3. BASIC PRINCIPLES OF PHARMACOKINETICS AND PHARMACODYNAMICS

a baby that needs iv fluids

gentamycin is given

physiologic barriers

Physical, Chemical, Biological barriers

physical: Epithelial lining of GIT

chemical: pH difference between stomach and fundal veins (pH trapping)

Blood brain barrier/ blood placental barrier/ blood testicular

Bi-lipid layer: Phospholipids, Glycolipids

Transmembrane proteins (G proteins)

Hydrophobic core and 2 Hydrophilic surfaces (most drugs are hydro and lipophilic)

Routes of Drug Administration

Oral (PO)

Inhalation

• Vapors, gases, smoke

Mucous membranes

• Intranasal (drug?)

• Sublingual (drug?)

• Rectal suppository (drug?)

• Vaginal pessary (drug?)

Injection (parenteral)

• Intravenous (IV)

• Intramuscular (IM)

• Subcutaneous (SC)

• Intraperitoneal (IP)

• Intra-arterial (arteries)

• Intra-articular (joints)

Transdermal

Oral Drug Administration: Advantages

Safe, economical, convenient, practical, reversible

Oral Drug Administration: Disadvantages

First pass effect (most is broken down)

Blood levels are difficult to predict due to multiple factors that limit absorption.

Some drugs are destroyed by stomach acids.

Drugs may get inactivated by GI enzymes

Drugs may get activated and then broken down

Drugs may irritate the GI tract

Advantages of Injection Routes

Absorption is more rapid than with oral administration.

Rate of absorption depends on blood flow to particular tissue site (I.V. > I.M. > S.C.).

Advantages specific to I.V. injection

No absorption involved (inject directly into blood)- Does not undergo first pass effect

Rate of infusion can be controlled.

A more accurate prediction of dose is obtained.

Disadvantages/Risks of Injection

A rapid onset of action can be dangerous if overdosing occurs.

If administered too fast, heart and respiratory function could be compromised

Drugs insoluble in water or dissolved in oily liquids can not be given I.V.

Sterile techniques are necessary

BIOAVAILABILITY

The fraction of an administered dose of drug that reaches the blood stream.

what factors affect bioavailability

Physical properties of the drug (hydrophobicity- will not be absorbed, pKa, solubility)

Drug formulation (Sustained release, Troche- lozenge, Pessary)

Fasting state- increased bioavailibility

Gastric emptying rate-

Interactions with other drugs

Age and gender- younger>,

Diet

Genetic, Disease, Ethno cultural, socioeconomic

passive vs active transport *know this slide and examples

passive = more often than active

kidney = main organ of filtration

ABC= active binding cassett

parkisons = L dopa deficiency