Thyroid hormones, Ecbolics,

Tocolytics & Others

Dr Sayeda Khanom
MBBS, MD
Objectives
• Thyroid hormones (thyroxine/levothyroxine, T4;
liothyronine, T3)
• Use of thyroid hormone: treatment of
hypothyroidism
• Antithyroid drugs & hyperthyroidism:
thionamides, drugs that block sympathetic
autonomic activity, iodide & radioiodine 131I,
preparation of patients for surgery, thyroid storm
(crisis), exophthalmos
• Drugs that cause unwanted hypothyroidism
Thyroid hormone
• Natural hormones of thyroid gland
– L-thyroxine/levothyroxine (T₄ or tetraiodo-L-
thyronine)
– liothyronine (T₃ or triiodo-L-thyronine)
• T₄: main circulating hormone, less active
precursor of T₃
• T₃: major mediator of physiological effect
• Both forms are available for oral use as therapy
Thyroid hormone
• Synthesis: Oxidation of dietary I → iodination of tyrosine
to mono- & diiodotyrosine → coupling of iodotyrosines
→ tetraiodotyronine & triiodotyronine
• Storage: in thyroglobulin in intrafollicular colloid
• Release: reuptake of colloid by apical cells → proteolysis
→ circulation
• 80% T4: deiodinated in peripheral tissues → active T3 &
inactive reverse T3
• Metabolism: Liver → further deiodination
• T4, T3: extensively (99.9%) bound to pl. proteins
– thyroxine-binding globulin (TBG)
– thyroxine-binding prealbumin (TBPA)
• ↑TBG: -oestrogens (OCP)
-prolonged use of neuroleptics
-pregnancy
• ↓TBG: -adrenocortical & androgen therapy
-urinary protein loss (NS)
• Phenytoin, salicylates: compete for TBG
• T4, T3: well absorbed from gut, except in myxoedema
coma (parenteral therapy)
• T4:
– PPB strong, extensive
– single dose reaches maximum effect in 10 days
– passes off in 2-3 weeks
• T3:
– 5 times potent than T4
– PPB weak
– single dose reaches maximum effect in 24 h
– passes off in one week
Pharmacodynamics
• TH passes into the cells of target organs → combines with
specific nuclear receptors → induces characteristic
metabolic changes:
– Protein synthesis during growth
– ↑metabolic rate ē ↑O₂ consumption
– ↑sensitivity to catecholamines ē proliferation of β-
adrenoceptors
Levothyroxine: clininal uses
• Treatment of deficiency (cretinism, adult hypothyroidism)
from any cause
– Adults monitored annually, dose not altered once
optimum found
– Monitoring frequent in children, ↑dose as they grow
– pregnant women monitored monthly, ↑50-100% dose
• Hypothyroidism due to panhypopituitarism
– replacement ē adrenocortical hormone & TH
– T4 alone can cause acute adrenal insufficiency
• Treatment of nontoxic nodular goiter
Treatment of hypothyroidism
1. Levothyroxine
• In old & patients ē heart disease/HTN: gradual ↑dose
(↓cardiovascular risk due to sudden ↑metabolic
demand)
• Single daily dose
• Plasma TSH: indicator of adequate treatment
• Absorption more complete & less variable: if taken well
apart from food
• Hypothyroid patients tend to be intolerant of drugs
owing to delayed metabolism
2. Liothyronine
• Tabs.: most rapidly effective, can induce heart failure (not
used in routine treatment of hypothyroidism)
• Main uses: myxoedema coma, psychosis
• Specialised use: during withdrawal of levothyroxine
replacement (to permit diagnostic radioiodine scanning)
in thyroid carcinoma
Myxoedema coma: prolonged total hormone deficiency;
emergency
– IV therapy: impaired absorption of oral drugs
– Liothyronine, 5-20 μg every 12 hrs
– Hydrocortisone i.v. (prolonged hypothyroidism →
adrenocortical insufficiency)
Subclinical hypothyroidism: patients ē normal free T4, but
elevated TSH
• Indications for treatment: symptoms of hypothyrodism,
presence of goitre, detectable thyroid antibodies or
hypercholesterolemia
Adverse effects
• Parallel increase in metabolic rate
• S/S of hyperthyroidism
• Myocardial ischemia, atrial fibrillation, heart failure
– T4 discontinued for a week & begun again at lower
dosage
– Slight overdose precipitate AF in patients >60 years
• Breast feeding not contraindicated: baby's thyroid status
should be watched
Antithyroid drugs
• Thionamides: block synthesis of thyroid hormone
• Iodine:
➢Radioiodine → destroys cells making TH
➢Iodide → excess iodide ↓production of TH temporarily
by unknown mechanism (both excess & deficiency can
cause goitre)
• Beta blockers
Thionamides (thiourea derivatives)
• Carbimazole, methimazole, propylthiouracil
Mode of action
1. ↓formation of TH by Θ oxidation & organisation of
