TERMS USED IN PHARMACOLOGY

1. Pharmacology represents an integrated body of knowledge that deals with the

actions of chemical and biologics on cellular functions. The term pharmacology is
derived from the Greek words pharmakon, meaning drug, and logos, meaning
rational discussion or study.

Thus pharmacology is the rational discussion or study of drugs and their interactions with
the body.

2. Pharmacodynamics is the study of actions of drugs on the body—what effects a

drug has on the patient, including mechanisms of action, beneficial and adverse
effects of the drug, and the drug’s clinical applications. Pharmacodynamics refers to
the relationship between drug concentration at the site of action and the resulting
effect, including the time course and intensity of therapeutic and adverse effects
3. Pharmacokinetics is the inverse: the study of actions of the body on drugs—the
absorption, distribution, storage, and elimination of a drug. Pharmacokinetics is the
effect of the body on the drug. It is made up of four phases: absorption, distribution,
metabolism, and excretion .
4. Pharmacotherapeutics. Pharmacotherapeutics is the clinical purpose or indication
for giving a drug
5. Clinical pharmacology. is the area of pharmacology that covers the use of drugs in
the prevention (prophylaxis) and treatment of diseases.
6. Toxicology
Toxicology is the area of pharmacology concerned with the undesirable effects of
chemicals and biologicals on cellular functions.
7. Agonist:
A drug that binds to a “receptor” and produces an effect. This drug is capable of
 binding and activating a receptor, leading to a pharmacological response that may
mimic that of a naturally occurring substance. Can be classified as full, partial or
inverse.

 Full agonist - Is capable of eliciting a maximal response as it displays full

efficacy at that receptor.
 Partial agonist - Binds to and activates a receptor but is only able to elicit
partial efficacy at that receptor. A maximal effect cannot be produced, even
when the concentration is increased. When full and partial agonists are present
the partial agonist may act as a competitive antagonist.
 Inverse agonist - Produces an effect that is pharmacologically opposite to an
agonist, yet acts at the same receptor. The receptor must elicit intrinsic or basal
activity in the absence of a ligand and the addition of an inverse agonist will
decrease the activity below the basal level. A receptor that possesses basal
activity is the GABAA receptor; agonists have a sedative effect whilst inverse
agonists have an anxiogenic effect.

8. Antagonist: A molecule that prevents the action of other molecules, often by

competing for a cellular receptor; opposite of agonist.
This drug does not produce a biological response on binding to a receptor but instead
blocks or reduces the effect of an agonist. It may be competitive or non-competitive.
 Competitive antagonist - competitive antagonists bind selectively to the active
site of the receptor without causing activation, preventing the agonist from
binding and causing its effect. The antagonism may be reversible; the effect can
be overcome by increasing the concentration of the agonist, which will lead to
a shift in the equilibrium.
  Non-competitive antagonist - non-competitive antagonists may affect the
reaction by irreversibly binding to the active site of the receptor or to an
allosteric site, therefore not competing with the agonist. The magnitude of the
maximal response is reduced, regardless of the amount of agonist present.
9. ED50 - Dose of drug that produces 50% of its maximum response or effect. Can be a
term used in vitro or in vivo (although it is more common in vivo).

10.Pharmacopoeia—it is a book published by authority of recognized body which

contains the list of drug, their properties, description, preparation and method of
prescribing.
11.Pharmacogenetics—it is that branch of pharmacology which deals with genetic
variations in the drug response.
12.Half-life Half-life of a drug is the amount of time needed to eliminate (by
metabolism and excretion) half of the drug molecules currently in the body.
13.Potency of a drug refers to how much of a drug is needed to create the desired
therapeutic effect.
14.Efficacy of a drug refers to how well the drug creates the desired therapeutic effect.
Drugs may have different potencies but the same efficacy.
15.Loading doses are larger-than-normal doses used when therapy is initiated with
drugs that have very long halflives. The purpose of the loading dose is to achieve
quickly a blood level of the drug that is in therapeutic range even though the drug
has not reached steady state.
16.Drug A drug is a chemical agent which can affect living processes. For purposes of
this course we will mainly be talking about small molecules which affect cellular
processeses.
17.Pharmacy, This is the science of preparation of drugs; much of it deals with
therapeutics, and the treatment of disease (by whatever means).
18.Therapeutics
This is a branch of medicine that deals with different methods of treatment especially
the use of drugs in the cure of diseases
19.Adverse Effect: An unintended and potentially dangerous pharmacological effect
that occurs when a medication is administered correctly.
20.Affinity: The strength of binding between drug and receptor.
21.Bioavailability: The presence of a drug in the blood stream after it is administered.
22.First Pass Effect: The inactivation of orally or enterally administered drugs in the
liver and intestines.
23.Mechanism/mode of Action: How a medication works at a cellular level within
the body.
24.Selectivity: A “selective” drug binds to a primary and predictable site creating one
desired effect. A “non-selective” drug can bind to many different and unpredictable
receptor sites with potential side effects.
25.Side Effect: Effect of a drug, other than the desired effect, sometimes in an organ
other than the target organ.
26.Therapeutic Index: A quantitative measurement of the relative safety of a drug
that compares the amount of drug that produces a therapeutic effect versus the
amount of drug that produces a toxic effect. Medication with a large therapeutic
index is safer than a medication with a small therapeutic index.
27.Therapeutic Window: The dosing window in which the safest and most effective
treatment will occur.
28.Bioavailability: The fraction of drug administered which is actually absorbed and
reaches the systemic circulation following oral dosing. Preparations of the same
drug by different manufacturers may have a different bioavailability.
29.Pharmacovigilence The area of Pharmacovigilence focuses on the effects of drugs
on patient safety. It involves the characterization, detection, and understanding of
adverse events associated with drug administration, including adverse drug
reactions, toxicities, and side effects that arise as a consequence of the short- or
long-term use of drugs.

30.An adverse reaction is any noxious and unintended response to a drug that occurs at
therapeutic doses used for prophylaxis, diagnosis, or therapy. Adverse reactions
associated with excessive amounts of a drug are considered drug overdoses.

31.An idiosyncratic response is a genetically determined abnormal or excessive

response to a drug that occurs in a particular patient. The unusual responsemay
indicate that the drug has saturated or overwhelmed mechanisms that normally
control absorption, distribution, metabolism, or excretion, thus altering the expected
response.

32.An allergic reaction is an adverse response that results from previous exposure to
the same drug or to one that’s chemically similar to it. The patient’s immune system
reacts to the drug as if it were a foreign invader and may produce a mild
hypersensitivity reaction, characterized by localized dermatitis, urticaria,
angioedema, or photosensitivity.

33.An anaphylactic reaction involves an immediate hypersensitivity response

 characterized by urticaria, pruritus, and angioedema. Left untreated, an anaphylactic
reaction can lead to systemic involvement, resulting in shock. It’s often associated
with life-threatening hypotension and respiratory distress.

34. A drug interaction occurs when one drug alters the pharmacokinetics of another
drug—for example, when two or more drugs are given concurrently. Such
concurrent administration can increase or decrease the therapeutic or adverse effects
of either drug. Some drug interactions are beneficial.

UNDERSTANDING DRUGS

Drugs are defined as chemical substances, other than nutrients or essential dietary
ingredients, that when administered to a living organism result in a distinct biological
outcome.

Drugs maybe purified chemicals, synthetic organic chemicals, substances purified from
either plant or animal products or recombinant proteins generated by genetic engineering.

In order for a drug to be effective it has to be administered by anappropriate route (i.e. oral,
intravenous or intramuscular etc) capable of achieving a sufficiently high enough
concentration within its target tissue(s) in a chemical form that allows it to interact with its
biological target to achieve its desired effect.

The factors that determine the ability of a drug to reach its target tissue and achieve its
desired therapeutic effect are determined by its inherent Pharmacokinetic and
Pharmacodynamic properties.
Drug nomenclature

A drug may have three categories of names, namely;

Chemical name

A drug’s chemical name describes its atomic and molecular structure. It describes the drug’s
chemical composition and the molecular structure.it is not normally used when prescribing
because it is cumbersome.

Generic name (non proprietary name)

Thegeneric name is the name approved by a competent drug body e.g food and drug
administration (FDA). It is much simpler than the chemical name and is commonly used in
prescribing.

Brandname (Trade or proprietary name)

The brand name is the copyrighted name that is given by the company manufacturing and
selling the drug.

Example

Chemical name (+/-)-2-(p-isobutylphenyl)propionic acid

Generic name: ibuprofen

Brand name: Brufen

 SOURCES OF DRUGS

Drugs for medical use can be obtained from any of the following sources;

 Plants e.g digoxin,morphin, quinine

 Animals e.g insulin, adrenalin
 Microorganismse.g penicillins,streptomycin
 Chemical substances (made from factories)

ESSENTIAL DRUG CONCEPT

The essential drug concept is a public health principle that promotes efficient use of
resources by establishing and using limited list of carefully selected drugs (medicines).

