General Principles

of Drug Action

Prepared by: MARIA ANDREA L. ENDENO

Learning Objectives:
➢ Differentiate the three phases of drug action.
➢ Explain the process of pharmacokinetics of drugs
➢ Discuss the process of pharmacodynamics of drugs
➢ Describe the nursing implications in the pharmaceutic, pharmacokinetic and
pharmacodynamic phases of drug action.
➢ Discuss the influences of the patient’s age/health status on the effects of drugs and drug
responses.
➢ Identify drug-related concerns during pregnancy and lactation and provide an explanation
of the physiologic basis for these concerns.
➢ Analyze the factors affecting responses to drugs
➢ Define drug–drug, drug–alternative therapy, drug–food, and drug–laboratory test
interactions.
➢ Differentiate the term adverse and toxic drug reaction and explain the clinical significance
of this types of drug reaction/effects
 1. PHARMACEUTIC 2.
Phase PHARMACOKINETIC
Phase
3
• Occur only for orally
taken drugs that are in • Absorption, Distribution,
solid form (tablet or Metabolism & Excretion
capsule)

Phases of
Drug 3. PHARMACODYNAMIC
Phase
Action • A biologic or physiologic
response occur
 PHARMACEUTIC PHASE

3 1st phase of drug action

80% of drugs are taken by
PHASES mouth
G.I. tract → drugs need to be in
of DRUG a solution before they can be
absorbed
ACTION NO PHARMACEUTIC PHASE
OCCURS – for drugs
administered parenterally
(subQ, IM, or IV routes)
 PHARMACEUTIC PHASE
• Disintegration – breakdown of solid form
of drug (tablet or capsule) into smaller
particles.

• Dissolution - dissolving of the smaller

particles in the GI fluid before
absorption.

• Rate of dissolution – refers to the time it

takes the drug to disintegrate and
dissolve to become available for the
body to absorb it.
• The more rapid the drug dissolution
→Faster drug absorption →Faster
onset of drug action
 PHARMACEUTIC PHASE

 Tablets are not 100% drugs!

 Excipients → fillers and inert substances used in drug preparation
 Allows drug to take particular size, shape or form
 Enhance drug dissolution
Additives: → Na and K salts
Penicillin → ↑ gastric acid → ↓ gastric pH → poorly
absorbed in G.I tract
Penicillin + Na/ K salts → inert composition → better
absorption
PHARMACEUTIC PHASE
 Pharmaceutic Phase

Tablet vs Liquid
 Pharmaceutic phase (con’t)

Enteric-Coated Tablets
Resist disintegration in the gastric acid of the stomach
Disintegration does not occur until the drug reaches the
alkaline environment of the small intestine.
They can remain in the stomach for a long time → their
EFFECT MAY BE DELAYED IN ONSET.
Enteric-coated tablets or capsules and sustained-
release (beaded) capsules– SHOULD NOT BE CRUSHED →
it would alter the place and time of absorption of the
drug.
Pharmaceutic phase (con’t)

 Extended-release tablets and capsules → release drug molecules in the

patient’s GI tract over a prolonged period of time.
• It ultimately prolongs drug absorption as well as duration of action.
• Examples of nomenclature: (identified by various capital letter
abbreviations attached to their names)
• SR - (slow release or sustained release),
• SA - (sustained action),
• CR - (controlled release),
• XL (extended length), and
• XT (extended time).
 Immediate-release dosage forms → which release all of the active
ingredient immediately upon dissolution in the GI tract.
 PHARMACEUTIC PHASE

Drugs in liquid form are more rapidly

available for G.I absorption than solids
Drugs disintegrate and dissolve faster
in acidic fluids (ph 1-2) than in alkaline
fluids
Young and elderly → less gastric acidic →
↓ drug absorption in the stomach
 Enteric coated tablets
dosage form, either tablet or
capsule, with special coating
PHARMACEUTIC which prevents
PHASE dissolution of drug particles in the
acidic environment of the
stomach
dissolution occurs in the alkaline
environment of the S. Intestines
 3 PHASES of DRUG ACTION

PHARMACOKINETIC PHASE
the process of drug movement to
achieve drug action.
Pharmacokinetics is the study of what
happens to a drug from the time it is
put into the body until the parent drug
and all metabolites have left the body.
 Pharmacokinetic Phase
It involves 4 processes:
Absorption,
Distribution,
Metabolism (or biotransformation), and
Excretion (or elimination).
Half-life - a measure of the rate at which drugs
are removed from the body.
 PHARMACOKINETIC PHASE:

Importance:
1. Help maximize beneficial effects and minimize harm
Intensity of the response is directly related to the concentration of
the drug at its site of action
To maximize beneficial effects: → achieve concentration high
enough to elicit desired response
To minimize harm → avoid unnecessarily high concentrations
How: Select the most effective route, dosage and schedule →
consider Pharmacokinetic factors
 PHARMACOKINETIC PHASE:

2. Medication Errors reduced

by understanding the reasons behind selection of
route, dosage and dosing schedule
less likely to commit errors
3. Question and challenge physician’s orders
DO NOT FOLLOW DOCTOR’S ORDERS BLINDLY!!!
present a rational argument to alter doctor’s
decision
need to understand pharmacokinetics
 PHARMACOKINETIC PHASE:

4. Knowledge of Pharmacokinetics can

Increase job satisfaction
working with medications is a significant
component of nursing practice

5. Decrease stress of nursing practice/

Increase intellectual and professional
satisfaction
→ demystify drug therapy
 Pharmacokinetic Phase
ABSORPTION
The primary pharmacokinetic factor
determining the length of time a drug
produces its effect
MOST DRUGS –> MUST BE ABSORBED FIRST
TO PRODUCE AN EFFECT
DRUGS ARE ABSORBED ACROSS THE:
1. Skin and associated mucous membranes
2. Membranes that lines the GI and Respiratory
tract
 Pharmacokinetic Phase
ABSORPTION
Definition of Terms:
BIOAVAILABILITY – % of the administered drug dose
that reaches the systemic circulation
FIRST-PASS EFFECT - the process by the drug passes
the liver first which reduces the bioavailability of the
drug to less than 100%.
BIOEQUIVALENT refers to two medications that have
the same bioavailability and same concentration of
active ingredient (e.g., a brand-name drug and the
same generic drug).
 ABSORPTION
Hepatic 1st pass – 1st pass effect
process by which drugs passes to the liver 1st
stomach → intestinal lumen → portal vein →
liver
in the liver: the drug may be metabolized into
an inactive form → excretion
Ex. Morphine, Warfarin Na
NTG/ Lidocaine → extensive 1st pass effect →
not given orally
 Pharmacokinetic Phase
ABSORPTION
 The movement of drug particles from the GI tract to body fluids by:
(1) Passive absorption - occurs mostly by diffusion (movement
from higher concentration to lower concentration); the
process of diffusion does not require energy to move across
the membrane

(2) Active absorption - requires a carrier such as an enzyme or

protein to move the drug against a concentration gradient;
Energy is required for active absorption.

