Motivated Behaviour: Addiction and Drugs of Abuse Flashcards
List the types of dependence.
1 - Physical dependence.
2 - Psychological dependence.
List 6 symptoms of withdrawal of a drug for which a patient has physical dependence.
1 - Cramps.
2 - Tachycardia.
3 - Piloerection.
4 - Diarrhoea.
List 2 symptoms of withdrawal of a drug for which a patient has psychological dependence.
1 - Compulsive behaviours.
2 - Anxiety.
List 3 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 the types of tolerance.
1 - Innate.
2 - Acquired.
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 (explained in a later card).
How does pharmacodynamic tolerance come about?
- 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).
Where is heroin sourced?
It is a derivative of morphine.
*NB both heroin and morphine are opiates.
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.
Give an example of an opiate that is different in structure to heroin and morphine.
What is the implication of this structural difference?
- Pethidine is structurally different from heroin and morphine.
- This means that, although pethidine acts on the same receptor as heroin and morphine, it doesn’t result in histamine release from mast cells, so it doesn’t leave a red mark (inflammation) when administered.
How quickly does tolerance to opiates come about relative to other drugs?
Tolerance to opiates is relatively quick.
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.
