Shock

Congestive Heart Failure
• CO is insufficient to meet the demands of tissue

perfusion. OR
• Able to do so by elevating filling pressure
• Progressive disease
• Cause:
Systolic dysfunction
Diastolic dysfunction
Renin Inhibitors CHF
Inotropic drugs
 Renin  Sympathetic tone
β-blockers
ACE 
 Angiotensin II
ARBs  HR, CO Vasoconstriction
Vasoconstriction, Vasodilator
 Aldosterone
 BP, Better Perfusion
Spirinolactone
Cardiac Na, water retention Diuretic
remodelling
Drugs for Heart Failure
Inotropes- for increasing ventricular contractions:
• Cardiac glycosides- digitalis, digoxin, oubain
•  Adrenergic and dopaminergic agonists- dobutamine
• PDE inhibitors- Inamrinone, milrinone
Diuretics
• Furosemide, Thiazides, Metolazones
RAS inhibitors
• ACE inhibitors/ARBs
Drugs for Heart Failure
Vasodilators
• Hydralazine, Nitrate, Nitroprusside
Synthetic BNP : Nesiritide
Beta Blockers
• Metoprolol, Bisoprolol, Carvedilol, Nebivolol
Aldosterone Antagonist
• Spironolactone, Eplerenone
Neprilysin Inhibitor : Sacubitril
• JG cells are specialized cells of afferent arteriole
• Prorenin and renin are synthesized and stored in JG cells
• Prorenin is converted to renin by proteolytic enzymes-
proconvertase I or cathepsin B
• Renin is released by exocytosis into renal artery circulation
• Angiotensinogen is synthesized in liver
• Renin converts angiotensinogen to angiotensin I
• Angiotensin I is converted to angiotensin II by Angiotensin
Converting Enzyme (ACE) in vascular endothelial cells
• Angiotensin II is the active form of the enzyme
Macula densa- control of renin release
AngII
Na + + ATP
Na+-K+-2Cl- Na+ -ve Feed back
symporter 2Cl- K+ AT1 NE release
K+ 1
_ ADP P2Y
(Gq-PLC-IP3 -
Tubular Adenosine PG
End nNOS Ca2+
A1 (-) (+)
Adenosine Renin Release
NO Receptor
COX-2
Macula densa JG Cell

