Pharmacology

• Endocrine Pharmacology Classes


  • Insulins
  • Sulfonylureas
  • Biguanides
  • GLP-1 analogues
  • Thiazolidinediones
  • DPP4i
  • Thyroid hormones
  • Thiourylenes
  • Corticosteroids
  • Bisphosphonates
• Insulins


  • Rapid: Insulin Lispro (Humalog), Insulin Aspart (Novorapid)
  • Short: Actrapid, Humulin S
  • Intermediate: Isophane insulin (Isulatard)
  • Long: insulin glargine (lantus), insulin determir (Levemir)
• Insulins effect


  Lowers blood glucose
• Mechanism of Action of Insulins

  Binds to a-subunit of insulin receptor -> phosphorylation cascade:

  • Reversal of glucagon stimulated phosphorylation
  • Phosphorylation of proteins
  • Induction and suppression of specific genes
  • Stimulation of protein synthesis
  • Stimulation of glucose transport (GLUT recruited to cell surface)
• Sulfonylureas


  • Gliclazide

  Glibenclamide

  Glipizide

  Tolbutamide
• Sulfonylureas


  Increased insulin levels leading to increased glucose uptake
• Mechanism of Action of Sulfonylureas

  Binds to sulfonylurea receptors on ATP sensitive K+ channels on B-islet cell plasma membranes

  Reduced K+ efflux -> B-cell depolarisation

  Ca++ entry and insulin secretion
• Biguanides


  Lowers blood glucose level
• Mechanism of Action of Biguanides

  Acts on AMP-kinase

  Increases sensitivity of peripheral tissues to insulin and inhibits gluconeogenesis in liver

  Increases uptake and use of glucose and reduces hepatic glucose output
• GLP-1 analogues


  Lowers blood glucose level
• Mechanism of Action of GLP-1 analogues

  Bind to and activate GLP-1 receptors

  Increases synthesis and release of insulin and suppress inappropriate glucagon secretion

  Increase glucose uptake

  Reduce hepatic glucose output

  Delay gastric emptying and promote satiety
• Thiazolidinediones


  • Pioglitazone
• Thiazolidinediones


  Reduce insulin resistance
• Mechanism of Action of Thiazolidinediones

  Binds to PPARy receptors

  Causes PPARy-RXR complex to bind to DNA promoting transcription of genes whose products are involved in insulin signalling (lipoprotein lipase, GLUT4 etc)
• DPP4i


  • Sitagliptin

  Saxagliptin

  Vildgliptin
• DPP4i


  Lower blood glucose
• Mechanism of Action of DPP4i

  Competitively inhibits Dipeptidyl Peptidase 4 enzymes

  Inhibit degradation of incretin hormones GLP-1 and GIP, increasing their levels

  Increased synthesis and release of insulin

  Reduces glucagon secretion

  Increased glucose uptake by target tissues

  Reduces hepatic glucose output

  Delays gastric emptying and promotes satiety
• Thyroid hormones


  • Levothyroxine
• Thyroid hormones


  Restore euthyroid state through synthetic replacement of deficient endogenous thyroid hormone
• Mechanism of Action of Thyroid hormones

  Binds to thyroid nuclear receptor

  Stimulates nuclear transcription of target genes – increases mRNA and protein synthesis
• Thiourylenes


  • Carbimazole

  Propylthiouracil
• Endocrine Pharmacology Classes


  • Insulins
  • Sulfonylureas
  • Biguanides
  • GLP-1 analogues
  • Thiazolidinediones
  • DPP4i
  • Thyroid hormones
  • Thiourylenes
  • Corticosteroids
  • Bisphosphonates
• Insulins


  • Rapid: Insulin Lispro (Humalog), Insulin Aspart (Novorapid)
  • Short: Actrapid, Humulin S
  • Intermediate: Isophane insulin (Isulatard)
  • Long: insulin glargine (lantus), insulin determir (Levemir)
• Insulins


  Lowers blood glucose
• Mechanism of Action of Insulins

  Binds to a-subunit of insulin receptor -> phosphorylation cascade:

  • Reversal of glucagon stimulated phosphorylation
  • Phosphorylation of proteins
  • Induction and suppression of specific genes
  • Stimulation of protein synthesis
  • Stimulation of glucose transport (GLUT recruited to cell surface)
• Thiourylenes


  Reduces output of T3 and T4 to reduce signs and symptoms of hyperthyroidism
• Mechanism of Action of Thiourylenes

  Inhibits thyroid peroxidase enzyme

  Inhibits iodination of tyrosyl residues in thyroglobulin

  Inhibits coupling of iodotyrosine molecules
• Sulfonylureas


  • Gliclazide

  Glibenclamide

  Glipizide

  Tolbutamide
• Corticosteroids


  • Prednisolone

  Dexamethasone

  Hydrocortisone

  Methylprednisolone
• Sulfonylureas


  Increased insulin levels leading to increased glucose uptake
• Corticosteroids


  Upregulation of gene transcription
• Mechanism of Action of Sulfonylureas

  Binds to sulfonylurea receptors on ATP sensitive K+ channels on B-islet cell plasma membranes

  Reduced K+ efflux -> B-cell depolarisation

  Ca++ entry and insulin secretion
• Mechanism of Action of Corticosteroids


  Mimic action of endogenous mediator cortisol at steroid receptors -> exposes DNA binding domain of receptor

  Allows steroid-receptor complex to associate with glucocorticoid response elements present in promotor region of target genes
• Bisphosphonates


  • Alendronate

  Clodronate

  Pamidronate

  Risedronate
• Bisphosphonates


  Prevents reduction in bone mass
• Biguanides


  Lowers blood glucose level
• Mechanism of Action of Bisphosphonates


  Absorb onto hydroxyapatite crystals on surface of bone and released once osteoclasts begin resorption

  Interferes with osteoclast ruffled border and impairs osteoclast ability to adhere to bone and produce protons needed for resorption

  Promote osteoclast apoptosis

  Inhibits osteoblast apoptosis
• Mechanism of Action of Biguanides

  Acts on AMP-kinase

  Increases sensitivity of peripheral tissues to insulin and inhibits gluconeogenesis in liver

  Increases uptake and use of glucose and reduces hepatic glucose output
• Myenteric plexus of large intestine

  Reduced tone in circular and longitudinal muscles of intestinal wall
• GLP-1 analogues


  Lowers blood glucose level