Name Of Drug / Type / Mechanisms of Action / Uses / Pharmacokinetics / Side-Effects of Drug
  • Hypopituitary disorders

Human recombinant GH /
  • Just like normal GH
/
  • GH deficiency in children (adults)
/
  • Administer subcutaneous/IM, daily or 4-5 times a week
  • Metabolised by liver/kidneys
  • Half life = 20mins (short) but actions take longer  transcription of proteins etc.
  • Absorption and maximal plasma conc 2-6hrs, peak IGF 1 levels after 20hrs.
/
  • Resistance can develop after about a year.
  • Intercranial hypertension
  • Headaches
  • Increased incidence of leukaemia
  • Lipotrophy at injection site.
  • In adults, increased risk of CV and cancer susceptibility, soft tissue growth  cardiomegaly.

  • Hyperpituitary disorders

Bromocriptine / Dopamine receptor agonist /
  • Acts as dopamine, decreasing prolactin and somatostatin secretion
/
  • Hyperprolactinaemia
  • Hypersomatotrophinism
  • Used in short term before pituitary surgery, or long term treatment in ppl not controlled by other means.
/
  • 1 a day, oral
  • Highly plasma bound (93%)
  • Half life =7 hours
  • Hepatic metabolism
/
  • Nausea, vomiting, abdominal cramps, dyskinesias, psychomotor excitation, postural hypotension, vasospasm (esp fingers and toes)

Cabergoline / Dopamine receptor agonist (DA2 receptor) /
  • Same as bromocriptine
/
  • Same as bromocriptine
/
  • 1-2 per week, oral
  • half life v long >45 hours
/
  • Same as bromocriptine but less pronounced

Octreotide / Somatostatin analogue /
  • Acts as somatostatin, inhibiting production of prolactin and somatotrophin
/
  • Hyperprolactinaemia
  • Hypersomatotrophinism
  • Used in short term before pituitary surgery, or long term treatment in ppl not controlled by other means.
/
  • Distributed in ECF
  • Metabolised by liver and kidneys
  • Half life = 2-4 hours
  • Administer subcutaneous/IM 3 times daily.
/
  • GI tract disturbances
  • initial reduction in insulin secretion
  • transient hyperglycaemia
  • gall stones

Lithium, DMCT / Vasopressin v2 receptor antagonists /
  • antagonise v2 receptors, stopping vasopressin action
/
  • used to treat syndrome of inappropriate ADH (SIADH) which is too much vasoperssin

Desmopressin (DDAVP) / V2 receptor agonist – these are much more sensitive to this than VP in kidneys, but not in heart, so reduce sideeffects /
  • Agonist at v2 receptors in kidneys, acts like vasopressin
/
  • Cranial diabetes insipidus (not enough vasopressin being made)
  • Nocturnal enuresis (weeing at night)
  • Haemophilia (make more fViii and vWF)
/
  • Administered orally or nasally
  • Retained in ECF
  • Half life = 5 hours
  • Hepatic/ renal metabolism
  • Has longer effect than VP = more powerful
/
  • Abdominal pain
  • Headaches
  • Nausea
  • Fluid retention
  • Hyponatraemia
  • No heart problems – not as effective on those v2 receptors

Thiazides /
  • Inhibit Na+/Cl- resorption in distal convoluted tubule  compensatory mechanism to increase Na+ resorption in proximal tubule  more water resorption in proximal tubule  reduced urine volume
/
  • Treatment of nephrogenic Diabetes Insipidus – cant just give VP analogue as the kidney wont react to this
  • This is PARADOXICAL
/
  • Given oral
  • Onset – 1-2hr
  • DoA: 8-12hr
  • Excretion – tubular secretion
  • N.B. competes with uric acid
/
  • K+ loss, Metabolic Alkalosis
  • Diabetes Mellitus – Inhibits insulin secretion
  • Reduced loss of Ca+ in urine

