Variability in drug response

[Ref: 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