iodine (iodotyrosines)
2. Θ coupling of iodotyrosines to form T4 & T3
→ Intrathyroidal iodine deficiency
• Maximum effect delayed until existing TH stores
exhausted (weeks)
• High dosage: ↓TH synthesis → hypothyroidism
• Propylthiouracil: also Θ peripheral conversion of T4 to T3
• Use
– principal therapy for hyperthyroidism
– adjuvant to radioiodine to control the disease until
radiation achieves effect
– to prepare patients for surgery
• Single daily dose
• Clinical improvement in 2-4 wks, euthyroid in 4-6 wks
• Guides to therapy: ↓nervousness & palpitations,
↑strength & weight gain, pulse rate
• Optimal treatment: gland decreases in size
• Overtreatment: ↓hormone conc. → activates pituitary
feedback system → induce TSH → goitre
Adverse reactions
• Minor: rash, urticaria, arthralgia, fever, anorexia, nausea,
abnormalities of taste & smell
• Major: agranulocytosis, thrombocytopenia, acute hepatic
necrosis, cholestatic hepatitis, lupus-like syndrome,
vasculitis
– Routine leucocyte counts
– Agranulocytosis: drug withdrawal, admission to
hospital, broad-spectrum antibimicrobials, granulocyte
CSF
• Cross allergy between drugs
• Pregnancy:
– smallest possible amount, cross placenta
– over- treatment → fetal goitre
– Surgery in 2nd trimester preferred
• During breastfeeding: Propylthiouracil - treatment of
choice, little passes into breast milk
• Antithyroid drug therapy: 12-18 months
β-adrenergic blockade
• TH: ↑tissue sensitivity to catecholamines, ↑no. of β-
adrenoceptors or ↑2nd messenger response (↑cAMP
synthesis)
• Some unpleasant symptoms of hyperthyroidism:
adrenergic
• β blockers: Quick relief, not block all metabolic effects
• Nonselective & those lack partial agonist effect
(propranolol or timolol): preferred
• Contraindications: asthma
Iodine (iodide, radioactive iodine)
• Iodide: well absorbed from intestine, rapidly excreted by
kidney
• Selectively taken up & concentrated (about x 25) by
thyroid gland (more in hyperthyroidism, less in
hypothyroidism)
• Deficiency of iodide → ↓TH production → stimulates
pituitary to secrete TSH → hyperplasia & ↑vascularity of
gland → goitre
Effects of iodide
• Complex; related to dose & thyroid status
• Hyperthyroid subjects:
– moderate excess ↑TH production (providing 'fuel' )
– substantial excess Θ TH release, promotes storage, &
involution of gland, make it firmer & less vascular
• Euthyroid subjects ē normal glands:
– excess of iodide cause goitre
– iodide-containing cough medicines & radio- contrast
media, amiodarone, seaweed eaters
• Euthyroid subject ē autonomous adenoma (hot nodule):
becomes hyperthyroid
Uses (Potassium iodide)
1. Thyroid storm (crisis)
2. Preparation for thyroidectomy: ↓TH release & renders
surgery easier & safer
3. To cover administration of radioiodine
4. Prophylactic:
– iodide (1 in 100 000 parts) added to salt, water, bread:
where goitre endemic
– iodised oil i.m. every 3-5 yrs: given early to women→
prevents endemic cretinism
5. Antiseptic for skin: povidone-iodine (I ē sustained-
release carrier, polyvinyl-pyrrolidone)
6. Expectorant
7. Contrast media in radiology
• Precaution: patients specifically asked whether allergic
to iodine before use
• I.V. test dose: half an hour before full i.v. dose if history
of any allergy
• Severe anaphylaxis, even deaths: iodine containing
contrast media being superseded by nonionic
preparations
Adverse reactions
• Tolerance: vary; some intolerant to both oral & topical
• Iodism:
– Metallic taste, excessive salivation ē painful salivary
glands, running eyes & nose, sore mouth & throat,
productive cough, diarrhea, rashes (mimic chicken-
pox)
– Elimination enhanced by saline diuresis
• Goitre: prolonged use of iodide-containing expectorant
• Hypothyroidism: Topical antiseptic to neonates
• Iodide intake >normal (diet): ↓thyroid uptake of radio-
iodine, two forms compete
• Diet, medication & water soluble radio-diagnostic
agents: interference ē thyroid function cease 2-4 wks
after stopping source
• Agents for cholecystography: 6 months/more (tissue
binding)
Radioiodine (131I)
• Swallowed: concentrated in thyroid gland
• Mainly β radiation (90%): penetrates 0.5 mm tissue →
therapeutic effects on thyroid without damage to
surrounding structures, parathyroids
• Some gamma rays: more penetrating
• Physical (radioactive) t½: 8 days
