Phases of Drug Action

Pharmaceutic
Pharmacokinetic
Pharmacodynamic

Dr. Caridad D. Garcia

Registered Pharmacist
DISINTEGRATION  DISSOLUTION
 Drug breaks down  drug dissolves in the
into smaller particles GI fluid
 Pharmaceutic Phase

• Disintegration Drug in solid oral form

breaks into fragments or
smaller particles
• Dissolution
The drug’s smaller particles are dissolved (suspended or
dispersed) in the GI fluid before absorption.
 Pharmaceutic Phase

Rate limiting
The time it takes the drug to disintegrate & dissolve
to become available for the body to absorb.
 Pharmaceutic Phase

• Drug form: liquid vs. solid

Drugs in liquid form are more rapidly available for

GI absorption than are solids.

• pH

Drugs are both disintegrated & absorbed faster in

acidic fluids (pH1 or 2) than in alkaline fluids
Pharmaceutic Phase

• Age

Both the very young & the elderly

have less gastric acidity;
therefore drug absorption is
generally slower for those
drugs absorbed primarily in the
stomach.
 Pharmaceutic Phase
• pH
Drugs are both disintegrated & absorbed faster
in acidic fluids (pH1 or 2) than in alkaline fluids
Acidic Foods Alkaline Foods
• Corn, grains • Most fruits, bananas,
• Meat, fish, fowl, liver & watermelon
organs, eggs, aged • Chocolate, orange juice
cheese • Most vegetables,
• Coffee, wine Potatoes, spinach
• Plums, prunes, yoghurt,
sour cream
 Pharmaceutic Phase
• Food in the GI Tract
• Food may interfere w/ the dissolution &
absorption of certain drugs; however,
there are foods that can enhance the
absorption of drugs.

• Some drugs irritate the gastric mucosa, so

fluids or food may be necessary to dilute
drug concentration & act as protectants.
 Why is there a need for a drug
to become a solution?
to be able to pass
through biologic
membranes
Enteric-coated tablets

Are meant to
disintegrate in the
alkaline
environment of
the small
intestines
Enteric-coated tablets

NO FATTY FOODS
- Fat decreases
absorption rate
Sustained-released
(SR)

 Sustained-action (SA), extended-

release (ER, XR, or XL), time-
release or timed-release,
controlled-release (CR), modified
release (MR), or continuous-release
(CR or Contin)
 is a mechanism used in pill tablets or
capsules to dissolve slowly and release a
drug over time.
Enteric-coated and Sustained-
released (SR) tablets/capsules

 NOT to be crushed
or chewed
 Swallow whole
 Will a liquid drug formulation
undergo the pharmaceutic phase?
 Pharmacokinetics (PK)

Is the process of drug movement across

body membranes to reach its target organ
and achieve drug action

• Absorption
4 Stages • Distribution
• Metabolism
Elimination
• Excretion
 Overview - ADME
Most drugs :
enter the body (by mouth or injection or…) - must cross
barriers to entry (skin, gut wall, alviolar membrane…..)
are distributed by the blood to the site of action - intra-
or extra- cellular - cross barriers to distribution (capillaries,
cell wall….) - distribution affects concentration at site of
action and sites of excretion and biotransformation
are biotransformed perhaps to several different compounds
by enzymes evolved to cope with natural materials - this
may increase, decrease or change drug actions
are excreted (by kidney or …….) which removes them and/or
their metabolites from the body
Pharmacokinetics is the quantification of these
processes
ADME
 Importance
Without the knowledge gained from PK
studies, patients may suffer:
 Toxic drugs may accumulate
 Useful drugs may have no benefit because
doses are too small to establish therapy
 A drug can be rapidly metabolized.
 Routes Of Administration
Routes Of Drug
Administration

Parenteral Enteral

Injection Topical Respiratory Rectal Oral

 Absorption
 The passage of drug from the site of
administration into the general circulation
(body fluids).
 Exception: Intravenous injections

