9/3 new lecture material (on exam) Drug-Body Interactions

drug

any substance that brings about a change in biologic
function through its chemical actions

Poisons

drugs that have almost exclusively harmful effects

Toxins

defined as poisons of biologic origin

Effector molecules

molecules that carry out the effect after a receptor is activated

pathway of drugs

drug → Receptor → Effector molecule → Cell response

Factors that influence drug-receptor interactions

Size, Electrical charge, Shape, and Composition

drug size

Smaller molecules cross barriers more easily than very large molecules, but specific size for receptor selectivity

Drugs bind to receptors by

covalent, electrostatic, and hydrophobic bonds

Covalent bonds

are strong and typically not reversible under physiological conditions

Electrostatic bonds

weaker than covalent bonds and include ionic bonds,
hydrogen bonds, and weak dipole interactions

Hydrophobic bonds

weak and involve interactions with hydrophobic moieties at the exclusion of water

Drug Shape

determines its ability to interact with a complementary shape of the receptor – “lock and key”

-enantiomers

Drug enantiomers

can be transported and metabolized differently

Drug-Receptor Interactions

Kd (equilibrium dissociation constant)

how strongly the drug tends to bind to the receptor

-lower=high affinity

Affinity

describes the strength of drug binding to the receptor – determines potency

Efficacy

describes the ability of drug binding to produce an effect

Full agonist

Binding to the receptor causes maximal activation

Partial agonist

Lesser maximal activation compared to full agonist
Lower intrinsic efficacy

Neutral antagonist

Does not activate receptor; blocks effects of agonists

Inverse agonist

Has effect opposite of an agonist – presumes some
constitutive activity

Potency

describes the amount/concentration of drug needed to produce a certain effect.

Dissociation

of drug from receptor terminates its effect

desensitization

Drug effects can diminish over time despite binding to the receptor

Pharmacodynamics

the actions of drugs on the body
Determine the classification of drugs and their therapeutic uses

Pharmacokinetics

the actions of the body on drugs
Absorption, distribution, metabolism, and elimination (ADME)

Bioavailability (F)

the fraction of an administered drug dose that reaches the systemic circulation unchanged

to be effective, a drug must be:

absorbed into the blood from its site of administration,
distributed to its site of action, permeating through various barriers that separate compartments

Drug diffusions

Aqueous diffusion, Lipid diffusion, Special carriers, Endocytosis and exocytosis

Fick’s Law of Diffusion

what makes a drug diffuse across a membrane faster or slower

Diffusion is faster with:

higher concentration gradient, higher surface area, more permeability/lipid solubility, and less thickness

Ionization of drugs

reduces their ability to cross cell membranes, neutral form can cross membranes easier

-many drugs are weak acids or weak bases

Acidifying urine

speeds elimination of a weak base

Alkalinizing urine

speeds elimination of a weak acid

Distribution phase

drug leaving the blood for tissues/organs, it moves rapidly

Elimination phase

drug leaving the body (slowly), drug is being metabolized by liver and/or excreted

metabolism

part of elimination phase, has 2 phases:

phase I metabolism and phase II metabolism

phase I metabolism

body chemically changes drug molecule by oxidation, reduction, and hydrolysis involving CYP450 enzymes

phase II metabolism

conjugated/add something to the drug like glucuronidation, sulfation, acetylation, glutathione conjugation

makes molecule more polar/water soluble to eliminate in urine or bile

metabolism phases I and II

not every drug goes thru both phases