Introduction to Pharmacology

 Pharmacology is the science that deals with the study of drugs and their
interaction with the living systems. The word Pharmacology derived from
Greek work pharmakon meaning drug and logo means study.

 Drug is a substance used in the diagnosis, prevention, or treatment of disease.

 Pharmacokinetics is the study of the absorption, distribution, metabolism, and

excretion of drugs, what the body does the drug (In Greek kinesis means
movement).

 Pharmacodynamics is the study of the effect of the drug on the body and their
mechanism of action, what the drug does the body.

 Therapeutics deals with the use of drugs in the prevention and treatment of
disease.

 Toxicology deals with the adverse effect of the drug and the study of poisons,
detection, prevention, and treatment of poisoning (In Greek toxicon means
poison).

 Chemotherapy is the use of chemical for the treatment of infections, the term
now also includes the use of chemical to treat malignancies.

 Pharmacy is the science of identification, compounding and dispensing of

drugs. It also includes collection, isolation, purification, synthesis, and
Standardization of medical substances.

 Pharmacognosy is the study of natural (plant and animal) drug sources.

 Types of Pharmacology
1. Experimental Pharmacology
Done in the laboratory on experimental animals such as rodents and non-rodents
2. Clinical Pharmacology
On human subjects normal or deceased

Classification of Drugs
Chemical nature
Drug is discussed by a chemist and based on chemical nature we divide drugs
into:
 Inorganic drugs
 Metals and their salts (ferrous, magnesium and zinc sulphate)
 Nonmetals include sulphur
 Organic drugs
 Alkaloids (atropine, morphine, strychnine)
 Glycosides (digitoxin, digoxin)
 Proteins (insulin, oxytocin)
 Ester, amide, alcohol, glycerides
Source
Sources of drugs are discussed by a pharmacologist and pharmacist
 Natural
a. Plants e.g., Atropine, Morphine,Quinine, digoxine, pilocarpine,
physostigmine
b. Animals e.g., Insulin, heparin, gonadotrophins and antioxic sera
c. Minerals e.g., magnesium sulpate, aluminium hydroxide, iron, sulphur and
radioactive isotopes
 d. Microorganism e.g., antibacterial agents are obtained from some bacteria
and fungi. We thus have penicillins, cephalosporins, tetracycline and other
antibiotics.
e. Human: some drugs are obtained from man e.g., immunoglobulin from
blood, growth hormone from the anterior pituitary and chorionic
gonadotrophins from the urine of pregnant woman.

 Synthetic
o Most drugs now synthesized e.g., quinolones, omeprazole, sulfonamides,
pancuronium, neostigmine.
o Many drugs are obtained from cell culture e.g., urokinase from cultured
kidney cells.
o Some are now produced by recombinant DNA technology e.g., human
insulin, tissue plasmogen activator and some drugs by hybridoma
techniques, e.g., monoclonal antibodies.

 Semi-synthetic
Amoxicillin, ampicillin, doxycycline

 Bio-synthetic
Recombinant human erythropiotin, recombinant bovine somattotropine
Target organ/site of action
Classification based on target organs are done by the physicians
 Drugs acting on CNS
Diazepam, phenobarbitone
 Respiratory system
Bromhexine
 CVS
Digitoxin, digoxin
 GIT
Omeprazole, kaoline, sulphadimidine
 Urinary system
Magnesium sulphate, lasix
  Reproductive system
Oxytocin, estrogen

Mode of action
Classification based on mode of action is done by physicians and pharmacologists
 Inhibitor of bacterial cell wall synthesis
penicillin
 Protein synthesis
tetracycline
 Calcium channel blocker
Verapamil, nifedipine

Therapeutic uses
Classification based on mode of action is done by physicians and pharmacologists
 Antimicrobial/antibacterial
Penicillin, streptomycin, quinolones, macrolides
 Antihypertensive
Clonidine, hydralazine
 Antidiarrheal
Loperamide, kaoline
 Antiemetics
Domperidone, meclizine and metoclopramide
Physiological system
 Sympathomimetics
Adrenaline, noradrenaline
 Parasympathomimetic
Carbachol, pilocarpine, neostigmine
 Neuromuscular blockers
Suxamethonium, gallamine
Physical effects
  Emollients
Lanolin, Vaseline
 Caustics
Silver nitrate
 Demulcents
Zinc oxide, tannic acid