I.V Drug Oral Drug

Immediately Delayed
completely incomplete
 Absorption
Drug Formulation Site of absorption
Oral Small intestine (villi)
IM Muscle
Ointment Skin
Inhalation lungs
 Site Of Absorption

 Most drugs are absorbed in the small

intestine, because
 It is the portal for absorption of nutrients into
blood
 It is surrounded by a very thin
membrane with a large surface
area
 Absorption Process

 Passive diffusion
 Active transport
 Pinocytosis
 Drug Movement: Passive Absorption

• diffusion: higher  lower concentration

• no energy requirement
 The Process

 Absorption relies on
 Passage through membranes to reach the
blood
 passive diffusion of lipid soluble species.
 The Process

 Active transport (carrier mediated &

facilitated)
 Carrier (enzyme or protein) + energy
 Large molecules
 Moving against a concentration gradient
(lower to higher)

 Not very important in drug absorption, but

often involved in excretion in the kidneys
 The Process
 Pinocytosis or Fluid Endocytosis
 “Cell drinking”
• small particles are brought
into the cell - forming an
invagination, and then
suspended within small
vesicles that subsequently
fuse with lysosomes to
hydrolyze, or to break
down, the particles.
• Energy (ATP)
FACTORS Affecting
ABSORPTION
BIOLOGICAL FACTORS

Gastro intestinal physiology

Gastro intestinal blood flow
Gastro intestinal pH
Gastric emptying
Effect of food on drug absorption
Mal absorption
Gastro Intestinal Physiology

STOMACH  Absorption of weakly

acidic drugs or
unionized drugs and
weak basic drugs takes
place.
Small intestine
generally carrier mediated
transport is seen in most
drugs.
Proximal part-absorption of
dietary constituents
includes mono saccharides,
AA, vits, minerals etc.
Ileum-Vit B12, bile salts.
Micro villi  The effective surface area
(ESA) can be made 10
times larger to that of
stomach because of the
presence of micro villi.
 Micro villi are finger like
projections arising from
and forming folds in
intestinal mucosa.
 ESA was decreasing from
proximal part to distill part
of small intestine.
BLOOD FLOW

 It plays a major role in absorption by

continuously maintaing the concentration
gradient across the epithelial membrane.
 Absorption of lipid soluble molecules
highly depends on the blood flow.
 Enter blood liver systemic
circulation
 Gastrointestinal pH

Acidity of the stomach

 HCl can destroy some drugs [penicillin G: larger
dosage is needed to offset partial dose loss]
 can be rectified by pro drug preparation.
 ex: penicillin-------------carindacillin
erythromycin--------erythromycinesfolate

 CaCO3 & “azole” antifungals: acidic environment for

greater absorption
 Gastric emptying

 It is the passage of food from the

stomach to the small intestine
 This process increases the bioavailability
of the drug because mostly the absorption
occurs in small intestine.
 Slow gastric emptying can delay the onset
of effect of the drug Ex: Analgesics &
sedatives
Fast GASTRIC EMPTYING IS
RECOMENDED
WHEN
 Dissolution of drug occur in the intestine.
ex: enteric coated dosage forms.

 Drug is best absorbed from the distal part

of the small intestine.
ex: Vit B12
Delayed gastric emptying
is recommended
WHEN
 Food promotes drug dissolution and
absorption. ex: griseofulvin
 Drugs irritate gastric mucosa.
ex: aspirin, phenyl butazone.
 Drugs are absorbed from the proximal
part of the SI & prolonged drug
absorption site is desired. Ex:Vit B12 & C
FACTORS EFFECTING
GASTRIC EMPTYING

 Volume of meal
 Drugs
 Posture
 Composition of meal
 Physical state
 Temperature
 PH.
 Disease state
Effect of food on drug absorption

 Food stimulate hepatic blood flow,

which have implication for the
bioavailability of the drug.
 Food tends to decrease the rate of
gastric emptying which effects drugs
like penicillin
 Forms poorly soluble and
unabsorbable complexes.
 Effect of food on drug absorption

