca –> increase inotropy (contractility)
Rate control. Which AA will we choose? Indications?
Class II (BB) and IV (CCB)
Age > 65
Hypertension
AF
Rhytm control. Which AA will we choose? Indications?
Class I and III Age < 65 More symptomatic No hypertension New AF
