Pharm

Question 1

What are the classes of anti arrhythmics?

Answer 1

Some Block Potassium Channels
(a) Class 1: Sodium channel blockers
- 1A: prolong repolarisation (AP duration)
1 Double Quarter Pounder
Disopyramide, Quinidine, Procanimide - can cause QT prolongation or torsades
- 1B: shorten repolarisation (shorten AP duration)
with Lettuce, Mayo + Tomato
Lidocaine, Mexeletine, Tocainide
- 1C: little effect on repolarisation, slow conduction velocity
and More Fries Please
Moricizine
Flecanide
Propefanone

(b) Class 2: Beta blockers
Propranolol, Atenolol, Metoprolol (B-PAM)

(c) Class 3: Potassium channel blockers
(SAD) - Sotalol, Amiodarone, Dofelitide
Can prolong QT

(d) Class 4: Calcium channel blockers 
I and V in class IV: diltiazem, verapamil

Question 2

Action potential and ion flux in myocardial contractile cells

Answer 2

Resting potential (approx. -90mV) relies primarily on potassium channels (inward-rectifier potassium channels), ensuring a steady POTASSIUM EFFLUX(iK1).

Phase 0 (depolarization): Neighboring cells stimulate voltage-gated sodium channels within the cell, causing them to open briefly. This results in a SODIUM INFLUX (iNa ), and, consequently, the membrane potential increases just beyond 0 mV (overshoot).

Phase 1 (partial repolarization): The brief INFLUX OF CHLORIDE and EFFLUX OF POTASSIUM (not shown here) causes membrane potential to decrease.

Phase 2 (plateau): The opening of voltage-gated L-type calcium channels causes an INFLUX OF CALCIUM ions (iCa), counteracting the repolarization and keeping the membrane potential at approximately 0mV.

Phase 3 (repolarization): Rapid repolarization occurs via the opening of outward-rectifier potassium channels, resulting in a net EFFLUX OF POTASSIUM

Phase 4 (resting potential): A steady EFFLUX OF POTASSIUM (ik1) occurs until the cell is stimulated again and the process begins again at phase 0.

Question 3

Digoxin MOA + toxicity

Answer 3

MOA: A cardiac glycoside that inhibits Na+/K+- ATPases in cardiomyocytes. Increased intracellular Na+ levels and decrease in intracellular K result, which in turn reduce the efficacy of Na+/Ca2+ exchangers and lead to higher intracellular Ca2+ concentrations. As a result, the force of contraction becomes stronger (positive inotropic effect). Also stimulates vagus nerve to decrease HR

Following initiation/change in digoxin dose, it takes at least 5 days (five half-lives) to achieve a steady state

ECG: atrial fibrillation with block
The classic digoxin toxic dysrhythmia combines:
- SVT due to increased automaticity
-Slow ventricular response (due to decreased AV conduction)

Question 4

Statins and myopathy

Answer 4

Simvastatin is the most likely to cause muscle pain

fluvastatin and pitavastatin are the least likely

Question 5

Which cardio medications cause rash?

Answer 5

• Photosensitivity is common adverse effect associated with AMIODARONE + THIAZIDE
• ACEi and ARB commonly also cause rashes which may be photosensitive

Question 6

What are lipid targets for at risk patients?

Answer 6

LDL < 1.8
HDL > 1
TG < 2
Non-HDL < 2.5

Question 7

When do you consider a PCSK9 inhibitor?

Alirocumab, evolocumab

Answer 7

If LDL goal is not achieved after 4-6 weeks despite maximal tolerated statin therapy + ezetimibe, add a PCSK9 inhibitor

Question 8

What is PCSK9?

Answer 8

PCSK9 binds to LDL receptors causing degradation of the receptor which prevents the receptor from being recycled.

Gain of function mutations in PCSK9 caused by autosomal dominant FH can result in a low level of LDL receptors, a high level of LDL-C and premature CHD

Absence or loss of function mutations of PCSK9 may lead to an increase in LDL receptors and a marked reduction in LDL plasma levels and protection from CHD

Thus PCSK9 inhibition is a rational therapeutic target

Question 9

MOA of statins

Answer 9

• Competitive inhibition of HMG-COA reductase

- Decreases LDL +++

Question 10

MOA of ezetimibe

Answer 10

Selective inhibition of cholesterol reabsorption at the brush border of enterocytes.

Decrease LDL ++
Otherwise + effect on HDL and trig

Question 11

MOA of fibrates

Answer 11

Activation of the peroxisome proliferator activated receptor alpha (PPAR-a)
Decrease LDL +
Increase HDL +
Decrease Trigs +++

SE:
Dsypepsia
Myopathy
Cholelithiasis
Elevated LFTs 

Contraindications
Renal insufficiency
liver failure

Question 12

The effect of fish oil (omega 3 fatt acid)

Answer 12

Decreased transportation of free fatty acids to the liver
Inhibition of triglyceride synthesising enzymes

LDL increase slighty
HDL increase slightly
Decrease trigs but only at high doses