 High protein food causes poor absorption

of drugs. ex: levodopa.
 High fat food causes poor absorption of
drugs. ex:isotertinonin.
 Administration of drug with large fluid
volume enhances the dissolution rate and
gastric emptying.
 Mal absorption

 It is a disorder with impaired absorption

of fat, protein, carbohydrate, vitamin,
minerals& water.
 Drugs which induce mal absorption
Neomycin, Phenytoin, Amino salicylate
 These drugs mainly damages the gastro
intestinal epithelium emphasis the function of
mucosa to serve as a barrier to large polar
molecule.
 Factors affecting Absorption

Presence of Foods or drugs

Milk, alcohol, protein = acidity 
breakdown   absorption
Solid, hot & fatty foods =  gastric emptying
time

Oral drugs: give 1h ac or 2 hrs pc

Physico -chemical factors

 Absorption of drug from solution

 Absorption of drug from solid
dosage form and suspension
 Drug stability and hydrolysis in the
gastro intestinal tract
 Complexation
 Adsorption
Role of dosage form in drug
absorption

 Different dosage forms:-

solutions suspensions
tablets capsules
Coated tab & enteric coated tab
 Disintegration test
 Dissolution test
 Excipients and adjuvant
 Product age and storage conditions.
 Route for administration
-Time until effect-

 intravenous 30-60 seconds

 intraosseous 30-60 seconds
 endotracheal 2-3 minutes
 inhalation 2-3 minutes
 sublingual 3-5 minutes
 intramuscular 10-20 minutes
 subcutaneous 15-30 minutes
 rectal 5-30 minutes
 ingestion 30-90 minutes
 transdermal (topical) variable (minutes to hours)
First-pass Effect
Hepatic first pass
 Phenomenon in which drugs given orally
are carried directly to the liver where they
will be largely inactivated by enzymes,
before they can enter the general
circulation
 Question

Explain the significance of first-pass effect

as related to drug absorption.

First-pass effect can delay absorption as

the drug has to be brought to the liver
before entering the general circulation .
Bioavailability
 the proportion of the drug in a
dosage form available to the body
i.v injection gives 100% bioavailability.
Says nothing about effectiveness.
 extent of absorption of a drug
following its administration by routes
other than IV.
Bioavailability
Destroyed Not Destroyed Destroyed
in gut absorbed by gut wall by liver
Dose
to
systemic
circulation
Bioavailability
 expressed as the % of the
administered drug dose that
reaches the general circulation.

 Oral route: bioavailability occurs

after absorption & hepatic drug
metabolism (20%-60%)
 Question
Explain the significance of first-pass effect
on bioavailability as related to drug
absorption.

First-pass effect can reduce the amount of

the active drug or bioavailability after
being metabolized and thus decreasing
the drug in the general circulation.
 Distribution
 The movement of drug from the blood
to and from the tissues
 Distribution
 The movement of drug from the blood
to and from the tissues
blood stream  interstitium (ECF) or cells
(site of action)
 stored
 Drug Storage Depot

 plasma proteins
 cellular depots
 transcellular depots
 extracellular deports

N.B. only free drugs are active

drugs
 As the concentration of the free drug
decreases due to elimination by
metabolism & excretion, the bound drug
dissociates from the storage site.