Oxytocin / Oxytocic – increased motility and decreased bleeding /
  • Induction of labour at term, needs careful control as causes v strong contractions of uterus and dilation of cervix
  • Prevention of post partum haemorrhage by vasoconstriction of umbilical arteries and veins.
  • Facilitation of milk let down by contraction of myoepithelial cells in mammary glands. Nasal spray
/
  • Distribution = ECF
  • Half life = 5 mins very short
  • Metabolised in liver kidneys and also plasma (as is placental derived enzyme)
/
  • Compromised placental exchange (02, nutrients) by vasoconstriction
  • Uterine rupture by crazy contraction s
  • Hypotension and tachycardia (transient)
  • Water intoxication as is antidiuretic

Ergometrine / oxytocic /
  • Increased tone of myometirum  prolonged stronger contractions, but these aren’t rhythmic so only used in end of 2nd stage/3rd stage of labour
  • Constriction of b. vessels, stops bleeding
/
  • Routine administration is IM
  • Give IV if high risk of haemorrhage
  • Oral for post partum atony
  • Half life = 3-4 hours, longer than oxytocin
  • Hepatic metabolism
/
  • Abdominal pain
  • Hypertension
  • Angina pain
  • Nausea/vomiting
  • Cant give to ppl with preeclampsia or vascular disease

Dinoprostone / Prostaglandin derivative (PGE2) = vasodilator /
  • Stimulates contractions throughout pregnancy and induces cervical ripening
/
  • INDUCES CERVICAL RIPENING AT TERM
  • INDUCTION OF ABORTION (intravaginally as gel or tablet)
/
  • Potentiate actions of oxytocin  dangerous contractions
  • N, V, diarrhoea
  • Pyrexia (fever)
  • Hypotension (vasodilator)

Carboprost / 15 methyl – PGE2alpha /
  • Vasoconstrictor
/
  • To control post partum haemorrhage in ppl resistant to oxytocin/ergometrine
/
  • Given IM
/
  • Potentiate actions of oxytocin  dangerous contractions
  • N, V, diarrhoea
  • Pyrexia (fever)
  • Hypertension (vasoconstrictor)

Mifepristone / Progesterone receptor antagonists
Abortifacients /
  • Blocks uterine progesterone receptors  detachment of blastocyst and reduced hCG production  reduced progesterone production by corpus leuteum  decidual breakdown & increased uterine prostaglandin production.
/
  • ABORTION Softens and dilates cervix prior to suction abortion, and causes therapeutic abortion with gemeprost.
/
  • Oral administration
  • Distribution: Enters cells but limited plasma protein binding
  • Metabolism = hepatic
  • Excretion is by bile, into faeces
  • Half life = 2—40 hours
/
  • Vaginal bleeding, headache

Tocolytics / B2 adenoceptor agonists, reduce motility /
  • Receptor activation increases intracellular cAMP  relaxation of uterine muscle  delay of premature labour
/
  • Delay of premature labour

  • Hyper and hypo thyroid disorders

Levothyroxine sodium/liothyronine sodium / Replacement T4/t3 /
  • analogue
/
  • used in hypothyroidism as replacement therapy.
  • Levothyroxine is usually drug of choice as is T4 so more long acting, liothyronine sodium is T3 so used in myxoedema coma as IV (emergency)
/
  • T3 half life is 6days, peak effect after 9 days, prohormone
  • T3 halflife of 2-5 days, peak effect 1-2 days
  • Almost 100% bound to plasma proteins, mainly thyroxine binding globulin (TBG)
/
  • hyperthyroidism

Radioiodine /
  • isotope of iodine, taken up into thyroid gland, emits B particles (v short range) and destroys gland
/
  • hyperthyroidism
/
  • give as single oral dose
  • radioactive half life = 8 days
  • must be isolated to avoid pregnant women and children
/
  • can cause hypothyroidism if too much destroyed

