Other

Question 1

Mannitol

Answer 1

• Carbohydrate derivative and polyhydric alcohol
• Prepared in water as a 10% or 20% solution
• Primarily used to reduce the pressure and volume of CSF. Also has a role in perioperative preservation of renal function in jaundiced / vascular patients, acute glaucoma, and rhabdomyolysis
• Mannitol is an osmotic diuretic. Its presence increases plasma osmolality, which therefore draws water into the plasma. It is freely filtered at the glomerulus and not reabsorbed, and increases the osmolality of the filtrate so that water follows and the volume of urine is increased
• Mannitol cannot pass the intact BBB, but if this is disrupted it may pass and worsen cerebral oedema
• The initial IV bolus dose for reduction of ICP is 1g/kg

Question 2

Acetazolamide

Answer 2

• Carbonic anhydrase inhibitor (reversible, non-competitive)
• Inhibits reabsorption of sodium and bicarbonate ions, resulting in diuresis, alkaline urine and hyperchloraemic metabolic acidosis

Question 3

Thiazide diuretics

Answer 3

• Examples include bendroflumethiazide, chlorothiazide
• Indapamide, xipamide and metolazone are thiazide-like diuretics - they have a different structure but still act at the same site
• Used in the treatment of heart failure and hypertension
• They act on the early segment of the distal convoluted tubule by blocking the thiazide-sensitive Na+-Cl− symporter, therefore reducing the reabsorption of sodium and chloride ions to cause diuresis. Increased Na+ ions at the distal convoluted tubule increases exchange with K+ and H+ so that hypokalaemia and alkalosis may result
• Also increase the reabsorption of calcium ions at the distal convoluted tubule

Side effects:
* Electrolytes - hyponatraemia, hypokalaemia, hypercalcaemia, hypochloraemic alkalosis, hypomagesaemia
* Gout due to reduced uric acid excretion
* Hyperglycaemia
* Aplastic and haemolytic anaemia, leucopenia, agranulocytosis, thrombocytopenia

Question 4

Loop diuretics

Answer 4

• Examples include furosemide, bumetanide
• Act on the NKCC2 channel of the ascending limb of the loop of Henle to inhibit sodium, chloride and potassium reabsorption - causing diuresis

Side effects:
* Electrolytes - hyponatraemia, hypokalaemia, hypocalcaemia, hypochloraemic alkalosis, hypomagesaemia
* Large doses may cause deafness, and potentiates ototoxicity of aminoglycoside antibiotics

Question 5

Heparin

Answer 5

Chemical

Uses

Presentation

Action

Dose / duration / route

Effects

Toxicity / side effects
* Thrombocytopenia
* Hyperkalaemia - due to inhibition of aldosterone secretion
* Hypersensitivity reactions
* Osteoporosis - caused by complexing of heparin with mineral substances from the bone

Absorption

Distribution

Metabolism

Excretion

Question 6

Bronchodilators

Answer 6

• Aminophylline is a non-selective phosphodiesterase inhibitor, which therefore increases cyclic AMP
• Salbutamol stimulates beta2 adrenergic receptors, which are GPCRs with a Gs alpha subunit - therefore activates adenylyl cyclase
• Salbutamol stimulates Na+/K+ ATPase - intracellular movement of K+ explains its role in lowering K+ concentration

Question 7

Cyclizine

Question 8

Warfarin

Answer 8

• Warfarin is a competitive inhibitor of the vitamin K epoxide reductase enzyme. This prevents the reduction of the oxidized form of vitamin K back to vitamin K, resulting in its depletion. This prevents the synthesis of vitamin K dependant clotting factors (2, 7, 9 and 10)