Catherine Luksic BSN, RN Level I. DRUG Any chemical that affects the physiologic processes of a living organism PHARMACOLOGY Study (science) of.

Catherine Luksic BSN, RNLevel I

DRUGAny chemical that affects the physiologic processes of

a living organism PHARMACOLOGY

Study (science) of drugs Includes:

AbsorptionDistributionMetabolismExcretionMechanism of ActionTherapeutic effectsAdverse effects

Subspecialty Areas of PharmacologyPharmaceuticsPharmacokineticsPharmacodynamicsPharmacotherapeuticsPharmacognosyToxicology

NURSES MUST UNDERSTAND BASIC PRINCIPLES OF PHARMACOLOGY

Therapeutic and Toxic SAFETY !

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

Drugs chemical composition, molecular structure GENERIC (acetaminophen)

Shorter than chemical name Used as official listing of drugs

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

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

Process of turning chemicals into safe medications

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

influence a drugs metabolism and use in the body

Design that will allow drug molecules to bind to a target site

Drug routesOral

Via mouth Includes sublingual, buccal

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

RectalParenteral

Intramuscular, Subcutaneous, Intravenous, Topical

Directly applied to skinMucosal

**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)

TopicalOintments, creams, pastes, powders,

patches

Mucosaleye, ear, nasal, vaginal

Inhaled

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)

Drug Dissolution & AbsorptionParenteral Preparations

Do NOT have to dissolve 1st

Subcutaneous, Intramuscular

Intravenous *directly into bloodstream *immediate absorption

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

4 phasesAbsorptionDistributionMetabolismExcretion

AbsorptionOccurs after dissolution of drugDrug → GI tract → blood/body fluids

→ tissue Affected by form of drugAffected by ROUTE of administration

(oral, parenteral,etc.)

Factors That Affect Absorption

Administration route Dosage formulation Food or fluids administered with the drug

Grapefruit, fruit juices, antacids, fat soluble vitamins, iron

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

BioavailabilityExtent of drug absorptionAmount of drug actually available to

circulationDepends upon “first pass effect”

Example: Aspirin Has high “first pass effect”

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 Circulation (distribution)

Liver may metabolize drug into smaller metabolites

Therefore, less amount of drug will pass into circulation

Intravenous drugs = no “first pass” in liver

Oral/Enteral Route Drug is absorbed into the systemic circulation

through the oral or gastric mucosa, the small intestine, or rectumOral – high “first pass” effectSublingual – dissolve under tongue, highly vascular

area, these drugs bypass liver, no “first pass” effectBuccal – same as sublingualRectal (suppository or topical) – rectal drugs have

SOME “first pass” effect

Routes that bypass the liver:

Sublingual TransdermalBuccal VaginalRectal* Intramuscular Intravenous Subcutaneous Intranasal Inhalation

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

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

*Fastest delivery into the blood circulation

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

Transport of drug by bloodstream to site of action

Areas of “rapid” distributionHeartLiverKidneysBrain

Areas of “slower” distributionMuscleSkinFat

Areas “difficult” to reach BoneBlood brain barrier **

BLOOD BRAIN BARRIERRestricts passage of various chemicals

between the bloodstream and the central nervous system

CNS = brain, spinal cordBBB

allows oxygen to pass may restrict certain bacteria &

viruses Not all meds can pass through

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

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

pharmacologically inactive “unbound” portion = pharmacologically

activeEasily distribute to body tissues (outside of

blood vessels) and reach site of action

Lasix, Coumadin, Aspirin, Digoxin

aka “Biotransformation” Process by which a drug is biochemically

altered inactive metabolite (compound)more potent, active metaboliteLess potent, active metabolite

LIVER – most responsible for metabolism of drugs

Also involved = kidneys, lungs, skeletal muscle, intestines

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

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

Delayed drug metabolism results in: Accumulation of drugs (toxicity) Prolonged action of the effects of drugs

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

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

Example: Digoxin - 36 hr. half-life Takes 7.5 (up to 9) days to clear

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

Liver or kidney diseaseCan prolong half-life Increases risk of toxicity

# of half lives remainder of drug

1 50 %

2 25 %

3 12.5 %

4 6.25 %

5 3.125 %

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

PeakPeak effect, maximum therapeutic responseHighest blood level of the drug If too high = toxicity of drug

TroughLowest blood level of the drug If too low, then may not be therapeutic

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 liverElimination: excreted by kidneys Onset: 1 hr. (oral) 5 minutes (IV) *store Peak: 1-2 hr. (oral) ½ hr. (IV) roomDuration: 6-8 hrs. (oral) 2 hrs. (IV) temp

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 effect Secondary 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

Drug-Receptor InteractionDrug binds to specific receptor

Alters cell function Produces desired effect Can bind completely or partially

Agonists Drugs that bind and produce desired effect

example, MorphineAntagonist

Drugs that block agonist effect at binding siteexample, Narcan, reverses effect of narcoticExample, Toprol, beta-blocker, lowers HR

Enzyme InteractionDrug 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

The treatment of pathologic conditions through the use of drugs

“drug therapy”

Desired therapeutic outcome Should be established before drug startedWhat is expected ?

Must be measurable and realistic Progress must be monitored (example =

antibiotics)

Types of therapyAcuteMaintenanceSupplemental PalliativeSupportiveProphylactic Empiric

Acute therapy Involves more intensive drug therapyUsed in the acutely or critically ill

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

Maintenance therapyMay not cure but prevents progression of disease

May prevent progressionUsed in chronic illnesses (example: hypertension,

diabetes) ie – lisinopril, oral contraceptives

Supplemental therapyReplaces body substances needed to

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

Palliative therapyGoal is to provide comfortUsed in end stage illnessesUsually all other therapy has failedExample: Morphine for pain

Supportive therapyMaintains integrity of body functions while

patient recovering from illnessExamples

Providing fluids/electrolytes to prevent dehydration In vomiting or diarrhea

Blood products or blood volume expanders Blood loss during surgery

Prophylactic therapyUsed to prevent illnessExample: pre-op antibiotics, vaccines

Empiric therapyUse of a drug based on probability, certain

illness/disease has likelihood of occurrenceExample: Antibiotic for UTI before actual

diagnosis

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

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

Patient’s condition - Physiological Weight

Average = 150lbDosage adjustments

Large weight differences

GenderWomen

Smaller Different fat/water ratio May need dosage adjustments

Patient’s condition - Pathological Liver/kidney disease

Inability to metabolize/excrete one normal dose before next drug given

Leads to drug toxicityLower doses are frequently given

Liver disease Kidney disease

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

substanceHistamine is releasedS/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 ?

A 78 y.o. man who has been diagnosed with a URI tells the nurse that he is allergic to Penicillin (PCN). Which is the most appropriate response by the nurse ? 1. “that’s to be expected, lots of people are

allergic to penicillin” 2. “this allergy is not a big concern right

now” 3. “what type of reaction did you have when

you took penicillin ?” 4. “drug allergies don’t usually occur in older

individuals”

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

Category 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, coumadin)

The study of natural drug sourcesPlants Animals

Four main sources of drugsPlantsAnimals

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

Minerals (salicylic acid, sodium chloride)Laboratory synthesis

Place drugs in similar categoriesSimilar general useSimilar mechanisms of actionsSimilar contraindicationsSimilar precautionsSimilar nursing implications

Examples:AntibioticsAntihypertensivesAntiepilepticsSedativesAnestheticsDecongestantsAntineoplastics Etc.

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

Handbooks/ReferencesDavis Drug Guide