INTRODUCTION TO PHARMACOLOGY

1. HISTORY

Early drug – plants, animals & minerals

2700 BB – 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 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 Jenner)

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 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 drug’s 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 drug’s 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

don’t become active until they’re 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)

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

DISTRIBUTION

BLOOD FLOW

PROTEIN-BINDING BODY TISSUE

AFFINITY PHARMACOLOGIC EFFECT

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 ½) – time it takes for one half of drug

concentration to be eliminated

o Short t ½ = 4-8 hrs: given several times a day (i.e. penicillin G)

o Long t ½ = > 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 cell’s 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 ½ 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

Nurse’s 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.