Opioids Flashcards
What are opioids?
(2 marks)
- Narcotic angalesics - reduce pain without producing unconciousness at correct dosage
- Can induce euphoria - BEST painkiller known
What does opium contain?
(4 marks)
Morphine - strongest active ingredient
Codeine
Heroin
Haloxone
What are naloxone and nalorphine?
(2 marks)
- Pure antagonists that are structurally similar to heroin but have no efficacy
- Prevent/ reverse effects of opioids
What are methadone and fentanyl?
(3 marks)
- Synthetic drugs
- Methadone: used for replacement therapy
- Fentanyl: important synthetic analogue of morphine used in pain therapy
How can morphine be taken?
(2 marks)
- Morphine normally injected intra-muscullary or can be given orally (medicinal)
- Can use IV for recreational use
- Small amount of moprhine passes blood brain barrier
How can newborns from opioid addict mothers experience withdrawal symptoms?
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- Opioid is lipophilic and can pass through placenta
How can opioids be used to treat diarrohea or certain tropical/ parasitic diseases?
It affects the GI tract and can cause constipation
What are some of the reinfrocing and adversive effects?
(2 marks)
- Reinforcer:‘rush’ encourages people to do it again
- Adverse effects: dysphoria, restlessness and anxiety
What can be seen at higher doses of morphine and overdose?
(2 marks)
- Sedative may lead to unconciousness
- Acts on brainstems respiratory center - respiratory failure is ultimate cause of death in overdose
How does opioid enhance the brains reward system?
(2 marks)
- Lowers electrical current threshold for self-stimulation
- In this way animals are able to learn to maintain stable blood levels by self administration
How does the dopaminergic mesolimbic pathway contribute to opioid reinforcement?
(5 marks)
- Opioids injected inot VTA of midbrain this increases dopaminergic cell firing
- Thus increasing release of dopamine inot nucleus accumbens
- β- endorphins and opioids, increase VTA cell firing by inhibiting inhibitory GABA cells
- Causes increased firing and greater release of DA in NAcc
- Dynorphin acts on κ-receptors on DA neuron terminals and can reduce release of DA by similar mechanism causing dysphoria
How can chronic use of opioids lead to cross tolerance?
- Cross tolerance among opioids - as many different types substitute for each other and can be used for therapy best way to avoid this is to use less harmful opioid e.g. codeine
- Can also lead to sensitisation
What happens if you become dependent on opioids?
(2 marks)
- Depresses CNS function - withdrawal is rebound hyperactivity
- ‘Neuroadaptive state’ in response to long-term occupation of opioid receptors
What is the difference in withdrawals of heroin and methadone?
Heroin: very strong but shorter time - high intesity of withdrawal symptoms
Methadone: much milder less intense form but longer lasting
What kind of replacement therapy is used in opioid treatment?
- Use milder opioid when abstinence signs end to prevent dangerous side effects
Which areas of the brain are involved in opioid withdrawal?
(3 marks)
It’s NEVER what you first initially think
- Locus coerulus (LC) and periacqueductal gray (PAG)
- Sensitive to opioid antagonist in withdrawal
- NAcc has been found to be important in reinforcement - may have aversive/ motivational effects
How can antagonist MK-801 help with prevention of opioid tolerance?
(5 marks)
- Glutamate and its NMDA receptor are involved in opioid tolerance and dependence.
- Tolerance to morphine was reduced in animal studies by the non-competitive NMDA antagonist dizocilpine (MK-801).
- MK-801 prevented acquisition of tolerance and dependence but did not reverse them once they had developed.
- Prevented the neural plasticity and learning component of tolerance and dependence.
What does MK-801 do to PKC that prevents chronic opioid use?
(2 marks)
- Prevents increase in PKC in dorsal horn of spinal cord
- PKC phosphroylates ion channel normally opened by glutamate, enahncing channel function - which may be responsible for tolerance
What is the most common form of treatment for opioid addiction?
(3 marks)
Methadone maintenance programme
- Cross-dependece with heroin
- Cross tolerance that develops to repeated methadone use means normal euphoric effects of heroin are reduced
What is buprenorphine?
- Partial agonist for opioid weaker than methadone but can be used for longer
- Can be abused if crushed and snorted
What is the most successful drug for treating nervous system disorders from opioids?
(3 marks)
- Naltrexone (Trexan)
- Longer duration of action than naloxone
- Effective when taken orally with few side effects
What is the opioid anatagonist that is similar to naltrexone?
(4 marks)
- Nalmefene (Revex) - newer opioid antagonist
- More potent and longer lasting
- Blocks opioid receptors HOWEVER craving of drug is not eliminated
- Less motivated people CAN return to drug use
What is the best form of treatment for opioid addiction?
(2 marks)
- Multidimensional approach
- Induce detoxification, pharmalogical support and group/ individual counselling
What are the different opioid receptors and what characteristics do they all share?
(4 marks)
- m, δ, κ and NOP-R = 4 receptors
- Expression varies dependent on where they are in brain
- Large group of endogenous ligands share same 4 receptors
- ALL metabotropic and all couple to Gi to inhbiit cAMP synthesis
What are opioid peptides?
(3 marks)
- Endogenous opioid peptides are released naturally in the body for opioid receptors
- Have 5 AA coding regions and combination of them in the brain give specifiicity of reaction with opioids