(3) Pinocytosis - a process by which cells carry a drug across

their membrane by engulfing the drug particles
Pharmacokinetic Phase
ABSORPTION

The three major

processes for drug
absorption through
the gastrointestinal
membrane are
passive absorption,
active absorption,
and pinocytosis.
 Pharmacokinetic Phase
ABSORPTION
FACTORS INFLUENCE THE RATE OF DRUG ABSORPTION:
1) ROUTE OF ADMINISTRATION
▪ Drugs are most rapidly absorbed when given via:
▪ IV route--> IM route--> SQ route, and lastly, oral route.
▪ IM/SQ – absorption affected by perfusion to the
muscle/tissue, fat content of the muscle/tissue &
Temperature of the muscle/tissue (cold→
vasoconstriction→ decreases absorption)
▪ PO (Oral) – absorption affected by acidity of stomach,
length of time in the stomach & blood flow to GI tract
 FACTORS INFLUENCE THE RATE OF DRUG ABSORPTION:
1) ROUTE OF ADMINISTRATION (con’t)

▪ Per RECTAL (PR) – affected by perfusion to the rectum, lesions in

the rectum and length of time retained for absorption
▪ Per MUCOUS MEMBRANE (Sublingual, Buccal) – affected by
perfusion to the area, integrity of mucous membrane and
presence of food or smoking
▪ TOPICAL (skin) – affected by blood flow to the area and
integrity of the skin
▪ INHALATION – Perfusion to the area, integrity of lung lining and
ability to administer drug properly
 Pharmacokinetic Phase
ABSORPTION
FACTORS INFLUENCE THE RATE OF DRUG ABSORPTION:
2) SOLUBILITY OF THE DRUG
Some drugs are more soluble→ thus are absorbed more rapidly than
others.
Drugs in elixir/syrup formulation = absorbed faster than capsule/tablets
Drugs in higher dosages = (refers to Concentration)
↑ the dose (concentration = ↑ rate of diffusion
Drugs that are lipid soluble & nonionized are absorbed faster than
water-soluble and ionized drugs.
Water-soluble drugs need a carrier, either enzyme or protein, to
pass through the membrane.
Large particles pass through the cell membrane if they are
nonionized (have no positive or negative charge).
Degree of ionizations depends on the surrounding pH →Acids are
absorbed in an acidic environment; bases are absorbed faster in an
basic environment
 Pharmacokinetic Phase
ABSORPTION
FACTORS INFLUENCE THE RATE OF DRUG ABSORPTION:
3) THE PRESENCE OF CERTAIN BODY CONDITIONS
❑ LIPODYSTROPHY - atrophy of the subcutaneous tissue which occur
from repeated subcutaneous injections, inhibit absorption of drug
given in the site of lipodystrophy
❑ Drug absorption may also be altered in patients who have had
portions of the small intestine removed because of disease, (SHORT
BOWEL SYNDROME).
❑ BARIATRIC WEIGHT LOSS SURGERY - reduces the size of the stomach.
❑As a result, medication absorption can be altered→ stomach
contents are delivered to the intestines more rapidly than usual
after such surgery → GASTRIC DUMPING.
3) THE PRESENCE OF CERTAIN BODY CONDITIONS (con’t)
❑ SEPSIS AND EXERCISE - are examples of circumstances under which
blood flow to the GI tract is often reduced
❑The stomach and small intestine are highly vascularized. When blood
flow to this area is decreased, absorption may also be decreased.
❑ THE SPEED OF DIGESTIVE MOTILITY, SURFACE AREA, PH, EXPOSURE TO
ENZYMES IN THE DIGESTIVE TRACT AFFECTS ABSORPTION
Protein-based drugs such as insulin and growth hormones are
destroyed in the small intestine by digestive enzymes →decreased
absorption
Generally, drugs are both disintegrated and absorbed faster in
acidic fluids (pH of 1 or 2) rather than in alkaline fluids
Pts. have less gastric acidity (Very Young and very old Pt.)
 Stomach vs. Small intestine

Comparison of the small intestine and stomach

in relation to absorption

Stomach Small intestine

Total absorptive area 1 m2 200 m2

Blood flow 150 ml/min 1L/min
Permeability  
 Pharmacokinetic Phase
ABSORPTION
FACTORS THAT INFLUENCE THE RATE OF DRUG ABSORPTION
4) INTERACTIONS WITH FOODS AND OTHER MEDS:
❑Food in the GI tract - may interfere with the dissolution of
certain drugs.
❑Some drugs (Herbal wt loss products) →exert laxative effect→
decreases intestinal transit time →reducing drug absorption
❑Anticholinergic drugs slow GI transit time → may reduce the
amount of drug absorption and therapeutic effect for acid-
susceptible drugs that become broken down by stomach
acids.
ABSORPTION

Bioavailability
subcategory of absorption
% of the administered drug that reaches systemic circulation
ORAL Route: → Bioavailability occurs after absorption and
hepatic drug metabolism
< 100%
IV route: → 100%
Drugs with high Hepatic 1st pass → Bioavailability of only 20-
40% upon entering systemic circulation
To obtain desired effect → oral dose 3-5 times larger than
IV dose
 ABSORPTION

Factors affecting Bioavailability:

1. Drug form → capsule, tablet etc..
2. Route of administration
3. G.I. mucosa and motility
4. Food and other drugs
5. Changes in liver metabolism → Liver dysfunction or ↓ Hepatic
B.F.
 Drug primarily metabolized by the liver
↓
Liver dysfunction, Liver Disease, ↓ Hepatic B.F.
↓
ABSORPTION Less drug metabolized/ converted into inactive form
↓
↑ Bioavailability of the drug
↓
↑ drug concentration
↓
Drug accumulation
↓
Drug Toxicity
ABSORPTION

Rapid absorption → ↑ drug

concentration → Drug Toxicity

Slow absorption → limit bioavailability

of drug → ↓ serum drug concentration
 Pharmacokinetic Phase
DISTRIBUTION
Process by which the drug becomes available to body fluids and body tissues

▪ Involves the transport of drugs throughout

the body
▪ 3 factors that determine distribution to tissues:
▪ Blood flow to tissues
▪ The ability of the drug to exit the vascular system
▪ To a lesser extent, the ability of a drug to enter
cells
 DISTRIBUTION

• Reversible process between drug and

protein carriers
Bound vs. Unbound form
• Drugs can be distributed to:
 receptor sites (produce effect)
 tissue depots (storage)
 liver (metabolism)
 kidneys (excretion)
 Pharmacokinetic Phase
DISTRIBUTION
FACTORS THAT AFFECT DRUG DISTRIBUTION
1. BLOOD FLOW TO TISSUES
The rate at which drug is delivered to that tissue is
determined by blood flow to that tissue
▪ AMOUNT OF BLOOD FOW TO BODY TISSUES – simplest factor
determining distribution of drugs
▪ HEART, LIVER, KIDNEY, BRAIN → Receives the most blood
supply
▪ SKIN, BONE, ADIPOSE TISSUE → receives lower blood
supply →therefore it is more difficult to deliver high
concentrations of drugs to these areas
1) BLOOD FLOW TO TISSUES (con’t)
Regional blood flow is the limiting factor to drug distribution
which can be noted in 2 pathologic process :
A) Abcesses - pus-filled internal vessels that has no
blood vessels—pus has to be drained for drug therapy
to be effective
B) Tumor – limited blood supply to the core of the tumor
→making them resistant to therapy
ABSCESS
Gangrenous foot

