Review of Basic Principles of Pharmacology
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
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
Pharmacodynamics
The effect of drugs on the body
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
Pharmacokinetics
Absorption
Distribution
Metabolism
Excretion
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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.
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
How Drug Dose Is Determined
Dose-response relationship
Therapeutic index
Plasma level profile
Half-life
Bioavailability
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
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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.
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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.
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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.
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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.
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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.
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
Factors That Influence Metabolism
Age
Genetically determined differences
Pregnancy
Liver disease
Time of day
Environment
Diet
Alcohol
Drug interactions
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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)
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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.
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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.
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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.
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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)
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
Renal Elimination
Passive glomerular filtration
Active tubular secretion
Tubular reabsorption
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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.
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
Factors That Affect Renal Excretion
Kidney function
Age
Hydration
Cardiac output
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
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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
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
Lung Excretion
Gases
General anesthetics and volatile liquids
Rate of excretion is based on respiratory rate and pulmonary blood flow.
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
Mammary Excretion
Many drugs are excreted in breast milk.
Smaller molecular weight
Lipid soluble
Breast milk is acidic.
Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Copyright © 2016 F.A. Davis Company
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