Endocrine Pharmacology Flashcards
Structure of insulin receptor
Mechanism of action
2 alpha and 2 beta subunits linked by disulphide bridges to form cylinder
Alpha subunits extracellular forming insulin binding site
Beta subunits span membrane and have intracellular tyrosine kinase activity
Alpha subunit inhibits tk activity until bound to insulin
Tk acts on insulin receptor substrate 1 triggering a chain reaction
Binding of insulin to alpha also causes formation of transmembrane tunnel allowing glucose entry to cell
How does an insulin receptor stop functioning
Internalised with recycling of receptor and insulin degraded in lysosomes
Amount of energy in 1L 5% dextrose
840kj/L
Where is glucagon formed in physiology
A cells in the pancreas and in upper gi tract
Half life of iV insulin
5 mins
Onset, peak and duration of short acting sc insulin in hrs
0.5-1, 2-4, 8
Onset, peak and duration of intermediate acting sc insulin in hrs
1-2, 4-12, 12-24
Onset, peak and duration of long acting sc insulin in hrs
2-4, 24-40, 36
How is the duration of action of insulin increased
By addition of zinc or protamine forming complexes with intermediate duration or both forming long duration
How many aa differences do bovine and porcine insulin have vs human
Bovine 3
Porcine 1
What is the disadvantage of porcine or bovine insulin over human
Non native sequences may be antigenic causing insulin resistance and immunoreactivity
How is human insulin synthesised
Bacteria
Enzymatic modification of porcine
Examples of sulphonylureas
Mechanism
Gliclazide, glipizide, tolbutamide
Augment endogenous insulin secretion from existing B cells - bind to receptors and increase sensitivity of the cells to glucose. Decreased K permeability so depolarisation, influx of ca and secretion of insulin.
Metabolism of sulphonylureas
Hepatic forming active metabolites excreted in urine
Effect of sulphonylureas in pregnancy
Cross placenta causing hypoglycaemia in newborn
Proteins binding of sulphonylureas
Highly protein bound thus displaced by eg aspirin
Example of biguanide
Mechanism
Metformin
Decrease hepatic gluconeogenesis
Increase insulin mediated peripheral glucose uptake
Do this by increasing sensitive of target tissues to insulin
Metaboism and protien binding of metformin
Excreted unchanged in urine
Not protine bound
Examples of thiazolidinediones
Mechanism
Piaglitazone, rosiglitazone
Sensitise target tissue to insulin
Mainly work in adipose tissues
Examples of meglitinied analogues
How do they work
Nateglinide
Inhibit atp dependant k channels in B cells stimulating insulin release
Examples of sglt2 inhibitors
Dapagliflozin, empagliflozin
Inhibit sglt2 stopping glucose reabsorption in urine
Side effects of sglt2 inhibitors
Diabetic ketoacidosis
Urine infections
Dehydration
Example of a dpp4 inhibitor
How do they work
Sitagliptin
Block dpp4 resulting in more incretin which increases insulin only when it is needed and reduce the amount of glucose from liver when it is not needed
Example of glp1 analogue
Mechanism
Exanatide
Mimic incretin producing more insulin only when needed and reducing hepatic glucose production when not needed
Perioperative management of non insulin diabetic meds
Meglitinide - omit on day when fasting (hypo risk)
Sluphonylureas - omit mane, if pm surgery omit pm dose too (hypo risk)
Sglt 2 inhibitors - omit on day (DKA risk)
All others inc metformin take as normal
What treatment should be used for a hypothyroid coma (thyroid replacement) why
t3 - faster onset than t4
How does carbimazole work
How long to take effect
Big side effect
Blocks organification of iodine
3-4 weeks
Agranulocytosis
Which steroid treatment is naturally occurring
Hydrocortisone (cortisol)
Disadvantage of hydrocortisone over prednisolone
Higher mineralocorticoid effect so more fluid retention
Prednisolone glucocorticoid and mineralocorticoid effect vs hydrocortisone
G 4
M 0.25
Dexamethasone gluco and mineralocorticoid effect vs hydrocortisone
25
0
Fludrocortisone gluco and mineralocorticoid effect vs hydrocortisone
10
300
How are glucocorticoids transported in blood
Corticosteroid binding globulin
Low capacity so easily saturated when large volumes of steroids used
Structure of oxytocin
What is the name of the pharmacological preparation, why
Octopeptide
Syntocinon as it is synthetic
Why does oxytocin cause uterine contraction
Binds causing increased k permeability making cell more excitable
How does uterine sensitivity to oxytocin change over pregnancy
Minimal at start to maximal at term
Action of ergometine
Stimulates 5Ht receptors causing uterine contraction and slight vascular smooth muscle contraction
Side effects of ergometrine
Hypertension
Vomiting - stimulates d2 receptors
Headache and blurred vision lasting several days
Metabolism ergometrin
Liver excreted into bile
What is carboprost
Side effects
A prostaglandin
Comiting, Bronchospasm, flushing, diarrhoea
Dose of ergometrine and carboprost
Ergometrine 250-500mcg
Carboprost 250mcg
Structure of vasopressin
Octopeptide
Half life of vasopressin
10minutes
Clinical effects of vasopressin and receptor
V1a - vasoconstriction
V2 - water reabsorption in collecting duct,
increased hepatic glycogenolysis, encourages platelet aggregation
V1b - triggers acth-rh release
Use of despmopressin
Comparison to vasopressin
Dx and Tx of diabetes insipidus
Strong antiduretic activity (12x vasopressin) but fraction of vasoconstriction activity
What is terlipressin
Route of administration
Prodrug for vaspressin
IV
What is demeclocycline
A vasopressin antagonist used in inappropriate vasopressin secretion
Examples of vasopressin receptor antagonists
Uses
Conivaptan, lixivaptan, tolvaptan
Use in heart failure and hyponatraemia where water loss is desired
Duration of action hydrocortisone;
8 hrs