 The stored drug is in equilibrium w/ that in

the plasma & is released as plasma
concentration is reduced.
 Plasma Protein Binding

 albumin: anticonvulsants
 globulin: antidyrrhythmics
lidocaine, quinidine
 fibrinogen
 Classification of drugs according to
Protein Binding capacity

 Highly protein-bound drugs (89%)

 Moderately Highly protein-bound (61-89%)
 Moderately protein-bound (30-60%)
 Low protein-bound drugs (%)
 2 highly protein-bound drug
compete for binding sites

competition for binding site  

free drug in the circulation drug
accumulation; possible toxicity
Protein Binding
Drug Displacement
Plasma Tissue
Drug B
Drug A
protein bound

Drug A Drug A
free free

Drugs A and B both bind to the same plasma protein

 After % increase in
Displace- UNBOUND
ment fraction
Drug A
% bound 95 90
% Unbound 5 10 +100
Drug B
% bound 50 45
% Unbound 50 55 +10
 Low protein level (liver/kidney
disease; malnutrition
  # of protein binding sites 
 free drug in the circulation
drug overdose
Nursing Implication?
 Check protein-binding % of ALL
drugs administered to a client to avoid
possible toxicity
 Check client’s plasma protein &
albumin levels
 Protein (total) 6-8 gm/dL
 Albumin: 4-5.5 g/dL
 Globulin: 1.7-3.3 g/dL
Cellular depot

 Many drugs accumulate in higher

concentration in cells than in ECF.
• Tissues (muscle)
• Eyes
• Liver
Extracellular depot

 Connective tissue
 Bone (tetracycline)
 Fat (thiopental)
Tanscellular depot

 GI fluid/genito urinary tract

 Luminal fluid of thyroid
 Aqueous humor
 Synovial fluid
Cerebrospinal Fluid

 NOT a depot
 No protein content
Blood-Brain
barrier (BBB)

 A mechanism
that inhibits
passage of
materials from
the blood into
brain tissues
Blood-Brain
barrier (BBB)

FUNCTIONS
 Protecting the brain from
"foreign substances" (such as
viruses and bacteria) in the
blood that could injure the
brain
 Shielding the brain from
hormones and
neurotransmitters in the rest
of the body
 Maintaining a constant
environment (homeostasis)
for the brain
 Lipid-soluble drugs readily
penetrate in the CNS:
 Alcohol
 Fats
 Respiratory gases
 Nicotine
 Anesthetics
Placental transfer of drugs
 Placental transfer
of drugs occurs
primarily by simple
diffusion, carrier-
mediated transport.
Non-ionized drugs
of high fat solubility
readily enter the
fetal blood from
maternal
circulation.
Drugs in Breast Milk

 Many drugs are

secreted into
breast milk &
therefore have
the potential to
affect the
neonate.
 Drug Metabolism
 The chemical modification of drugs with
the overall goal of getting rid of the drug
 Enzymes are typically involved in
metabolism
Metabolism More polar Excretion
Drug
(water soluble)
Drug
 Sites of Drug Metabolism

 Metabolism occurs in many tissues

 E.g. brain, kidney, lung
 But mostly in the liver because …
all of the blood in the body passes
through the liver.
 Intravenous
Administration

Oral
Administration

Metabolism Liver

Intestines
 Consequences Of Metabolism

 Drug metabolism != Drug inactivation

 The metabolite may have
 Equal activity to the drug
 No or reduced activity
 Increased activity (Prodrugs)
 Toxic properties, not seen with the parent
drug
 Hepatic Microsomal System or
Hepatic Cytochrome P450

 Enzyme system
lining the
intracellular structure
of the liver
 Act on structurally
unrelated drugs
 Metabolize the
widest range of
drugs.
 Hepatic Cytochrome P450:
enzyme induction

 Some drugs can induce, speed-up or increase

the activity of cP450:
 Nicotine
 Alcohol
 Glucocorticoids
Nursing implication?
 Hepatic Cytochrome P450:
enzyme inhibition

 Some drugs can inhibit or decrease the

activity of cP450:
 ketoconazole
 quinidine
 mexiletine
Nursing implication?
 Why is liver disease
often a contraindication
or a reason to use
caution when
administering certain
drugs?
 A nurse is caring for a client receiving a
medication metabolized by the liver. The
nurse notes that the client’s liver enzyme
levels are elevated. The nurse would
anticipate the dose to be:
A.Increased
B.Decreased
C.Maintained at the usual dose
D.Titrated based on physician judgment
ALT (alanine transaminase) or SGPT (serum glutamic pyruvate)
Normal: 9 to 40 IU/L
AST (aspartate transaminase) or SGOT (serum glutamic oxaloacetic
transaminase
Normal = 10 to 35 IU/L
 Elimination
 The irreversible removal of the parent
drugs from the body

