Pharmacology of addiction

Question 1

Define addiction

Answer 1

The compulsive use of a drug even in the face of negative health and social consequences.

Question 2

Long-term treatment options of alcohol addiction

Answer 2

Disulfiram
Naltrexone
Acamprosate

Question 3

MOA dilsulfiram and ARx

Answer 3

Aversion therapy: blocks the aldehyde dehydrogenase (2nd step in EtOH metabolism), resulting in accumulation of aldehyde which produces the aldehyde reaction (ie intense flushing, sweating, palpitations, tachycardia, dyspnoea, hyperventilation and the development of a pounding headache). Chest pains, restlessness and a sense of impending doom may develop. There is an associated steep rise in blood pressure followed by hypotension. Severe reactions may have an effect on the heart, or be associated with seizures and loss of consciousness. Occasionally death may occur from cardiorespiratory failure. Treatment of the interaction involves intensive supportive therapy. Patient compliance and education essential.

Question 4

MOA Naltrexone

Answer 4

Opioid receptor antagonist that reduces the alcohol induced reward via a mechanism involving u-receptors

Question 5

MOA Acamprosate

Answer 5

Weak antagonist of NMDA receptors which normalises disregulated neurotransmission and is used to reduce cravings

Question 6

Pharmacological options for smoking cessation

Answer 6

Nicotine replacement therapy
Varenicline
Bupropion

Question 7

MOA Varenicline and ARx

Answer 7

Partial agonist of nicotine receptors (therefore competitive antagonist when nicotine is given), thus producing a submaximal effect.
Has been linked to suicide ideation.

Question 8

MOA Bupropion and ARx

Answer 8

Neuronal uptake inhibitor of dopamine and noradrenaline; reduces withdrawal symptoms of depression, irritability and anxiety. Lowers the seizure threshold so should not be prescribed if there are other risk factors for seizures. Also CI in history of eating disorders or bipolar, use with caution in liver/renal disease.

Question 9

Treatment options for opioid cessation

Answer 9

A) Transfer to prescription opioid (methadone/buprenorphine)
B) Alleviation of withdrawal (clonidine: a2 receptor agonist which decreases adrenergic neurotransmission and reduces symptoms of withdrawal like sweating, nausea, vomiting, cramps, tachycardia and HT)
C) Antagonists (Naloxone, naltrexone): used in acute opioid overdose - rapid effect reverses the effect of opioids by acting on all three receptors (u, k, d)