Opioid Analgesics Flashcards
What are the major analgesic drugs?
Major analgesic drugs are:
Opioids
NSAIDS
Tricyclic antidepressants
Anti-convulsants (Na+ channel blockers)
Ca2+ channel blockers
Cannabinoids
What do opiates act on? + 3 opioid receptor subtypes
Opioids/ates act at G-protein-coupled receptors
All linked to alpha subunit Gi (inhibit adenylate cyclase, cAMP, PKA)
Opioid receptor subtypes - MOP (µ), DOP (delta), KOP (kappa)
What are MOP receptors?
where are they expressed + associated & linked with?
MOP, or mu receptors are opioid receptors, one of 3 subtypes (MOP, DOP, KOP)
MOP (µ/mu) most expressed in the pain pathway
Often associated with actions of morphine
Most prominently linked to analgesia
4 places opioid receptors are found?
Opioid receptors found in peripheral nerves, dorsal root ganglion, dorsal horn + involved in descending inhibitory pain pathways in brain.
Opioids have pre + postsynaptic effects which reduce nociceptive conduction
compare pre VS post-synaptic cellular mechanisms of opioids??
Presynaptic: opioids decrease VGCCs –> ↓ NT release
They also ↑ K channels -> K efflux/hyperpolarisation –> ↓ presynaptic depolarisation which ↓ VGCCs etc
Postsynaptic: ↑ K+ channels= K efflux and hyperpolarisation –> ↓ neuronal firing
Why do Opioids also switch on neuronal areas involved in producing analgesia, e.g., Increase descending inhibition?
In PGM and N. raphe magnus, opioids switch neurones on, and switch interneurons off (interneurones in PGM inhibit analgesic pathway)
So opioid receptors on inhibitory interneurons deactivate VGCCs + cause K+ efflux –> decrease firing of interneuron = disinhibition of anti pain
How is euphoria an effect of opioids?
Opioids –feel good, stress relief
due to ↑ dopamine neurotransmission –> reduced release of GABA neurotransmitter in ‘reward’ areas of brain (nucleus accumbens)
How can opioid use lead to respiratory depression?
Opioid receptors are in brain areas which cause drive to breathe: pre-Botzinger complex, brain stem, medullary chemoreceptors
Opioids makes medullary chemoreceptors less sensitive to PCO2-> suppression of respiratory pattern
↑ arterial PCO2 normally ↑ ventilation, but can’t occur due to opioid, causing resp failure =commonest cause of death in opioid OD :(
What is the effect of opioids on cough, vomiting and pupils?
Cough: suppress cough reflex – codeine used in cough meds
Vomiting: stimulate ctz (area postrema) –> vomiting. Hence morphine is often given w metoclopramide (anti-emetic)
Pupil: stimulates oculomotor nerve –> ↑ parasym pupil constriction. This diagnoses OD as most other loss of consciousness cause pupil dilation!
3 effects of opioids on the GI tract?
therefore which opioid is used for a common GIT problem + why?
opioids increases tone + reduces motility of GIT –> leading to constipation & reduces absorption of other drugs !
Loperamide (opioid) used for diarrhoea (doesn’t cross BBB –> therefore no euphoria/dependence)
Opioids receptors on mast cells cause histamine release. Why is this important + therefore when should you not prescribe opioids?
Histamine release from mast cells –> inflammation, bronchoconstriction, hypotension = dangerous!
therefore avoid opioids in acute asthma– low doses/monitor in asthmatics
Why do we tend to give opioids intravenously or intramuscularly?
Opioids in alkaline intestinal solution behave as a weak acid, donating H+ = unionised - therefore are easily absorbed in the intestine, but also have significant first-pass liver metabolism ! - Therefore you lose opioid effects esp. when taken orally –> Hence why you give the drug iv or im
compare codeine vs methadone vs diamorphine?
+ explain their metabolism using a diagram.
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For opioids, give examples +compare: full agonist, antagonist and partial agonist. What they are used for?
Full agonist: (dia)morphine/methadone=high affinity + efficacy
Antagonist: naloxone= no effect. Competitive inhibitor –> therefore reverses morphine induced symptoms + OD problems.
Partial agonist: buprenorphine= high affinity, medium efficacy. Long duration of action –> therefore helps heroin withdrawal + treats heroin addiction
What are the signs of an opioid OD?
