Ways of Standardizing Drugs

 All drugs must meet certain rigid standards.

 Approval of new drugs through
o US FDA
o FDA of the Philippines (formerly BFAD)

Philippine Laws Related to Drugs

 RA 6675 - otherwise known as the Generic Act of 1988 – an act to promote, require and
ensure the production of an adequate supply, distribution, use, and acceptance of drugs
and medicines identified by their generic names.

 Dangerous Drugs Act of 1972 – Dangerous Drugs include

o Prohibited Drugs - opium, heroin
o Restricted Drugs - barbiturates, narcotics, hypnotic drugs
 RA 9165 - Comprehensive Dangerous Drugs Act of 2002 – an act instituting the
Comprehensive Dangerous Drugs act of 2002, repealing Republic Act No. 6425

 RA 953 – NARCOTICS DRUG LAW - An act to provide for the registration of, with the
Collector of Internal Revenue, and the imposition of fixed and special taxes upon all
persons who produce, import, manufacture, compound, deal in, dispense, sell,
distribute, or give away opium, marihuana, opium poppies, or coca leaves, or any
synthetic drugs which may hereafter be declared habit forming by the President of the
Philippines, their salts, derivatives or Preparations, and for other purposes

 RA 9502 – “Universally Accessible Cheaper and Quality Medicines Act of

2008 DRUG STANDARDS

Objectives:
(a) To standardize the names and formulas for extensively used drugs;
(b) To provide standards and test for the identity, purity and quality of drugs well
established in medical practice; and
(c) To issue as far as practical uniformity in physical properties and active constituents

References:
 PIMS
 MIMS
 Pharmacopoeia - United States Pharmacopeia (USP)
 Formulary – National Formulary (NF)
 Essential Drugs List (EDL
o derived from the Philippine National Drug Formulary (PNDF) and is
intended for use in the Rural Health Units (RHUs) for primary medical care

Philippine National Formulary

 Allows primary healthcare prescribers – physicians and dentists to quickly find
important medicine information and practice guidelines for diseases and other health
conditions commonly encountered in the primary setting.
 The essential medicine list, monograph, and cross-reference index have been
integrated into a single manual.
 Initial Section: emphasizes the fundamental points in the rational approach to the use of
medicines
 Main Section: essential medicines for the primary care facilities.
Arranged using the Anatomical Therapeutic Chemical (ATC) Classification System

DRUG NOMENCLATURE
 Chemical Name - first name to be applied to a drug during its early stages of
development usually reflecting the chemical structure of the drug.
 Brand Name/ Trademark/ Proprietary name - superscript ®
 Generic name - non-proprietary name or common name -
 Official name - the name under which the drug is listed by the United States FDA

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Three Phases of Drug Action
1. Pharmaceutic
2. Pharmacokinetic
3. Pharmacodynamic

PHARMACEUTIC PHASE
Dissolution- 1st phase of drug action
80% of drugs taken by mouth
Ex. Tablet → disintegrate → dissolution
o Drugs need to be in solution so they can be absorbed in the GI tract
o Drugs in solid form must
 disintegrate into small
 particles to dissolve into liquid
o Drugs in liquid form are already in solution
 Excipients – fillers and inert substances = size, shape and enhance dissolution
 Additives- K (ions), NA in penicillin, K and NA increase absorbability
 Disintegration – breakdown into smaller particles
 Dissolution – dissolving of the smaller particles in the GI tract fluid before absorption
 Rate limiting – the time it takes the drugs to disintegrate and dissolve to become
available for the body to absorb it
o absorbed faster in acidic fluids with a pH of 1 or 2 rather than alkaline fluids
o younger and older individuals have less acid in stomach = less absorption rate
o enteric-coated drugs- disintegration does not occur until in alkaline environment
(small intestine); stay longer in stomach- effects delayed onset; should not be
crushed. ex: diclofenac, naproxen

PHARMACOKINETIC PHASE – process of drug movement to achieve drug

action: absorption, distribution, metabolism, excretion
 The nurse applies knowledge of pharmacokinetics when assessing the client
for possible adverse effects.
 ABSORPTION - the process by which a drug
o first step in the passage of a drug through the body (routes)

