OPIOID ANALGESICS EXTRACTS OF OPIUM POPPY (OR SYNTHETIC DERIVATIVES) ARE THE MOST POTENT ANALGESICS KNOWN All work at endogenous opioid receptors, especially the æ receptor And all have side-effects at other opioid sites in brain and body biological effects of the opioids: Analgesia via the æ opioid system Miosis - constriction of the pupils Respiratory depression Depression of the cough reflex Nausea Constipation, control of diarrhea Euphoria, hence abuse "Nodding off"; sedation not sleep Dependence, in that withdrawal is unpleasant + Most withdrawal effects are rebounds, due to up-regulation of opioid receptors + Withdrawal is not unlike a bad case of flu Tolerance and cross-tolerance: Tolerance increases by as much as ten-fold in a period of months, and cross-tolerance is shown to almost all opioids MAJOR CLASSES OF OPIOID ANALGESICS IN CLINICAL PRACTICE: Morphine: includes the codeines, heroin, and æ antagonists such as naltrexone Morphine itself is still made from opium Major first-pass effect means that oral administration is possible, but requires substantial dosages Codeine is better taken orally, has a strong ability to inhibit coughing, but less analgesia The Phenylpiperidines: synthetic compounds Meperidine (Demerol): very similar to morphine, but more efficacious given orally for control of pain Loperimide (Imodium) - common antidiarrhetic, Doesn't cross the blood-brain barrier, hence is not abused Fentanyl (Sublimaze) + Used with nitrous oxide or droperidol ( a neuroleptic) as in i.v. anesthetic + 50 times as potent as morphine! + Also used in transdermal patches for control of chronic pain Methadone: Good oral efficacy Much longer half-life than morphine Otherwise much like morphine Used for treatment of heroin addiction AND for control of chronic pain LAAM is a methadone congener which can be taken once every 72 hrs! Propoxyphene (Darvon) Has the lowest analgesic potency Almost always given with aspirin, for control of mild to moderate pain Very popular clinically due to misplaced concerns about the abuse potential of codeine LOCAL ANESTHETICS MOST ARE RELATED TO COCAINE Act by blocking nerve conduction NOT by affecting the dopamine reuptake transporter Hence remove all sensation, not just pain Usually administered with a vasoconstrictor like epinephrine to keep the compound at the injection site Use in spinal analgesia: The spinal cord per se actually ends in the lower back region Below this region there is a pool of CSF transversed by a fan of nerves going to the lower body A local in this region produces general loss of sensation in the lower body CHRONIC PAIN, SUFFERING AND SOCIETY CHRONIC PAIN: The most devastating of conditions Continuous pain dominates the patient Reducing ordinarily strong persons to "a whimpering, pitiable state that may arouse the scorn of healthy observers" This effect on observers partly explains the failure of the medical profession to deal adequately with pain CHRONIC PAIN SYNDROMES Facial Pain - especially excruciating pain Enters the brain directly via the trigeminal nerve Includes a whole range of excruciating headaches, from sinus headaches through migraine to cluster headaches Toothache, of course And trigeminal neuralgia Opioids are sometimes ineffective against this type of pain Visceral Pain Notoriously, visceral or "deep" pain is: + excruciating pain + extremely poorly localized Referred pain - visceral pain will sometimes be accompanied by skin pain, in the same dermatome innervated by the viscera involved + thought to involve "cross talk" in neurons in the dorsal horn Pain from nerve damage Phantom limb "thalamic" pain syndromes Psychosomatic pain Often seen in hysterical personality disorders One reason doctors are suspicious of people with pain RELIEF OF PAIN The opioids can control most forms of chronic pain Often in conjunction with: + NSAIDS + Serotonin reuptake inhibitors, either tricyclics or more rarely the SSRIs But of course opioid analgesia is only obtained at the cost of: Possible respiratory depression and death Ever-increasing tolerance Possible withdrawal Possible addiction Societal hysteria about addiction, plus MD intolerance of suffering, combined to deny adequate pain control throughout most of the last century True even for patients with terminal disorders such as cancer Current improvements in analgesia Today health care professionals are SOMEWHAT more willing to provide adequate pain relief Including opioid patches and drip systems which the patient can control EUTHANASIA Barbiturates in euthanasia Barbs have become the method of choice in all forms of amnesia - quick, painless unconsciousness followed by flaccid paralysis, cessation of breathing and death Have replaced the gas chamber for strays Always used for putting down pets The Death Penalty: Government euthanasia of the impoverished criminal increasingly uses the same techniques, which are doubtlessly more humane Euthanasia in terminal disease and suffering Still a real problem area! Now not uncommon for hospitals/MDs to provide sufficient morphine for suicide But legal liability is still a very real problem, for MDs and family care-givers And surprisingly few opt for such choices, even when available More common - go out high as a kite on good drugs! + some even provide admixtures of morphine and speed!