Pharmacologic Principles Chapter 2

Cristen Walker, MS, CRNPLevel I

Pharmacology

• DRUG– Any chemical that affects the physiologic processes of

a living organism• PHARMACOLOGY– Study (science) of drugs– Includes:

– Absorption– Distribution– Metabolism– Excretion– Mechanism of Action– Therapeutic effects– Toxic effects

Pharmacology

• Subspecialty Areas of Pharmacology– Pharmaceutics– Pharmacokinetics– Pharmacodynamics– Pharmacotherapeutics– Pharmacognosy– Toxicology

– NURSES MUST UNDERSTAND BASIC PRINCIPLES OF PHARMACOLOGY

– Therapeutic and Toxic

Pharmacology – Drug development

Drugs will acquire 3 names CHEMICAL (N-4 hydroxyphenyl acetamide)

Drugs chemical composition, molecular structure GENERIC (acetaminophen)

Shorter than chemical nameUsed as official listing of drugs

TRADE (Tylenol)Registered trademark, “brand” nameName is restricted to “owner” (company, ie, Merck)

**Patent lasts 17 years - 10 years for research and development - 7 years of marketability

Pharmacology – Drug Development

Pharmaceutics

• Process of turning chemicals into safe medications

• Science of dosage form & design– ie – tablet, capule, liquid, powder, etc.– Study of how various dosage forms/designs

influence a drugs metabolism and use in the body

Pharmaceutics

• Drug routes– Oral

• Via mouth• Includes sublingual, buccal

– Enteral• Via intestine• Via NG tube, feeding tube (or rectal)

– Rectal– Parenteral

• Intramuscular, Subcutaneous, Intravenous, – Topical

• Directly applied to skin– Mucosal

Pharmaceutics

**Forms/designs of drugs:• Oral

– Tablets, capsules, powder, liquid, elixir, suspension– EC, ER, SR

• Enteral– Meds given via NG or feeding tube (solid or liquid)– Crushed meds – must be dissolved

• Rectal– Suppositories, creams, enema– Also considered as ENTERAL route

• Parenteral– Injections (solutions, powder)

Pharmaceutics

• Topical– Ointments, creams, pastes, powders,

patches

• Mucosal– eye, ear, nasal, vaginal

• Inhaled

Pharmaceutics Drug Dissolution & Absorption

**Drugs must dissolve 1st (before absorbed) Oral Preparations

Liquids, elixirs, syrups FastestSuspension solutions Powders Capsules Tablets Enteric coated tablets Extended release tablets Slowest

*Extended Release (forms) = SR (slow release), CR (controlled release), XL (extended length)

Pharmaceutics

• Drug Dissolution & Absorption• Parenteral Preparations

»Do NOT have to dissolve 1st

»Subcutaneous, Intramuscular

» Intravenous *directly into bloodstream *immediate absorption

Pharmacokinetics

Study of what happens to a drug from entrance into body until it leaves the body

4 phasesAbsorptionDistributionMetabolismExcretion

Pharmacokinetics - absorption

AbsorptionOccurs after dissolution of drugDrug → GI tract → blood/body fluids → tissue Affected by form of drugAffected by ROUTE of administration (oral,

parenteral,etc.)

Pharmacokinetics—Absorption

Factors That Affect Absorption• Administration route • Dosage formulation• Food or fluids administered with the drug

• Grapefruit, fruit juices, antacids, fat soluble vitamins

• Rate of blood flow to the small intestine• Acidity of the stomach• Status of GI motility

Pharmacokinetics - Absorption

BioavailabilityExtent of drug absorptionAmount of drug actually available to circulationDepends upon “first pass effect”

Pharmacokinetics - absorption

First Pass effectDrugs must dissolve & be absorbed by GI tractMust pass through LIVER before reaching

circulation (bloodstream)Drug GI system Portal vein Liver Hepatic vein Heart (distribution)

Liver may metabolize drug into smaller metabolitesTherefore, less amount of drug will pass into

circulationIntravenous drugs = no “first pass” in liver

Pharmacokinetics—Absorption Oral/Enteral Route• Drug is absorbed into the systemic circulation

through the oral or gastric mucosa, the small intestine, or rectum– Oral – high “first pass” effect– Sublingual – dissolve under tongue, highly vascular

area, these drugs bypass liver, no “first pass” effect– Buccal – same as sublingual– Rectal (suppository or topical) – rectal drugs have

SOME “first pass” effect

Pharmacokinetics — Absorption

• Routes that bypass the liver:

– Sublingual Transdermal– Buccal Vaginal– Rectal* Intramuscular– Intravenous Subcutaneous– Intranasal Inhalation

*Rectal drugs may have some degree of first-pass effect

Pharmacokinetics—Absorption

Parenteral Route *No “first pass” effect• Intravenous*• Intramuscular• Subcutaneous• Intradermal• Intraarticular (physician)

*Fastest delivery into the blood circulation

Pharmacokinetics—Absorption

Topical/Mucosal Route Skin

Includes transdermal route, patches Eyes Ears Nose Vagina

Topicals = slower onset, longer duration No “first pass” effect, bypass liver Exception = rectal

