Analgesia

Question 1

Opioids - Mechanism of Action

Answer 1

• Bind and stimulate μ receptors. With increasing doses, starts to stimulate κ and δ receptors
• Pre-synaptic - close calcium channels, decreasing intracellular calcium in presynaptic terminals of afferent fibres, inhibiting NT release
• Post-synaptic - opens potassium channels, increasing intracellular calcium causing hyper-polarisation (inhibitory post-synaptic potential)

Question 2

Opioids - Central Effects

Answer 2

• Analgesia
• Sedation, but no amnesia
• Cough reflex suppression (e.g. codeine and dextromethorphan)
• Euphoria
• Respiratory depression (important to note in asthmatics), increases carbon dioxide, causing vasodilation. Pethidine does so less than morphine (so used in labour)
• Raised intracranial pressure (secondary to vasodilation)
• Miosis/ pinpoint pupils (pre-existing miosis must be diagnosed before drug administration, important consideration with suspected head injury, does not occur with pethidine)
• Nausea and vomiting (counteracted by cyclizine/ H1 receptor antagonist)
• Truncal muscle rigidity at supraspinal level - particularly fentanyl (counteracted by a neuromuscularblocker)

Question 3

Opioids - Peripheral Effects

Answer 3

• Constipation (worsened with atropine and metoclopramide)
• CVS - peripheral arterial and venous dilation and decreased TPR, resulting in hypotension (mediated by histamine release)
• Histamine release - pruritis/ rash, bronchospasm (therefore opiates CI in poorly controlled asthmatics or COPD patients)
• Genitourinal tract - increased sphincter tone, and urine retention
• Neuroendocrine - increased ADH, prolactin and somatotrophin release
• Biliary tract - biliary colic (use pethidine rather as it has an antimuscarinic effect)
• Uterus - morphine can prolong labour and decrease contraction rate (use pethidine as it has an antimuscarinic effect)

Question 4

Opioids - Contraindications

Answer 4

• Head injury
• Shock
• Liver dysfunction
• Heroin addicts
• Asthma
• COPD

Question 5

Pethidine

Answer 5

• Antimuscarinic properties (counteracts miosis and causes tachycardia)
• Drug of choice in asthmatics
• Metabolised to norpethidine, which is neurotoxic (resulting in seizures)
• Naloxone reversal is less effective
• Half lives - pethidine 2.5-4 hours; norpethidine 8-21 hours
• Serotonin syndrome with monoamine oxidase inhibitors

Question 6

Fentanyl

Answer 6

• Rapid onset of action
• Short duration of action (half life 1-1.6 hours)
• Effective for continuous infusion (especially the analogue remifentanil)
• Potent analgesic that does not depress the CVS, therefore used as post-surgical analgaesia in cardiac patients
• Duration of reparatory depression is less than that of morphine
• Less histamine release, therefore less side effects

Question 7

Tramadol

Answer 7

• Partial μ receptor antagonist and serotonin & noradrenaline reuptake inhibitor
• Causes nausea and vomiting
• High oral bioavailability
• At analgesic doses, there is no respiratory depression or CVS adverse effects
• May cause seizures (especially if there is head trauma)
• CNS depressent effects
• No histamine release
• Drug interactions with serotnin and noradrenaline drugs

Question 8

NSAIDS - Contraindications

Answer 8

Absolute

• GIT bleeding or ulceraton on history
• Hypersensitivity
• Severe liver dysfunction
• Cardiac failure
• Dehydration, hypotension, hypovolemia
• Hyperkalemia
• Renal impairment
• Aspirin-induced asthma

Relative

• Bleeding or coagulation disorders
• Surgery with high risk of hemorrhage
• Surgery where absence of bleeding is important
• Drugs (ACE-I, anticoagulants, methotrexate, cyclosporin, gentamycin)
• Pregnancy and lactation
• Age > 65

Question 9

Ketamine

Answer 9

• MOA: antagonist at NMDA glutamate receptors
• No respiratory depression
• Psychiatric effects

Question 10

Morphine Dose

Answer 10

• Infusion: 0.07-0.5mg/kg/hour
• Intermittent dose: 0.01-0.5mg/kg 1-2 hourly (10-30mg usually…)

Question 11

Fentanyl Dosage

Answer 11

100-200mcg IV