Drugs of Congestive heart failure Flashcards
CONGESTIVE HEART FAILURE(CHF)
- Occurs when ———— (———-) is inadequate
to provide —————-needed by the body.
CO = ——-(rate of contraction of heart) X ———–
(volume of blood ejected with each beat).
cardiac output(CO)
o2
HR X SV
HF occurs due to ———-cardiac
contractility or ———– preload and/or
afterload.
decreased-increased
The patient has:
- Low COP manifestations e.g., —-,—–,—-,—-,—-
- Congestive manifestations e.g.,
- —,—–,—-,—-,——
fatigue,
dizziness, cold hands, cyanosis, and syncope
leg oedema, congested liver, cough, dyspnea,
and pulmonary oedema.
Cardiac performance is a function of four
primary factors: ========,=======,=========,======
————: load on the heart created by the volume
of blood injected in the left ventricle (at the end of
diastole). It is a volume load.
———–: load on the contractile ventricle
created by the resistance to the blood injected into
the arterial system by the left ventricle i.e. total
peripheral resistance. Thus, it is a pressure load.
———–: the capacity of myocardial to
generate force to respond to preload and
overcome after load.
———–: a major determinant of cardiac output
Preload, after load, contractility& heart rate (HR) Preload After load Contractility Heart rate
-------------- blockers directly affect the sympathetic activity also it reduces both preload and afterload by working on the kidney (inhibits Renin release)
Beta1
First we decrease both preload and afterload then we work on the heart activity(by-----------)
Digitalis
Pathophysiogy of heart failure:
They provide short term hemodynamic compensation for decreased CO but ultimately cause deterioration of
decompensated HF
1————- sympathetic activity:
a- ———- Force of contraction
b- ———–Heart rate
c ————— of RAAS leads to : Vasoconstriction:
Venoconstriction————-preload
Arterioloconstriction————– afterload
2-Activation of RAAS: -
a-stimulate aldosterone ——-salt &water retention lead
——-preload
B- ————– of the heart & blood vessels.
C -Angiotensin II lead to VC ———preload &after load
3- Myocardial ————–
inc inc inc stimulation inc inc Remodeling inc hypertrophy
Functional classification
Generally relies on the New York Heart
Association functional classification. The classes
(I-IV) are:
Class I: no limitation is experienced in any
activities; there are ——— from ordinary
activities.
Class II: ————-, mild limitation of activity; the
patient is comfortable at rest or with mild
exertion.
Class III: marked limitation of any activity; the
patient is comfortable only ————–
Class —-: any physical activity brings on
discomfort and symptoms occur at rest.
no symptoms
slight
at rest.
IV
Therapeutic strategies:
————– physical activity
———- sodium intake
treatment of comorbid conditions
Use of diuretics,ACEIs &inotropic agents
Avoid ———-,———-,——-, some drugs
Decrease
Decrease
NSAIDs,CCBs,alcohol
Chronic failure is best treated with ——– (———–) plus an —–, if tolerated, a ——–. Digitalis may be helpful if
systolic dysfunction is prominent.
- acute heart failure should be treated with a ——-; if severe, a prompt-acting positive inotropic agent
such as a———– or—————,
and ————– should be used as required to optimize
filling pressures and blood pressure.
diuretics(often loop agent plus spironolactone)+ ACE inhibitor- beta blocker-Digitalis
loop diuretic
beta agonist
phosphodiesterase inhibitor
vasodilators
Drugs used in heart failure :
Drugs reduce mortality working on remodeling
3 drugs
ABS
- ACEIs
- Beta blockers
- Spironolactone
Drugs used in heart failure :
-Drugs improve symptoms
- Digitalis(Digoxin)
- Diuretics
- Vasodilators (nitrates or hydralazine)
———— is the most effective drug in
treatment of H.F it decreases both
preload and afterload and prevents
deterioration of the heart.
ACE-I
Angiotensin converting enzyme inhibitors(ACEIs) e.g. captopril: - Mechanism of action: Pharmacokinetics: _Incompletely absorbed, must be taken on empty stomach (food decreased absorption). _ -Excreted by ------------
Decreased Angiotensin II production& NE
release leading to:
1- Decreased preload &after load.
2- Decreased cardiac hypertrophy, dilatation
&remodeling.
3- Decrease HR or does not increase it.
empty
kidney
Adverse effects of ACEI:
7 things
1 - First dose hypotension (start with a small
dose at bed time).
2 -Acute angioedema & chronic dry cough (inc
BK).
