Opiate Addiction and Neuropharm of Opiates Flashcards Preview

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Flashcards in Opiate Addiction and Neuropharm of Opiates Deck (45)
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1
Q

What affect do opiates have on the CNS? (name 7)

A

Analgesia, euphoria, sedation, respiratory depression, release of prolactin, nausea, anti-tussive effect.

2
Q

Effect of opiates on the cardiovascular system?

A

Peripheral vasodilatation.

3
Q

Effect of opiates on eyes?

A

Pupil constriction.

4
Q

Effect of opiates on lungs?

A

Respiratory depression

5
Q

Effect of opiates on GI?

A

Decrease in propulsive contractions in small intestine. Spasms. Note that loperamide (Imodium) for diarrhea is an opioid receptor agonist.

6
Q

What’s the new epidemic in opioid abuse / dependence?

A

Non-medical use of pain relievers. (now about twice as common as heroin use)

7
Q

What is cross-tolerance?

A

Somebody who uses heroin regularly will need a higher dose of methadone…

8
Q

What “pathway” in the brain produces the high from opioids (or winning a race)?

A

The mesolimbic pathway. And it’s all about dopamine.

9
Q

What separates buprenorphine from other opiates?

A

It’s a partial agonists. It stimulates the opioid receptors, but has a “ceiling effect” - activity plateaus at a lower level of activation.

10
Q

What are the 3 opioid receptor families, and what do effect does agonism produce?

A

Mu - analgesia/euphoria
Kappa - dysphoria, hallucinations, analgesia
Delta - analgesia? unclear.

11
Q

4 medical signs of opiate abuse?

A

Infection (esp things like endocarditis, abcesses), nasal/pulmonary scarring, scars from injection, drug requests

12
Q

4 pharmacological treatment modalities for opioid dependence?

A

Detox - use agonist and taper
Substitution - methadone/buprenorphine
Antagonist - naltrexone
Relapse prevention - naltrexone +/- buprenorphine

13
Q

3 most common signs of opiate withdrawal?

A

Anxiety
Dilated pupils
Craving
(other signs include diaphoresis, yawning, increased BP and RR, piloerection, rhinitis, abdominal cramps, diarrhea)

14
Q

What’s the major advantage of using buprenorphine instead of methadone for substitution?

A

Buprenorphine can be given by a trained PCP. You don’t have to send patients to a methadone clinic.

15
Q

Advantages of methadone?

A

Cheap
Oral -> gets rid of injection risk (vs. using heroin)
Smooths out experience

16
Q

How well does methadone treatment work?

A

Not that well. Lots of people drop out then relapse. It’s good at preventing HIV injection while people are in treatment, though…

17
Q

MoA of naltrexone?

A

Specific antagonist of mu opioid receptors.

18
Q

Is there any proven advantage to rapid detox?

A

Nope.

19
Q

How does the subjective experience of local anesthesia vs. an opioid analgesic contrast?

A

Local: It’s numb.
Opioid: It hurts, but who cares?

20
Q

Where are mu opioid receptors, anatomically?

A
Spinal cord (dorsal root ganglia)
Supra-spinal: periaqueductal grey, thalamus, sensory cortex
21
Q

Where are delta opioid receptors, anatomically?

A

Mainly spinal cord: dorsal horn, spinothalamic tract.

22
Q

Which neurons / what brain regions produce the euphoria from opioids?

A

Ventral tegmental area (VTA) dopaminergic neurons project to nuc. accumbens and medial prefrontal cortex.

23
Q

Where in the brain does opioid-induced nausea come from? What kind of receptors?

A

the area postrema (in the medulla) - kappa receptors

24
Q

How do opioids cause respiratory depression?

A

Mu receptors in brainstem -> dampens relexes in response to high P(CO2).

25
Q

Are anti-tussive effects caused by opioids acting in the brainstem?

A

yep

26
Q

What isomers of opiates do all the analgesia?

A

L-isomers

27
Q

What isomers of opiates predominantly have an anti-tussive effect? (Prototypical drug that does this?)

A

D-isomers. Dextromethorphan (i.e. Robitussin)

levomethorphan does have analgesic effects, but was never clinically developed, says Wikipedia

28
Q

Where do opiates act to cause constipation? What kind of receptors?

A

Local gut autonomic ganglia. Mu receptors.

29
Q

What do you do if you see an unconscious person in the ER with pinpoint pupils?

A

Give IV naloxone, as they might have an opioid OD. (and naloxone won’t hurt them if they don’t)

30
Q

Why does IV morphine help fluid buildup in the lungs of a person with congestive heart failure?

A

Peripheral vasodilatation -> fluid drawn away from lungs.

31
Q

Where do opioids act to cause peripheral vasodilatation?

A

the vagal nucleus (or as we called it, the dorsal motor nucleus of CN X)

32
Q

What are the 3 endogenous opioid receptor ligands, and to what receptor do they bind?

A

Endorphin -> Mu
Enkephanlin -> delta
Dynorphin -> kappa

33
Q

What are the downstream cellular effects of Mu agonism? (more simply, to what G protein is the receptor coupled?)

A

Coupled to Gi. Thus adenylated cyclase inhibition -> low cAMP -> decreased CREB -> altered gene expression.
Also neuronal hyperpolarization via increased K+ permeability.

34
Q

What is injected antagonize Mu in opiate OD?

A

Naloxone

35
Q

What is taken orally to help combat alcohol and opioid addiction?

A

Naltrexone.

Mnemonic?: “trex” -> trek = journey, and breaking an addiction is a long journey

36
Q

2 enzymes responsible for opioid tolerance?

A

Src kinases

G-protein kinases

37
Q

What’s the mechanism for src kinase-mediated opioid tolerance?

A

Phosphorylation causes Mu receptor not bind Gi as well, thus increasing cAMP levels.

38
Q

What’s the mechanism of G-protein kinase-mediate opioid tolerance?

A

Phosphorylation of Mu receptor leads to internalization, and thus less mu receptor on cell surface.

39
Q

Clinical implication of opioid tolerance? Is there a ceiling to tolerance?

A

If somebody is on a opioid painkiller for multiple days, they may need their dose increased to control the pain.
Yes, there is a ceiling effect.

40
Q

4-5 symptoms of opioid withdrawal? (and symptom of opioid intoxication to which it is opposite)

A
Anxiety (instead of euphoria)
Agitation (instead of sedation)
Diarrhea (instead of constipation)
Pupil Dilation (instead of constriction)
Craving
41
Q

Can opioid withdrawal kill you?

A

Nah. But it sucks.

42
Q

Which withdrawal symptom most drives relapse?

A

Craving

43
Q

What 2 drugs compose suboxone? Why is the 2nd drug given?

A

Buprenorphine - for safer substitution therapy

Naloxone - so you can’t inject the buprenorphine.

44
Q

What genetic variation most predicts euphoria in response to EtOH? Which specific allele? Downstream effect?

A

The “G” allele of the Mu opioid receptor.

Ultimately affects dopamine levels (in the ventral striatum).

45
Q

For what genotype does naltrexone work best for treating alcohol use disorder?

A

People with the G allele, who tend to get a “high” more from alcohol.