Pharmacodynamics = drug does to body
Pharmacokinetics = body does to drug

Absorption – process by which unchanged drug enters circulation (blood).

Distribution – dispersion of a drug among different compartments of body i.e. fluids & tissues of the body (some will remain in circulation).

Metabolism – transformation of a drug into daughter compounds i.e. metabolism (biotransformation).

Excretion – removal of drugs (parent drug)/metabolites from body.

Rule: ADME determines key properties of drug like speed of onset, duration, action and potential problems.

• Essential for safe use of treatment
• Important in designing reginmens
• Can be used to monitor treatment by doing a urine or blood test
• Used in the ER to monitor substance abuse
• A requirement to medicine licensing

Def: BNF – Books that give info on licensed medications including indications, cautions, dosage & side effects

Rule: Pharmacokinetics is most common reason for withdrawal of candidate drugs from development.

Example: Drug too poorly absorbed from oral dosage only absorbed well in IV and so not convenient for everyday usage

Rule:

We desire a certain threshold conc of drug to be absorbed into bloodstream, as soon as drug in plasma it can be delivered not only to site of action but also the liver, kidneys & other sites of metabolism

So concn of drug in circulation (plasma) is determined by the supply rate, distribution * removal from body.

Def: drug absorption - process by which unchanged (parent) drug gets from site of delivery to circulation
*parent drug because it must reach bloodstream to be metabolized first

Rule: unless given IV, medicines must pass the necessary cell barriers to be absorbed

Example: oral – drug -> stomach -> intestine -> intestinal wall -> liver. t/f drug must be lipophilic and be able to survive

Rule: choice of delivery route is a compromise b/w different things. These are following:

 Speed of onset: how quickly want drug to start acting. If an emergency, most direct route would be IV.
 Convenience: as it is linked to compliance of patient. If dosage regiment is too inconvenient then patient won’t follow it.
 Bioavailability: proportion of administered drug that reaches circulation.
 Side effects & specificity of action.

Examples
Oral – must common / IM – intramuscular / SC - subcutaneous

Inhalers – Local acting drugs (don’t necessarily have to enter systemic circulation)

Topical applications – steroid creams absorbed through skin do not need to enter circulation

Single cell barriers (two options)

• Transcellular route: goes straight thru CSM, thru cell & out other side.
• Paracellular route: gaps b/w cells which certain drugs can pass thru.

*Multiple cell barriers (Most drugs) – also takes transcellular and paracellular

Most medicines are absorbed via transcellular route using driving force passive diffusion where drug conc. gradient drives its movement through barriers

Some drug use facilitated diffusion (use carrier proteins)

Little drugs use active transport

Rule: Fick’s law

Equation: Rate of diffusion = surface area x conc difference x permeability

Rule: Permeability of a membrane to a particular chemical is determined by molecular size, lipid solubility & presence of charged/ionizable groups.

Rules:

Charge can be modified to modify a drugs solubility

Most drugs are weak acids and bases and so can be ionized into neutral form to cross barrier

MOA:

Weak acid = proton donor -> will donate protons & become negatively charged (anion).

Weak base = proton acceptor -> will accept protons & become positively charged (cation).

Def: acid-base dissociation constant of drug = how easily the drug will accept or donate a proton based on its chemical structure.

Rule:
If drugs ionized too much ↓ likely to move thru membranes.

Extent of ionization of the drug depends on pH of environment and acid base dissociation constant.

Examples:
AH (acidic drug) -> passes through membrane as neutral -> depending on acid-dissociation constant of drug and pH of environment on the other side -> ionizes donating a proton to alkaline env. -> becomes active

Equations:
• For acids: pH = pKa – log [non-ionised]/[ionised]
• For bases: pH = pkA + log [non-ionised]/[ionised]

Def: pKa = acid-base dissociation constant.

Rules:
pH = pKa -> half of drug is ionized

Acidic drugs = the more acidic the environment the more unionized the drug will be.

Basic drugs = the more basic the environment the more unionized the drug will be.