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that is poorly localized and emotionally influenced 3. Spinal Cord 4. Hypothalamus 5. Limbic System STRONG AGONISTS
A. Morphine Mechanism of Action - causes hyperpolarization of nerve cells, inhibition of nerve firing and presynaptic inhibition of transmitter release. - acts at receptors - decreases the release of Substance P Actions - Analgesia: raises the pain threshold at the spinal cord level and alters the brains perception of pain - Euphoria - Respiratory depression: reduces the sensitivity of respiratory center neurons to CO2. - Antitussive - Miosis: pinpoint pupil effect - Emesis - GIT: relieves diarrhea but may cause constipation - Cardiovascular: at large doses, hypotension and bradycardia occurs
Moderate/Low Antagonists
Codeine Oxycodone Propoxyphene
Antagonists
Naloxone Naltrexone
Others
Tramadol
OPIOID RECEPTORS
- Histamine releasing: causes urticaria, sweating and vasodilation. It also causes bronchoconstriction [contraindicated in asthmatic pt] - Hormonal actions: inhibits release of gonadotropin-releasing hormone and corticotrophin-releasing hormone. It decreases the [] of LH, FSH, adrenocorticotropic hormone and endorphins. Decreases levels of
- major effects of opioids are mediated by the three major receptors : (mu), (Kappa) and (delta) - opioid receptors are known to be involved in integrating information about pain in 5 general areas of the CNS 1. Brainstem 2. Medial thalamus mediates deep pain
testosterone and cortisol. Increase prolactin and GH releasing. Therapeutic Uses - Analgesia - Treatment of diarrhea : decreases motility and increases tone of smooth muscles - Relief of cough - treatment of acute pulmonary edema : IV injection of morphine relieves Dyspnea caused by PE associated with left HF due to the vasodilatory effect. Pharmacokinetics - given by IM, IV or subcutaneous injections - enters all body tissues including fetuses of pregnant women - is conjugated in the liver to glucoronic acid - conjugates are excreted in urine with small amounts appearing in bile
peripheral resistance and peripheral blood flow - causes pupils to dilate (not like morphine!) Therapeutic Uses - commonly employed in obstetrics Pharmacokinetics - well absorbed orally - commonly given IM - duration of action is 2-4 hours Side Effects - anxiety - tremors - msc twitches - convulsions - dilates the pupil - dry mouth and blurred vision C. Methadone - synthetic Mechanism of Action
Side Effects - severe respiratory depression - vomiting - sedation - constipation - urinary retention - potential for addiction B. Meperidine - synthetic opioid used for acute pain Mechanism of Action - binds to opioid receptors, in particular receptors Actions - no significant cardiovascular action when given orally but in IV administration, can cause HR,
- mediated by receptors Actions - analgesic action equivalent to Morphine Therapeutic Uses - used for the controlled withdrawal of heroin and morphine abusers - it is substituted and then slowly weaned Pharmacokinetics - absorbed orally - biotransformed in the liver and excreted in urine as inactive metabolites
D. Fentanyl - has 100-fold the analgesic potency of morphine - used post-operatively and in labor - has a rapid onset and short duration of action - causes papillary constriction
- well absorbed orally - can produce anorexia, nausea and constipation - in toxic doses, can cause respiratory depression, convulsions, hallucinations and confusion MIXED AGONIST-ANTAGONISTS AND PARTIAL AGONISTS
E. Heroin - no accepted medical use - has greater lipid solubility than morphine which causes exaggerated euphoria MODERATE AGONISTS
A. Pentazocine - agonist at receptors but weak antagonists at and receptors - causes analgesia by activating receptors in the spinal cord - used to relieve moderate pain - in pt with angina, pentazocine increases the mean aortic pressure and pulmonary arterial pressure = increases work of heart
A. Codeine - good antitussive action at doses that do not cause analgesia - lower potential for abuse and rarely causes dependence - produces less euphoria than morphine - often used in mixture with aspirin or acetaminophen - Actions: analgesia, sedation, euphoria and depresses cough reflex
B. Buprenorphine - partial agonist, acting at the M receptor - used in opiate detoxication - causes little sedation, respiratory depression and hypotension OTHER ANALGESICS
Tramadol B. Oxycodone - semi synthetic derivative of morphine - orally active - formulated with aspirin or acetaminophen too - treats moderate to severe pain C. Propoxyphene - derivative of methadone - relieves mild to moderate pain - weaker analgesic compared to codeine - centrally acting analgesic that binds to the m receptor - weakly inhibits reuptake of NE and serotonin - should be avoided in pt taking MAOI, selective serotonin reuptake inhibitors or tricyclic antidepressants ANTAGONISTS
- rapidly displaces all receptor-bound opioid molecules and therefore, is able to reverse the effect of a heroin overdose - half-life of 60-100 minutes - competitive antagonist at , and receptors
Naltrexone - longer duration of action than Naloxone - single oral dose can block the effect of injected heroin for up to 48 hours - is hepatotoxic - can treat chronic alcoholism by an unknown mechanism