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
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller muammalal-bayati. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for £10.48. You're not tied to anything after your purchase.
