UNIT 1

General pharmacology
NEETHU MV
❑ Pharmacology is the branch of medicine with a unique
combination of several biomedical sciences- chemistry,
biochemistry, physiology and clinical medicine.

❑ Pharmacology is both basic and an applied science.

❑ Pharmacology deals with the knowledge of drugs, their sources,

biochemical and physiological effects, mechanism of action, and
therapeutic use of drug.

❑ Pharmacology studies the effect of drugs and how they exert

their effect.
Ancient Era (Before 500 CE)
• Early humans used plants, minerals, and animal products for healing.
• Ancient Egyptians, Chinese, and Indians documented medicinal plants (e.g., the
Ebers Papyrus from Egypt, Ayurveda from India).
• Hippocrates (460–370 BCE) and Dioscorides (1st century CE) contributed to
rationalizing medicine and drug use.
• Galen (129–216 CE) developed the concept of Galenic pharmacy, preparing
complex mixtures of herbs.
Middle Ages (500–1500 CE)
• Arab scholars like Avicenna (Ibn Sina) wrote the "Canon of Medicine," a
foundational text in pharmacology.
• The development of alchemy in the Islamic world led to the discovery of new
drug formulations.
• Monasteries in Europe preserved and copied medical texts.
Renaissance & Early Modern Period (1500–1800)
▪ The rise of scientific experimentation led to improved drug
formulations.
▪ Paracelsus (1493–1541) challenged Galenic medicine and promoted
the idea that "the dose makes the poison”.
▪ The Materia Medica books expanded with new herbal discoveries.
19TH CENTURY – BIRTH OF MODERN PHARMACOLOGY
• Rudolf Buchheim (1820–1879) established the first pharmacology lab in
Estonia.
• Oswald Schmiedeberg (1838–1921) is considered the father of modern
pharmacology.
• Development of synthetic drugs like aspirin (1899).
• The study of drug mechanisms and effects became more systematic.

20TH CENTURY – THE GOLDEN AGE OF PHARMACOLOGY

• Discovery of antibiotics (e.g., penicillin in 1928 by Alexander Fleming).
• Development of vaccines, anesthetics, and chemotherapy.
• Pharmacokinetics and pharmacodynamics became core scientific
concepts.
• Establishment of regulatory agencies (FDA, WHO) for drug safety.
• 6. 21st Century – The Era of Personalized Medicine
DRUGS
• French :Drogue – a Dry herb
• “Drug is any substance or product that is used or intended to be used
to modify or explore physiological system or pathological state for the
benefit of the recipient”
Essential Drugs
• Definition “Essential drugs are those that satisfy the health care
needs of majority of population”

• Should available at all times

• In adequate amounts
• In the adequate dosage forms
History of the WHO Model List of Essential Drugs
1977 First Model list published, ± 200 active substances
• List is revised every two years by WHO Expert Committee
• Last essential drug list established in the year 2022

Guidelines for establishing a national programme for essential drugs

• National drug regulatory authority should be established
• National drug and therapeutic committee (NDTC) should be established
• Committee includes people from
Medical
Clinical Pharmacology
Pharmacy Public health fields
Also from other appropriate health care fields
• Generic names should be used for all drugs
• Concise, accurate and comprehensive drug information should be
prepared
• Stability and bioavailability should be assured
• Efficient administration of supply, storage and distribution of drugs
• Management of stocks and eliminate waste
Criteria for the selection of essential drugs
• Pattern of prevalent disease and treatment facilities
• Financial resources available in the country
• Genetic, demographic and environmental factors
• Evidence based and not situation based
• Selected drugs should have adequate data on their efficacy and safety
• Performance of drugs in general has been proved in a variety of
medical setting
• Available in adequate quantities and in the dosage forms that is
recommended by NDTC
• Assured quality, stability and bioavailability
• Two or more drugs having same quality, stability and bioavailability,
choice on the basis of efficacy, safety, quality, price and availability
Cost.
• unit cost of drug alone should not be considered. Cost of total
treatment, cost/benefit ratio should also be considered
• Comparative pharmacokinetic properties of drugs in the same
therapeutic category
• Local facilities to manufacture and storage also be considered
• Should contain only single drug,
• Safety and patient compliance
 Selection of Pharmaceutical dosage forms
• General utility and wide availability of the dosage forms
• Tablets have wide acceptability and also cost effective
• Stability of dosage form under ambient climate conditions
• Established local preference
• Bioavailability and pharmacokinetics of dosage forms
• Selection of convenient dosage forms for selected population
Eg: Paediatric dosages, SR/CR dosage inclusion require adequate documentation
• Selection of specified salt form for a particular drug
• Example: Chloramphenicol Palmitate, Amlodipine Besylate,Erythromycin estolate
 DRUG NOMENCLATURE

