22. Pharmacology revision Flashcards
In what ways do drugs act?
Mimic a natural transmitter / hormone: An agonist
Block the effects of a natural transmitter / hormone: An antagonist
Induce synthesis of a natural transmitter / hormone
Block synthesis of a natural transmitter / hormone
Induce metabolism / breakdown of a natural transmitter / hormone
Block metabolism / breakdown of a natural transmitter / hormone
Name 14 hormones
Growth Hormone Prolactin Oxytocin ADH Thyroid hormones Parathyroid hormone / Vitamin D Calcitonin Insulin Adrenaline Glucocorticoids Mineralocorticoids Oestrogens Progesterone Androgens
Where is growth hormone made?
Growth hormone is synthesised in the somatotrophe cells of the anterior pituitary gland
Secretion of growth hormone controlled by?
Hypothalamus via: Growth Hormone Releasing Hormone (GHRH) and Growth Hormone Release Inhibiting Hormone (GHRIH, somatostatin).
How does GH act in some tissues?
In some tissues, GH acts via second messengers which are produced in the liver. Via Insulin-like growth factor 1 and Insulin-like growth factor 2
Effect of GH
The primary effect of GH is to promote the linear growth of adolescence by increasing protein synthesis and collagen deposition. This is mediated via the nucleus.
Foetal growth is relatively independent of GH
GH is also involved in tissue turnover and repair.
At physiological concentrations GH mimics the actions of insulin on carbohydrates (IGF1 & 2)
At high concentrations GH is diabetogenic.
Growth hormone used pharmacologically to treat
deficiency of the hormone in children and in adults
In children it is used in:
- Prader-Willi syndrome
- Turner’s syndrome
- in chronic renal insufficiency
- short children considered small for gestational age at birth.
GH contraindications
tumours, renal transplantation, closed epiphyses, Prader-Willi syndromes, severe obesity, severe respiratory impairment in Prader-Willi syndrome, pregnancy
GH side effects
Headaches, nausea, vomiting, diarrhoea, visul problems, cardiomegaly, ventricular hypertrophy, tachycardia, convulsions
Somatomedins?
Insulin like growth factors
Group of peptides structuarally related to insulin
Mecasermin is a IGF-I which is the principle mediator of somatotropic effects of human GF and is used to treat growth failure in children and adolescents with IGF-I deficiency.
Mecasermin
IGF-I analogue
Corrects hypothyroidism before initiating treatment, diabetes mellitus, growth failure in children and adolescents with IGF-I deficiency
Contraindicated in tumours
Growth hormone receptor antagonists
e.g. pegvisomant
Used to treat acromegaly in patients with inadequate response to surgery, radiation or both, and to treatment with somatostatin analogues
when are thyroid hormones used?
hypothyroidism (myxoedema)
diffuse non-toxic goitre
Hashimoto’s thyroiditis (lymphadenoid goitre)
thyroid carcinoma
What are some thyroid hormone agonists?
levothyroxine soidum liothyronine sodium (faster effect)
levothyroxine sodium
thyroid hormone agonist used as treatment of choice for maintenance therapy
Dose titred according to clinical response in infants and children with congenital hypothyrodism and juvenile myxodema
Liothyronine sodium
Thyroid hormone agonist
More rapidly metabolised with a more rapid effect than levothyroxine sodium
thyrotrophin use
aka thyroid stimulating hormone
thyrotropin alfa is recombinant form
used for detection of thyroid remnants and thyroid cancer after thyroidectomy
used with or without radioidine imaging, and with serum thyroglobulin testing
Antithyroid drugs
Used for hyperthyroidism
Either to prepare for thyroidectomy or for long-term management
Interfere with synthesis of thyroid hormones
Carbimazole most commonly used
Propylthiouracil
Carbimazole
treats hyperthyroidism
prodrug which is converted to active form methimazole after absorption
Prevents peroxidase iodinating the tyrosine residues on thyroglobulin
reducing production of thyroid hormones T3 and T4
Good oral bioavailability
Adverse effects: rashes and pruritus (treat with antihistamines). Neutropenia, agranulocytosis, teratogenic.
Propylthiouracil (PTU)
treats hyperthyroidism (including Grave's). Inhibits thyroperoxidase, which acts in thyroid hormone synthesis Also inhibits tetraiodothyronine deiodinase which converts T4 to T3.
Drug of choice to treat hyperthryodisim in 1st trimester (non-teratogenic)
good oral bioavailability, hepatic metabolism
Adverse effects: rashes, puritus, agranulocytosis, serious liver injury inc liver failure and death
Oestrognes and HRT
HRT uses small doses of oestrogen with some progesterone to stop cystic hyperplasia of the endometrium
Alleviates menopausal symptoms such as vaginal atrophy or vasomotor instability
Diminishes post-menopausal osteoperosis
Should only be given for a few years after menopause to stop osteoperosis, reduced libido etc then stopped because of side effects and risks
HRT risks
Breast cancer Endometrial cancer Ovarian cancer Venous thromboembolism Stroke Coronary heart disease
Combined oral contraceptive
mixture of an eostrogen (usually ethinyloestradiol) and a progesterone (usually northisterone)
Progesterone inhibits ovulation by:
suppressing LH surge
thickening cervical mucus
rendering endometrium hostile
Oestrogen stops follicular development by suppressing FSH (negative feedback)
Bioavailability 40-50%. Tablet taken daily for 21 days with 7 drug-free days
Adverse effects of combined oral contraceptive pill
Nausea, vomiting, abdominal cramps, fluid retention, changes in body weight, hepatic impairment, cardiovascular changes including DVT, breast tenderness, cervical erosion
Progesterone-only oral contraceptive
E.g. norethisterone, levonorgestrel, desogestrel
Inhibit ovulation by:
- suppressing LH surge
- thickening cervical mucous
- rendering endometrium hostile
oral bioavailability is 60-85%.