Drug Nomenclature (naming of drugs)

Chemical Name
Technical description of the actual molecule
e.g., Cozaar is 2-butyl, 4 chlorotetrazol, 5 phenylbenzylimidazole and 5 methanol
sodium
Generic Name
The official medical name Cozaar’s generic name is Losartan
Brand or Propriety Name
The name under which the product is marketed i.e., Cozaar

Routes of Drug Administration

The choice of the route in a given patient depends on the properties of the drug
and the patient’s requirements.

The route can be broadly divided into:

 Enteral
This is the most common, oldest and safest routes of drug administration.
The large surface area of the GI, the mixing of its content and the
differences in pH at different parts of the guts help effective absorption of
the drugs given orally.
Advantages:
  Safest route
 Most convenient
 Most economical
 Drugs can be self-administered
 Non-invasive route
Disadvantages:
 Onset of action is slower as absorption needs time.
 Irritant and unpalatable drugs cannot administer.
 Some drugs may not be absorbed due to certain physical
characteristics e.g., streptomycin
 There may be irregularities in absorption
 Irritation to the GIT may lead to vomiting
 Some drugs may be destroyed by gastric juiced e.g., insulin
 Cannot be given to unconscious and uncooperative patients
 Some drugs may undergo extensive first pass metabolism in liver
 Patients may forget to take the tablet which is the practical problem
Enteric Coated Tablet
o Some tablets are coated with substances like cellulose acetate,
phthalate, gluten, etc., which are not digested by the gastric acid
but get disintegrated in the alkaline juices of the intestine
o Prevent gastric irritation
o Avoid destruction of the drug by the stomach
o Provide higher concentration of the drug in the small intestine
o Slow the absorption, and there by prolong the duration of action.
Advantages:
 Frequency of administration may be reduced
 Therapeutic concentration may be maintained for along
time Specially when nocturnal symptoms are to be treated.
Disadvantages:
 It is more expensive
 There may be release of the entire amount of the drug in a
short time leading to toxicity.
 Parental
 Routes of administration other than the enteral route are known as
parenteral routes. Here the drugs are directly delivered into tissue fluids or
blood.
Advantages:
 Action is more rapid and predictable than oral administration.
 These routes can be employed in unconscious or uncooperative
patients
 Gastric irritant can be given parenterally and therefore irritation to
the GIT can be avoided.
 It can be used in patients with vomiting or those unable to swallow.
 In emergencies parenteral routes are very useful
 Digestion by the gastric and intestinal juices and the first pass
metabolism are avoided.
Disadvantages:
 Asepsis must be maintained
 Injection may be painful
 More expensive less safe and inconvenient
 Injury to nerve and other tissues may occur
Parental Route includes:
Injections
a. Intradermal
The drug is injected into the layers of the skin by:
1. Raising a bleb e.g., BCG vaccine, tests for allergy
2. By multiple punctures of the epidermis through a drop of the drug e.g.,
smallpox vaccine.
3. Only a small quantity can be administered by this route, and it may be
painful.

b. Subcutaneous (SC) injection

here the drug deposited in the SC tissues e.g., insulin, heparin. As this tissue is less
vascular, absorption is slow and largely unfirm and this make the drug long-acting.
Disadvantages:
 As SC tissue is richly supplied by nerves, irritant drugs cannot be injected
 In shock absorption is not dependable because of vasoconstriction
 Repeated administration at the same site can cause lipoatrophy
resulting in erratic absorption

Drugs can also be administered subcutaneously as:

