[PHA6120] UNIT 1.1: Definition of Terms and Basic Concepts

MAIN DRUG

• Chemical entity, substance

• aka. API (Active Pharmaceutical Ingredient)

DRUG PRODUCT

• End or finished product

• Sold in the market

LIBERATION

starts with drug discovery (first step); biopharmaceutic process

ADME

drug is already taken; pharmacokinetic process

RESPONSE

how our body responds to the drug taken; pharmacodynamic process

TOXICITY

When the drug is already toxic in the body

BIOPHARMACEUTICS

interrelationship of the physicochemical properties of the drugs, the dosage form in which the drug is given, the route of administration on the rate and extent of drug absorption

BIOPHARMACEUTICS

• Relation of the physical and chemical properties of the drug to:

1. Bioavailability

2. Pharmacokinetics

3. Pharmacodynamics

4. Toxicologic Effects

BIOAVAILABILITY

rate & extent (amount) of systemic absorption of the therapeutically active drug

BIOAVAILABILITY

A measure of systemic availability of a drug

BIOAVAILABILITY

• Factors:

  • Nature of drug molecule

  • Route of Delivery

  • Formulation of dosage form

BIOAVAILABILITY

• If drug is:

  • Therapeutically effective

  • Toxic

  • No Apparent effect

PHARMACOKINETICS

time course of drug movement in the body during  absorption, distribution, metabolism, & excretion (ADME);

PHARMACOKINETICS

process of how the body deals with the drug

Pharmakon

Greek word meaning “drug”

Kinesis

Greek word meaning “movement”

PHARMACOKINETICS

• GOAL OF APPLICATION: 

  • “Assure maintenance of therapeutic drug concentration in the body while preventing danger of toxicity.”

PHARMACODYNAMICS

relation of the drug concentration or amount at the site of action (receptor) & its pharmacologic response including the biochemical and physiologic effects that influence their interaction with the receptor

Receptor

component of a cell or organism that interacts with a drug and initiates the chain of events leading to the drug’s observed effects

AGONIST

Occupy receptors and activate them

AGONIST

may be Full, Partial, Inverse

ANTAGONIST

Occupy receptors but do not activate them; it blocks receptor activation by agonist

ANTAGONIST

may be Competitive, Non-competitive, Chemical, Physiologic

TOXICOLOGIC

harmful or undesirable effects; T in LADMERT

DRUG EXPOSURE

Refers to dose and various measures of acute or integrated drug concentrations in plasma and other biological fluid

DRUG RESPONSE

Direct measure of the pharmacologic effect of drug

DRUG RESPONSE

Includes endpoints or biomarkers from: remote, presumed mechanistic effect to a potential or accepted surrogate and to a full range short/long term clinical effect

DRUG RESPONSE

• Involves Factors that influence:

1. Design of drug Product

2. Stability of the drug within the drug product

3. Manufacture of drug product

4. Release of drug from drug product

5. Rate of dissolution/release of drug from absorption site 

6. Delivery of drug to the site of action

administration of the drug

SCOPE OF BIOPHARMACEUTICS

All possible effects observed following the _ in its various dosage forms

• therapeutic effect, adverse effect, drug-drug interaction

biological response

SCOPE OF BIOPHARMACEUTICS

1. All possible effects of various dosage forms on _

• onset of action, duration of action

MINIMUM EFFECTIVE CONCENTRATION (MEC)

reflects the minimum concentration of drug needed at the receptors to produce the desired pharmacologic effect

MINIMUM TOXIC CONCENTRATION (MTC)

represents the drug concentration needed to just barely produce a toxic effect

THERAPEUTIC WINDOW

the concentration between MTC and MEC

THERAPEUTIC INDEX

ratio between toxic and therapeutic dose

onset time

corresponds to the time required for the drug to reach the MEC

intensity

The _ of the pharmacologic effect is proportional to the number of drug receptors occupied, which is reflected in the observation that higher plasma drug concentrations produce a greater pharmacologic response, up to a maximum

duration of drug

The _ action is the difference between the onset time and the time for the drug to decline back to the MEC.