• Angiotensin receptors: two types- AT1 and AT2
• It produces a pressor response – immediate due to
vasoconstriction and slow due to sodium and water
retention
• It produces cardiac and vascular hypertrophy & remodeling
• Action of AngII on brain increases central sympathetic
tone
• Also produces Dipsogenic effect ( thirst)
• Releases catecholamines and aldosterone from adrenal
medulla and cortex respectively
• ACE is a glycoprotein, present in vascular endothelium
• It is a nonspecific enzyme that catalyzes diverse amino acids
including angiotensin and bradykinin
• RAS inhibitors are ACE inhibitors, ARB and DRI
Uses of ACE Inhibitors:
• Essential hypertension
• Left ventricular systolic dysfunction: prevents or delays
progression of heart failure
• Acute MI
• High risk patients of cardiovascular disorders
• Diabetes mellitus with renal failure- has renoprotective effects
in type I D. mellitus
• Scleroderma renal crisis
ADRs:
• Hypotension- first dose effect in high renin patients
• Cough- due to accumulation of bradykinin, substance P and/or
PGs in lungs. Thromboxane, aspirin and iron helpful
• Hyperkalemia in patients of renal failure/D.mellitus
• Acute renal failure- in patients of renal artery stenosis, single
renal artery or heart failure - due to dilatation of efferent
arteriole
• Fetopathic effect: may be due to fetal hypotension- ACE
inhibitors to be stopped during pregnancy
Interactions:
• NSAIDs may reduce antihypertensive effect
• K+ sparing diuretics and K+ supplements may
precipitate hyperkalemia
-Adrenoceptor antagonists:
•  agonists dobutamine as also dopamine provide relief in CHF but
their long term use increases mortality
• Long term administration of -antagonists reduce mortality rate in
CHF
• Initially the systolic function decreases but over 2-4 months it
recovers and improvement beyond baseline occurs
• Mechanism of beneficial effects in CHF not clear
By preventing myocardial ischemia without significantly
influencing serum electrolytes, they may decrease frequency of
unstable tachyarrhythmias
Betterment of left ventricular morphology by decreasing left
ventricular size and increasing ejection fraction
By inhibiting sustained sympathetic discharge, they reduce
catecholamine induced cardiomyote toxicity and prevent or
delay myocardial contractile dysfunction
Decrease cardiomyocyte apoptosis
May induce positive myocardial remodeling by decreasing
oxidative stress on myocardium
• Drugs used: metoprolol, carvedilol, bisoprolol- other -blockers
are not effective
• Combined  and  blocker is preferred
• Carvedilol has additional advantages that it reduces free radical
induced lipid peroxidation and prevents cardiac and vascular
smooth muscle mitogenesis independent of its  or  receptor
blocking activity
•  Adrenoceptor blockers have proven utility in improving
symptoms, hospitalization and mortality in patients of CHF
• They are recommended for use in patients along with ACE
inhibitors or ARBs
• Recommended only when the ejection fraction of heart is
<35% to counter the deleterious effects of circulating
catecholamines
• They are usually given in small doses initially, less than
1/10th of the final dose and gradually titration of dose is done
• Not recommended for use in patients with severe, new onset
or acutely decompensated CHF
• Cardiac glycosides bind and inhibit the phosphorylated 
sub unit of sarcolemal Na+K+ATPase
• They  Na+ extrusion from cell and  its level in cell
• At therapeutic serum levels they:
Increase vagal tone and decrease sympathetic tone
Decrease automaticity
Increase maximal diastolic resting membrane potential in
atrial and AV nodal tissues
Prolongs ERP and slows conduction in AV nodal tissues
These effects result in sinus bradycardia or arrest,
prolongation of AV nodal conduction and AV block
• In higher concentrations it increases sympathetic
activity. Simultaneously, there is Ca2+ overload which
together may cause development of cardiac arrhythmias
• Non-cardiac effects:
Blood vessels- constriction (direct) in normal; in CHF
vasodilatation due to decreased sympathetic activity
Kidney- Diuresis
GIT- anorexia, nausea,vomiting (CTZ)
CNS- disorientation, hallucinations, visual & colour
disturbances
• Uses:
CHF
PSVT
Atrial flutter/Atrial fibrillation
ADRs:
• Cardiac
• CNS- fatigue, neuralgia, blurred vision
• GIT- anorexia, nausea, vomiting, abdominal
cramps
• Endocrinal- gynaecomastia in males
Contraindications: Hypokalemia, children
below 10 years age, elderly with renal/hepatic
impairment
MI, hypothyroidism, myocarditis
Dobutamine:
• Racemic mixture that stimulates both 1 and 2 receptors and
(-) enantiomer that is agonist and (+) enatiomer that is partial
agonist of  adrenoceptors
• 1-positive ionotropic and increase in stroke volume
• Relatively little increase in heart rate
• Vasoconstriction by (-) enantiomer is countered by (+)
enatiomer and 2 agonist activity- ultimate result is a decrease
in PVR and mild decrease in systemic blood pressure
• Continuous infusion 2-3 g/kg/min
• Tolerance may occur after some time
• ADRs: tachycardia, arrhythmias
PDE Inhibitors: Inamirinone, milrinone
• Decrease cellular degradation of cAMP resulting in increased
levels in cardiac and smooth muscle myocytes
• Produces positive inotropic effect on heart and dilatation of
resistance and capacitance vessels
• Nett effect: positive ionotropy and decrease in pre and after
load resulting in improvement in cardiac output
• Also called “inodilator” (inotropy + vessel dilatation)
• Theophylline, caffeine have low cardiac specificity and side
effects, so are not used
• Inamirinone and milrinone are selective PDE3 inhibitors
• Directly stimulate myocardial contractility & relaxation

Shock

Uploaded by

Copyright:

Available Formats

Shock

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Shock

Uploaded by

Copyright:

Available Formats

Congestive Heart Failure

• CO is insufficient to meet the demands of tissue

Macula densa JG Cell

You might also like