• Preferred initial treatment for hypethyroidism caused by
Graves' disease
• C/I: children, pregnant, breast-feeding women (induce or
worsen ophthalmopathy)
• In combination ē surgery in thyroid carcinoma
• Beneficial effects (single dose): one month
• Patients reviewed at 6 wks to monitor onset of
hypothyroidism
• Maximal effect may take 3 months
• β- blockade & in severe cases, an antithyroid drug
needed to make patient comfortable
• Very rarely radiation thyroiditis causes excessive release
of hormone and thyroid storm
• Repeated doses sometimes needed
Adverse effects of radioiodine
• Slow acting & difficult to judge the dose to euthyroid
• Iodism
• Overdose: Treatment
– large doses NaI or KI (compete ē radioiodine for
thyroid uptake, hasten excretion by ↑iodide turnover)
– ↑fluid intake & diuretic (adjuvants)
• Hypothyroidism
– capacity of thyroid cells to divide permanently
abolished → cell renewal ceases
• Must be followed up indefinitely: most need treatment
for hypothyroidism eventually
• Risks
– Children
– Pregnant women, (131I): crosses placenta
– Teratogenic effect, should not conceive for 12 months
after treatment
– Larger doses used for thyroid carcinoma: late
leukaemia
Tests
• Radioiodine uptake to test thyroid function
• Scanning for identification of solitary nodules, D/D of
Graves' disease from thyroiditis (de Quervain's
thyroiditis)
Preparation for surgery
• Making euthyroid with antithyroid drugs plus a β-
adrenoceptor blocker for comfort and safety & adding
iodide for 7-10 days before operation (not sooner) to
reduce the surgically inconvenient vascularity of the
gland
Choice of treatment of hyperthyroidism
• 1) Antithyroid drugs 2) Radioiodine 3) Surgery
• Antithyroid drugs: preferred provided goitre small &
diffuse. Nodular goitre generally large, relapses when
therapy withdrawn, best treated surgically. Drugs do not
↓thyroid size; may increase. Used in pregnancy
• Radioiodine: commonly used for adults; not pregnancy.
Affects diffuse & nodular goitre. Goitre becomes smaller.
Monitoring indefinitely for subsequent hypothyroidism.
Single hyperfunctioning adenoma ('hot nodule') also
suitable for treatment, higher doses used
• Surgery: 2nd choice for thyrotoxicosis
Thyroid storm/Thyroid crisis
• Life-threatening emergency
• Liberation of large amounts of TH in circulation:
untreated or incompletely treated patients
• Precipitating factor: infection, trauma, surgical
emergencies or operations, radiation thyroiditis,
toxemia of pregnancy, parturition
Treatment of thyroid storm
1. Propranolol iv: immediately (Atropine to Θ
↑bradycardia)
2. Large doses antithyroid: Propylthiouracil (NG tube/PR)
3. Iodide: Θ further hormone release from gland
4. Large doses adrenocorticoid: Dexamethasone, Θ
release of TH from gland & peripheral conversion of T4
to T3
5. Chlorpromazine: Mental disturbance
6. Cooling, aspirin: Hyperthermia
7. Heart failure: ordinary way
Exophthalmos of hyperthyroidism
• Antithyroid drugs do not help
• Patient should be rendered euthyroid
• Mild to moderate cases regress spontaneously
• Artificial tears (hypromellose)
• Severe cases: high systemic doses of
prednisolone, alone or in combination ē another
immunosuppressive (azathioprine)
• A course of low-dose orbital radiation: rapid
regression of ophthalmopathy
• Urgent cases: orbital decompression by surgery
Drugs that cause hypothyroidism
• drugs used for antithyroid effects
• lithium (for mania/depression)
• amiodarone (cardiac antiarrhythmic)
• PAS (for tuberculosis)
• phenylbutazone (antirheumatic)
• iodide
• cobalt salts (for anaemia)
• resorcinol (for leg ulcers)
Effects are generally reversible on withdrawal
• Treatment of thyroiditis (Hashimoto's thyroiditis,
subacute thyroiditis of de Quervain):
– Where hyperthyroidism: β- adrenoceptor blocking
drug (Antithyroid drugs should not be used)
– Where permanent hypothyroidism: thyroid hormone
replacement
• Autoimmune disease of thyroid: can cause over- or
underproduction of thyroid hormone
• Hypothyroidism: readily treated by oral levothyroxine 50-
200 μg daily, continued indefinitely
• Hyperthyroidism due to Graves' disease: either 12
months treatment ē carbimazole/propylthiouracil or a
single dose of I3II
• Natural history of Graves' disease: alternating remission
& relapse. Progression to hypothyroidism can occur, esp.
