Pain+Medication

=Nonopioid Analgesics=

Miscellaneous Non-Opioid Analgesics
=Opioid Analgesics=

Heroin
=Mixed Opioid Agonists/Antagonists=

Dexocine
=Opioid Antagonists=

Benzonatate
=Guiding Principles= Use adjuvatnt medications where indicated, but...
 * Select the analgesic class that's su8tble for the intesity and nature of pain that needs to be controlled
 * Titrate analgesics to severity of pain if possible
 * Use regularly scheudled dosing, not "As needed"


 * Don't use benzodiazepines or any other anxiety-relieving/generally sedating drugs as, or in lieu of, analgesics: They lack analgesic activity at doses consistent with life


 * With opiod, be //concerned// about tolerance, dependence when it's appropriate to do so, but don't keep the patient in pain because of your worries


 * Goal: Complete pain relief

NSAIDs, or acetaminophen in absense of inflammation > NSAIDs, Acetaminophen not on exam (more in future presentation) > //However//, may not get enough pharmacological info
 * Analgesic Gradation**


 * Low potency "Moderate" opioid analgesics (codeine, oxycodone, hydrocodone)


 * Adjuvant Medications (clonidine, TCAs, some antiepileptic drugs) + strong opioid--phenytoin, etc


 * Hihg-potency ("strong" ) opioids (morphine, hydromorphone, methadone, fentanyl, levorphanol)

=Opioids=
 * Opioid: Any natural or synthetic chemical with morphien-like actions
 * Opiate: Natural product from the opium poppy
 * Narcotic: nebulous term with different legal and pharmacologic meannings, fanging from morphine-like analgeics, to any CNS depressant, to any drug with CNS efects and an abuse potential...cocaine, marijuana, PCP, etc


 * Endogenous Opioid Peptides**

> mu, kappa, delta, sigma
 * DYnorphins, endorphins, enkephalins as neurotransmitters, neurohormones, or neuromodulators
 * Act on some or all the same opioid receptors
 * Four main classes of receptors:


 * mu receptors, and to some extent K repcetors are the most important therapeutically


 * Resposne||mu||kappa||
 * analgesia||Yes||Yes||
 * sedation||Yes||Yes||
 * degrease gut motility||Yes||Yes||
 * Ventilatory depression||Yes||No||
 * Euhoria||Yes||No||
 * physical dependence||Yes||No||


 * Pure Opioid Receptors**

Act only as agonists
 * Prototype drug: Morphine Suflace: abbreviated MS
 * Stimulate opioid receptors: mu, kappa

Partial Agonists
 * Examples: pentazocine, nalbuphine
 * Stimulate kapa receptors reasonably well, weaklys timulate or outright block mu, either of which blocks...

Pure opioid antagonists
 * Prototype Naloxone
 * Only bloc receptors

where cause effects?
 * Brainstem
 * Spinal cord
 * primary afferent peripheral nerve terminals

Other sites of action...
 * meducllary repsiratory control center
 * Medullary CTZ (chemoreceptor trigger zone: nausea, emesis)
 * GI tract
 * Others -- CNS, vascular, PNS

extensive 1st pass hepatic metabolism
 * Morphine**
 * oral morphine okay for maintenance...once P450 system is saturateed by sufficient prior doses 1st pass clearance lessens

Equianalgesic doses: 60 mg oral v 10 mg parenteral


 * How is morphine used?**


 * Gold standard for pain
 * allays anxiety, sedates....pain described as 'still there, but less bothersome'
 * Use in acute MI based on above + venodilation...decrease pulmonary congestion
 * Use in acute pulmonary dema
 * sometimes used as general anaesthetic //(at lethal doses!))//

> main reason for abuse > Schedule II > Few report dysphoria > increase in tone of bladder sphincter, decrased awareness of full bladder > urgency because of increased detrusor tone
 * Common Side Effects**
 * Euphoria
 * Ventilatiory depression, icnreases intracranial pressure
 * Nausea, emesis (CTZ activation)
 * Constiption (decrease gut musculature ativation)
 * Urinary Retention or urgency
 * Gall BLadder pain/bile duct spasm
 * Hypotension, Orthostatic Hypotension


 * Morphine & Ventilation**

> Cranial vessels dilate in response to change in blood gasses
 * //Ventilatory Depression #1 cause of death!//
 * Dose-dependent medullary depression: decrased ventilatory rate and/or depth: decrease P)2, increase PCO2, increase in ICP