Essential medicines are those of utmost importance, basic, indispensable, and necessary for
the healthcare needs of the population.

Essential medicines are those that satisfy the priority health care needs of the population.
They are selected with due regard to public health relevance, evidence on efficacy and
safety, and comparative cost-effectiveness; they should therefore be

 Available at all times

 in adequate amounts

 with assured quality

  in the appropriate dosage forms and

 at a price that individuals and the community can afford."

Selection criteria of essential drugs

Essential medicines are selected with due regard to;

• disease prevalence
• evidence on efficacy
• Evidence of safety,
• comparative cost-effectiveness
• any drug included must meet the needs of the majority of the population
• sufficient proven scientific data regarding effectiveness must be available
• substantial safety and risk/benefit ratio
• all products must be of an acceptable quality, and must be tested on a continuous
basis
• Should contain single pharmacologically active ingredients
• combination products, as an exception, will be included where patient compliance
becomes an important factor, or when two pharmacologically active ingredients are
synergistically active in a product
 RATIONAL USE OF DRUGS

Definition

In simplest words rational use means “prescribing right drug, in adequate dose for the
sufficient duration & appropriate to the clinical needs of the patient at lowest cost

The rational use of drugs requires that patients receive medications appropriate to their
clinical needs, in doses that meet their own individual requirements for an adequate period
of time, and at the lowest cost to them and their community (WHO

Reasons for Irrational use of Drugs

1.Lack of information

2.Role models – Teachers or seniors

3.Lack of diagnostic facilities/Uncertainty of diagnosis – medicine for all possible causes

4.Demand from the patient

5.Patient load

6.Promotional activities of pharmaceutical industries

7.Drug promotion and exaggerated claim by companies

8.Defective drug supply system & ineffective drug regulation

INDICATORS OF IRRATIONAL USE OF DRUGS

1. Injudicious use of antimicrobials: Antibiotics in Viral fever and diarrhea

2.Unnecessary combinations

3. Use of drugs not related to diagnosis

4. Incorrect route

5. Incorrect dosing – under or overdose

6. Incorrect duration – prolong or short term use

7. Unnecessary use of expensive medicines

8. Unsafe use of corticosteroids

9. Polypharmacy

The use of drugs when no drug therapy is indicated, e.g. antibiotics for viral upper
respiratory infections.

The use of the wrong drug for a specific condition requiring drug therapy, e.g. tetracycline
in childhood diarrhea requiring ORS.

The use of drugs with doubtful or unproven efficacy, e.g. the use of antimotility agents in
acute diarrhea

 Failure to provide available, safe and effective drugs, e.g. failure to vaccinate for
measles or tetanus, or failure to prescribe ORS for acute diarrhea.

 The use of correct drugs with incorrect administration, dosage and duration, e.g. using
intravenous route where oral or suppository routes would be appropriate.

 The use of unnecessarily expensive drugs, e.g. the use of a third generation, broad-
spectrum antimicrobial when a first line, narrow spectrum agent is indicated.
Hazards of Irrational Use of drugs

 Ineffective & unsafe treatment i.e over-treatment of mild illness or inadequate

treatment of serious illness
 Exacerbation or prolongation of illness
 Distress & harm to patient
 Increased cost of treatment
 Increased drug resistance - misuse of anti-infective drugs
 Increased Adverse Drug Events
 Increased morbidity and mortality

VARIOUS OBSTACLES IN RATIONAL DRUG USE

1. Lack of objective information & of continuing education & training in pharmacology.

2. Lack of well organized drug regulatory authority & supply of drugs.

3. Presence of large number of drugs in the market & the lucrative methods of
promotion of drugs employed by pharmaceutical industries.

4. The prevalent belief that “every ill has a pill.”

STEPS OF RATIONAL DRUG USE OF DRUGS

Step I: Identify the patient’s problem based on symptoms & recognize the need for
action
Step:- II Diagnosis of the disease – define the diagnosis

Step:- III List possible intervention or treatment (drug or no drug) – Identify the drug

Step:- IV Start the treatment by writing an accurate & complete prescription e.g.
name of drugs with dosage forms, dosage schedule & total duration of the treatment

Step:-V Give proper information, instruction & warning regarding the treatment
given e.g. side effects (ADR), dosage schedule & dangers/risk of stopping the therapy
suddenly

Step:-VI Monitor the treatment to check, if the particular treatment has solved the
patient’s problem. Passive monitoring – done by the patient himself. Explain him
what to do if the treatment is not effective or if too many side effect occurs Active
monitoring - done by physician and makes an appointment to check the response of
the treatment

STRATEGIES TO IMPROVE RATIONAL USE OF DRUGS

1. Educational strategies

Training for Providers

Undergraduate education

Continuing in-service medical education (seminars, workshops)

Face-to-face persuasive outreach e.g. academic detailing

Clinical supervision or consultation

Printed Materials

Clinical literature and newsletters

Formularies or therapeutics manuals

Persuasive print materials

Media-Based Approaches

Posters

Audio tapes, plays

Radio, television

2. Managerial strategies

Changes in selection, procurement, distribution to ensure availability of essential

drugs

Essential Drug Lists, morbidity-based quantification, kit systems

Strategies aimed at prescribers;

Targeted face-to-face supervision with audit, peer group monitoring, structured

order forms, evidence-based standard treatment guidelines

Dispensing strategies ;

Course of treatment packaging, labelling, generic substitution

3. Economic strategies

Avoid perverse financial incentives e.g

 prescribers’ salaries from drug sales

 insurance policies that reimburse non-essential drugs or incorrect doses
 flat prescription fees that encourage polypharmacy by charging the same
amount irrespective of number of drug items or quantity of each item
4. Regulatory strategies

o Drug registration

o Banning unsafe drugs - but beware unexpected results

substitution of a second inappropriate drug after banning a first inappropriate or

unsafe drug

o Regulating the use of different drugs to different levels of the health sector e.g.

licensing prescribers and drug outlets

scheduling drugs into prescription-only & over-the-counter

o Regulating pharmaceutical promotional activities

 CLASSIFICATION OF DRUGS

Drugs may be classified as follows

 Prescription classification
 Pharmacological classification
 According to drug legislation
1. Prescription classification

Drugs are classified into prescription and non prescription drugs

 Prescription drugs: These drugs can only be obtained when a patient presents a valid
prescription or order (from a licensed health care provider, such as a physician,
dentist, or nurse practitioner) to a pharmacy. Example of prescription drugs include –
Amoxicilin, ciprofloxacin, diclofenac and nifedipine among others
 Non prescription drugs (Over the counter drugs): They can be obtained from either
the pharmacy or drug shop without a prescription. Examples of over the counter drugs
include:- Panadol® , Hedex® , Vitamins etc
2. Pharmacological classification

Drugs can be classified basing on

Molecular Targets

Based on Pharmacological Effect – Based on the action of drugs on our body, they are
classified based on their therapeutic actions. Such as antacids reduce acidity in the stomach,
analgesics are pain killers, antiseptics kill microorganisms, etc.

Based on Chemical Structure – Based on the common chemical structures, drugs are
classified into various classes. As chemical structures, functional groups, etc., are
responsible for their chemical properties. Mostly, drugs having similar chemical structures
show similar effects on the body. For example, sulphonamide drugs, barbiturates, etc.
Based on Drug Action – Drugs are also classified based on their action on molecular targets
and effects on our body. For example, histamines are responsible for causing inflammation
in the body, and we take anti-histamines to block their actions.

Based on Molecular Targets – Some drugs target protein, carbohydrates, etc. Generally,
drugs that have similar structures target similar molecules in our body and produce
responses accordingly.

3. Legal classification

 Class A drugs (narcotics): They may be obtained on prescription of a duly qualified

medical practitioner, dentist for medical, dental and may be supplied only by a
registered pharmacist or licensed pharmacy, e.g. morphine, Pethidine, Cocaine
 Class B drugs: They may only be on the prescription of a duly qualified medical
practitioner or dentist but only for medical or dental treatment respectively, e.g
Phenobarbitone, Ciprofloxacin, Amoxicillin, Diazepam, Griseofulvin, Metformin
 Class C drugs: They may be sold by retail only by a person or company operating a
licensed pharmacy or a licensed drug seller. Over the counter drugs, e.g. Panadol® ,
Hedex® , Vitamins etc
 SCHEDULES OF CONTROLLED DRUGS

Drug Schedules
Drugs, substances, and certain chemicals used to make drugs are classified into five
(5) distinct categories or schedules depending upon the drug’s acceptable medical use
and the drug’s abuse or dependency potential. The abuse rate is a determinate factor
in the scheduling of the drug
There are currently 5 schedules and their meanings are as follows:

Schedule I:
Drugs with no current medical use with high potential for abuse and/or addiction. The
drugs that are considered the most dangerous by the DEA are known as Schedule I
substances. These are drugs with no current medical use, per analysis by the DEA and
FDA. These substances also carry a high potential for abuse and addiction.
Some Schedule I drugs include:
 Heroin
 Marijuana
 Ecstasy
 Quaaludes
 Bath salts

Schedule II:
Drugs with some medically acceptable uses, but with high potential for abuse and/or
addiction. These drugs can be obtained through prescription. Schedule II drugs are
also considered highly addictive with a dangerous potential for abuse. What makes
them different from Schedule I drugs? Unlike the group above, Schedule II drugs are
considered medically acceptable in particular cases, like for treating chronic pain or
addiction. For this reason, Schedule II drugs can be obtained with a doctor’s
prescription, but the risks of long-term use are still great.
Examples of Schedule II drugs include:
 Methadone
 Demerol
 Vicodin
 OxyContin
 Fentanyl
 Morphine
 Codeine

Schedule III:
Drugs with low to moderate potential for abuse and/or addiction, but less dangerous
than Schedule I or II. These drugs can be obtained through prescription, but generally
are not available over the counter. The DEA classifies substances with a low to
moderate potential for physical and psychological dependence under Schedule III.
When misused, these drugs can still lead to abuse or addiction, but they are still less
dangerous than drugs in Schedules I and II. You can purchase these drugs at a
pharmacy with a prescription, but you generally will not find them available over the
counter.