(a) Chemical name

It describes the sub stance chemically, e.g. 1-(Isopropylamino)-3 (1-naphthyloxy) propan-2-ol for propranolol.

(b) Non-proprietary (Generic) name

It is the name accepted by a competent scientific body/ authority, e.g. the United States Adopted Name (USAN) by the
USAN council. Similarly, there is the British Approved name (BAN) of a drug.
e.g. ‘meperidine’ and ‘pethidine’ or ‘lidocaine’ and ‘lignocaine’ for the same drugs.

(c) Proprietary (Brand) name

It is the name assigned by the manufacturer(s) and is his property or trade mark. One drug may
have multiple proprietary names, e.g. AMCARD, AMLOGARD, AMLOCOR, AMLONG, AMLOPIN, AMLOVAS, STAMLO
for amlodipine from different manufacturers.
ROUTES OF DRUG ADMINISTRATION
• Factors governing choice of route
• 1. Physical and chemical properties of the drug (solid/liquid/gas; solubility,
stability, pH, irritancy).
• 2. site of desired action—localized and approachable or generalized and not
approachable.
• 3. rate and extent of absorption of the drug from different routes.
• 4. effect of digestive juices and first pass metabolism on the drug.
• 5. rapidity with which the response is desired (routine treatment or
emergency).
• 6. accuracy of dosage required (i.v. and inhalational can provide fine tuning).
• 7. condition of the patient (unconscious, vomiting)
 • Routes can be broadly divided into those
(a) Local action
(b) Systemic action.
LOCAL ROUTES SYSTEMIC ROUTES
These routes can only be used for localized lesions at The drug administered through systemic routes is
accessible sites and for drugs whose systemic intended to be absorbed into the blood stream and dis
absorption from these sites is minimal or absent. tributed all over, including the site of action, through
Systemic side effects or toxicity are consequently absent circulation
or minimal 1. Oral
1. Topical 2. Sublingual (s.l.) or buccal
2. Deeper tissues 3. Rectal
3. Arterial supply 4. Cutaneous
5. Inhalation
6. Nasal
7. Parenteral
LOCAL ROUTES
1. Topical
❑This refers to external application of the drug to the surface for localized
action. It is often more convenient as well as reassuring to the patient.
❑Drugs can be efficiently delivered to the localized lesions on skin,
oropharyngeal/ nasal mucosa, eyes, ear canal, anal canal or vagina in the form
of lotion, ointment, cream, powder, rinse, paints, drops, spray, lozengens,
suppositories or pesseries.
❑Nonabsorbable drugs given orally for action on g.i. mucosa (sucralfate,
vancomycin), inhalation of drugs for action on bronchi (salbutamol cromolyn
sodium) and irrigating solutions/jellys (povidone iodine, lidocaine) applied to
urethra are other forms of topical medication.
2. Deeper tissues
❑Certain deep areas can be approached by using a syringe and needle,
but the drug should be in such a form that systemic absorption is
slow,
❑e.g. intra-articular injection (hydrocortisone acetate in knee joint),
❑e.g. infiltration around a nerve or intrathecal injection (lidocaine),
❑e.g. retrobulbar injection (hydrocortisone acetate behind the
eyeball).
3. Arterial supply
❑Close intra-arterial injection is used for contrast media in
angiography;
❑anticancer drugs can be infused in femoral or brachial artery to
localize the effect for limbmalignancies.
 SYSTEMIC ROUTES
• The drug administered through systemic routes is intended to be absorbed
into the blood stream and dis tributed all over, including the site of action,
through circulation
1. Oral
2. Sublingual (s.l.) or buccal
3. Rectal
4. Cutaneous
5. Inhalation
6. Nasal
7. Parenteral
 SYSTEMIC ROUTES

