APO (drugs that trigger AKI)

Question 1

Diclofenac MOA

Answer 1

MOA
* Have analgesic, antipyretic and anti-inflammatory actions.
* They inhibit synthesis of prostaglandins, thromboxanes and prostacyclins by inhibiting cyclo-oxygenase (COX) present as COX‑1 and COX‑2:
· inhibition of COX‑1 results in impaired gastric cytoprotection and antiplatelet effects
· inhibition of COX‑2 results in anti-inflammatory and analgesic action
· reduction in glomerular filtration rate and renal blood flow occurs with both COX‑1 and COX‑2 inhibition (causes afferent arteriole constriction)

Question 2

Diclofenac S/E and CI

Answer 2

S/E
* nausea
* dyspepsia/GI bleeding/ulceration/gastritis
* raised liver enzymes
* bronchospasm - arachidonic acid is shunted through the 5 lipooxygenase pathway, to produce leukotrienes
* diarrhoea
* hypertension

CI
* Heart failure, angina
* active peptic ulcer disease
* history of gastrointestinal bleeding
* severe renal or hepatic disease

Question 3

Digoxin MOA

Answer 3

MOA

• inhibits Na/K ATPase, causing increase in intracellular sodium concentration, causing increase in intracellular calcium  increases release and availability of calcium  increased contractility (also lengthens phase 4 of action potential, decreasing HR)
• also increases vagal tone to the heart, decreasing heart rate and AV noda conduction

Question 4

Digoxin S/E and CI

Answer 4

S/E
* may worsen arrhythmia
* bradycardia
* anorexia
* nausea/vomiting/diarrhoea
* visual disturbances
* headache

CI
* Heart block
* VT, ventricular arrythmia 
* Mitral stenosis 
* Hypersensitivity 
* poor compliance (narrow therapeutic index)

Question 5

Frusemide MOA

Answer 5

Class: Loop diuretic

MOA
* work on the Na/K/Cl symporter in the ascending loop of Henle to prevent the reabsorption of Na, K and Cl, increasing diuresis
* effect is rapid and potent (20% of filtered Na reabsorbed here)

Question 6

Frusemide S/E and CI

Answer 6

S/E
* electrolyte disturbances (hyponatraemia, kalaemia, magnesaemia)
* dehydration
* hypotension, orthostatic hypotension
* fainting
* metabolic alkalosis
* increased creatinine concentration
* hyperuricaemia
* gout

CI
* anuria
* hyponatraemia
* hypokalaemia
* hypochloraemia
* fluid depletion

Question 7

Metoprolol MOA

Answer 7

Class:beta-blocker

MOA
· Blocks B1 adrenergic receptors on heart –> -ve ionotropic and chronotropic effect
· Block B1 receptors on juxtaglomerular cells –> decrease renin

Question 8

Metoprolol S/E and CI

Answer 8

S/E
* bradycardia
* hypotension, orthostatic hypotension
* nausea, diarrhoea
* bronchospasm, dyspnoea
* alters glucose and lipid metabolism

CI
* shock
* bradycardia
* heart block
* severe/poorly controlled asthma

Question 9

Quinapril MOA

Answer 9

Class: Angiotensin converting enzyme inhibitor

MOA
* block conversion of angiotensinI to angiotensinII and also inhibit the breakdown of bradykinin
* they reduce the effects of angiotensinII-induced vasoconstriction, sodium retention, ADH and aldosterone release
* they also reduce the effect of angiotensinII on sympathetic nervous activity and growth factors

Question 10

Quinapril S/E and CI

Answer 10

S/E
* cough - increased bradykinin in the lungs
* hyperkalaemia
* angioedema 
* renal impairment 

CI
* pregnancy

Question 11

Warfarin MOA

Answer 11

Class: anticoagulant

MOA
* Vitamin K antagonist - competitively inhibits Vitamin K epoxide reductase
* inhibits the synthesis of vitamin K dependent clotting factors 2, 7, 9, 10
* also inhibits anti-thrombotic factors Protein C and S - thus, initially prothrombotic

Question 12

Warfarin S/E and CI

Answer 12

S/E
* bleeding
* skin necrosis
* alopecia
* fever
* rash
* nausea/vomiting
* hypersensitivity

CI
* alcoholism
* protein C or protein S deficiency (increases skin necrosis)
* active bleeding or increased risk of blooding
* pregnancy