TUMOR
 DISTRIBUTION
Abscess/ Exudates/ Tumors
↓
↓ Blood Flow to area
↓
Hinder Drug distribution
↓
↓ level of circulating drug to area
↓
↓ Drug action
↓
↑ serum level of drug needed (Higher doses)
 Pharmacokinetic Phase
DISTRIBUTION
BLOOD BRAIN BARRIER – refers to the unique anatomy of
capillaries in the CNS
These are tight junctions between cells that compose the
walls of most capillaries in the CNS → JUNCTIONS are so tight
that they prevent drug passage → drugs must be able to
pass through them to reach the site of action
ONLY DRUGS THAT ARE LIPID SOLUBLE AND HAVE A
TRANSPORT SYTEM CAN CROSS THE BBB to a significant
degree
 Pharmacokinetic Phase
DISTRIBUTION
Blood brain barrier (cont’)
P-glycoprotein – another protective component of the
BBB in the CNS→ it is transporter that pumps a variety of
drugs out of the cells and back to the blood→ limiting the
access to the brain
ADVANTAGES: protects brain from injury by potentially toxic
substances
DISADVANTAGES: a significant obstacle to therapy in CNS
disorders
not yet fully developed at birth → thus increases risk of
children to develop CNS infection
 Pharmacokinetic Phase
DISTRIBUTION
FETAL-PLACENTAL BARRIER (Placental drug transfer)
 Membranes of placental separate the maternal from the fetal circulation
 Serves an important protective function, because it prevents potentially
harmful substances from passing from the mothers bloodstream to the fetus.
 Does not constitute an absolute barrier to the passage of drugs
 Accordingly NONIONIZED, LIPID-SOLUBLE compounds readily pass
 Substances such as alcohol, cocaine, caffeine, and certain prescription
medications, however, easily cross the placental barrier and can potentially
harm the fetus.
 A patient who is pregnant should not take any prescription medication, over-
the- counter (OTC) drug, or herbal therapy without first consulting with a health
care provider.
 Pharmacokinetic Phase
DISTRIBUTION
PROTEIN BINDING
 Protein-binding effect
ability of drug to bind with a specific protein receptor in the body
 Drug-Protein complexes are too large to cross capillary
membranes→ Drugs bound to protein are pharmacologically
inactive (not available for distribution).
Example: warfarin (Coumadin), are highly bound; 99% of the
drug in the plasma is bound in drug-protein complexes and is
unavailable to reach target cells
 Free drugs - (drugs not bound to protein) are active and can cause
a pharmacologic response.
 DISTRIBUTION

PLASMA CHON BINDING - drugs are

bound with varying degrees (%) to CHON
1. 89% ↑ - High CHON Bound
2. 61%-89 % - Moderately High CHON
Bound
3. 30-60% - Moderately CHON Bound
4. ↓ 30% - Low CHON Bound
 DISTRIBUTION
INACTIVE DRUG
→ portion of drug bound to CHON
→ not available to receptors
FREE DRUGS – portion of drug that remains
unbound
→ ACTIVE DRUG
→ can cause pharmacologic response
* ↓ Free drug iN Circulation → release of drugs
bound to CHON → maintain balance of free drug
 Pharmacokinetic Phase
DISTRIBUTION
PROTEIN BINDING (con’t)
 Drug-drug and drug-food interactions - may occur when one drug
displaces another from plasma proteins.
Drugs and other chemicals compete with one another for plasma
protein binding sites, and some agents have a greater affinity for these
binding sites than other agents..
The displaced medication can immediately reach high levels in the
bloodstream and produce adverse effects.
Examples: Drugs such as Aspirin or valproates, for example, displace
Coumadin from the drug-protein complex, thus raising blood levels of
free Coumadin and dramatically enhancing the risk of hemorrhage
 DISTRIBUTION
2 Highly CHON Bound Drugs
↓
Given Concurrently
↓
Compete for CHON Binding Sites
↓
More available free drug released into the
circulation
↓
Drug accumulation
↓
Drug Toxicity
 DISTRIBUTION
↓ CHON level
(Kidney, Liver Disease, Malnutrition, low Serum
Albumin level, elderly)
↓
↓ # of CHON Binding sites
↓ ↓
↓ level of Inactive Drug (Drugs bound to CHON)
↑ amount of free drug in plasma
↓
Drug accumulation
↓
Drug Toxicity
 PROTEIN BINDING AND HALF LIFE OF
DRUGS

HIGHLY CHON BOUND DRUGS (>89%)

DRUGS % T ½ (H)
DIAZEPAM 98 30-80
FUROSEMIDE 95 1.5
IBUPROFEN 98 2-4
RIFAMPICIN 89 2
DIGITOXIN 90 8
PROPRANOLOL 92 4
 PROTEIN BINDING AND HALF LIFE OF
DRUGS

MODERATELY HIGHLY CHON BOUND DRUGS (61-89%)

DRUGS % T ½ (H)

ERYTHROMYCIN 70 3

PHENYTOIN 88 10-40

QUINIDINE 70 6

TRIMETHOPRIM 70 11
 PROTEIN BINDING AND HALF LIFE OF
DRUGS

MODERATELY CHON BOUND DRUGS (30-60%)

DRUGS % T ½ (H)
ASPIRIN 49 0.25-2
LIDOCAINE 50 2
MEPERIDINE 56 3
THEOPHYLLINE 60 9
 PROTEIN BINDING AND HALF LIFE OF
DRUGS

LOW CHON BOUND DRUGS (<30%)

DRUGS % T ½ (H)
AMIKACIN 4-11 2-3
AMOXICILLIN 20 1-1.5
CEPHALEXIN 10-15 0.5-1.2
DIGOXIN 25 36
NEOSTIGMINE 15-25 1-1.5
 DISTRIBUTION

DRUG RESERVOIRS
→ non-specific tissue binding sites
→ drugs accumulate in certain areas
(fats, tissues, muscles, bones, liver, eye
tissues)
Drugs transported to Drug Reservoirs
are released more slowly into the body
than drugs evenly distributed at the
start.
 DISTRIBUTION
↓ CHON level
↓
↓ # of CHON Binding sites
↓
Transport of Free drugs to Drug Reservoirs
↓
Maintain balance of free drug in circulation
↓
↓ circulating free drug
↓
Release of Active drug from reservoir
Theoretical volume – also called the volume of distribution is
sometimes used to describe the various areas in which
drugs may be distributed.
These areas, or compartments, may be the:
blood (intravascular space),
total body water,
body fat, or
Other body tissues and organs.
Drug that is highly water soluble(hydrophilic) - will have a
smaller volume of distribution and high blood
concentrations.
Fat-soluble drugs (lipophilic) - have a larger volume of
distribution and low blood concentrations.
 Pharmacokinetic Phase
DISTRIBUTION
FACTORS THAT AFFECT DRUG DISTRIBUTION
3. ENTERING THE CELLS
Some drugs must enter cells to reach their sites of action, and
practically all drugs must enter cells to undergo metabolism
and excretion.
The factors that determine the ability of a drug to cross cell
membranes are the same factors that determine the passage
of drugs across all other membranes, namely:
Lipid solubility,
Presence of a transport system, or both.
 DRUG DISTRIBUTION
IM IV ABSORBED DRUG

