Pharmacology of GORD Flashcards
What are some examples of NSAIDS?
- ibuprofen
- naproxen
- diclofenac
What is the primary mechanism of action of NSAIDS?
inhibition of cyclo-oxygenase (COX) enzyme - the rate limiting step of the production of prostaglandins and thromboxanes from arachidonic acid.
Leading to the anti-inflammatory and antipyretic actions of NSAIDS - tend to be due to inhibition of COX2. Side effects due to COX1 inhibition.
What is the drug target of NSAIDS?
cyclo-oxygenase (COX) enzyme
What are the main side effects of NSAIDS?
- gastric irritation
- gastric ulceration
- gastric bleeding
- gastric perforation (extreme)
- reduced creatine clearance
- nephritis
- bronchoconstriction
- skin rashes
- dizziness
- tinnitus
- hypertension, stroke, MI
- chronic renal failure
What are NSAIDS contraindicated with?
asthma due to possible bronchoconstriction
What has aspirin been linked with?
post-viral encephalitis
Reyes syndrome in children
What are the main uses of NSAIDS?
- analgesia
- antipyretics
- anti-inflammatories
- anti-aggregatory agent (aspirin ONLY)
What are some examples of Proton Pump Inhibitors?
- omeprazole
- lansoprazole
What is the primary mechanism of action of PPIs?
irreversible inhibition of H+/K+ ATPase in the gastric parietal cells.
weak bases that accumulate in the canaliculi of the parietal cells - increases concentration and duration of action
Inhibit basal and stimulated gastric acid secretion by >90%
What is the main drug target of PPIs?
H+/K+ ATPase (proton pump)
What are the main side effects of PPIs?
- headache
- diarrhoea
- bloating
- abdominal pain
- rashes
What is omeprazole and inhibitor of?
cytochrome P2C19 and reduced the activity of eg clopidogrel when platelet function is monitored
How are PPIs administered?
- orally
- degrade rapidly at low pH
- therefore capsules contain enteric-coated granules
What does it mean that PPIs are pro-drugs?
at a low pH are converted into 2 reactive species withreact with the sulphydryl groups in the H+/K+ ATPase responsible for getting H+ out the parietal cell
What is an example of a Histamine (H2) receptor antagonist?
- ranitidine
What is the primary mechanism of action of Histamine (H2) receptor antagonists?
competetive antagonist of H2 receptors
- inhibits the stimulatory action of histamine released from enterochromaffin-like (ECL) cells on the gastric parietal cells
- inhibit gastric acid secretion by around 60%
What is the drug target of H2 receptor antagonists?
Histamine H2 receptors
What are the side effects of H2 receptor antagonists?
- diarrhoea
- dizziness
- muscle pains
- transient rashes
What happens in Climetidine?
- inhibits cytochrome P450
- can retard the metabolism and potentiate the metabolism and the effects of a range of drugs (TCAs and oral anti-coagulants).
What is the normal dose of ranitidine?
2 x daily well tolerated half life: 2-3 hours 1st metabolism = 50% bioavailability low dose available over the counter
What is the primary mechanism of action of Paracetamol?
- actions restricted to nervous tissue
- unclear mechanism of action
current hypothesis: central and peripheral action and interaction with COX3 isoform (inhibition of PG synthesis), cannabinoid receptors or the endogenous opiods.
Interactions at 5HT and adenosine receptors have also been proposed.
What is the possible drug target of paracetamol?
unknown - COX 3 isoform
What are the main side effects of Paracetamol?
few side effects at therapeutic dosage
at overdose:
- hepatoxicity
occasionally: skin reactions
Why is paracetamol not considered an NSAID?
it has very little anti-inflammatory activity
What are the main effects of Paracetamol?
- anti-pyretic
- analgesic (mild to moderate)
