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INTRODUCTION TO PHARMACOLOGY

1. HISTORY
Early drug plants, animals & minerals

2700 BC earliest recorded drug use found in Middle East & China

1550 BC Egyptians created Ebers Medical Papyrus

Castor oil laxative


Opium pain
Moldy bread wounds & bruises
Galen (131-201 AD) Roman physician; initiated common use of
prescriptions
1240 AD introduction of apothecary (pharmacy) system (Arab doctors)
1st set of drug standards & measurements (grains, drams,
minims), currently being phased out
15th century apothecary shops owned by barber, surgeons, physicians,
independent merchants
18th century small pox vaccine (by Eward Jenner, British Doctor)
Digitalis from foxglove plant for strengthening & slowing of
heartbeat Vitamin C from fruits
19th century morphine & codeine extract from opium
Introduction of atropine & iodine
Amyl nitrite used to relieve anginal pain
Discovery of anesthetics (ether, nitrous oxide)
Early 20th century aspirin from salicylic acid
Introduction of Phenobarbital, insulin, sulforamides
Mid 20th century
1940 Discovery antibiotics (penicilline, tetracycline,
streptomycin), antihistamines, cortisone
1950 discovery antipsychotic drug, antihypertensives, oral
contraceptives, polio vaccine

2. DEFINITION & SUBDIVISIONS


Drug chemical introduced into the body to cause some changes
WHO def: any product/subs used to modify/explore physiologic
system/pathologic states for the benefit of the patient
Pharmacology study of the manner in which the function of living system is
affected by chemical agents/drugs
Science concerned with history, sources, physical & chemical properties
of drugs & the way in which drug affects living system

Subdivisions of pharmacology:
1. pharmacodynamics study of the biochemical & physiological effects of drugs
& mechanisms of action
what the drug does to the body
2. pharmacokinetics deals with the absorption, distribution, biotransformation &
excretion of drugs
what the body does to the drug
3. pharmacotherapeutics study of drugs used in the diagnosis, prevention,
suppression, & treatment of diseases
deals with beneficial effects of the drugs (medicines)
4. pharmacognosy study of drugs in their original unaltered state; origin of drugs
source of drugs
ex: penicillin from penicillium (fungi)
5. Toxicology study of biologic toxins: study of poison & its effects deals with
deleterious effects of physical & chemical agents (including drugs) in human
Pharmacoeconomics study of relationship of drugs & economics
Pharmacovigilance science of collecting,researching, analyzing, & evaluating set of
information about adverse drug effects.
Receptor a component of the cell that interacts with drug, initiating a chain of
biochemical events leading to drugs observed effects
Human body works through complicated series of chemical reactions & processes
Important aspects of nursing: understanding how drug ant on body to cause
changes & apply that knowledge in clinical setting
Patients take complicated drug regimen & receive potentially toxic drug
Some manage their own care at home
Nursing responsibilities regarding drug therapy:
Administering drugs
Assessing drug effects
Intervening to make drug regimen more tolerable
Provide patient teachings about drugs & drug regimen
Knowing how drug works --- easier to handle --- enhances drug therapy

DRUG NOMENCLATURE
1. CHEMICAL NAME atomic/molecular structure of drug
2. GENERIC NAME/NON-PROPERTY NAME original designation given to the
drug when the drug company applies for approval patents
- universally accepted & not capitalized; before drug becomes official, used
in all countries
- protected by law; not capitalized
3. TRADE/BRAND/PROPRIETY NAME name given by the drug company that
developed it
- followed by the symbol R or TM, 1st letter is capitalized
chemical name acetylsalicylic acid
generic name aspirin
trade name aspilet
COMMON SOURCES /4 MAJOR SOURCES (ORIGINS) OF DRUGS:

