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26 Cards in this Set
- Front
- Back
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Structure |
Analgesic Drugs - targets Opioids: Mechanism of action, Morphine NSAIDS. Mechanism, Side effects, COX-2 inhibitors Psychotropic agents Combinations |
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What is Analgesia? |
· Pain-relief · Electrical stimulation of periaqueductal grey and medulla causes analgesia · Analgesiacan be blocked with naloxone, an opiate antagonist. Antagonises actions of morphine |
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Where do Analgesic Drugs act? |
PNSand CNS. |
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What are targets for drugs? |
neurotransmitters.
· Glutamate and GABA · 5-HT noradrenaline · Adenosine · Eicosanoids – polyunsaturated FA derive from FAprecursor arachidonic acid – synthesized in liver from linoleic acid derivedfrom diet – vegetable oil. E.g. PG, TX, LT |
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Examples of Opioids? |
Natural - heroin Opium alkaloids - codeine and morphine. Synthetic –methadone, meperidine |
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What do opioids mimic? |
· Mimic endogenous opioids
Enkephalins B-endorphin - acts through u-opioid receptor Dynorphin - k-opioid receptor. Widely distributed in CNS - esp. arcuate nucleus and in both oxytocin and ADH neurons in the supraoptic nucleus. Endomorphins- Most potent opioid for u-opioid receptors. |
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What are opioid receptors? |
- Mu – found at all levels of pathway. Causes respiratorydepression, pupil constriction, reduced GI motility, euphoria, sedation,physical dependence - Delta – brain, spinal - Kappa – brain, spinal cord Action is associated with spinal analgesia, miosis (pinpoint pupils). Diuretic effects due to negative regulation of ADH. Side effects - dysphoria, hallucinations |
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What does the pharmacodynamic response depend upon? Give an example |
- Pharmacodynamic response depends upon depend towhich it binds, its affinity for that receptor, whether the opioid is anagonist or an antagonist.
E.g. the supra-spinal analgesic properties of theopioid agonist morphine are mediated by activation of mu1 receptor; respiratorydepression and physical dependence by mu2 and sedation and spinal analgesia bythe kappa receptor. |
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Mechanism of action |
· Acts on opioid receptor, GPCRs acting onGABAergic neurotransmission. Decrease cAMP, increase K channels and decrease Cachannels. · Presynaptic inhibitory action to decreasetransmitter release e.g. Glu. · Mu receptors mediate most effects |
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Morphine- what is it? What pain? |
· The ‘reference’ mu -agonist analgesic. · Rapid-acting narcotic, binds very strongly tomu-opioid receptor Moderateto severe pain. |
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Uses?
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· Main Uses: Preop – relieve anxiety, analgesia,reduce anaesthetic required. Postop – pain relief. · Other uses: reduces affective component of pain,relieves anxiety, euphoria, sedation. |
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What is Morphine antagonised by? |
naloxone inverse-agonist |
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Side effects of morphine? |
nausea,respiratory depression, constipation, sustained gut muscle contraction –decreased propulsion in SI. Pupil constriction |
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Tolerance Relate to morphine |
higherdose required to produce a given effect. Or, given dose produces quantitativelyless effect over time. Depends on dose, repetition, regularity. Attenuated byCa channel blocked, NMDA antagonists, zinc. |
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Dependence Relate to morphine |
alteredphysiological state produced by LT administration. Target tissues adapt andrequire drug for normal functioning. Discontinuation produces withdrawal or abstinence.Or in the case of opioids, when an antagonist (naloxone) is administered. |
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Syndrome of dependence for morphine? |
· The acute opioid withdrawal (abstinence)syndrome – strong flu-like symptoms, muscle tremor, increased HR and BP,hyperventilation |
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What are NSAIDs used for? |
· Uses: treat mild to moderate pain. Reducesinflammation – aspirin (unlike opioids and paracetamol). Adjunct to opioid insevere pain |
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Examples of NSAIDs |
· E.g. aspirin, paracetamol, ibuprofen |
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Effects of NSAIDs |
analgesic,anti-inflammatory, antipyretic – fever caused by elevated prostaglandin E2, which alters the firing rate of neurones within the hypothalamu. Inhibit COX, less PGE2. |
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Mechanism of NSAIDs |
· Exact mechanism is uncertain. Appears to actcentrally in brain. · Acts as a non-selective inhibitor of cyclo-oxygenase(COX-1 and COX-2) - attenuate production of prostaglandins, thromboxanes fromarachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipaseA2) · Inhibition is competitively reversible, unlikeaspirin. |
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NSAIDs side effects |
· Paracetamol is safe in low and infrequencedoses. · GI irritation and bleeding, platelet dysfunction · Liver and occasionally kidney dysfunction |
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COX-2 inhibitors- examples and derivation |
· E.g. rofecoxib · Derived from NSAIDs. |
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COX-2 inhibitors mechanism and advantage but issue |
· Research suggested most of the adverse effectsof NSAIDs to be mediated by blocking the COX1 (constitutive) enzyme, with theanalgesic effects being mediated by the COX2 (inducible) enzyme. · Equally as effective as NSAIDs but causes lessGI haemorrhage · Increase risk of CV events by 40% - led to withdrawal |
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What are Psychotropic agents effective for? Active component? Receptors? |
· Effective in some forms of intractable pain· main active component: D9-tetrahydrocannabinol(THC) · specific cannabinoid receptors - CB1(brain))and CB2 ketamine(NMDA receptor antagonist) |
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Psychotropic agents: use ? |
· A recent study finds that inhaled cannabis iseffective in alleviating neuropathy and pain resulting from spinal injury andmultiple sclerosis |
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Combinations |
· Analgesics are frequently used in combination,e.g. paracetamol and codeine · Paracetamol, aspirin and ibuprofen withmid-range opiates show beneficial syngergistic effects by combatting the painat multiple sites of action |
