Selected Drugs Flashcards
What are examples of Drug Target sites?
Cell membrane receptor sites, nuclear receptors, transport mechanisms, ion channels, enzyme inhibitors
Where are opioid receptors found?
Brain, spinal cord, GI tract
What is an example of an opioid agonist?
Morphine
What are the opioid receptors?
mu, kappa, delta, sigma
What are opioid agonist effects?
Analgesia, miosis (constrict of pupil), cough suppression, sedation, constipation, nauseas & vomiting, rashes & itching, hypotension, respiratory depression, tolerance & dependence. WH
Where in the spinal cords are high in opioid receptors?
Thalamus & dorsal horn
What opioid receptor subtype has the most involvement with analgesia?
Mu
What are the main side effects of opioid agonists?
Respiratory depression, pupil constriction, reduced GI motility, euphoria, dysphoria, sedation, physical dependence
What causes opioid agonist adverse effects?
Unwanted effect are attributable to stimulation of the various sub groups and locations of opioid receptors: therefore difficult to eliminate side effects
What differences between opioid agonists?
All opioid agonists have the same mechanism of action (i.e. opioid receptor agonists) but differ in receptor selectivity, potency, duration of action, metabolism & this determines their clinical use
What are other uses of opioid agonists?
Diarrhoea (loperamide), cough suppression (pholcodine)
What are natural opioids?
Morphine and codeine are naturally occurring opioids
Morphine
Gold standard opioid analgesia, relatively short half-life, available immediate and sustained release
Codeine
Mild to moderate analgesia, anti-diarrhoea agent & cough suppressant. Isa pro-drug - it must be partially metabolised to morphine (active drug) in the liver to have an effect
Oxycodone
Twice as potent as morphine (care with dose conversation), immediate and sustained release
Pethidine
Fast acting, short duration, less respiratory depression. Has toxic metabolite norpethidine
Methadone
long half-life (24 hours) less frequent dosing required, but risk of accumulation. Main agent in opioid substitution therapy
Fentanyl
Fast onset of action, very potent
Buprenorphine
Partial agonist so has an analgesic ceiling as much h less risk of respiratory depression
What is the use of a competitive antagonist in opioid agnostic?
Reversal of opioid overdose. e.g. naloxone
How does tramadol work?
Is a weak agonist for opioid receptors it act principally by inhibition of noradrenaline rey-take and stimulation of serotonin release at nerve synapses in the CNS/spinal cord thus modifying pain impulses to the CNS
What are some side effects of tramadol?
Nausea, dozzine, increased risk of seizures and serotonin syndrome
What are the natural corticosteroids?
Adrenal context produces the natural corticosteroids hydrocortisone (cortisol) and aldosterone
What is hydrocortisone?
A glucocorticoid (it has metabolic, anti-inflammatory and immunosuppressant effects)
What is aldosterone?
A mineralocorticoid (helps maintain blood volumes, promotes retention of sodium & water, increases excretion of hydrogen & potassium)
What are hydrocortisone & aldosterone important?
In the maintenance of homeostasis, reaction to stress & tissue maintenance
What is hydrocortisone as a drug used for?
Anti-inflammatory agent e.g. dermatitis
How do synthetic hydrocortisone differ from natural?
Have a similar action to natural but are longer-acting (longer half-life) and more potent) e.g. prednisolone, methylprednisolone, beclomethasone, dexamethasone
What is the mechanism of action of glucocorticoids?
They enter the cell and bind to glucocorticoid receptors (GR) in the cytosol. The steroid-GR complex enters the cell nucleus. The complex undergoes binding with various tissue factors that allow it to attach to specific genes in the nuclear. This binding causes either induction or suppression of specific messenger RNS (mRNAs) involved in the production of inflammatory mediators (suppressed) or anti-inflammatory proteins (induced)
What are some examples of the use of glucocorticoids?
Prevention of transplant rejection, severe allergic reactions, autoimmune disease, inflammatory disorders, prevent preoperative nausea & vomiting, in haematological malignancies
What are some side effects of glucocorticoids?
Cushingoid effects (weight gain, fat redistribution, osteoporosis, hyperglycaemia, poo wound healing), HPA Axis suppression e.g. adrenal atrophy, decreased growth, decreased response to infection, mineralocorticoid effects (hypertension, oedema), CNS effects (euphoria, headache, restlessness, depression, anxiety), visual disturbances (cataract, glaucoma), GI effects (bleeding, ulcer)
What is an example of a pro-drug glucocorticoid?
Prednisone - turned into active drug prednisolone
What is the general mechanism of action of diuretics?
Diuretics promote the excretion of sodium ions by the kidney (known as naturesis) by blocking the sodium transporters at various parts of the nephron so that sodium is not reabsorbed and stays in the urine. As a consequence water is also excretion.
What diuretics cause vasodilation?
thiazides therefore reducing blood pressure
What are some potassium sparing diuretics?
Amiloride + Spironolactone. Act on Collecting duct
What are some Loop diuretics?
Frusemide + Bumetanide. Working on Loop of Henle
What is the use of diuretics?
Increase urine output in oedematous states e.g. congestive heart failure, renal failure, liver failure. Reduce high blood pressure. To correct electrolyte imbalances (amiloride)