Chapter 2Review of Basic Principles of Pharmacology .docx

Chapter 2
Review of Basic Principles
of Pharmacology
Pharmacotherapeutics for Advanced Nurse Practitioner
Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
Introduction
Pharmacodynamics
Drug-receptor interaction
Drug-receptor activity
Dose-response relationship
Drug potency and efficacy
Pharmacokinetics
Absorption
Distribution
Metabolism
Elimination
Pharmacodynamics
The effect of drugs on the body

Pharmacokinetics
Absorption
Distribution
Metabolism
Excretion
Drug-Receptor Interactions
Most drugs work by binding to receptors.
Receptors are located on the cell surface.
The drug molecule must “fit” into the receptor.
Like a lock and key mechanism
Drug-Receptor Binding
Drug-receptor binding is reversible.
Drug-receptor binding is selective.
Drug-receptor binding is graded.
The more receptors filled, the greater the pharmacological
response.
Drugs that bind to receptors may be agonists, partial agonists,
or antagonistic.
How Drug Dose Is Determined
Dose-response relationship
Therapeutic index

Plasma level profile
Half-life
Bioavailability
Drug-Dose Relationship
Dose-response curve: depicts the relation between drug dose
and magnitude of effect
Doses below the curve do not produce a pharmacological
response.
Doses above the curve do not produce much additional
pharmacological response.
May have unwanted effects → toxicity
Plasma Level Profile
Onset of action: time between administration and first sign of
drug effect
Peak of action: maximum concentration of drug
Point at which amount of drug being absorbed and distributed is
equal to amount being metabolized and excreted
Duration of action: continued entry of drug into body with
levels above minimum effective concentration
Termination of action
Minimum Effective and Minimum Toxic Concentration

Minimum effective concentration (MEC): level below which
therapeutic effects will not occur
Minimum toxic concentration (MTC): level above which toxic
effects begin
Therapeutic index or range: MTC to MEC
Drug Bioavailability
Percentage of drug that is absorbed and available to reach the
target tissues
By definition, when a medication is administered IV, its
bioavailability is 100%.
When a medication is administered via other routes (e.g., PO),
its bioavailability decreases due to incomplete absorption and
first-pass metabolism.
Therapeutic Blood Level
It usually takes 4 to 5 ½ lives to get to steady state blood levels.
Loading dose
It takes 4 to 5 ½ lives to totally eliminate a drug from the body.
Absorption
Definition: movement of a drug from its site of administration
into the blood
Variables that influence absorption

Nature of the cell membrane
Blood flow at site of administration
Solubility of drug
pH
Molecular weight
Drug concentration
Dosage form
Distribution
Definition: movement of absorbed drug in bodily fluids
throughout body to target tissues
Distribution requires adequate blood supply.
Drug distributed to areas of high blood flow first
Areas of low blood flow
Protein Binding
In circulation, drugs are bound to protein.
Some of the drug is not bound and is called free drug.
Free drug + Bound drug ⬄Drug-protein complex
Dynamic
Free drug is active drug.

Degree of Drug Binding
Drugs exist in bound and unbound states.
Travel when bound, cross membranes when unbound
“Highly” protein-bound
Ratio of bound drug usually remains stable
Low plasma proteins (low albumen) will result in more free
drug in circulation.
Competition for Protein-Binding Sites
Finite number of plasma proteins
Compete and displace each other → more free drug
Higher risk for toxicity
More drug may be eliminated
Tissue Distribution
Fat
Lipid-soluble fats have a high affinity for adipose tissue.
Adipose tissue has low blood flow.
Bone
Some drugs have affinity for bone.
For example, tetracyclines deposit in bones and teeth.
Blood-brain barrier
The blood-brain barrier is relatively impenetrable.
Usually protective
Only lipid-soluble drugs cross barrier.
Placental barrier
Many drugs pass barrier.
Low molecular weight drugs pass easier.

Metabolism
AKA: biotransformation
Definition: chemical change of drug structure to:
1. Enhance excretion
2. Inactivate the drug
3. Increase therapeutic action
4. Activate a prodrug
5. Increase or decrease toxicity
Factors That Influence Metabolism
Age
Genetically determined differences
Pregnancy
Liver disease
Time of day
Environment
Diet
Alcohol
Drug interactions
Factors That Influence Metabolism (cont’d)
Drugs undergo one or both of two types of chemical reactions in
the liver:

Phase I: oxidation, hydrolysis, or reduction to increase water
solubility of drug molecules
Phase II: conjugation or union of drug molecule with water-
soluble substance
Phase I Enzymes:
Cytochrome P450 Isoenzymes
The majority of drugs are metabolized in the liver by the
hepatic isoenzymes.
Cytochrome P450 isoenzymes
CYP 450
Most common
1A2, 2C9, 2C19, 2D6, 3A4 (3A3/4)
CYP 450 Enzymes
There are developmental differences in the isoenzymes.
There are genetic differences in isoenzymes.
Some disease states alter isoenzyme activity.
For example, cystic fibrosis has altered
CYP 2D9 activity.
Phase I Enzymes: CYP 450
The enzymes may be slowed (inhibited) or increased (induced).
Concurrent therapy with an inhibitor or inducer may alter the

metabolism of a medication.
Prodrug Metabolism
A prodrug is a drug which is administered in an inactive (or
significantly less active) form.
Once administered, the prodrug is metabolized in the body into
the active compound.
Elimination
AKA: excretion
Definition: removal of the drug from the body by organs of
elimination
Most drugs are eliminated by the kidneys.
Drugs are also eliminated by
Lungs
Gastrointestinal (GI) tract
Sweat and saliva
Mammary glands (breast milk)
Renal Elimination
Passive glomerular filtration
Active tubular secretion
Tubular reabsorption

Glomerular Filtration
The availability of the drug for glomerular filtration
Drug must be unbound from protein
Free-, unbound, and water-soluble metabolites are filtered by
the glomeruli.
Factors That Affect Renal Excretion
Kidney function
Age
Hydration
Cardiac output
GI Tract Excretion
Biliary excretion
After being metabolized in the liver, the metabolite is excreted
into the bile.
Some drugs may then be reabsorbed in the intestine.
Enterohepatic cycle
Fecal excretion

Lung Excretion
Gases
General anesthetics and volatile liquids
Rate of excretion is based on respiratory rate and pulmonary
blood flow.
Sweat/Salivary Excretion
Not very many drugs
Excretion in sweat may be a cause of adverse effects, such as a
rash (dermatitis).
Salivary excretion
May be the reason patients complain of “taste” in their mouth
with certain drugs
Mammary Excretion
Many drugs are excreted in breast milk.
Smaller molecular weight
Lipid soluble
Breast milk is acidic.

Chapter 2Review of Basic Principles of Pharmacology .docx

Chapter 2Review of Basic Principles of Pharmacology .docx

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