Schedule III drugs include:

 Suboxone
 Ketamine
 Anabolic steroids

Schedule IV:
Drugs with viable medical use and low probability of use or misuse.
is the next classification level down in the DEA’s roster. Once again, these drugs
have clear evidence of viable medical use, and they also possess a low probability for
misuse and abuse. Of course, it is important to remember that a low probability does
not mean there is no probability. Schedule IV drugs could still lead to addiction if
they are seriously misused or mixed with other substances of abuse.
Schedule IV drugs include:
 Xanax
 Soma
 Klonopin
 Valium
 Ativan

Schedule V:
Drugs with low potential for abuse (lower than Schedule IV).
Finally, the DEA labels the least addictive substances under Schedule V. Most
Schedule V substances involve preparing the drug with a small quantity of some
narcotic. A common example is cough syrup. Schedule V substances have a very low
potential for abuse; however, if the substance is misused to a large degree, physical or
psychological dependency could develop.

Schedule V drugs include:

 Robitussin AC
 Ezogabine
 DRUG FOMULATIONS

Solid Formulations

 Tablets – a tablet is disc-shaped and prepared by compressing a granulated powder in

a die of suitable machinery. They are mostly coated with inert substances like starch
to help them disintegrate in the digestive tract of the patient. A binding agent,
lubricating material, and flavors are added to the tablets to make them palatable.

 Enteric Coated Tablets – are coated with a material that does not disintegrate in the
acidic medium of the stomach but in the alkaline medium of the intestine. They can’t
be chewed but consumed only by swallowing.

 Controlled Release Tablet – is designed to release the active ingredient of the drug
in a specific amount over a specified period of time. Here, the amount of drug
released is gradual over the day and doesn’t depend upon the pH of the digestive tract
of the patient. Thus, a uniform amount of drug is released at a uniform rate.

 Sustained release preparations – release a fixed amount of drug over an extended

period of time. Thus, they improve the treatment compliance by the patient.

 Capsules – can be hard or soft. Hard capsules contain the drug in solid form, which
gets dissolved easily in water. Soft capsules have the drug in liquid or semi-solid
form, which is non-soluble in water and soluble in propylene or glycol.

Liquid and Semi-Solid Formulations

They are more readily absorbed than the solid formulations and can be administered by
various routes like:
1. Oral preparations – Oral preparations are easier to swallow and administer
medicines to children and old-age patients. Flavourings and sugar are added to some
liquids to make them palatable. They are available as solutions, suspensions, or
emulsions and must be shaken well before use.

2. Topical Preparations – The application of a drug to an area of the body for direct
treatment is called topical application. It includes:

 Eye drops

 Ear drops

 Nasal drops

 Nebulisers and inhalers

 Creams and ointments for skin application

 Gels and lotions

 Pessaries for vaginal administration of the drug

3. Sublingual and Buccal Administration – It is useful for drugs which are active in
very low concentration in the blood. Such drugs are administered as tablets under the
tongue or between the cheek and the gum and allowed to dissolve. In this manner, the
drug directly enters the bloodstream, bypassing the digestive tract and acts faster.

4. Rectal Administration

 Suppositories: are used for drugs which are administered through the rectum.
The drug is absorbed by the rectal mucosa and directly enters the bloodstream.
The method is useful when a patient is unconscious, has nausea or difficulty in
swallowing.
  Enemas: are liquid preparations for rectal administration. They can be used for
topical or systemic treatment and also for a bowel movement.

DOSAGE FORM
Definition: Dosage forms are the means ( or the form ) by which drug molecules are
delivered to sites of action within the body.
The need for dosage forms:
1- Accurate dose.

2- Protection e.g. coated tablets, sealed ampules.

3- Protection from gastric juice.

4- Masking taste and odour.

5- Placement of drugs within body tissues.

6- Sustained release medication.

7- Controlled release medication.

8- Optimal drug action.

9- Insertion of drugs into body cavities (rectal, vaginal) 10- Use of desired vehicle
for insoluble drugs.
They are classified according to:

Route of administration Physical form

Oral Solid
Topical Semisolid
Rectal liquid
Parenteral Gaseous
 Vaginal
Inhaled
Ophthalmic
Otic

ORAL DOSAGE FORMS:

1- Tablet :
A tablet is a hard, compressed medication in round, oval or square shape. Solid
dosage form containing unit dose of one or more medicament.
-Prepared by mould method or compression method The
excipients include:
-Binders, glidants (flow aids) and lubricants to ensure efficient tabletting.
-Disintegrants to ensure that the tablet breaks up in the digestive tract.
-Sweeteners or flavours to mask the taste of bad-tasting active ingredients.
-Pigments to make uncoated tablets visually attractive.
A coating may be applied to:

 hide the taste of the tablet's components.

 make the tablet smoother and easier to swallow .
 make it more resistant to the environment.
 extending its shelf life.
 2-BUCCAL AND SUBLINGUAL TAB
:

- Sublingual and buccal medications are administered by placing

the mouth, either under the tongue (sublingual) or between
and the cheek ( buccal ).

- The medications dissolve rapidly and are absorbed through the mucous membranes
of the mouth, where they enter into the bloodstream.

- Avoid the acid and enzymatic environment of the stomach and the drug
metabolizing enzymes of the liver.

- Examples of drugs administered by this route: e.g. vasodilators, steroidal hormones.

3- EFFERVESCENT TABLET :
Effervescent tablets are uncoated tablets that generally contain acid substances (citric and
tartaric acids) and carbonates or bicarbonates and which react rapidly in the
presence of water by releasing carbon dioxide.

-They are intended to be dissolved or dispersed in water before use providing:

A- Very rapid tablet dispersion and dissolution.

B- pleasant tasting carbonated drink.
4- CHEWABLE TABLET:

- They are tablets that chewed prior to swallowing.

- They are designed for administration to children e.g. vitamin products.

Soft gelatin capsule

 Hard gelatin

5- CAPSULE:

A capsule is a medication in a gelatin container.

-solid dosage form

- Advantage: mask the unpleasant taste of its contents.

- The two main types of capsules are:

1- Hard-shelled capsules, which are normally used for dry, powdered
ingredients,

2- Soft-shelled capsules, primarily used for oils and for active ingredients
that are dissolved or suspended in oil.

6- LOZENGE:

-It is a solid preparation consisting of sugar and gum, the latter giving strength and
cohesiveness to the lozenge and facilitating slow release of the medicament.
- It is used to medicate the mouth and throat for the slow administration of indigestion
or cough remedies.

- 7- PASTILLES

- They are solid medicated preparations designed to dissolve slowly in the mouth. They
are softer than lozenges and their bases are either glycerol and gelatin, or acacia and
sugar.

8- DENTAL CONES:

- A tablet form intended to be placed in the empty socket following a tooth

extraction, for preventing the local multiplication of pathogenic bacteria
associated with tooth extractions.

- The cones may contain an antibiotic or antiseptic.

- 9- PILLS :

- Pills are oral dosage forms which consist of spherical masses prepared from one
or more medicaments incorporated with inert excipients.

- Pills are now rarely used.

10- GRANULES:

- They are consisting of solid, dry aggregates of powder particles often supplied
in single-dose sachets. They are irregular shape particle which are made to
improve flow property of powder

- Some granules are placed on the tongue and swallowed with water, others are
intended to be dissolved in water before taking.

- Effervescent granules evolve carbon dioxide when added to water.

11- POWDER (ORAL):

----Solid dosage forms -- intimate mixtures of dry finely divided drug or chemicals
intended for internal or external use.
- The mixed powders may be stored in dry form and mixture prepared by the pharmacist
when required for dispensing , by suspending the powders in the appropriate
vehicle.

