11)Effects after repeated or continous drug administration

Question 1

Repeated aministration

Answer 1

• Accumulation occurs if drug is administered before the previous dose is completely eliminated
• The amount of drug will progressively ⇡
• When the rate of drug elimination compensates rate of drug administration ⇢ avg drug conc reaches plateau

Question 2

Factors affecting steady state

Answer 2

• Rate of dose administration proportionally affects steady state of plasma conc
• Bioavailability ⇢ modulates rate of dose of administration
• Clearance ⇢ ⇣ clearance = ⇡ steady state conc

Question 3

Multiple applications of the same drug may cause:

Answer 3

Hypersensitivity

Accumulation of drug

• due to strong binding w/proteins in blood/adipose tissue = ⇡ drug toxicity

Changes of receptors

• Homologous desensitisation ⇢ When receptor ⇣ response to agonist at ⇡ conc
• Heterologous desensitisation ⇢ repeated stimulation of receptor by antagonist = desensitisation #

Tolerance

• High conc of a substance constantly binding w/receptor leads to pharmacodynamic tolerance ⇢ desensitising receptor
• ⇣ receptor density
• Other mechanism leads to changes in AP firing rate

Behavioural tolerance ⇢ occurs w/use of psychoactive drugs ⇢ pharmacodynamic tolerance in brain