Thiourylenes (carbimazole or propylthiouracil= PTU) / Thiourylenes (takes long time for effect as have stores of T3 and T4 /
  • inhibit thyroperoxidase, so inhibit T3/T4 synthesis and secretion
/
  • Hyperthyroidism – reduces CV system, diffuses toxic goitre, exophthamic goitre, used whilst waiting for surgery or radioactive iodine to work
/
  • Orally active
  • Half life = 6-15 hours
  • Metabolised by liver, excreted in urine
  • Crosses placenta and milk, has bad effects on babies/ children
/
  • Rashes (common)
  • Headaches
  • Nausea
  • Jaundice
  • Joint pain
  • Granulocytopenia/agraulocytosis

Iodide / Usually potassium iodide /
  • Massive amounts of iodine causes inhibitory response, inhibiting h2o2 production
/
  • Used to prepare hyperthyroid pts for surgery
  • In severe thyrotoxic crisis (thyroid storm)
/
  • 30x normal daily requirement
  • Given orally
  • Mex effects after 10 days continuous administration (use up stores of T3 and T4 first)
/
  • Allergic reaction  rash, fever angiooedema.

  • Hyperadrenal disorders

Metyrapone / Steroid inhibitor, Inhibits 11 b-hydroxylase. /
  • Stops 11-deoxycortisol  cortisol, and 11-deoxycosterone  corticosterone.
/
  • Treat some cushings syndrome – inoperable tumours.
  • Control symptoms of cushings syndrome before surgery, to regain health state.
/
  • Orally active
/
  • N, V , D, sedation
  • Hypertension as deoxycortiserone accumulates and turns into aldosterone  salt retention  hypertension.

Trilostane / Steroid inhibitor, inhibits 3b-hydroxysteroid dehydrogenase /
  • One of the first steps, so stops aldosterone, corticosterone, cortisol and sex steroids.
/
  • Cushings syndrome
  • Primary aldosteronism
  • Reduction of sex steroid hormone production
/
  • Orally active
/
  • N, V , D
  • FLUSHING

Ketoconazole / Steroid inhibitor, inhibits cytochrome p450 /
  • This is first step, so blocks production of EVERYTHING
/
  • Cushings syndrome
/
  • Orally active
/
  • N, V , D, liver damage
  • Alopecia, ventricular tachycardias
  • Gynacomastia, oligospermia
  • Reduced androgen production

Aminoglutethamide / Steroid inhibitor, i /
  • Inhibits cholesterol to pregnenolone, VERY TOXIC
/
  • Adrenocortical carcinoma (malignant)
  • Prostatic cancer (malignant – need to replace corticosteroids!)
/
  • Orally active
/
  • Same as ketoconazole

Spironolactone / Aldosterone receptor antagonists /
  • Prodrug canrenone
  • competitive antagonist of aldosterone receptor.
/
  • CONN’S DISEASE
  • Antialdosterone effect, therefore blocks Na+ resorption and k+ excretion in kindey = potassium sparing diuretic.
/
  • Orally active
  • Highly protein bound
  • Metabolised in liver
/
  • Menstrual irregularities
  • Gynaecomastia
  • Gi tract irritation
  • Don’t give if renal/hepatic disease

  • Adrenal steroids as anti inflammatories and immunosuppressives

Cortisol/
hydrocortisone / Corticosteroid, mineralocorticoid actions at high doses /
  • Acts as corticosteroid
/
  • ANTIINFLAMMATORY/IMMUNOSUPRESSIVE THERAPY = asthma, inflam conditions of skin,eye,ear,joints, autoimmune/inflame disease like rheumatoid arthritis, prevent rejection after organ/bone marrow transplants.
  • NEOPLASTIC DISEASE (abnormal proliferation of cells) = in combination with cytotoxic drugs eg: leukaemia, to reduce cerebral oedma in pts with brain tumours, part of anti emetic treatment with chemo, elevate mood in terminally ill pts.
  • PREGNANCY = mature foetal lung in preterm births –helps produce surfactants.
/
  • Used for short term administration.
  • 90-95% bound to plasma protein corticosteroid binding globulin (CBG)
  • Half life = 1 hr, duration of action = 8 hr.
/ To minimise unwanted effects:
  • Administer locally if possible (oral/im rather than iv)
  • Use glucocorticoid selective steroid.
  • Withdraw steroids slowly
  • Use ACTH in children to avoid the growth suppression caused by steroids.
  • Pts should carry a steroid card
With prolonged glucocorticoid excess/steroid treatment can cause iatrogenic cushings sydrome
Prednisolone / Corticosteroid and weak mineralocorticoid activity /
  • 4-5 times more active on corticosteroid receptors than cortisol
/
  • Binds to CBG
  • Hepatic metabolism, excreted in bile and urine
  • Half life = 1.5 hrs, duration of action =12hr.