1-Bulk Powders are multidose preparations consisting of solid, loose, dry particles of
varying degrees of fineness.--contain one or more active ingredients, with or without
excipients and, if necessary, coloring matter and flavoring substances.
usually contain non-potent medicaments such as antacids since the patient measures
a dose by volume using a 5ml medicine spoon. The powder is then usually dispersed
in water or, in the case of effervescent powders, dissolved before taking.
x
13- LIQUID PREPARATIONS :

a- Oral solution:
Oral solutions are clear Liquid preparations for oral use containing one or
more active ingredients dissolved in a suitable vehicle.

b- Oral emulsion:
Oral emulsions are stabilized oil-in-water dispersions, either or both phases of which may
contain dissolved solids either oil is dispersed in finely divided form in water or vice
versa

c-Oral suspension:
- Liquid preparations for oral use containing one or more active ingredients suspended
in a suitable vehicle.
- may show a sediment which is readily dispersed on shaking to give a uniform
suspension which remains sufficiently stable to enable the correct dose to be
delivered
d- Syrup:
- It is a concentrated aqueous solution of a sugar, usually sucrose to which medicaments
are added.
- Flavored syrups are a convenient form of masking disagreeable tastes.
13- LIQUID PREPARATIONS (CONT. ):

e- Elixir:
-It is pleasantly flavored clear liquid oral preparation of potent or nauseous drugs.
- The vehicle may contain a high proportion of ethanol or sucrose together with
antimicrobial preservatives which confers the stability of the preparation.
f- Linctuses:
- --are viscous, liquid oral preparations that are usually prescribed for the relief of
cough.
- --contain a high proportion of syrup and glycerol which have a demulcent effect on the
membranes of the throat.
- The dose volume is small (5ml) and, to prolong the demulcent action, they should be
taken undiluted.
- .

13-LIQUID PREPARATIONS
)
(CONT. :
Oral Drops:

Oral drops are Liquid preparations for oral use that are intended to be administered in small
volumes with the aid of a suitable measuring device.
They may be solutions, suspensions or
emulsions h- Gargles:
- They are aqueous solutions used in the prevention or treatment of throat infections.
- Usually they are prepared in a concentrated solution with
directions for the patient to dilute with warm water before
use.

i- Mouthwashes:
These are similar to gargles but are used for oral hygiene and to treat infections of the

mouth.
TOPICAL DOSAGE FORMS:
1- Ointments:

- Ointments are semi-solid, greasy preparations for application to the skin, rectum
or nasal mucosa.

- The base is usually anhydrous and immiscible with skin secretions.

- Ointments may be used as emollients or to apply suspended or

dissolved medicaments to the skin.
2- Creams:

- Creams are semi-solid emulsions, that is mixtures of oil and water. -

They are divided into two types:

A- oil-in-water (O/W) creams: which are composed of small droplets of oil dispersed in
a continuous aqueous phase.
Oil-in-water creams are more comfortable and cosmetically acceptable as they are less
greasy and more easily washed off using water.

B- water-in-oil (W/O) creams: which are composed of small droplets of water dispersed
in a continuous oily phase.
 Water-in-oil creams are more difficult to handle but many drugs which are
incorporated into creams are hydrophobic and will be released more readily from
a water-in-oil cream than an oil-in-water cream.
Water-in-oil creams are also more moisturising as they provide an oily barrier which
reduces water loss from the stratum corneum, the outermost layer of the skin.

3- Gels (Jellies):

-Gels are semisolid system in which a liquid phase is constrained within a

3-D polymeric matrix (consisting of natural or synthetic gum) having a
high degree of physical or chemical cross-linking.

-They are used for medication, lubrication and some miscellaneous applications
like carrier for spermicidal agents to be used intra
vaginally .

4- Poultice:
It is soft, viscous, pasty preparation for external use.
They are applied to skin while they are hot. Poultice
must retain heat for a considerable time because they are intended to supply
warmth to inflamed parts of body.
E.g. Kaolin poultice ( B.P.C. )
5- Pastes :
- Pastes are basically ointments into which a high percentage of insoluble solid
has been added
-The extraordinary amount of particulate matter stiffens the system.
-Pastes are less penetrating and less macerating and less heating than ointment.
-Pastes make particularly good protective barrier when placed on the skin, the
solid they contain can absorb and thereby neutralize certain noxious
chemicals before they ever reach the skin.
-Like ointments, paste forms an unbroken relatively water – impermeable film
unlike ointments the film is opaque and therefore can be used as an effective
sun block accordingly.
TOPICAL DOSAGE FORMS (CONT.):

There are two types of paste:

a) Fatty pastes ( e.g: leaser's paste) .

b) Non greasy pastes (e g: - bassorin paste).

6- Dusting powders:

- These are free flowing very fine powders for external use.

- Not for use on open wounds unless the powders are sterilized.

TOPICAL DOSAGE FORMS (CONT.):

9- Liniments:

- Liniments are fluid, semi-fluid or, occasionally, semi-solid preparations

intended for application to the skin.

- They may be alcoholic or oily solutions or emulsions.

 - Most are massaged into the skin (e.g. counter-irritant).

- Liniments should not be applied to broken skin

10- Lotions :
- These are fluid preparations (aqueous) for external application without friction--
either dabbed on the skin or applied on a suitable dressing and covered with a
waterproof dressing to reduce evaporation.
TOPICAL DOSAGE FORMS (CONT.):

11- Collodion:
Collodion is a solution of nitrocellulose in ether or acetone, sometimes with the
addition of alcohols.

-Its generic name is pyroxylin solution.

-It is highly flammable.

- As the solvent evaporates, it dries to a celluloid-like film.

- Compound Wart Remover consists of acetic acid and salicylic acid in an

acetone collodion base used in Treatment of warts by keratolysis.
TOPICAL DOSAGE FORMS (CONT.):

11- Paints:

- Paints are liquids for application to the skin or mucous membranes.

- Skin paints contain volatile solvent that evaporates quickly to leave a dry
resinous film of medicament.

- Throat paints are more viscous due to a high content of glycerol, designed to
prolong contact of the medicament with the affected site.
TOPICAL DOSAGE FORMS (CONT.):

13- Pressurized dispensers (aerosol sprays):

- Several different types of pharmaceutical product may be packaged in
pressurized dispensers, known as aerosols.

- Surface sprays produce droplets of 100 um diameter or greater.

- May be used as surface disinfectants, wound or burn dressing, relieve irritation of bites.
- Spray-on dusting powders are also available from pressurized containers.

RECTAL DOSAGE FORMS:

1- Suppository:
It is a small solid medicated mass, usually coneshaped ,that is inserted either into the
rectum (rectal suppository), vagina (vaginal suppository or pessaries) where it melts
at body temperature .

RECTAL DOSAGE FORMS (CONT.):

2- Enema:
An enema is the procedure of introducing liquids into the rectum and colon via the anus.
Types of enema:
1- Evacuant enema: used as a bowel stimulant to treat constipation. E.g. soft soap enema &
Mgso4 enema
-The volume of evacuant enemas may reach up to 2 liters.

-They should be warmed to body temperature before administration.

RECTAL DOSAGE FORMS (CONT.):

2- Retention enema:
- Their volume does not exceed 100 ml.

- No warming needed. - May exert:

A- Local effect: e.g. a barium enema is used as a contrast substance in the

radiological imaging of the bowel.

B- Systemic effect:
e.g. the administration of substances into the bloodstream. This may be
done in situations where it is impossible to
deliver a medication by mouth, such as
antiemetics.
e.g. nutrient enema which contains
carbohydrates, vitamins & minerals.
VAGINAL DOSAGE FORMS:

1- Pessary:
- Pessaries are solid medicated preparations designed for insertion into the vagina
where they melt or dissolve.
- There are three types:
 A- Moulded pessaries: they are cone shaped and prepared in a similar way to
moulded suppositories.

B- Compressed pessaries: made in a variety of shapes and are prepared by

compression in a similar manner to oral tablets. C- Vaginal capsules: are similar to
soft gelatin oral Capsules differing only in size and shape.

PARENTERAL DOSAGE FORMS:

An injection is an infusion method of putting liquid into the body, usually with a hollow
needle and a syringe which is pierced through the skin to a sufficient depth for the
material to be forced into the body.
There are several methods of injection, including:
1- An intravenous injection :

It is a liquid administered directly into the bloodstream via a vein.

It is advantageous when a rapid onset of action is needed.
PARENTERAL DOSAGE FORMS (CONT.):

2- Intramuscular injection:

-It is the injection of a substance directly into a muscle.

- Many vaccines are administered intramuscularly.

-Depending on the chemical properties of the drug, the medication may either
be absorbed fairly quickly or more gradually.

- Intramuscular injections are often given in the deltoid, vastus lateralis,

ventrogluteal and dorsogluteal muscles.