Vascular pathway Of drugs absorbed from various systemic route of administration and sites of first pass metabolism
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• Oral ingestion is the oldest and commonest mode of drug

administration.
• It is safer, more convenient, does not need assistance, non invasive,
often painless, the medicament need not be sterile and so is cheaper.
• Solid dosage forms (powders, tablets, capsules,moulded tablets,
gastrointestinal therapeutic systems—GITs) and Liquid dosage forms
(elixirs, syrups, emulsions, mixtures) can be given orally
Limitations of oral route of administration
• Action of drugs is slower and thus not suitable for emergencies.
• Unpalatable drugs (chloramphenicol) are difficult to administer; drug
may be filled in capsules to circumvent this.
• May cause nausea and vomiting.
• Cannot be used for uncooperative/unconscious/ vomiting patient.
• Absorption of the drug may be variable and erratic; certain drugs are
not absorbed (streptomycin).
• others are destroyed by digestive juices (penicillin g, insulin) or in liver
(GTN, testosterone, lidocaine)
[Link] (s.l.) or buccal

• The tablet or pellet containing the drug is placed under the tongue or
crushed in the mouth and spread over the buccal mucosa.
• Only lipid soluble and non-irritating drugs can be so administered.
Absorption is relatively rapid—action can be produced in minutes.
• Though it is somewhat inconvenient, one can spit the drug after the
desired effect has been obtained.
• The chief advantage is that liver is bypassed and drugs with high first
pass metabolism can be absorbed directly into systemic circulation.
• Drugs given sublingually are—GTN, buprenorphine, desamino-oxytocin.
3. Rectal

• Certain irritant and unpleasant drugs can be put into rectum as

suppositories or retention enema for systemic effect.
• This route can also be used when the patient is having recurrent
vomiting or is unconscious
• Disadvantage: inconvenient and embarrassing; absorption is slower,
irregular and often unpredictable
• Diazepam solution and Paracetamol suppository are rapidly and
dependably absorbed from the rectum in children.
 [Link]

• Highly lipid soluble drugs can be applied over the skin for slow and
prolonged absorption.
• The liver is also bypassed.
• The drug can be incorporated in an ointment and applied over specified
area of skin.
• Absorption of the drug can be enhanced by rubbing the preparation, by
using an oily base and by an occlusive dressing.
• Eg. Transdermal therapeutic systems (TTS)
• Transdermal therapeutic systems (TTS)
5. Inhalation

• Volatile liquids and gases are given by inhalation for systemic action,
e.g. general anesthetics.
• Absorption takes place from the vast surface of alveoli—action is very
rapid.
• When administration is discontinued the drug diffuses back and is
rapidly eliminated in expired air.
• Irritant vapours (ether) cause inflammation of respiratory tract and
increase secretion
6. Nasal

• The mucous membrane of the nose can readily absorb many drugs;
digestive juices and liver are bypassed.
• However, only certain drugs like GnRH agonists, calcitonin and
desmopressin applied as a spray or nebulized solution have been
used by this route.
• This route is being tried for some other peptide drugs like insulin, as
well as to bypass the blood-brain barrier.
7. Parenteral (Par—beyond, enteral—intestinal)
• Parenteral refers to administration by injection which takes the drug directly into the
tissue fluid or blood without having to cross the enteral mucosa.
• The limitations of oral administration are circumvented.
• ADV: Drug action is faster and surer (valuable in emergencies).
1. Gastric irritation and vomiting are not provoked. Parenteral routes can be
employed even in unconscious, uncooperative or vomiting patient.
2. There are no chances of interference by food or digestive juices. Liver is bypassed.
• Disadvantages:
1. parenteral routes are—the preparation has to be sterilized and is costlier, the
technique is invasive and painful,
2. assistance of another person is mostly needed (though self injection is possible, e.g.
insulin by diabetics),
3. there are chances of local tissue injury and, in general, parenteral route is more risky
than oral.
 PARENTERAL

(i) Subcutaneous (s.c.)

