WEEK 3 - Substance Abuse

Question 1

What are the pharmacodynamics of alcohol?

Answer 1

Binds to GABA(A), enhances GABA-ergic transmission, alters NMDA and 5-HT(3) receptors.

Question 2

Where is alcohol excreted?

Answer 2

90% oxidised in the liver, rest eliminated via lungs and urine.

Question 3

What is the goal of pharmacological management of alcohol dependence?

Answer 3

Aimed at controlling the effects of physical and psychological dependence (tremors, NV, agitation, drug cravings).

Question 4

What is the standard first-line therapy for acute alcohol withdrawal syndrome?

Answer 4

Benzodiazepines (oxazepam & lorazepam)

Question 5

What are signs of alcohol withdrawal syndrome?

Answer 5

Tremors, sweating, N/V, disorientation, ALOC, hallucinations, paranoid delusions, anxiety, agitation, seizure

Question 6

What are adverse effects of naltrexone?

Answer 6

Insomnia, headache, fatigue, dizziness, hepatotoxicity (serious but rare)

Question 7

What is naltrexone? And what does it do?

Answer 7

Opioid receptor antagonist, long action (24-72hrs), prevents euphoria.
Blocks actions of endogenous opioids released by alcohol and blocks activation of DA reward pathways.
Decreases pleasurable effects linked to alcohol consumption and reduces cravings (PO or IM every 4 weeks).

Question 8

What are adverse effects of disulfiram?

Answer 8

Potent vasodilator=vasodilation=intense flsuhing, headache (throbbing), sweating, changes in BP.
GI disturbances (N/V), hyperventilation.`

Question 9

What does disulfiram do?

Answer 9

Promotes abstinence in motivated alcoholics after initial detoxification (making them feel physically ill after).
Inhibitor of aldehyde dehydrogenase:
Blocks degradation of acetaldehyde to acetate.
Acetaldehyde accumulates in the body causing a variety of unpleasant symptoms.

Question 10

What is acamprosate used for?

Answer 10

Maintenance of abstinence in alcohol dependence.

Question 11

What is the MOA of acamprosate?

Answer 11

Has many molecular effect = complex MOA.
Restoration of normal activity in glutamate and GABA systems.
5-HT, NA and DA receptor effects.
Duration of therapy = up to 1 yr.
Renal impairment reduces elimination so check creatinine before starting therapy.
Adverse effects: rash, diarrhoea, vomiting.

Question 12

What is the MOA of caffeine?

Answer 12

Adenosine A2 receptor antagonist

Inhibitor of PDE

Question 13

What are symptoms of high caffeine intake?

Answer 13

Anxiety, tremors, CVS instability (caffeine overdose)

Question 14

What are the effects of caffeine intake?

Answer 14

Increases alertness and well-being, postpones fatigue and stimulates intellectual and motor performance without causing euphoria.

Question 15

What are the pharmacological treatments used with counselling for nicotine addiction?

Answer 15

Nicotine patch: slows absorption into circulation, helps reduce cravings.
Bupropion: inhibits NA and DA re-uptake, active metabolite t1/2=20 hrs, insomnia, agitation, anxiety, visual disturbances, impaired concentration, rash.

Question 16

What are the pharmacodynamics of nicotine?

Answer 16

Nicotine -> catecholamine release -> increases HR, vascular resistance and hypertension -> increases risks for CAD.
Catecholamines stimulate mobilisation of FFAs.
Nicotine increases LDL, decreased HDL, increases inflammatory marks of CAD (CRP).
At the neuronal level nicotine acts as a nAChR agonist (cortex, hippocampus, VTA), increases activity of DA neurons in the VTA.

Question 17

What are the different types of illicit drugs?

Answer 17

Psychostimulants eg. cocaine, ice: produce excitement and euphoria, decrease fatigue, violence (ice).
Hallucinogens eg. LSD, PCP, ecstasy, GHB: affect thought pattern, perception, violent behaviours w/o causing sensations of reward and euphoria (non-addictive drugs of abuse).

Question 18

What part of the brain do addictive drugs target?

What part of the brain do non-addictive drugs target?

Answer 18

Addictive: target mesolimbic DA system.

Non-addictive” target cortical and thalamic circuits.

Question 19

What is are the effects of cocaine?

Answer 19

Intense euphoria followed by dysphoria/irritability -> craving for more of the drug.

Question 20

What is the pharmocodynamics of cocaine?

Answer 20

Rapidly absorbed causing CNS and PNS effects.

Blocks neuronal uptake of DA, NA and 5-HT, blocks DAT, NET, SERT.

Question 21

What are side effects of cocaine?

Answer 21

Overdose (opioid antagonists)

Acute fear, psychotic symptoms, hypertension, tachycardia, coronary vasospasm.

Question 22

What are the side effects of amphetamines (ice and speed)?

Answer 22

Anxiety, tremors, confusion, dizziness in high doses, neurotoxic, mood elevation/euphoria, agitation

Question 23

What are the pharmacodynamics of amphetamines?

Answer 23

Indirectly acting sympathomimetic stimulating release of biogenic amines i.e. NA, DA and 5-HT.
Act on transporters and interfere with VMAT.

Question 24

What are the effects of LSD?

Answer 24

Visual, tactile and auditory hallucinations, thought process disturbed but aware that it is a drug-induced situation.
‘Bad trip’ - homicide/suicide attempts.
Psychological dependence.

Question 25

What are the pharmacodynamics of LSD?

Answer 25

5-HT(2A) agonist in the PRC enhancing glutamatergic tranmission.
Inhibits 5-HT neurons (firing) in raphe nuclei (DRN and MRN)

Question 26

What are the effects of PSP (angel dust)?

Answer 26

Euphoria, excitation, dysphoria, aggression, chronic use may lead to irreversible schizophrenia-like psychosis.

Question 27

What are the pharmacodynamics of PCP (angel dust)?

Answer 27

Glutamate NMDA-receptor antagonist.

Inhibits uptake of DA, NA and stimulates DA release.

Question 28

What are the effects of ecstasy (MDMA) and GHB?

Answer 28

Stimulant and hallucinogenic effects - causes psychological dependence.
Euphoria, enhanced sensory perceptions, social closeness, amnesia, sedation, coma.
Affects mood, sleep, memory, appetite.
Acute toxicity = hyperthermia.

Question 29

What are the pharmacodynamics of ecstasy (MDMA) and GHB?

Answer 29

Stimulates release of DA and 5-HT.

Greater affinity for SERT thus increases 5-HT extracellular concentration.

Question 30

What is hyperserotonergic state?

Answer 30

Potentially fatal, from ecstasy (MDMA) and GHB.
Abnormal muscle movements, muscle rigidity, sweating, disruption in thermoregulation (hyper/hypothermia), confusion, agitation, restlessness, hallucinations, tachycardia, hypertension, LOC, death.