Introduction to Pharmacology

Pharmacology the study of science of drugs

Drug any chemical that affects the processes of a living organism

I. Drug sources: a. plantsb. animalsc. mineralsd. chemical synthesis/ biogenetic engineering

II. Drug uses: prevent diseases treat diseases diagnose diseases prevent pregnancy maintain health

III. Drug names Chemical name

o the drug’s chemical composition and molecular structureo ex.( +/- ) – 2 – ( p-isobutylphenyl ) proponic acid

Generic Name ( Nonproprietary name )o name given by the United States Adopted Name Councilo universally acceptedo ex.ibuprofen

Trade Name ( Brand name/ Proprietary name)o the drug has a registered trademark ; use of the name restricted by the drug’s

ownero ex. Motrin

IV. Drug Standards: same drug name must have same strength, quality & purity based on United States Pharmacopeia and National Formulary (USP-NF)

V. Drug references: American Hospital Formulary Service (AHFS) Drug Information Physicians’ Desk Reference (PDR) Package inserts Drug Facts and Comparisons Saunders/ Lipincott’s Nursing Drug Guide Journals Internet

VI. Phases of Drug Development1. Preclinical trial2. Phase 13. Phase 24. Phase 35. Phase 4

VII. Legal Regulation

A. Food and Drug Administration (FDA) Pregnancy Categories:

Category A no risk to fetusCategory B no risk in animal fetus; no human studies availableCategory C adverse effects to animal fetus; no human studies availableCategory D possible fetal risk in humans reportedCategory X fetal abnormalities reported; + evidence of fetal risk in animal/& human

studies.

B. Controlled Substances: controlled substances OTC drugs prescription drugs orphan drugs dependence

Drug Enforcement Agency (DEA) Schedules of Controlled Substances:

Schedule I Drugs high potential for abuse used for research only ex. heroin, marijuana, lysergic acid diethylamide (LSD)

Schedule II Drugs high abuse potential severe physical & psychologic dependence acceptable medical use, with restrictions ex. amphetamines, cocaine, mepiridine (Demerol) , morphine, anabolic steroids

Schedule III Drugs moderate potential for abuse psychological dependence , low physical dependence acceptable medical use, by prescription only ex. secobarbital (Seconal), Tylenol with codeine

Schedule IV low potential for abuse limited physical & psychological dependence ex. diazepam (Valium), phenobarbital, chlordiazepoxide (Librium)

Schedule V low potential for abuse acceptable medical use OTC narcotic drugs, sold only by registered pharmacists: buyer must be 18yo Ex. cough syrups with codeine eg. Guaifenesin, diphenoxylate HCL with atropine ( Lomotil)

Pharmacologic Principles

I. Drug Action: Pharmaceutics Pharmacokinetics Pharmacodynamics

II. Drug Effect: Pharmacotherapeutics

Pharmaceutics the study of how various drug forms influence pharmacokinetic and pharmacodynamic

activities.o disintegrationo dissolution

Pharmacokinetics the study of what the body does to the drug:

o Absorptiono Distributiono Metabolism or biotransformationo Excretion or elimination

Pharmacodynamics the study of what the drug does to the body :

o the mechanism of drug action in living tissues.

Pharmacotherapeutics the use of drugs and the clinical indications for drugs to prevent and treat diseases.

Pharmacognosy the study of natural ( plant and animal ) drug sources.

I. The 3 Phases of Drug Action:

A. Pharmaceutic Phase1. disintegration2. dissolution

Rate limiting – time it takes for drug to disintegrate & dissolve to be absorbed by the body

B. Pharmacokinetic Phase 1. Absorption:

passage of a drug into the bloodstream from site of administration

Processes of drug absorption: passive absorption active absorption pinocytosis

Drug absorption of Oral Preparations:

Liquids, elixirs, syrups FastestSuspension solutionsPowdersCapsulesTabletsCoated tabletsEnteric-coated tablets Slowest

The rate at which the drug leaves its site of administration, and the extent to which absorption occurs. Bioavailability