ORAL
drug enters the bloodstream
SITES OF
TISSUE ACTION
RESERVOIR (Receptor) DRUG LEAVES THE
BLOODSTREAM

GIT FREE DRUG drug attaches to receptor sites

LIVER (ACTIVE) KIDNEY

CREATING AN EFFECT
BINDS TO PLASMA  RECEPTOR SITES – active
PROTEINS sites or the sites of action –
once drug attaches to
receptor (active) sites→
METABOLITE therapeutic effect
(INACTIVE)  ACCEPTOR SITES – inactive
sites→ binding of drug to
EXCRETION EXCRETION acceptor (inactive) sites will
(stool) BLOODSTREAM (urine) not produce any effects
Pharmacokinetic Phase
DISTRIBUTION
 DISTRIBUTION

NURSING CONSIDERATION:
*Check the patient’s plasma
CHON and albumin levels, to
prevent drug toxicity which could
be life threatening.
 Pharmacokinetic Phase
METABOLISM (biotransformation)
A.k.a. biotransformation
Defined as the chemical alteration of drug structure.
process by which a drug is converted by the liver to
inactive compounds through a series of chemical
reactions →purpose is to make the chemicals less
active and more easily excreted from the body
Most drug metabolism takes place in the liver
The kidneys, lungs, plasma, and intestinal mucosa also
aid in the metabolism of drugs.
 2 main type of Metabolic Reactions
A. “Destructive” (Phase I) Reaction
1. HYDROLYSIS – “lysis” – break apart
 H20 is incorporated into a chemical substance (‘splitting the molecule”)
2. OXIDATION – either you remove hydrogen or add oxygen
 Hydrogen atoms are removed from the molecule/oxygen is added
3. REDUCTION – either you add hydrogen or remove oxygen
 Hydrogen atoms are attached to the molecule
4. DEAMINATION – nitrogen atoms are removed from the molecule
B. “Conjugate” (Phase II) Reaction
 Transferase enzymes join GLUCORONIC ACID (an amino acid) to alcohol, organic acids
and amines that makes them water soluble
*** METABOLIC REACTIONS GENERALLY TRANSFORMS THE DRUGS INTO INACTIVE FORM
and/or MAKE IT MORE WATER-SOLUBLE TO FACILITATE EXCRETION THROUGH THE KIDNEYS***
METABOLITE – refers to the transformed Drug
FACTORS THAT AFFECT THE RATE OF DRUG METABOLISM
 AGE
Very young – immature liver
Very old – too mature liver/ does not work well anymore
 Both cannot metabolize drug quickly → thus, they need lower dosage of drugs

DRUG TOLERANCE
Taking drugs every→ liver enzymes produces more enzymes than normal→
Increase metabolizing activity of the liver → increased drug tolerance (needs
higher and higher amount/dosage to achieve/feel the effect)
LIVER DISEASE
(see next slide)
 Pharmacokinetic Phase
METABOLISM (biotransformation)
Patients with liver disease (cirrhosis and hepatitis)
alter drug metabolism by inhibiting the drug
metabolizing enzymes in the liver.
When the drug metabolism rate is decreased → excess
drug accumulation can occur → lead to toxicity.
Thus, they may
require lower dosages of a drug detoxified by the liver, or
the primary care provider may select a drug that does not
undergo a biotransformation by the liver.
Frequent liver function tests are necessary when liver disease
is present.
 Drug
↓
METABOLISM
Site of absorption
↓
Bloodstream
↓
Portal Vein
↓
Liver (Primary site of metabolism)
↓
Hepatic/ Liver enzymes (CHON)
↓
Inactivates drug components
↓
Break down drug particles
↓
Detoxification (Removal of harmful/toxic components of drugs)
↓
Transformation of drugs to inactive metabolites/ water soluble substances
↓
Bloodstream → Kidneys → Excretions
Hepatic Drug-Metabolizing Enzymes
•Drug metabolism is performed by the hepatic
microsomal enzyme system (aka P450 system)
•It refers to cytochrome P450, a key component of
this enzyme system.
•It is not a single molecular entity, but rather a group
of 12 closely related enzyme families.
•Three of the cytochrome P450 (CYP) families—
designated CYP1, CYP2, and CYP3—metabolize
drugs.
•The other nine families metabolize endogenous
compounds (e.g., steroids, fatty acids).
half-life (t½) of a drug - the time it takes for one half of the
drug concentration to be eliminated.
Metabolism and elimination affect the half-life of a drug.
A short half-life - 4 to 8 hours
A long one - 24 hours or longer.
If the drug has a long half-life (such as digoxin at 36 hours), it
takes several days for the body to completely eliminate the
drug.
By knowing the half-life, the time it takes for a drug to reach
a steady state of serum concentration can be computed.
A drug goes through several half-lives before more than
90% of the drug is eliminated.

Administration of the drug for three to five half-lives

saturates the biologic system to the extent that the
intake of drug equals the amount metabolized and
excreted.
 DRUG Half-Life (t ½)

