L15 - Motivated Behaviour: Addiction & Drugs of Abuse Flashcards
What are the symptoms of withdrawal of a drug for which a patient has physical dependence?
1 - Cramps
2 - Nausea & vomiting
3 - Tachycardia
4 - Piloerection
5 - Diarrhoea
What are the symptoms of withdrawal of a drug for which a patient has psychological dependence?
1 - Compulsive behaviours
2 - Anxiety
What are the origins of drug dependence?
1 - Degree of reward of the drug (drug variable)
2 - Genetics affecting absorption and metabolism of the drug (user variable)
3 - Peer pressure (environmental variable)
List 3 sources of acquired tolerance.
1 - Metabolic, e.g. alcohol tolerance develops with repeated administration due to upregulation of the P450 system in the liver, resulting in faster metabolism
2 - Behavioural, e.g. adjusting behaviour to appear less intoxicated
3 - Pharmacodynamic
How does pharmacodynamic tolerance arise?
- The opiate receptor is a GPCR that is coupled to a Gi alpha subunit
- Activation of the GPCR reduces the concentration of cAMP, because the Gi alpha subunit inhibits adenylyl cyclase
- With repeated use of opiates, the synthesis of adenylyl cyclase expression increases, raising the concentration of cAMP in the cell
- Therefore, the opiate GPCR must be stimulated more frequently in order to maintain a normal cAMP concentration in the cell (tolerance)
How does heroin differ pharmacologically from morphine?
What is the implication of this?
- Heroin is more lipophilic than morphine
- This means heroin gives a faster high
What is the role of cAMP in neuronal signalling?
How do opiates affect the dopaminergic pathways to produce a rewarding sensation?
- cAMP increases neuronal excitability
- Since opiates reduce intracellular concentrations of cAMP, the opiate receptor can’t be in the dopaminergic pathway
- Therefore, opiates act on GABAergic interneurones in the ventral tegmental area of the midbrain, adjacent to the substantia nigra
- Inhibition of these GABAergic interneurones decreases inhibition of the dopaminergic pathways, producing a rewarding sensation
What is the main treatment for opiate overdose?
Describe the mechanism of action of this treatment.
Give an example of a disadvantage of this treatment.
- Naloxone is the main treatment for opiate overdose
- It is an opiate receptor antagonist
- It has a short half life of 30 minutes, therefore it must be frequently infused to match the half life of the opiate drugs, which can have a half life of 15 hours
What is the main treatment for opiate dependence?
Describe the mechanism of action of this treatment.
List 2 advantages of this treatment.
- Methadone is the main treatment for opiate dependence
- It is an opiate that mimics the reward of other opiate drugs
- It is orally active, therefore it can bypass the issues of infections from injection
- It also has a long half life, so once the individual is maintained on methadone, withdrawal only occurs very slowly, therefore it is a tolerable drug
List 2 pharmacological functions of caffeine.
What effect do these functions have on neuronal activity?
1 - It is a phosphodiesterase inhibitor
2 - It is an adenosine receptor antagonist
- These mechanisms increase neuronal excitability
- Remember phosphodiesterase degrades cAMP
Describe the mechanism of action of cocaine.
Cocaine inhibits catecholamine reuptake, therefore increasing the synaptic concentration
Why does chronic use of cocaine by inhalation result in necrosis of nasal tissue?
NAd uptake inhibited -> sympNS excitation -> vasoconstriction -> tissue necrosis especially nasal septum
What is the mechanism of action of amphetamines?
They release & block re-uptake of catecholamines e.g. dopamine & NAd, resulting in a rewarding effect
Which drug class is used to treat amphetamine overdose?
Overdose treated with neuroleptics (dopamine receptor antagonists)
What is the mechanism of action of methylenedioxymethamphetamine (MDMA)?
Releases & blocks re-uptake of 5-HT at synapses