Dexamethasone / V high corticosteroid activity, no mineralocorticoid action /
  • 40 x more active on corticosteroid receptors than cortisol.
/
  • Binds WEAKLY to ALBUMIN only, so can be active in blood.
  • Half life =1.5 hrs, duration of action = 40hours.

  • Therapeutic and replacement therapy with adrenal steroids

Fludrocortisone / analogue of aldosterone /
  • Acts as aldosterone
/
  • In deficiency of aldosterone (primary / secondary adrenocortical failure)
  • Congenital adrenal hyperplasia (salt losing)
/
  • Given orally
  • Used as aldosterone is not effective orally.
/
  • Neonatal kidney is quite insensitive to this, so need higher doses in children

Hydrocortisone/
dexamethasone / Cortisol analogues /
  • Primary/secondary adrenocortical failure
  • Acute adrenocortical failure = emergency treatment IV/IM infusion, every 6 hrs + saline for rehydration and glucose.
  • Congenital adrenal hyperplasia (CAH) – replace cortisol, and also suppress ACTH and adrenal androgen production by massive doses of these.
/
  • Orally active
  • If trying to suppress ACTH, dexamethasone 1 per day, or hydrocortisone 2-3 x a day.
  • Wont have normal stress response, so if have minor illness need 2-3 x norm dose, surgery = much higher doses.
/
  • Dexamethasone impairs growth so don’t give to children
  • Long high dose treatment  iatrogenic adrenal insufficiency by switching of HPA axis, so if need to come off, wean them off gradually to restart natural system.

  • Oral contraceptives, HRT and SERMS

Oestriol / Oestrogen treatment drug /
  • Natural oestrogen, produced in pregnancy, may protect against multiple sclerosis in fetus
/
  • Orally active
  • 70% OF CIRCULATING OESTROGENS ARE BOUND TO PLASMA PROTEINS
/
  • Increases blood clotting factors  increased incidence of thromboembolic disease
  • Proliferation of endometrium increased risk of cancer (reduced if progesterone coadministered)
  • Discomfort to breasts, increased risk of breast cancer
  • Na+ & water retention by kidneys  oedema and weight gain
  • Hypertension, nausea, headaches
  • Can act on chemoreceptor trigger zone and cause nausea at high doses (like morning sickness)

Oestrone sulphate /
  • Conjugated, hydrolysed to normal oestrogen in tissues.
  • Orally active

Ethinyl oestradiol /
  • DRUG OF CHOICE
/
  • Semi synthetic oestrogen (has ethinyl group added)
  • Orally active
  • Resistant to metabolism

Transdermal skin patches /
  • Avoids first pass metabolism
  • Oestrogens readily cross membranes into blood

Testosterone analogues / Progestogens eg:
Norethisterone /
  • Change in structure, so it acts on progesterone receptors not androgen receptors.
/
  • Orally active
  • Metabolised to other biologically active steroids eg: testosterone, oestrogen
/
  • May need co administration of oestrogen to prevent the adrogenic effects of the metabolites.

