CVS drugs (SN)

Question 1

Loop diuretics MOA? Examples? Uses? SEs?

Answer 1

↓ Na + -Cl − -K + co-transport in thick ascending limb of loop of Henle

Furosemide
Bumetanide – better oral bioavailability than furosemide – more beneficial effects than furosemide on venous capacitance in left ventricular failure.
Torasemide

USes: Volume overload (CCF, nephrotic syndrome, CKD)
SIADH

SEs: • urate retention, causing gout
• hypokalaemia
• hypercalciuria leading to increased risk of calcium-based renal stones
• hypomagnesaemia
• decreased glucose tolerance
• allergic tubulointerstitial nephritis and other allergic reactions
• myalgia – especially with high-dose bumetanide
• ototoxicity (due to an action on sodium pump activity in the inner ear) – particularly with furosemide
• interference with excretion of lithium, resulting in toxicity.

Question 2

Thiazides MOA? Examples? Uses? SEs?

Answer 2

↓ Na + -Cl co-transport in early distal convoluted tubule

Bendroflumethiazide
Chlortalidone
Metolazone - not dependent for its action on glomerular filtration, and therefore retains its potency in renal impairment
Indapamide

Uses: Hypertension
Volume overload (CCF)
Hypercalciuria

SEs: cause relatively more urate retention, glucose intolerance and hypokalaemia than loop diuretics
interfere with water excretion and may cause hyponatraemia
hypercalcaemia

Question 3

Causes of resistance to diuretics?

Answer 3

• poor bioavailability
• reduced GFR, which may be due to decreased circulating volume despite oedema (e.g. nephrotic syndrome, cirrhosis with ascites) or intrinsic renal disease
• activation of sodium-retaining mechanisms, particularly aldosterone.

Question 4

K+ sparing diuretics MOA? Examples? Uses? SEs?

Answer 4

↓ Na + reabsorption (in exchange for K + ) in collecting duct (principal cells)

Aldosterone antagonists, e.g. spironolactone, eplerenone (devoid of antiandrogenic or antiprogesterone properties)
Others: amiloride, triamterene

Uses:Hyperaldosteronism (primary and secondary)
Bartter’s syndrome
Heart failure
Cirrhosis with fluid overload
Prevention of K + deficiency in combination with loop or thiazide

SEs: Spiro causes gynaecomastia

Question 5

Carbonic anhydrase inhibitors diuretics MOA? Examples? Uses? SEs?

Answer 5

(weak diuretics)
↓ Na + HCO 3 − reabsorption in proximal collecting duct
↓ Aqueous humour formation

Acetazolamide - cause metabolic acidosis and hypokalaemia.

Uses: Metabolic alkalosis
Glaucoma

Causes sulfonamide hypersensitivity

SEs: Rash: Erythema multiforme –> SJS
peripheral tingling

Question 6

Vasopressin/ADH receptor blockers (aquaretics) MOA? Examples? Uses? SEs?

Answer 6

Block V 2 receptor in collecting ducts producing free water diuresis

Lixivaptan
Tolvaptan
Satavaptan

Uses: Heart failure, cirrhosis, SIADH

Question 7

Effect of diuretics of renal function?

Answer 7

All diuretics may increase plasma urea concentrations - increase urea reabsorption in the medulla.
Thiazides may also promote protein breakdown.

May decrease GFR due to:
o Excessive diuresis (volume depletion, pre-renal failure)
o Diuretics can cause allergic tubulointerstitial nephritis.
o Thiazides may directly cause a drop in GFR; the mechanism is complex and not fully understood

Question 8

Use of Mannitol?

Answer 8

Osmotic diuretic

reduce IOP and ICP

Question 9

ACEi examples? MOA? SEs? CIs? Interactions? Monitoring?

Answer 9

Lisinopril, Captopril, Ramipril, Perindopril

Inhibits Ang 1 –> ang 2 conversion

SEs: Hypotension - esp. c¯ diuretics, HF
RF
↑K+
Dry cough: 10-20%
- 2ndary to ↑ bradykinin
Angioedema (~0.1%)

CIs: suspected/confirmed RAS

Interactions:
↑ risk of RF c¯ NSAIDs
Diuretics, TCAs and
antipsychotics → risk of ↓↓BP
Caution c¯ drugs that ↑ K+
- e.g. spiro

Check U+Es before starting and after increasing dose - acceptable changes = 30% drop from baseline

Question 10

Name ARBs?

Answer 10

Candesartan
Irbesartan
Losartan

Question 11

Indications of ACE-is?

Answer 11

Principal Indications
 Heart failure
 HTN
 Post-MI
 Angina
 Diabetic Nephropathy