3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.3. Pharmacology
                  3.1.3.1. Pharmacology principles
                      3.1.3.1.2. Pharmacodynamics
                          3.1.3.1.2.3. Dose-response relationship
 3.1.3.1.2.3.2. Altered drug response 

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