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Flashcards in Cardiac pharmacology Deck (73):
1

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.

2

What are the pharmacological properties of heparin

1. inactivates factor Xa
2. inhibits conversion of prothrombin to thrombin
3. prevents fibrin formation from fibrinogen

3

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*

4

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

5

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

6

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.

7

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

8

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

9

Pharmacological properies of Transexamic acid

lysine analogue anti-fibrinolytic agent
Binds to plasminogen, therby inhibiting fibrinolysis
possible renal function and graft patency issues

10

Pharmacological properties of statins



competitively inhibit hepatic HMG-CoA reductase, which is involved in last step of cholesterol synthesis

11

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

12

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

13

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

14

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

15

What are pharmacological mechanism of nitroprusside

relaxes arterial smooth thereby reducing systemic and pulmonary afterload

use for aortic dissection

16

What are pharmacological properties of dopamine

Dopaminergic and adrenergic receptor agonist ug/kg/min
Good for low cardiac output and post MI

17

What are pharmacological properties of dobutamine

synthetic inodilator that activates B1 adrenergic receptors and has moderate B2 (vasodilaton)

18

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

19

What are pharmacological properties of noradrenaline

Potent alpha 1 agonist producing systemic vasoconstriction and beta 1 increasing myocardial contracility

20

How does Milrinone work

Inhibition of phosphodiesterase enzyme, which normally converts to cAMP to inactive 5 -AMP

21

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

22

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

23

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

24

What are the pharmacological properties of loop diuretics

loop diuretics inhibit water and electrolyte reabsorption from the ascending limb of henle

25

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

26

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

27

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

28

List 5 effects on the vascular endothelium from Nitric Oxide

Vasodilation
inhibits vascular smooth muscle growth
inhibits platelet aggregation and adhesion
inhibits neutrophil adhesion

29

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

30

What are toxic byproducts of NO

Nitric dioxide
methemoglobin
peroxynitrite
nitrate

31

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

32

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.

33

What is Vaughn-Williams Classification

Class I = sodium
Class II = beta blockers
Class III = Prolong reploraization (think K)
Class IV = Calcium channel

34

How do Fibrates work?

Increase HDL
Reduce HDL

35

How do Resins work

Reduced LDL and Increase HDL

36

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

37

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

38

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

39

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

40

How do you diagnose amiodarone toxicity

a drop in 15% DLCO
High resolution CT and PFT
treatment is drug withdrawal and corticosteroid

41

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

42

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

43

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

44

List 3 actions of amiodarone

decreased SA node automaticity
decreased AV node refractory time
decreased ventricular and atrial automaticity

45

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

46

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)

47

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

48

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)

49

Describe how Inotropes increase cardiac contractility

Increase the intracellular cyclic adenosine monophosphate (cAMP) levels. cAMP augments calcium influx into myocardial cells thereby increasing contractilty

50

How do DA, NE, Epi effect cAMP levels

Stimulation of adnylate cyclase, which catayses the conversion of ATP to cAMP

51

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

52

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

53

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.

54

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

55

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.

56

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.

57

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

58

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

59

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

60

What does Sotalol do and what is risk

Nonselective beta-blocker that also has K chalennl-blocking activity

risk of Torsade de Pointe

61

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.

62

How does Adenosine work

Decreases AV node conductivity and breaks AV nodal reentrant tachycardia

63

How does Epi work

alpha and beta1 effects but little beta2
both an inotrope and a vasopressor

64

What is Levosimendan

Calcium sensitizer
used to treat decompensated heart failure

65

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

66

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.

67

How does Spironolactone (Aldactone) function

competitive antagonist of aldosterone
Late distal tuble
Decreases the electrogenic Na+ entry into cells (which is the driving

68

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.

69

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

70

What is methylene blue?

What is dose?

.

71

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

72

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

73

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

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