- Injection fibrosis is a complication that may occur if the injections are

delivered with great frequency or with improper technique.
PARENTERAL DOSAGE FORMS (CONT.):

3- Subcutaneous injection:

Subcutaneous injections are given by injecting a fluid into the subcutis,the layer
of skin directly below the dermis and epidermis.
 Subcutaneous injections are highly effective in administering vaccines and such
medications as insulin.

INHALED DOSAGE FORMS:

1- Inhaler :
- Inhalers are solutions, suspensions or emulsion of drugs in a mixture
of inert propellants held under pressure in an aerosol dispenser.

- Release of a dose of the medicament in the form of droplets of 50 um

diameter or less from the container through a spring-loaded valve
incorporating a metering device. The patient then inhales the released drug
through a mouthpiece.

- In some types, the valve is actuated by finger pressure, in other types

the valve is actuated by the patient breathing in through the mouthpiece.
- It is commonly used to treat asthma and other respiratory problems.
INHALED DOSAGE FORMS (CONT.):

2- Nebulizer or (atomizer):

A nebulizer is a device used to administer medication to people in forms of a

liquid mist to the airways.
- It is commonly used in treating asthma, and other respiratory diseases. - It
pumps air or oxygen through a liquid medicine to turn it into a vapor, which
is then inhaled by the patient.
-As a general rule, doctors generally prefer to prescribe inhalers for their
patients, because: 1-These are cheaper
2- more portable
3- carry less risk of side effects.
Nebulizers, for that reason, are usually reserved only for serious cases of respiratory
disease, or severe attacks.

OPTHALMIC DOSAGE FORMS

1. Eye drops are saline-containing drops used as a vehicle to administer medication

in the eye.
Depending on the condition being treated, they may contain steroids, antihistamines
or topical anesthetics.
Eye drops sometimes do not have medications in them and are only lubricating and
tear-replacing solutions.
 2. Ophthalmic ointment & gel:
These are sterile semi-solid Preparations intended for application To the
conjunctiva or eyelid margin.

OTIC DOSAGE FORMS:

1- Ear drops:

- Ear drops are solutions, suspensions or emulsions of drugs that are instilled into the
ear with a dropper.

- It is used to treat or prevent ear infections, especially infections of the outer ear and
ear canal.

NASAL DOSAGE FORMS:

1- Nasal Drops and Sprays:

Drugs in solution may be instilled into the nose from a dropper or from a plastic squeeze
bottle.

The drug may have a local effect, e.g. antihistamine, decongestant.

Alternatively the drug may be absorbed through the nasal mucosa to exert a systemic effect.
The use of oily nasal drops should be avoided because of possible damage to the cilia of the
nasal mucosa.

INTERMEDIATE PRODUCTS USED IN COMPOUNDING:

Extracts: These are concentrated preparations containing the active principals

of vegetable or animal drugs which have been extracted with suitable
solvents and concentrated to form liquid, soft or dry extract.

Glycerins: These are solutions of medicaments in glycerol with or without the

addition of water.

Infusions: These are dilute solutions containing the readily soluble constituents
of crude drugs and prepared by diluting 1 part of concentrated infusion
with 10 parts of water. Concentrated infusions are prepared by cold
extraction of crude drugs with 25% ethanol.
Oxymels: These are preparations in which the vehicle is a mixture of acetic acid and
honey.

Spirits: They are alcoholic or aqueous alcoholic solutions of volatile substances used
as flavouring agents.

Tinctures: These are alcoholic preparations containing the active principals of

vegetable drugs. They are relatively weak compared to extracts.

Aromatic waters: These are aqueous solutions, usually saturated of volatile oils or
other volatile substances. Used as flavoring agents.
ESSENTIAL MEDICINES

Essential medicines are those that satisfy the priority health care needs of the population.
They are selected with due regard to public health relevance, evidence on efficacy and
safety, and comparative cost-effectiveness.

Essential medicines are those of utmost importance, basic, indispensable, and necessary for
the healthcare needs of the population.

Essential medicines are intended to be available within the context of functioning health
systems at all times in adequate amounts, in the appropriate dosage forms, with assured
quality and adequate information, and at a price the individual and the community can
afford.
The implementation of the concept of essential medicines is intended to be flexible and
adaptable to many different situations. It incorporates the need to regularly update
medicines selections to reflect new therapeutic options and changing therapeutic needs; the
need to ensure drug quality; and the need for continued development of better medicines,
medicines for emerging diseases, and medicines to meet changing resistance patterns.

SELECTION CRITERIA

Selection decisions are recommended based on many different factors, such as the
pattern of prevalent diseases, treatment facilities, the training and experience of available
personnel, financial resources, and genetic, demographic and environmental factors. The
following criteria are used by the WHO Expert Committee on the Selection and Use of
Essential Medicines:

 Only medicines for which sound and adequate evidence of efficacy and safety in a
variety of settings is available should be selected.

 Relative cost-effectiveness is a major consideration for choosing medicines within the

same therapeutic category. In comparisons between medicines, the total cost of the
treatment - not only the unit cost of the medicine - must be considered, and be compared
with its efficacy.
 In some cases, the choice may also be influenced by other factors such as
pharmacokinetic properties or by local considerations such as the availability of
facilities for manufacture or storage.

 Each medicine selected must be available in a form in which adequate quality, including
bioavailability, can be ensured; its stability under the anticipated conditions of storage
and use must be determined.

 Most essential medicines should be formulated as single compounds. Fixed dose

combination products are selected only when the combination has a proven advantage in
therapeutic effect, safety, adherence or in decreasing the emergence of drug resistance in
malaria, tuberculosis and HIV/AIDS.

Other criteria used for the selection of essential medicines, some of them linked to
those mentioned above, include:

 Needs – meets health care needs of the majority of the population

 Affordability for patients
 Effectiveness - proven over time in the real world
 Substantial safety and risk benefit ratio
 Quality – for example ensured regulatory bodies such as the Medical Control Councils in
South Africa
 Evidence based decision-making – sufficient proven scientific data available regarding
effectiveness and safety
 Implications for practice – viable and implementable in particular context

IMPORTANCE OF AN ESSENTIAL MEDICINES LIST (EML)

An EML promotes health delivery equity and helps to set health related priorities, by
promoting the use of a limited number of carefully selected medicines based on agreed
clinical guidelines. The use of an EML leads to:

• a better supply of medicines

• more rational prescribing
• lower costs
• improved price competition through economies scale
• more focused training of health workers
• improved medicine information for patients and health workers
• prescribers gaining more experience with fewer drugs

Rational Medicine use.

Definition

In simplest words rational use means “prescribing right drug, in adequate dose for the
sufficient duration & appropriate to the clinical needs of the patient at lowest cost
The rational use of drugs requires that patients receive medications appropriate to their
clinical needs, in doses that meet their own individual requirements for an adequate period
of time, and at the lowest cost to them and their community (WHO

Reasons for Irrational use of Drugs

1.Lack of information

2.Role models – Teachers or seniors

3.Lack of diagnostic facilities/Uncertainty of diagnosis – medicine for all possible causes

4.Demand from the patient

5.Patient load

6.Promotional activities of pharmaceutical industries

7.Drug promotion and exaggerated claim by companies

8.Defective drug supply system & ineffective drug regulation

INDICATORS OF IRRATIONAL USE OF DRUGS

1. Injudicious use of antimicrobials: Antibiotics in Viral fever and diarrhea

2. Unnecessary combinations

3. Use of drugs not related to diagnosis

4. Incorrect route

5. Incorrect dosing – under or overdose

6. Incorrect duration – prolong or short term use

7. Unnecessary use of expensive medicines

8. Unsafe use of corticosteroids

9. Polypharmacy

The use of drugs when no drug therapy is indicated, e.g. antibiotics for viral upper
respiratory infections.

The use of the wrong drug for a specific condition requiring drug therapy, e.g. tetracycline
in childhood diarrhea requiring ORS.

The use of drugs with doubtful or unproven efficacy, e.g. the use of antimotility agents in
acute diarrhea

 Failure to provide available, safe and effective drugs, e.g. failure to vaccinate for
measles or tetanus, or failure to prescribe ORS for acute diarrhea.

 The use of correct drugs with incorrect administration, dosage and duration, e.g. using
intravenous route where oral or suppository routes would be appropriate.

 The use of unnecessarily expensive drugs, e.g. the use of a third generation, broad-
spectrum antimicrobial when a first line, narrow spectrum agent is indicated.
Hazards of Irrational Use of drugs

Ineffective & unsafe treatment i.e over-treatment of mild illness or inadequate treatment of
serious illness

Exacerbation or prolongation of illness

Distress & harm to patient

Increased cost of treatment

Increased drug resistance - misuse of anti-infective drugs

Increased Adverse Drug Events

Increased morbidity and mortality

VARIOUS OBSTACLES IN RATIONAL DRUG USE

1. Lack of objective information & of continuing education & training in pharmacology.

2. Lack of well organized drug regulatory authority & supply of drugs.

3. Presence of large number of drugs in the market & the lucrative methods of
promotion of drugs employed by pharmaceutical industries.

