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 made by COX-1 and 2 increase and decrease Na+ retention in response to changes in CI- extracellular tonicity or low BP
- aspirin (NSAIDs) promote Na+ retention whcih increases BP, this counteracts the effect of anti-hypertensives
- PGs are important when the kidney is comprised- making one at risk of renal ischemia
what is the role of PGs, generated by COX-1 in the GI system
1) inhibit secretion acid secretion
2) stimulate mucus and HCO3- secretion, vasodilation and therefore
3) are cytoprotective for gastric mucosa
what is the effect of aspirin on the GI system
- inhibits COZ-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 cuases Reyes syndrome and dose dependent hepattis
Explain how aspirin affects renal activity?
- prostaglandins made by cox-1 and 2 increase and decrease Na+ retention in response to changes in CI- 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) inhbiit 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:
1. gastric distress
2. gastric bleeding - acute haemorrhage all due to increased acid secretion and reduced mucus production to protect the gastric lining
- this cuases reyes syndrome and dose dependent hepatitis
what is the effect of NSAID inhbiition of PGs generated by COX-2 on labor and delivery
it inhbiits 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 it from rising preventing increase in brain PGs
what role do brain PGs play in body temp?
as IL-1 release increases from the leukocytes they act on hypothalamus which increases body temp. this is associated wirh brain PGs
what is the advantage of COX-2 selective inhibitors?
anti-inflammatory response with less adverse effects especially those associated with the GI system
can have a role in cancer prevention and Alzheimers disease
what is the disadvantage of COX-2 selective inhbitors
associated with MI and stroke as they don’t inhbit platelet aggregation
potential toxicities in kidney therefore increased risk of thrombotic events
what is the process of cell death called during inflammation?
apoptosis
what is the role of Lipoxins as anti-inflammatory mediators?
signal macrophages to clean up dead cells from inflammation
give an example of an anticonvulsant and its role in pain?
carbamazepine
used for trigeminal neuralgia more specifically but not good for neuropathic pain
na+ channel blocker
others anticonvulsants are used for migraines
give an example of an anti-epileptic and its role in pain?
gabapentin and pregabalin
used for diabetic neuropathy, fibromyalgia and postherpetic neuralgia
act on alpha-beta subunit of the voltage gated Ca2+ channel
how do tricyclic antidepressants work in pain treatment?
e.g. amitryptilline
work to increase serotonin levels hence engaging the descending pain inhibitory circuit
may also inhibit voltage-gated Na+ channels and NMDA receptors
used for neuropathic pain, diabetic neuropathy, facial pain and sometimes migraines