1 hour
Penicillin

Acetaminophen 3 hours

4 hours
Morphine

8 hours
Tetracycline

Pentobarbital 30 hours

Phenobarbital 80 hours

Digitoxin 4 days
 METABOLISM
Importance of t ½ :
1. Able to compute time it takes for a drug to
reach a steady state of serum
concentration.
determines frequency of drug administration
2. Administration of the drug for 3-5 t ½
saturates the Biologic system to the extent that
intake of drug equals amount metabolized
and excreted.
 METABOLISM
Liver/ Kidney Dysfunction
↓
Prolonged half life of a drug
↓
↓ Metabolism and Elimination of Drug
↓
If drug is taken continually…
↓
Drug accumulation → Drug Toxicity
Six (6) Therapeutic Consequences of Drug Metabolism
1) Accelerated renal excretion of drugs
most important consequence
Kidneys - the major organs of drug excretion, are unable to
excrete drugs that are highly lipid soluble.
Hence, by converting lipid-soluble drugs into more
hydrophilic (water-soluble) forms, metabolic conversion can
accelerate renal excretion of many agents.
 Ex. highly lipid-soluble drugs(e.g., thiopental)-complete
renal excretion would take years were it not for their
conversion into more hydrophilic forms
Six (6) Therapeutic Consequences of Drug Metabolism
1) Accelerated renal excretion of drugs (con’t)
 Two important mechanisms , panels 1A and 1B.
In panel 1A, a simple structural change (addition of a hydroxyl
group) converts pentobarbital into a more polar (less lipid-soluble)
form.
In panel 1B, a highly lipophilic drug (phenytoin) is converted into a
highly hydrophilic form by undergoing glucuronidation → a process
in which a hydrophilic glucose derivative (glucuronic acid) is
attached to phenytoin.
As a result of glucuronidation, phenytoin is rendered much more
water soluble, and hence can be rapidly excreted by the kidneys.
 ENTEROHEPATIC RECIRCULATION
• a repeating cycle in which the drug moves
from the liver into the duodenum (via the
bile duct) and back to the liver (via the
portal blood)
• this process is limited to drugs that first
undergone hepatic glucoronidation
Six (6) Therapeutic Consequences of Drug Metabolism
2) Drug Inactivation
Drug metabolism can convert pharmacologically active
compounds to inactive forms.
This process is illustrated by the conversion of procaine (a local
anesthetic) into paraaminobenzoic acid (PABA), an inactive
metabolite
Six (6) Therapeutic Consequences of Drug Metabolism
3) Increased Therapeutic Action
 Metabolism can increase the effectiveness of some drugs.
 This concept is illustrated by the conversion of codeine into morphine.
The analgesic activity of morphine is so much greater than that of
codeine that formation of morphine may account for virtually all the
pain relief that occurs following codeine administration.
Six (6) Therapeutic Consequences of Drug Metabolism
4) Activation of Prodrugs
prodrug - a compound that is pharmacologically inactive as
administered and then undergoes conversion to its active
form via metabolism.
Activation of a prodrug is illustrated by the metabolic
conversion of fosphenytoin to phenytoin
Six (6) Therapeutic Consequences of Drug Metabolism
5-6) Increased or Decreased Toxicity
• By converting drugs into inactive forms, metabolism can decrease toxicity.
• Conversely, metabolism can increase the potential for harm by converting relatively safe
compounds into forms that are toxic.
• Increased toxicity is illustrated by the conversion of acetaminophen [Tylenol, others] into a
hepatotoxic metabolite (N-acetyl-p-benzoquinone)
• It is this product of metabolism, and not acetaminophen itself, that causes injury
when acetaminophen is taken in overdose
 Pharmacokinetic Phase
METABOLISM (biotransformation)
Special Considerations in Drug Metabolism
A. Age
Drug-metabolizing capacity
Infants is limited
Liver does not develop its full capacity to
metabolize drugs until about 1 year after birth.
Older adults commonly decreased.
Drug dosages may need to be reduced to
prevent drug toxicity.
 Special Considerations in Drug Metabolism
2. Induction and Inhibition of Drug-Metabolizing Enzymes
 Drugs may be P450 substrates, P450 enzyme inducers, or P450
enzyme inhibitors.
Often a drug may have more than one property.
For example, a drug may be both a substrate and an inducer.
 Substrates - Drugs that are metabolized by P450 hepatic enzymes,
rate at which they are metabolized is affected by drugs that act as
P450 inducers or inhibitors.
• Inducers - drugs that act on the liver to increase rates of drug
metabolism (Induction - process of stimulating enzyme synthesis)
• Inhibitors - drugs that act on the liver to decrease rates of drug
metabolism (the process is known as inhibition)
 Special Considerations in Drug Metabolism
3. First-Pass Effect (hepatic first pass)
refers to the rapid hepatic inactivation of
certain oral drugs.
Drugs absorbed from the GI tract → carried
directly to the liver via the hepatic portal vein.
If capacity liver to metabolize a drug is extremely
high, that drug can be completely inactivated on its
first pass through the liver.
As a result, no therapeutic effects can occur.
 Special Considerations in Drug Metabolism
4. Nutritional Status
 Hepatic drug-metabolizing enzymes require a number of cofactors to
function.
 In the malnourished patient, these cofactors may be deficient, causing
drug metabolism to be compromised.
5. Competition Between Drugs
 When two drugs are metabolized by the same metabolic pathway, they
may compete with each other for metabolism, and may, thereby,
decrease the rate at which one or both agents are metabolized.
 If metabolism is depressed enough, a drug can accumulate to
dangerous levels.
 Pharmacokinetic Phase
ELIMINATION
Excretion - elimination or removal of drugs from the
body
After the liver renders drugs inactive - the kidney
excretes the inactive compounds from the body.
some drugs are excreted unchanged by the kidney
without liver involvement.
Drugs and their metabolites can exit the body in urine,
bile, sweat, saliva, breast milk, and expired air.
Most important organ for drug excretion - kidney.
 Pharmacokinetic Phase
ELIMINATION
The rate at which medications are excreted determines the
concentration of the drugs in the bloodstream and tissues.
the concentration of drugs in the bloodstream determines
their duration of action
Pathologic states (liver disease or renal failure) → increase
the duration of drug action in the body because they
interfere with natural excretion mechanisms.
Dosing regimens must be carefully adjusted in these
patients.
 Pharmacokinetic Phase
ELIMINATION
Patients with kidney disease - require a dosage reduction
and careful monitoring of kidney function.
Monitoring of serum creatinine and BUN as well as the
creatinine clearance; Ideally GFR are monitored.
Children have immature kidney function and may require
dosage reduction and kidney function tests.
Similarly, older adults have diminished kidney function
and require careful monitoring and lower dosages.
 Pharmacokinetic Phase
ELIMINATION

Condition of excreting organs

Kidney Disease → ↓ Blood Flow (Hepatic
insufficiency) → ↓ GFR → ↓ Renal Tubular
Secretion → ↓ Drug Excretion → Drug
accumulation → Drug Toxicity → Severe
Adverse drug reactions
 Half-Life
 Half-life refers to the time required for the body to eliminate 50% of
the drug.
 It is important in planning the frequency of dosing.
Drugs with a short half-life (2–4 hours) need to be administered
frequently, Drug with a long half-life (21–24 hours) requires less
frequent dosing.
It takes five to six half-lives to eliminate approximately 98%
of a drug from the body
 Half-life - fairly stable, But patients with liver or kidney disease may
have problems excreting a drug → increases the half-life and
increases the risk of toxicity.
 Factors affecting
EXCRETION
Urine pH (4.5 – 8)
• Acid urine – promotes elimination of weak
base drugs
• Alkaline urine – promotes elimination of
weak acid drugs
Examples: Aspirin (weak acid) → excreted rapidly
in alkaline urine
Overdose of Aspirin → Alkalinize urine → Give
NaHCO3 → Potentiates excretion of aspirin
 EXCRETION

CREATININE CLEARANCE (85-135

ml/min)
→ most accurate test to
determine renal function
→ varies with age and gender
→ Elderly / Females = ↓ Creatinine
Clearance
 EXCRETION

Creatinine – metabolic byproduct of

cells and muscles, that is excreted
by the kidneys
↓ GFR
↓
↑ Serum Creatinine Level
↓
↓ Urine Creatinine Clearance
Pharmacokinetic Phase
EXCRETION (elimination)
 Pharmacokinetic Phase
EXCRETION (elimination)
Steps in Renal Drug Excretion
Urinary excretion is the net result of three processes:
(1) GLOMERULAR FILTRATION,
begins at the glomerulus of the kidney tubule.
moves drugs from the blood into the tubular
urine.
Because large molecules are not filtered,
drugs bound to albumin remain behind in the
blood.
 Pharmacokinetic Phase
EXCRETION (elimination)
(2) PASSIVE TUBULAR REABSORPTION,
lipid-soluble drugs can readily cross the membranes undergo
passive reabsorption from the tubule back into the blood.
In contrast, drugs that are not lipid soluble (ions and polar
compounds) remain in the urine to be excreted.
(3) ACTIVE TUBULAR SECRETION
There are active transport systems in the kidney tubules that pump
drugs from the blood to the tubular urine
two primary classes of pumps
one for organic acids and one for organic bases.
In addition, tubule cells contain P-glycoprotein, which can
pump a variety of drugs into the urine.
 Pharmacokinetic Phase
EXCRETION (elimination)
 BILIARY EXCRETION.
 Drugs that are eliminated by this route are taken up by the liver, released into the bile, and
eliminated in the feces.
 Once fat-soluble drugs, are in the bile, they may be reabsorbed into the bloodstream,
returned to the liver, and again secreted into the bile, a process known as enterohepatic
recirculation.