after I3II treatment. Patients should have long-term
follow-up, likely to require TH replacement therapy
• Severe forms of thyroid eye disease: should be treated ē
steroids & immunosuppresants or low-dose radiotherapy.
Urgent surgical decompression can be required for
exophthalmos
Drugs acting on uterus
• At parturition, oxytocin: causes regular coordinated
uterine contractions, each followed by relaxation
• Ergometrine, ergot alkaloid: causes uterine
contractions ē an increase in basal tone
• Prostaglandin analogues eg. dinoprostone (PGE₂) &
dinoprost (PGF₂α): contract pregnant uterus but
relax cervix
• Atosiban, antagonist of oxytocin: delays labour
• Cyclooxygenase inhibitors: inhibit PG synthesis
& delay labour, alleviate symptoms of
dysmenorrhea & menorrhagia
• β₂-agonists (eg. ritodrine): inhibit both
spontaneous & oxytocin-induced contractions
of pregnant uterus
Myometrial stimulants (oxytocics)
• Oxytocin:
– to induce or augment labour when uterine muscle is
not functioning adequately
– used to treat postpartum haemorrhage
• Ergometrine:
– to treat postpartum haemorrhage
– Carboprost if patients do not respond to ergometrine
• Preparation containing both oxytocin & ergometrine:
– used for management of third stage of labour
– prior to surgery, to control bleeding owing to
incomplete abortion
• Dinoprostone:
– given by extra-amniotic route, for late (2nd trimester)
therapeutic abortion
– given as vaginal gel, for cervical ripening & induction
of labour
• Gemeprost:
– given as vaginal pessary following mifepristone,
medical alternative to surgical termination of
pregnancy (up to 63 days of gestation)
Myometrial relaxants (Tocolytics)
• β-adrenoceptor agonists (e.g. ritodrine): to delay
preterm labour
• Oxytocin antagonist (Atosiban): delays preterm
labour
• Adrenaline, acting on β2-adrenoceptors: inhibits
uterine contraction
• Noradrenaline, acting on α-adrenoceptors:
stimulates contraction
Drugs that stimulate pregnant uterus
• Oxytocin, ergometrine, E & F type prostaglandins
Oxytocin
• neurohypophyseal hormone, an octapeptide
• regulates myometrial activity
• release stimulated by cervical dilatation & by suckling;
role in parturition incompletely understood
• for clinical use prepared synthetically
Actions of oxytocin
• On the uterus
– Given slow iv infusion to induce labour, causes regular
coordinated contractions that travel from fundus to
cervix, uterus relaxing completely between
contractions
– Larger doses ↑frequency of contractions &
incomplete relaxation between them
– Still higher doses cause sustained contractions that
interfere ē bl. flow through placenta & cause fetal
distress or death
• Other actions
– contracts myoepithelial cells in mammary gland →
'milk let-down‘ (expression of milk from alveoli &
ducts)
– vasodilator action
– weak antidiuretic action → water retention,
occurs if large doses infused
• Caution: in pts ē cardiac or renal disease, or pre-
eclampsia
Pharmacokinetic aspects
• iv or im injection, most often given by iv infusion
• Inactivated in liver & kidneys, and by circulating
placental oxytocinase
Unwanted effects of oxytocin
• Dose-related hypotension (vasodilator action)
• Reflex tachycardia
• Antidiuretic hormone-like effect on water
excretion by kidney causes water retention,
unless water intake is curtailed→ hyponatraemia
Ergometrine
• Ergot (Claviceps purpurea): a fungus growing on rye,
contains variety of pharmacologically active substances
• Ergot poisoning was often associated with abortion
• Ergometrine: oxytocic principle in ergot
Actions
• Contracts human uterus
– Depends partly on contractile state of the organ
– On contracted uterus (normal state following
delivery): relatively little effect
– If uterus inappropriately relaxed: initiates strong
contractions → reduce bleeding from placental bed
• Moderate degree of vasoconstrictor action
Mechanism of action on smooth muscle:
• Acts partly on α-adrenoceptors & partly on 5-
hydroxytryptamine (5-HT) receptors
Pharmacokinetic aspects
• Can be given orally, intramuscularly or intravenously
• Very rapid onset of action & effect lasts for 3-6 hr
Unwanted effects
• Nausea & vomiting: effect on D₂-receptors in CTZ
• Vasoconstriction, increase in blood pressure
• Blurred vision, headache
• Vasospasm of coronary arteries → angina
Prostaglandins
