Endocrine System

Question 1

Sulphonylureas (1)

Answer 1

Gliclazide (although I’m assuming we can also have Tolbutamide)

Sulphonylureas bind to the ATP-dependent K+ channel on the cell membrane of pancreatic beta cells. This leads to an increased intracellular K+ concentration which depolarise the cell, leading to an influx of calcium due to activation of voltage gated calcium channels. The rise in calcium causes more insulin granules to fuse with the cell membrane and there is a subsequent increase in secretion of (pro)insulin.

Question 2

Biguanides (1)

Answer 2

Metformin

This is the first line treatment for patients with Type II diabetes mellitus (especially obese patients and those with normal renal function). Metformin decreases hyperglycaemia primarily by suppressing gluconeogensis in the liver. It also increases insulin sensitivity and enhances peripheral glucose uptake and decreases glucose absorption from the GI tract.

Few ADRs - GI disturbance and lactic acidosis (only in overdose of if prescribed to patients with contraindications).

Question 3

Meglitidines (2)

Answer 3

Repaglinide and Nateglinide

Meglitidines have a similar mechanism of action to sulhponylureas in that they bind to the ATP-dependent K+ channel on the cell membrane of pancreatic beta cells. However, Meglitidines have a weaker binding affinity and faster dissociation.

The binding to the ATP-dependent K+ channel increases the intracellular potassium concentration which depolarises the cell. This depolarisation opens Voltage gated Calcium channels, causing a rise in intracellular calcium. This subsequently leads to increased fusion of insulin granules with the cell membrane and therefore increased secretion of proinsulin.

ADRs include weight gain and hypoglycaemia (but less than for sulhponylureas).

Question 4

Thiazolidinediones (TZDs) (2)

Answer 4

Rosiglitazone, Pioglitazone

TZDs activate PPARs (peroxisome proliferater-activated receptors). These are nuclear receptors which have greatest specificity for PPAR-gamma. When these receptor are activated, they increase transcription of specific genes and decrease transcription of others. The main effect of this expression is to increase storage of fatty acids that are present in the circulation. As a result of this, cells become more dependent on oxidation of carbohydrates (more specifically glucose) in order to yield energy for cellular processes.

Main ADRs include - water retention (resultin in oedema) and there may be an increased risk of coronary heart disease from rosiglitazone (but not Pioglitazone)

Question 5

Other treatment of Diabetes Mellitus Type II (4)

Answer 5

Alpha-glucose case inhibitors
Glucagon-like Peptide I (GLP-1) analogues
Dipeptidyl-peptidase 4 (DPP4) Inhibitors
Sodium-glucose co-transporter 2 inhibitors

Question 6

Thyroid Disease drugs (2)

Answer 6

Levothyroxine and Carbimazole

Levothyroxine is a synthetic thyroid hormone that is chemically identical to T4. Therefore it mimics the T4 produced normally by thyroid follicular cells and so is used in the treatment of hypothyroidism.
ADRs include cardiac side-effects and decreased bone mineral density (as a result of long term TSH suppression).

Carbimazole is used to treat hyperthyroidism. It prevents the iodination of tyrosine residues on thyroglobulin so reduced the production of T3 and T4. ADRs include rashes and pruritus (skin itchiness) and rarely (but severely) bone marrow suppression causing neutropenia and agranulocytosis.

Question 7

Corticosteroids (6)

Answer 7

Fludrocortisone
Hydrocortisone
Betamethasone
Hydrocortisone
Prednisolone
Dexamethasone

Corticosteroids are used to treat inflammatory diseases, malignancy and adrenal insufficiency as well as cause immunosuppression (e.g. For acute transplant rejection). Dexamethasone is used in the diagnosis of Cushing’s disease (dexamethasone suppression test).

Question 8

Hormone Replacement Therapy (HRT) (2)

Answer 8

Oestradiol, medroxyprogesterone

Progesterone actions: secretory endometrium, anabolic, increased bone density
Progesterone ADRS: weight gain, fluid retention, mood changes, nausea and vomiting, irritability, lack of concentration.

Oestrogen actions: mild anabolic, raise HDL and lower LDL, decrease bone reabsorption, improve blood coagulability.
Oestrogen ADRs: nausea, vomiting, water retention, increased risk of thromboembolism, impaired glucose tolerance, endometrial hyperplasia and cancer.

Question 9

Insulins (5)

Answer 9

Actrapid, Humulin S, Novorapid (short acting), Insulin Glargine, Isophane Insulin (e.g. Humulin I).

Question 10

Anti-Oestrogens (SERMS) (2)

Answer 10

Clomiphene and Tamoxifen

Clomiphene is an oestrogen antagonist at the anterior pituitary gland that induces ovulation by inhibiting negative feedback.

Tamoxifen acts as an anti-oestrogenic at breast tissue (decreased risk of breast cancer by 50%) but acts as an oestrogenic in the endometrium (increased risk of endometrial carcinoma). It protects against osteoporosis.