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Time Completed: 01:07:02

Final Score 54%

98
82

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Pharmacology

Central Nervous System

Question 114 of 180

Regarding codeine, which of the following statements is INCORRECT:

Answer:

Codeine phosphate is a weak opioid and can be used for the relief of mild to moderate pain where other painkillers such as paracetamol or ibuprofen have proved ineffective. Codeine is metabolised to morphine which is responsible for its therapeutic effects. Codeine 240 mg is approximately equivalent to 30 mg of morphine. The capacity to metabolise codeine can vary considerably between individuals; there is a marked increase in morphine toxicity in people who are ultra rapid metabolisers, and reduced therapeutic effect in poor codeine metabolisers. Codeine is contraindicated in patients of any age who are known to be ultra-rapid metabolisers of codeine (CYP2D6 ultra-rapid metabolisers). Codeine is also contraindicated in children under 12, and in children of any age who undergo the removal of tonsils or adenoids for the treatment of obstructive sleep apnoea due to reports of morphine toxicity.

Mechanism of Action

Opioid analgesics are usually used to relieve moderate to severe pain particularly of visceral origin. Opioid analgesics mimic endogenous opioid peptides by causing prolonged activation of opioid receptors that are widely distributed throughout the central nervous system, primarily the mu(μ)-receptors which are the most highly concentrated in brain areas involved in nociception.

Activation of these opioid receptors produces a range of central effects including analgesia, respiratory depression (direct inhibition of respiratory centre in brainstem), euphoria, sedation, postural hypotension (depression of the vasomotor centre), miosis (IIIrd nerve nucleus stimulation), nausea/vomiting (stimulation of chemoreceptor trigger zone) and constipation (decreased GI motility).

Repeated use of opioid analgesics can result in tolerance and dependence, although this is less relevant in the acute clinical context. Opioid dependant patients may require much higher doses of opioids to control their pain.

Morphine

Morphine is the most valuable opioid analgesic for severe pain although it frequently causes nausea and vomiting. In addition to relief of pain, morphine also confers a state of euphoria and mental detachment. The efficacy of other opioids are often measured against morphine.

Tramadol

Tramadol may be prescribed for the treatment of moderate to severe pain, and may have special use for neuropathic pain. Tramadol hydrochloride produces analgesia by two mechanisms: an opioid effect and an enhancement of serotonergic and adrenergic pathways. It has fewer of the typical opioid side-effects (notably, less respiratory depression, less constipation and less addiction potential); psychiatric reactions have been reported.

Codeine

Codeine phosphate is a weak opioid and can be used for the relief of mild to moderate pain where other painkillers such as paracetamol or ibuprofen have proved ineffective.

Codeine is metabolised to morphine which is responsible for its therapeutic effects. Codeine 240 mg is approximately equivalent to 30 mg of morphine. The capacity to metabolise codeine can vary considerably between individuals; there is a marked increase in morphine toxicity in people who are ultra rapid metabolisers, and reduced therapeutic effect in poor codeine metabolisers. Codeine is contraindicated in patients of any age who are known to be ultra-rapid metabolisers of codeine (CYP2D6 ultra-rapid metabolisers).

Codeine is also contraindicated in children under 12, and in children of any age who undergo the removal of tonsils or adenoids for the treatment of obstructive sleep apnoea due to reports of morphine toxicity.