The movement of drug particles from the GI tract to body fluids is by:
a. Passive absorption - occurs mostly by diffusion (movement from
higher concentration to lower concentration) does not require energy to
move across membrane
b. Active absorption - requires a carrier such as an enzyme or protein to move the
drug against a concentration gradient. Energy is required in active transport.
c. Pinocytosis - a process by which cells carry a drug across their cell membrane
by engulfing the drug particles.
The rate by which absorption occurs depends on:
1. the route of drug administration
2. the blood flow through the tissue at the point of drug administration
3. the solubility of the drug
a. Drugs that are lipid soluble and nonionized are absorbed faster
than water soluble and ionized drugs
b. First-pass effect (metabolism) or Hepatic first pass - aka presystemic
metabolism is the phenomenon which occurs whenever the drug is administered
orally, enters the liver, and suffers extensive biotransformation to such an extent
that the bioavailability is drastically reduced, thus showing subtherapeutic action
(Chordiya et al., 2017). It happens when the drug is absorbed through GIT and
then via the enterohepatic circulation the drug is absorbed directly into the liver
where it undergoes metabolism before being released into the systemic
circulation.
c. GI membrane is compost mostly of lipids (fats) and protein – so drugs that are
lipid soluble pass rapidly thru GI membrane
d. Water soluble drugs need a carrier such as enzymes or protein to pass thru
membrane
Note:
 Aspirin – weak acid drugs – are less ionized in the stomach = they pass
thru stomach lining easily and rapidly
 Infants increase in pH (alkaline) = can absorb more penicillins
 Calcium carbonate and antifungals = need acidic environment for better
absorption
 HCl acid destroys Pen G = increase oral dose
 Parenteral routes do not pass thru GIT and liver: parenteral drugs, also
eyedrops, eardrops, suppositories, nasal sprays, respiratory inhalants,
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 transdermal patch, and buccal or sublingual drugs.
d. Bioavailability - a subcategory of absorption, the percentage of the
administered drug dose that reaches the systemic circulation; when a
medication is administered intravenously, its bioavailability is 100%.
Factors that alter bioavailability
o The drug form
o Route of administration
o GI mucosa and motility
o Food and other drugs
o Changes in liver metabolism

DISTRIBUTION - drug becomes available to body fluids and body tissues

 involves the movement of a drug to the body’s tissues; the portion of the drug that gets
through the first-pass effect is delivered to the circulation for transport throughout the
body.
Factors that can affect drug distribution include:
1. the drug’s lipid solubility and ionization
2. perfusion of the reactive tissue
3. protein binding - many drugs are bound to proteins and are not lipid soluble.

This protein-drug complex is relatively large and cannot enter into the capillaries and then
into the tissues to react. the drug must be freed from the protein at the tissues.

Some drugs are loosely bound. These drugs tend to act quickly and to be excreted quickly.
Some drugs may compete for protein binding sites and alter the effectiveness or toxicity of
a drug when the two drugs are given together.

The portion of the drug that bound is inactive because it is not available to receptors, and
the portion that remains unbound is the free, active drug and can cause a pharmacologic
response.

METABOLISM or BIOTRANSFORMATION – the process by which the body

inactivates drugs. LIVER – the primary site for metabolism

Factors affecting metabolism

 Age
 Nutrition
 Insufficient amounts of major body hormones

 Large percentage of drugs are lipid soluble thus the liver metabolizes the lipid-soluble
substances to a water-soluble substance for renal excretion.
 Some drugs are transformed into active metabolites causing an increased
pharmacologic response
 - measure of the time required for elimination. It is the amount of time
required for the drug to be eliminated from the body.
 Half-life in the context of medical science typically refers to the elimination half-life. The
definition of elimination half-life is the length of time required for the concentration of a
particular substance (typically a drug) to decrease to half of its starting dose in the body.

Time (Hours) Half-Life Drug Remaining in The Body

0 -- 100 mg (100%)
12 -- 50 mg (50%)
24 -- 25 mg (25%)
36 -- 12.5 mg (12.5%)
48 -- 6.25 mg (6.25%)
60 -- 3.12 mg (3.25%)

 EXCRETION or ELIMINATION – the elimination of metabolites of drugs and, in some

cases the active drug itself. The skin, saliva, the lungs, bile and feces are some of the
routes used to excrete drugs.

