29 - CHF drugs Flashcards
_ heart failure occurs when the heart muscle cannot efficiently pump blood out of the heart
systolic
weakened heart muscle, can’t squeeze as well - less blood pumped out of ventricles
ventricles still fill, but only 40-50% of blood pumped out compared to normally 60%
_ heart failure occurs when the heart muscles are stiff, the hearts chambers do not properly fill up with blood
diastolic
stiff heart muscle can’t relax normally - less blood fills the ventricles
ventricles fill with less blood than normal - ventricles still pump out 60% of blood - but 60% of a lesser volume
Heart failure is a condition in which the heart can’t _ to meet the body’s needs. In some cases, the heart can’t fill with enough blood. In other cases, the heart can’t
pump blood to the rest of the body with enough
force. Some people have both problems.
pump enough blood
Much of the tx is superficial
causes of heart failure
MI, coronary artery disease, valve disease, idiopathic, viral/bacterial, myocarditis, pericarditi, arrhytmias, chronic hypertension, thyroid, pregnancy, septic shock
big picture?
big picture is that some of these causes are choices/preventable some we have no say over can’t do anything about
An action potential in skeletal or cardiac muscle triggers
muscle contraction.
This is called _.
In cardiac muscle, contraction is the result of _ from
depolarization causing the release of more Ca++ from the
sarcoplasmic reticulum. The liberated Ca++ binds to troponin
leading to a change in the interaction between actin and
tropomyosin, exposing sites on the actin filament for myosin.
Myosin pulls on the actin as it hydrolyzes ATP, contracting the
muscle.
excitation-contraction coupling
cardiac - Ca++ influx
Ca++ induced Ca++ release
- Ca exposes binding sites
Different than sketal and SM
Depolarization of the cardiac myocyte leads to opening of
_ channels
voltage gated Ca++
Skeletal muscle and cardiac muscle similar, but things happen much faster in skeletal muscle
cardiac muscle
Ca++ influx from the voltage gated Ca++ channel activates
_ receptors on the sarcoplasmic reticulum, leading to
more Ca++ release.
ryanodine
in skeletal muscle depolarization activates a protein
that is linked to the sarcoplasmic reticulum, directly
causing Ca++ release
cardiac or skeletal muscle
Ca++ binding to troponin alters the interaction between tropomyosin and actin, exposing myosin binding sites on the actin
ATP-hydrolysis fueled movement of the actin-myosin complex
produces contraction.
both
Factors that contribute to how well the heart pumps blood
deals with 1 ion
- Sensitivity of contractile proteins to Ca++
- Amount of Ca++ that is released
- Amount of Ca++ that is stored
in the sarcoplasmic reticulum - Amount of Ca++ that enters
the cell upon depolarization - Activity of the Na+/Ca++ Exchanger
- Intracellular Na+
concentration and activity of
the Na+/K+ ATPase (affects
Ca++ via 5.
_ drugs alter the force or energy of muscular
contractions.
Inotropic
Negative inotropes weaken the force of
muscular contractions.
Positive inotropes increase the
strength of muscular contraction.
_ drugs may change the heart rate by
affecting the nerves controlling the heart, or by changing the rhythm produced by the sinoatrial node.
Chronotropic
Positive chronotropes increase heart rate;
negative
chronotropes decrease heart rate.
_ drugs
Cardiac glycosides (inhibit Na+/K+ ATPase; Ca++) - digoxin
β-adrenergic receptor agonists
Bipyridines
positive inotropic
increase the
strength of muscular contraction.
Drugs without positive inotropic effects used to treat _
β adrenergic receptor blockers diuretics angiotensin converting enzyme inhibitors Angiotensin receptor blockers Aldosterone receptor antagonists Vasodilators
to tx heart
failure
a positive inotropic drug
blocks Na+/K+ ATPase
Internal Na+ increases. This slows the Na+/Ca++
exchanger, slowing removal of Ca++.
Cardiac glycosides:
(in the US) digoxin only one
used
Digitalis (name for any of the cardiac glycosdes
Cardiac glycosides
blocks Na+/K+ ATPase
Internal Na+ increases. This slows the Na+/Ca++
exchanger, slowing removal of Ca++
_ condition increases the effect of the drug
hypokalemia - low potassium
Cardiac glycosides
the increase in contractility results in reversal of the compensatory responses to heart failure:
_ ventricular ejection
_end diastolic and end systolic cardiac size
_CO
_renal perfusion
increase ventricular ejection
decrease end diastolic and end systolic cardiac size
increase CO
increase renal perfusion
the above effects lead to a decrease in sympathetic and renal responses - increase renal perfusion - no renin release no angiotensin
the decrease in sympathetic tone is benefical, decrease HR, preload and after load improve the efficiency of heart
positive inotropic drugs to tx heart failure
The effect of _ is cardiac stimulation, such as increased heart rate, heart contractility, heart conduction velocity and heart relaxation.
