Cardiac pharmacology Flashcards
What are pharmacological properties of clopidogrel
Class of drug: Platelet ADP (adenosine diphosphate) receptor antagonist
Clopidogrel irreversibly modifies the platelet ADP receptor thereby directly inhibiting the binding of ADP and subsequent ADP-mediated activation of the glycoprotein IIb/IIIa complex.
What are the pharmacological properties of heparin
- inactivates factor Xa
- inhibits conversion of prothrombin to thrombin
- prevents fibrin formation from fibrinogen
More details of heparin physiology
Acts near the end of the coagulation cascade
The first target is thrombin (Factor II) –by activation Anti-Thrombin III (AT III) to a form > 1000times more potent
also targets Xa, XIIIa, XIa
Full dose does not completely suppress thrombin
Heparin comes pork intestine or beef lung* different*
What are differences between UF heparin and low moelecular weight heparin
a) longer half-life, about 12 hours compared to 90 min
b) does not require monitoring
c) greater anti-factor Xa activity
d) lower incidence of thrombocytopenia and osteoporosis
What is advantage LWMH
↓ heparin resistance ↓ inhibition of platelet function ↓ incidence of HIT 1 vs 5 % ↓ risk of bleeding ↑ bioavailability ↑ half life No need for monitoring
What are pharmacological properties of warfarin
Coumadin derivative that interferes with vitamin K metabolism.
Vit K is a co-factor in the hepatic production of Factors II, VII, IX, and X.
What are pharmacological properties of glycoprotein IIb/IIIa blockers
Inhibit platelet aggregation by binding to the glycoprotein IIb/IIIa receptors on platelets thereby preventing these receptors from linking to other platelets by fibrinogen cross-bridges.
examples
1) Abciximab
2) tirogibran
3) eptifibatide
Pharmacological properties of fibrinolytics
convert plasminogen to plasmin which in turn degrades fibrin-containing thrombi.
Two categories
a) non-specific thrombolytic agents
b) fibrin-specific
Pharmacological properies of Transexamic acid
lysine analogue anti-fibrinolytic agent
Binds to plasminogen, therby inhibiting fibrinolysis
possible renal function and graft patency issues
Pharmacological properties of statins
competitively inhibit hepatic HMG-CoA reductase, which is involved in last step of cholesterol synthesis
What are pharmacological properties of beta blockers
Bind to beta adrenoreceptors to produce negative inotropic and chrontropic effects, thereby reducing myocardial oxygen demand.
cardiomyocyte membrane stabilizing effect, thereby acting as an anti-arrhythmic agent
What are pharmacological properties of calcium channel blockers
inhibit calcium influx during phase 2 of cardiac action potential (plateau phase) thereby reducing cardiac contractility and the propagation of cardiac electrical impulses
also relax vascular smooth muscle, dilating coronary and peripheral arteries
What are pharmacoloical properties of ACE inhibitors
Prevent conversion of inactive angiotensin I to active angiotensin II, thereby reducing the release of aldosterone by the adrenal cortex.
ARBs have similar mechanism as ACE but do not break down bradykinin which is thought to be responsible for the cough
What are pharmacological properties of nitrates
smooth muscle relaxants that
1) coronary vasodilation and reduced coronary spasm
2) peripherally vasodilate
3) reduce preload and afterload, thereby reducing myocardial oxygen demand
What are pharmacological mechanism of nitroprusside
relaxes arterial smooth thereby reducing systemic and pulmonary afterload
use for aortic dissection
What are pharmacological properties of dopamine
Dopaminergic and adrenergic receptor agonist ug/kg/min
Good for low cardiac output and post MI
What are pharmacological properties of dobutamine
synthetic inodilator that activates B1 adrenergic receptors and has moderate B2 (vasodilaton)
what are pharmacological properties of adrenaline
A potent alpha 1 agonist producing increased myocardiac contractility and increased heart rate. At low doses it does B2 vasodilation.
