Aletered drug response

[SH4:p18]

Elderly patients

In elderly

• Decreased cardiac output
• Enlarged fat content
  * Accumulation of lipid-soluble drugs (e.g. diazepam, thiopental)
• Decreased protein binding
• Decreased renal function

Also,

Duration of action may be prolonged due to:

• Decreased cardiac output (thus hepatic blood flow)
• Possible decreased hepatic enzyme activity
• For example, lidocaine, fentanyl

Increased Vd due to:

• Increased total body fat content
• Decreased protein binding

Receptor responsiveness is not affected by aging.

Enzyme activity

• Cigarette smoke contains polycyclic hydrocarbon
  --> Induce cytochrome P-450 enzymes
  --> Increase dose requirement of theophylline and tricyclic antidepressants
• Acute EtOH intake
  --> Inhibit drug metabolism
• Chronic EtOH intake (>200g/day)
  --> Induce enzymes
  --> Tolerance to barbiturates

Genetic disorders

• Atypical cholinesterase enzyme
  --> Prolonged duration of action of succinylcholine or mivacurium
• Malignant hyperthermia
  --> Triggered by succinylcholine or volatile anaesthetics
• Glucose-6-phosphate dehydrogenase deficiency
  --> Some drugs can cause hemolysis
• Intermittent porphyria
  --> Barbiturate may trigger an acute attack

Drug interactions

Drugs can interact with each other by

• Impairing absorption
• Compete with plasma protein-binding sites
• Alter metabolism by enzyme induction or inhibition
• Change renal excretion rate
• Physicochemical interaction
  * e.g. precipitation when pancuronium and thiopentone are mixed together