CNS drugs and analgesia

The same dose that stopped working

• After weeks of a strong painkiller, a patient needs a bigger dose for the same relief. Their nerve cells have adapted.
• Each brain drug acts at a known synapse, and tolerance and dependence are what that synapse learns.

Opioids

• Opioids 阿片类 act at μ receptors: strong pain relief, with slowed breathing, constipation and tiny pupils.
• Naloxone is a competitive μ antagonist that reverses an overdose, but it wears off faster than many opioids, so breathing can slow again.

NSAIDs and paracetamol

• NSAIDs 非甾体抗炎药 block cyclo-oxygenase (COX), so less prostaglandin is made: less pain and inflammation, but a cost to the stomach lining and kidneys.
• Paracetamol relieves pain and fever with little anti-inflammatory effect. In overdose it uses up glutathione, and its toxic metabolite kills liver cells.

Sedatives and antidepressants

• Benzodiazepines 苯二氮䓬类 make GABA-A receptors respond more strongly to GABA (positive allosteric modulation): calm, sleep, less anxiety.
• SSRIs block serotonin reuptake at once, but the mood effect takes weeks, as the receptors adapt.

Tolerance and dependence

• Tolerance 耐受性 is receptors down-regulating under constant stimulation, so the same level does less. Dependence 依赖性 shows when the drug stops suddenly and the adapted state is left unopposed.
• Constipation and tiny pupils from opioids show little tolerance, so they persist at stable doses.

Worked example: three pains, three sites

Worked example: naloxone wears off

Three common slips

Recap