B1 - adrenergic receptor agonist \NOT FIRST LINE OF DEFENSE
positive inotropic drugs to tx heart failure
phosphodiesterase - 3 inhibitors
this enzyme is responsible for the degradation of cAMP, inhibitory this raises cAMP levels - leading to contractility and vasodilation
Bipyridines
Drugs without positive inotropic effects used
to treat heart failure
β-adrenergic receptor antagonists
Decreased _-mediated remodeling
Decreased catacholamine-mediated remodeling
excessive stimulation of B1 leads to activation of Bcl-2 ( anti-apoptotic protein because it inhibits the activity of Bax)
This leads to Bax-mediated cytochrome c release and cell death by apoptosis and is thought to be significant in heart failure. Blockade of β1 adrenergic receptors is thought to lead to Bcl2 mediated survival
β blockers might provide effective
treatment of heart failure
Proteases called _ do the dirty
work of Apoptosis
Caspases
Proteases with an active site cysteine
that cleave at aspartic acid residues
(about 10 of them)
Proenzymes that require proteolytic
cleavage for activation
Some act as initiators (initiation phase)
Some act as effectors (aka executioners, execution phase)
β blockers might provide effective
treatment of heart failure
Activation of something called the Intrinsic Pathway of
Apoptosis leads to activation of an _
(and therefore initiation of apoptosis)
Initiator Caspase
beta blockers
Initiation Phase of the Intrinsic Pathway Depends on
_ and _
1. Stress signals leads to release of cytochrome c
2. Cytochrome c in cytoplasm binds to
apoptotic protease activating factor 1 (apaf
1)
3. This leads to formation of an apoptosome
(hexamer of cytochrome c and apaf 1)
4. This leads to binding of the initiator
procaspase 9. Putting them in proximity leads to
their activation. Activated caspase 9 activates
downstream executioner caspases
Mitochondria and Cytochrome c
beta blockers
The _family of proteins regulates the intrinsic pathway by
regulating cytochrome c release from the mitochondrion
Bcl 2
The antiapoptotic proteins bind to proapoptotic proteins and inhibit them When activated, these aggregate on mito outer membrane and promote cyto c release
The BH3-only proteins are proapoptoic and produced or are activated in response to an apoptotic signal. The promote apoptosis by binding and inhibiting the antiapoptoic proteins
_ is a pro-apoptotic protein because it enhances
cytochrome c release from the mitochondrion
_ is an anti-apoptotic protein because it inhibits
the activity of Bax
Bax - proapoptotic
Bcl-2 anti-apoptotic
Drugs without positive inotropic effects used
to treat heart failure
_
This is a mainstay in treatment of congestive heart failure.
Diuretics
Try thiazide, then
move on to a loop
diuretic
Drugs without positive inotropic effects used to treat heart failure ACE inhibitors and Angiotensin receptor antagonists Aldosterone receptor antagonists Direct vasodilators
more than just blood pressure, also cardiac _
remodeling
MOA not sure - decreased catacholamine mediated remodeling - finely tuned specialized cells of tissue not good -still present but not as good as once was
_Americans disproportionately affected by heart failure. Clear evidence
that the _ help as supplements to other treatment strategies.
African-
vasodilators
the medications for CHF can cause dry mouth and gingivitis
people with more severe heart failure should not lie down in the dental chair too far because _
they should also take it slow when moving from standing position to the chair, and when from standing up from the chair. because they can become dizzy and light-headed easily
the fluid buildup in their lungs may affect breathing
Cardaic - electrical signals are telling heart to contract - moving from _ to _ - atrial first contract then ventricles - slow wave that comes thru the heart
Arrithmias - electrical signals are not in sync wave
100msec for cardaic
1msec - for skeletal muscle
atria to ventricles
pain or discomfort in the chest that happens when some part of the heart does not receive enough oxygen from the blood
angina
classical/typical stable/ exertional - due to fixed or stable plaque
prinzmetal/variant - due to spasm of coronary artery
unstable - due to unstable plaque and thrombus
Drugs used to treat _ nitrates/nitrites β-adrenergic receptor blockers calcium channel blockers aspirin, antiplatelet, and anticoagulant drugs ranolazine
Angina
drugs used to treat Angina
are esters of nitrous or nitric acid or prodrugs that spontaneously produce nitric oxide
NO - is the vasodilator - lowers BP
nitrates/nitrites
which drugs to treat immediate angina
nitrates/nitrites
organic - extremely volatile, crushed, inhaled, rapid effects
drugs to tx Angina
rapidly absorbed from oral mucosa
well absorbed from the GI and thru skin
extension first-pass metabolism
1-3 min sublingual tabslets
adverse effects?
nitroglycerine -
taking L=arginine as supplement doesn’t do anything
most common side effect is headaches
high doses of organic nitrates can calso cause postural hypotension, facial flushing, and tachycardia
Sildenafil (viagra) - potentiates the action of the _, to preclude the danergous hypotension that may occur - this combo is contraindicated
nitrates
drugs to tx Angina
Verapramil
Ca++ channel blocker
blocks contraction
most common drugs used in tx of Angina Pectoris
2 classes
3 MOAs
Vasodilators - Nitrates and Ca blockers
Cardiac Depressants - Beta-Blockers and Ca blockers
