A very concise set of notes covering the important aspects of endocrine drugs & diseases required to pass the GPhC exam. Topics include:
- Diabetes mellitus & insipidus
- Systemic Corticosteroids
- Osteoporosis
- Hormone Replacement Therapy (HRT)
- Infertility in women
- Thyroid Disorders
ANTIDIURETIC HORMONE (ADH) DISORDERS – Diabetes Insipidus
Insipidus = tasteless, mellitus = sweet (in relation to urine)
ADH RECAP:
- ADH/Vasopressin: released during states of dehydration to increase water-
reabsorption from the kidney’s collecting ducts (CDs) more conc. urine
- MECHANISM:
1- Dehydration increases osmolarity in blood & interstitial fluid
2- Hypothalamus detects increase in osmolarity
3- Hypothalamus responds by stimulating POSTERIOR PITUITARY GLAND (PPG)
4- PPG releases ADH into bloodstream travels to kidneys
5- ADH upregulates aquaporins in CDs more water reabsorption (less water lost
to urine)
DIABETES INSIPIDUS (DI) – AN ADH DISORDER (OVERVIEW):
- DI: chronic condition in which the effects of ADH are REDUCED
- TWO TYPES:
o Pituitary DI: the PPG produces LESS ADH (abnormal production)
o Nephrogenic DI: kidneys are LESS RESPONSIVE to ADH (normal production)
- SYMPTOMS:
o Polyuria
o Polydipsia
o Dehydration
o Postural hypotension
o HYPERnatraemia
LITHIUM = Most common drug that CAUSES nephrogenic DI
TREATMENT:
- Pituitary DI: Vasopressin or Desmopressin (ADH replacement therapy)
- Nephrogenic DI: Thiazides (have a paradoxical anti-diuretic effect)
DESMOPRESSIN
OVERVIEW:
- Desmopressin = synthetic analogue of ADH/vasopressin
- Why Desmo is favoured over vasopressin:
o More potent
o Orally bioavailable
o Longer T1/2
o NO vasoconstrictor/hypertensive effect (unlike vasopressin)
INDICATIONS:
- Pituitary DI
- Differential diagnosis of pituitary and nephrogenic DI (H2O DEPREIVATION TEST)
- Nocturnal Enuresis (Bedwetting) in 7+ years
Enuresis = Incontinence, but ‘enuresis’ is typically reserved for children
,DESMOPRESSIN IN THE WATER DEPRIVATION TEST (WDT):
1- Pt’s urine osmolarity is measured prior to Desmo dose (should be LOW in DI)
2- Pt given dose of Desmo
3- Pt’s urine osmolarity re-measured after dose
Results of WDT:
- If osmolarity increases = urine is MORE concentrated – pt has responded to ADH =
Pituitary DI
- If osmolarity remains low = pt has NOT responded to ADH = nephrogenic DI
SIDE EFFECTS:
- Fluid retention (worsened by drinking XS fluids HEADACHES)
- HYPOnatraemia: caused by fluid retention (dilutes solutes in blood)
- Hyponatraemic convulsions: worsened by fluid retention
COUNSELLING POINTS: (all aim to reduce risk of HYPOnatraemia & Convulsions)
- LIMIT FLUID INTAKE: esp 1 hour before and up to 8 hours after dose
- SWIMMERS: avoid swallowing large amounts of water whilst swimming
- D&V: STOP Desmo during D&V (also causes HYPOnatraemia) – restart doses once
symptoms resolve
CORTICOSTEROIDS
PHARMACOLOGY RECAP OF CORTISOL:
- CORTISOL: main endogenous corticosteroid - plasma-[cortisol] increases during
times of STRESS e.g. during illness, starvation (hypoglycaemia), emotional stress
- Cortisol has both GLUCOCORTICOID & MINERALOCORTICOID effects:
o Glucocorticoid: anti-inflammatory, immunosuppressive, catabolic effects
o Mineralocorticoid: Na+ & Water RETENTION, K+ & Ca2+ EXCRETION (i.e. same
effects as aldosterone – the main mineralocorticoid)
EFFECTS OF GLUCOCORTICOIDS (clinically relevant effects):
- ANTI-INFLAMMATORY: reduces production of PGs, LTs, & IL-2
- IMMUNOSUPPRESSIVE: prevents neutrophils from leaving vessels less
inflammation in tissues
- PROTEOLYSIS: causes muscular atrophy/wasting – amino acid by-products also serve
as a substrate for gluconeogenesis (diabetes)
- DIABETES: steroids promote hyperglycaemia by increasing gluconeogenesis and
increasing INSULIN RESISTANCE (by reducing ability to store glucose)
- HYPERTENSION: upregulates alpha-1 receptors on vessels vasoconstriction (and
mineralocorticoid effects of some steroids water retention)
, GLUCOCORTICOID (GC) VS MINERALOCORTICOID (MC) ACTIVITY OF STEROIDS:
- Hydrocortisone is IDENTICAL to cortisol – has equal GC and MC activity – so mainly
INDICATED for cortisol replacement therapy & NOT often used in inflammation
- Fludrocortisone = almost entirely MC activity – INDICATED in hormone replacement
(alongside hydrocortisone) & hypotension
- Beta- & Dexamethasone: almost entirely GC activity – LONGEST T1/2 - & HIGHEST
POTENCY – suitable for high dose treatment of inflammation
- Prednisolone: 1st line oral steroid in inflammation – moderate GC effects w minimal
MC effects
Summary of GC vs MC
activity of exogenous
corticosteroids
If a pt has Addison’s disease &
is acutely ill, they’ll need to
DOUBLE their steroid dose
during that time to mimic the
normal HPA response in a non-
Addison’s disease pt.
SIDE EFFECTS OF STEROIDS:
GC EFFECTS:
MC EFFECTS:
- INFECTION RISK: e.g. acne & fungal infections
- HYPERtension/HYPERvolemia
- OSTEOPROSIS: esp dangerous in elderly
- HYPERnatremia
- DIABETES: insulin resistance
- WEIGHT GAIN: stimulate appetite
- HYPOkalaemia
- MYOPATHY: muscle weakness/pain & stretch marks
- HYPOcalcaemia
- STUNTS GROWTH IN KIDS
- CATARACTS: blurred vision
- PSYCHIATRIC EFFECTS: depression, insomnia, anxiety
- ADRENAL INSUFFICIENCY: if stopped abruptly
MANAGING SIDE EFFECTS:
- Take doses TOGETHER IN MORNING – mimics endogenous cortisol release &
reduces risk of HPA-axis inhibition less risk of adrenal insufficiency (and helps
avoid SLEEP DISTURBANCE)
- ALTERNATE DAY DOSING: same reasoning as above – two days’ worth of doses can
be taken as a single dose on alternate days – ONLY IF INSTRUCTED BY DOCTOR
CORTICOSTEROID WITHDRAWAL:
- Doses of steroid should gradually be lowered ONLY IF:
o Daily dose > 40mg prednisolone (or equivalent) for > 1 week
o Duration > 3 weeks (any strength)
o Evening doses are required (mainly in replacement therapy)
o Taking a short course & stopped long-term therapy in last year
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