Week 18 Pharmacology

Insulin

  • Preparations.
    • Previously other animal insulins were used but antibodies developed so now bacteria are used to synthesis human insulin for injection
    • Preparations differ in AA sequence, concentration, solubility and time of onset and duration of action.
    • IV insulin –> max drop in BSL in 30mins later
    • SC insulin slows down absorption and breakdown
      • Rapid –
        • clear
        • Lispro, aspart, glulisine
        • Peak in 1hr
      • Short acting
        • Clear
        • Novolin, humulin R
        • Peak in 3-4hrs
      • Intermediate
        • turbid, with protamine
        • Humulin N, Norvolin N
        • Peak 4-8hrs
      • Long acting
        • Clear
        • Levemir, glargine
        • Low level of effect for a long time 6-23 hrs.
      • Pre mixed
  • Delivery system
    • Portable pen injectors
    • Continuous SC infusion pumps
  • Complications of therapy.
    • Hypoglycaemia
    • Allergy
    • Immune insulin resistance
    • Lipodystrophy at injection site – rare seen since development of human insulin

 

Oral hypoglycaemics:

  • Sulphonylureas.
    • Bind to receptor –> inhibits efflux of K+ –> depolarisation –> Ca2+ influx –> release of preformed insulin
    • Increase insulin release from pancreas
    • Reduce serum glucagon
    • Close extrapancreatic K channels
    • Glimepiride, Glibenclamide
  • Biguanides.
    • Metformin
    • Increases peripheral tissue sensitivity to insulin
    • Increased tissue uptake of glucose and tissue glycolysis.
    • Reduce hepatic glucose production through activation of AMP activated protein kinase, slowing GI absorption of glucose –> increase conversion of glucose to lactate in GIT.
    • Don’t cause hypoglycaemia
    • Not metabolised, excreted by kidney as an active compound.
    • SE due to inhibiting hepatic gluconeogenesis it can impair hepatic metabolism of lactic acid.
    • In renal imp metformin accumulates –> lactic acidosis
    • SE – nausea, vomiting, annorexia, diarrhoea, abdo discomfort(GIT effect – 20% of ppl)
  • Acarbose
    • Reduce GIT conversion of starch and dischcharides to monosachcharides –> reduce post prandial hyperglycaemia
  • Rosiglitazone/Pioglitazone
    • Reduce insulin resistance
    • Regulate gene expression via PPAR-gamma
    • SE – fluid retention, wt gain, anaemia. Not to use in CCF, hepatic disease.
  • Sitagliptin
    • Blocks degradation of GLP 1

 

Glucagon.

  • Indications
    • Hypoglycaemia
    • Beta-blocker OD (positive ionotrope at higher doses due to increased cAMP)
    • Oesophageal FB (relaxes lower oesophageal sphincter)

 

Viva questions:

  • What pharmacological agents can be used to lower blood glucose ?
  • What pharmacological agents can be used to raise blood glucose ?
  • Tell me about insulin
  • Tell me about oral hypoglycaemic agents
  • Tell me about glucagon