Common drugs

Question 1

Explain the mechanism of frusemide

Answer 1

• works in the thick ascending loop of Henle
• competes with the CL pore of the main transport protein (NKCC2) -> nothing gets transported
  > decreased reabsorption of Cl, Na and K
  > K and chloride are lost via the urine
  > sodium reabsorbed by the ENaC channels (aldosterone regulated, and is activated due to hypovolemia in the setting that frusemide reduces total body water)

Question 2

What are the key electrolyte disturbances with frusemide?

Answer 2

• hypokalemia
• metabolic alkalosis (increased HCO3- reabsorption due to loss of Cl- and K+)

Question 3

What is the role of the ENAC channel in the kidney

Answer 3

The ENAC channel that is located in the collecting duct promotes Na reabsorption and K extrection (MOA of spironalactone)

Question 4

Where are b1 receptors located and what is the function of b1 antagonists?

Answer 4

Beta blockers that are selective (b1) antagonists are usually located in the heart and the kidney
> Known for reductive activity in HR
> Decrease in renin  reduces heart oxygen demand (reduces ECF volume + increases tissue perfusion of the blood)
> Counter inappropriately high sympathetic activity

Question 5

What is the function of DHP calcium channel blockers?

Answer 5

Aim to reduce systemic vascular resistance and arterial pressure

Question 6

What is the limitation of using DHP calcium channel blockers for angina?

Answer 6

Sometimes when used to treat angina this can lead to vasodilation + hypotension. This can subsequently result can lead to reflex tachycardia, detrimental in patients with ischaemic symptoms as the tachycardia causes increased O2 demand

Question 7

How do calcium channel blockers work?

Answer 7

CCB in general prevent movement of Ca into a cell by binding to L-type voltage gated calcium channels –> reduction in heart + vascular smooth muscle contraction –> lowers blood pressure + O2 perfusion to heart

Question 8

Out of verapamil vs diltiazem, what would be the preferred choice?

Answer 8

veramapil has shows to lower HR and contractility more than diltiazem

Question 9

What is the mechanism of hypokalemia secondary to fursemide?

Answer 9

Blockage of NKCL2 –> lack of K into the cell

Question 10

Explain how frusemide downstream causes hypomagneisa and hypocalcaemia?

Answer 10

• K channels in the tubular side cause potassium to escape and chloride to be reabsorbed
  > Positive change in the lumen because K constantly moved into cell and Cl- reabsorbed
  > This difference causes Ca + Mg to be reabsorbed
  -
  When frusemide blocks NKCL2
  > Decreases +ve charge inside the cell
  > Discourages reabsorption of Ca + Mg

Question 11

List 5 side effects of frusemide

Answer 11

Hypotension (esp. orthostatic)
RAAS activation
Ototoxicity, especially in combination with aminoglycosides

Electrolyte disturbances:
Hypokalemia
Metabolic alkalosis (hypochloraemia)
Hypernatremia (as sodium is retained)
Hypomagnesemia
Hypophosphatemia

Question 12

How could b1 antagonists cause arrithmiyas?

Answer 12

A key feature to remember is that b1 receptors increase conduction velocity –> prolonged refractory periods can cause arrithmiyas

Question 13

Describe the approach to the treatment of acute Hep B

Answer 13

Options
- nucleotide reverse transrciptase inhibitors - entacavir (1st line); TAF (preferred) over TDF (2nd line)
- neucleoside analougs - lamivudine (3rd line)

Question 14

In what setting would adefovir be used?

Answer 14

chronic Hepatitis B

Question 15

What is the K103N mutation in HIV antivirals associated with?

Answer 15

confers resistance to NNRTIs (e.g. efavirenz) due to altered configuration of the enzyme