Opiods

Question 1

Composition of opium?

Answer 1

• Morphine.
• Codeine.
• Thebaine.
• Narcotine.

Question 2

How is heroin synthesized biochemically?

What does this addition do?

Drug used for rehab of Heroine?

Answer 2

• Addition of 2 acetyl groups to morphine.
• Lipid soluble, so reaches the brain faster.

oxycodon.

Question 3

Opioid receptors:

• What type of receptors are they?
• Properties and consequence of activation?[4 marks]

Answer 3

Metabotropic receptors:

• All coupled to Inhibitory G proteins(Gi);
  
  • inhibiting adenylyl cyclase, which normally results in secondary messenger cAMP.

Overall reduce cAMP:

• resulting in decrease function of cAMP-dependent protein kinase:

Question 4

Mesolimbic dopaminergic pathway in opioids?

• pathway projection?
• Results of opioids and B-endorphins?
• function of Dynorphin?

Answer 4

Pathway:

• VTA——-> nucleus accumbens(NAcc).

Effect of opioids & B-endorphin:

• inhibiting the inhibitory GABA cells (within VTA)—>mesolimbic cells, allowing an increase in VTA dopaminergic cell firing.

Effect of Dynorphin:

• acting on K-receptors, reduce DA from mesolimbic neuron to NAcc.

Question 5

Characteristics of Morphine?

• Ways of intake?
• BBB penetration?
• the area where opioids can pass through and what pathologies occur as a result?
• Clinical use of opioids?

Answer 5

Intake:

• Snorting, intro-muscularly or orally.

Small penetration to BBB.

• Easily passes through the placenta:
  
  • Newborns suffer withdrawal symptoms, stabilized with a low dose of opioids.

Clinical use: as Heroin affects the GI tract:

• Prevents fluid loss and is used to treat diarrhea, therefore constipation is a common side effect.

Question 6

Effects of Opioid on the CNS?

Low doses:?

Higher doses?

Highest doses?

Answer 6

Low doses:

• Pain relief, constricted pupils, drowsiness, inability to concentrate and dreamy sleep.

High doses:

• “rush” feeling, acting as positive reinforcement.
  
  • dysphoria, anxiety, abnormal state of euphoria and vomiting.

Highest dose:

• sedative effects, leading to unconsciousness.
  
  • body temp and BP fall, pupils become very constricted.

Question 7

• Tolerance of Opioids?
• Cross-tolerance of opioids?
• Sensitization?

Answer 7

• Tolerance:
  
  • the diminishing effects of a repeated drug.
• Cross-tolerance:
  
  • tolerance to other opioids when administered heroin.
• Sensitization:
  
  • increase in drugs effect after repeated administration:
    
    • craving and desire for the drug undergo sensitization.

Question 8

Physical dependence and Abstinence syndromes associated with opioids?

Examples?

Answer 8

Physical dependence:

• neuroadaptive state in response to long term occupation of the drug/

Abstinence syndrome:

• withdrawal symptoms when drug is no longer present.
  
  • Examples: rebound hyperactivity,.
• As loss of inhibitory loss of opioid action is achieved.

Question 9

Evidence of Methadone use?

Answer 9

• Intensity of withdrawal
  
  • Methadone:
    
    • the intensity of drug effect is more gradual in comparison to heroine.

Question 10

Brain areas that are particularly sensitive to antagonists?

Answer 10

• Locus Coeruleus(LC) and the Periacqueductal gray(PAG)
  
  • precipitating to withdrawal.

Question 11

Environmental cues and factors influencing opioid development:

Answer 11

Tolerance development:

• Tolerance is lowered in new environment leading to overdosing.
• In same environment shows signs of anticipation.

Environmental factors:

• drug injection rituals.
  
  • becoming secondary reinforcers.

Question 12

Changes in brain activity to individuals with opioid reinforcement?

• Imaging used?
• regions located?

Answer 12

PET scans:

• Increase blood flow to the amygdala and anterior cingulate( similar to cocaine users).
  
  • Suggesting emotional memory and expectation.

These regions connected to NAcc, linking to learning cues associated with reward.

• cues acts as primers, promoting drug intake.

Question 13

The neurotransmitter associated and its receptor?

• Function of MK-801?
  
  • Type of inhibitor?
  • Its effects on physical dependence?
  • Mechanism of MK-801?

Answer 13

Glutamate and NMDA receptors.

MK801:( dizocilpine).

• Non-competitive inhibitor antagonist for NMDA receptors.
  
  • reduced tolerance to morphine.
• Mechanism:
  
  • Prevents the increase PKC in dorsal horn in spinal cord.
    
    • PKC, enhances channel function by phosphorylating ion channel which would normally be opened by glutmate.

Question 14

How is detoxification achieved with drugs such as heroin?

• Treatment involved?
• Characteristics of this treatment?

Answer 14

Methadone maintenance program.

• Methadone has cross dependence with heroin, so prevents severe withdrawal symtoms.
• Also withdrawal intensity gradually decreases at a slower, less severe rate.

Cross-tolerance: use of methadone can reduce euphoric effects of heroin.

Overall: reduces drug craving and addition to be redirected.

Question 15

Benefits of oral administration of methadone?

Answer 15

• Reduces the use of needles and ritual administrations.
  
  • eliminates the danger of diseases that can be transmitted due to unsterile needles, e.g. HIV.

Question 16

Use of Buprenorphine( Buprenex)?

• why is Suboxone used with Buprenorphine?

Answer 16

Buprenorphine:

• opioid partial agnoist:
  
  • used same way as methadone, weaker effects but longer duration.

Use of Suboxone;

• reduces potential use of IV, block Buprenorphine’s euphoric effects, however can be still be abused if snorted

Question 17

Antagonist treatment for opioids?

Answer 17

• Naltrexone( Trexan):
  
  • longer duration then naloxone, and is effective when taken orally.
• Nalmefene(revex):
  
  • more potent and last longer then naltrexone.