 RESPIRATORY EXCRETION
 The rate of respiratory excretion is dependent on factors that affect gas exchange, including
diffusion, gas solubility, and pulmonary blood flow.
 The elimination of volatile anesthetics following surgery is primarily dependent on respiratory
activity
 The respiratory removal of water-soluble agents such as alcohol is more dependent on blood
flow to the lungs
 Pharmacokinetic Phase
EXCRETION (elimination)
Factors that can affect drug excretion.
Liver or kidney impairment
Blood flow
Degree of ionization
Lipid solubility
Drug Protein complexes.
Metabolic activity
Acidity or alkalinity (pH)
Respiratory, glandular or biliary activity
In Summary….
DRUG

Absorption
Metabolic sites Receptor sites

Distribution
Effect
Plasma
Free Drug  Bound Drug

Excretion sites Tissue Depots

 3 PHASES of DRUG ACTION

 PHARMACODYNAMIC PHASE
the study of the way drugs affect the body.
Drug response can cause a primary or secondary physiologic
effect or both.
PRIMARY EFFECT is desirable, and
SECONDARY EFFECT may be desirable or undesirable.
Example :
diphenhydramine (Benadryl) - an antihistamine.
Primary effect - Treat the symptoms of allergy
Secondary effect - CNS depression - causes drowsiness.
PHARMACODYNAMIC PHASE
 FREQUENCY DISTRIBUTION CURVE
 a graphical representation of the number of patients responding to
a drug action at different doses.
 Peak of the curve - indicates the largest number of patients
responding to the drug.
 curve does not show the magnitude of response, only whether
a measurable response occurred among the patients. (ex.
Antihypentensive medication will call a drop of at least 20
mmHg from baseline of SBP and DBP)
 MEDIAN EFFECTIVE DOSE (ED50) - The dose in the middle of the
frequency distribution curve
 It is the dose required to produce a specific therapeutic response
in 50% of a group of patients.
 Drug guides sometimes report the ED50 as the average or
standard dose.
PHARMACODYNAMIC PHASE
 Dose Response and Maximal Efficacy
 Dose response - the relationship between the minimal versus the
maximal amount of drug dose needed to produce the desired
drug response
 Maximum drug effect - maximal efficacy, which is present in all
drugs
 Onset, Peak, and Duration of Action
 ONSET OF ACTION -the time it takes to reach the minimum
effective concentration (MEC) after a drug is administered
 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 three parameters of drug action:
the onset of drug action, peak action, and duration of action.
 Uses T (time) with subscripts (e.g., T, T , Tз).
2
 PHARMACODYNAMIC PHASE
RECEPTOR THEORY
 Four (4) receptor families:
 (1) kinase-linked receptors - Drug binding is on the cell surface.
 The drug activates the enzyme (inside the cell), and a response is initiated
 (2) ligand-gated ion channels - The channel spans the cell membrane and, with
this type of receptor, the channel opens, allowing for the flow of ions into and
out of the cells.
 The ions are primarily sodium and calcium
 (3) G protein–coupled receptor systems - There are three components to this
receptor response: (1) the receptor, (2) the G protein that binds with guanosine
triphosphate (GTP), and (3) the effector that is either an enzyme or an ion channel.

 (4) nuclear receptors - Found in the cell nucleus (not on the surface) of the cell
membrane.
 Activation of receptors through the transcription factors is prolonged.
 Mechanisms of Drug Action

1. Interaction with receptors

2. Interaction with enzymes
Enzyme induction
Enzyme inhibition
→ ACE inhibitors, Carbidopa in
Sinemet
 Mechanisms of Drug Action
3. Interaction with DNA/RNA
Folic acid analogs (methotrexate) –
inhibits dihydrofolate reductase
Purine analogs (6-MP, thiguanine) –
anatagonize purine synthesis
Pyrimidine analogs (5-FU) – inhibits
thymidine synthetase
 Mechanisms of Drug Action

Intercalating agents (anthracylines,

dactinomycin)
Alkylating agents (nitrogen mustards,
nitrosoureas)
Antimetabolites
*** inhibit DNA replication and function
 Mechanisms of Drug Action

Drugs that produce free radicals

(bleomycin, anthracyclines)
Drugs that inhibit topoisomerase
(topotecan, epipodophyllotoxins)
*** damage and destroy DNA
 Mechanisms of Drug Action

4. Inhibition of protein synthesis

Tetracyclines
Chloramphenicol
Erythromycin
Aminoglycosides
 Mechanisms of Drug Action

5. Interaction with cell membranes

Digitalis glycosides – inhibits Na-K pump
Local anesthetics – interferes with
membrane permeability to Na and K
Omeprazole, Lansoprazole – inhibit H/K
pump (located in parietal cell
membranes)
 Pharmacodynamic Phase
ALTERATION IN CELLULAR FUNCTION

• Receptor-Mediated Drug Action

• The function of a cell alters when a drug interacts with
a receptor cell.
• A receptor - a specialized macromolecule (a large
group of molecules linked together) that attaches
or binds to the drug molecule.
• This alters the function of the cell and produces the
therapeutic response of the drug.
 Pharmacodynamic Phase
ALTERATION IN CELLULAR FUNCTION
• Receptor-Mediated Drug Action (con’t)
1. Agonists - drugs that bind with a receptor to
produce a therapeutic response.
❑ Partial binding of drug-receptor - some
although slight, therapeutic response.
❑ Partial agonists - drugs that have some
drug receptor fit and produce a response
but inhibit other responses
 Receptor-Mediated Drug Action (con’t)

2. Antagonists - join with a receptor to prevent the action of an

agonist.
❑ When the antagonist binds more tightly than the
agonist to the receptor, the action of the antagonist is
strong.
❑ Drugs that act as antagonists produce no
pharmacologic effect.
❑ Ex. Narcan - a narcotic antagonist that completely
blocks the effects of morphine, including the
respiratory depression.
❑ It is useful in reversing the effects of an overdose of
narcotics.
 Pharmacodynamic Phase
ALTERATION IN CELLULAR FUNCTION
• Receptor-Mediated Drug Effects
• The number of available receptor sites influences the effects of a drug.
• If only a few receptor sites are occupied, although many sites are
available, the response will be small.
• If the drug dose is increased, more receptor sites are used and the
response increases.
• If only a few receptor sites are available, the response does not
increase if more of the drug is administered.
• However, not all receptors on a cell need to be occupied for a drug to
be effective.
• Some extremely potent drugs are effective even when the drug
occupies few receptor sites.
 PHARMACODYNAMIC PHASE
Agonists and Antagonists
 AGONIST - Drugs that produce a response
 Epinephrine (Adrenalin) stimulates beta 1 and beta receptors, so it is an agonist.
 ANTAGONIST - drugs that block a response
 Atropine, an antagonist, blocks the histamine (H2) receptor, thus preventing
excessive gastric acid secretion.
 Nonspecific and Nonselective Drug Effects
 NONSPECIFIC DRUGS - Drugs that affect various sites and have properties of non
specificity
Drugs that evoke a variety of responses throughout the body have a nonspecific
response
 NONSELECTIVE DRUGS - Drugs that affect various receptors are or have properties of
nonselectivity.
Drugs that produce a response but do not act on a receptor may act by
stimulating or inhibiting enzyme activity or hormone production.
NON SPECIFIC DRUG NON SELECTIVE DRUG
 PHARMACODYNAMIC PHASE
Categories of Drug Action
(1) STIMULATION OR DEPRESSION
In drug action that stimulates - the rate of cell activity or
the secretion from a gland increases.
In drug action that depresses - cell activity and
function of a specific organ are reduced.
(2) REPLACEMENT
Replacement drugs such as insulin replace essential
body compounds.
 PHARMACODYNAMIC PHASE

