NAME OF DRUG
TYPE
MECHANISMS OF ACTION
USES
PHARMACOKINETICS
SIDE -E FFECTS OF DRUG
• Hypopituitary disorders • 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.
Dopamine receptor agonist
• Acts as dopamine, decreasing prolactin and somatostatin secretion
• • • •
• Nausea, vomiting, abdominal cramps, dyskinesias, psychomotor excitation, postural hypotension, vasospasm (esp fingers and toes)
Dopamine receptor agonist (DA2 receptor)
• Same as bromocriptine
• Hyperprolactinaemia • Hypersomatotrophinism • Used in short term before pituitary surgery, or long term treatment in ppl not controlled by other means. • Same as bromocriptine
• 1-2 per week, oral • half life v long >45 hours
• Same as bromocriptine but less pronounced
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.
• • • •
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
• Distributed in ECF • Metabolised by liver and kidneys • Half life = 2-4 hours • Administer subcutaneous/IM 3 times daily. •
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
• • • • • •
• Inhibit Na+/Clresorption in distal convoluted tubule compensatory mechanism to
• 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
Human recombinant GH
• Hyperpituitary disorders Bromocriptine
Cabergoline
Octreotide
Thiazides
1 a day, oral Highly plasma bound (93%) Half life =7 hours Hepatic metabolism
GI tract disturbances initial reduction in insulin secretion transient hyperglycaemia gall stones
•
Abdominal pain Headaches Nausea Fluid retention Hyponatraemia No heart problems – not as effective on those v2 receptors
NAME OF DRUG
TYPE
MECHANISMS OF ACTION
USES
PHARMACOKINETICS
SIDE -E FFECTS OF DRUG
increase Na+ resorption in proximal tubule more water resorption in proximal tubule reduced urine volume Oxytocic – increased motility and decreased bleeding
•
oxytocic
•
Prostaglandin derivative (PGE2) = vasodilator
• Stimulates contractions throughout pregnancy and induces cervical ripening • Vasoconstrictor
• INDUCES CERVICAL RIPENING AT TERM • INDUCTION OF ABORTION (intravaginally as gel or tablet)
• To control post partum haemorrhage in ppl resistant to oxytocin/ergometrine
• Given IM
• Blocks uterine progesterone receptors detachment of blastocyst and reduced hCG production reduced progesterone production by corpus leuteum decidual breakdown &
• 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
Oxytocin
Ergometrine
Dinoprostone
15 methyl – PGE2alpha
Carboprost Mifepristone
Progesterone receptor antagonists Abortifacients
• 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 • 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
• 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
• 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
• Potentiate actions of oxytocin dangerous contractions • N, V, diarrhoea • Pyrexia (fever) • Hypotension (vasodilator) • Potentiate actions of oxytocin dangerous contractions • N, V, diarrhoea • Pyrexia (fever) • Hypertension (vasoconstrictor) • Vaginal bleeding, headache
NAME OF DRUG
TYPE
MECHANISMS OF ACTION
USES
PHARMACOKINETICS
SIDE -E FFECTS OF DRUG
increased uterine prostaglandin production.
Tocolytics
B2 adenoceptor agonists, reduce motility
• Hyper and hypo thyroid disorders Replacement T4/t3 Levothyroxine sodium/liothyronine sodium
Radioiodine
Thiourylenes (carbimazole or propylthiouracil= PTU)
Thiourylenes (takes long time for effect as have stores of T3 and T4 Usually potassium iodide
Iodide
• Receptor activation increases intracellular cAMP relaxation of uterine muscle delay of premature labour
• Delay of premature labour
•
•
• 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)
• hyperthyroidism
• isotope of iodine, taken up into thyroid gland, emits B particles (v short range) and destroys gland • inhibit thyroperoxidase, so inhibit T3/T4 synthesis and secretion
• hyperthyroidism
• 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) • give as single oral dose • radioactive half life = 8 days • must be isolated to avoid pregnant women and children
• Massive amounts of iodine causes inhibitory response, inhibiting h2o2 production
• Used to prepare hyperthyroid pts for surgery • In severe thyrotoxic crisis (thyroid storm)
• Orally active • Half life = 6-15 hours • Metabolised by liver, excreted in urine • Crosses placenta and milk, has bad effects on babies/ children • 30x normal daily requirement • Given orally • Mex effects after 10 days continuous administration (use up stores of T3 and T4 first)
• • • • • • •
• Stops 11deoxycortisol cortisol, and 11deoxycosterone 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.
• Hyperthyroidism – reduces CV system, diffuses toxic goitre, exophthamic goitre, used whilst waiting for surgery or radioactive iodine to work
• can cause hypothyroidism if too much destroyed
Rashes (common) Headaches Nausea Jaundice Joint pain Granulocytopenia/agraulocytosis Allergic reaction rash, fever angiooedema.
• Hyperadrenal disorders Metyrapone
Steroid inhibitor, Inhibits 11 bhydroxylase.