Factors that affect absorption : solubility of drug food or fluids administered with the drug dosage formulation status of the absorptive surface rate of blood flow to the small intestine acidity of the stomach status of GI motility administration route of drug

Routes : a drug’s route of administration affects the rate and extent of absorption of the

drug.o Enteralo Parenteralo Topical

Enteral Route drug is absorbed into the systemic circulation through

the oral or gastric mucosa, the small intestine, or rectum.o oral o sublingual*o buccalo rectal

Parenteral Route Intravenous * Intramuscular Subcutaneous Intradermal Intrathecal Intraarticular

Topical Route skin ( including transdermal patches ) eyes, ears & nose lungs ( inhalation )* vagina

First – Pass Effect

the metabolism of a drug and its passage from the liver into the circulation.

A drug given via the oral route may be extensively metabolized by the liver before reaching the systemic circulation ( high first – pass effect ).

The same drug – given IV – bypasses the liver, preventing the first – pass effect from taking place, the more drug reaches the circulation.

Routes that bypass the liver :o sublingual transdermalo buccal vaginalo rectal* intramuscularo intravenous subcutaneouso intranasal inhalation

2. Distribution transport of a drug by the bloodstream to its site of action

Factors affecting drug distribution: protein-binding water soluble vs fat soluble areas of rapid distribution

o heart, liver, kidneys, brain areas of slow distribution

o muscle, skin, fat

3. Metabolism or biotransformation the transformation of a drug into an inactive metabolite, a more soluble compound or a

more potent metabolite

liver* others: kidneys, lungs, plasma ,intestinal mucosa

Factors that decrease metabolism: cardiovascular problem renal problem starvation liver problem erythromycin or ketoconazole drug therapy

Factors that increase metabolism: nicotine alcohol barbiturates & glucocorticoids rifampin therapy

Half-lifeo time it takes for one half of the original amount of a drug in the body to be

removed.o a measure the rate at which drugs are removed from the body

4. Excretion

elimination of drugs from the body kidneys* others: lungs, exocrine glands (sweat, salivary or mammary glands), skin & intestinal tract

C. Pharmacodynamics Phase

Onset of Action time it takes for the drug to elicit a therapeutic response

minimum effective concentration (MEC)

Peak Action time it takes for drug to reach its maximum therapeutic response

Duration of Action the time a drug concentration is sufficient to produce its therapeutic response

Receptor Theory most receptors are found on cell membrane drug binding occurs on receptors lock & key interaction

: Agonist & antagonist:

Agonists drugs that attracts to receptors stimulate/ enhance a response ex. Insulin, isoproterenol – stimulate beta 1 receptor

Antagonists drugs that attracts to receptors block a response ex. cimetidine – blocks H2 receptor

Nonspecific & Nonselective Drugs Nonspecific Drugs

affect various sites of the body ex. Bethanecol stim. cholinergic receptor strengthen bladder

contraction,increases HR, decreases BP, bronchiole & pupil constriction

Nonselective Drugs affect various receptors ex. Epinephrine acts on alpha1, beta 1 & 2 receptors

Categories of drug action:a. depress cellular activitiesb. stimulates cellular activitiesc. inhibit or kill organismsd. act as substitute for missing chemicals

Therapeutic Index & therapeutic Range: Therapeutic Index (TI)

relationship bw the drug’s therapeutic effects & its adverse effects

TI= LD50

ED50

High TI wide margin of safety Low TI narrow margin of safety

Therapeutic Range (therapeutic window) drug concentration bw therapeutic effect & toxic effect Ex. Digoxin = 0.5 to 2 ng/ml

Peak & Trough Level Peak drug level

highest plasma concentration of drug at a specific time indicate rate of absorption

Trough level lowest plasma concentration indicate rate of elimination

Loading dose large initial dose given for immediate response. given to achieve a rapid minimum effective concentration. Ex. Digoxin (digitalization)

II. Pharmacotherapeutics use of drugs to treat disease.

A. Types of Therapies:1. acute therapy

px is critically ill & requires immediate intensive therapy

2. empiric therapy based on practical experience rather than on pure scientific data

3. maintenance therapy chronic conditions that don’t resolve

4. supplemental or replacement therapy replenish or substitute missing substances in the body

5. supportive therapy doesn’t treat the cause of disease but maintains other threatened body systems

until the patient’s condition resolve.