3 -Hyperkalemia (potassium supplement or
spironolactone are CI).
4 -Renal impairment (in renal artery stenosis,
high renin states as CHF).
5 -Metallic taste (captopril), neutropenia in some
cases.
6 -Fetotoxic (CI in pregnancy).urinary abnormality
7-CI in Asthma
Angiotensin II type ———– receptor
blockers(ARBs):
———— is the prototype and differs from other
in that it ———– extensive 1st pass
metabolism.
Mechanism of action:
antagonizing angiotensin II ____———-preload and afterload
Block AT1 receptors ____ vasodilatations
&antiproliferative action.
No increase in ————– so no
angioedema &cough.
Adverse effects: same as ACEIs
CI in ——————.
1 Losartan undergoes decrease bradykinines pregnancy
2-Diuretics:
1 -Decrease blood volume ——–venous
return———- preload.
2 -Decrease CO————blood pressure ——–after
load
3 ————— are used in mild to moderate
cases while ———- diuretics are used in
sever, acute or in renal impairment
dec-dec-dec-dec
Thiazide
loop
3- Beta blockers:
three members are recommended for use:
————, —————- and ————–.
carvedilol, bisoprolol and metoprolol
Alpha and Beta blocker with antioxidant activity ?
Carvedilol
Beta Blocker
Beneficial actions in——– mortality and
morbidity is due to; prevention of changes
due to chronic ————
stimulation,including ———– in
HR,inhibition of ———– release,———— of
deleterious effects of norepinephrine,
decreasing ————-,hypertrophy and cell
death (apoptosis).
used in ———– stages
Not given to ———— HF
reducing sympathetic decrease renin prevention remodelling acute
Inotropic agents:
The only oral positive inotropic drug
available for chronic use
Digitalis or cardiac glycosides (digoxin):
Digitalis or cardiac glycosides (digoxin):
Mechanism of myocardial contraction:
- The force of contraction is directly
proportional to the concentration of free
intracellular (IC) calcium. - The amount of calcium sequestered in the SR
is dependent on the balance of calcium influx
and calcium efflux.
- Mechanism of action of digitalis:
A-Mechanical: Inhibits membrane bound Na+/K+
ATPase_————— IC Na+ thus concentration gradient
across the membrane ————– _____decrease the
driving force for the Na+/Ca++ exchanger ___ decrease
calcium expulsion and ——–IC Ca++
-The concentration gradient for—— and ——- is the
major determinant of the net movement of ions
especially ———-.
-The increased IC Na+ and Ca++ results in: - 1-increased myocardial contractility____—— EDV &_____ CO,
tissue & renal perfusion ____—- renin secretion ____——— salt&water retention &induce diuresis___——- preload and after
load. - 2- Decrease sympathetic activity____—– HR, oxygen
demand, VC& renin secretion.
increase decreases increase Na+ and Ca++ Na+ dec inc dec dec dec dec
B- Electrical: autonomic stimulation (mainly
————–, sympathetic only in ———–
doses) decreasing HR which is a sign of
improvement
Therapeutic uses: ———– with AF (due to
combined inotropic & bradycardic
effect).Also, sever HF after ACEIs, BBlocker &
diuretics. Mild to moderate cases do not
require————-.
—————is an early sign of
improvement.
parasympathetic toxic HF digoxin Bradycardia
Pharmacokinetics:
———- has rapid onset &shorter
duration compared to digitoxin.
-Has a high volume of distribution, used
in acute digitalization.
-Widely distributed including CNS,
eliminated (2/3) unchanged through
kidney(dose adjustment is needed).
———– is extensively metabolized via
liver.
-Narrow safety margin.
Digoxin - digitoxin
patient has a kidney dysfunction can use ? ————- metabolized by ————–
Digitoxin
patient has a live dysfunction can use ? ————- metabolized by ————–
Digoxin
Digoxin CI
Absloute in
Ventricular arrhythmia
Hypertrophy obstructive cardiomyopathy (thickening intraventrieular septum) -Never give +ve inotropes or +ve chronotropes
Wolf Parkinson’s white syndrome
H-Block (-ve AV conduction) delay
Digoxin CI
relative in
Patients with Brndycardia On beta blockers On Verapamil Myodema= Hypothyroidism Sick sinus syndrome (Low SA node rate) Hyperactive carotid sinus
Systemic or Pulmonary H TN
So, give VD first before Digoxin such
C.C B ( not verapamil nor nifedipine) ive Amlodipine
NO brady,c NO Tachy_ C
Renal impairment (Digoxin toxicity)
Cardiovesion (arrhythmia)
MI (Increase infarct size)
Acute rheumatic fever myocarditis
Digitalis or cardiac glycosides (digoxin):
Adverse effects:
4 things
1- Cardiac dysrhythmias: all types can be encountered: (Increased automaticity, and increased vagal tone). 2-GIT(Early early sign of Toxcity): nausea, vomiting &diarrhea . 3- CNS(late late sign of Toxcity): confusion, hallucinations, convulsions& colored vision(green and yellow) 4- Gynecomastia due to its steroid nucleus.
