L4 Drugs Bioavalability And Distrbution Flashcards
What two processes should drugs undergo in order to be in effect
Absorption: means the transport of drug from site of administration to blood
Distribution: means delivery of drug from blood to tissues
What is pharmacokinetics
The study of changes to drug concentration with time after oral administration where after absorption and distribution the drug will be eliminated from body by metabolism and excretion and time course of drug concentration is represented by area under the curve
Where must drugs go through first before absorption and what happens there
Through portal blood to the liver where drugs are metabolized to metabolites that are diff from administered drug
What is bioavailability
Fraction of administered drug reaching the systemic circulation as intact drug
How is oral bioavailability estimated
By comparing the AUC of the drug concentration-time relationship corrected for the dose
Formula:
F= dose IV x AUC oral/dose oral x AUC IV
What is the clinical relevance of bioavailability
Important for when switching from IV to oral and vice versa
Drugs with low bioavailability will have their oral dose much higher than their iv dose ex: propranolol
Drugs with high oral bioavailability have almost the same oral and IV dose
Ex:phenytoin(anti elliptic drug)
Drugs with very low bioavailability are not suitable as oral and always IV or other routes ex: vancomycin
What is bioequivalance
Time-concentration curves of two formulations are identical and this means they should not only have same AUC but also same c max and t max
What is the clinical significance of bio equilvalence
Practical for drugs with low safety margin or where dosage needs precise control
What are factors affecting distribution relating to tissue itself
Local tissue blood flow—high blood flow(kidney liver)= larger amount of drug
Presence of special barriers like blood brain barrier and blood placental barrier blood testicular barrier which limit the passage of drugs in to these tissues
What are factors affecting distribution relating to the drug itself
Molecular characteristics of drug
Drug affinity to plasma protein:large molecular weight protein molecules that carry substances including hormones and other chemicals in blood
Ex albumin that binds to acidic drugs such as aspirin
Basic drugs such as propranolol
Highly protein bound drugs such as sulphonylurea
Why would drug be retained in vascular compartment (3L)
Has high molecular weight ex: heparin
Highly bound to plasma protein ex: warfarin
Why would drug be in extracellular fluid(15L)
Polar and small mol weight it may escape endothelial lining and reach interstitial space in addition to plasma ex
Gentamicin
Why would drug be distributed to whole body of water (42 L)
Highly lipid soluble ex: propranolol
Very small molecular weight: alcohol
What is volume of distribution
Means the volume un to which a drug appears to be distributed with a concentration equal to that of plasma
Vd=drug dose/ drug plasma conc at zero time
How can vd help determine where drugs are concentrated
Drugs with very high Vd such as digoxin concentrated mainly in the intracellular while those with low Vd such as heparin are limited to blood
