Pharmacology - Endocrine & Toxicology Flashcards
What is the mechanism of action and side effects of Carbimazole
mechanism:
prevents synthesis of T3/T4 by inhibiting thyroid peroxidase (TPO) = limits organification of iodine
side effects:
- GIT disturbance: nausea, vomiting, altered taste sensation
- Skin: maculopapular rash, pruritus, hair loss
- Hepatic: transaminitis
- Haematological: bone marrow suppression, agranulocytosis
How does Carbimazole differ from Propylthiouracil
Carbimazole is a prodrug and is converted to the more potent Methimazole
Propylthiouracil also inhibits peripheral conversion of T4 to T3 and crosses the placenta less (better in pregnancy)
Both inhibit TPO
What is the mechanism of action and side effects of steroids
mechanism:
works via widely distributed glucocorticoid receptors
enters cell to have its effect by binding to intracellular receptor, causing increased transcription of target genes
side effects: short term (\<2 weeks) = insomnia, behaviour changes, peptic ulcer, pancreatitis, hyperglycaemia long term (\>2 weeks) = cushing syndrome, diabetes, osteoporosis, adrenal suppression, poor wound healing
How are corticosteroid classified
- length of action: long acting (dexamethasone and bethamethasone), short acting (hydrocortisone, prednisolone)
- anti-inflammatory activity: dexamethasone > fludrocortisone > prednisolone > hydrocortisone
- mineralocorticoid activity: fludrocortisone > hydrocortisone > prednisolone
What are the effects of hydrocortisone?
- anti-inflammatory, immunosuppression, immunomodulatory
- metabolic effects, increase blood glucose levels (increased gluconeogenesis and anti-insulin action), increase breakdown of proteins (stress response)
- electrolyte and fluid balance
- vasoconstrictive increase arterial contractile sensitivity to NA
- antipruritic and vasoconstrictive when applied to skin
- decreased bone mineral density, osteoporosis
- psychological effects: mood, behaviour, depression
What is the usual dose of Dexamethasone in the treatment of croup
-PO 0.15-0.6mg/kg single does
What are routes of Dexamethasone and how does its anti-inflammatory property compare to Hydrocortisone
- route: PO, IV, IM, topical
- Dexamethasone is 30 times more potent and is longer lasting than Hydrocortisone and contains no salt retention
What are the uses of Dexamethasone
- anti-inflammatory: (think about hypersensitivities) allergy, anaphylaxis, RA, SLE, IBD, eczema, asthma, COPD, croup
- immunosuppression: MS, MG
- adrenal insufficiency: Addisonian crisis
- DST for dx of Cushing’s syndrome
- antiemetic: chemo induced n & v
Describe the anti-inflammatory and immunosuppressive effects of glucocorticoids
- Reduces concentration, distribution and function of peripheral leucocytes
- Suppression of inflammatory mediators (cytokines, chemokines)
- Inhibits function of macrophages and APCs
- Decreases histamine release by mast cells
Outline the drugs used to treat hyperglycaemia in diabetes
- insulin (novorapid): mimics endogenous insulin
- sulphonylurea (gliclazide): binds to sulphonylurea receptor and causes release of pre-formed insulin
- biguanides (metformin): mechanism unclear but causes decreased hepatic glucose production
- thiazolidinediones (pioglitgazone): decreases insulin resistance
What is the mechanism of action and different formulations of insulin?
Mechanism:
- activates insulin receptor (transmembrane receptor tyrosine kinase)
- promotes uptake of glucose from blood into tissues (fat, liver, skeletal muscle) by translocating GLUT
- promotes protein and glycogen synthesis
Formulations:
- rapid/short acting (novorapid) = clear solution, neutral pH, rapid onset, short DOA
- intermediate acting (isophane) = turbid solution, neutral pH
- long acting (lantus) = clear solution, soluble, slow onset, prolonged action
What are the actions of insulin on the liver
- anabolic = increased glycogen synthesis, increased lipogenesis
- anti-catabolic = reduced glycogenolysis and gluconeogenesis
What methods are used to optimise blood sugar control when giving insulin?
- sliding scale: titration of dose to BSL
- basal-bolus insulin regime: combinations of insulins with different durations
- carbohydrate counting and insulin dose titration
- individualised insulin regime (diet, activity level, lifestyle)
- continuous SC insulin infusion devices
- continuous glucose monitoring
What type of insulin is used for IV infusions and why
short acting insulin because it immediately dissociates on dilution and is more precisely delivered
Describe the principles of an insulin pump
- delivers individual basal and bolus insulin replacement doses based on blood glucose monitoring
- consists of insulin reservoir, program chip, keypad and display screen attached to subcutaneous infusion set