NAME OF DRUG
Trilostane
Ketoconazole
TYPE
USES
PHARMACOKINETICS
SIDE -E FFECTS OF DRUG
• One of the first steps, so stops aldosterone, corticosterone, cortisol and sex steroids. • This is first step, so blocks production of EVERYTHING
• Cushings syndrome • Primary aldosteronism • Reduction of sex steroid hormone production
• Orally active
• N, V , D • FLUSHING
• Cushings syndrome
• Orally active
Steroid inhibitor, i
• Inhibits cholesterol to pregnenolone, VERY TOXIC
• Adrenocortical carcinoma (malignant) • Prostatic cancer (malignant – need to replace corticosteroids!)
• Orally active
• • • • •
N, V , D, liver damage Alopecia, ventricular tachycardias Gynacomastia, oligospermia Reduced androgen production Same as ketoconazole
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
• 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. • Binds to CBG • Hepatic metabolism, excreted in bile and urine • Half life = 1.5 hrs, duration of action =12hr. • Binds WEAKLY to ALBUMIN only, so can be active in blood. • Half life =1.5 hrs, duration of action = 40hours.
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
• In deficiency of aldosterone (primary / secondary adrenocortical failure) • Congenital adrenal hyperplasia (salt losing) • Primary/secondary adrenocortical failure • Acute adrenocortical failure = emergency treatment IV/IM infusion, every 6 hrs +
• Given orally • Used as aldosterone is not effective orally. • Orally active • If trying to suppress ACTH, dexamethasone 1 per day, or
• Neonatal kidney is quite insensitive to this, so need higher doses in children • Dexamethasone impairs growth so don’t give to children • Long high dose treatment
Steroid inhibitor, inhibits 3bhydroxysteroid dehydrogenase Steroid inhibitor, inhibits cytochrome p450
Aminoglutethamide
Spironolactone
MECHANISMS OF ACTION
• Adrenal steroids as anti inflammatories and immunosuppressives
Cortisol/ hydrocortisone
Prednisolone
Dexamethasone
Corticosteroid, mineralocorticoid actions at high doses
• Acts as corticosteroid
Corticosteroid and weak mineralocorticoid activity
• 4-5 times more active on corticosteroid receptors than cortisol
V high corticosteroid activity, no mineralocorticoid action
• 40 x more active on corticosteroid receptors than cortisol.
With prolonged glucocorticoid excess/steroid treatment can cause iatrogenic cushings sydrome
• Therapeutic and replacement therapy with adrenal steroids Fludrocortisone Hydrocortisone/ dexamethasone
analogue of aldosterone
• Acts as aldosterone
Cortisol analogues
•
NAME OF DRUG
TYPE
MECHANISMS OF ACTION
USES
PHARMACOKINETICS
SIDE -E FFECTS OF DRUG
saline for rehydration and glucose. • Congenital adrenal hyperplasia (CAH) – replace cortisol, and also suppress ACTH and adrenal androgen production by massive doses of these.
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.
iatrogenic adrenal insufficiency by switching of HPA axis, so if need to come off, wean them off gradually to restart natural system.
•
• Natural oestrogen, produced in pregnancy, may protect against multiple sclerosis in fetus
•
•
• Orally active • 70% OF CIRCULATING OESTROGENS ARE BOUND TO PLASMA PROTEINS • Conjugated, hydrolysed to normal oestrogen in tissues. • Orally active
•
• DRUG OF CHOICE
•
•
• 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)
• 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.
•
•
•
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
• • • • • •
• Oral contraceptives, HRT and SERMS
Oestriol
Oestrone sulphate
Oestrogen treatment drug
Ethinyl oestradiol Transdermal skin patches Testosterone analogues
Progesterone and its analogues
Combined oral contraceptives
Progestogens eg: Norethisterone
Progestogens eg: MEDROXYPROGESTERONE ACETATE Orally active oestrogen (ethinyl oestradiol) + progestogen (norethisterone)
• Semi synthetic oestrogen (has ethinyl group added) • Orally active • Resistant to metabolism • Avoids first pass metabolism • Oestrogens readily cross membranes into blood
Poorly absorbed Rapidly metabolised by liver Given IM in oily vehicle Excreted in urine Orally active Take for 21 days, stop for 7 days • Can be monophasis (same conc throughout) or triphasic (3 step wise changes in conc)
•
NAME OF DRUG
TYPE
•
Progesterone only contraceptives Emergency contraception Morning after pill
Hormone replacement therapy
Combined O & P (prescription only) or P alone (over counter)
• Stops implantation, causes shedding of endometrium
O only – in women without uterus O + P in everyone else
•
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.