Elimination

Excretion Drug Metabolism

(Biotransformation)
 Excretion
 The main process that body eliminates
"unwanted" substances, including drugs
and its metabolites or by-products
 Routes?
 Main organ for drug excretion?
 Excretion
 The main process that body eliminates
"unwanted" substances, including drugs
and its metabolites or by-products
 Routes:
 GIT: feces
 Renal tubules: urine
 Skin, lungs, saliva, sweat, breast milk
 Total Body Clearance
 The sum total of the clearances from the
various drug-metabolizing & drug-
eliminating organs
 Clearance: volume of drug removed in a
given time
 Clearance (total) = Clearance (hepatic) +
Clearance (renal) + Clearance (pulmonary) +
clearance (others)
Creatinine Clearance (CLcr)
 Test to determine renal function
 Creatinine is a metabolic byproduct of the
muscle; excreted by the kidney
 Normal CLcr = 75 to 135 ml/min
 12-24 hr urine collection
 Blood sample
 Elderly: 60 ml/min
 women & children
Relate drug effects to
changes in clearance test.
Drug Half-life or Elimination Half-life
or Half-life (t ½ )

 The time required for

50% of the drug to be
eliminated from the
body.
Time t 1/2 Amt of drug in the body
(hrs)
0 - 100 mg (100%)
12 1 50 mg (50%)
24 2 25 mg (25%)
36 3 12.5 mg (12.5%)
48 4 6.25 mg (6.25%)
60 5 3.12 mg (3.12%)
 When t ½ is known, dosages &
frequencies of administration can be
calculated
 Dosing schedule
 Duration of effects
 Long t ½ : digoxin 360 – OD
 Short t ½ : aspirin 50 – q40-60
 Patient w/ impaired renal or hepatic
function:
 t ½ may be longer because of inability to
metabolize or excrete the drug
 Digoxin t ½ : 360 (normal renal function)
: 1050 (complete renal failure)
Explain the clinical implications
of
short half-live?
long half-life?
ADME - Summary
A client sustains significant burns to his skin
and is experiencing fluid shift associated
with the fluid overload phase. The nurse
would anticipate that this will most interfere
with which phase of pharmacodynamics?

A.Absorption
B.Distribution
C.Metabolism
D.Excretion
Pharmacodynamics
 is the study of drug concentration and its
effects in the body.

PRIMARY EFFECT SECONDARY EFFECT

 Desirable  Desirable
 Undesirable
Ex: Chlorpheneramine (Benadryl)

 Primary effect: treat symptoms of allergy

(antihistamine)
 Secondary effect: depression of CNS 
drowsiness
Desirable?
Undesirable?
Dose Response

 is the relationship between the minimal

versus the maximal amount of drug dose
needed to produce the desired response.

Some patients respond to a lower drug dose

while others need a high drug dose to
elicit the desired response.
Maximal Efficacy
 maximum drug effect
 refers to the maximum response
achievable from a drug
 It is often described by the parameter
Emax
 Synonym: intrinsic activity
Maximal Efficacy
Ex: Morphine has a greater maximal efficacy than
propoxyphene hydrochloride (Darvon) in treating
pain, regardless of the amount of propoxyphene HCl
that is given.

The pain relief with the use of propoxyphene

HCl is not as great as morphine.
Parameters of Drug Action

 Onset of Action is the time it takes to

reach the minimum effective
concentration.
 Peak Action occurs when the drug
reaches its highest blood or plasma
concentration.
 Duration of Action is the length of time
the drug has a pharmacologic effect.
Time Response Curve – evaluates
the 3 parameters of drug action

The time-response curve evaluates three parameters of drug action: (1) onset, (2) peak,
and (3) duration.
MEC, Minimum effective concentration; MTC, minimum toxic concentration.
 Why is it necessary to understand the time
response in relation to drug administration?

