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14 Cards in this Set

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By what mechanism do opioids promote analgesia?
Opioids bind to mu receptor in CNS.

Hyperpolarization of cells (increases outward K flux)

Decreases cAMP, which decreases PKA, which decreases CREB. This leads to long-term changes.

HOWEVER, IN CHRONIC USERS, THIS PATHWAY IS REVERSED...INCREASE IN cAMP b/c adenlyate cyclase chronically inhibited by opioid, INCREASE PKA, INCREASE CREB
By what mechanism do opioids promote euphoria?
REWARD PATHWAY!

Mu opioid receptor binding to VTA/nuc.acc./PFC
What are side effects of opioid usage?
Constipation, pupillary constriction, dilation of peripheral circulation, NAUSEA (in area postrema of brain), respiratory depression

DXM = anti-tussive. ROBITUSSIN (L and D-isomers)
Opioid withdrawal symptoms?
Flu-like symptoms, pili erectae (hair standing up), pupillary dilation, dysphoria, anxiety, diarrhea

Related to PROTRACTED ABSTINENCE, opioid dependent individuals will undergo long-term PHYSIOLOGICAL changes.
Opioid neuroanatomy
MU receptors mediate spinal (DRG) and supraspinal effects in periaqueductal grey, thalamus, sensory cortex.

Delta receptors meditate spinal analgesia for pain C fibers in spinothalamic tract. Located in dorsal horn of spinal cord.
What is the primary cause of death in opioid OD?
Depression of neuronal sensitivity to pCO2 levels in brainstem.
What are the three types of opioid receptors?
Mu, kappa, delta.

All are GPCR
What are the three types of endogenous opioid ligands?
Dynorphin (BINDS KAPPA)

Endorphin, Enkephalin (BINDS MU, DELTA)
What receptor binds preferentially to Dynorphin?

Endorphin?

Enkephalin?
Dynorphin = KAPPA

Enkephalin/Endorphin (the two E's) = MU, DELTA
What's the difference between naltrexone and naloxone?
BOTH ARE MU OPIOID ANTAGONISTS

Naltrexone is longer lasting, used for alcohol dependence.

Naloxone is shorter lasting, only used IV (combined with buprenorphine).
What happens to Mu receptors in tolerance?
Downregulation of mu receptors...internalized, etc.
What is methadone?
Partial agonist/antagonist of mu opioid receptor. Blocks euphoric and analgesic effect. Users won't feel effect of heroin.

Increased rates of productivity while decreasing deliquency/STDs
What is buprenorphine-naloxone for heroin addiction?
Buprenorphine is an orally-active partial opioid agonist with slow dissociation from opioid receptor. Few withdrawal symptoms. Combination cannot be injected bc naloxone (only active IV) would cause IMMEDIATE ACUTE WITHDRAWAL SYMPTOMS
What is the difference between benzos and naltrexone in treating alcohol dependence?
Benzos are used for withdrawal (DT) symptoms.

Naltrexone is used for preventing/limiting further abuse. Naltrexone not effective for ABSTINENCE, but DOES REDUCE EUPHORIA AND REDUCES HEAVY DRINKING RELAPSE.