Tamoxifen
Raloxifene
MECHANISMS OF ACTION
Treatment and protection of postmenopausal osteoporosis Fertility drug with some HRT effects
Clomiphere
Tibolone
USES
PHARMACOKINETICS
• When oestrogens are contradicted = CVS problems, thrombosis, before major surgery, during lactation (as oestrogens could cross in milk) • After unprotected sex
• Oral administration • Can use Depot-Provera (medroxyprogesterone) for long acting use. • 2 doses, 12 hrs apart • Begin asap (within 72hrs) • Prevents 75-85% of pregnancies which might occur
• • • • • • •
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 Antioestrogenic in breast tissue (oestrogen dependent breast cancer treatment) Oestrogenic effects in: • Liver lowers cholesterol • Bone increases bone density • Endometrial tissue hyperplasia • Agonist in bone, antagonist in breast and uterus. • Reduced risk of vertebral fractures and breast cancer • Binds to oestrogen receptors and stops neg fb to HPA so increase in secretion of GnRH, LH, FSH. •
• Can give orally (1st pass metabolism) • Intranasal spray, intravaginal oestrogens, transdermal HRT. • By giving it locally, try to avoid systemic side effects •
•
•
Synthetic prohormone = designer HRT
•
• Oestrogeninc, progesterogenic and weak androgenic actions. • As effective as HRT for relieving vasomotor symptoms, increases bone density
•
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
SIDE -E FFECTS OF DRUG •
• N & V – if vomit, will need a repeat dose, and anti emetics • Non known risks if unsuccessful • Caution – cannot terminate established pregnancy • Increased risk of endometrial carcinoma • Increased risk of breast cancer after 5 yrs of use • Increased risk of gallstone, CVA, venous thromboembolism. • Endometrial changes hyperplasia, polyps, cancer • Bone pain if have bone metastases • Hot flushes • Menstrual irregularities • GI disturbances • Increased risk of fatal stroke and f venous thromboembolism • Doesn’t reduce vasomotor symtoms • Ovarian hyperstimulation, abdominal discomfort • Hot flushes & • Endometriosis • N AND V, headache • Not drug of choice until more tests done (link to endometrial and breast cancer)
• Endocrine Infertility
Testosterone
• Masculinisation/virilisation • Salt and water retention, weight gain, oedema due to aldosterone like activity at high levels – caution with heart and kidney disease • Acne
NAME OF DRUG
TYPE
GnRH
MECHANISMS OF ACTION
USES
PHARMACOKINETICS
SIDE -E FFECTS OF DRUG
• Stimulates pituitary to produce LH & FSH testosterone
• For fertility in Hypothalamic – pituitary diseases, IF PITUITARY IS INTACT.
•
• IIF PITUITARY NOT INTACT, GIVE LH AND FSH TESTOSTERONE.
•
• DIABETES MELLITUS TYPE 1 Soluble = short acting NPH = immediate acting Or combination
•
•
• HYPOGLYCAEMIA
• Lispro/novorapid rapid onset, short duration, so can eat instantly • Glargine long acting, flat 24hr profile • Rapidly absorbed glucose (solution/tablets) + complex carbs to maintain levels • If unconscious IM/ IV
• 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
• Increase in non minerosteoid formation • Gastric pain and GI upsets • Osteophagitis and bone pain
•
• 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 •
• 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)
• • • • •
• Diabetes Mellitus Insulin analogues
Glucose
•
Glycaemia drugs for • Metformin = acts on insulin resistance in liver. Very effective. Unwanted effects = Gi side effects. DIABETES MELLITUS • Acarbose = alpha glucosidose inhibitor prolonged sugar absorption. • Thiazzolidinediones = act on insulin in adipocytes TYPE 2 • Metabolic bone disorders Calcium chloride, calcium gluconate
•
Sodium etidronate Alendronate
• Indirectly stimulates osteoblast activity
Calcium salts
Bisphosphates/ Diphosphates
Oestrogen receptor ligands
Calcitonin
• Tamoxifen, raloxifene, ethinyl oestradiol
Peptide hormone made by parafollicular cells
• Decreases plasma Ca+ levels • Decreases 1 alpha hydroxylase in kindey • Inhibits osteoclasts
• OSTEOPOROSIS (reduced bone mass and disolation of bone microstructure) • HYPOCALCAEMIAS (dietary insufficiencies, malabsorption, hypoparathyroidism, hypocalcaemic tetany) • CARDIAC DYSRHYTHMIAS (severe hyperkalaemia) • Paget’s disease • Manage hypercalcaemias • Delay bone metastases in cancer treatment • In osteoporosis
• Increased risk of breast and endometrial cancer • Minor GI problems Inflam reaction at site of injection Nausea, vomiting Facial flushing Tingling sensation in hands Unpleasant taste in mouth
NAME OF DRUG
Vit d
TYPE Fat soluble vitamin. Enhances transcription of ca+ transporter protein so ca+ and po34 absorption is increased.
MECHANISMS OF ACTION • Maintains ca+ and regulates cell growth • Most potent form is CALCITRIOL = 1,25 (02) D3. • Can use ERGOCALCIFEROL to prevent osteomalacia and rickets
USES • 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)
PHARMACOKINETICS •
SIDE -E FFECTS OF DRUG •