* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Opioid Anelgesics
Survey
Document related concepts
NMDA receptor wikipedia , lookup
Pharmacogenomics wikipedia , lookup
Drug interaction wikipedia , lookup
Discovery and development of angiotensin receptor blockers wikipedia , lookup
Polysubstance dependence wikipedia , lookup
5-HT2C receptor agonist wikipedia , lookup
Dextropropoxyphene wikipedia , lookup
Toxicodynamics wikipedia , lookup
Cannabinoid receptor antagonist wikipedia , lookup
NK1 receptor antagonist wikipedia , lookup
Nicotinic agonist wikipedia , lookup
Neuropharmacology wikipedia , lookup
Transcript
PAIN MANAGEMENT:NARCOTIC ANELGESICS Lecture Objectives • • • • • At the end of the lecture, you should be able to: State Mechanism of action of opioids State actions and uses of opioids State adverse effects of opioids Enlist individual differences between different opioid drugs Analgesics Narcotic Analgesics OPIOIDS Non narcotic Mainly NSAIDS Opioid Anelgesics • Mechanism of Action: – Act in part via receptors for endogenous opiopeptides such as enkephalins, dynoprhins, and β endorphins – Opioid receptors are of multiple types, all G-protein-linked • • • Μ (mu) δ (delta) Κ (kappa) MOA • • • • Effects of specific opioid drugs depend on the receptor subtype with which they interact as – Full agonist – Partial agonists – Antagonists Some drugs (mixed agonist-antagonist) may activate one receptor subtype and act as antagonist at another subtype MOA Activation of pre-synaptic opioid receptors causes inhibition of Ca+2 influx through voltage regulated ion channels ↓ neurotransmitter activation of post synaptic opioid receptors results in ↑ K+ MOA • • • Opioid receptors are also located presynapticaally on primary afferents (type C and A fibres) in the dorsal horn of the spinal cord Activation of these receptors ↓ release of substance P Substance P is a peptide neurotransmitter that cuases excitatory actions in pain pathways • • • Opioid receptors involved in spinal anelgesia are of both of μ (mu) and Ќ( kappa) subtypes Opioid Anelgesic Phamracology Variations exist between individual drugs in terms of the following actions which are based on morphine as the prototype drug of the class Anelgesia: – Increase pain tolerance and ↓ peception and reaction to pain – Variable efficacy – Morphine is full agonist and gives maximum pain relief – Persistent dull aching pain responds better than intermittent • Sedation • Respiratory Depression – Drowsiness – Possible euphoria – Short term memory loss – Decreased response to ↑ pCO2 (even at Rx doses) via depression of neurons in brainstem respiratory center-major problem in overdose • Cardiovascular – Minimal effects on heart – Cerebral vasodilation ↑ intracerebral pressure (avoid in head traumma) – Morphine (but not most of the other opitates) releases • • • GI tract – – – Decreased peristalsis Constipation (potential clinical use in diarrheal state) e.g. loperamide, diphenoxylate Smooth muscle – – – Increased tone of biliary system, bladder, ureter Possible spasm (except meperidine) which blocks M receptors ↓ tone of vasculature (hypotension via histamine) and uterus (slow delivery) Pupils – Miosis via cholinrgeic activity (except meperidine) • Cough supression • Nausea and emesis – Anti tussive action – Stimulation of CTZ in the area postrema – Dual action Kinetics • • Morphine undergoes first pass metabolism in the liver (low oral bioavailibity) One of its metabolites morphine-6-glucuronide is highly active, contributing greatly to anelgesia and causing possible toxicity in renal dysfunction Clinical Corelate • Contraindication and caution for opioids • Pulmonary dysfunction • Hepatic/ renal dysfunction • Adrenal or thyroid deficiencies – Head injuries – (possible increased intracranial pressure) – Except pulmonary edema – Possible accumulation • – Exaggerated responses Pregnancy – Possible neonatal depression or dependence Adverse Effects • Acute toxicity – Extensions of the pharmacodynamic actions – Severity greatest with full agonists like morphine – Characteristic triad: pin point pupils, respiratory depression, comatose state • Management – Maintain patent airway and assist ventilation – Avoid oxygen ( decreased breathing) – IV naloxone Adverse Effects • Tolerance – Occurs with continued use – Changes in cellular adaptive responses but not receptor numbers – Tolerance is marked for CNS actions such as analgesia, euphoria, respiratory depression – Occurs minimally in terms of miosis and GI motility – Cross tolerance between individual opioid analgesics Dependence • Both psychological and physical components • • • • • • • Latter evident by withdrawal syndrome which may include anxiety, lacrimation, rhinorrhea, sweating, goosebumps, hot or cold flushes, mucle cramps and spasms Intensity of the symptoms depend on drug use, the dosage that the individual had been using Full agonists cause most severe withdrawal Management involves oral methadone with gradual dose tapering Methadone maintenance programs: provision of daily oral doses to registered clinics at methadone clinics Properties of Various Opioid Analgesics Properties of Various Opioid Analgesics Abuse liability Prescription regulations for most CNS drugs are based on their abuse liability Potent opioids such as morphine, meperidine, methadone etc are judged to have the highest potential for abuse THANK YOU