Cardiovascular System 1 Flashcards
Inhibitors of RAAS
- Sympathetic blockers (B blockers)
- Direct renin inhibitor (aliskiren)
- ACE
- ARB
- Aldosterone antagonist (spironolactone)
Examples of ACE
Captopril
Enalapril
Ramipril
MOA of ACE
Inhibit angiotensin converting enzyme and hence bp falls due to vasodilation due to decrease in PVR and increase in compliance of large vessels.
Fall in BP dependent on Na+ levels
Angiotensin 1 converted to 1-7 which are vasodilators
Also inhibit substance P/bradykinin which is also converted by ACE
Pharmacokinetics of ACE
Food in stomach decreases bioavailability
70% absorbed
ADR of ACE inhibitors
Hypotension
Hyperkalemia
Cough
Dysgeusia
Angioedema
Rashes, urticaria
Foetopathic
Headache dizziness vomiting
Acute renal failure
Interactions of ACE inhibitors
Diuretics
NSAID like indomethacin
K+ sparing diuretics
Antacids
Uses of ACE inhibitors
Hypertension
CHF
MI
Prophylaxis is high risk CAD
Diabetic nephropathy
Non diabetic nephropathy
Scleroderma crisis
Advantages of using ACE inhibitors in hypertension
Free of postural hypotension
No CNS effects
Can be used in asthmatics, PVD, diabetics
Long term reduce incidence of Diabetes Type 2
No K+ loss
Renal blood flow maintained
LVH reversed
ACE inhibitors first choice in
Diabetics with hypertension
Renovascular and resistant hypertension
ARB examples
Losartan
Telmisartan
Valsartan
MOA of ARB
Competitive antagonist and inverse agonist of AT receptors
All actions of angiotensin: vasoconstriction, sympathetic stimulation, release of aldosterone and adr, renal actions promotinh salt and water Reabsorbtion, vasopressin release all inhibited
Advantages of ARB over ACE inhibitors
Do not interfere with degradation of bradykinin or substance P hence no cough
No angioedema commonly
No dysgeusia
Complete blockade of AT1 receptor
Oral absorption not affected by food
ADR of ARB
Hypotension
Hyperkalemia
Fetopathic
Headache dizziness weakness GI side effects
Uses of ARB
Hypertension
CHF
Diabetic nephropathy
MI
Example of direct renin inhibitor and MOA
Aliskiren
Acts by blocking attachment of angiotensinogen by binding to renin
Examples of cardiac glycosides
Digoxin
Digitoxin
Oubain
Actions of digoxin
- Heart: ionotropic effect, increases contractility, vagomimetic action, CNS actions altering sympathetic activity
Increases force of contraction
Decreases heart rate
ECG changes include Inversion of T wave, Prolonged P-R interval and depressed ST segment - Blood vessels: vasoconstriction
No increase in BP - CNS: activates CTZ so vomiting, hyperapnoea, mental confusion, visual distrubances
4.kidney: diuresis in CHF patients
MOA of digoxin
Inhibits Na-k channels
Increase in NA concentration in cell
Opening of L type transient Ca channels
Increase in Ca
CA activated CA channels: ryanodine receptor channels activated
Further increase in ca from sarcoplasmic reticulum
Increase in contraction
Manifestations of digitalis toxicity
Extracardiac: anorexia, vomiting, nausea, abdominal pain. Fatigue, mental confusion, hyperapnoea, psychosis
Cardiac: all types of arrhythmia, severe bradycardia, ventricular tachycardia
Treatment of digoxin toxicity
Tachyarrhythmia: KCL
Ventricular arrhythmia: Lidocaine IV
Supraventricular arrhythmia: propanolol
For AV block: Pacemaker
Digitoxin antibody: DIGIBEND, DIGIFAB
Uses of digoxin
Atrial fibrillation, Atrial flutter
Cardiac failure
Two goals of treatment of heart failure
- Relief of congestive/low output symptoms, restoration of cardiac performance
- Arrest/reversal of disease progression
Drugs for relief of congestive symptoms
Inotropic drugs: digoxin digitalis dobumatine dopamine
Diuretics: furesemide, thiazide
RAS inhibitor: ACE, ARB
Vasodilator: nitrates, hydralazine, nitroprusside
B blocker: Metoprolol, bisprolol
Drugs for arrest/reversal of heart failure progression
ACE and ARB
B blocker
Aldosterone antagonist: spironolactone, eplerenone
Why diuretics given in HF
Decrease preload and improve ventricular efficiency by reducing circulating volume
Remove peripheral edema and pulmonary congestion
Why RAS inhibitors given
To prevent remodeling
Vasodilators examples
Veins: nitrates
Artery: hydralazine
Both: nitroprusside
Why vasodilators are given for HF
Decrease pre load : nitrates
Decrease after load : hydralazine
Pre and after load reduction: nitroprusside
Why B blockers are given in HF
To reduce sympathetic counter mechanism that cause remodeling
Why aldosterone antagonist are given in HF
To prevent:
1. Expansion of ecf volume: increase preload
2. Remodeling of heart due to proliferation of fibroblast and fibrotic change in myocardium
3. Hypokalemia and hypomagnesemia: leads to ventricular arrhythmia
Inamrinone/Amrinone and Milrinone MOA
Phosphodiesterase 3 inhibitors
No degradation of cAMP
Hence increase contraction
What is inamrinone? Most imp adr
It is a ionodilator
Thrombocytopenia
Use of drugs in asymptomatic LVD
ACE/ARB
Use of drugs in mild HF( class1)
ARB/ACE
B blocker
Diuretic
Use of drugs in moderate HF(class2)
ACE/ARB
B blocker
Diuretic
Digoxin
Use of drugs in severe HF( class3)
ACE/ARB
B blocker
Diuretic
Digoxin
Spironolactone
Use of drugs in refractory and emergent HF (class 4)
ACE/ARB
DIURETIC
Digoxin
spironolactone
Iv vasodilator
Iv inotropes