6. palliative therapy used for end-stage or terminal diseases to make the patient as comfortable as

possible

Drug Effects: Main effect

desired therapeutic effect reason drug is administered

Side effects physiologic effects that are not related to desired drug effects expected, well-known reactions that result in little or no change in patient intervention

Adverse Reactions more severe than side effects undesirable & unexpected effects occurring even at normal dose

Local vs Systemic drug effect

Placebo Effect a therapeutic effect that results from a patient’s belief in the benefits of a medication

Factors affecting Drug Effects: Age Size

Sex Genetic factors Disease conditions Emotional conditions Route of administration Time of day Drug taking history Environmental conditions Drug-interactions

Drug Interactions

Drug interactions occur bw drugs or bw drugs & foods

I. Drug – Drug Interactions:

1. additive drug effect 2 drugs produce equivalent effects when either drug is given alone in higher doses.

ex. diuretic & beta blocker aspirin & codeine

2. synergistic/potentiation – 2 drugs produce same effects but one drug enhances the effect of the other drug greater effect

ex. meperidine (Demerol) & promethazine alcohol & sedatives

3. antagonistic – combined effects of 2 drugs are less than the effect produced by the 2 individual drugs

ex. tetracycline & antacid morphine & naloxone

4. Incompatibility – 2 drugs mixed together chemically incompatibleex. ampicillin & gentamicin

II. Drug – Food Interactions:

tetracycline & dairy products levodopa & high protein meals monoamine oxidase inhibitor (MAO) inhibitor & tyramine-rich foods nitrofurantoin Metoprolol & food lovastatin

Adverse Drug Reactions

I. Dose- related adverse reactions: Secondary effects Hypersensitivity or hypersusceptibility Overdose

Iatrogenic Tolerance Dependence

II. Patient sensitivity-related adverse reactions Allergic reaction Idiosyncrasy

I. Dose-related adverse reactions:a. Secondary effects

ex. morphine antihistamine

b. Hypersensitivity or hypersusceptibility excessive therapeutic response even with usual therapeutic dose

ex. anticholinergics dry mouth, blurring of vision, urinary retention & constipationnarcotic analgesic

oral contraceptivesdigitalis

aspirin

c. Overdose & toxicity excessive dose exaggerated response pediatric & elderly

ex. CNS depressants digoxin

d. Iatrogenic effects adverse reactions that caused by drugs that are part of medical tx. drug-induced diseases

ex. antineoplastics, aspirin, corticosteroids GI irritation & bleeding propanolol gentamicin

e. tolerance decrease response to drug over time

ex. psychoactive drugs (e.g. benzodiazepines) propanolol cocaine morphine

f. dependence strong physical & psychological need for a certain drug

habituation addiction

g. cumulation body cannot metabolize & excrete one dose of a drug completely before

the next dose.

II. Patient sensitivity-related adverse reactions: result from unusual & extreme sensitivity to a drug

a. Allergic reaction abnormal response due to antibodies against a certain drug

ex. antibiotics (penicillin) , aspirin, sulfonamides

Types:1. Immediate allergic reaction :

Urticaria sxs:

skin rash with severe itching swelling

Anaphylaxis sxs:

dyspnea extreme weakness nausea & vomiting cyanosis hypotension circulatory collapse