will cause metabolic acidosis
What are pharmacological properties of noradrenaline
Potent alpha 1 agonist producing systemic vasoconstriction and beta 1 increasing myocardial contracility
How does Milrinone work
Inhibition of phosphodiesterase enzyme, which normally converts to cAMP to inactive 5 -AMP
What are pharmacoligcal properties of milirinone
Acts as an inodilator by reducing systemic and pulmonary vascular resistance as well as having moderate positive inotropic effects
phosphodiesterase- 3–inhibitor
What are pharmacological properties of digoxin
Inhibits the action of the sarcolemmal membrane Na-K-ATPase thereby inhibiting the sodium pump.This results in a greater influx of sodium and development of bound intracellular calcium producing weak inotropic effect.
prolongs the atroventricular node refractory period and conduction, as well as stimulating vagal function thereby slowing down the ventricular rate
What are the pharmacological properties of amiodarone
increases the action potential duration throughout the cardiac conduction system, thereby reducing the excitability of both atrial and ventricular myocytes
What are the pharmacological properties of loop diuretics
loop diuretics inhibit water and electrolyte reabsorption from the ascending limb of henle
List 2 source of Nitric oxide and the effects of NO on endothelium
Source of NO
Active byproduct of nitrates and NA nitroprusside
Inhaled NO
The effects of NO on endothelium reduced cytosolic CA+ reduce platelet aggregation increase cGMP increase guanylate cyclase
What is the mechanism of nitrate intolerance
Reduced bioconversion to NO Desensitization of guanyl cyclase increased vasopressin and catecholamines Renin-angiotensive system activation Increased production of endothelin-1 increased superoxide anion production
What are usual doses of inotropes that maybe required to come off CPB for difficult wean are
Milrinone: 50u/KG loading dose, then 0.5u/kg/min infusion
Epinephrine -0.01-to0.1u/kg/min
NE is 0.01 to 0.03 u/kg/min
Dopamine 5 to 15 u/kg/min
Dobutmaine 5 to 15 u/kg/min
Phenylephrine 40 to 70 u boluses every few minutes
List 5 effects on the vascular endothelium from Nitric Oxide
Vasodilation
inhibits vascular smooth muscle growth
inhibits platelet aggregation and adhesion
inhibits neutrophil adhesion
List indications for nitric oxide
pulmonary hypertension post-heart transplant
pulmonary hypertension post repair of congential heart lesion—VSD
pulmonary hypertension following mitral valve repair
treat acute right heart failure/dysfunction
massive acute PE
ARDS
following lung transplantation
What are toxic byproducts of NO
Nitric dioxide
methemoglobin
peroxynitrite
nitrate
What is mechanism of Abciximab (Reopro)
Non-competitive monocolonal antibody against GIIB/IIIa which inhibits platelet aggregation
The bleeding time is prolonged for 12 -48 hours
Risk of bleeding is very high
How does Eptifibatide (Integrilin) and Tirofioban (Aggra stat) work
Competitive binders of GIIbIIIa, BT is prolonged for 8 hours
for urgent surgery wait a few hours.
What is Vaughn-Williams Classification
Class I = sodium
Class II = beta blockers
Class III = Prolong reploraization (think K)
Class IV = Calcium channel
How do Fibrates work?
Increase HDL
Reduce HDL
How do Resins work
Reduced LDL and Increase HDL
Describe mechanisms of amiodarone toxicity
Direct injury: high affinity of amiodarone to lung tissue and its long half life, it accumulates in the lung causing direct cell injury. Alternation of the lipid bilayer, release of toxic O2 radicals and chronic inflammation– pulmonary fibrosis
Indirect: (immune-mediated) injury: hyper sensitivity reaction leading to acute inflammation and severe pneumonitis resembling BOOP. Mediated by CD8-T cells and IgG antibodies.
Treatment of cessation of amiodarone and steroids
Describe the mechanism of action of amiodarone, half life and usually loading dose
has all 4 classes of action in VW classification
Reduces SA node automaticity, AV node refractoriness, and ventricular and atrial automaticity
35-45% is absorbed when given orally
The elimination half life is 40 to 60 days
Name side effects of amiodarone
Corneal deposits causing halos and blurred vision Hyperthroidism and hypothyroidism Acute hypersensitivity pneumonitis Interstitial pneumonitis Hepatitis (watch for increase in GGT) Bradycardia and AV block Hearing loss Blue-Gray skin Hypotension when given IV
What is mechanism of amiodarone toxicity
Indirect (immune-mediated) –mediated by CD8 T-cells and IgGAb–hypersensitivity rxn leading to acute inflammation and severe
Direct: high affinity to lung tissue–injury mediated by phsolopodidosis in alveolar macrophages.type II cells, chronic inflammation
occurs in the 6 to 15% pts
How do you diagnose amiodarone toxicity
a drop in 15% DLCO
High resolution CT and PFT
treatment is drug withdrawal and corticosteroid
What is mechanism of Aprotinine
serine protease inhibitor that strongly inhibits plasmin.