time of peak plasma level

The _ is the time of maximum drug concentration in the plasma and is a rough marker of average rate of drug absorption

peak plasma level or maximum drug concentration

The _ is related to the dose, the rate constant for absorption, and the elimination constant of the drug

Area under the Curve (AUC)

The _ is related to the amount of drug absorbed systemically.

physiological factors

SCOPE OF BIOPHARMACEUTICS

1. All possible _ which may affect the drug contained in the dosage form. 

• pH of the stomach & intestine, surface area of skin

bioavailable

A drug that is _ is most likely to cause an effect in the body

design; physicochemical properties

The sequence of events is affected by the _ of dosage form and _ of the drug

PHARMACOKINETICS

process of how the body deals with the drug, “what your body does to your drug”

PHARMACODYNAMICS

process of how your drug deals with the body, “what your drug does to your body”

CLINICAL PHARMACOKINETICS

Application of pharmacokinetic models to drug therapy

CLINICAL PHARMACOKINETICS

• Factors affecting drug disposition:

  • Drug disposition serves as basis of dosing regimens

  • Disease

  • Age

  • Gender

  • Genetic and ethnic differences

THERAPEUTIC DRUG MONITORING (TDM)

used for very potent drugs ex. w/ narrowtherapeutic range; optimize efficacy and prevent adverse toxicity

THERAPEUTIC DRUG MONITORING (TDM)

• Monitoring plasma drug conc ( theophylline, chemotherapeutic drugs, anticonvulsants, aminoglycosides)

• Monitor specific pharmacodynamic endpoint such as Prothrombin clotting time ( warfarin)

plasma drug concentration

THERAPEUTIC DRUG MONITORING (TDM)

• theophylline, chemotherapeutic drugs, anticonvulsants, aminoglycosides

specific pharmacodynamic endpoint

THERAPEUTIC DRUG MONITORING (TDM)

• Prothrombin clotting time ( warfarin)

Soluble

PREREQUISITES FOR A DRUG TO EXERT BIOLOGICAL EFFECT

_ in body fluids

Transported by bodyguards

PREREQUISITES FOR A DRUG TO EXERT BIOLOGICAL EFFECT

• Indiscriminate distribution to all parts of the body:

  • Site where it has no action

  • Storage site

  • Site of action

Pass membrane barriers

PREREQUISITES FOR A DRUG TO EXERT BIOLOGICAL EFFECT

• More lipid soluble -> transverse cell membrane easily

• Ionized drug -> more water soluble

• Non-ionized drug -> more lipid soluble

• Low molecular weight

• BBB, placental barrier

body depots 

PREREQUISITES FOR A DRUG TO EXERT BIOLOGICAL EFFECT

• Escape excessive distribution to inert _

  • e.g. fats, muscle tissues

Endure metabolic attack

PREREQUISITES FOR A DRUG TO EXERT BIOLOGICAL EFFECT

• Stomach enzymes that catalyze drug degradation

• Ex. Erythromycin

  • pH dependent stability profile

  • Decomposition in acidic medium

  • Relatively stable in neutral and alkaline medium

  • Erythromycin are enteric coated

Penetrate to its site of action

PREREQUISITES FOR A DRUG TO EXERT BIOLOGICAL EFFECT

Blood perfusion in tissue or organ

Act so as to alter a particular function

PREREQUISITES FOR A DRUG TO EXERT BIOLOGICAL EFFECT

ex. High blood pressure

Action

Bioresponse to drug; consequence of drug-living system interaction

Action

Cause changes in biological state that was present before drug administration

amount; place; time

To deliver the right _ of drug that is EFFECTIVE and SAFE at the right (site of action) and at the right _ (oral, SL or IV/ fast or slow-release)