1. Animal sources from organs, organ secretion or organ cells


Used to replace human chemical not produces because of disease or
genetic problems
Thyroid drugs & growth hormones preparations from animal thyroid &
hypothalamus tissue (many of these preparations are now created
synthetically safer & purer)
Insulin from pancreas of animals (hog, cattle, sheep): thru genetic
engineering cld produce human insulin by altering E. coli bacteria
making it a better product without impurities that come with animal
products
2. vegetable/plant sources roots, bark, sap, leaves, flowers, seeds of medicinal
plants
digitalis (use as a herat stimulant) from wildflower, purple foxglove, dried
leaves of plant
active principles of plants
alkaloids alkaline in reaction, bitter in taste, powerful in
physiologic activity
o atropine & scopolamine
o morphine sulfate, cocaine, quinine, nicotine, caffeine
o procaine

glycosides digitalis
resin soluble in alcohol; example colonic irritant found in laxative
cascara
gums used in bulk-type laxatives: some used in certain skin preparations
for their soothing relief
oils castor oil, oil of wintergreen
3. Mineral sources from free elements, both metallic & non-metallic usually in
form of acids bases, salts found in food
Dilute HCI control/prevent indigestion
Calcium, aluminum, fluoride, iron, gold, potassium

4. synthetic sources many drugs developed synthetically after chemical in plants,


animals, or environment have been screened for signs of therapeutic activity
more potent, more stable, less toxic
steroids arthritis & other diseases
sulfonamides/chemotherapeutic agents kill microorganism slow their growth
meperidine HCI (Demerol)

DRUG CLASSIFICATION
A. by action
Anti infectives antiseptics, disinfectants, sterilants
Antimicrobials, metabolic, diagnostic materials, vitamins & minerals
Vaccine & serums, antifungals, antihistamines, antineoplastics, antacids
B. By body system
CNS (+)/(-) actions of neural pathways & centers: Phenobarbital
ANS governs several bodily functions so that drugs that affect ANS will
at the same time affect other systems functions
GIT acts on mascular & glandular tissues: leperamide
RESPIRATORY SYSTEM act on resp. tract, tissues, cough center,
suppress, relax, liquefy & stimulate depth & rate of respiration
Urinary system act on kidney & urinary tract
Circulatory system act on heart, blood vessels, blood; metoprolol

KINDS OF DRUGS
Prescription/legend drug can be dispensed if with prescription order; with specific name
of drug & dosage regimen to be used by patient
non-prescription drug can be dispensed over the-counter/without prescription order
- for self treatment of variety of complaints
- vitamin supplements, cold/cough remedies, analgesics, antacids, herbal
products
- cautions in use of OTC drugs:
1. delay in professional diagnosis & treatment of
serious/potentially serious condition may occur
2. symptoms may be masked making the diagnosis more
complicated
3. clients health care provider/pharmacist should be consulted
before OTC preparations are taken
4. labels/instructions should be followed carefully
5. ingredients in OTC drug may interact with prescribed drug
6. inactive ingredients may result in adverse reactions
7. potential for overdose
8. multiple medication users are at risk as more medications
are added to therapy regimen
9. interactions of medications are potentially dangerous
Investigational drug new drugs undergoing clinical trails
Illicit/street drug used/distributed illegally for non-medical purposes to alter mood of
feeling

**when drug is taken by mouth, it undergoes 3 phases:


1. pharmaceutic/dissolution
2. pharmacokinetics
3. pharmacodynamics

I. PHARMACEUTIC/DISSOLUTION
- Drug goes into solution so that it can cross the biologic membrane
- Not found in drug administered parenterally
- 1st phase of drug action of agents taken by mouth
- Additive enhances absorbability of drugs
- EXCIPIENTS: filters & inert substances
Allows drugs to take on particular size & shape
Enhance drug dissolution potassium (K) --- losartan K (cozaar); sodium (Na)
---cloxacillin Na (Prostaphlin-A)
2 phases:
- Disintegration breakdown into smaller parts
- Dissolution futher breakdown into smaller parts in GIT
absorption; dissolved into liquid
- rate limiting: time it takes drug to disintegrate & dissolve to become available for
body to absorb it
- factors affecting dissolution
form of drug (LIQUID VS. SOLID) liquid more absorbed than solid,
already in solution, rapidly available for GI absorption
Gastric ph (acid vs alkaline) acidic media (ph=1.2) faster disintegration &
absorption
Age young vs elderly inc ph. Dec absoption
Enteric coated drugs resist disintegration in gastric acid
Disintegration occurs only in alkaline environment (intestine)
Should not be crushed
Presence of food interfere with dissolution & absorption, enhance
absorption of other drugs, may be protectants of gastric mucosa

