Session 5.2 - Diabetes - insulins and oral hypoglycaemics

Question 1

Metformin

Answer 1

Drug Class: Biguanide

Mechanism of Action: Lowers glucose production in the Liver by inhibiting gluconeogenesis

Common Indicators: Diabetes

ADRs: GI Upset - nausea, vomiting, diarrhoea

Contraindications: Excretion unchanged by kidneys, stop if eGFR < 30mL/min

Important drug-drug rxns: Drugs that impair renal function (ACEi, loop diuretics)
Loop & Thiazide diuretics increase glucose, reducing metformin action.

Question 2

Gliclazide

Answer 2

Drug Class: Sulfonylurea (SU)

Mechanism of Action: Blocks ATP-dependant K+ channels, depolarised the cell, stimulating pancreatic insulin secretion from B-cells

Common Indicators: Type 2 DM

ADRs: Hypoglycaemia (gliclazide works at low [glucose])
GI upset - nausea, vomiting, diarrhoea

Contraindications: Hepatic and renal disease

Important drug-drug rxns: other hypoglycaemic agents
Loop & Thiazide diuretics increase glucose, reducing gliclazide action

Question 3

Pioglitazone

Answer 3

Drug Class: Glitazones

Mechanism of Action:
Increase insulin sensitisation in muscle & adipose
Decrease hepatic gluconeogenesis

Common Indicators: Diabetes Mellitus

ADRs: GI upset, fracture risk, bladder cancer, fluid retention

Contraindications: HF due to the fluid retention

Important drug-drug rxns: other hypoglycaemic agents

Question 4

Sitagliptin

Answer 4

Drug Class: Dipeptidyl peptidase-4 (DPP-4) inhibitors

Mechanism of Action: DPP-4 breaks down GLP-1 (incretin). Inhibition prevents incretin degradation, increasing plasma [incretin] –> increasing insulin secretion and decreasing glucagon secretion in the pancreas.
Also reduces satiety in the brain

Common Indicators: Type 2 DM

ADRs: GI upset, small pancreatitis risk

Contraindications: avoid in pregnancy, pancreatitis

Important drug-drug rxns: other hypoglycaemic agents
Drugs that increase [glucose], reducing gliclazide action - (Loop & Thiazide diuretics)

Question 5

Dapagliflozin

Answer 5

Drug Class: SGLT-2 inhibitors

Mechanism of Action: Decreases glucose absorption in tubular cells from tubular filtrate, increasing urinary glucose excretion

Common Indicators: Type 2 DM, HFrEF

ADRs: UTI & genital infection, thirst, polyuria

Contraindications: hypovolaemia, hypotension

Important drug-drug rxns: other hypoglycaemic agents, Antihypertensive

Question 6

Exenatide

Answer 6

Drug Class: GLP-1 receptor agonists

Mechanism of Action: Resistant to degradation by DPP-4, pancreatic insulin secretion from B cells

Common Indicators: Type 2 DM

ADRs: GI upset, decreased appetite causing weight loss

Contraindications: Renal impairment

Important drug-drug rxns: other hypoglycaemic agents