4. The prevalent belief that “every ill has a pill.”

Steps of rational drug use of drugs

Step I: Identify the patient’s problem based on symptoms & recognize the need for action

Step:- II Diagnosis of the disease – define the diagnosis

Step:- III List possible intervention or treatment (drug or no drug) – Identify the drug

Step:- IV Start the treatment by writing an accurate & complete prescription e.g. name of
drugs with dosage forms, dosage schedule & total duration of the treatment

Step:-V Give proper information, instruction & warning regarding the treatment given e.g.
side effects (ADR), dosage schedule & dangers/risk of stopping the therapy suddenly

Step:-VI Monitor the treatment to check, if the particular treatment has solved the patient’s
problem. Passive monitoring – done by the patient himself. Explain him what to do if the
treatment is not effective or if too many side effect occurs Active monitoring - done by
physician and makes an appointment to check the response of the treatment

Strategies to Improve rational Use of Drugs

1. Educational strategies

Training for Providers

Undergraduate education
Continuing in-service medical education (seminars, workshops)

Face-to-face persuasive outreach e.g. academic detailing

Clinical supervision or consultation

Printed Materials

Clinical literature and newsletters

Formularies or therapeutics manuals

Persuasive print materials

Media-Based Approaches

Posters

Audio tapes, plays

Radio, television

2. Managerial strategies

Changes in selection, procurement, distribution to ensure availability of essential drugs

Essential Drug Lists, morbidity-based quantification, kit systems

Strategies aimed at prescribers

targeted face-to-face supervision with audit, peer group monitoring, structured order forms,
evidence-based standard treatment guidelines

Dispensing strategies

course of treatment packaging, labelling, generic substitution

3. Economic strategies

Avoid perverse financial incentives e.g

• prescribers’ salaries from drug sales

• insurance policies that reimburse non-essential drugs or incorrect doses

• flat prescription fees that encourage polypharmacy by charging the same amount
irrespective of number of drug items or quantity of each item

4. Regulatory strategies

o Drug registration

o Banning unsafe drugs - but beware unexpected results

substitution of a second inappropriate drug after banning a first inappropriate or unsafe drug

o Regulating the use of different drugs to different levels of the health sector e.g.

licensing prescribers and drug outlets

scheduling drugs into prescription-only & over-the-counter

o Regulating pharmaceutical promotional activities

PHARMACOKINETICS

The effect of the body on the drug. To produce its characteristic effects, a drug must
be present in appropriate concentrations at its sites of action. Thus, it is important to
know the interrelationship of the administration, absorption, distribution, metabolism,
and excretion/elimination of a drug and its concentration at its locus of action.

ROUTES OF ADMINISTRATION OF DRUGS

Definition

- A route of administration in pharmacology and toxicology is the path by

which a drug, fluid, poison, or other substance is taken into the body.
- Most of the drugs can be administered by different routes. Drug- and
patient-related factors determine the selection of routes for drug administration.
The factors are:
1. Characteristics of the drug.
2. Emergency/routine use.
 3. Site of action of the drug—local or systemic.
4. Condition of the patient (unconscious, vomiting, diarrhoea).
5. Age of the patient.
6. Effect of gastric pH, digestive enzymes and first-pass metabolism.
7. Patient’s/doctor’s choice (sometimes).

- Before consider the various routes of drug administration, let study of how drugs move
ody:- within the b

(Schematic diagram showing the various pharmacokinetic processes following administration of a drug.
eptor)
D drug, P protein, R r
1. LOCAL ROUTES

- It is the simplest mode of administration of a drug at the site where the

desired action is required. Systemic side effects are minimal.

i. Topical: Drug is applied to the skin or mucous membrane at various sites for local
action.

a) Oral cavity: As a suspension, e.g. nystatin; as a troche, e.g.

clotrimazole (for oral candidiasis); as a cream, e.g. acyclovir (for
herpes labialis); as ointment and jelly, e.g. 5% lignocaine
hydrochloride (for topical anaesthesia); as a spray, e.g. 10%
lignocaine hydrochloride (for topical anaesthesia).
b) GI tract: As tablet that is not absorbed, e.g. neomycin (for
sterilization of gut before surgery).
c) c) Rectum, Vaginal and anal canal:

 As an enema (administration of drug into the rectum in liquid form):

 - Evacuant enema (for evacuation of bowel): For example, soap water
enema—soap acts as a lubricant and water stimulates the rectum.
- Retention enema: For example, methylprednisolone in ulcerative colitis.

 As a suppository (administration of the drug in a solid form into the rectum), e.g.
bisacodyl— for evacuation of bowels.

 Advantages

- Used in children.
- Little first pass effect.
- Can be given in vomiting.
- Can be given in unconscious patient.
- Higher therapeutic concentrations of drug are achieved rapidly in rectum.
- For rapid evacuation of bowel, usually during gut sterilization before any
surgical or radiological procedure.

 Disadvantages

- Inconvenient.
- Drug absorption is slow and erratic.
- Irritation or inflammation of rectal mucosa can occur.

d) Eye, ear and nose: As drops, ointments and sprays (for infection,
allergic conditions, etc.), e.g. gentamicin eye/ear drops.
e) Bronchi: As inhalation, e.g. salbutamol (for bronchial asthma and
chronic obstructive pulmonary disease). Gases, volatile liquids and solids (in the
 form of finely divided powders) are inhaled for systemic and local effects.
Inhalation of solids is called insufflation.  Advantages
- Rapid absorption of the drug due to large surface area.
- First pass effect is avoided.
- Rapid local effects.

 Disadvantages

- Only few drugs can be administered.

- May produce irritation of pulmonary mucosa.
- Inconvenient procedure.
- Chances of cardiotoxicity.

f) Skin: As ointment, cream, lotion or powder, e.g. clotrimazole (antifungal) for

cutaneous candidiasis.
g) Transdermal: Transdermal patches can provide prolonged or controlled
(iontophoresis) drug delivery. Systemic absorption (Transdermal) is better with
low dose, low MWt, lipid soluble drugs

ii. Intra-arterial route: This route is rarely employed. It is mainly used during
diagnostic studies such as coronary angiography and for the administration of some
anticancer drugs, e.g. for treatment of malignancy involving limbs.
iii. Administration of the drug into some deep tissues by injection, e.g.
administration of triamcinolone directly into the joint space in rheumatoid arthritis.

- Typical Plot of Concentration versus Time after Topical Administration

- Typical Plot of
Concentration
versus Time after Inhalation Administration

- Typical Plot of
Concentration
versus Time after Rectal Administration

2. a) Systemic Routes (Enteral)

 Drugs administered by this route enter blood and produce systemic effects. Enteral
Routes It includes (i) Oral route, (ii) Buccal or Sublingual route and (iii) Rectal
route.

i. ORAL ROUTE
 It is the most common and acceptable route for drug administration. Dosage forms are
tablet, capsule, syrup, mixture, etc., e.g., paracetamol tablet for fever, omeprazole
capsule for peptic ulcer are given orally.
 Advantages:
- Convenient - portable, safe, no pain, can be self-administered.
- Cheap - no need to sterilize (but must be hygienic of course)
- Variety of dosage forms available - fast release tablets, capsules, enteric coated,
layered tablets, slow release, suspensions, mixtures
- Convenient for repeated and prolonged use.
 Disadvantages:
- Sometimes inefficient :- high dose or low solubility drugs may suffer poor
availability, only part of the dose may be absorbed. Griseofulvin was reformulated to
include the drug as a micronized powder. The recommended dose at that time was
decreased by a factor of two because of the improved bioavailability.
- First-pass effect :- drugs absorbed orally are transported to the general
circulation via the liver. Thus drugs which are extensively metabolized will be
metabolized in the liver during absorption.
e.g. the propranolol oral dose is somewhat
higher than the IV, the same is true for
morphine. Both these drugs and many others
are extensively metabolized in the liver.
 First Pass Effect

- Food :- Food and G-I motility can effect drug absorption. Often patient
instructions include a direction to take with food or take on an empty stomach.
Absorption is slower with food for tetracyclines and penicillins, etc. However, for
propranolol bioavailability is higher after food, and for griseofulvin absorption is
higher after a fatty meal.
- Local effect :- Antibiotics may kill normal gut flora and allow overgrowth of
fungal varieties. Thus, antifungal agent may be included with an antibiotic.
- Unconscious patient :- Patient must be able to swallow solid dosage forms.
Liquids may be given by tube.
 Typical Plot of Concentration versus Time after Oral Administration Fast and Slow
Release Dosage Forms
 ii. BUCCAL and SUBLINGUAL ROUTE (SL)

 Some drugs are taken as smaller tablets which are held in the mouth or under the
tongue.
 These are buccal or sublingual dosage forms.
 Buccal tablets are often harder tablets [4 hour disintegration time], designed to
dissolve slowly. Nitroglycerin, as a softer sublingual tablet [2 min disintegration time],
may be used for the rapid relief of angina.
 This Route of administration is also used for some steroids such as testosterone and
oxytocin. Nicotine containing chewing gum may be used for cigarette smoking
replacement.