I. PHARMACOKINETICS action of body to the drug:


Study of absoption (taken into the body), distribution (moved into various
tissues), metabolism/biotransformation (changed into a form that can be
excreted) & excretion (removed from the body) of drugs
What happens to the drug when it enters the body
kinetics movement: deals with drugs actions as it moved through the body
Also concerned with a drugs onset of action, peak concentration level, &
duration of action

4 processes involved:
I. Absorption route of drug takes from the time it enters the body until it is absorbed
in circulating fluids
Movement of drug molecules from site of administration to circulatory
system
Movement of drug particles from GIT to body fluids involve 3 processes
Passive absorption (diffusion) movement from higher
concentration
o No energy required: occurs when smaller molecules
diffuse across membrane
o Stops when drug concentration on both sides of the
membrane is equal
o Major process through which drugs are absorbed into
the body
Active absorption needs carrier (enzymes or
protein) to move against a concentration gradient
o Energy is required: from lower concentration to higher
concentration
o Used to absorb electrolytes (i.e. sodium, potassium) &
some drugs (levodopa)
Pinocytosis engulfs the drug to carry it across
the membrane
o Transport fat-soluble vitamins (vit.A,D,E,K)
Factors affecting absorption:
Drug solubility lipid soluble drugs pass readily through GI
membrane,
Water soluble drugs need an enzyme or protein
Local condition at site of absorption weak acids less ionized
in stomach
- - - readily pass through the SI
Pain / stress / solid foods / fatty or hot foods slows
down gastric emptying time
Drug concentration drugs can take several hours/days to
reach peak concentration levels (slow rate: rectal
administration or sustained release drugs)
Circulation at site of absorption poor circulation hampers
absorption (i.e. shock)
The more blood vessels, the faster the absorption
Exercise decrease blood flow to GI slows
absorption
Application of heat/massage increases blood flows
at site
Muscles area selected for IM administration:
Blood flows faster through deltoid
muscle (upper arm) vs gluteal muscle
(buttocks)
Gluteal muscle can accommodate larger
volume of drug than deltoid muscle
3. Metabolism biotransformation: essential for termination of a drugs biologic activity
so can be easily excreted
Sites of metabolism
o Liver main organ for drug metabolism
Through the drug metabolizing enzymes (microsomal
enzymes, non-microsomal enzymes)
1st pass effect hepatic 1st pass some drugs do not directly go
into circulation but pass thru intestinal lumen to liver via portal
vein - - drug metabolized in liver into inactive form - - decrease
amount of active drugs - - - increase recommended dose for
oral drugs
Lidocaine extensive 1st pass not given orally
o Plasma
o Kidneys
o Membranes of intestine
Process by which body changes a drug from its dosage form to a more water-
soluble form that can then be excreted
Can be metabolized in several ways:
o Most drugs metabolized into inactive metabolites (products of
metabolism), which are then excreted
o Other drugs converted to active metabolites capable of exerting their
own pharmacologic action
May undergo further metabolism or may be excreted from
body unchanged
Prodrugs some drugs administered as inactive drugs which
dont become active until theyre metabolized
o Permits the body to inactive a potent drug before it accumulates &
produces toxic effects
Phases of drug metabolism:
o Phase 1: endoplasmic reticulum; introduce/expose a functional group
on the parent compound (i.e. alkylation, alipathic hydroxylation,
oxidation, deamination, hydrolysis, microsomal oxidases)
Cytochrome p450 inducer inc drug metabolism, dec
bioavailability
Cytochrome p450 inhibitor dec drug metabolism, inc levels
of drug prolonged effect & inc toxicity
o Phase 2 conjugation reactions that lead to formation of covalent
linkage between parent compound with glucoronic acid, sulfate,
glutathione or acetate (glucoronidation, sulfation, acetylation);
synthetic reactions
Factors affecting biotransformation:
o Genetic some people metabolize drugs rapidly, other more slowly
o Physiologic
Liver diseases (cirrhosis), heart failure dec circulation in liver
Infants immature livers dec rate of metabolism
o Area of absorbing surface to which a drug is exposed (+) chemical
agents may destroy the drug
o Types of transport diffusion, active, pinocytosis
o Routes of administration skin absorption slower than IM
Absorption with in seconds/minutes: sublingual, IV, by
inhalation route
Slower rate absorption: oral, IM SC routes
o Bioavailability consideration of highest importance in drug
effectiveness & safety
Subcategory of absorption
% of administered drug does that reaches systemic circulation
Oral route <100%(usually 20-40%); IV route = 100%
Factors that alter bioavailability:
Drug form (tablet, capsule)
Route of administration
GI mucosa & motility
Food & other drugs (+) food - - - pord of gastric acid
inc drug absorption (i.e. azole)
Changes inliver metabolism, liver disorder dec liver
function inc bioavailability
II. distribution process by which drug becomes available to body fluids & tissues
the ways a drug is transported from the site of administration to the site of
action (transportation)
factors affecting distribution:
o size of the organ
o blood flows drug is quickly distributed to organs with large supply of
blood (heart, liver, kidneys)
distribution to other internal organs, skin, fat, muscle is slower
o solubility lipid soluble drugs can also cross the blood-brain barrier
& enter the brain
o Binding as drug travels trough the body, it comes in contract with
proteins (albumin). The drug can remain free or bind to protein.
Portion of drug bound to protein is inactive, no therapeutic
affect
Free/unbound portion active - - - - (+) pharmacologic
response
Highly protein bound drug - > 89% of drug is bound to protein
Diazepam, piroxicam, valproic acid
Moderately highly protein bound drugs (61-89% bound
protein)
Erythromycin, phenytoin
Moderately protein bound drugs 30-60%
Aspirin, lidocaine, pindolol, theophyliine
Low protein-bound drugs - < 30% bound to protein (amikacin,
amoxicillin)