Reducing the inflammatory reponse to CPB
Full Hammersmith dose is 4 Million KIU (allikrenin inhibitory units) as a loading dosease then 0.5 Million KIU/Hr
Why would Aprotinin work
During CPB endothelial cells produce TPA which activates plasmin, a serine protease,
plasmin leads to clot lysis by degrading fibrin to fibrin degradation products
What is dosing and drug treatment for Type B dissections
Esmolol 500 ug/kg bolus over 1 minute 50 o 200 ug/kg/min infusion give another bolus of 500 ug/kg to achieve an acceptable SBP < 100 Nitroprussude 0.3 ug/kg/min infusion
List 3 actions of amiodarone
decreased SA node automaticity
decreased AV node refractory time
decreased ventricular and atrial automaticity
What are contraindications to nitrates
Angina caused by HOCM
Acute inferior myocardial infarction
with right ventricular involvement
fall in filling pressure may lead to hemodynamic and clinical deterioration
Glaucoma
no objective evidence to show any increase in intraocular pressure
What is treatment of Torsade
Magnesium (stabilize the membrane)
Isopril (isoproternol)
pace at a faster rate (shorten the QT interval and avoid pause related initiation
Lidocaine (shorten the QT)
What is nipride toxicity
Excessive nipride produces free cyanide radicals that cannot all bind with avilable methemaglobin Signs of toxicity: tachyphylaxis elevated mixed venous Po2 metabolic acidosis No cynanosis
What are loop diuretics and side effects
act on tubular epithelial cells in thick ascending loop of Henle to inhibit Na, K, and 2Cl-
deafness (rare)
Describe how Inotropes increase cardiac contractility
Increase the intracellular cyclic adenosine monophosphate (cAMP) levels. cAMP augments calcium influx into myocardial cells thereby increasing contractilty
How do DA, NE, Epi effect cAMP levels
Stimulation of adnylate cyclase, which catayses the conversion of ATP to cAMP
What are pharmacological properties of aprotinin
Anti-fibrinolytic agent
inhibits serine proteases including; plasmin, kallikren
side effects: renal dysfunction, graft patency
HMMERSMITH regime
BART-study killed it
What are pharmacological properties of ARB
ARB are similar to ACE but do not break down bradykinin
TGF–can be used in those with family history of TAAA/Marfan
What is difference between abicimab and Intergrellin and Aggra stat
Abicimab is a non-competitive monoclonal antibody against GP2b3A receptor which inhibits platelet aggregation. Need to wait 12 to 48 hours
Integrelline and Aggrastat are competitive binders. Bleeding time is only up for 8 hours. Can wait a few hours. Give platelets to over come.
What are difference among calcium channel blockers
Non-dihydropyridine CCBs are considered to have negative inotropic and chronotropic effects. The dihydropyridine CCBs increase contractility and heart rate, therefore decreasing vascular resistance
Dihydropyridine reduce systemic vascular resistance and arterial pressure, but are not used to treat angina (with the exception of amlodipine, nicardipine, and nifedipine, which carry an indication to treat chronic stable angina as well as vasospastic angina) because the vasodilation and hypotension can lead to reflex tachycardia. Dihydropiridine calcium channel blockers can worsen proteinuria in patients with nephropathy
How do ACE and ARB effect afterload
antagonizing the vasopressor effect of angiotensin, thereby decreasing the amount of work the heart must perform.
angiotensin directly affects cardiac remodeling, and blocking its activity can thereby slow the deterioration of cardiac function.
How does spironalctone work for heart failure
The RALES trial showed that the addition of spironolactone can improve mortality, particularly in severe cardiomyopathy (EF < than 25%.)
Eplerenone was shown in the EPHESUS trial[27] to have a similar effect, and it is specifically labelled for use in decompensated heart failure complicating acute myocardial infarction.
