1. Suppress inward Ca²⁺ flux-presynaptic inhibition
2. Activate outward K current - postsynaptic inhibition

Mu-supraspinal and spinal analgesic, respiratory depressant, physical dependent, euphoria

Kappa-spinal analgesia, miosis, sedation-found more in women

Delta-unknown, but fails to produce tolerance

Morphine, heroin, methadone, fentanyl, meperidine (demerol), hydromorphone (dilaudid)

-full mu agonists

-Schedule II

-Meperidine - antimuscarinic, metabolite causes seizures, some serotonin agonist action

Codeine, oxycodone (percocet, oxycontin, percodan), hydrocodone (vicodin)

-agonist of mu

-often combine w/tylenol

-lower abuse potential (schedule II) - don't need DEA licence

Propoxyphene - dangerous in overdose, limited effectiveness, schedule IV

Pentazocine, buprenorphine

-Pentazocine: agonist of Kappa, antagonist of mu

-Buprenorphine: partial agonist of mu, no binding to others

-mild to moderate pain

lower ceiling for causing analgesia, respiratory depression

-can produce abstinence syndrome, increased pain

-extensive first-pass metabolism

-short t1/2

-Fentanyl comes in patch form

-heroin and fentanyl have rapid onset of action

-not teratogens

-phase I/II metabolism, CYP450 2D6 - genetic polymorphisms

Effects of Opioids

Analgesia, euphoria, drowsiness, mental clouding

-can cause dysphoria if not in pain

-respiratory depression

-miosis

-nausea, interference with vestibular system

-CONSTIPATION

-urinary retention

-the itch, no myocardial effect

Pain management: fixed schedule better than "as needed" for cancer/terminal illness

PCA devices: best for patient-controlled anesthesia

General anesthesia: pain control, esp. fentanyl

Regional anesthesia

Dyspnea & acute pulmonary edema: relief from dyspnea

Antitussive effects - codeine, dextromethorphan

antidiarrheal

Adverse effects: constipation, urinary retention, nausea and vomiting, sedation

Miosis - no tolerance

OD-respiratory arrest, pinpoint pupils, coma

-additive CNS and respiratory depression

-Inhibition of CYP450 2D6 enhance effect of opioids