Progesterone and its analogues / Progestogens eg:
MEDROXY-PROGESTERONE ACETATE /
  • Poorly absorbed
  • Rapidly metabolised by liver
  • Given IM in oily vehicle
  • Excreted in urine

Combined oral contraceptives / Orally active oestrogen (ethinyl oestradiol) + progestogen (norethisterone) / Progestogen:
  • Thickens cervical mucus (inhospitable to sperm)
  • Suppress menstrual cycle by fb to hyp & pit
Oestrogen:
  • Upregulates sensitivity of progestogen receptors.
  • Counteracts androgenic effects of P
  • Contributes to –ve fb to hyp and pit
/
  • Orally active
  • Take for 21 days, stop for 7 days
  • Can be monophasis (same conc throughout) or triphasic (3 step wise changes in conc)

Progesterone only contraceptives /
  • When oestrogens are contradicted = CVS problems, thrombosis, before major surgery, during lactation (as oestrogens could cross in milk)
/
  • Oral administration
  • Can use Depot-Provera (medroxyprogesterone) for long acting use.

Emergency contraception Morning after pill / Combined O & P (prescription only) or P alone (over counter) /
  • Stops implantation, causes shedding of endometrium
/
  • After unprotected sex
/
  • 2 doses, 12 hrs apart
  • Begin asap (within 72hrs)
  • Prevents 75-85% of pregnancies which might occur
/
  • N & V – if vomit, will need a repeat dose, and anti emetics
  • Non known risks if unsuccessful
  • Caution – cannot terminate established pregnancy

Hormone replacement therapy / O only – in women without uterus
O + P in everyone else /
  • Advantages (licensed for):
  • Control vasomotor symptoms in 90%
  • Delays osteoporosis
  • Advantages (possible, not licensed for):
  • Reduces symptoms of alzheimers
  • V small risk reduction of colon cancer
/
  • Can give orally (1st pass metabolism)
  • Intranasal spray, intravaginal oestrogens, transdermal HRT.
  • By giving it locally, try to avoid systemic side effects
/
  • Increased risk of endometrial carcinoma
  • Increased risk of breast cancer after 5 yrs of use
  • Increased risk of gallstone, CVA, venous thromboembolism.

Tamoxifen / Anti cancer drug /
  • Selective oestrogen receptor modulating drug
  • Don’t have the typical steroid structure
  • Actions are TISSUE SELECTIVE.
  • ‘designer oestrogens’  bind to receptors and are either oestrogenic or antioestrogenic there.
/
  • Antioestrogenic in breast tissue (oestrogen dependent breast cancer treatment)
Oestrogenic effects in:
  • Liver  lowers cholesterol
  • Bone  increases bone density
  • Endometrial tissue  hyperplasia
/
  • Endometrial changes  hyperplasia, polyps, cancer
  • Bone pain if have bone metastases
  • Hot flushes
  • Menstrual irregularities
  • GI disturbances

Raloxifene / Treatment and protection of postmenopausal osteoporosis /
  • Agonist in bone, antagonist in breast and uterus.
  • Reduced risk of vertebral fractures and breast cancer
/
  • Increased risk of fatal stroke and f venous thromboembolism
  • Doesn’t reduce vasomotor symtoms

Clomiphere / Fertility drug with some HRT effects /
  • Binds to oestrogen receptors and stops neg fb to HPA so increase in secretion of GnRH, LH, FSH.
/
  • Ovarian hyperstimulation, abdominal discomfort
  • Hot flushes &
  • Endometriosis
  • N AND V, headache

Tibolone / Synthetic prohormone = designer HRT /
  • Oestrogeninc, progesterogenic and weak androgenic actions.
  • As effective as HRT for relieving vasomotor symptoms, increases bone density
/
  • Not drug of choice until more tests done (link to endometrial and breast cancer)

  • Endocrine Infertility

Testosterone / Androgen therapy /
  • Primary hypogonadism/primary testicular failure
  • Secondary hypogonadism
  • Will increase lean body mass, muscle size, strength, bone density, libido
  • WILL NOT RESTORE FERTILILTY
/
  • Can be:
  • Orally active androgens
  • Transdermal delivery/topical gels
  • Monthly/3monthly injections
  • Subcutaneous implant
/
  • Masculinisation/virilisation
  • Salt and water retention, weight gain, oedema due to aldosterone like activity at high levels – caution with heart and kidney disease
  • Acne

GnRH /
  • Stimulates pituitary to produce LH & FSH  testosterone
/
  • For fertility in Hypothalamic – pituitary diseases, IFPITUITARY IS INTACT.
/
  • IIF PITUITARY NOT INTACT, GIVE LH AND FSH  TESTOSTERONE.

