LD50 / ED50: used as a measure of drug safety
-Imperfect, but drugs with a wide therapeutic index are generally safer.
-Doesn't account for allergies.
Dose that exhibits therapeutic effect in 50% of population
Does that generates death in 50% of population
Concentration that generates 50% of maximal response
Passage of drug through the body (dose-concentration relationships)
Effects of drug on the body (concentration-effect relationships)
-Uncharged in protonated form (below pKa)
-Negatively charged in deprotonated form (above pKa)
-Ion trapping occurs in basic environments
-Uncharged in deprotonated form (above pKa)
-Positively charged in protonated form (below pKa)
-Ion trapping occurs in acidic environments
Acidic Henderson Hasselbech
[AH] / [A-] = 10 ^ pKa - pH
Basic Henerson Hasselbech
[B] / [BH+] = 10 ^ pH - pKa
Calculation of ion trapping
Assume uncharged drug concentration on both sides of membrane = 1. Then use Henderson-Hasselbech to calculate the amount of charged drug & sum.
Milk is more acidic than blood --> basic drugs are ion trapped in milk & secreted in high concentrations
Nicotine is basic --> acidic substances like cola & coffee decrease absorption
In order to facilitate ion trapping of drugs in the ultra filtrate: acidic urine traps basic drugs, and basic urine traps acidic drugs.