(a) Dermojet
(b) Pellet implantation
(c) Sialistic (nonbiodegradable) and bio degradable implants
(ii) Intramuscular (i.m.)
(iii) Intravenous (i.v.)
(iv) Intradermal injection
• SUBCUTANEOUS (S.C.)
The drug is deposited in the loose subcutaneous tissue which is richly supplied by nerves
(irritant drugs cannot be injected) but is less vascular (absorption is slower than
intramuscular).
▪ Only small volumes can be injected s.c. Self injection is possible because deep
penetration is not needed
(a) Dermojet In this method needle is not used; a high velocity jet of drug solution is
projected from a microfine orifice using a gun like implement. The solution passes
through the superficial layers and gets deposited in the subcutaneous tissue. It is
essentially painless and suited for mass inoculations.
(b) Pellet implantation The drug in the form of a solid pellet is introduced with a trochar
and cannula. This provides sustained release of the drug over weeks and months, e.g.
DOCA, testosterone
(c) Sialistic (nonbiodegradable) and bio degradable implants Crystalline drug is packed in
tubes or capsules made of suitable materials and implanted under the skin. Slow and
uniform leaching of the drug occurs over months providing constant blood levels. The
nonbiodegradable implant has to be removed later on but not the biodegradable one.
This has been tried for hormones and contraceptives (e.g. NORPLANT).
Dermojet Pellet implantation (c) Sialistic (nonbiodegradable) and bio
degradable implants
(ii) INTRAMUSCULAR (I.M.)
The drug is injected in one of the large skeletal muscles—deltoid,
triceps, gluteus maximus, rectus femoris, etc.
Muscle is less richly supplied with sensory nerves (mild irritants can be
injected) and is more vascular (absorption of drugs in aqueous solution
is faster).
It is less painful, but self injection is often impracticable because deep
penetration is needed.
Depot preparations (oily solutions, aqueous suspensions) can be
injected
Intramuscular injections should be avoided in anticoagulant treated
patients, because it can produce local haematoma.
(iii) INTRAVENOUS (I.V.)
The drug reaches directly into the blood stream and effects are produced immediately
(great value in emergency). The intima of veins is insensitive and drug gets diluted with
blood, therefore, even highly irritant drugs can be injected i.v.,
ADR
thrombophlebitis of the injected vein and necrosis of adjoining tissues if extravasation
occurs.
These complications can be minimized by diluting the drug or injecting it into a running i.v.
line. Only aqueous solutions (not suspensions, because drug particles can cause embolism)
are to be injected i.v. and there are no depot preparations for this route.
Chances of causing air embolism is another risk.
The dose of the drug required is smallest (bioavailability is 100%) and even large volumes
can be infused.
Advantage with this route is—in case response is accurately measurable (e.g. BP) and the
drug short acting (e.g. sodium nitroprusside), titration of the dose with the response is
possible.
However, this is the most-risky route—vital organs like heart, brain, etc. get exposed to
high concentrations of the drug.
INTRADERMAL INJECTION
The drug is injected into the skin raising a bleb (e.g. BCG vaccine,
sensitivity testing) or scarring/multiple puncture of the epidermis
through a drop of the drug is done.
This route is employed for specific purposes only.
• Agonist: An agent which activates a receptor to produce an effect
similar to that of the physiological signal molecule.

• Antagonist: An agent which prevents the action of an agonist on a

receptor or the subsequent response, but does not have any effect of
its own.
Spare receptors are receptors that remain unbound when an agonist
is producing its maximal biologic response.

Eg. Morphine (µ receptor), clonidine receptor (a2 )