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KIDNEYS – the main route of drug -
elimination Factors that affect drug
excretion
• Renal excretion
• Skin, rectal, oral, respiratory, other orifices and body openings
• Drugs can affect elimination of other drugs
• Blood concentration levels
• Half-life of a drug

PHARMACODYNAMIC PHASE
Pharmacodynamics - study of the biochemical and physiological effects of drugs as well as
their mechanism of action or it is the study of the actions of drugs on the living organisms
- the study of drug concentration and its effects on the body

DOSE RESPONSE - the relationship between the minimal versus the maximal amount of
drug dose needed to produce the desired drug response
 All drugs have a maximum drug effect (maximal efficacy).

RECEPTOR THEORY – many drugs are thought to act on specific areas on cell
membranes called receptor sites
The receptor sites react with certain chemicals to cause an effect within the cells. The
activated enzyme systems then produce certain effects such as increased or decreased
cellular activity, changes in cell membrane permeability or alterations in cellular
metabolism.

Drug binding sites are primarily on proteins, glycoproteins, proteolipids and at enzymes.

Four Receptor Families:

1. Kinase-linked receptors - the ligand-binding domain for the drug is on the cell
surface. The drug activates the enzyme (inside the cell) and a response is initiated

2. Ligand-gated ion channels - the drug spans the cell membrane and with this type of
receptor, the channel opens allowing for the flow of ions (primarily Na and Ca) into
and out of the cells
3. G protein couple receptors – There are 3 components to this receptor response:
 Receptor
 G protein (binds with guanosine triphosphate – GTP)
 Effector (either an enzyme or an ion channel)

Drug ---> Receptor ---> G Protein ---> Effector

4. Nuclear Receptors – Cell Nucleus

Ligand-binding domain – site on the receptor in which the drug bind
Drug acts through receptors by binding to the receptor to produce or block a
response.
The better the drug fits into a receptor site, the more biologically reactive the drug is

Agonists and Antagonist

 Agonist – drugs that a response
 Antagonist – drugs that a response

Nonspecific and Nonselective Drug effects

 Almost all drugs –agonists and antagonists - lack specific and selective effects
 Nonspecific drugs – drugs that affect various sites and have properties of nonspecificity
 Nonselective drugs – drugs that affect various receptors or have property 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

Categories of Drug Action

1. stimulation or depression
2. replacement
3. inhibition or killing of organisms
4. irritation
 Drug action might last hours, days, weeks or months – depending on the half-life of
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 the drug

WAYS HOW DRUGS ACTS/WORKS IN THE BODY

According to purposes/use/actions:
a. PROPHYLACTIC (or prophylactic drugs) - prevent occurrence of a disease or to lessen
its severity if it does occur. (use of vaccines)
b. PALLIATIVE OR SYMPTOMATIC – relieve distressing symptoms
c. CURATIVE OR SPECIFIC - (e.g. antibiotics) - eliminate the disease.
d. SUPPORTIVE - sustain the patient until measures can be instituted that will either cure
or alleviate the condition.
e. SUBSTITUTIVE OR REPLACEMENT - replace substances normally found in the body
but which, because of disease, injury or other factors, are absent or diminished in
amount.
f. SUPPLEMENTARY - added as a supplement or something that supplies a deficiency
g. CHEMOTHERAPEUTIC – use of certain chemicals or drugs in the treatment of certain
diseases
h. RESTORATIVE- drugs used to help return the body to its normal healthy state
i. DIAGNOSTIC- (e.g. radiopaque dyes) help the physician determine whether a disease
is present.

According to the body system affected:

 Drugs affecting the Central Nervous System
 Drugs affecting the Cardiovascular System
 Drugs affecting the GI System, etc.

May be classified by:

 Therapeutic use – given for its desired effect
 Clinical indications – antacids and antibiotics
 Prescription drugs – require an order by a health care professional licensed to prescribe
such as the physician or dentist

 Non-prescription drugs or OTC (over-the-counter drugs) are sold without

prescription in a pharmacy or the drug section of department stores and grocery stores

What is the difference between prescription drugs and over the counter drugs?

