Pharmacology of Pain: Non-opioids Flashcards
what is the classification of anti-inflammatory drugs?
- NSAIDS (antipyretic and anti-inflammatory drugs)
- steroid anti-inflammatory drugs
- 5-LOX inhibitors and Leukotriene receptor antagonist
what are prostaglandins synthesised from?
arachidonic acid
what do prostaglandins cause?
- smooth muscle contraction
- inhibition of platelet aggregation
- bronchoconstriction
- vasodilation
- Fever
- diuresis
- immunomodulation
what does thromboxane cause?
- vasoconstriction
2. platelet activation
what are common pharmacological effects of NSAIDS?
- Analgesic (CNS and peripheral effect) may involve non-PG related effects.
- Antipyretic (CNS effect).
- Anti-inflammatory (except acetaminophen) due mainly to PG inhibition.
- Inhibit activation, aggregation, adhesion
of neutrophils & release of lysosomal enzymes. - Uricosuric - uric acid in urine
what are common Adverse Effects of NSAIDS?
- platelet dysfunction
- Gastritis and peptic ulceration
- renal failure
- Na+ and H20 retention and edema
- analgesic nephropathy
- prolonged gestation and inhibition of labor
- hypersensitivity
- GI bleed and perforation
what effect do NSAIDs have when they inhibit cox-1 ?
-cause GI toxicity
what effect do NSAIDs have when they inhibit cox-2?
anti-inflammatory actions
give 3 examples of cox 2 selective inhibitors
celecoxib
etoricoxib
valdecoxib
what is the issue with cox 2 selective drugs?
-no cardio protection and increased MI
what is the effect of the uncoupling phosphorylation of aspirin on respiration?
- increases CO2
- stimulates respiration
what effect does aspirin have on the direct stimulation of the respiratory centre?
- can cause hyperventilation
- respiratory alkalosis
- renal compensation
what happens when aspirin depresses the respiratory and cardiovascular centres?
- lower BP
- respiratory acidosis
- no compensation
- metabolic acidosis
what is the metabolic effect of aspirin?
- uncoupling of oxidative phosphorylation due to increased CO2 production - resulting in hyperventilation.
- hyperglycemia and depletion of muscle and hepatic glycogen
why can’t you give children under 12 years old aspirin?
as their kidneys may not be well developed enough to metabolise and clear the aspirin which can cause toxicity.
what is the effect of aspirin on platelets?
- irreversibly inhibits platelet cox-1 derived TxA2 hence increasing bleeding time by inhibiting platelet aggregation.
- COX-2 derived PGI2 inhibit platelet aggregation
- so basically aspirin only works on the thromboxane part to inhibit platelet aggregation as prostaglandins already inhibit platelet aggregation themselves.
Explain how aspirin affects renal activity?
- prostaglandins (PG) made by cox-1 and 2 increase and decrease Na+ retention in response to changes in Cl- extracellular tonicity or low BP.
- aspirin (NSAIDs) promote Na+ retention which can increase BP. this counteracts the effect of anti-hypertensives
- PGs are important when the kidney is compromised - Making one at risk of renal ischemia
what is the role of PGs, generated by COX-1, in the GI system?
1) inhibit stomach acid secretion
2) stimulate mucus and HCO3- secretion, vasodilation and therefore
3) are cytoprotective for the gastric mucosa.
what is the effect of aspirin on the GI system?
-inhibits COX-1 hence producing opposite effects to COX-1:
- gastric distress
- gastric bleeding
- acute haemorrhage
all due to increased acid secretion, and reduced mucus production to protect the gastric lining.
-This causes Reyes syndrome and dose dependent hepatitis
what is the effect of NSAID inhibition of PGs generated by COX-2 on labor and delivery?
it inhibits PG production hence prolonging gestation.
why is paracetamol used?
no anti-inflammatory effect but has mild analgesic effects
what is the result of high paracetamol doses in the body?
hepatotoxicity
how does paracetamol cause analgesia?
- works centrally and peripherally
- inhibits PG synthesis in inflamed tissues
what effect do NSAIDs have on decreasing body temperature?
- none as temperature change is more to do with hypothalamic problems so NSAIDs don’t decrease body temp.
- but they do prevent prevent it from rising by preventing the increase in brain PGs.
