Rules Acid drugs – become more NON ionized in acidic pH Basic drugs – become more NON ionized in basic pH (alkaline pH)‏ Acid DrugBasic Drug Acid pH Environment Basic pH Environment

Rules Acid drugs – become more NON ionized in acidic pH Basic drugs – become more NON ionized in basic pH (alkaline pH)‏ Acid Drug Basic Drug Acid pH Environment Basic pH Environment NON-ionized

Rules Acid drugs – become more NON ionized in acidic pH Basic drugs – become more NON ionized in basic pH (alkaline pH)‏ Acid Drug Basic Drug Acid pH Environment Basic pH Environment NON-ionized

Rules Acid drugs – become more NON ionized in acidic pH Basic drugs – become more NON ionized in basic pH (alkaline pH)‏ Acid Drug Basic Drug Acid pH Environment Basic pH Environment NON-ionized IONIZED

Rules Acid drugs – become more NON ionized in acidic pH Basic drugs – become more NON ionized in basic pH (alkaline pH)‏ Acid Drug Basic Drug Acid pH Environment Basic pH Environment NON-ionized IONIZED

Rules Hydrophilic = Ionized molecules (charged)‏ Lipophilic = Non-ionized molecules (non charged)‏ Lipophilic molecules penetrate membranes Hydrophilic molecules dissolve in water

Depending if a molecule is ionized or not determines if it can pass through a cell membrane C E L L M E M B R A N E Ionized Molecule Non-Ionized Molecule

Need three things to figure out whether drug is MAJORITY in lipophilic or hydrophilic form 1.Whether the drug is an acid drug or a base drug. 2.The pKa of the drug (pH at which number of ionized = number of nonionized molecules)‏ 3.pH into which the drug is going to be placed

Acid Drug = Non ionized molecules = Ionized molecules Acid drugs – become more NON ionized in acidic pH pH 2 NI pH 6 NI pH 9 I pH 8 I N

Acid Drug = Non ionized molecules = Ionized molecules Acid drugs – become more NON ionized in acidic pH pH 2 NI pH 6 NI pH 9 I pH 8 I N What’s the pKa for this drug?

Basic Drug = Non ionized molecules = Ionized molecules Basic drugs – become more NON ionized in basic pH pH 9 NI pH 8 NI pH 2 I pH 6 I N What’s the pKa for this drug?

WHEN GIVEN: 1.Acid / Base nature of the drug 2.Drug’s pKa 3.Environmental pH drug is put into ionizednon-ionized Be able to predict whether majority of drug is in the ionized form or non-ionized form hydrophiliclipophilic Be able to state whether majority of drug is in the hydrophilic form or lipophilic form Be able to predict whether it can be absorbed across membrane (PO) or dissolved in water (SQ, IM)‏

Acid 7 2 stomach Acid Drug pKa = 7 pH put into = 2 (stomach) Absorbed well from stomach? ==================================== pH = 1pH = 12  Non-ionizedIonized  pKa ↓ pH=7 pH 2 ▼ More drug is in the NON-IONIZED form Is the drug readily absorbed from stomach?YES

Acid intestine Acid Drug pKa = 7 pH put into = 6.0 (duodenum) Absorbed well from intestine? ==================================== pH = 1pH = 12  Non-ionizedIonized  pKa ↓ pH=7 pH 6 ▼ More drug is in the NON-IONIZED form Is the drug readily absorbed from intestine?YES

Acid SQ injection Acid Drug pKa = 7 pH put into = 7.4 (SQ) Absorbed well from SQ injection? ==================================== pH = 1pH = 12  Non-ionizedIonized  pKa ↓ pH=7 pH 7.4 ▼ More drug is in the IONIZED form Is the drug readily absorbed from SQ injection?YES

Basic 7 2 stomach Basic Drug pKa = 7 pH put into = 2 (stomach) Absorbed well from stomach? ==================================== pH = 1pH = 12  IonizedNon-Ionized  pKa ↓ pH=7 pH 2 ▼ Is the drug readily absorbed from stomach?No More drug is in the IONIZED form

Basic SQ injection Basic Drug pKa = 7 pH put into = 7.4 (SQ) Absorbed well from SQ injection? ==================================== pH = 1pH = 12 pKa ↓ pH=7 pH 7.4 ▼ Is the drug readily absorbed from SQ injection?No More drug is in the NON-IONIZED form Non-Ionized   Ionized

WHEN GIVEN: 1.Acid / Base nature of the drug 2.Drug’s pKa 3.Environmental pH drug is put into ionizednon-ionized Be able to predict whether majority of drug is in the ionized form or non-ionized form hydrophiliclipophilic Be able to state whether majority of drug is in the hydrophilic form or lipophilic form Be able to predict whether it can be absorbed across membrane (PO) or dissolved in water (SQ, IM)‏