PH2113 - Abuse of drugs in theory & practice 2

Question 1

What is long-term desensitisation?

Answer 1

After repeated or prolonged activation downregulation
- delivered to lysosomes and degraded after internalisation
- gene transcription may be downregulated to stop production of new receptors
- decreased response over hours
- as opposed to seconds/minutes
- RGS proteins may be changed
- GTPase activating proteins accelerate the rate of GTP hydrolysis
- speeds up receptor deactivation
Homologous vs heterologous
- homologous
- may cause phosphorylation of own receptor
- heterologous
- may change response to other drugs when other receptors phosphorylated as well

Question 2

How does receptor up-regulation take place?

Answer 2

Naive
- antagonist blocks endogenous transmitter or exogenous agonist
Tolerance
- cell synthesises and inserts new receptors into cell membrane
- higher number of receptors so more antagonist needed to produce same response

Question 3

What is receptor uncoupling?

Answer 3

Compensatory changes

• receptor-second messenger uncoupling
• G-protein coupled adenyl cyclase or guanylyl cyclase
• receptor-ion channel uncoupling

Question 4

How does receptor-second messenger uncoupling take place?

Answer 4

Agonist stimulates adenylyl cyclase linked to G-protein

Repeated drug exposure uncouples enzyme from G-protein on internal side of membrane

Question 5

How does receptor-ion channel uncoupling take place?

Answer 5

Drug causes a change in ion flux to alter ion concentration and potential across membrane
Receptor-ion channel uncoupling impairs ion fluxes, ion concentration and potential across membrane

Question 6

What is functional tolerance with regards to exhaustion of mediators?

Answer 6

Tolerance associated with depletion of intermediate substances

• amphetamine and cocaine release neuronal noradrenaline, dopamine and other amines
• releasable transmitter stores can be depleted

Question 7

How does tolerance at reuptake transporters take place?

Answer 7

Cocaine frequent-use tolerance

• tolerance to inhibition of dopamine uptake
• tolerance to noradrenaline uptake and positive chronotropic action

Longer term

• some down-regulation of dopamine receptors
• some exhaustion of dopamine stores

Question 8

What is conditioned tolerance?

Answer 8

Repeated administration of drug in given circumstances
- surroundings and/or company

Conditioned response

Question 9

What causes conditioned tolerance?

Answer 9

Physiological tolerance factor

Psychological anticipation of drug effect

Question 10

What can conditioned response lead to?

Answer 10

Positive tolerance

Negative tolerance

Question 11

What is negative conditioned tolerance?

Answer 11

Reverse tolerance

- environment enhances the so-called ‘desired effect’ of the drug

Question 12

What is positive conditioned tolerance?

Answer 12

Conditioned response opposite to that expected of drug

- reduction in response based on environment

Question 13

How does level of tolerance depend on the drug?

Answer 13

2 - 3x the naive dose

• CNS depressants
• alcohol
• barbiturates

10 - 20x the naive dose

• opioids
• cocaine
• CNS stimulants

Question 14

What is acute tolerance?

Answer 14

Intra-sessional tolerance

• develops after single exposure to drug
• may develop during exposure to drug

Question 15

What is chronic tolerance?

Answer 15

Inter-sessional tolerance

- develops after several exposures to drug

Question 16

Why do insulin-dependent diabetics take insulin?

Answer 16

To avoid discomfort of absence of insulin

Question 17

Why do patients take beta-blockers?

Answer 17

Long term withdrawal = hypertensive rebound

Question 18

What is drug abstinence caused by?

Answer 18

Drug taking cessation
- e.g. smoking
Antagonism by other drugs
- drugs to block drugs
- naloxone

Question 19

What does the severity of drug abstinence depend on?

Answer 19

Drug
Dose
Duration of use

Question 20

What are withdrawal symptoms?

Answer 20

Physical and mental symptoms that occur after stopping or reducing intake of a drug

Question 21

What is withdrawal relief?

Answer 21

What is withdrawal relief?

Question 22

What is salience?

Answer 22

Compulsion to continue taking the drug in spite of all other considerations

• legal
• financial
• health

The value of the reward

Question 23

What are the classifications of drugs of dependence?

Answer 23

Alcohol-barbiturate type
Amphetamine type
Cannabis type
Cocaine type
Hallucinogen type
Khat type
Opioid type
Volatile solvent type

Also
Tobacco type
Caffeine type
Betel type
Designer drugs
OTC medicines