year 2 endocrinology drug table

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)

CabergolineDopamine 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, DMCTVasopressin 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+

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

NAME OF DRUG TYPE MECHANISMS OF ACTION USES PHARMACOKINETICS SIDE-EFFECTS OF DRUG

resorption in proximal tubule more water resorption in proximal tubule reduced urine volume

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

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


prostaglandin production.

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

Cushings syndrome Primary aldosteronism Reduction of sex steroid hormone

production

Orally active N, V , D FLUSHING


steroids.

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

AminoglutethamideSteroid 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

Fludrocortisoneanalogue 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 & pitOestrogen: 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 uterusO + 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, IF PITUITARY IS INTACT.

IIF PITUITARY NOT INTACT, GIVE LH AND FSH TESTOSTERONE.

Diabetes Mellitus

Insulin analogues

DIABETES MELLITUS TYPE 1Soluble = short actingNPH = immediate actingOr 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 etidronateAlendronate

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)


year 2 endocrinology drug table

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