• Endogenous prostaglandins
• Endometrium & myometrium have substantial
prostaglandin-synthesising capacity, particularly in the
second, proliferative phase of menstrual cycle
• Prostaglandin (PG) F₂α: generated in large amounts,
cause ischaemic necrosis of endometrium that precedes
menstruation (relatively little vasoconstrictor action on
many human blood vessels)
• Vasodilator prostaglandins, PGE₂ and PGI₂ (prostacyclin):
also generated by the uterus
• In addition to their vasoactive properties, E- and F-
prostaglandins contract non-pregnant as well as pregnant
uterus
– sensitivity of uterine muscle to prostaglandins
increases during gestation
– role in parturition (if any): not fully understood
• Prostaglandins also play a part in two of the main
disorders of menstruation: dysmenorrhoea (painful
menstruation) & menorrhagia (excessive blood loss)
Dysmenorrhoea
• Associated with increased production of PGE₂ and
PGF₂α, both of which cause uterine contractions
• Non-steroidal anti-inflammatory drugs: inhibit
prostaglandin biosynthesis, used to treat spasmodic
dysmenorrhoea
Menorrhagia
• Caused by a combination of increased vasodilatation &
reduced haemostasis
• Increased production of PGE₂ & PGI₂ compared with
PGF₂α → Increased vasodilatation
Exogenous prostaglandins
• Prostaglandins of E & F series: coordinated contractions
of body of pregnant uterus, while relaxing cervix
– cause abortion in early & middle pregnancy, unlike
oxytocin, which generally does not cause expulsion of
uterine contents at this stage
• Prostaglandins used in obstetrics:
– dinoprostone (PGE₂): intravaginally as gel or tablets, or
by extra-amniotic route as solution
– carboprost (15-methyl PGF₂α): deep im injection
– gemeprost or misoprostol (PGE₁ analogues):
intravaginally
Unwanted effects:
• Uterine pain, nausea & vomiting: in about 50% of
patients when used as abortifacients
• Dinoprost (PGF₂α): cardiovascular collapse if escapes
into circulation after intra-amniotic injection
• Phlebitis at the site of intravenous infusion

• When combined with mifepristone, a progestogen

antagonist that sensitises uterus to prostaglandins: lower
doses of prostaglandins (e.g. misoprostol) can be used to
terminate pregnancy & side-effects are reduced
Drugs that inhibit uterine contraction
• Selective β₂-adrenoceptor agonists: ritodrine or
salbutamol, inhibit spontaneous or oxytocin-induced
contractions of pregnant uterus
• Clinical use: in selected patients to prevent premature
labour occurring between 22 & 33 weeks of gestation in
otherwise uncomplicated pregnancies
• Adverse effects: Risks to mother, esp. pulmonary
oedema, increase after 48 hours & myometrial response
is reduced, so prolonged treatment avoided
• Cyclooxygenase inhibitors e.g. indometacin: inhibit
labour, can cause problems in baby including renal
dysfunction & delayed closure of the ductus arteriosus
• Oxytocin receptor antagonist, atosiban:
– inhibit uncomplicated premature labour
– provides an alternative to β2-adrenoceptor agonist
– given as an intravenous bolus followed by an
intravenous infusion for not more than 48 hours
– Adverse effects: symptoms of vasodilation, nausea,
vomiting, hyperglycaemia, rash
Androgens
• Testosterone: main natural androgen
• Synthesised mainly by interstitial cells of testis, in
smaller amounts by ovaries & adrenal cortex
• Adrenal production of androgens is under the
control of adrenocorticotrophic hormone (ACTH,
corticotrophin)
• Cholesterol is the starting substance
• Dehydroepiandrosterone and androstenedione
are important intermediates
– released from gonads & adrenal cortex and converted
to testosterone in liver
Actions
• Effects of exogenous androgens are the same as those of
testosterone and depend on the age and sex of the recipient
• If administered to boys at the age of puberty, there is rapid
development of the secondary sexual characteristics,
maturation of the reproductive organs and a marked increase in
muscular strength. Height increases more gradually. The
anabolic effects can be accompanied by retention of salt and
water. The skin thickens and may darken, and sebaceous glands
become more active (which can result in acne). There is growth
of hair on the face and on pubic and axillary regions. The vocal
cords hypertrophy, resulting in a lower pitch to the voice.