Treatment of toxicity of Digitalis:
5 things
1 -Drug withdrawal with symptoms suggestive of
toxicity (GIT& visual).
2 -Potassium supplement (CI in heart block,
renal impairment). (K & digoxin inhibit each
binding to ATPase).
3 -Antidysrhythmic drugs to treat dysrhythmia.
4 - Digoxin immune fab (antibodies) which
inactivate the drug.
5 -Plasma pheresis: in renal failure since
digoxin AB can not be given as they would
accumulate.
————–vs Digitalis
POTASSIUM
- Factors predisposing to digitalis toxicity:
4 things
1-Hypokalemia (K-losing diuretics &corticosteroids), hypercalcemia, hypomagnesaemia (magnesium opposes calcium). 2-Antidysrhythmic drugs: verapamil, amiodarone and quinidine ĺ displace digoxin from tissues &compete for excretion. 3- Hypothyroidism and hypoxia. 4- Renal impairment
cGMP > ———-
cAMP > ————–+—————-
V.D
V.D in Smooth ms , V.C
in myocardial ma
Other positive inotropic agents:
1- Beta adrenoceptors agonists:
(direct)(emergency)a-Dobutamine: used in acute HF& given by IV
infusion (inc.cAMP___ phosphorylation of calcium
channels____ inc calcium entry into myocardium and
VD).
b-Dopamine: inc CO, inc renal blood flow &inc blood
pressure (depending on the dose_ stimulate
dopamine, beta or alpha receptors)
2-Phosphodiesterase inhibitors(indirect): Amrinone
&milrinone
___inc cAMP_____incIC calcium___-inc myocardial
contractility.
-Indicated for short term therapy___ rapid
tolerance, thrombocytopenia& hepatotoxicity.
It causes smooth muscle relaxation, and increases heart contractility————-
-Phosphodiesterase inhibitors
Used in acute
HF or
cardiogenic
shock———–
Dobutamine
use only with acute CHF , for maximum 48h
———–
Phosphodiesterase inhibitors:
Spironolactone:
-Small dose added to—,—–,—- _ decrease mortality by 30% due to prevention of ———– production__
decrease salt and water retention. Also,
counteracts ————- which
predisposes to digitalis toxicity & decreases
remodeling.
-Should not be taken with ————— or in
—————–.
ACEIs, diuretics& digoxin-aldosterone hypokalemia potassium renal impairment
6- Vasodilators
- ———dilators as nitrates_dec preload by
shifting blood to venous capacitance vessels
(——–of whole vascular system) ĺ
dec congestive symptoms.
- Arteriolodilators:
- e.g. hydalazine_ dec peripheral resistance
dec after load _inc CO &tissue perfusion.
Hydralazine should not be used alone (———+——-) _combined with
——————–.
Veno 80% reflex tachycardia& edema nitrates
Management of Acute Heart Failure
I. Management of Acute Pulmonary Edema
———– IV, ————— IV, ————- IV,
and Oxygen to control hypoxia
II. Restoring Hemodynamics
(———-COP
& tissue perfusion and maintain BP):
Drugs used differ according to level of the
systolic BP: ——, ——-, or ——-.
Frusemide Nitroglycerin Morphine increase NE Dobutamine nitrates
Diastolic dysfunction
CHF with preserved EF
Is best treated with:
β-blockers;
- Prevent tachycardia; Maximizing diastolic filling) - Reduce B.P and MI - Promote regression of LV Hypertrophy - Associated with improved survival Diuretics to reduce ---------------
preload
Beta blocker treatment should not be:
• Prescribed without ————-in patients with current or recent history of fluid retention.
• Prescribed to patients with higher degree AV heart block, and should be used with caution in those with second degree AV block.
• Prescribed for initiation in patients with acute HF symptoms or ———— HF.
• If a non-cardioselective beta blocker (e.g., carvedilol)), prescribed to patients with significant asthma or bronchoconstrinction, especially if with a ——- methacholine challenge
diuretics
decompensated
positive
