CLASS - MOA/EFFECT

Question 1

Aspirin

Answer 1

Aspirin

Irreversibly inhibit COX1/2 [non-selective]
↓ TXA2 synthesis in platelets and PGI2 in endothelial cells
Endothelium can produce more COX1 to continue PGI2 synthesis
↓ Platelets forming COX1/TXA2

Effects: Inhibition of TXA2 synthesis and platelet aggregation
TXA2 synthesis does not recover until more platelets produced (7-10 days)

Question 2

glycoprotein IIb/IIIa inhibitors

Answer 2

tirofiban, eptifibatide

inhibits fibrinogen from binding to IIa/IIIb receptors
Preventing linkage of adjacent platelets

Effects: block platelet aggregation

Question 3

Neprilysin inhibitors

Answer 3

Sacubitril (with valsartan) [ARNI]

Sacubitril inhibits neprilysin, preventing natriuretic peptide degradation.
Valsartan blocks AngII levels increasing.

Effects: vasodilation, increases glomerular filtration rate, reduces sympathetic tone and aldosterone release.

Question 4

digoxin

Answer 4

digoxin

Competitively inhibits Na+/K+ ATPase on cardiac cell membrane, leading to intracellular Na+ and Ca2+ accumulation

Effects: enhances vagal tone; decreasing heart rate, slowing AV conduction

Question 5

Nicotinic acid

Answer 5

Nicotinic acid

exact MOA unknown.
Thought to decrease the release of FFA from adipose tissue:
↓ Hepatic synthesis of TG
↓ Hepatic VLDL secretion
↓ Plasma TG and LDL

Effects: decrease TG [20-40%], decrease LDL [15-30%], increase HDL [20-35]

Question 6

potassium channel blockers

Answer 6

amiodarone, sotalol

Mechanism of action: bind and block potassium channels responsible for phase 3 repolarisation

Effects: increased action potential duration

Question 7

adenosine

Answer 7

adenosine

activates A1 receptors on AV node
- Inhibits adenylates cyclase → decreased cAMP
- Decreases inward pacemaker and Ca2+ current

Effects: decreases AV conduction

Question 8

SGLT2 inhibitors

Answer 8

Dapagliflozin, empagliflozin

inhibits sodium glucose co transporter 2 [SGLT2]
Reducing glucose reabsorption in the kidneys, increasing excretion in the urine

Effects: glucosuria and osmotic diuresis, reducing fluid overload

Question 9

Fibrates

Answer 9

Fenofibrate, gemfibrozil

Activate PPARα nuclear receptors
↑ Transcription of genes for lipoprotein lipase
↑ TG degradation [from VLDL and chylomicrons]
↑ Removal of TG from plasma

Effects: decrease TG [40-80%], increase HDL [10-30%], decrease LDL [5-15; >25% fenofibrate]

Question 10

Thrombolytics

Answer 10

Alteplase, reteplase, tenecteplase

Converting plasminogen to plasmin, to catalyse the breakdown of fibrin

Effects: Dissolve clots to reopen occluded artery (unlike antiplatelets or anticoagulants)

Question 11

Bile acid binding resins

Answer 11

Cholestyramine

Bind to bile acids and prevent reabsorption from intestinal lumen  decreased cholesterol absorption, increased cholesterol metabolism
↑ Demand for cholesterol
↑ Expression of LDL receptors
↑ Clearance of plasma LDL

Effects: decrease plasma LDL [15-25%]

Question 12

AT1 receptor antagonists [ARBs]

Answer 12

Candesartan, irbesartan, valsartan, Olmesartan

inhibit the action of AngII on AT1 receptors

inhibited AII = decreased aldosterone secretion = increase Na+/water excretion and K+ retaining = decrease blood volume = decrease BP

Question 13

Dipyridamole

Answer 13

Dipyridamole

Inhibits phosphodiesterase enzymes (PDE3) that break down cAMP
↑ cAMP, PKA, IP3
↓ Ca2+ release
Block adenosine uptake into RBC

Effects: coronary vasodilation

Question 14

A2 receptor agonists

Answer 14

clonidine, methyldopa, monoxnidine

Inhibit further release of noradrenaline.
Activate A2 receptors in CNS and inhibit NAD release, decreasing SNS outflow

Effects: Reduce SNS outflow

Question 15

crystalloids

Answer 15

normal saline

can cross semi-permeable membranes easily
requires frequent and large volume administration
hypovolaemic shock

Question 16

vasopressors: noradrenaline

Answer 16

• preferentially activates A1 receptors in the vasculature - vasoconstriction
• some activation of B1 receptors in the heart

increasing MAP, SVR, organ perfusion

Question 17

sodium channel blockers

Answer 17

Class Ia: disopyramide
Class Ib: lidocaine
Class Ic: flecainide

binds to and blocks fast Na+ channels that are responsible for rapid depolarisation of non-nodal cardiac action potentials

Effects: slower cell depolarisation, reduced AP velocity, suppress tachyarrhythmias

Question 18

Statins

Answer 18

Atorvastatin, simvastatin

Competitively inhibit HMG-CoA reductase
↓ Hepatic cholesterol synthesis
↑ Demand for cholesterol in the liver
↑ Expression of LDL receptors on hepatic cells
↑ Clearance of plasma LDL

