CPTP 3.15 NSAIDs, non-opioid analgesics, anti-migraines

Question 1

Aspirin

Pharmacodynamics + interactions

Answer 1

Pharmacodynamics:
NSAID, COX inhibitor

Interactions: warfarin

Question 2

Ibuprofen

Pharmacodynamics + Contraindication

Answer 2

Pharmacodynamics:
NSAID, COX inhibitor

Contraindication: pregnancy

Question 3

Celecoxib

Pharmacodynamics + Contraindication + significant pharmacokinetics + significant side effects

Answer 3

Pharmacodynamics:
NSAID, COX inhibitor

Contraindication: pregnancy

Pharmacokinetics:
Lipophilic, less useful in obese patients as accumulates in fat

Significant side effects:
Increased risk of stroke & heart attack

Question 4

Paracetamol

Pharmacodynamics

Answer 4

Non-competitive inhibitor, reduces COX active site, prevents ligand interaction

Also removes free ROS that activate phospholipase A2 (to make arachdonic acid)

Question 5

Sumatriptan, Almotriptan, Zolmitriptan

Pharmacodynamics + Clinical use + interactions + side effects + Contraindication

Answer 5

Pharmacodynamics:
5HT agonist

Clinical use: Relief from migraine acute attack

Interactions:
-SSRIs, MAOIs, St John’s wort

Side effects:
-CNS toxicity

Contraindications:

• IHD, MI
• Uncontrolled/severe hypertension
• Pregnant/breastfeeding
• Hepatic impairment

Question 6

Pizotifin

Pharmacodynamics + Clinical use + side effects + Contraindication

Answer 6

Pharmacodynamics:
5HT & Histamine ANTAGONIST
(similar structure to TCA)

Clinical use: Migraine prophylaxis

Side effects:
-Anti muscarinic (pupil dilation, dry mouth, bronchodilation, etc)

Contraindications:

• Epilepsy hx
• Urinary retention
• Susceptibility to angle closure glaucoma
• Pregnant/breastfeeding
• Hepatic/renal impairment

Question 7

Which conditions must NSAIDs be used with caution in? Why?

Answer 7

1. Asthma
   Exacerbates symptoms through unrestrained leukotriene synthesis (due to COX1 inhibition)
2. Renal insufficiency
   Such pts rely on prostaglandin production to maintain normal fx –> COX inhibition knocks out this reserve fx

Question 8

General side effects of NSAIDS

Answer 8

• GI: increased risk of bleeding, irritation
• CVS: increased risk of heart attack, stroke
• kidney: increased risk of renal insufficiency

Note:

• Hypertension is due to COX inhibition in macula densa
• PGI2/E2 normally regulate renal vasodilation

Question 9

What do 5HT agonists & antagonist do re: migraine control

Answer 9

AGONIST (relief from acute attack)

• constricts large blood vessels
• inhibits CN V
• desensitises sensory nerves

ANTAGONIST (prophylaxis)
-limits initial pro-inflammatory & vascular changes

Question 10

Effects of inhibiting COX-1 & COX-2

Answer 10

Main target: COX-2

COX-1:
Housekeeper enzyme, inhibition causes side effects

COX-2:
Inhibition is anti-inflammatory, analgesic, anti-pyretic

Question 11

Effects of eicosanoids on pain stimulation

Which are the eicosanoids

Answer 11

• Kinin & serotonin stimulate pain
• Eicosanoids sensitise receptors to kinin & serotonin (don’t stimulate pain themselves)

Eicosanoids: prostacyclin, prostaglandin, thromboxanes, leukotrienes