Dependence

Question 1

Varenicline

Indications

Answer 1

• To aid in smoking cessation

Question 2

Varenicline

Answer 2

• Binds with high affinity and selectivity to neuronal nicotinic acetylcholine receptors where it acts as a partial agonist
• A compound that has both agonist activity with lower intrinsic efficacy than nicotine and antagonist in the presence of nicotine
• By blocking nicotine ability to fully activate its receptors in the mesolimbic dopamine system, the neuronal mechanism underlying reinforcement and reward experienced upon smoking

Question 3

Varenicline

Warnings

Answer 3

• Conditions that may lower seizure threshold
• Predisposition to seizures
• History of CVD
• History of psychiatric illness- may exacerbate underlying illness including depression

Question 4

Varenicline

Adverse effects

Answer 4

• Metabolism- weight increase, change in appetite
• Psychiatric- Abnormal dreams, insomnia
• CNS- Headache, somnolence, dizziness
• Respiratory- Dyspnoea, cough
• GI upset
• MSK- Arthralgia, myalgia, back pain
• Abnormal LFTs

Question 5

Varenicline

Interactions

Answer 5

• No clinically meaningful drug interactions

Question 6

Methadone

Common indications

Answer 6

• Severe pain
• Adjunct in the treatment of opioid dependence, particularly if tolerence is particularly low, high or unknown
• Cough in palliative care

Question 7

Methadone

MOA

Answer 7

• Methadone is a full agonist at mu receptor
• It is a synthetic opioid analgesic similar to morphine although less sedative. It acts on the CNS system and smooth muscles via the peripheral nervous system.
• The analgesic effect of methadone occurs about 10 to 20 minutes following parenteral administration.
• Miosis and respiratory depression can occur for more than 24 hours after a single dose.
• Methadone also reduces heart rate, systolic blood pressure and body temperature.
• Sedation is seen in some patients receiving repeated doses and sudden cessation of treatment can result in withdrawal symptoms.
• Like morphine, it also has effects on bowel motility, biliary tone and secretion of pituitary hormones as well as on cough suppression.
• Methadone also causes the release of histamine from mast cells resulting in a number of allergic-type reactions.

Question 8

Methadone

Warnings

Answer 8

• Contraindicated in
  
  • Acute respiratory depression
  • Comatose patients
  • Head injury (opioids interfere with pupillary response, vital for neurological assessment)
  • Raised intracranial pressure (same as above)
  • Risk of paralytic ileus
• Cautioned in
  
  • Sleep apnoea, convulsive disorders, diseases of biliary tract, elderly, impaired resp function, IBD, myasthenia gravis
  • QT prolongation

Question 9

Methadone

Adverse effects

Answer 9

• Respiratory depression- reverse with naloxone
• Dependence, addiction and withdrawal
• Overdose- coma, resp depression and pinpoint pupils
• Arrythmias- QT prolongation
• Confusion, drowsiness
• Constipation- paralytic ileus
• Hypotension
• NB- methadone even in low doses may be cumulative which increases risk of toxicity

Question 10

Methadone

Interactions

Answer 10

• CYP inhibitors-
• MAOI- use is contraindicated as they may prolong and enhance respiratory depressant effects of methadone
• Naloxone- be careful of withdrawal symptoms
• CNS depressants- BZs, antipsychotics, alcohol
• pH of urine- sodium bicarbonate decreased clearance
  *

Question 11

Methadone

Patient communications

Answer 11

• Discuss with patients that prolonged use can cause addiction
• Agree a treatment strategy prior to initiation
• counsel on side effects as well as overdose signs
• Taper dosage slowly
• Consider hyperalgesia, in patients with long term opioid treatment who present with increased pain sensitivity