PHARMACOKINETIC PARAMETERS

#3.Basic Pharmacologic Principles

Dr. Erwin Taguinod Clearance
- volume of plasma cleared of drug (mL/min) by renal
excretion or metabolism, or both in the liver or other
PHARMACOKINETICS organs.
- describes the absorption, distribution, metabolism
and excretion of inhaled and or injected drugs. Volume of Distribution
- Vd is a calculated number (i.e.,dose of drug
PHARMACODYNAMICS administered IV, divided by the plasma
- describes the responsiveness of receptors to drugs concentration) that reflects the apparent volumes of
and the mechanism by which these effects occurs. the compartments that constitutes the
compartmental model for that drug
PHARMACOKINETICS
Elimination Half-Time
DRUG IONIZATION - the time necessary for the plasma concentration of
Ionized drug to decrease 50% during elimination phase.
Nonionized
Context-Sensitive Half-Time
DRUG ABSORPTION - describes the time necessary for the drug
- rate at which a drug leaves its site of administration. concentration to decrease to a predetermined
- membrane transport percentage (e.g., 50%, 60%, 80%) after
discontinuation of a continuous IV infusion of a
ROUTE OF ADMINISTRATION specific duration.

DRUG DISTRIBUTION Effect-Site Equilibration

pH of the drug’s environment - the delay between the IV administration of a drug
degree of ionization and the onset of its clinical effect reflects the time
dissociation constant (pKa) necessary for the circulation to deliver the drug to its
protein binding site of action.
molecular weight
lipid solubility Bioavailability
- the amount of active drug that is absorbed and
Protein binding reaches the systemic circulation.
- determines the concentration of the drug in the
plasma and various other tissues.
- acts as a temporary reservoir for a drug that PHARMACODYNAMICS
prevents large flactuations in the concentration of
the unbound or free drugs. RECEPTORS
- Albumin, a1-acid glycoproteins - are excitable transmembrane proteins that are
responsible for transduction of biologic signals.
ION TRAPPING - voltage sensitive ion channels
ligand-gated ion channels
REDISTRIBUTION and STORAGE transmembrane receptors

DRUG METABOLISM RECEPTOR AGONIST and ANTAGONISTS

- converts pharmacologically active, lipid soluble drugs AGONIST
to water soluble and often inactive metabolites. - a drug that initiates pharmacologic effects after
- may also result in conversion of an inactive form combining with the receptor.
(prodrug) to an active drug - when bound to receptor, induce stimulatory or
inhibitory effects that mimic endogenous hormones
Phase I Reaction and neurotransmitters.
oxidation, reduction, hydrolysis
Phase II Reaction ANTAGONIST
conjugation - bind to receptors but are not capable of eliciting a
pharmacologic response.
DRUG EXCRETION - prevents receptor mediated agonist effects by
occupying agonist sites
THERAPEUTIC INDEX
- the ratio between the lethal dose (LD50) in 50% of
patients and the effective dose (ED50) in 50% of
patients.
- the higher the therapeutic index of a drug, the safer
it is for clinical administration because the LD is far
above the ED.

DRUG TOLERANCE
- present when a large dose of a drug is required to
elicit an effect that is usually produced by the
smaller (therapeutic)dose of the drug.

TACHYPHLAXIS

DRUG DEPENDENCE
- a psychic or physical state characterized by
behavioral responses that include a compulsion to
take the drug on a continuous or periodic basis to
experience its psychic effects and sometimes to
avoid the discomfort of its absence.