EFFECTS OF DRUGS:
1. Local - or Topical - drugs whose major effect takes place at the point of contact with the
body or the desired site of action – eyes, skin, etc.
2. Systemic result from the entrance of the drug into the circulatory system and its
subsequent transport to the cellular site of its action.
A. Selective action-systemic drugs that affect a specific organ or organs.
B. General action -drugs appear to affect the body as a whole.
3. Therapeutic effect-the primary effects intended; the reason the drug is intended or the
desired effect.
4. Side effect-secondary effects –unintended
5. Adverse / Toxic effect-implies abnormal, undesirable or harmful effects
6. Idiosyncratic effect – unexpected peculiar response to drug- either over response, under
response, different response than expected; unpredictable or unexplained response
7. Allergic effect -also known as hypersensitivity reaction; the immunologic reaction to a drug
8. Drug tolerance- decreased physiologic response to repeated administration of a drug
9. Drug interaction-effects of one drug are modified by the prior or concurrent
administration of another
➪Synergistic -increase the potency or reduce the undesirable effects of the drugs,
➪Antagonistic-counteracts effects
10. Anaphylactic reaction -a severe life-threatening or allergic reaction.
11. Cumulative effect - when a drug is excreted slowly, it tends to accumulate in the system,
giving rise to toxic symptoms
12. Drug tolerance-developing resistance to the effects of a drug – needing increased dose
or frequency of drug administration
13. Drug Abuse / Dependence-maybe:
A. Physical drug dependency - body becomes accustomed to the drug - cannot
function normally unless drug is present
B. Psychological drug dependency - drug is the centre of the person’s thoughts,
emotions

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Therapeutic Index and Therapeutic Range
THERAPEUTIC INDEX - 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 or animals (ED50) and the lethal (LD) in 50% of animals (LD50)
𝐿𝐷50
𝑇𝐼 = 𝐸𝐷50
 In some cases, the ED maybe 25% (ED25) or 75% (ED75).
 Drugs with a low TI – narrow margin of safety
 Drug with high TI – wide margin of safety
 Therapeutic range (Therapeutic Window) – drug concentration in the plasma between
the minimum effective concentration in the plasma for obtaining the desired action and
the minimum toxic concentration.
 If therapeutic range is narrow, the plasma drug level should be monitored periodically to
avoid drug toxicity.

Peak and Trough Drug Levels

 PEAK DRUG LEVEL - the highest plasma concentration of a drug at a specific
time; also indicates the rate of absorption
 TROUGH DRUG LEVEL - the lowest plasma concentration of a drug; it measures the
rate at which the drug is eliminated

Peak and Trough drug levels are requested for drugs with narrow therapeutic index and
are considered toxic

Drug Commonly Monitored

Drug Therapeutic Range (mg/L)
Amiodarone 1.0 – 2.5
Digoxin 0.5 – 2.1
Quinidine 2.0 – 5.0
Theophylline 10 – 20
Phenytoin 10 – 20

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 Carbamazepine 5.0 – 12
Sodium Valproate 50 – 100
Phenobarbitone 15 – 40
Gentamicin Peak > 5, trough < 2
Amikacin Peak > 15, trough < 5
Vancomycin Peak 20-40, trough < 10
Lithium 0.6 – 1.2 mmoL/Li

Side effects, Adverse reactions and Toxic effects

 All drugs have side effects, desirable or undesirable, and even with correct drug
dosages. They are predictable.
 Side effects result mostly from drugs that lack specificity
 At times side effects are also called Adverse reactions. The terms Side effects and
Adverse reactions might be used interchangeably.
 Adverse reactions are more severe than side effects; untoward effects
 Toxic effects or toxicity –harmful effects which can be identified by
monitoring the plasma therapeutic range of the drug.

PHARMACOGENETICS – the effects of a drug action that varies from a predicted drug
response because of genetic factors or hereditary influence

Tolerance/Tachyphylaxis
 Tolerance - decreased responsiveness over the course of therapy
 Tachyphylaxis – rapid decrease in response to the drug; it is an “Acute Tolerance”
 Drug categories that can cause tachyphylaxis include Narcotics, Barbiturates,
Laxatives and Psychotropic drugs.

 Placebo effect - a psychological benefit from a compound that may not have the
chemical structure of a drug effect.