Pharmacology, therapeutics and patient safety - Pharmacology and prescribing Flashcards
Describe the hypothalamic - pituitary - adrenal axis
- Hypothalamus releases cortictrophic releasing hormone (CRH)
- This in turn stimulates the pituitary gland to produce adrenocorticotrophic hormone (ACTH)
- This in turn stimulates the adrenal cortex to produce cortisol
- The levels of cortisol also influence the activity of the hypothalamus - if someone has high levels of cortisol the hypothalamus reduces the production of CRH
- Stress increases the production of CRH
- The fight or flight response leads to higher cortisol levels
Cholesterol is metabolised to 4 different types of hormones. Name the 4 hromones and describe their role
- Aldosterone - helps regulate blood pressure, renal alt, and water resorption
- Dihydrotestosterone - sex hormones
- Oestradiole - sex hormone
- Cortisol - stress hormone
Describe the levels of cortisol during a 24hr period
- Cortisol levels are at lowest when we get to bed at night and rise overnight, so the highest levels are when we get out of bed in the moring
- Cortisol levels then fall of during the day
Describe the effects of cortisol on corticotrophic releasing hormone (CRH) and adenocorticotrophic hormone (ACTH)
- Has negative feedback on the hypothalamus and pituitary gland, therefore reducing the production of CRH and ACTH in those glands respectively
- When cortisol levels are low the hypothalamus and pituitory work harder to produce CRH and ACTH to bring levels up by stimulating the adrenal gland
Describe the physiological effects of cortisol
- Catabolises tissue and releases amino acids
- Breaks down fats to fatty acids and glycerol
- Reduces bone formation and enhances resoprtion
- Increase gluconeogenesis and causes insulin resistance
- Mineral corticoid effects on blood pressure
- Effects on mood
- Modulates immune system
- Releases catecholamines
a) What is Addison’s disease/addisonian crisis caused by?
b) Describe the symptoms of addison’s disease
c) Describe the symptoms of Addisonian crisis
a) When the adrenal gland is damaged, so it does not produce enough cortisol or aldosterone.
- Low blood pressure
- Hyperpigmentation
- Fatigue
- Muscle weakness
- Hypoglycaemia
- Low Na/raised K
- Nusea, vomiting
b)
- Collapse
- Hypoglycaemia
- Abdominal pain, diarrhoea, and vomiting
a) What is Cushing’s disease?
b) What is a common cause of Cushing’s disease?
c) Describe the symptoms
a) Cushing’s disease occurs when there are high cortisol levels
b) Prolonged exposure to elevated endogenous or exogenous glucocorticoids
c)
- Truncal obesity
- Moon face
- Striae
- Hypertension
- Hirsutism (hairiness)
- Osteoporosis
- Diabetes
Describe the actions of glucocorticoids
- Bind to receptors in cytoplasm which dimerise and translate to the nucleus
- They bind to responsive genes
- They increase transcription of anti-inflammatory proteins
- They block transcription of inflammatory cytokines and adhesion molecules
- They have actions inhibitng phagocytosis and supressing COX-2 synthesis
How can steroids be administrated
- Oally
- Topically
- Intravenously
- Intraarticularly
- Inhaled
Describe the side effects of glucocorticoids
Dermatologic/visial side effects
- Truncal obesity
- ‘bufallo hump’
- Moon face
- Acne
- Striae
- Alopecia
- Bruising - blood vessels and collagen is affected by steroid so it is more easily ripped
- Skin atrophy - skin is drier and thinner
Metabolic changes
- Glucose - hyperglycaemia, diabetes (insulin resistance)
- Protein - catabolism (break down of protein) in muscle and bone
- Electrolyte - Sodium retention and Potassium loss (can cause peripheral oedema)
Infections
- Reactivation of latent infections - TB, Hepatitis B/C, herpes
- Raised risk of new infections - Less phagocytosis when taking steroids + a diabetic with high blood sugar has a higher risk of developing infections
MSK
- Myopathy
- Osteoporosis
- Osteonecrosis
- Tendon rupture
Cardiovascular
- Fluid retention (ankle oedema)
- Hypertension
- Altered lipid profiles (increased risk of coronry heart disease)
- Arrhythmias with iv infusion
- Accelerated atherosclerosis (increased thickening of the artery wall with lipid forming - increases risk of myocardial infarction)
GI
- Peptic ulcers - de novo (new) or reactivation & exacerbates ulcerogenic properties of NSAIDS x2
- Pacreatitis
- GI perforation
- Steatohepatosis (fatty livers)
Opthalamic
- Cataracts
- Glaucoma - increased pressure within eye
CNS
- Psychosis
- Depression
- Mood and sleep disturbance
- Benign intercranial hypertension
Adrenal crisis
- Lightheadedness or dizziness
- Weakness
- Sweating
- Abdominal pain
- Nausea and vomiting
- Loss of consciousness
a) What is adrenal crisis and explain how this relates to steroids
b) What are the symptoms?
c) How can adrenal crisis be avoided?
a) Adrenal crisis is caused by a lack of cortisol. This can occur in patients who have been taking long term steroids and they are suddenly withdrawn. This is because taking long term steroids, suppresses the HPA (hypothalamic-pituitory-adrenal) axis leading to adrenal suppression.This takes ages to recover from/may never recover
b)
- Light headedness or dizziness
- Weakness
- Sweating
- Abdominal pain
- Nausea and vomiting
- Loss of consciousness
c)
- When the drug is no longer required it must be withdran slowly at a rate dictated by the duration of the treatment
- All patients must be advised to avoid sudden drug withdrawal
- Patients should be issued with a steroid card and/or wear an engraved bracelet that they should carry at all time. It gives information regarding diagnosis, steroid dose and doctor
Describe the action of glucocorticoids on bone
- Reduced oestrogen and testosterone, leads to increases rate of bone resorption which leads to reduced bone volume
- Increased urine calcium and decreased calcium resoprtion leads to increased rate of bone resorption
- Direct action on bone cells, leads to reduced bone formation which leads to reduced bone volume
- Reduced serum testosterone which leads to reduced bone formation
- Reduced muscle strength, leads to reduce bone fromation which leads to reduce bone volume
Descrie the relationship between dose of glucocorticoids and fracture risk
The higher the dosage of glucocorticoids, the higher the fracture risk
Describe the general measures to reduce bone loss from glucocorticoids
- Reduce the dose of glucocorticoids to a minimum
- Consider alternative formulations, routes of administration and prescription of alternative immunosuppressive agents
- Consider precribing bisphosphonate and Vitamin D and calcium supplements
- Good nutrition - adequate dietary calcium
- Weight-bearing physical excercise
- Avoid alcohol and tobacco
- Falls risk assessment in those at risk of falling
What is gout?
When monosodium urate crystal exert (painful) pressure around joints
Describe the mechanism for allopurinal
- It is an xanthine oxidase inhibitor so prevents xanathine from being converted to uric acid
- This lowers uric acid production and therefore lowers serum levels