2. Delayed allergic reaction Serum sickness

Sxs. itchy rash fever swollen & stiff joints

Interventions: notify prescriber & discontinue drugs emergency tx for anaphylactic shock Epinephrine Antihistamines or topical corticosteroids Cool environment

b. Idiosyncratic reactions: unique or strange responses to certain drugs thought to be caused by genetic factors

ex. succinylcholine primaquine

III. Other drug- related effects:

a. Teratogenic produce organ defects in developing fetus

ex. marijuana/ cocaine

alcohol aminoglycoside

b. Carcinogenic induce malignant changes in cells

ex. estrogen therapy antineoplastics for pediatric leukemias

c. Mutagenic produce genetic mutations

IV. Drug-induced tissue & organ damage:

A. Dermatological reactions: Sxs:

hives/ urticaria rash exfoliative dermatitis Stevens- Johnson syndrome

Ex. procainamide - butterfly- rash sulfonamide - Stevens-Johnson syndrome

Tx: frequent skin care notify prescriber & discontinue drug topical corticosteroids, antihistamine & emollients

B. Stomatitis S/sxs:

swollen gums & tongue. difficulty swallowing bad breath pain in mouth & throat

ex. antineoplastic agents (eg fluorouracil)

Tx: frequent mouth care frequent, small meals

D. Gingival hyperplasia S/sxs:

red, & enlarged gums

ex. phenytoin (anticonvulsant)

E. Superinfections S/sxs:

fever diarrhea hairy tongue mucous membrane lesions vaginal discharge

ex. antibiotics

F. Blood dyscrasias agranulocytosis* anemia thrombocytopenia

s/sxs: fever & chills extreme weakness sore throat high risk to infection high risk for bleeding/hemorrhage

ex. antineoplastics & antipsychotics antibiotics (eg. chloramphenicol, sulfonamides)

anti-inflammatory (eg non-steroidal anti-inflammatory drugs (NSAID)

tx. monitor blood counts protect from exposure to infection avoid activities that result in injury or bleeding

G. Hepatotoxicity s/sxs:

jaundice* fever nausea & vomiting increase in liver enzymes (AST & ALT) altered bilirubin

ex. isoniazid (INH) acetaminophen

H. Nephrotoxicitys/sxs

edema increase Crea & BUN decrease hematocrit electrolyte imbalances

ex. aminoglycosides (eg gentamicin) sulfonamide

I. Ototoxicity

s/sxs dzziness ringing in ears loss of balance hearing problem

ex. aminoglycoside (eg. Gentamicin) azithromycin, erythromycin

aspirin quinidine

J. Ocular toxicity s/sxs

burring of vision color vision changes blindness

ex. chloroquine (anti-malarial )

K. Hypoglycemias/sxs headache tremors drowsiness cold clammy skin seizures/coma

ex. antidiabetic agents (eg. Insulin, glipizide)L. Hyperglycemia

s/sxs polyphagia polyuria polydipsia kussmaul’s respiration fruity breath

ex. ephedrine ( bronchodilator)

M. Hypokalemias/sxs

serum K irregular, weak pulse weakness & numbness of extremities paralytic ileus

o absent bowel soundso abdominal distention

ex. loop diuretics (eg, furosemide)

N. Hyperkalemias/sxs same as hypokalemia

ex. potassium-sparing diuretics (eg. Spironolactone) antineoplastic drugs

O. General CNS effectss/sx anxiety insomnia nightmaresex. beta-blockers (eg. Metoprolol)

P. Atropine- like (Cholinergic) effectss/sxs dry mouth constipation urinary retention decrease sweating, hot dry skin

ex. antidepressants (eg. TCA)

Q. Extrapyramidal reactions/ parkinson- like syndromes/sxs immobility (akinesia) rigidity muscular tremors violent movement of head & arms (dystonia) restlessness (akathisia)

ex. antipsychotic drugs

R. Neuroleptic Malignant syndromes/sxs

extrapyramidal symptoms hyperthermia

ex. general anesthetics

S. Photosensitivitys/sxs itching scaling reddening of skinEx. sulfonamides, tetracycline

T. Cough - ACE inhibitors

U. Gray Baby Syndrome - chloramphenicol

V. Osteoporosis – corticosteroids, heparin

W. Pseudomembranous colitis – clindamycin

X. Discolors teeth – tetracycline

Y. Nasal stuffiness – reserpine

Z. cervical cancer – estrogen

hemorrhage – oral anticoagulants, heparin

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