Opioids vs non opiods Flashcards
(7 cards)
Intro - complex physiological and psychological experience
Analgesic drugs are fundamental in managing both acute and chronic pain, a complex physiological and psychological experience. They are broadly classified into opioid and non-opioid agents, each with distinct mechanisms of action, pharmacokinetic behaviour, and clinical uses. Understanding their pharmacodynamic and pharmacokinetic characteristics provides a rational basis for appropriate therapeutic application.
2nd para - pharmacodynamics, non-opioid analgesics
In terms of pharmacodynamics, non-opioid analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol, act primarily by inhibiting cyclooxygenase (COX) enzymes involved in the synthesis of prostaglandins—mediators of pain, inflammation, and fever
. NSAIDs such as aspirin and ibuprofen non-selectively inhibit both COX-1 and COX-2 isoforms, while agents like celecoxib selectively target COX-2, minimising gastrointestinal toxicity. This inhibition reduces peripheral sensitisation of nociceptors, providing analgesic, anti-inflammatory, and antipyretic effects. Paracetamol, while structurally and functionally distinct, exerts analgesic and antipyretic effects via preferential inhibition of COX activity in the central nervous system. It lacks significant anti-inflammatory action and does not inhibit platelet aggregation, making it a safer alternative when NSAIDs are contraindicated.
3rd para - opioid analgesics, G protein coupled
Opioid analgesics, by contrast, act centrally on the nervous system. They bind to G protein-coupled opioid receptors—particularly μ (mu), δ (delta), and κ (kappa) subtypes—located in the brain, spinal cord, and peripheral tissues
. The μ-opioid receptor (MOR) is chiefly responsible for analgesia. Upon activation, opioids inhibit presynaptic calcium influx and promote postsynaptic potassium efflux, leading to neuronal hyperpolarisation and reduced neurotransmitter release. This suppresses nociceptive signal transmission both at the spinal level and in descending inhibitory pathways involving the periaqueductal grey and raphe nuclei. Although effective, opioids also produce euphoria, respiratory depression, and constipation, and long-term use can result in tolerance and dependence due to receptor desensitisation and neuroadaptive changes.
4th para - pharmacokinetics of these agents
The pharmacokinetics of these agents differ considerably. Non-opioid drugs such as aspirin are well absorbed orally, with high plasma protein binding and hepatic metabolism. Aspirin has a relatively short half-life (2–3 hours) and is rapidly distributed to inflamed tissues
. Ibuprofen exhibits similar properties, while paracetamol is extensively metabolised in the liver via glucuronidation and sulfation pathways. Importantly, paracetamol’s toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI) may accumulate in overdose scenarios, necessitating cautious dosing.
5th para - opioids morphine and codeine
Opioids show more variable pharmacokinetics. Morphine is poorly absorbed orally due to first-pass metabolism and is more effectively administered parenterally. It has a half-life of 3–6 hours and undergoes hepatic glucuronidation. Codeine, in contrast, is better absorbed orally and relies on CYP2D6-mediated conversion to morphine for its analgesic effect. Methadone, a synthetic μ-opioid agonist, has a long elimination half-life exceeding 24 hours, allowing once-daily dosing in opioid substitution therapy. These kinetic differences influence onset, duration, and dosing frequency in clinical practice
.
6th para - non-opiod analgesics first line defense
Clinically, non-opioid analgesics are first-line treatments for mild to moderate pain, particularly when inflammation is involved. Their accessibility and favourable safety profile make them appropriate for long-term use, though NSAIDs are associated with gastrointestinal, renal, and cardiovascular risks when used chronically. Paracetamol offers a safer alternative for patients with contraindications to NSAIDs, especially in the context of upper gastrointestinal disease or bleeding risk.
7th para - opioids reseved for moderate pain methadone
Opioids are reserved for moderate to severe pain, such as that associated with surgery, malignancy, or palliative care. They provide superior analgesia in these settings but require cautious use due to their potential for tolerance, physical dependence, and misuse. Methadone’s pharmacokinetics make it particularly suited for managing opioid addiction, offering a steady-state plasma level and attenuated withdrawal symptoms.