Antagonism of aldosterone will decrease the effects of sodium and water retention, the main mechanism of action is by antagonizing the deleterious effects of aldosterone on cardiac remodeling.
What is role for nitrates in systolic heart failure
The combination of isosorbide dinitrate/hydralazine is the only vasodilator regimen, other than ACE inhibitors or angiotensin II receptor antagonists, with proven survival benefits
What is role for BNP therapy in heart failure
Nesiritide, a recombinant form of B-natriuretic peptide, is indicated for use in patients with acute decompensated heart failure who have dyspnea at rest.
Promotes diuresis and natriuresis, thereby ameliorating volume overload.
BNP is elevated in heart failure, the peptide that is produced during CHF is dysfunctional or non-functional and thereby ineffective
List exams of each of the VW class of antiarrythmics
Class I —Na+ channel (procainamide)
Class II—metoprolog
Class III most accurate to say prolong action potential duration * Soltalol
Class IV–verapamil
What does Sotalol do and what is risk
Nonselective beta-blocker that also has K chalennl-blocking activity
risk of Torsade de Pointe
What is quick action of Digoxin
Direct effect is to Inhibit Na_, K+ ATPase pump leading to decrease K+ inctracellular
the indirect effect is to stimulate the vagotonic effect on the AV now to slow it down.
How does Adenosine work
Decreases AV node conductivity and breaks AV nodal reentrant tachycardia
How does Epi work
alpha and beta1 effects but little beta2
both an inotrope and a vasopressor
What is Levosimendan
Calcium sensitizer
used to treat decompensated heart failure
How does Acetazolamide function
Diamox
alkalinzation of urine in the presence of metabolic alkalosis which is common with prolonged diuretic therapy
Acts in the proximal convoluted tubule to inhibit carbonic anhydrase, which reduced the destruction of bicarbonate ions.
Both Na+ and HCO3 reabsorption is diminished in the proximal tuble
What is mechanism of action in HCTZ
Class of Benzothiazides
Act in the early distal convoluted tubules to decrease the electroneutral N+/Cl- costransport reabsorption of Na.
Enhanced action when combined with osmotic diuretic.
How does Spironolactone (Aldactone) function
competitive antagonist of aldosterone
Late distal tuble
Decreases the electrogenic Na+ entry into cells (which is the driving
What is mechanism of Mannitol
Osmotic diuretic
1) used for prophylazis and early treatment of ARF
2) enhancing the action of other diuretics by retaining water and solutes in the tubular lumen, therby providing the substrate for other diuretics to act.
It limits the reasbsortopm of water and dilutes the proximal tubular fluid which reduces the gradient for sodium and limits its reabsorption so that more is delievered to the distal portions of the nephron.
usually 25 to 50g is in the prime.
List common herbs and the potential effects
Ginger---potentiate ASA and warfarin Ginkgo-- potentiate ASA and warfarin Eichancea--decrease effect of steroids Garlic----potentiate warfarin Ginseng--decrease effects of warfarin
What is methylene blue?
What is dose?
.
What is penicillin G
Penicillin G is noted to possess effectiveness mainly against Gram-positive organisms
Bacteria constantly remodel their peptidoglycan cell walls, simultaneously building and breaking down portions of the cell wall as they grow and divide. β-Lactam antibiotics inhibit the formation of peptidoglycan cross-links in the bacterial cell wall; this is achieved through binding of the four-membered β-lactam ring of penicillin to the enzyme DD-transpeptidase
a synergistic effect with aminoglycosides, since the inhibition of peptidoglycan synthesis allows aminoglycosides to penetrate the bacterial cell wall more easily, allowing their disruption of bacterial protein synthesis within the cell
What is Prostaglandin E1
Prostaglandin E1 (PGE1), known pharmaceutically as alprostadil, is a prostaglandin
maintaining a patent ductus arteriosus in newborns. This is primarily useful when there is threat of premature closure of the ductus arteriosus in an infant with ductal-dependent congenital heart disease, including cyanotic lesions
What are the pharmacological properties of aspirin
Class: cyclo-oxygenase inhibitor
ASA inhibits platelet cyclo-oxygenase reducing the production of thromboxane A2 and effecting platelet adhesiveness