  • Diabetes Mellitus

Insulin analogues /
  • Diabetes Mellitus TYPE 1
Soluble = short acting
NPH = immediate acting
Or combination /
  • Lispro/novorapid  rapid onset, short duration, so can eat instantly
  • Glargine  long acting, flat 24hr profile

Glucose /
  • HYPOGLYCAEMIA
/
  • Rapidly absorbed glucose (solution/tablets) + complex carbs to maintain levels
  • If unconscious  IM/ IV

Glycaemia drugs for DIABETES MELLITUS TYPE 2 /
  • Metformin = acts on insulin resistance in liver. Very effective. Unwanted effects = Gi side effects.
  • Acarbose = alpha glucosidose inhibitor  prolonged sugar absorption.
  • Thiazzolidinediones = act on insulin in adipocytes

  • Metabolic bone disorders

Calcium salts / Calcium chloride, calcium gluconate /
  • OSTEOPOROSIS (reduced bone mass and disolation of bone microstructure)
  • HYPOCALCAEMIAS (dietary insufficiencies, malabsorption, hypoparathyroidism, hypocalcaemic tetany)
  • CARDIAC DYSRHYTHMIAS (severe hyperkalaemia)
/
  • Calcium chloride = IV
  • Calcium gluconate = orally active, IV in sever hypocalcaemic tetany
/
  • Calcium chloride = vasodilation, cutaneous burnin g feeling, decreased bp so give slowly
  • Calcium gluconate = doesn’t cause gastric irritation

Bisphosphates/
Diphosphates / Sodium etidronate
Alendronate /
  • Indirectly stimulates osteoblast activity
/
  • Paget’s disease
  • Manage hypercalcaemias
  • Delay bone metastases in cancer treatment
  • In osteoporosis
/
  • Orally active but poorly absorbed so take on empty stomach
  • Can remain for yrs/months in bone where it is absorbed
  • Excreted in urine unmetabolised
/
  • Increase in non minerosteoid formation
  • Gastric pain and GI upsets
  • Osteophagitis and bone pain

Oestrogen receptor ligands /
  • Tamoxifen, raloxifene, ethinyl oestradiol
/
  • Increased risk of breast and endometrial cancer
  • Minor GI problems

Calcitonin / Peptide hormone made by parafollicular cells /
  • Decreases plasma Ca+ levels
  • Decreases 1 alpha hydroxylase in kindey
  • Inhibits osteoclasts
/
  • Pagets disease – relieves bone pain and neurological components
  • Osteoporosis – post menopausal and glucocorticoid induced
  • Hypercalcaemias
/
  • Given subcutaneously or IM injection for Pagets
  • Intranasally for the others
  • Can develop resistance (antibody formation)
/
  • Inflam reaction at site of injection
  • Nausea, vomiting
  • Facial flushing
  • Tingling sensation in hands
  • Unpleasant taste in mouth

Vit d / Fat soluble vitamin. Enhances transcription of ca+ transporter protein so ca+ and po34 absorption is increased. /
  • Maintains ca+ and regulates cell growth
  • Most potent form is CALCITRIOL = 1,25 (02) D3.
  • Can use ERGOCALCIFEROL to prevent osteomalacia and rickets
/
  • Osteomalacia and rickets
  • Disorders of vit d absorption
  • Hypocalcaemias associated with hypoparathyroidism
  • Osteodystrophy due to chronic renal failure and decreased calcitrol production (cant give them ergocalciferol as they cant convert it in the kidney)