Endocrine System

Question 1

Actrapid, Humulin S

Answer 1

Short Acting Insulin - start to work in 30-60 minutes, peaks after 2-3 hours, duration 8-10 - inject several times daily to cover meals.
Insulin stimulates uptake of glucose into liver, muscle and adipose, inhibits hepatic gluconeogenesis, inhibits glycogenlysis and promotes fat uptake
Indication - T1DM, T2DM (if oral hypoglycaemic drugs not providing adequate control)
ADRs: Hypoglycaemia, hyperglycaemia, Lipodystrophy, Painful Injections, Insulin Allergy

Question 2

Isophane Insulin

Answer 2

Intermediate Acting Insulin - onset 2-4 hours, peak at 4-8, duration 12-20 hours
Insulin stimulates uptake of glucose into liver, muscle and adipose, inhibits hepatic gluconeogenesis, inhibits glycogenlysis and promotes fat uptake
Indication - T1DM, T2DM (if oral hypoglycaemic drugs not providing adequate control)
ADRs: Hypoglycaemia, hyperglycaemia, Lipodystrophy, Painful Injections, Insulin Allergy

Question 3

Gliclazide

Answer 3

Sulphonylurea
MOA: Stimulate beta cells to release insulin, decrease microvascular risk - Antagonise K+/ATP channel activity, depolarisation leads to increased calcium entry, increased exocytosis.
Indication: T2DM, hepatic metabolism so can be used in renal impairment
ADRs: Hypoglycaemia, weight gain

Question 4

Metformin

Answer 4

Biguanide.
MOA: Reduced insulin resistance, reduced hepatic glucose production, decrease CVS events
Indication: T2DM
Contraindication CKD with GFR<30ml/min
ADRs: GI Symptoms, lactic acidosis (rare), Vitamin B12 deficiency, limited weight gain

Question 5

Repaglinide, Nateglinide

Answer 5

Meglitinides
MOA: Stimulate beta cells to release insulin, decrease microvascular risk - Antagonise K+/ATP channel activity, depolarisation leads to increased calcium entry, increased exocytosis. Similar efficacy but different site of action to sulphonylureas.
ADRs: low risk of hypoglycaemia, not assocaites with weight gain.

Question 6

Rosiglitazone, Pioglitazone

Answer 6

Thiazolidinediones
MOA: Increase insulin sensitivity of muscle and adipose tissue and decrease hepatic glucose output by binding and activating peroxisome proliferator-activated receptors (PPARs)
ADRs: Cardiovascular concerns with Rosiglitazone, Piglitazone is rarely used - associated with weight gain, fluid retention, heart failure, altered bone metabolism and bladder cancer

Question 7

Alpha-glucosidase inhibitors

Answer 7

eg: Acarbose
Inhibits breakdown of carbohydrates to glucose.
Indication: T2DM - modest reduction in HbA1c, rarely used.
ADRs: Flatulence, loose stools and diarrhoea

Question 8

Glucagon-like Peptide 1 (GLP1) Analogues

Answer 8

Agonises GLP-1 receptor agonists
Examples - Exenatide, Liraglutide
Potentiates effect of GLP-1 - increased insulin secretion, decreased glucagon secretion, decreased hepatic glucose production, increased satiety, slowed gastric emptying.
ADRs: Hypoglycaemia (low risk), no effect on weight, GI symptoms (nausea, diarrhoea, gastro-oesophageal reflux), pancreatitis

Question 9

Dipeptyl-peptidase 4 (DPP4) Inhibitors

Answer 9

Protect native GLP-1 from inactivation by DPP4. Examples include Sitagliptin, Wildagliptin, Saxagliptin, Linagliptin.
Potentiates effect of GLP-1 - increased insulin secretion, decreased glucagon secretion, decreased hepatic glucose production, increased satiety, slowed gastric emptying.
Indication: 2nd line to metformin or sulphonylurea if at high risk of hypoglycaemia and its consequences and sulphonylurea is not tolerated/contraindicates. Can use as triple therapy. Only continue if effective due to high cost.
ADRs: Hypoglycaemia (low risk), no effect on weight, GI symptoms, pancreatitis

Question 10

Sodium-glucose co-transporter 2 inhibitors

Answer 10

eg: Dapagliflozin, Canagliflozin, Empagliflozin
Prevents reabsorption of glucose in the PCT by SGLT2 - leads to renal excretion of glucose.
Indication: Add on therapy for T1DM, T2DM
ADRs: Genital and urinary infections, polyuria, low risk of hypoglycaemia.

Question 11

Levothyroxine

Answer 11

Indications: Hypothyroidism
MOA: Replaces endogenous thyroxine (T4)
ADRs: Symptoms of hyperthyroidism at high doses - arrthymias, palpitations, tremor, diarrhoea, weight loss, heat intolerance, muscle weakness

Question 12

Carbimazole

Answer 12

Indication: Hyperthyroidism - reduces production of thyroid hormones
ADRs: Bone marrow suppression - neutropenia, nausea, taste disturbance, headache, rash, jaundice, arthralgia

Question 13

Fludrocortisone, Hydrocortisone, Betamethasone, Prednisolone, Dexamethasone

Answer 13

Corticosteroids
Uses - various - immune suppression in autoimmune disease, Addison’s disease, inflammation
MOA - bind intracellular receptors and alter gene expression, reduce inflammation

Question 14

Oestradiol

Answer 14

Replaces endogenous oestradiol - effects include growth of endometrium and breasts, stimulates production of progesterone receptor
Uses: Used with progestin as COCP - suppresses ovulation, inhibits FSH and LH, makes cervical mucus more viscous, prevents secretory phase of endometrium. Metabolised by CYP450 - efficacy reduced by drugs that induce CYP450.
Used in HRT - with or without medroxyprogesterone depending on whether you have a uterus.
ADRs: Breast tenderness, nausea and vomiting, water retention, hypercoagulability and thromboembolism, impaired glucose tolerance, endometrial, ovarian & breast hyperplasia and cancer, increased risk of stroke in women with focal migraines, cholestatic jaundice, gallstones.

Question 15

Medroxyprogesterone

Answer 15

Replaces endogenous progesterone - stimulates growth of endometrium and breast, maintains pregnancy, inhibits production of the oestrogen receptor
Progestin - used as progesterone-only-pill or in combination with oestrogen as COCP. Makes cervical mucous more viscous.
ADRs: Weight gain, fluid retention, acne, nausea & vomiting, irritability, depression and PMS, lack of concentration.

Question 16

Clomiphene

Answer 16

Selective Oestrogen Receptor Modulator - inhibitits oestrogen binding to oestrogen receptor in the anterior pituitary, inhibiting negative feedback and resulting in higher levels of FSH and LH.
Uses: Induction of ovulation in anovulatory infertility
ADRs: Visual disturbances, ovarian hyperstimulation, hot flushes, abdominal discomfort, nausea, vomiting, depression, insomnia, breast tenderness, menorrhagia

Question 17

Tamoxifen

Answer 17

Selective Oestrogen Receptor Modulator - binds oestrogen receptor in breast tissue and blocks oestrogen stimulated myoepithelial cell division.
Uses: Oestrogen receptor expressing breast cancer
ADRs: Agonises receptors in endometrium, can cause endometrial cancer, hot flushes, suppression of menstruation, thromboembolism, headache, hypersensitivity.