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Introduction To Pharmacology
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
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
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:
• 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
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
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)
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 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)
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
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.