Pharmacokinetics —Distribution Transport of drug by bloodstream to site of

action Areas of “rapid” distributionHeartLiverKidneysBrain

Areas of “slower” distributionMuscleSkinFat

Areas “difficult” to reach BoneBlood brain barrier **

Pharmacokinetics - distribution

• BLOOD BRAIN BARRIER– Restricts passage of various chemicals between

the bloodstream and the central nervous system– CNS = brain, spinal cord– BBB

» allows oxygen to pass»may restrict certain bacteria & viruses» Not all meds can pass through

Pharmacokinetics - distribution• Distribution depends upon protein-binding• Albumin = most common blood protein,

carries protein-bound drug molecules• “bound” portion of drug =

pharmacologically inactive• “unbound” portion = pharmacologically

active– Easily distribute to body tissues (outside of

blood vessels) and reach site of action

• Lasix, Coumadin, Aspirin

Pharmacokinetics —Metabolism

• aka “Biotransformation”• Process by which a drug is biochemically

altered – inactive metabolite (compound)– more potent, active metabolite– Less potent, active metabolite

• LIVER – most responsible for metabolism of drugs

• Also involved = kidneys, lungs, skeletal muscle, intestines

Pharmacokinetics — Metabolism

Factors that decrease metabolism:• Cardiovascular dysfunction• Kidney failure• Liver failure• Genetics• Starvation

Factors that increase metabolism:• Certain drugs (dilantin, barbiturates, rifampin)

Pharmacokinetics —Metabolism

Delayed drug metabolism results in:• Accumulation of drugs (toxicity)

• Prolonged action of the effects of drugs

Pharmacokinetics — Excretion

• Elimination of drugs from the body• All drugs must eventually be excreted• Kidney = organ most responsible for

excretion of drugs (urine)• Also, liver (bile), bowel (feces), sweat

glands• Liver metabolizes most drugs, kidney

excretes what is “left behind”• Kidneys can also metabolize certain drugs– insulin

Pharmacokinetics — Half-Life

• Time required to eliminate (½) 50% of a drug• Example:

• Digoxin - 36 hr. half-life• Takes 7.5 days to clear

• Takes 5–6 half-lives to eliminate ~ 98% of a drug

• Liver or kidney disease– Can prolong half-life– Increases risk of toxicity

Pharmacokinetics –

Onset—Peak—Duration Onset• The time it takes for the drug to elicit a

therapeutic response• Insulin: 10-20 min

Peak• The time it takes for a drug to reach its maximum

therapeutic response• 30-60 min

Duration• The time a drug concentration is sufficient to elicit a

therapeutic response• 2-4 hours

PHARMACOKINETICS –ONSET-PEAK-DURATION

• Peak– Peak effect, maximum therapeutic

response– Highest blood level of the drug– If too high = toxicity of drug

• Trough– Lowest blood level of the drug– If too low, then may not be therapeutic

Onset-Peak-Duration

Pharmacokinetics: Example• Furosemide (LASIX)• Pharmaceutics: Tablet, Oral solution, Injection• Pharmacokinetics:– Absorption: Bioavailability = 64% tablet, 60% oral

soln, 100% IV• Tablet, oral soln – 60 min. delay if taken w/ food

– Distribution: highly protein bound to albumin, 91-99%

– Metabolism: metabolized in liver– Elimination: excreted by kidneys – Onset: 1 hr. (oral) 5 minutes (IV) *store – Peak: 1-2 hr. (oral) ½ hr. (IV) room– Duration: 6-8 hrs. (oral) 2 hrs. (IV) temp

Pharmacodynamics

Mechanism of drug action - how drugs act at sites of activity

Involves receptors and enzymes Not all drugs have a known mechanism of action Most drugs produce more than one effect

Therapeutic effect – desired or primary effectSecondary effect – may be desirable or not

1. Drug-receptor interaction: drug binds to a receptor site on cell surface, causes or blocks an action 2. Enzyme interaction: drug binds to enzyme molecule & either enhances or inhibits its action 3. Nonselective interactions: do not bind to enzyme or receptor, act on cell membrane or cell wall

Pharmacodynamics

• Drug-Receptor Interaction– Drug binds to specific receptor

• Alters cell function• Produces desired effect• Can bind completely or partially

– Agonists• Drugs that bind and produce desired effect

– example, Morphine– Antagonist

• Drugs that block agonist effect at binding site– example, Narcan, reverses effect of narcotic– Example, Toprol, beta-blocker, lowers HR

Pharmacodynamics

• Enzyme Interaction– Drug interacts with enzyme system• Inhibits the action of the enzyme• The action of the cell is changed or altered

» Example: ACE inhibitor (Lisinopril)» Inhibits conversion of angiotensin I to

angiotensin II

Pharmacotherapeutics

• The treatment of pathologic conditions through the use of drugs

“drug therapy”

• Desired therapeutic outcome – Should be established before drug started– What is expected ?• Must be measurable and realistic• Progress must be monitored (example =

antibiotics)