Effects: ↑ hepatic cholesterol uptake, ↓ plasma cholesterol [25-55%], ↓ TG 10-20%]

Question 19

P2Y12 antagonists

Answer 19

Clopidogrel, prasugrel, ticagrelor

inhibit P2Y12 receptor
- Prevention of ADP-mediated activation of the GPIIb/IIIa complex

Effects: decrease platelet aggregation

Question 20

vasopressors: dopamine

Answer 20

low doses: works on D1 receptors = vasodilation
* high doses: works on B1 and A1 receptors = vasoconstriction, positive inotropic and chronotropic.

increasing MAP, SVR, organ perfusion

Question 21

Beta blockers

Answer 21

atenolol, metoprolol, propranolol

block B1 receptors [GPCR] in cardiac muscle, ↓ intracellular Ca2+, cAMP, PKA

Effects: Oppose action of SNS = decrease HR, AV conduction and contractility, CO, BP

Question 22

vasopressors: vasopressin

Answer 22

• causes vasoconstriction by acting on V1 receptors
• also activates V2 receptors in kidneys to ↑ water reabsorption

increasing MAP, SVR, organ perfusion

Question 23

A1 receptor antagonists

Answer 23

Prazosin, terasozin

block α1 receptors in smooth muscle
Decrease effect of NA on postsynaptic receptors = Decrease phospholipase C = decrease inositol triphosphate (IP3) and diacylglycerol = decrease intracellular Ca2+

Effects: vasodilation

Question 24

vasopressors: adrenaline

Answer 24

• low doses: preferentially activates B1 [↑HR and contractility]; B2 [decrease TPR]
• high doses: ↑activation of A1 = vasoconstriction [↑TPR]

increasing MAP, SVR, organ perfusion

Question 25

Thiazide diuretics

Answer 25

Hydrochlorothiazide, chlorthalidone, indapamide Inactivate the Na+/Cl- co-transporter in the DCT = loss of Na+ and Cl- reabsorption into blood = promoting excretion in urine reduce blood volume

Question 26

Aldosterone antagonists

Answer 26

Spironolactone competitively inhibiting the action of aldosterone at receptor sites in collecting tubules. Decreased aldosterone, Na+ and water reabsorption Increased K+ retention Effects: diuresis, natriuresis

Question 27

colloids

Answer 27

albumin contains large molecules that do not readily cross capillary walls remains in blood longer hypovolaemia if not crystalloids

Question 28

nitrates

Answer 28

GTN, isosorbide mononitrate causes endothelial cells to release nitric oxide [via sulfhydryl groups] NO diffuses into smooth muscle o Activates guanylate cyclase o ↑ cGMP o ↑ Protein kinase G [PKG] Induces smooth muscle contraction ↓ intracellular Ca2+ and K+ ↑ increases MLC phosphatase Effects: dose related Low dose: vasorelaxation, decreased preload, VEDP + CO High dose: vasodilation, increased coronary artery perfusion, decrease CO + afterload

Question 29

ACE inhibitors

Answer 29

Captopril, ramipril, enalapril, perindopril inhibiting ACE and the production of Angiotensin II inhibited AngII = decreased aldosterone secretion = increase Na+/water excretion and K+ retaining = decrease blood volume = decrease BP

Question 30

Ezetimibe

Answer 30

Ezetimibe Decreased intestinal absorption of cholesterol by blocking transport protein to plasma [NPC1L1] ↑ demand of cholesterol ↑ expression of LDL receptors ↑ clearance of LDL from plasma ↓ LDL plasma concentration Effects: decrease plasma LDL [15-25%]

Question 31

calcium channel blockers

Answer 31

Dihydropyridines: amlodipine, clevidipine Phenylalkylamines: verapamil Benzothiazepines: diltiazem Block VG Ca2+ channels in the cardiac and smooth muscle = relaxation dihydropiridines = vascular smooth muscle. arterial vasodilation to decrease arterial pressure non-dihydropiridines = cardiac muscle. decrease HR and contractility = decrease CO = decrease arterial pressure

Question 32

Loop diuretics

Answer 32

Furosemide inhibiting Na+/K+/Cl- symporter in loop of henle; preventing reabsorption into bloodstream. Effects: increased loss of Na+/K+/Cl- in urine. Decreased venous return and venous pooling

Question 33

antimuscarinics

Answer 33

atropine non-selective muscarinic receptor antagonist. Blocks M2 receptors and causes increase firing rate of SA node, and increased conduction through AV node. Effects: increasing heart rate; inhibits vagal slowing

Question 34

PCSK9 inhibitors

Answer 34

Evolocimab, Alirocumab binds to inhibit PCSK9 on LDL receptors = prevent LDL receptor degradation = increase LDL clearance from blood Effects: decrease plasma LDL [55-75%]

Question 35

inotropics

Answer 35

dobutamine, isoprenaline Predominately β agonists. Agonistic effect on beta adrenoreceptors: stimulating. β1 – heart; β2 – vascular smooth muscle, bronchi, GI smooth muscle, skeletal muscle vessels Effects: increase CO