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. plants
b. animals
c. minerals
d. 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 structure
o ex.( +/- ) – 2 – ( p-isobutylphenyl ) proponic acid

 Generic Name ( Nonproprietary name )

o name given by the United States Adopted Name Council
o universally accepted
o ex.ibuprofen

 Trade Name ( Brand name/ Proprietary name)

o the drug has a registered trademark ; use of the name restricted by the drug’s
owner
o 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 Development
1. Preclinical trial
2. Phase 1
3. Phase 2
4. Phase 3
5. Phase 4

VII. Legal Regulation

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

Category A  no risk to fetus

Category B  no risk in animal fetus; no human studies available
Category C  adverse effects to animal fetus; no human studies available
Category D  possible fetal risk in humans reported
Category 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 disintegration
o dissolution

Pharmacokinetics
• the study of what the body does to the drug:
o Absorption
o Distribution
o Metabolism or biotransformation
o 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 Phase
1. disintegration
2. 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 Fastest
Suspension solutions
Powders
Capsules
Tablets
Coated tablets
Enteric-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 Enteral
o Parenteral
o 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 buccal
o 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 transdermal
o buccal vaginal
o rectal* intramuscular
o intravenous subcutaneous
o 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-life
o 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 activities
b. stimulates cellular activities
c. inhibit or kill organisms
d. 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 incompatible

ex. 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 & constipation
narcotic analgesic
oral contraceptives
digitalis
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. Nephrotoxicity
s/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. Hypoglycemia
s/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. Hypokalemia
s/sxs
• serum K
• irregular, weak pulse
• weakness & numbness of extremities
• paralytic ileus
o absent bowel sounds
o abdominal distention

ex. loop diuretics (eg, furosemide)

N. Hyperkalemia
s/sxs
• same as hypokalemia

ex. potassium-sparing diuretics (eg. Spironolactone)

antineoplastic drugs

O. General CNS effects

s/sx
• anxiety
• insomnia
• nightmares
ex. beta-blockers (eg. Metoprolol)

P. Atropine- like (Cholinergic) effects

s/sxs
• dry mouth
• constipation
• urinary retention
• decrease sweating,
• hot dry skin

ex. antidepressants (eg. TCA)

Q. Extrapyramidal reactions/ parkinson- like syndrome

s/sxs
• immobility (akinesia)
• rigidity
• muscular tremors
• violent movement of head & arms (dystonia)
• restlessness (akathisia)

ex. antipsychotic drugs

R. Neuroleptic Malignant syndrome

s/sxs
• extrapyramidal symptoms
• hyperthermia

ex. general anesthetics

S. Photosensitivity
s/sxs
 • itching
• scaling
• reddening of skin
Ex. 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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