DISTRIBUTION

PROTEIN-
BINDING BLOOD BODY TISSUE
FLOW AFFINITY PHARMACOLOGIC
EFFECT
Elderlies dec liver size, blppd flow, enzyme production - - - slows
metabolism
Environment cigarette smoke may affect rate of some drugs
o Stressful environment prolonged illness, surgery, injury

III. Excretion/elimination removal of drug from the body: drug is changed into
inactive form & excreted by the body

Routes:
o Kidney main organ for drug elimination: leaves the body through
urine
Free/unbound/water soluble drugs filtered in kidney
Protein bound drug cannot be filtered in kidney
(+) kidney dose dose must be decreased
o Lungs, exocrine (sweat, salivary, mammary) glands, skin, intestinal
tract
Factors affecting drug excretion
o Urine ph normal: 4-5.8
Acid urine promotes elimination of weak base drugs
i.e. cranberry juice dec urine ph - - - (-) elimination of
aspirin
alkaline urine (+) elimination of weak acid drug
overdose aspirin - - - give Nabicarbonate inc urine ph
- - - (+) excretion of drug
o glomerular filtration rate (GFR) dec GFR - - - drug excretion
slowed/impaired
can result to drug accumulation
extent of filtration directly proportional to GFR & to fraction of
unbound drug to plasma
ratio of clearance = fu x GFR - - - cleared by filtration
ratio of clearance < fu x GFR - - - cleared tubular
reabsorption
ratio of clearance > fu x GFR - - - cleared by tubular
secretion
o creatinine clearance most accurate test to determine renal function
creatinine excreted in kidney
dec renal GFR inc serum creatinine level & dec urine
creatinine clearance
12-24 hrs urine collection & blood sample
Normal 85-135 ml/min; elderly 60ml/min
Renal clearance amount of substance removed from the blood by the
kidneys
Half-life/elimination half-life (t ) time it takes for one half of drug
concentration to be eliminated
o Short t = 4-8 hrs: given several times a day (i.e. penicillin G)
o Long t = > 12 hrs: given 2x or 1x / day (digoxin)

