Pharmacology : Opioid Analgesics & Antagonists

Opioid Analgesics & Antagonists

Strong Antagonists
Fentanyl Heroin Meperidine Methadone Morphine Sufentanil Remifentanil

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

Mixed Agonist-Antagonist and Partial Agonists

Buprenorphine Butorphanol Nalbuphine Pentazocine

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

Pharmacology : Opioid Analgesics & Antagonists

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

Pharmacology : Opioid Analgesics & Antagonists

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

Naloxone - reverses coma and respiratory depression of opioid overdose

Pharmacology : Opioid Analgesics & 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