 Advantages:

- Quick onset of action.

- Action can be terminated by spitting out the tablet.
- Bypasses first-pass metabolism.
- Self-administration is possible.
 Disadvantages

- It is not suitable for bitter tasting and unpalatable drug.

- It is not suitable for Irritant and lipid-insoluble drugs.
- cannot give to unconscious patient.
- Large quantities cannot be given.
 - Cannot be given in severe vomiting.

 Typical Plot of Concentration versus Time after

Buccal Administration

 Typical Plot ofConcentration versus Time after

Sublingual Administration

iii. RECTAL ROUTE  Drugs can be given in the form of solid or liquid.

- Suppository: It can be used for local (topical) effect as well as systemic effect,
e.g. indomethacin for rheumatoid arthritis.
- Enema: Retention enema can be used for local effect as well as systemic
effect. The drug is absorbed through rectal mucous membrane and produces systemic
effect, e.g. diazepam for status epilepticus in children.
 Advantages

- Used in children.
- Little first pass effect.
 - Can be given in vomiting.
- Can be given in unconscious patient.
- Higher therapeutic concentrations of drug are achieved rapidly in rectum.
- For rapid evacuation of bowel, usually during gut sterilization before any
surgical or radiological procedure.
 Disadvantages

- Inconvenient, not well accepted. May be some discomfort - Drug absorption is

slow and erratic.
- Irritation or inflammation of rectal mucosa can occur
 Typical Plot of Concentration versus Time after Rectal Administration

2. b) Systemic Routes (Parenteral)

• Routes of administration other than enteral route are called parenteral routes.
• Advantages of parenteral routes
- Onset of action of drugs is faster; hence it is suitable for emergency.
- Useful in:
- Unconscious patient.
- Uncooperative and unreliable patients.
- Patients with vomiting and diarrhoea.
- It is suitable for:
- Irritant drugs.
- Drugs with high first-pass metabolism.
- Drugs not absorbed orally.
- Drugs destroyed by digestive juices.
• Disadvantages of parenteral routes - Require aseptic conditions.
- Preparations should be sterile and is expensive.
- Requires invasive techniques that are painful.
- Cannot be usually self-administered.
 - Can cause local tissue injury to nerves, vessels, etc.

i. INTRAVENOUS (IV)

Drugs may be given into a peripheral vein over 1 to 2 minutes or longer by infusion,
or Drugs are injected directly into the blood stream through a vein.

• Drugs are administered as:

 a) Bolus: Single, relatively large dose of a drug injected rapidly or slowly as a
single unit into a vein. For example, i.v. ranitidine in bleeding peptic ulcer.
b) Slow intravenous injection: For example, i.v. morphine in myocardial
infarction.
c) Intravenous infusion: For example, dopamine infusion in cardiogenic shock;
mannitol infusion in cerebral oedema; fluids infused intravenously in dehydration.
 Advantages

- Bioavailability is 100%.
- Quick onset of action; therefore, it is the route of choice in emergency, e.g.
intravenous diazepam to control convulsions in status epilepticus.
- Large volume of fluid can be administered, e.g. intravenous fl uids in patients with
severe dehydration.
- Highly irritant drugs, e.g. anticancer drugs can be given because they get diluted in
blood.
- Hypertonic solution can be infused by intravenous route, e.g. 20% mannitol in
cerebral oedema.
- By i.v. infusion, a constant plasma level of the drug can be maintained, e.g. dopamine
infusion in cardiogenic shock.
• Disadvantages
- Once the drug is injected, its action cannot be halted.
- Local irritation may cause phlebitis.
- Self-medication is not possible.
- Strict aseptic conditions are needed.
- Extravasation of some drugs can cause injury, necrosis and sloughing of tissues.
- Depot preparations cannot be given by i.v. route.
• Precautions
- Drug should usually be injected slowly.
- Before injecting, make sure that the tip of the needle is in the vein.
• Typical Plot of Concentration versus Time during an IV Infusion
Administration

• Typical Plot of Concentration versus Time

during an IV Bolus Administration

ii. SUBCUTANEOUS (s.c.) ROUTE

 The drug is injected into the subcutaneous tissues of the thigh, abdomen and arm, e.g.
adrenaline, insulin, etc.

• Advantages:
- Actions of the drugs are sustained and uniform.
- Drugs can be given in presence of vomiting and diarrhea.
- Drugs can be given to unconscious patients.
- First pass effect is avoided.
- Drugs that are not absorbed from G.I.T can be given.
- Self-administration is possible (e.g. insulin).
- Depot preparations can be inserted into the subcutaneous tissue, e.g. norplant
for contraception.
• Disadvantages
- Only non-irritant drugs can be given otherwise severe irritation, pain and
necrosis of subcutaneous tissues can occur.
- Absorption of the drugs is slow than I/M injection.
- Expensive.
- Danger of infection, if proper sterilization techniques are not used.
- Large volumes of drug cannot be given.
• Typical Plot of Concentration versus Time during subcutaneous Administration
 iii. INTRAMUSCULAR (i.m) ROUTE

The drug is injected deep in the belly of a large skeletal muscle. The muscles that are
usually used are detoid, triceps, Gluteus,. Maximus, rectus, femurs depending on the
specie of animal.

• The muscle is less richly supplied with sensory nerves, hence injecting a drug 1m is
less painful.
• Absorption of drug from gluteal region is slow especially in females due to high fat
deposition.
• Deep intramuscular injections are given at upper outer quadrant of buttock to prevent
the injury to major nerves.
• Deep I/M injections are less painful than I/M injections on arm due to high fat
content.
• Intramuscular injections are given at an angle of 90 degrees.
• Advantages
- Rate of absorption is uniform.
- Rapid onset of action.
 - Irritant substances can be given.
- Drugs can be given to unconscious patients.
- Accuracy of dosage is ensured.
- Useful in emergency situations.
- First pass effect is avoided.
- Drugs producing gastric irritation can be given.
- Drugs that are not absorbed from G.I.T can be given.
• Disadvantages
- Small quantities up to 10 ml of the drug can be given at a time.
- Local pain and abscess formation.
- Technical person is needed, self-administration is difficult.
- Expensive.
- Danger of infection, if proper sterilization techniques are not used. - Chances of
nerve damage.
• Typical Plot of Concentration versus Time during Intramuscular
Administration
 iv. INTRATHECAL ROUTE

• Drug is injected into the subarachnoid space (spinal anaesthetics, e.g. lignocaine;
antibiotics, e.g. amphotericin B, etc.).

v. INTRA-ARTICULAR ROUTE

• Drug is injected directly into the joint space, e.g. hydrocortisone injection for
rheumatoid arthritis. Strict aseptic precautions should be taken. Repeated administration
may cause damage to the articular cartilage.

v. TRANSDERMAL ROUTE

The drug is administered in the form of a patch or ointment that delivers the drug into
the circulation for systemic effect.

• For example, scopolamine patch for sialorrhoea and motion sickness, nitroglycerin
patch/ointment for angina,
 oestrogen patch for hormone replac ement therapy (HRT).

Transdermal drug-delivery system.

vi. INTRAPERITONEAL ROUTE

 Indication: Colon and Ovarian

• Peritoneal space has much surface area; may not be reached by IV chemo
• Catheters used: implanted port
• Chemotherapy agents used: Cisplatin, Taxol  Advantages: less systemic side
effects  Disadvantages: infection, pain. vii. INTRAPLEURAL
• Seeding of pleura
• Used as sclerosing agent to stop pleural effusions
• Injected by physician into chest tube and clamped. Patient changes position 15 min
for 1 hour
• Chemotherapy agents used: Bleomycin, Adriamycin, Talc slurry  Side effects:
severe pain
ABSORPTION

Before a drug can begin working, it must be transformed from its pharmaceutical
dosage form to a biologically available (bioavailable) substance that can pass through
various biological cell membranes to reach its site of action. This process is known as
absorption. A drug’s absorption rate depends on its route of administration, its
circulation through the tissue into which it’s administered, and its solubility—that is,
whether it’s more water-soluble (hydrophilic) or fatsoluble (lipophilic).

Factors affecting drug absorption and bioavailability:

a) Physico-chemical properties of drug

b) Nature of the dosage form

c) Physiological factors

d) Pharmacogenetic factors

e) Disease states.

a) Physico-chemical properties of drug:

i) Physical state: Liquids are absorbed better than solids and crystalloids absorbed
better than colloids.

ii) Lipid or water solubility: Drugs in aqueous solution mix more readily than those
in oily solution. However at the cell surface, the lipid soluble drugs penetrate into the
cell more rapidly than the water soluble drugs.

iii) Ionization: Most of the drugs are organic compounds. Unlike inorganic
compounds, the organic drugs are not completely ionized in the fluid. Unionized
component is predominantly lipid soluble and is absorbed rapidly and an ionized is
often water soluble component which is absorbed poorly. Most of the drugs are weak
acids or weak bases.

