Endocrine pharmacology revision Flashcards
Growth hormone synthesised in
Somatotrophe cells of the anterior pituitary
GH secretion controlled by
Hypothalamus via
- GHRH
- GHRIH
Second messengers with GH
Insulin like growth factor 1
Insulin like growth factor 2
Primary effect of GH
Promote the linear growth of adolescence
Increases protein synthesis and collagen deposition
Also involved in tissue turnover and repair
GH at physiological concentrations
Mimics the actions of insulin on carbohydrates
GH at high concentrations
Diabetogenic
Use of GH
Treat deficiency of hormone in adults and children
In children used in Prader-WIlli, Turner’s and chronic renal insufficiency
Somatotropin
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
Somatomedins
Polypeptide hormone structurally related to insulin, known as IGFs
Mecasermin
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
Growth hormone receptor antagonist example
Pegvisomant
Pegvisomant
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
Thyroid hormone use
Hypothyroidism
Non- toxic goitre
Hashimoto’s thyroiditis
Thyroid carcinoma
Thyroid hormone treatment of choice
Levothyroxine sodium
Levothyroxine sodium
Cautions: panhypopituitarism, elderly, CV disorders, long standing hypothyroidism, MI, DM, pregnancy
Side effects: diarrhoea, vomiting, anginal pain, arrhythmias, palpitation, tachycardia, tremor, headache, flushing
Thyrotrophin
Recombinant form of thyrotrophin
Use with or without radioiodine imaging for detection of thyroid remnants and thyroid cancer in post thyroidectomy patients
Antithyroid drugs
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
Carbimazole
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
Carbimazole side effects
Rashes and pruritis
Neutropeania
Agranulocytosis
Tetragenic
Propylthiouracil
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
Propylthiouracil adverse effects
Rashes and pruritis
Agranulocytosis
Serious liver injury (liver failure and death)
Oestrogens
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
Hormone replacement therapy
Small dose of oestrogen alleviates menopausal symptoms such as vaginal atrophy or vasomotor instability
Combined oral contraceptive
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
Combined oral contraceptive adverse effects
Nausea and vomiting
Abdominal cramps
Fluid retention
Changes in body weight
Hepatic impairment
DVT
Breast tenderness
Cervical erosion
Migraine
Progestogen only oral contraceptive
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
Progestogen only oral contraceptive adverse effects
Menstrual irregularity
Nausea and vomiting
Headache
Breast discomfort
Weight changes
Changes in libido
Two subtypes of oestrogen receptor
ERalpha: hypothalamus, breast, endometrium
ERbeta: bone and brain
Selective oestrogen receptor modulator
SERM
e.g. raloxifen
Selectively acts on oestrogen receptor of bone and is used to prevent osteoporosis
Raloxifen hydrochloride
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
Tibolone
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
Anti-oestrogens
e.g. tamoxifen, clomifene
Used in the treatment of fertility due to oligomenorrhoea or secondary amenorrhoea
Induce gonadotrophin by occupying oestrogen receptors in hypothalamus
Breast cancer management
Surgery, radiotherapy, drug therapy
Tamoxifen effective in premenopausal, perimenopausal and postmenopausal women
Gonadotrophin
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
Hypothalamic hormones
Gonadorelin leads to rapid rise in plasma LH and FSH
Indicated in endometriosis and infertility and breast and prostate cancer
Long term GnRH
Suppresses LH and FSH
Stops oestrogen and testosterone
Used in cancers instead of tamoxifen or anti-androgen
