3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.3. Pharmacology
                  3.1.3.1. Pharmacology principles
 3.1.3.1.5. Variability in drug response 

Variability in drug response

[RD5:p712-p723]

  • Types of variability
    * Pharmacokinetics
    * Pharmadynamic
    * Idiosyncratic
  • Main causes of variability
    * Ethnicity
    * Age
    * Pregnancy
    * Genetic factors
    * Idiosyncratic reactions
    * Disease
    * Drug interaction

Ethnicity

[RD5:p712]

Examples in ethnic differences:

Ethanol

  • Chinese metabolise ethanol differently
    --> Higher plasma concentration of acetaldehyde
    --> Flushing and palpitation

Propranolol

  • Chinese are more sensitive to CVS effects of propranolol than Caucasians
    * But metabolise propranolol faster than Caucasians
    --> Pharmacodynamic reasons for the sensitivity
  • Afro-Caribbean individuals are less sensitive

Age

[RD5:p713-p714]

  • Main reason: Drug elimination is less efficient in neonates and in elderly
  • Other factors:
    * Pharmacodynamic sensitivity
    * Physiological factors (e.g. CVS reflexes)
    * Pathological factors (e.g. CVS diseases)
    * Body composition
    * Concurrent drug administration

Effect of age on renal excretion

Paediatrics

  • GFR in the newborn is about 20% of adult value
  • Tubular function in the newborn is also reduced
  • In term babies, renal function increases to adult values in less than a week
    --> Continues to increase up to double the adult values at 6 months of age
    * [RD5:p713]
  • Increase in renal function occurs slowly in premature babies

 

Example:

  • Gentamicin
    * Halflife > 18 hours in premature babies
    * Halflife = 10 hours in term babies
    * Halflife = 1-4 hours in adults

Elderly

  • GFR declines slowly from 20 years of age
    * Falling by 25% at 50 years old
    * Falling by 50% at 75 years old
  • Plasma creatinine level may remain normal
    * Creatinine synthesise is reduced in elderly due to reduced muscle mass

Example:

  • Chronic administration of digoxin may lead to progressive increase in plasma concentration
    --> A common cause of glycoside toxicity in the elderly

 

 

 

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Placental transfer of drugs increases in late pregnancy

[MCQ, Wood and Wood apparently is the source]

 

Lipid soluble drugs cross placenta with increasing difficulty up to 1000 Da [BGK9:p1025]