It may be assumed for all practical purposes, that the mucosal lining of the G.I.T is

impermeable to the ionized form of a weak organic acid or a weak organic base.
These drugs exist in two forms.

Acidic drugs: rapidly absorbed from the stomach e.g. salicylates and barbiturates.

Basic drugs: Not absorbed until they reach to the alkaline environment i.e. small

intestine when administered orally e.g. pethidine and ephedrine.

b) Dosage forms:

i) Particle size: Small particle size is important for drug absorption.

Drugs given in a dispersed or emulsified state are absorbed better e.g. vitamin D and

vitamin A.

ii) Disintegration time and dissolution rate.

Disintegration time: The rate of break up of the tablet or capsule into the drug
granules.

Dissolution rate: The rate at which the drug goes into solution.
iii) Formulation: Usually substances like lactose, sucrose, starch and calcium
phosphate are used as inert diluents in formulating powders or tablets. Fillers may not
be totally inert but may affect the absorption as well as stability of the medicament.
Thus a faulty formulation can render a useful drug totally useless therapeutically.

c) Physiological factors:

i) Gastrointestinal transit time: Rapid absorption occurs when the drug is given on
empty stomach. However certain irritant drugs like salicylates and iron preparations
are deliberately administred after food to minimize the gastrointestinal irritation. But
some times the presence of food in the G.I tract aids the absorption of certain drugs
e.g. griseofulvin, propranolol and riboflavin.

ii) Presence of other agents: Vitamin C enhances the absorption of iron from the
G.I.T.

Calcium present in milk and in antacids forms insoluble complexes with the
tetracycline antibiotics and reduces their absorption.

iii) Area of the absorbing surface and local circulation:

Drugs can be absorbed better from the small intestine than from the stomach because
of the larger surface area of the former. Increased vascular supply can increase the
absorption.

iv) Enterohepatic cycling: Some drugs move in between intestines and liver before
they reach the site of action. This increases the bioavailability e.g. phenolphthalein.
v) Metabolism of drug/first pass effect: Rapid degradation of a drug by the liver
during the first pass (propranolol) or by the gut wall (isoprenaline) also affects the
bioavailability.

Thus a drug though absorbed well when given orally may not be effective because of
its extensive first pass metabolism.

d) Pharmacogenetic factors:

Individual variations occur due to the genetically mediated reason in drug absorption
and response.

e) Disease states:

Absorption and first pass metabolism may be affected in conditions like

malabsorption, thyrotoxicosis, achlorhydria and liver cirrhosis.
 DISTRIBUTION OF DRUGS

Definition:
Penetration of a drug to the sites of action through the walls of blood vessels from
the administered site after absorption is called drug distribution. Drugs distribute
through various body fluid compartments such as (a) plasma (b) interstitial fluid
compartment (c)trans-cellular compartment.

Factors determining the rate of distribution of drugs:

1. Protein binding of drug:

A variable and other significant portion of absorbed drug may become reversibly
bound to plasma proteins. The active concentration of the drug is that part which is
not bound, because it is only this fraction which is free to leave the plasma and site of
action.

(a) Free drug leave plasma to site of action

(b) binding of drugs to plasma proteins assists absorption

(c) protein binding acts as a temporary store of a drug and tends to prevent large
fluctuations in concentration of unbound drug in the body fluids

(d) protein binding reduces diffusion of drug into the cell and there by delays its
metabolic degradation e.g. high protein bound drug like phenylbutazone is long
acting.

Low protein bound drug like thiopental sodium is short acting.

2. Plasma concentration of drug (PC): It represents the drug that is bound to the
plasma proteins (albumins and globulins) and the drug in free form. It is the free form
of drug that is distributed to the tissues and fluids and takes part in producing
pharmacological effects.

The concentration of free drug in plasma does not always remain in the same level
e.g.

i) After I.V. administration plasma concentration falls sharply

ii) After oral administration plasma concentration rises and falls gradually.

iii) After sublingual administration plasma concentration rise sharply and falls
gradually.

3. Clearance: Volume of plasma cleared off the drug by metabolism and excretion
per unit time.

Protein binding reduces the amount of drug available for filtration at the glomeruli
and hence delays the excretion, thus the protein binding reduces the clearance.

4. Physiological barriers to distribution: There are some specialized barriers in the

body due to which the drug will not be distributed uniformly in all the tissues. These
barriers are:
a) Blood brain barrier (BBB) through which thiopental sodium is easily crossed but
not

dopamine.

b) Placental barrier: which allows non-ionized drugs with high lipid/water partition

coefficient by a process of simple diffusion to the foetus e.g. alcohol, morphine.

5. Affinity of drugs to certain organs: The concentration of a drug in certain tissues

after a single dose may persist even when its plasma concentration is reduced to low.
Thus the hepatic concentration of mepacrine is more than 200 times that of plasma
level. Their concentration may reach a very high level on chronic administration.
Iodine is similarly concentrated in the thyroid tissue.

METABOLISM OF DRUGS

Drugs are chemical substances, which interact with living organisms and produce
some pharmacological effects and then, they should be eliminated from the body
unchanged or by changing to some easily excretable molecules. The process by which
the body brings about changes in drug molecule is referred as drug metabolism or
biotransformation.

EXCRETION OF DRUGS
Excretion of drugs means the transportation of unaltered or altered form of drug out
of the body. The major processes of excretion include renal excretion, hepatobiliary
excretion and pulmonary excretion. The minor routes of excretion are saliva, sweat,
tears, breast milk, vaginal fluid, nails and hair.

The rate of excretion influences the duration of action of drug. The drug that is
excreted slowly, the concentration of drug in the body is maintained and the effects of
the drug will continue for longer period.

DIFFERENT ROUTES OF DRUG EXCRETION

a) Renal excretion: A major part of excretion of chemicals is metabolically

unchanged or changed. The excretion of drug by the kidney involves.

i) Glomerular filtration

ii) Active tubular secretion

iii) Passive tubular reabsorption.

The function of glomerular filtration and active tubular secretion is to remove drug
out of the body, while tubular reabsorption tends to retain the drug.

b) Hepatobiliary excretion: the conjugated drugs are excreted by hepatocytes in the

bile.
Molecular weight more than 300 daltons and polar drugs are excreted in the bile.
Excretion of drugs through bile provides a back up pathway when renal function is
impaired. After excretion of drug through bile into intestine, certain amount of drug is
reabsorbed into portal vein leading to an enterohepatic cycling which can prolong the
action of drug e.g. chloramphenicol, oral estrogen are secreted into bile and largely
reabsorbed and have long duration of action. Tetracylines which are excreted by
biliary tract can be used for treatment of biliary tract infection.

c) Gastrointestinal excretion:

When a drug is administered orally, a part of the drug is not absorbed and excreted in
the faeces. The drugs which do not undergo enterohepatic cycle

after excretion into the bile are subsequently passed with stool e.g. aluminium
hydroxide

changes the stool into white colour, ferrous sulfate changes the stool into black and
rifampicin into orange red.

d) Pulmonary excretion: Drugs that are readily vaporized, such as many inhalation

anaesthetics and alcohols are excreted through lungs. The rate of drug excretion
through
lung depends on the volume of air exchange, depth of respiration, rate of pulmonary
blood flow and the drug concentration gradient.

e) Sweat: A number of drugs are excreted into the sweat either by simple diffusion or
active secretion e.g. rifampicin, metalloids like arsenic and other heavy metals.

f) Mammary excretion: Many drugs mostly weak basic drugs are accumulated into
the milk.

Therefore lactating mothers should be cautious about the intake of these drugs
because they may enter into baby through breast milk and produce harmful effects in
the baby e.g.

ampicillin, aspirin, chlordiazepoxide, coffee, diazepam, furosemide, morphine,

streptomycin

etc.

Pharmacodynamics
Pharmacodynamics is the study of a drug's molecular, biochemical, and physiologic
effects or actions.

It comes from the Greek words "pharmakon" meaning "drug" and "dynamikos"
meaning "power."

Pharmacodynamics is the study of how drugs have effects on the body.

All drugs produce their effects by interacting with biological structures or targets at
the molecular level to induce a change in how the target molecule functions in regards
to subsequent intermolecular interactions.

The most common mechanism is by the interaction of the drug with tissue receptors
located either in cell membranes or in the intracellular fluid. The extent of receptor
activation, and the subsequent biological response, is related to the concentration of
the activating drug (the 'agonist').

Some drugs acting at the same receptor (or tissue) differ in the magnitude of the
biological responses that they can achieve (i.e. their 'efficacy') and the amount of the
drug required to achieve a response (i.e. their 'potency').

Drug receptors are the cellular components affected at the site of action.Many drugs
form chemical bonds with drug receptors, but a drug can bond with a receptor only if
it has a similar shape—much the same way that a key fits into a lock.