Endocrine pharmacology revision

Question 1

Growth hormone synthesised in

Answer 1

Somatotrophe cells of the anterior pituitary

Question 2

GH secretion controlled by

Answer 2

Hypothalamus via

• GHRH
• GHRIH

Question 3

Second messengers with GH

Answer 3

Insulin like growth factor 1

Insulin like growth factor 2

Question 4

Primary effect of GH

Answer 4

Promote the linear growth of adolescence

Increases protein synthesis and collagen deposition

Also involved in tissue turnover and repair

Question 5

GH at physiological concentrations

Answer 5

Mimics the actions of insulin on carbohydrates

Question 6

GH at high concentrations

Answer 6

Diabetogenic

Question 7

Use of GH

Answer 7

Treat deficiency of hormone in adults and children

In children used in Prader-WIlli, Turner’s and chronic renal insufficiency

Question 8

Somatotropin

Answer 8

Cautions: diabetes mellitus, malignant disease, intracranial hypertension

Contraindications: evidence of tumour activity, not to be used after renal transplantation

Side effects: headache, visual problems, nausea and vomiting, athraglia, myalgia, carpal tunnel syndrome, parasthesia, hyperglycaemia

Question 9

Somatomedins

Answer 9

Polypeptide hormone structurally related to insulin, known as IGFs

Question 10

Mecasermin

Answer 10

Human insulin like growth factor

Treat growth failure in children and adolescents with severe IGF1 deficiency

Side effects: headaches, cardiomegaly, tachycardia, sleep apnoea, night terrors

Question 11

Growth hormone receptor antagonist example

Answer 11

Pegvisomant

Question 12

Pegvisomant

Answer 12

Highly selective growth hormone receptor antagonist

Treatment of acromegaly without response to surgery and radiation

Contraindications: pregnancy and breast feeding

Side effects: diarrhoea, constipation, nausea, vomiting, abdominal distension, dyspepsia, flatulence, hypertension, tremor, weight gain

Question 13

Thyroid hormone use

Answer 13

Hypothyroidism

Non- toxic goitre

Hashimoto’s thyroiditis

Thyroid carcinoma

Question 14

Thyroid hormone treatment of choice

Answer 14

Levothyroxine sodium

Question 15

Levothyroxine sodium

Answer 15

Cautions: panhypopituitarism, elderly, CV disorders, long standing hypothyroidism, MI, DM, pregnancy

Side effects: diarrhoea, vomiting, anginal pain, arrhythmias, palpitation, tachycardia, tremor, headache, flushing

Question 16

Thyrotrophin

Answer 16

Recombinant form of thyrotrophin

Use with or without radioiodine imaging for detection of thyroid remnants and thyroid cancer in post thyroidectomy patients

Question 17

Antithyroid drugs

Answer 17

Used for hyperthyroidism to prepare for thyroidectomy or for long term management

Carbimazole is the most commonly used drug

Propylthiouracil in patients sensitive to carbimazole

Both act by interfering with thyroid hormone synthesis

Question 18

Carbimazole

Answer 18

Used to treat hyperthyroidism

Pro-drug, converted to active form methimazole which prevents peroxidase iodinating the tyrosine residues so less T3 and T4 production

Oral bioavailability: >90%
Protein binding: 85%
Excretion: 90% in urine as metabolites

Question 19

Carbimazole side effects

Answer 19

Rashes and pruritis

Neutropeania

Agranulocytosis

Tetragenic

Question 20

Propylthiouracil

Answer 20

Used to threat hyperthyroidism

Inhibits thyroperoxidase and tetraiodothyronine deiodinase so less T4 to T3

Drug of choice in first trimester

Oral bioavailability: 80-95%
Protein binding: 70%
Excretion: renal

Question 21

Propylthiouracil adverse effects

Answer 21

Rashes and pruritis

Agranulocytosis

Serious liver injury (liver failure and death)