Categories of Drug Action

(3) INHIBITION OR KILLING OF ORGANISMS
Drugs that inhibit or kill organisms interfere with
bacterial cell growth (e.g., penicillin exerts its
bactericidal effects by blocking the synthesis of the
bacterial cell wall).
(4) IRRITATION
Drugs also can act by the mechanism of irritation
(e.g., laxatives irritate the inner wall of the colon,
thus increasing peristalsis and defecation).
 Important PD terms

• Idiosyncrasy - unusual response to a drug

• Tolerance -  dose is given to produce effect
• Therapeutic index - measure of a drugs safety
- LD50/ED50
• Potency - relates to dose/conc to produce effect
• Efficacy - relates to maximal response
PHARMACODYNAMICS
 Therapeutic Index and Therapeutic Range
(Therapeutic Window)
THERAPEUTIC INDEX (TI) - estimates the
margin of safety of a drug through the use
of a ratio that measures the effective
(therapeutic) dose (ED) in 50% of people
(ED50) and the lethal dose (LD) in 50% of
people (LD50)
The closer the ratio is to 1, the
greater the danger of toxicity
PHARMACODYNAMICS

 THERAPEUTIC RANGE
(THERAPEUTIC WINDOW) OF A
DRUG - concentration in
plasma is the level of drug
between the minimum
effective concentration (MEC)
in the plasma for obtaining
desired drug action and the
minimum toxic concentration
(MTC) (the toxic effect).
 PHARMACODYNAMICS
Peak and Trough Drug Levels
 Peak drug levels - indicate the rate of absorption of the drug
 the highest plasma concentration of drug at a specific time
 If a peak drug level is ordered, a blood sample should be drawn at the proposed peak time,
according to the route of administration.
 Trough drug levels - indicate the rate of elimination of the drug.
 The lowest plasma concentration of the drug
 Trough levels are drawn immediately before the next dose of drug is given, regardless of route
of administration.
 PHARMACODYNAMICS
Loading Dose
a large initial dose of drug is given to achieve a rapid
minimum effective concentration in the plasma, when
immediate drug response is desired.
After a large initial dose, a prescribed dosage per day is
ordered.
Digoxin (Digitek, Lanoxicaps, Lanoxin), a digitalis preparation,
requires a loading dose when first prescribed.
Digitalization is the process by which the minimum effective
concentration level for digoxin is achieved in the plasma within a
short time.
 Pharmacodynamic Phase
ALTERATION IN CELLULAR ENVIRONMENT
Physical changes in the cellular environment include:
• Changes in osmotic pressures - mannitol → it produces a change in
the osmotic pressure in brain cells, causing a reduction in cerebral
edema.
• Lubrication – sunscreen→ acts by altering the cellular environment
by lubrication.
• Absorption - activated charcoal → administered orally to absorb a
toxic chemical ingested into the gastrointestinal tract
• Changes in the conditions on the surface of the cell membrane –
docusate (stool softerner) → has emulsifying and lubricating activity
that causes a lowering of the surface tension in the cells of the
bowel, permitting water and fats to enter the stool. → this softens the
fecal mass, allowing easier passage of the stool
 Pharmacodynamic Phase
ALTERATION IN CELLULAR ENVIRONMENT
Chemical changes in the cellular
environment include:
▪ Inactivation of cellular functions
▪ The alteration of the chemical
components of body fluid, such as a
change in the pH – antacids →
neutralize gastric acidity in patients
with peptic ulcers
 EFFECTS OF DRUGS
Other ways of describing the effects of drugs
Local effects – acts on the site of application (e.g.
sunscreen on skin)
Systemic effects – drugs taken into body---circulated
and absorbed into the bloodstream---eventually
eliminated from the body
Most drugs are given for this effect
Immediate effects – given in acute problems such as
pain or infection
Long term effects – given to relieve s/sx of chronic
disorder
Many drugs are given for this effects
 UNINTENDED RESPONSES TO DRUGS

SIDE EFFECT – unavoidable “secondary drug effect”

produced at therapeutic doses
Usually predictable and may be either harmless or potentially
harmful.
Usually tolerated
Example:
digitalis - increases the strength of myocardial contractions
(desired effect), but it can have the side effect of inducing
nausea and vomiting
Gastric irritation caused by aspirin (Acetyl Salicylic Acid)
 UNINTENDED RESPONSES TO DRUGS

ADVERSE DRUG REACTIONS – Undesired response to a

drug; may range from mild to life threatening
more severe side effects, may justify the discontinuation of a
drug.
a.TOXICITY
b.ALLERGIC REACTION
c.IDIOSYNCRATIC REACTION

****Nurses should monitor for dose-related side or adverse effects and

report these to the health care provide for possible discontinuation of
the drug or change of dosage****
 Types of Adverse Drug Reaction
 DRUG TOXICITY - (harmful effects of a drug on an organism or
tissue) results from:
over dosage,
ingestion of a drug intended for external use, or
build-up of the drug in the blood because of impaired
metabolism or excretion (cumulative effect).
Some toxic effects are apparent immediately; some are not
apparent for weeks or months.
MOST DRUG TOXICITY IS AVOIDABLE IF CAREFUL ATTENTION IS
PAID TO DOSAGE AND MONITORING FOR TOXICITY.
Example of a toxic effect - RESPIRATORY DEPRESSION due
to the cumulative effect of morphine sulphate in the body.
 Types of Adverse Reactions:
OVERDOSE AND TOXICITY
 DRUG OVERDOSE
 a dose that is too large for a person’s age, size, and/or physical
condition
 dangerous; large dose of drug = poison
 TOXICITY
 “toxic effects”
 drug’s ability to poison the body
 to prevent toxicity → monitor the plasma therapeutic range of the
drug
 ANTIDOTE
 drug that has the opposite effect and can reverse the overdose
symptoms
 Types of Adverse Drug Reaction
 DRUG ALLERGY - an immunologic reaction to a drug.
When a client is first exposed to a foreign substance (antigen),
the body may react by producing antibodies.
Drug (antigen) = Allergic reaction
Allergic reactions can be either mild or severe:
Mild – e.g., rashes
Severe – Anaphylactic Reaction
Earliest Symptom -a subjective feeling of swelling in the
mouth and tongue, acute shortness of breath, acute
hypotension, and tachycardia.
can occur anytime from a few minutes to 2 weeks
Allergic (Hypersensitivity) Reactions::
Drug absorbed into the system
↓
Release of antigen
↓
Initiation of the Immune Response
↓
Migration of Eosinophils and Basophils to site of reaction
↓
Release of antibodies by B-Cells
↓
Antigen-Antibody reaction
↓
Release of histamine by injured cells
↓
Symptoms of allergic reactions (bronchospams, urticaria, facial edema,
diffused macular patches)
 Allergic (Hypersensitivity) Reactions:
ANAPHYLAXIS – extreme hypersensitivity reaction to a
previously encountered antigen
generalized reaction characterized as a systemic
condition that may be life threatening
Symptoms: Bronchial constriction, edema of
pharynx and larynx, severe wheezing, dyspnea
→ asphyxiation → death
Treatment: - Establish airway
Administering IV corticosteroids & Epinephrine
 Types of Adverse Reactions:

IDIOSYNCRATIC EFFECT
abnormal or peculiar effects to a certain
drug
opposite of expected drug effect
caused by abnormal metabolism of
drugs, as a result of enzyme deficiency
Idiosyncratic response:
Overreact or Underreact
 EFFECTS OF DRUGS
DRUG TOLERANCE
 need for increasingly large doses of a drug to
produce the same physiological and/or
psychological effects
TACHYPHYLAXIS
drug tolerance to a frequently repeated
administration of a certain drug
Examples: Opiates, Nitates, Barbiturates, tobacco
and alcohol, Laxatives,psychotropic agents
EFFECTS OF DRUGS
CUMULATIVE EFFECT
body cannot metabolize and excrete
one dose of a drug completely before
the next dose is given
with repeated dose, the drug starts to
collect in the blood and body tissues
Example: Ethyl alcohol (rapid), lead
(gradual)
 EFFECTS OF DRUGS:

DRUG INTERACTIONS
taking 2 or more drugs at the
same time as part of drug
therapy to produce a
pharmacologic response or
taking an OTC medication for
some other ailment
 Types of Drug Interactions:
1. SYNERGISM
– when 2 drugs are administered
together to produce a more
powerful response than the effect of
each drug given separately
- Examples: Anti- HPN drugs, Anti-
Koch’s chemotherapy
 Types of Drug Interactions:

2. POTENTIATION
– administration of 2 drugs at the
same time, wherein one drug
increases the effect of the other
drug.
- Example: Alcohol and Sedatives,
Kaopectate and NaHCO3/ CaCO3
 Types of Drug Interactions:
3. ANTAGONISM
drug interaction in which 2 drugs inhibit or cancel each
other’s effect
Example: * Tetracycline + Maalox (Antacid) + FeSO4
Monoamine Oxidase Inhibitors (MAOI’s) + Tyramine
containing foods (alcohol, cheese, beef &chicken liver,
banana, raisins)
Doctors sometimes use drug interactions to control
unwanted side effects or to increase therapeutic effect of
a particular drug
 Remember:

“The NET EFFECT OF DRUG THERAPY is

the sum of the PHARMACOLOGICAL
EFFECTS of the drug and the
NONSPECIFIC PLACEBO EFFECT
associated with the therapeutic effort.”
 Pharmacodynamic Interactions

Addition 1+1=2

Synergism 1 + 1 = 3 or more

Potentiation 0 + 1 = 2 or more

Antagonism 1+1=0
 DRUG DEPENDENCE
strong psychological and/or physical
need to take a certain drug
develops when a person takes a drug
over a period of time

PSYCHOLOGICAL DEPENDENCE
person has a drive/ craving to take the
drug for pleasure or to relieve discomfort
no physical sx. when drug is taken away
 DRUG DEPENDENCE
PHYSICAL DEPENDENCE
body grows accustomed to the drug, that
it needs it to function
develops withdrawal symptoms when
drug is taken away
involves extreme physical discomforts
Examples: Anti-depressants, Narcotics,
Anti-psychotic drugs
 DRUG ABUSE
 self-administration of a drug in a
chronically excessive quantities, resulting
in physical or psychological dependence
 taking of a drug to the point where it
interferes with health and daily living
patterns
Examples: Nicotine, alcohol, steroids,
barbiturates (downers), sedatives/hypnotics,
marijuana, amphetamines (uppers),
narcotics and opium etc..
Summary

The three phases of drug action.

 FACTORS AFFECTING DRUG ACTION

1. Age – all drugs have a standard doses

that considered safe for infants, children,
and adults
Infants – immature body systems→ lack
necessary enzymes to metabolize drugs
Elderly – degenerative changes in body
system (↓ GFR)
 FACTORS AFFECTING DRUG ACTION

2. Size – proper drug dose is computed based

on a person’s weight
 Obese – requires higher dose of drug to
achieve desired result due to high % of body fat
drug works quickly & effectively in a thin/ lean
individual with a lower % of fat
 Elderly – requires smaller dose of a drug due to
decrease size
 FACTORS AFFECTING DRUG ACTION
3. Diet – combining drugs with certain foods
can alter the drug’s effect
Example: Coumadin Therapy (Anti-
coagulant) ↓ effect when eating green leafy
vegetables
Tetracycline (Antibiotic) ↓ effect when taken
with milk/ milk products
Fat soluble vitamins (ADEK) ↓ effect when
taken with Castor oil (Laxative)
 FACTORS AFFECTING DRUG ACTION
4. Sex
Female- react more strongly to certain drugs than men
do
smaller size and higher % of fat
5. Genetic Factors
a person’s individual make-up causes slight differences
in basic processes like metabolism and excretion
some people are more sensitive to a drug because
they lack the naturally occurring enzymes to break
down drug for excretion
 FACTORS AFFECTING DRUG ACTION
6. Pathological Condition
Kidney and Liver Diseases – affect drug
metabolism and excretion
Cancer patients – needs stronger analgesics to
achieve therapeutic effect
7. Psychological Factors
Positive attitude vs. State of depression and
despair
Placebo effect
Explain to patients the benefits of drug therapy
 FACTORS AFFECTING DRUG ACTION
8. Route of Administration
drugs are absorbed, distributed and metabolized
differently when given in different routes
Intravenous, Intramuscular, Subcutaneous, Sublingual,
Oral, Topical
9. Time of Administration
time related factors influencing drug action
Drugs taken before and after meals
Stimulants – AM
Depressants – PM or HS
 FACTORS AFFECTING DRUG ACTION
10. Drug Taking History
drugs tend to collect in the body producing a
cumulative effect
smaller doses to prevent overdose
repeated doses of a drug make a patient less
responsive to its effects
higher doses to achieve pharmacologic effect
Check patient’s drug history
prevent drug to drug interactions
ascertain allergies to drug products
 FACTORS AFFECTING DRUG ACTION

11. Environmental Conditions

extremes of weather affect
drug action
influenced by hot and
cold, changes in altitude
Determinants That Affect Drug Therapy
 REFERENCES:

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 Abrams, Anne Collins, Carol Barnett Lammon, Sandra Smith Pennington; consultant, Tracey L. Goldsmith.—
Clinical Drug Therapy: Rationales For Nursing Practice, 9th ed. Copyright © 2009 Wolters Kluwer Health |
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Approach — 4th ed. Copyright © 2014 by Pearson Education, Inc.
 Burchum, J.R., & Rosenthal, L.D., Lehne’s PHARMACOLOGY for NURSING CARE, 10th Edition Copyright © 2019,
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