 * Impairs normal medullary response to increased PCO2


 * Head injury can decarse ventilation, incrase ICP
 * Opioids exacerbate these effects...
 * Mental clouding, miosis, emesis, other drug actions can confound diagnosis of CHI & sequelae


 * Physical Dependence**

//Schlafer's Definition: pt physically dependent when there is characteristic withdrawal syndrome that appears on discontinuation//

develops WRT anaglesia, envitlatory depression, euphoric effects DOES NOT develop regarding miosis
 * Tolerance**

As tolerance develops, the LD rises omore or less in parallel with the effective dose


 * Therapeutic index doesn't change mch
 * explains why opioid tolerant people can survive otherwise leathal doses
 * Differs from situation wtih EtOH for which LD does not rise enarly as much as the ED does.


 * Cross-Tolerance,Cross-Dependence**


 * //Cross-Tolerance// a pt tolerant to one opioid agonsit aautomatically developed tolerance to all tohers
 * //Cross-Dependence// a pt who has withdraawal symtoms from one opioid agonist can substitute any other opioid agonist


 * Explains how heroin addicts can be substituted w/ methadone


 * //Opioid tolerance DOES NOT confer tolerance to alchohol or other CNS depressants!//

> Morphine, Heroin: very potent, relatively fast onset of action, short duration >> Very intense, brief withdrawal > Methadone: Longer-lasting but milder withdrawal
 * Opioid Withdrawal **
 * Duration, severity proportional to pharmacokinetics of agent
 * Withrdrawal rarely fatal


 * ((Break))**


 * Other Agonists**


 * Overall potency 50-75x morphine
 * Parenteral:**
 * general anestheisa induction maintennace
 * Given + midazolam (benzodiazapine) as common coctail for 'conscious sedation'
 * Transdermal:**
 * Maintenance for severe, chronic pain
 * not for initiating analgesia or breakthrough pain


 * transmucosal**
 * Lozenges for preaneasethetic medication, conscioussedation
 * 'lollipops' for breakthrough pain in cancer


 * Methadone**
 * Equipotent to MS, parenterally
 * MUch better oral bioavaliability
 * Repeated administration increases T1/2

long-term pain control Detox
 * Uses:


 * Other opioid agonists*
 * DEMEROL**, aka meperidine

> Less biliary tracr spasm than morphine > Shorter half-life: shorter duration of typical opioid adverse resnses
 * One a first line drug for severe pain
 * Main advanttages:

> Relatively short T1/2 --> frequent dosing > Frequent dosing -- accumulation of normeperidine that can --> tremor, convulsions/seizures, other severe toxicities > DDIs with MAOIs, other serotonergic drugs.. (SSRIS, TCAs) --> delerium, fever, status epilepticus, coma,death
 * Problems:

Hydromorphone (Dilaudid) Oxymorphone (Numorpphan)
 * ther Agonists**

Morphine-like oral, parenteral, analgesics Noteworthy because 5-10x as potent as morphine... Subtitution for morhjphine on mg-for-mg basis may have lethal outcomes

Codeine, hydrocodone (vicodin) Oxycodone (Oxycontin, Percocet, Percodan)
 * Moderate Opioids**
 * Oral
 * Suitable for moderate pain only
 * SE/toxicity limit safe use of higher doses
 * Analgesia potentiated by ASA, acetaminophen, combo theapy commmon, rational
 * Excellent antitussive activity


 * Tablest swallowed shole, gradual release....target therapeutic blood level, analgesia as drug-in is balanced b drug-ouse
 * Abusers chew or grind and inject for rapid onset

Propoxyphene...DARVON

Analgesic efficacy about same as ASA...synergistc ith ASA, aceaminophen low abuse potential
 * Structrally similar to methadone
 * Toxicity: Toxic psychosis and meperidine-like symptoms, often fatal

Naloxone not orally absorbed, doesn't decrease analgesic effectiveness of oral pentazocine but if tablets are dissolved and injected, the antagonist blocks analgesic and other afects, and prevent the euphoria for which the product was illictly used
 * Talwin tablets containe Naloxone

WHy have drugs like pentazocine, Nalpuphine
 * hope awas to have opioid analgestic, w/o potential for ventilatory depression, abuse
 * hope hasn't been realized
 * See Ketorolac (Toradol) in supplements