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B&B Week 7 Flashcards > Lecture 43: Neuropharmacology of Opioids (and Alcohol Addiction) > Flashcards

Lecture 43: Neuropharmacology of Opioids (and Alcohol Addiction) Flashcards

1
Q

What is an opioid?

A

Any chemical compound with pharmacologic actions similar to those of morphine
“narcotic analgesic”
Morphine is the prototype drug

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2
Q

What are morphine and codeine?

A

Alkaloids of the poppy plant

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3
Q

What is Naltrexone?

A

ORALLY active antagonist of opium

-used in alcohol addiction treatment

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4
Q

What is Naloxone?

A

PARENTERALLY (not oral) antagonist of opiate receptor

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5
Q

What are the two approaches to pain pharmacotherapy?

A
  1. Local anesthetic
    • it doesn’t hurt anymore. It’s numb
  2. Opioid analgesic
    • it HURTS but who cares?
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6
Q

What is opioid’s effect on the body?

A

Makes you not care about pain…you feel pain but don’t care about it
-acts at the THALAMIC and CORTICAL (post central gyrus) levels to decrease pain sensation

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7
Q

What is the purpose of mu opioid receptors? Location?

A 
They mediate both spinal (DRG) and supra spinal analgesia 
Location:
	-in periaqueductal gray
	-thalamus
	-sensory cortex
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8
Q

What is the purpose of delta receptors?

A

Mediate spinal analgesia for pain C fibers in spinothalamic tracts
Location: dorsal horn of the spinal cord

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9
Q

What are the ascending tracts of opioids?

A
  1. spinothalamic

2. spinoreticular

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10
Q

Where is the euphoria of opioid coming from?

A

VTA dopaminergic neurons project to nucleus and medial prefrontal cortex

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11
Q

Where is the nausea of opioids mediated by?

A

Kappa receptors of area postrema

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12
Q

What is the Area Postrema?

A

Located in the MEDULLA
Controls vomiting
Area Postrema connects to the solitary nucleus and is excited by impulses from GI tract

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13
Q

How do opioids cause respiratory depression?

A

Produced in brainstem
Decreases neuronal sensitivity to PCO2
Cause of death in overdose

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14
Q

How do opioids cause antitussive activity?

A

Produced in brainstem

D-isomers of opioid lack euphoria but retains anti-tussive action

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15
Q

What does antitussive mean?

A

Capable of relieving or suppressing coughing

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16
Q

What are the actions of opioids?

A 
Euphoria
Nausea
Respiratory Depression
Antitussive
Constipation
Constriction of the pupil
Peripheral vasodilation (DMX)
THINK PARASYMPATHETIC except for constipation lol
17
Q

What is the cause of death in opioid overdose?

A

Respiratory depression

18
Q

What are the 3 main endogenous opioid receptor ligands in the CNS?

A
  1. endorphin
  2. Enkephalin
  3. Dynorphin
19
Q

What is endorphin?

A

An endogenous opioid receptor LIGAND

-binds to mu and delta opioid receptors

20
Q

What is enkephalin?

A

An endogenous opioid receptor LIGAND

-binds to mu and delta opioid receptors

21
Q

What is dynorphin?

A

An endogenous opioid receptor LIGAND

  • binds to kappa opioid receptors
  • causes the DYSPHORIC effects of opioids
22
Q

What is the ACUTE cellular response to morphine?

A
  1. Decreased levels of cAMP
  2. Decreased levels of CREB phosphorylation
  3. Opens K+ channels and HYPERPOLARIZES GABA releasing neurons
  4. Less GABA release; decrease in firing
23
Q

What are the mechanisms of opioid tolerance?

A
  1. mu receptor phosphorylation by src kinases at 2nd intracellular loop
    - leads to INCREASE of cAMP
    - switches from an inhibitory to stimulatory cAMP signal (switch from Gi to Gs)
  2. mu receptor phosphorylation by G protein kinases at 2nd intracellular loop
    -uncouples G-protein from Mu opioid receptor
    -leads to DECREASE of mu receptors due to increase of mu receptor internalization
    -mediated by Beta-Arrestin
    Receptor downregulation alters RATIO of high affinity vs low affinity receptor forms
24
Q

What is the CHRONIC cellular response to morphine?

A
  1. DECREASED levels of Gi proteins
  2. cAMP no longer inhibited…cAMP is upregulated
  3. because cAMP is upregulated, CREB and PKA is upregulated as well
  4. PKA = opens Na channels, DEPOLARIZATION
  5. Depolarization leads to INCREASE neurotransmitter release
25
Q

What does beta-arrestin-2 do?

A

Mediates Mu opioid receptor (MOR) internalization

26
Q

What does Filamin A (FILA) do?

A

Links the Mu opioid receptor to the C-terminus of actin

No FILA = no internalization

27
Q

What are the symptoms of opioid withdrawal?

A

12 hours after last dose of morphine
Physical symtpoms are mild (wont kill you but sucks) and are OPPOSITE of morphine actions
1. Anxiety
2. Agitation
3. Diarrhea
4. Pupillary Dilation
5. Craving for opioid (can be cued by drug-related perceptions
Sympathetic response except for the diarrhea lol

28
Q

What is the epidemiology of opioid addiction?

A

~1 million opioid addicts in the US
50% of risk of opioid addiction is inherited
85% relapse in 1 year
Relapse is initiated by carving … the gordian knot of opioid addiction

29
Q

How do we treat opioid addiction?

A
  1. Methadone maintenance
    • if an addict injects heroin under methadone treatment, euphoria is markedly attenuated
  2. Buprenorphine-Naloxone
  3. Naltrexone
30
Q

What are advantages of methadone treatment?

A
  1. lowers rates of HIV & hepatitis
  2. Lowers rate of re-arrest
  3. Increases employment rates
31
Q

What is heroin?

A

An opioid analgesic

32
Q

What is buprenorphine-nalozone (Suboxone)?

A

Buprenorphine is an orally-active partial mu agonist that dissociates slowly from MOR
-causes less severe withdrawal symptoms
Also blocks euphoria if heroine is concomitantly injected

33
Q

What are the significant genetic variations of MOR?

A

Single Nucleotide Polymorphism in MOR…changes A to a G allele
Those who are AA for N40D polymorphism are less susceptible to alcohol abuse
Those who are AG are much more susceptible to alcohol abuse because self-reported stimulation is seen as greater

34
Q

The more G allele in N40D in MOR means?

A

More dopamine release in striatum with ingestion of alcohol

-can be blocked by Naltrexone

35
Q

OPRM1 (opioid mu receptor) AA homozygotes have what disadvantages?

A

Cannot be blocked by Naltrexone so it doesn’t work as a treatment

36
Q

What is the significance of Naltrexone?

A

Because it REDUCES the euphoria associated with ethanol…but only with people G alleles in the opioid receptr
Can also be used as opioid addiction treatment

37
Q

What do opioids do acutely?

A

Decrease cAMP activity

38
Q

What happens when you get tolerance of opioid activity?

A

cAMP is UPREGULATED so you no longer have the same effect as before
Gi is replaced by Gs subunit

B&B Week 7 Flashcards (16 decks)

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