Question 22

Oestrogens

Answer 22

Necessary for development of female secondary sexual characteristics

Stimulate myometrial hypertrophy with endometrial hyperplasia

Natural oestrogens have more appropriate profile for HRT

Oestrogen therapy given cyclically or continuously

Question 23

Hormone replacement therapy

Answer 23

Small dose of oestrogen alleviates menopausal symptoms such as vaginal atrophy or vasomotor instability

Question 24

Combined oral contraceptive

Answer 24

Mixture of oestrogen and progestogen

Progestogen inhibits ovulation by LH suppression, thickens cervical mucus and renders endometrium hostile

Oestrogen prevents follicular development by suppression of FSH

Oral bioavailability: 40-55% (EE), 65-80% (NOR)
Protein binding: high
Metabolism: hepatic
Excretion: faeces and urine

Question 25

Combined oral contraceptive adverse effects

Answer 25

Nausea and vomiting Abdominal cramps Fluid retention Changes in body weight Hepatic impairment DVT Breast tenderness Cervical erosion Migraine

Question 26

Progestogen only oral contraceptive

Answer 26

e.g. norethisterone, levonorgestrel, desogestrel Inhibit ovulation by suppression of LH surge, thicken cervical mucus and render the endometrium hostile Oral bioavailability: 65-80% Protein binding: high Excretion: faeces and urine

Question 27

Progestogen only oral contraceptive adverse effects

Answer 27

Menstrual irregularity Nausea and vomiting Headache Breast discomfort Weight changes Changes in libido

Question 28

Two subtypes of oestrogen receptor

Answer 28

ERalpha: hypothalamus, breast, endometrium ERbeta: bone and brain

Question 29

Selective oestrogen receptor modulator

Answer 29

SERM e.g. raloxifen Selectively acts on oestrogen receptor of bone and is used to prevent osteoporosis

Question 30

Raloxifen hydrochloride

Answer 30

Cautions: VTE, breast cancer, hypertriglyceridaemia Contraindications: VTE, uterine bleeding, endometrial cancer, hepatic impairment, cholestasis, severe renal impairment, pregnancy and breast feeding Side effects: VTE, hot flushes, leg cramps, peripheral oedema, influenza like symptoms, GI disturbances, hypertension

Question 31

Tibolone

Answer 31

Has oestrogenic, progestogenic and weak androgenic properties Used in short term treatment of oestrogen deficiency, osteoporosis prophylaxis Cautions: vaginal bleeding, renal impairment, liver disease, epilepsy, migraine Contraindications: hormone dependent tumours, CV or cerebrovascular disease Side effects: abdominal pain, weight changes, vaginal bleeding, facial hair, amnesia

Question 32

Anti-oestrogens

Answer 32

e.g. tamoxifen, clomifene Used in the treatment of fertility due to oligomenorrhoea or secondary amenorrhoea Induce gonadotrophin by occupying oestrogen receptors in hypothalamus

Question 33

Breast cancer management

Answer 33

Surgery, radiotherapy, drug therapy Tamoxifen effective in premenopausal, perimenopausal and postmenopausal women

Question 34

Gonadotrophin

Answer 34

FSH and LH used in treatment of infertility in women with hypopituitarism Occasionally used in hypogonadotrophic hypogonadism Contraindications: ovarian cysts, tumours (pituitary, hypothalamus, breast, uterus, ovaries, testes, prostate), vaginal bleeding Side effects: ovarian hyperstimulation, multiple pregnancies, miscarriage, hypersensitivity reactions, GI disturbances, headaches, joint pain

Question 35

Hypothalamic hormones

Answer 35

Gonadorelin leads to rapid rise in plasma LH and FSH Indicated in endometriosis and infertility and breast and prostate cancer

Question 36

Long term GnRH

Answer 36

Suppresses LH and FSH Stops oestrogen and testosterone Used in cancers instead of tamoxifen or anti-androgen