Androgens cause a feeling of well-being and an increase in
physical vigour and may increase libido.
• If given to prepubertal males, the individuals concerned do not
reach their full predicted height because of premature closure
of the epiphyses of the long bones.
• Administration to women results in masculinisation
Mechanism of action
• Active metabolite, dihydrotestosterone, to which
it is converted locally by a 5α-reductase enzyme
• Both testosterone and dihydrotestosterone
modify gene transcription by interacting with
intracellular receptors, in common with other
steroids
• Preparations
– Testosterone itself can be given by subcutaneous
implantation
– Various esters (e.g. enanthate and proprionate) are
given by intramuscular depot injection
– Testosterone undecanoate and mesterolone can be
given orally
• Pharmacokinetic aspects
• If given orally, rapidly metabolised in liver: usually injected
• Virtually all testosterone in the circulation is bound to plasma
protein-mainly to the sex-steroid-binding globulin
• elimination half-life of free testosterone short (10-20 min)
• inactivated in the liver by conversion to androstenedione: weak
androgenic activity and can be reconverted to testosterone
• 90% of testosterone eliminated as metabolites
• Synthetic androgens less rapidly metabolised and some are
excreted in the urine unchanged
Unwanted effects
• decrease of gonadotrophin release, with resultant infertility
• salt and water retention leading to oedema
• Adenocarcinoma of the liver
• impair growth in children (via premature fusion of epiphyses)
and cause acne and masculinisation in girls
Clinical use of androgens and anti-androgens
• Androgens (testosterone preparations) are used
for replacement therapy in testicular failure and
as anabolic agents
• Anti-androgens (e.g. flutamide, cyproterone) are
used as part of the treatment of prostatic cancer
• 5α-Reductase inhibitors (e.g. finasteride) are used
in benign prostatic hypertrophy
Anabolic steroids
• Androgens can be modified to enhance the anabolic
effects and decrease other effects
• nandrolone, stanozolol
• increase protein synthesis and enhance muscle
development, resulting in weight gain
• used to decrease itching of chronic biliary obstruction
and in the therapy of some aplastic anaemias
• treating debilitating and wasting conditions, in
terminal disease: improve appetite and promote
well-being
• used in some cases of hormone-dependent
metastatic mammary cancer
• Unwanted effects: cholestatic jaundice
• Anabolic steroids are used by some athletes to
increase strength and athletic performance
• Serious unwanted effects can occur-testicular
atrophy, sterility and gynaecomastia in men, and
inhibition of ovulation, hirsutism, deepening of
the voice, alopecia and acne in women.
• Increased aggressiveness and psychotic
symptoms have been described
• In both sexes, there is increased risk of coronary
heart disease, sudden death in young athletes
Anti-androgens
• Oestrogens, progestogens: anti-androgen activity,
oestrogens mainly by inhibiting gonadotrophin secretion
& progestogens by competing androgens in target organs
• Cyproterone:
– derivative of progesterone, weak progestational activity
– partial agonist at androgen receptors, competes ē
dihydrotestosterone in androgen-sensitive target tissues
– in hypothalamus depresses synthesis of gonadotrophins
– used as an adjunct in treatment of prostatic cancer
– therapy of precocious puberty in males, masculinisation &
acne in women
– CNS effect, decreasing libido
– to treat hypersexuality in male sexual offenders
• Flutamide: non-steroidal anti-androgen, used ē
GnRH in treatment of prostate cancer
• Drugs can have anti-androgen action by inhibiting
synthetic enzymes
• Finasteride: inhibits enzyme (5α-reductase) that
converts testosterone to dihydrotestosterone
• Dihydrotestosterone: greater affinity than
testoserone for androgen receptors in prostate
gland
– well absorbed after oral administration
– used to treat benign prostatic hyperplasia