Dosage Adjustments

Question 1

Describe patient factors to select/adapt dosage/dose.

Answer 1

1. Breed
   -herding breeds sensitive to drugs
   >MDR1 & ivermectin
2. Body weight & physiology
   -adipocytes -> effect on disposition liposoluble drugs
   -body SA -> chemotherapeutic drugs
3. Age
   -newborn to pediatric
   -geriatric
4. Health status
   -hepatic dysfunction
   -renal insufficiency
   -heart failure
5. Gender
   -preg: affect distribution
   -lactation: affect distribution & elim
6. Temperament
   -aggressive, stress, excitement
   >high sympathetic -> lower response for sed
   -docile
   >may not require full dose sed

Question 2

Describe how age affects drug dosage.

Answer 2

-newborn to pediatric
>inc intestinal permeability -> PO absorption
>distribution: dec plasma protein binding, dec BBB function, inc total body water
>dec metabolism & excretion
-geriatric
>distribution: dec CO, dec total body water, dec plasma protein, dec body mass & inc body fat
-metabolism/excretion: dec metabolic enzymes, dec hepatic blood flow, dec renal function

Question 3

Describe how health status affect drug dosage.

Answer 3

1. Hepatic dysfunction
   -dec drug metabolism & excretion = longer t1/2
   -ascites -> no distribution of liposoluble drugs
2. Renal insufficiency
   -dec drug excretion
3. Heart failure
   -IV or IM routes preferred
   -shunt blood flow to brain & heart = peripheral vasoconstriction
   >blood flow affect ADME
   -prerenal failure
   -RHF edema in GI -> PO absorption

Question 4

Describe the concept of drug accumulation.

Answer 4

rate of elim slower than rate of absorption
1. Renal insufficiency
-dec drug excretion
2. Hepatic insufficiency
-dec drug metabolism
3. Adipose tissue = accumulate lipophilic drugs
-inc drug redistribution
-slower drug excretion

Question 5

Describe drug factors to select/adapt dosage/dose.

Answer 5

1. Route & timing of administration
   -onset & duration of action
   >IV = rapid onset, short duration
   >extravascular: rate of absorption
2. Drug interaction
   -hepatic enzyme inducing mediation
3. PD of the drug
   -steady state

Question 6

Describe how health status - renal disease adjusts the dosage.

Answer 6

-narrow safety margin + renal elim
-creatinine clearance used in human med
*adjusted dose LOWER
*adjusted dose interval will be LONGER

Question 7

Describe how therapeutic drug monitoring adjusts dosage.

Answer 7

-indicated w use of drug w narrow safety margin
>aminoglycosides
>phenobarbital, potassium
-if lack of clinical response = investigate if its a PK problem
-clinician adapt dose/dosage by monitoring Cp
>require access to lab facility

Question 8

Describe phenobarbital therapeutic drug monitoring.

Answer 8

-measure after 2 weeks of therapy = 1 blood sample
-calc new dosage from therapeutic drug monitoring

Question 9

Describe aminoglycosides therapeutic drug monitoring.

Answer 9

-time of collection is key for TDM
-2 time points (C1 & C2 C2 must not be too late after administration to be detectable)
-adapt dose based on Cmax (peak) & Cmin (trough) - OR discontinue treatment based on if the t1/2 has increased