If the drug plasma or

serum level deceases
below threshold or MEC,
adequate drug dosing is
not achieved; too high a
level, above the
minimum toxic
concentration (MTC),
can result in toxicity.
Discuss the significance of
onset, peak and
duration of action of
various drugs?
Receptors
Drug

 Receptors = drug binding sites

 location: cell membrane Receptor
 nature: proteins, glycoproteins,
proteolipids, enzymes
 Receptors are chemicals which bind to the
drug to exert an effect

D + R = D-R  Drug Response/block a

response
Note: Binding of a drug to the receptor is usually reversible
Agonists
 Drugs that produce a response
 activates receptors
 affinity (attraction) and high intrinsic activity

For example:
Isoproterenol (Isuprel) – stimulates the β1-receptors on
the heart causing positive chronotropic [ heart rate],
dromotropic (speed in the AV node, and subsequently
the rate of electrical impulses in the heart], and
inotropic effects [ muscular contractility].
Definition of Terms

 Affinity – allows the agonist to bind to

receptors.

 Intrinsic Activity – allows the bound

agonist to activate or turn on its receptor
function.
Antagonist

 Antagonist – drug or molecule that

act against or block drug actions.

Example:
cimetidine (Tagamet) blocks histamine (H2)
receptor preventing excessive acid secretion.
Two drug agonists attach to the receptor site.
The drug agonist that has an exact fit is a strong agonist
and is more biologically active than the weak agonist.
Receptor Theory
 Traditional model was a
rigid “Lock and Key” [E.
Fischer]
 Lock  Receptor surface
 Key  Drug or Ligand
 Nonspecific Drug Effect
Stimulation
or blockage
of the
receptor at
all or various
anatomical
parts

Cholinergic receptors are located in the bladder, heart, blood vessels, stomach, bronchi, & eyes.
Betanechol (Urecholine) for postop urinary retention to increase bladder contraction
Nonselective Drug Effect
Stimulation or
blockage of all
types of
receptors

Epinephrine affects three different receptors: alpha, beta1, and beta2.

Categories of Drug Action
 Stimulation or Depression
 Stimulation: rate of cell activity or secretion from a
gland increases
 Depression: cell activity & function of a specific organ
are reduced.
 Replacement: substitution of essential body
compound [ex: insulin]
 Inhibition or Killing of organisms
 Irritation: sensitivity; exacerbation [ex: laxatives
irritate the inner wall of the colon, thus increasing
peristalsis & defecation]
 Therapeutic Index

The therapeutic index A. A low therapeutic index

measures the margin of safety drug has a narrow margin of
safety, and the drug effect
of a drug. It is a ratio that should be closely monitored.
measures the effective  B. A high therapeutic index
therapeutic dose (ED) and the drug has a wide margin of
lethal dose (LD). safety and carries less risk of
drug toxicity.
The ‘therapeutic index’

Toxic dose

Therapeutic dose

Toxic dose
Therapeutic index =
Therapeutic dose
Therapeutic Range

 Synonym: Therapeutic window

 The range of concentrations at which a
drug is effective with minimal toxic effect
 drug concentration in the plasma should
be between the minimum effective dose
for obtaining desired drug action and the
minimum toxic concentration or toxic
effect.
Nursing implication:

 Monitor therapeutic
range of highly toxic
drugs; to avoid
toxicity.
Peak and Trough Levels

Peak drug level is the highest plasma

concentration of the drug in a specified
time; it measures rate of absorption of a
drug.
 Oral: peak is 1-3 hrs
 IV: peak in 10 min
 Blood sample is drawn according to route
of administration.
Peak and Trough Levels

Trough level is the lowest plasma

concentration of the drug; it measures the
rate at which drug is eliminated.

