Block 7 Drugs

Question 1

Carbimazole (Neomercazole)

Answer 1

Blocks thyroid peroxidase -> prevent coupling of iodide with iodotyrosine molecules to form triiodothyronine (T3) and thyroxine (T4)

Used for thyrotoxicosis (1st line except for pregnancy)

1/2 life: 8 hrs

Question 2

Propyl-thiouracil (PTU)

Answer 2

Blocks thyroid peroxidase & 5’-deiodinase (which converts T4 to T3 peripherally) -> less active metabolite in blood stream and lowered thyroid hormone production

Used for thyrotoxicosis (if pregnant or other contraindications to carbimazole)

1/2 life: 2 hrs

Question 3

Thyrogen

Answer 3

Recombinant human TSH to prepare patients for remnant ablation therapy without the need for thyroxine withdrawal

Question 4

Thyroxine (T4)

Answer 4

T4

Treatment for hypothyroidism

Question 5

Cabergoline

Answer 5

Dopamine agonist (ergot) -> inhibit synthesis and release of prolactin & reduce serum prolactin

Question 6

Octreotide

Answer 6

Synthetic somatostatin analogue -> decrease GH levels & tumour size (pituitary tumour, GH secreting)

Question 7

Ketoconazole

Answer 7

Anti fungal agent that inhibits adrenal steroidogenesis

Question 8

Indications for medical therapy for pituitary tumour

Answer 8

1. Patients unsuitable for surgery

2. Recurrent tumour after surgery or radiation

Question 9

Metabolic Syndrome (X)

Answer 9

Type 2 Diabetes
Hypertension
Abdominal obesity
Dyslipidaemia (Low HDL, High TGs, Normal/elevated LDL)

Question 10

Biguanides (1st line)

Answer 10

Metformin

1. Increased glucose uptake into skeletal muscle and fat
2. Decreased gluconeogenesis
3. Apetite suppression (due to gastric irritation?)
4. Decreased intestinal glucose absorption

Excreted in kidneys (accumulate in renal failure)

Question 11

Sulphonylureas (2nd line)

Answer 11

Bind to sulphonylurea receptors linked to ATP dependent K+ channels on beta cells of pancreas -> close K+ channel -> increase intracellular K+ -> increase intracellular Ca2+ -> potentiate glucose stimulated insulin release

GLIBENCLAMIDE (long), GLICAZIDE, GLIPIZIDE

SE: weight gain

Question 12

Meglitinide agents

Answer 12

Modified sulphonylureas

Stimulates same receptor but at slightly different site (do not x react w/ sulphonylureas)

Used in ppl with sulphonylurea allergy

REPAGLINIDE (short acting)

Withdrawan from Australian market due to lack of demand, not currently available in Australia

Question 13

Alpha-Glucosidase Inhibitors

Answer 13

Inhibits alpha-glucosidase that breaks down dietary complex carbohydrates to sugars on intestinal brush border -> delayed sugar hydrolysis & glucose absorption -> reduce post-prandial hyperglycaemia

ACARBOSE

SE: malabsorption of carbohydrates due to fermentation of colonic bacteria -> abdominal distension, pain & flatulence

Question 14

Glitazones (Thiazolidinediones)

Answer 14

Inducing Peroxisome Proliferator Receptors (PPAR-gamma) in fat cells -> increase insulin sensitivity

SE: substantial weight gain

ROSIGLITAZONE, PIOGLITAZONE, TROGLITAZONE (1st gen, liver failure in some)

Question 15

DPP-IV inhibitors

Answer 15

Gliptins

Inhibit activity of enzyme DPP-4 which rapidly breaks down gut hormone GLP-1 (glucagon like peptide 1) & GIP (gastric inhibitory peptide)

GLP-1 & GIP are INCRETINS which…

1. Stimulate glucose dependent insulin release from pancreas following oral glucose load
2. GLP-1 inhibits secretion of glucagon
3. GLP-1 reduces gastric emptying time to delay glucose absorption

SITAGLIPTIN, VILDAGLIPTIN, SAXAGLIPTIN, LINAGLIPTIN (under PBS)

All hepatically metabolised except linagliptin (renal)

Question 16

SGLT-2 Inhibitors

Answer 16

Prevent glucose reabsorption from proximal renal tubule by inhibiting at the site ATP dependent Na+/GLUT co-transporter

DAPAGLIFOZIN

SE: Increase genitourinary tract infections

Question 17

Treatment of STIs

Answer 17

Azithromycin -> Chlamydia
Metronidazole -> Anaerobes
Ceftriaxone -> Gonorrhoea & gram -ve rods

Question 18

Prostaglandin synthetase inhibitors

Answer 18

Inhibit synthesis of prostaglandins

May also interfere with myometrial binding of prostaglandin E2 (FENAMATES)

FENAMATES

20-40% reduction in menstrual blood loss

Tx for abnormal menstrual bleeding -> reduce by 20-30%

Question 19

DDAVP (Desmopressin)

Answer 19

Synthetic ADH (vasopressin)

Tx for Diabetes Insipidus (posterior pituitary ADH deficiency)

Question 20

Ethinyl Estradiol

Answer 20

Pubertal induction in girls

Question 21

Andriol

Answer 21

Pubertal induction in boys

Question 22

Cyclical progestogen therapy

Answer 22

Medroxyprogesterone acetate
Norethisterone
Dydrogesterone

DEPO PROVERA (long acting injectable) 
IMPLANON (subcut removable rod)

Tx for anovulatory dysfunctional uterine bleeding but less effect on ovulatory type

Question 23

Combined estrogen-progestogen formulation

Answer 23

This is the OCP

Reduction in menstrual blood loss 40-50%
Regulates menstrual cycle
Well tolerated

Safe in older women up to age of menopause IF they do not have hx of HT, smoking or VTEs (venous thromboembolic disorders)

Question 24

Danazol

Answer 24

Derivative of 17 alpha ethinyl testosterone

1. Inhibits endometrial proliferation & cause endometrial atrophy
2. Displaces oestrogen from receptors
3. Reduces pituitary gonadotrophins
4. Inhibits enzymes involved in ovarian steroidogenesis

Tx for heavy menstrual bleeding

Duration of use limited by androgenic SEs

Question 25

GnRH agonists

Answer 25

Induce down-regulation of the pituitary with with initial agonist phase followed by exhaustion of pituitary -> amenorrhoea or oligomenorrhoea

LT use -> decreased bone mass -> should be limited to 6 months

GOSERELIN, NAFARELIN

Question 26

Progestogen releasing intrauterine system

Answer 26

Decreases menstrual loss by 80-90% after 12 months
Amenorrhoea in ~50% of women after 12 months

Very effective contraception

FIRST LINE for menstrual bleeding disorders in Australia

Realistic alternative to surgery

Change every 5 yrs