Q11

Describe the pharmacokinetics of metformin?

Well absorbed, not protein bound, not metabolised, elimination t1/2: 1.5-3 hours, excreted by kidney as unchanged compound

Pass: Bold

What are the side effects of metformin?

Gastrointestinal most common 20%, decreased absorption Vit B12, lactic acidosis esp with renal

disease, ETOH, chronic cardiopulmonary disease

Pass: Bold

With regard to sulphonylureas, what is the mechanism of action of glipizide?
Prompt: It's a sulphonylurea.

Increase insulin release from the pancreas bind to receptor associated with ATP sensitive K channel, inhibits efflux of K ions, results in depolarization and opens ca channel, influx of Ca causes release of preformed insulin

Reduction of serum glucagon levels

Closure of potassium channels in extrapancreatic tissues

Notes: Patients more prone to hypo than with biguanides eg metformin


Q12

What are the effects of hydrocortisone?



Mediated by glucocorticoid receptors

Physiologic + permissive effects

Metabolic effects

Catabolic and anti-anabolic effects

Anti-inflammatory + immunosuppressive effects

Other effects: CNS, pituitary axis, psychiatric, renal, neonatal lung

Pass: Bolded and one other

Extra. Prompt: Describe the anti-inflammatory and immunosuppressant effects of hydrocortisone.

Effect concentration, distribution + function of peripheral leukocytes
Suppress inflammatory mediators
(cytokines + chemokines, as well as PGs + leukotrienes)

Inhibit tissue macrophages + APCs Suppress mast cell degranulation

Reduce antibody production (in large doses)

What are the effects of chronic steroid use?

Cushings Syndrome
Metabolic effects (moon face, fat redistribution, striae, weight gain, myopathy, muscle wasting, thin skin, bruising, hyperglycaemia, osteoporosis, diabetes, aseptic necrosis, wound healing impaired

Other effects (peptic ulcers, psychosis, depression, cataracts, glaucoma, salt retention, hypertension)

Adrenal suppression (> 2 weeks dosage)

Pass: Bolded and 3 others


Q13

Describe the pharmacokinetics of metformin.

  • Well absorbed, not protein bound, not metabolised, elimination half-life 1.5 to 3 hours
  • Excreted by kidney as unchanged compound

Pass Criteria

  • Bold and one other to pass

Outline some common side effects of metformin.

  • GI most common (20%) – limits compliance with this drug
  • High anion gap metabolic acidosis (lactic acidosis) especially in patients with co-existent renal disease, ethanol, chronic cardiopulmonary disease

Pass Criteria

  • Bold to pass

Contrast the mechanism of action of metformin (biguanide) and glipizide (sulfonylurea).

  • Glipizide
    • Increases insulin release from pancreas (patients more prone to hypoglycaemia with glipizide compared with metformin)
    • Decreases serum glucagon levels
  • Metformin
    • Mechanism unclear but:
    • May reduce hepatic gluconeogenesis
    • Not dependent on functioning pancreatic Beta cells – so doesn’t influence insulin release from pancreas
    • May directly stimulate glycolysis in tissues with increased glucose removal from blood
    • Decreases glucose absorption in the gut

Pass Criteria

  • Bold to pass

Q14

Describe the mechanism of action of corticosteroids at a cellular level.

  • Most of known effects via widely distributed glucocorticoid receptors
  • Present in blood in bound form on Corticosteroid Binding Globulin (CBG)
  • Enters cell as free molecule
  • Intracellular receptor bound to stabilising proteins (most important heat shock protein 90, Hsp90)
  • Complex binds molecule of cortisol then actively transported into nucleus where binds to Glucocorticoid Receptor Elements (GRE) on the gene
  • Interacts with DNA and nuclear proteins regulating transcription. Resulting mRNA exported to cytoplasm for protein production for final hormone response.

Pass Criteria

  • Bold to pass

How can corticosteroids be classified?

PROMPT – How do they differ in their action?

  1. Length of action (hydrocortisone short to medium-acting, dexamethasone or betamethasone long-acting)
  2. Anti-inflammatory activity (Potency: hydrocortisone 1, prednisolone 5, dexamethasone 30)
  3. Mineralocorticoid activity i.e. salt retaining (fludrocortisones 250 times that of hydrocortisone)
  4. Topical vs non topical

Pass Criteria

  • Bold to pass

What are the side effects of corticosteroid use?

PROMPT – What about long term effects?

  • Short term (<2 weeks)
    • Insomnia
    • Behaviour changes
    • Acute peptic ulcer
    • Acute pancreatitis
    • Hyperglycaemia
  • Long term
    • Cushing’s syndrome (moon facies, fat redistribution, fine hair growth, acne) secondary to hormonal actions. (Rate of development function of dose and genetic background).
    • Hyperglycaemia, diabetes
    • Myopathy
    • Osteoporosis, aseptic necrosis
    • Psychiatric (hypomania, acute psychosis, depression)
    • Sodium, fluid retention, potassium loss
    • Adrenal suppression/Addisonian crisis
    • Poor wound healing
  • Immunosuppressant

Pass Criteria

  • Bold and 4 others

Q15

What are the complications of insulin administration?

  • Hypoglycaemia
  • Hypoglycaemic unawareness
  • Insulin allergy (usually due to non-insulin contaminants)
  • Immune insulin resistance
  • Lipodystrophy at injection sites

Pass Criteria

  • Bold + 1 to pass

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