 Blood sample is drawn immediately before

the next dose is given.
Peak and Trough Levels
Peak and Trough Levels
They are requested for drugs with narrow
therapeutic index
[ex: aminoglycosides – amikacin,
gentamicin, tobramycin]
 If either peak or trough are too high,
toxicity can occur.
 If peak is too low, no therapeutic effect is
achieved.
Which of the following nursing actions
would be most appropriate for
ensuring client safety with a
medication that has a low therapeutic
index?

A.Monitoring patient’s urine output

B.Assessing vital signs hourly
C.Maintaining strict isolation
precautions
D.Monitoring serum peak and trough
levels
Loading Dose
 Large initial dose of a drug; commonly larger
than maintenance dose
 Given to achieve a rapid minimum effective
concentration

 Digitalization – loading dose for digitalis

preparation [ex: digoxin]
Heart Failure: Adults Rapid digitalization with a loading dose 400
to 600 mcg (0.4 to 0.6 mg) IV 500 to 750 mcg (0.5 to 0.75 mg) PO as
a single dose; additional doses of 100 to 300 mcg (0.1 to 0.3 mg) or
125 to 375 mcg (0.125 to 0.375 mg) PO may be given cautiously at 6-
to 8-h intervals until clinical evidence of an adequate effect is noted.
 SIDE EFFECTS
ADVERSE DRUG REACTIONS
TOXIC EFFECTS
Side Effects

 are physiologic effects not related to

desired drug effects.
 desirable or undesirable
Adverse Reaction

 Any unexplained, unintended, undesired,

unwanted or excessive response to a
medication, used at recommended doses
 Range from mild response to debilitating,
chronic or life-threatening problems
 Can be dose-related or sensitivity related
 Types of Adverse Reactions
1. Dose-related reactions: reactions to
the drug’s primary effect [ex: bleeding
from anticoagulant] or secondary effects
[ex: drowsiness from antihistamine] or
overdose
 can be prevented in most cases with careful
prescribing and administration
 Types of Adverse Reactions
2. Sensitivity-related reaction:
hypersensitivity or allergic response to a
drug or one of its components (can be
dose-related)
 In hypersensitivity or allergic reactions,
sensitized patient is exposed to a drug that
elicits an antigen-antibody reaction
 Reactions may be immediate (resulting in
anaphylaxis or urticaria) or delayed (serum
sickness)
 Types of Adverse Reactions
3. Iatrogenic effect: reaction that mimics
a pathogenic condition

 ex: GI irritation and bleeding with aspirin or

NSAIDs
 Types of Adverse Reactions
4. Toxicity reaction that occurs when drug
levels exceed the therapeutic range;
possibly causing additional adverse effects
 may develop because of overdosage resulting from
failure to consider hepatic impairment, renal function
or client’s age
 May result from patient misuderstanding the dosage
or administration instructions
 May require dosage modification
 Prevention: close monitoring therapeutic blood levels
 Types of Adverse Reactions
5. Idiosyncrasy an unaccepted abnormal
or peculiar response to a drug
Ex: a person who becomes nervous or
excited after being administered a
sleeping medication such as barbiturate

6. Miscellaneous reactions
DRUG INTERACTIONS
Drug Interactions

 Alterations of the pharmacokinetic,

pharmacodynamic, or pharmacotherapeutic
characteristics of drugs which affect overall
therapeutic effects.
 Types:
 Incompatibilities
 Pharmacokinetic interactions
 Pharmacodynamic interactions
Incompatibilities

 result from chemical or physical reactions

between 2 or more drugs
 may occur when preparing IV admixtures,
administering medications in an IV bolus
or piggyback, or mixing medications in a
syringe
 Usually seen as crystallization of a solution
or a change in color of the solution
Pharmacokinetic interactions