Pharmacotherapeutics

• Types of therapy– Acute– Maintenance– Supplemental – Palliative– Supportive– Prophylactic – Empiric

Pharmacotherapeutics

• Acute therapy– Involves more intensive drug therapy– Used in the acutely or critically ill

– Example: to maintain heart rate or BP– Usually needed to maintain life– ie – dopamine (vasopressor to maintain BP)

• Maintenance therapy– May not cure but prevents progression of disease

• May prevent progression– Used in chronic illnesses (example: hypertension, diabetes)– ie – lisinopril, oral contraceptives

Pharmacotherapeutics

• Supplemental therapy– Replaces body substances needed to maintain normal

functioning• May not be produced by the body• Produced in insufficient amounts• Example: Insulin

• Palliative therapy– Goal is to provide comfort– Used in end stage illnesses– Usually all other therapy has failed– Example: Morphine for pain

Pharmacotherapeutics

• Supportive therapy– Maintains integrity of body functions while

patient recovering from illness– Examples • Providing fluids/electrolytes to prevent

dehydration– In vomiting or diarrhea

• Blood products or blood volume expanders– Blood loss during surgery

Pharmacotherapeutics

• Prophylactic therapy– Used to prevent illness– Example: pre-op antibiotics, vaccines

• Empiric therapy– Use of a drug based on probability, certain

illness/disease has likelihood of occurrence– Example: Antibiotic for UTI before actual

diagnosis

Adverse Effects - Monitoring

• Adverse effects – unintended effects• Side Effects

• Therapeutic index – ratio of toxic level to therapeutic level – Low therapeutic index: difference between toxic

and therapeutic dose is low – dangerous !– Example: coumadin (anticoagulant)

• Tolerance – Pts. decreasing response to repeated doses – ie – valium, pain meds

• Dependence – Physiologic or psychologic need for drug

• addiction

Adverse Effects – Monitoring

Patient’s condition - Physiological• Age

– Infants & children need ↓ dose• Immature organ function

– Elderly may require ↓ dose • Decreased gastric acidity• Dry mouth/decreased saliva• Decreased liver blood flow/mass• Increased body fat, decreased muscle mass• Decreased kidney function

Adverse Effects – Monitoring

Patient’s condition - Physiological• Weight– Average = 150lb– Dosage adjustments

• Large weight differences

• Gender– Women

• Smaller• Different fat/water ratio• May need dosage adjustments

Adverse Effects – Monitoring

Patient’s condition - Pathological

• Liver/kidney disease– Inability to metabolize/excrete one normal dose

before next drug given– Leads to drug toxicity– Lower doses are frequently given• Liver disease• Kidney disease

Adverse Effects

• Allergic Reactions (hypersensitivity)– Usually begins after 2nd dose or more – May occur within minutes or delay for hours or

even days– Immune system views “drug” as foreign

substance– Histamine is released– S/S = skin rashes, hives, itching (urticaria or

pruritis), facial swelling, difficulty breathing, sudden LOC, throat swelling (angioedema), wheezing

– Anaphylactic Shock• Severe allergic rx, severe respiratory distress, life

threatening

• Mr. Carter has a rash and pruritis. You suspect an allergic reaction and immediately assess him for other more serious symptoms. What question would be most imortant to ask Mr. Carter ?

Adverse Effects

• Idiosyncratic reaction: unexpected reaction in a particular patient, not common reaction

• Pharmacogenetics: study of genetic traits that result in abnormal metabolism of drugs

• ie: coumadin, codeine, psych drugs (chap. 5)• Teratogenic effects: result in structural defects

of in fetus• FDA – 5 categories (A,B,C,D,X) of teratogens– Category A – studies show NO risk (multivitamin)– Category X – Completely contraindicated in

pregnancy, HIGH fetal risk

TeratogensCategory ANo risk to fetus in first, second or third trimesters

Category BStudies have not shown fetal risk in animals, but no controlled studies in pregnant womenConsidered safe in all trimesters (benadryl,tylenol,PCN)

Category CAnimal studies have revealed adverse effects on fetusDrugs should be given only if benefit outweighs risk

Category DPositive evidence of harm to fetusUse may be acceptable absolutely necessary (life threatening situations)

Category XStudies have shown fetal abnormalities, drug is completely contraindicated (acutane)

Pharmacognosy

• The study of natural drug sources– Plants – Animals

• Four main sources of drugs– Plants– Animals

– Source of many hormone drugs (premarin – urine of pregnant mares; insulin – pigs & humans; heparin – pigs)

– Minerals (salicylic acid, sodium chloride)– Laboratory synthesis

Drug Classifications

• Place drugs in similar categories– Similar general use– Similar mechanisms of actions– Similar contraindications– Similar precautions– Similar nursing implications

Drug Classifications

• Examples:– Antibiotics– Antihypertensives– Antiepileptics– Sedatives– Anesthetics– Decongestants– Antineoplastics – Etc.

Drug References

• Physicians Desk Reference (PDR)• U.S. Pharmacopia• National Formulary• Various Nursing Drug

Handbooks/References– Davis Drug Guide