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BSMS203 endocrinology (Theme 1) > 22. Pharmacology revision > Flashcards

22. Pharmacology revision Flashcards

1
Q

In what ways do drugs act?

A

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

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2
Q

Name 14 hormones

A 
Growth Hormone
Prolactin
Oxytocin
ADH
Thyroid hormones
Parathyroid hormone / Vitamin D
Calcitonin
Insulin
Adrenaline
Glucocorticoids
Mineralocorticoids
Oestrogens
Progesterone
Androgens
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3
Q

Where is growth hormone made?

A

Growth hormone is synthesised in the somatotrophe cells of the anterior pituitary gland

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4
Q

Secretion of growth hormone controlled by?

A 
Hypothalamus via:
Growth Hormone Releasing Hormone (GHRH)
and
Growth Hormone Release Inhibiting Hormone 
(GHRIH, somatostatin).
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5
Q

How does GH act in some tissues?

A 
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
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6
Q

Effect of GH

A

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.

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7
Q

Growth hormone used pharmacologically to treat

A

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.
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8
Q

GH contraindications

A

tumours, renal transplantation, closed epiphyses, Prader-Willi syndromes, severe obesity, severe respiratory impairment in Prader-Willi syndrome, pregnancy

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9
Q

GH side effects

A

Headaches, nausea, vomiting, diarrhoea, visul problems, cardiomegaly, ventricular hypertrophy, tachycardia, convulsions

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10
Q

Somatomedins?

A

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.

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11
Q

Mecasermin

A

IGF-I analogue
Corrects hypothyroidism before initiating treatment, diabetes mellitus, growth failure in children and adolescents with IGF-I deficiency
Contraindicated in tumours

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12
Q

Growth hormone receptor antagonists

A

e.g. pegvisomant
Used to treat acromegaly in patients with inadequate response to surgery, radiation or both, and to treatment with somatostatin analogues

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13
Q

when are thyroid hormones used?

A

hypothyroidism (myxoedema)
diffuse non-toxic goitre
Hashimoto’s thyroiditis (lymphadenoid goitre)
thyroid carcinoma

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14
Q

What are some thyroid hormone agonists?

A 
levothyroxine soidum
liothyronine sodium (faster effect)
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15
Q

levothyroxine sodium

A

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

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16
Q

Liothyronine sodium

A

Thyroid hormone agonist

More rapidly metabolised with a more rapid effect than levothyroxine sodium

17
Q

thyrotrophin use

A

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

18
Q

Antithyroid drugs

A

Used for hyperthyroidism
Either to prepare for thyroidectomy or for long-term management
Interfere with synthesis of thyroid hormones
Carbimazole most commonly used
Propylthiouracil

19
Q

Carbimazole

A

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.

20
Q

Propylthiouracil (PTU)

A 
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

21
Q

Oestrognes and HRT

A

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

22
Q

HRT risks

A 
Breast cancer
Endometrial cancer
Ovarian cancer
Venous thromboembolism
Stroke
Coronary heart disease
23
Q

Combined oral contraceptive

A

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

24
Q

Adverse effects of combined oral contraceptive pill

A

Nausea, vomiting, abdominal cramps, fluid retention, changes in body weight, hepatic impairment, cardiovascular changes including DVT, breast tenderness, cervical erosion

25
Q

Progesterone-only oral contraceptive

A

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.

26
Q

Oestrogen receptors and drugs

A

ER-alpha is found in the hypothalamus, breast and endometrium
ER-beta is found in bone and brain

27
Q

SERMs

A

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

28
Q

Raloxifene

A

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

29
Q

Tibolone

A

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

30
Q

Anti-oestrogens

A

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.

31
Q

Breast cancer

A

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

32
Q

Gonadotrophins

A

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

33
Q

Human menopausal gonadotrophins (HMG)

A

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

34
Q

Hypothalamic hormones

A

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

35
Q

What do gonadorelin analogues do?

A

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

36
Q

What are gonadorelin analogues used for?

A

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

BSMS203 endocrinology (Theme 1) (26 decks)

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