1. Altered drug absorption: may result

from changes in stomach pH, presence
or absence of food in the GIT, or the
presence of other drugs in the stomach.
2. Toxicity can occur when protein-bound
drugs compete for protein binding sites,
causing the drugs to displace one
another and circulate.
Pharmacokinetic interactions
3. Induction or inhibition of hepatic
metabolisms: may occur with increases
or decreases of some hepatically
metabolized drugs.
4. Altered drug excretion may be
planned or coordinated to enhance or
inhibit excretion of certain drugs [ex:
probenecid given w/ penicillin to delay
renal excretion & prolong the antibiotic’s
effect
Pharmacodynamic interactions

1. Additive effects
2. Synergism
3. Potentiation
4. Antagonistic effect
Additive Effect

 Combining 2 or more drugs to cause an

effect equal to the sum of their separate
effects
1+1=2

 Ex: aspirin + codeine = increased pain relief

Synergism

 Combining 2 or more drugs to cause an

effect greater than the sum of their
separate effects
1 + 1 = 3 or 5

 Ex: alcohol + barbiturate = coma or death

Potentiation

 One drug intensifies the action of another

a+b=B
 Ex: Vit D helps with the absorption and
action of calcium in the body
 Ex: promethazine (Phenergan) [antihistamine]
+ meperidine (Demerol) [narcotic analgesic]
= greater pain relief than meperidine alone
Antagonistic Effect

 combining 2 or more drugs to produce an

effect less than the sum of their separate
effects.
 Two drugs given together will have an
opposite effect on the body.
1+1=0
 Ex: antidote [narcan for nubain overdose]
Pharmacogenetics
 Effect of drug action that varies from a
predicted response because of genetic
factors or hereditary influence.
 Generic factors may alter the metabolism of
the drug; drug action may be enhanced or
diminished.
 ex: African Americans do not respond as
well as whites to some classes of
antihypertensive
Tachyphylaxis

 Drug tolerance to repeated administration

of a certain drug.
 Narcotics
 Laxatives
 Psychotropic drugs
Placebo Effect

 A psychological benefit from a compound

that may not have the chemical structure
of a drug but can produce the perceived
effect.
 Placebo- a substance or procedure that is
objectively without specific activity for the
condition being treated but has a
perceived effect
Summary
Nursing Assessment
 Recognize that drugs in the liquid form are
absorbed FASTER than those in solid form.

 Assess for S/Sx of toxicity when giving 2 drugs

that are HIGHLY protein bound.
 The drugs compete for protein-binding sites &
displacement of drug occurs.
 More free drugs is in circulation because
there are not enough protein-binding sites.
 Too much of a free drug can result in DRUG
TOXICITY
Nursing Assessment
 Identify side effects of drugs that are
nonspecific (same receptor at different tissue &
organ sites)
if nonspecific drugs are given in large
doses or at frequent intervals, many side effects
are likely to occur.

 Check peak and trough levels of drugs that have

a narrow therapeutic range.
If trough level is high, toxic effects can
result.
Nursing Intervention
 Advise client not to eat fatty food when taking
enteric coated drugs (fats can decreased
absorption).

 Check drug literature for protein-binding

percentage of the drug.
 Drugs with high protein-binding effect have a large
portion of drug bound to protein, which causes the
drug to become inactive until t is released from the
protein. The portion not bound to proteins is free ad
active drug,
Nursing Intervention
 Report to the physician if drugs with long half-
life (e.g., greater than 24hr) are give more than
once a day.
 Some drugs with a long half-life, such as the
anticoagulatn warfarin (Coumadin) can be more
dangerous than others and should be monitored
frequently.

 Monitor the therapeutic range of drugs that are

more toxic or have a narrow therapeutic range,
such as digoxin.
Cultural Consideration

 Be aware that individuals from some

cultures metabolize drugs different than
the general population.
 Assess for adverse reactions that may
result from the variation in metabolism.
Evaluation

 Evaluate the determinants that affect drug

therapy.
Determinants That Affect
Drug Therapy