 Dermo jet
In this method, a high velocity jet drug solution is projected from a fine
orifice using a gun. The solution gets deposited in the SC tissue from where
it is absorbed. It is suitable for vaccines.
 Pellet implantation
Small pellets packed with drugs are implanted SC. The drug is slowly
released for weeks or months to provide constant blood levels e.g.,
testosterone, desoxycortocosterone acetate
 Sialistic implants
The drug is packed in sialistic tubes and implanted SC. The drug gets
absorbed over months to provide constant blood levels e.g., hormones and
contraceptives. The empty nonbiodegradable implants has to be removed.
c. Intramuscular
o Aqueous solution of the drug is injected into one of the large skeletal
muscle-deltoid, triceps, gluteus or rectus femoris.
o Absorption into the plasma occurs by simple diffusion. Large molecules
enter through the lymphatic channels. As the muscle are vascular,
absorption is rapid and quite uniform.
o Drugs are absorbed faster from the deltoid region than gluteal region
especially in women. The volume of injection should not exceed 10 ml. For
infant’s rectus femoris is used instead of gluteus which is not well-
developed till the child start walking. Oily solution or suspension, the
absorption is slow and steady, smaller volume (1-2ml) deltoid muscle is
used if large volumes gluteal muscles should be used.
 o Soluble substances, mild irritant, depot preparations, suspensions and
colloids can be injected by this route

Advantages:
 Intramuscular route is reliable
 Absorption is rapid
Disadvantages:
 IM injection may be painful
 It may result in an abscess
 Risk of nerve injury-irritant solutions can be damaging the nerve if
injection near the nerve. The needle may also be puncturing the
blood vessel
d. Intravenous (IV)
Here, the drug is injected into one of the superficial veins so that it directly
reaches the circulation and is immediately available for action
Drug can be given IV as:
 A bolus: the drug is dissolved in a suitable amount of vehicle and
injected slowly. An initial large dose is given e.g., heparin.
 Slowly: over 15 to 20 min e.g., aminophylline
 Slow infusion: when constant plasma concentration is required e.g.,
oxytocin in labor or when large volumes have to be given e.g.,
dextrose, saline
Advantages:
 IV route is useful in emergencies because the drug is immediately
available for action.
 It gives 100% bioavailability
 Large volume and irritants can be given, they quickly diluted in blood
 Rapid dose adjustments are possible-if unwanted effects occur,
infusion can be stopped.
Disadvantages:
 Once injected, the drug cannot be withdrawn
 Irritation of the vein may cause thrombophlebitis
  Self-medication is difficult
 The solution should be sterile and strict aseptic measure should be
taken
Administration of IV Solution
 Maintain strict asepsis
 Before starting infusion, the IV line should be flushed with saline
 Watch for sign of extravasation of fluid and thrombophlebitis
 Make sure that there are no air bubbles in syringe and tubing
e. Intraperitoneal
 peritoneum offers a large surface area for absorption
 this route is also used for peritoneal dialysis
f. Intrathecal
drugs can be injected into the subarachnoid space for action on the CNS
e.g., spinal anesthetics. Some antibiotics and corticosteroids are also
injected by this route to produce high local concentrations.
g. Intra-articular
drugs are injected directly into a joint for the treatment of arthritis and
other disease of the joints strict aseptic precautions are required e.g.,
hydrocortisone us injected into affected joint in the rheumatoid arthritis
h. Intra-arterial
here the drug is injected directly into the arteries. It is used only in the
treatment of peripheral vascular disease, local malignancies, and
angiograms.
i. Intramedullary
this route involves injection into a bone marrow now but not this rarely
used

Inhalation
Volatile liquids and gases are given by inhalation e.g., GA. Solution of drug
particles and the fine droplets are inhaled as aerosol, e.g., Salbutamol. Inhaled
drugs and vapor may act and absorbed on the pulmonary epithelium and mucous
membranes of the respiratory tract.
Advantages:
 Almost instantaneous absorption of the drug achieved because large
surface area of the lungs.
 Hepatic first pass metabolism is avoided
 Absorption and excretion through lunges
Disadvantages:
Irritant gasses may enhance pulmonary secretions and should be avoided
by this route.

Transdermal route
Highly lipid soluble drugs can be applied over the skin for slow and prolonged
absorption e.g., nitroglycerin ointment in angina pectoris. Adhesive units,
inunction, iontophoresis, and jet injection are some forms of transdermal drug
delivery.
Adhesive units:
Adhesive patches of different sizes and shapes made to suit the area of
application. Site of the application are chest, abdomen, upper arm, back or
mastoid region, e.g., hyoscine, nitroglycerin fentanyl, estrogen,
testosterone transdermal patches.