II. PHARMACODYNAMICS refers to action of drug to the body


What happens to the body in response to the drug
Effects of drugs on the cells biological & physiological functions &
mechanisms of action
Interactions between chemical components of living systems & foreign
chemicals including drugs that enter these system
Mechanism of action: means by which a drug produces alteration in function
of their action
Drug actions:
a. To replace/act as substitute for missing chemicals
b. To inc or stimulate certain cellular activities
c. To depress/slow cellular activities
d. To interfere with functioning of foreign cells (i.e. invading
microorganisms/neoplasms) chemotherapeutic Agents
Theories of Drug Actions
a. Drug-receptors interaction certain portion of drug molecule (active
site) selective combines with some molecular structure (reactive site)
on the cell to produce a biologic effect
Receptor site drugs act at specific areas on cedil memb.; react
with certain chemicals to cause an effect with in cell
lock & key theory specific chemical (key) approaches a cell
membrane & finds a perfect fit (the lock) at receptor site
affects enzymes system within a cell produce certain effects
Specificity selectivity theory
Drug action may be:
Agonists drugs that produce a response
o insulin reacts with specific insulin receptor site
to change cell membrane permeability - - - (+)
movement of glucose into cell
competitive antagonist act with receptor sites to block
normal stimulation producing no effect
o curare use on spear in Amazon to paralyze
prey & cause death: occupies receptor sites for
Acetylcholine (needed in muscle contraction &
movement) - - - prevents nerve stimulation
causing paralusis
o noncompetitive antagonist - prevent reaction of
another chemical with different receptor site on
that cell
b. drug-enzymes interaction interferes with enzyme systems that act as
catalyst from various chemical reations
enzyme systems cascade effect; one enzyme activating
another - - - causing cellular reaction
if single step in one of enzyme system is blocked normal cell
function is disrupted
ex: acetazolamide (diamox) diuretic that block carbonic
anhydrase alters H+ & H2O exchange systems in kidneys &
eye
c. nonspecific drug interaction act by biophysical means that do not
affect cellular enzymatic reactions
d. selective toxicity all chemotherapeutic agent would act only on 1
enzyme system needed for life of a pathogen or neoplastic cell & will
nor affect healthy cells
ex: penicillin
unfortunately most of it cause destruction of normal human
cells

Drug response may be:


1. primary always desirable / physiologic effects
2. secondary desirable or undesirable
ex: diphenhydramine (benadryl) 1st effect: antihistamine, treat symptoms of
allergy; 2: CNS depression - - - drowsiness
desirable: when given at bedtime: undesirable: when client is driving

Classification of drug action:


1. rapid few seconds to minutes (IV, SL, inhalation)
2. intermediate 1-2 hrs after administration (IM, SC)
3. Delayed/slow several hrs after administration (rectal, oral)

Parameters of Drug Action:


1. onset of action latent period: interval between time drug is administered & 1st sign
of its effect
time it takes to reach the minimum effective concentration (MEC) after a drug
is administered
time from drug administration to 1st observable effect _T0 T1)
2. duration of action period from onset until drug effect is no longer seen
length of time the drug exerts pharmacologic effect (T1 T3)
3. peak action drug reaches its highest blood / plasma concentration (T0 T2)

Termination of action point from onset at which drug effect is no longer seen
Minimal effective concentration lowest plasma concentration that produces the desire
effect
Peak plasma level highest plasma concentration attained from a dose
Toxic level plasma concentration at which a drug produces adverse effects
Therapeutic range range of plasma concentration that produces the desire effect without
toxicity (range between minimal effective concentration & toxic level)
Loading dose bolus of drug given initially to attain rapidly a therapeutic plasma
concentration
large initial dose; when immediate drug response is desired
given to achieve a rapid MEC in the plasma
i.e. digoxin - - - requires LD
Maintenance dose amount of drug necessary to maintain a steady therapeutic plasma
concentration
Dose response relationship between minimal vs. maximal amount of drug dosed needed
to produce desired drug response
i.e. some clients respond to lower drug dose while others need a high
dose
Maximal efficacy (maximum drug effect) all drugs give a maximum drug effect
(maximal efficacy)
i.e. simvastatin 40mg vs rouvastatin 10mg

