Analgesics

Question 1

NSAIDs and acetysalic acid (aspirin)

Answer 1

Inhibited COX enzyme, thereby inhibiting the biosynthesis of prostaglandins and thromboxanes. Prostaglandins sensitize nociceptive neurons cause inflammation due to vasodilation recruiting proinflammatory compounds, stimulate mucus secretion (COX1), and inhibit secretion og HCl.

Question 2

Paracetamol

Answer 2

Is not anti-inflammatory because it binds to COX allosterically. During inflammation, allosteric binding site is protonated, and paracetamol cannot bind.

Question 3

Opioid receptor agonists

Answer 3

Three different opioid receptors μ-, δ-, and κ-receptors.
Opioid receptors are Gi coupled -> inhibits AC activity -> decreases cAMP -> low PKA activity. On the presynaptic neuron, this results in less phosphorylation of voltage gated Ca2+ channels, which means less glutamate release and less NMDA receptor activation -> less pain. On the postsynaptic neuron, opioid receptors will open K+ channels to hyperpolarize the neuron and make it more difficult to be activated.

Question 4

Morphine

Answer 4

Activates μ-, δ-, and κ-receptors (agonist; technically a partial agonist, but very close to full agonist)
● Inhibits nociceptive neurotransmission in dorsal horn
● Decreases the subjective effects of pain
● Decreases central sensitization
● Inhibits cough reflex through unclear mechanism

Side-effects:
- People can die because of respiratory depression that occurs even at therapeutic doses  because thalamic chemoreceptors of CO2 will be less sensitive  don’t have to feel the need for respiration.
- Sedation
- Inhibits GI motility (constipation).
- Euphoria (DA release onto the nucleus accumbens).