Advantages:
 Duration of action is prolonged
 Provide constant plasma levels
 Patient compliance is good

Inunction:
In this route of administration, the drug is rubbed into the skin and it gets
absorbed to produce systemic effects
Iontophoresis:
  In this procedure, galvanic current is used for bringing about
penetration of lipid insoluble drugs into the deeper tissues where its
action is required, e.g., salicylates, fluoride iontophoresis is used in
the treatment of dental hypersensitivity
 Jet injection
 As absorption of drug occurs across the layers of the skin
Transmucosal
Drugs are absorbed across the mucous membranes. It includes sublingual, nasal
and rectal routes.
Sublingual:
Here, the tablet or pellet containing the drug is placed under the tongue. It
dissolved and the drug is absorbed across the sublingual mucosa, e.g.,
Nitroglycerin, nifedipine, buprenorphine

Advantages:
Absorption is rapid- within minutes the drug reached the circulation.
First pass metabolism is avoided
After the desired effect of obtained, the drug can be spat out to avoid the
unwanted effects.
Disadvantages:
Buccal ulceration can occur.

Nasal:
Drugs can be administered through nasal routes e.g., oxytocin spray,
oxymetazoline, budesonide for allergic rhinitis

Rectal:
o Rectum has a rich blood supply and drugs can cross the rectal
mucosa to be absorbed for systemic effect.
o Drugs absorbed from the upper part of the rectum are carried by the
superior hemorrhoidal vein to the portal circulation e.g.,
indomethacin, chlorpromazine, diazepam can be given rectally.
Advantages:
 Gastric irritation is avoided
Can be administered by unskilled persons
Useful in geriatric patient and others with vomiting and those unable to
swallow
Disadvantages:
Irritation of the rectum can occur
Absorption may be irregular and unpredictable (enema)

Enema
Is the administration of a drug in liquid form into the rectum. Enema may be
evacuant or retention enema
Evacuant enema:
In order to empty the bowel, about 600 ml of soap water
administered per rectum. It is given prior to surgeries, obstetric
procedures and radiological examination of gut

Retention enema:
The drugs are administered with about 100ml of fluid and is retained
in the rectum for local action e.g., prednisolone enema in ulcerative
colitis

 Local
Topical
Drugs may be applied on the skin for a local action as ointment cream, gel,
powder, paste, etc., drugs may also be applied on the mucous membrane ascin
the eyes, ears, and nose as ointment, drops and sprays.
Drugs may be administered as suppository for rectum, bougie for urethra and
pessary (oval shape) and douche for vagina e.g., antifungal pessaries in vaginal
candidiasis

Special Drug Delivery System:

In order to improve drug delivery, to prolong the duration of action and improve
the patient compliance, special drug delivery system is used.
Some such systems are:
Ocusert
Systems that are thin elliptical units that contains the drug reservoir which slowly
release the drug by diffusion e.g., pilocarpine ocusert used in glaucoma is placed
under the lid can deliver the pilocarpine for 7 days.
Progestasert
Inserted into the uterus where it delivers progesterone constantly for one year.
Transdermal adhesive unit:
 Prodrug
is an inactive form of a drug which gets metabolized to the active derivative
in the body e.g., dopamine does not cross BBB but levo dopa a prodrug
crosses BBB and it is converted to dopamine in the CNS.
 Osmotic pumps
are smaller tablet shape units containing the drug and an osmotic
substance in two different chambers. The tablet swallowed and reached
the gut, water enter into the tablet through SPM. The osmotic layers swells
and pushes the drug slowly.
 Computerized pumps
These are programed to release drugs at a definite rate and continuously
e.g., insulin and anticancer drugs.

Method using monoclonal antibodies

Are antibodies against the tumor
Liposome as carriers
Are phospholipids suspended in aqueous vehicles to form minute vesicles. Drugs
encapsulate in liposomes mainly used for malignant tumors.
 Nurses Responsibilities
 Ensure the correct drug is administered by the right route and in the right
dose.
 History of allergy should be taken particularly before parental
administration of the drugs.
 Monitor the adverse effect.
 Drugs should be kept in safe place.
 Check the prescription, drug label and the patients name before the
administration of drugs.