Adverse effects: menstrual irregularity, nausea, vomiting, headache, breast discomfort, weight changes, libido changes.
Oestrogen receptors and drugs
ER-alpha is found in the hypothalamus, breast and endometrium
ER-beta is found in bone and brain
SERMs
Some drugs are agonists at one oestrogen receptor subtype but antagonists at other e.g. tamoxifen is an antagonist at ER-alpha but an agonist at ER-beta. Called Selective oestrogen receptor modulators (SERMS)
e.g. Raloxifene, selectively acts on oestrogen receptors of bone, used to prevent osteoperosis
Raloxifene
Raloxifene hydrochloridde
selective oestrogen receptor modulator (SERM)
used to treat and prevent postmenopausal osteoperosis
risks: venous thromboembolism, breast cancer, oestrogen-induced hypertriglyceridaemia
Contraindications: venous thromboembolism history, undiagnosed uterine bleeding, endometrial cacner, hepatic impairment, cholestasis, severe renal impairment, pregnancy and breast-feeding
Side effects: venous thromboembolism, thrombophlebitis, hot flushes, leg cramps, peripheral oedema, influenza-like symptoms
Tibolone
used in short-term treatment of oestrogen deficiency, e.g. hormone replacement therapy, or osteoperosis prophylaxis in women at risk of fractures
cautions: vaginal bleeding (investigate for endometrial cancer if bleeding continues beyond 6 months or after stopping treatment), renal impairment, liver disease histroy, epilepsy, migraine, diabetes mellitus
Contrainidications: hormone-dependent tumours, history of cardiovascular or cerebrovascular disease, uninvestigated vaginal bleeding, severe liver disease, pregnancy, breast-feeding
side effects: abdominal pain, weight changes, vaginal bleeding, leucorrhoea, faial hair
Anti-oestrogens
e.g. clomifene and tamoxifen
used to treat female infertility due to oligomenorrea or secondary amenorrhoea (e.g. associated with PCOS)
Induce gonadotrophin release by occupying oestrogen receptors in the hypothalamus, interfering with feedback mechanisms.
Risk of multiple pregnancies with this.
Breast cancer
managed by surgery, radiotherapy, drug therapy, or combination of these
For operable breast cancer, treatment before surgery reduces size of the tumour and facilitates breast-conserving surgery. Hormone antaogonist therapy e.g. letrozole is chosen for steroid hormone-receptor-positive breast cancer and chemotherapy for steroid hormone-receptor-negative tumours or for younger women.
Use tamoxifen in premenopausal, perimenopausal and and postmenopausal women
Aromatase inhibitors effective in postmenopausal women only - anastroxole, exemestane, letrozole
Gonadotrophins
FSH and LH or chorionic gonadotrophin used to treat women with infertility due to hypopituitarism or not responding to clomifene or in superovulation treatment for assisted conception
Can also be used for hypogonadotrophic hypogonadism and associated oligospermia
Chorionic gonadotrophin can also be used in delayed puberty in males to stimulate endogenous testosterone
Human menopausal gonadotrophins (HMG)
Used to promote ovulation and in fertility treatments. Mix of LH and FSH. Derived from the urine of post-menopausal women.
Cautions: rule out infertility caused by hypothyroid, adrenocortical deficiency, hyperprolactinaemia, or pituitary/hypothalamus tumouts
Contraindications: ovarian cysts (not PCOS), tumours of pituitary, hypothalamus, breast, uterus, ovaries, testes or prostate, pregnancy and breast-feeding
Side effects: ovarian hyperstimulation, increased risk of multiple pregnancy and miscarriage, hypersensitivity reactions, GI distubrances, headache, gynaecomastia, joint pain, fever
Hypothalamic hormones
e.g. gonadorelin
when injected leads to rapid rise in plasma LH and FSH.
Can be given to treat endometriosis or infertility.
If give for long period of time, longer than a few days, LH and FSH become downregulated, so giving GnRH for a few days suppresses FSH and LH.
Given when want to stop oestrogen production in females and testosterone in males - e.g in breast and prostate cancer
What do gonadorelin analogues do?
Gonadorelin is a GnRH analogue.
produces initial phase of stimulation of gonadotrophins
using this continuously leads to down-regulation of gonadotrophin-releasing hormone (GnRH) receptors, thereby reducing gonadotrophin (FSH and LH) release, leading to inhibition of androgen and oestrogen production
What are gonadorelin analogues used for?
treatment endometriosis, precocious puberty, infertility, anaemia due to uterine fibroids, breast cancer, prostate cancer, before intra-uterine surgery.
Cautions: need to use non-hormonal, barrier methods of contraception