Drug-response relationship:
Biologic half-life (t1/2) = time required to reduce to amount of unchanged drug that is
in the body
short t1/2 drugs need to be administered more often than one with a
longer t1/2
Lethal dose (LD50) dose lethal to 50% of animals tested
Effective dose (ED50) dose required to produce therapeutic effect on 50% animals
tested
Therapeutic index (TI) ratio between LD50 and ED50; the closer the ratio is to 1, the
greater the danger involved in giving the drug to humans
estimates the margin of safety of a drug through the use of a ratio that
measures the effective (therapeutic or concentration) dose (ED) in 50%
of persons/animals (ED50) & lethal dose in 50% of animals (LD50)
TI=LD50/ED50
low therapeutic index: narrow margin of safety; might need to adjust
drug dose & plasma drug levels need to be monitored
high therapeutic index: wide margin of safety less danger of producing
toxic effects

4 Categories of Drug Action:


1. stimulation/depression
stimulation inc rate of cell activity/secretion from the gland
depression dec cell activity & function of a specific organ
2. replacement replaces essential body compounds; i.e. insulin
3. inhibition/killing of organism interfere with bacterial cell growth ; i.e. antibiotics
4. irritation i.e. laxative irritate inner wall of colon - - - inc peristalsis - - - inc
defecation

Drug potency relative amount of drug required to produce desired response


also used to compare a drug
dose response curve graphical representation of relationship between dose of drug &
response it produces
low dose low response
dosage increased produce slight increase response, as dose further increases, drug
response increases markedly, at certain point however, inc dose yield little or no
inc in response - - - drug have reached Maximum Effectiveness
Factors Affecting Dose Response Curve:
- nurse must be aware that human factor has tremendous influence on
what actually happens when it enter the body
- no 2 people react in exactly the same way to any given drug
1. weight heavier patient larger dose to get therapeutic effect (more tissue to
perfuse & inc receptor site in some reactive tissues)
- dec weight dec dose
2. age children (immune system for handling drugs) & older adults
- older patients: less absorption, distribution between fewer plasma
proteins & less efficient perfusion: geriatric dosages
- nurse should monitor closely for desired effects (may adjust dose)
3. toxicity
4. pharmacogenetics effect of a drug action that varies from a predicted drug
response because of genetic factors or hereditary influence
people have different genetic makeup do not always respond identically to a
drug dosage or planned drug therapy
ex: African Americans do not respond as well as whites to some classes of
antihypertensive medications
5. route of administration
6. emotional factors
7. pre-existing disease state liver disease
8. drug history drug interaction synergistic/excretion
9. tolerance
10. cumulative effect
11. drug- drug interaction
12. BMR inc BMR inc drug metabolism & excretion

Drug Interaction
1. Additive effect 2 drugs with similar actions are taken for a doubled effect
(desirable/undesirable) (1 + 1 = 2)
Ibuprofen + paracetamol + added analgesic effect
2. Synergistic combined effect of 2 drugs is greater than sum of the effect or each
drug given alone (1 + 1 = 3)
Aspirin + codeine = greater analgesic effect
3. potentiation a drug that has no effect enhances the effect of a 2nd drug (0 + 1= 2)
4. Antagonistic one drug inhibits the effect of another drug (1 + 1 = 0)
Tetracycline + antacid = dec absorption of tetracycline

SIDE EFFECTS
Physiologic effects not related to desired drug effects
All drugs have side effects
Desirable: diphenhydramine (Benadryl) at bedtime s/e:
drowsiness
Undesirable
Result mostly from drugs that lack specificity
Might be used interchangeably with adverse reactions
Not a reason to discontinue drug therapy
Nurses role: teach clients to report any side effects

ADVERSE REACTIONS
More severe than side effects
Range of untoward effects (unintended, occurring at normal doses) of drug
that cause mild-severe side effects: anaphylaxis (cardiovascular collapse)
Always undesirable
Must always be reported & documented because they represent variances
from planned therapy.

TOXIC EFFECT/TOXICITY
Can be identified by monitoring the plasma (serum) therapeutic range of the
drug
Narrow TI (aminoglycoside & antibiotics) therapeutic range is monitored
When drug level exceeds therapeutic range, toxic effects are likely to occur
from overdosing or drug accumulation.