Contraindications

Opioids should be avoided in people who have:

  • A risk of paralytic ileus (opioids reduce gastric motility)
  • Acute respiratory depression
  • An acute exacerbation of asthma (opioids can aggravate bronchoconstriction as a result of histamine release)
  • Conditions associated with increased intracranial pressure (opioids can interfere with pupillary response making neurological assessment difficult and may cause retention of carbon dioxide aggravating the increased intracranial pressure)

Cautions

Opioids should be used with caution in:

  • Elderly people (more susceptible to side effects)
  • People with hypothyroidism and adrenocortical insufficiency (opioids can affect endocrine function and lead to hypogonadism and adrenal insufficiency)
  • People with moderate-to-severe chronic kidney disease (adverse effects may be increased because elimination time is prolonged)
  • People with impaired respiratory function, asthma, COPD or acute respiratory depression (risk of respiratory depression)
  • People with hepatic impairment (adverse effects such as sedation and constipation can precipitate hepatic encephalopathy)
  • People with prostatic hyperplasia (urinary retention has been reported)
  • People with obstructive or inflammatory bowel bowel disorders (opioids reduce gastric motility)
  • People with diseases of the biliary tract (ureteric or biliary spasm has been reported)
  • People with chronic constipation (opioids reduce gastric motility)
  • People with convulsive disorders (tramadol may reduce seizure threshold)

Side Effects

All opioids have the potential to cause:

  • Gastrointestinal effects
    • Nausea, vomiting, constipation, difficulty with micturition, biliary spasm
  • Central nervous system effects
    • Sedation, euphoria, respiratory depression, miosis
  • Cardiovascular effects
    • Peripheral vasodilation, postural hypotension
  • Dependence and tolerance

In addition tramadol can cause:

  • Convulsions (mainly after high doses or during concomitant therapy with other drugs that reduce seizure threshold or induce convulsions such as SSRIs and TCAs)
  • Psychiatric reactions including hallucinations and confusion
  • Hypoglycaemia
  • Hyponatraemia

Interactions

All opioids interact with central nervous system depressants such as sedatives or hypnotics, phenothiazines or alcohol. Concomitant use may potentiate the effects of CNS depressants and cause respiratory depression or sedation.

Tramadol has also been reported to increase the anticoagulant effects of warfarin and concomitant use of tramadol with MAOIs may precipitate the serotonin syndrome.

Overdose

In overdose opioids cause coma, respiratory depression, and pinpoint pupils (miosis). Naloxone is a specific antagonist at opioid receptors and reverses respiratory depression caused by opioid drugs.

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  • Biochemistry
  • Blood Gases
  • Haematology
Biochemistry Normal Value
Sodium 135 – 145 mmol/l
Potassium 3.0 – 4.5 mmol/l
Urea 2.5 – 7.5 mmol/l
Glucose 3.5 – 5.0 mmol/l
Creatinine 35 – 135 μmol/l
Alanine Aminotransferase (ALT) 5 – 35 U/l
Gamma-glutamyl Transferase (GGT) < 65 U/l
Alkaline Phosphatase (ALP) 30 – 135 U/l
Aspartate Aminotransferase (AST) < 40 U/l
Total Protein 60 – 80 g/l
Albumin 35 – 50 g/l
Globulin 2.4 – 3.5 g/dl
Amylase < 70 U/l
Total Bilirubin 3 – 17 μmol/l
Calcium 2.1 – 2.5 mmol/l
Chloride 95 – 105 mmol/l
Phosphate 0.8 – 1.4 mmol/l
Haematology Normal Value
Haemoglobin 11.5 – 16.6 g/dl
White Blood Cells 4.0 – 11.0 x 109/l
Platelets 150 – 450 x 109/l
MCV 80 – 96 fl
MCHC 32 – 36 g/dl
Neutrophils 2.0 – 7.5 x 109/l
Lymphocytes 1.5 – 4.0 x 109/l
Monocytes 0.3 – 1.0 x 109/l
Eosinophils 0.1 – 0.5 x 109/l
Basophils < 0.2 x 109/l
Reticulocytes < 2%
Haematocrit 0.35 – 0.49
Red Cell Distribution Width 11 – 15%
Blood Gases Normal Value
pH 7.35 – 7.45
pO2 11 – 14 kPa
pCO2 4.5 – 6.0 kPa
Base Excess -2 – +2 mmol/l
Bicarbonate 24 – 30 mmol/l
Lactate < 2 mmol/l

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