Drug Dependence and tolerance

Question 1

What is a drug?

Answer 1

Any chemical compound

Question 2

What is the ICD 10 criteria for diagnosis of substance dependence?

Answer 2

• desire or sense of compulsion
• difficulties in controlling substance use
• a physiological withdrawal state
• tolerance
• prioritising use
• persisting with subtance use despite consequences

Question 3

Name examples of Class A drugs

Answer 3

• Ecstasy
• LSD
• Heroin
• Cocaine
• Crack
• Magic Mushrooms
• Amphetamines (if prepared for injection)

Question 4

Name examples of Class B drugs

Answer 4

• Amphetamines
• Cannabis
• Methylphenidate (Ritalin)
• Pholcodine

Question 5

Name examples of Class C drugs

Answer 5

• Tranquilisers
• Some painkilers
• Gamma hydroxybutyrate
• Ketamine

Question 6

What other conditions is drug abuse/dependence often linked with (co-morbidity)?

Answer 6

• Depression
• Anxiety
• Schizophrenia (smoking might help)
• PTSD

Question 7

What is the difference between psychological addiction and physical addiction?

Answer 7

• Physical addiction is to self-medicate withdrawal symptoms eg. dysphoria, cramping, agitation
• Psychological addiction drugs of abuse activate same brain systems as natural and so are ‘rewarding’ - much more complex.

Question 8

In what parts of the brain does self-stimulation act - ie the reward centres?

Answer 8

• Median forebrain bundle
• Ventral tegmental area

Also these (but less effective):

• Prefrontal cortex
• Nucleus accumbens

Question 9

What effect does cocaine have at the dopamine nerve terminal?

Answer 9

• Cocaine blocks dopamine transporter (responsible for reuptake)
• More dopamine in cleft binding to post-synaptic receptors
• More reward/pleasure

Question 10

What is the effect of amphetamine on dopamine nerve terminal?

Answer 10

Amphetamines can get into the cell via the dopamine transporter and displace dopamine from synaptic vesicles, so called ‘reverse transport’.

They are also lipophillic and cationic so can get into cells and intracellular organelles quite easily eg. mitochondria.

Question 11

How can methamphetamine abuse lead to Parkinson’s?

Answer 11

Loss of dopamine transporter in human methamphetamine abuser -> neurotoxic -> can lead to early onset parkinson’s.

Question 12

What are the general treatments for addiction?

Answer 12

• Psychological mainly
• Disulfiram for alcohol
• Methadone replacement therapy and opioid antagonists for heroin

Question 13

What are treatments for heroin dependence?

Answer 13

• Mu opioid receptor activity
• Agonists treatment can work, but antagonist would cause terrible withdrawal symptoms (only for overdose)

Question 14

Name a full agonist, a partial agonist and an antagonist for the mu opioid receptor

Answer 14

• Full agonist - heroin
• Partial agonist - buprenorphine
• Antagonist - naloxone

Question 15

What are the types of drug tolerance?

Answer 15

• Dispositional tolerance (metabolic)
• Functional tolerance (cellular)
• Context-specific tolerance (environmental)
• Cross-tolerance

Question 16

What are the acute effects of alcohol on transmitter systems?

Answer 16

• Increases GABA effects
• Decrease excitatory transmitters (glutamate + aspartate)
• Particular effect at NMDA receptors
• 5-HT transmission altered
• Inc release of endogeneous opiates
• Inc mesolimbic dopamine tranmission

Question 17

What is the physiology of a hangover?

Answer 17

• Formation of acetaldehyde (metabolism of alcohol)
• Dehydration
• Irritant effect on GI

Question 18

How does disulfiram (treatment) make you feel sick when taken with alcohol?

Answer 18

• Disulfiram blocks the ALDH enzyme
• -> build up of acetaldehyde
• toxic -> nausea