[7] Pharmacokinetics in Special Conditions Flashcards
Are most active drugs Basic or Acidic?
Basic
Assessment of Renal Function (3)
- Hourly urine output
- Amount of circulating Urea and Nitrogen Concentration
- Creatine clearance and GFR
Average Hourly Urine Output?
60mL
Limitation of Creatinine Clearance
Less muscle bulk or in elderly patients would give a lower than average creatinine clearance value
Formula: Dose Adjustment Factor
1 / F (kf -1) +1
F: Fraction of Drug Excreted Unchanged
Kf: Relative Kidney function calculated by dividing actual creatinine clearance with 120 mL/min
Example:
Digoxin F = 0.75
If the oral digoxin dose is 0.25mg orally, what is the DAF for a patient with creatinine clearance of 60 mL/minute?
DAF = 1/0.75 (60/120 - 1) + 1
= 1.6
Adjusted dose is 0.25 / 1.6 or 1.6mg daily
Conditions for Validity of DAF
o Only for first order kinetic (one compartment) in the therapeutic concentration range →What you excrete is proportionate to what’s in your body
o Metabolites of the drug are not active and non-toxic; otherwise, it would follow a 2 compartment model
o No difference in the absorption, metabolism and distribution of the drug between normal and uremic patients
o No alterations in drug sensitivity in uremic patients
o A direct relationship is assumed between ClCr and the renal elimination of the drug
o Stable kidney function
Reduction in Drug Dosage Depends on? (3)
- Therapeutic Index of Drug
- Proportion of Renal Clearance of Total Clearance
- Severity of Renal Impairment
How does renal damage affect drugs in terms of protein bound forms?
With less albumin present, the drugs that are unbound are in their active form and as such would be stronger than usual
[Binding to Plasma Proteins in Patients with Poor Renal Function]
Amoxicillin
Slight decrease
[Binding to Plasma Proteins in Patients with Poor Renal Function]
Bilirubin
Decrease
[Binding to Plasma Proteins in Patients with Poor Renal Function]
Cefazolin
Decrease
[Binding to Plasma Proteins in Patients with Poor Renal Function]
Furosemide
Decrease
[Binding to Plasma Proteins in Patients with Poor Renal Function]
Indomethacin
Normal
[Binding to Plasma Proteins in Patients with Poor Renal Function]
Cefoxitin
Decrease
[Binding to Plasma Proteins in Patients with Poor Renal Function]
Clofibrate
Decrease
[Binding to Plasma Proteins in Patients with Poor Renal Function]
Diazoxide
Decrease
[Binding to Plasma Proteins in Patients with Poor Renal Function]
Phenobarbital
Decrease
[Binding to Plasma Proteins in Patients with Poor Renal Function]
Phenytoin
Decrease
[Binding to Plasma Proteins in Patients with Poor Renal Function]
Salicyclate
Decrease
How do you achieve diuresis in patients with renal disease?
Loop Diuretics
What can you never give pregnant women at any stage?
ACE Inhibitors, they would cause renal damage
Most important drug you cannot give to patients with renal failure
Potassium, since only kidneys excrete K
Highly cardiotoxic
Most Common of Pathway of Biotransformation in the Liver?
A. Conjugation
B. Oxidation
C. Sulfuridation
D. Glucorination
A
Filipinos are rapid acetylators
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2 Examples of Hetapic Derangement that can Affect Drug Fate and Action
- Hepatocellular loss with absolute decrease in quantity of Drug Metabolizing Enzymes
- Effect of Altered Perfusion
Which drug will give more adverse reactions with cirrhosis?
Lidocaine ER: 0.9
Antipyrine ER: 0.1
Lidocaine, because of the high extraction ratio
Large volume of distribution indicates high affinity of drug to tissues or plasma?
Tissues
Define: Extraction Ratio
Extent to which a drug is cleared in one passage in the liver
What are the drugs that can have prolonged or unchanged Half-Life?
Pentobarbital
Phenytoin
Prednisone
Tolbutamide
TP3
Liver problems cause losses of which vitamin?
Vitamin K
Examples of Drugs Extensively Metabolized by the Liver
Benzodiazepines
NSAIDs
Opiods
Plasma Volume increases by how much during pregnancy?
40-50%
Effect on:
Plasma Albumin Levels
Plasma Total Protein
A1 Acid Glycoprotein
PA: Decreases
PTP: The Same
A1AG: The Same
Example of a drug that would increase in concentration during pregnancy?
Probenicin
Drug with high protein binding affinity
What causes the delay in gastric emptying time in pregnant women?
Progesterone, increased during pregnancy
[Pregnancy]
What happens to acid secretion during the 1st, 2nd, and 3rd trimester?
1st: Decreased
2nd: Decreased
3rd: Increased
Effect of Smoking on Babies in Utero
Low Birth Weight
Effect of Drugs on Fetus Before 20th Day
All-or-Nothing Effect
Effect of Drugs on Fetus 3rd to 8th Week (3)
- No Measurable Effect/Abortion
- Permanent Subtle Metabolic/Functional Defect
- Sublethal Gross Anatomic Defect
Effect of Drugs on Fetus 2nd and 3rd Trimester
Altered growth and function of normally formed organ and tissues
Most delicate organ that can be affected at any point of growth in utero and onward
Reproductive System
The Brain is also counted