Drug Attachment
Agonist
Chemical fits at receptor site well
Antagonist
a chemical from getting to a receptor
Partial agonist
Attach to the receptor but only produce a small effect
Basics of Drug Action:
Desired action
The expected response of a medication
Side effects
Known and frequently experienced, expected reaction to drug
Adverse reaction
Unexpected, unpredictable reactions that are not related too usual effects of a
normal dose of the drug

Drug Interaction:
 Takes place when one drug alters the action of another drug.
 Some are helpful but often produce adverse effects.
Common Drug Interactions:
 Additive effect
takes place when 2 drugs are given together and double the effect is produced.
e.g., Alcohol + aspirin = pain relief
 Antagonist
a chemical blocks another chemical from getting to a receptor
 Antagonistic effect
Takes place when 1 drug interferes with the action of another drug
e.g., protamine sulpha to counteract heparin toxicity
 Displacement effect
Takes place when 1 drug replaces another at the drug receptor site, increasing the
effect of the 1st drug.
 Incompatibility
Occurs when 2 drugs mixed together in a syringe produce a chemical reaction so
they cannot be given.
e.g., protamine sulfate and vit K
 Interference
Occurs when 1 drug promotes the rapid excretion of another, thus reducing the
activity of the 1st.
  Synergistic effect
Takes place when the effect of 2 drugs taken at the same time is greater than the
sum of each drug given alone
e.g., combining diuretics and adrenergic blockers to lower the BP

Pharmacokinetics
 Is the study of the absorption, distribution, metabolism, and excretion of
the drugs, i.e., the movement of the drugs into, within and out of the body.
 Once drug is administered, it is absorbed, i.e., enters the blood, is
distributed to different parts of the body, reaches the site of action, is
metabolized, and excreted.
 All these processes involve passage of the drug molecules across various
barriers- like the intestinal epithelium, cell membrane, renal filtering
membrane, capillary barrier.
 Drugs may be transported across the membrane by passive or active
transport.
Passive transport:
The drug moves across a membrane without any need for energy
Active transport:
 It is the transfer of drugs against a concentration of drugs against a
concentration gradient and needs energy. It is carried by a specific
carrier protein
 Only drugs related to natural metabolites are transported by this
process
 e.g., levodopa, iron, amino acids, penicillin and probenecid are given
together, the excretion of penicillin is delayed by probenecid
Absorption
Is defined as the passages of the drug from the site of administration into the
circulation. For a drug to reach its site of action, it must pass through various
membranes depending on the route of administration.
Factors influence the rate and extent of absorption of a drug:
 1. Disintegration and dissolution time
2. Formulation
3. Particle size
4. Lipid solubility
5. pH and ionization
6. Area and vascularity of the absorbing surface
7. Gastrointestinal motility
8. Presence of food
9. Metabolism
10.Diseases

First pass metabolism

Is the metabolism of the drug during its passage from the site of absorption to the
systemic circulation. It is also called presystemic metabolism or the first pass
effect.
 Bioavailability
 Bioequivalence
Distribution
After a drug reaches the systemic circulation, it gets distributed to various tissues.
It should be cross several barriers before reaching the site of action.

Plasma Protein Binding

On reaching the circulation, most of the drug bind to plasma protein; acid drug
mainly binds with albumin and basic drugs to acid glycoprotein. The free or
unbound fraction of the drug is the only form available for action, metabolism
and excretion.
 Tissue binding
 Blood brain barrier (BBB)
 Placenta barrier
Metabolism
Or biotransformation is the process of biochemical alteration of the drug in the
body. Body treats most of the drugs as foreign substance and tries to inactivate
and eliminate them by various biochemical reactions.
Chemical reaction take place into two phases:
1. Phase 1 (non-synthetic reactions
2. Phase 2 (synthetic reaction)

Excretion
 The major organ of excretion are the kidneys, intestine, biliary system, and
the lungs. Drugs are small amount are excreted in saliva, sweat, and milk.
 Renal secretion
 Kidney is the most important organ of drug excretion. Highly lipid soluble
drugs are reabsorbed in the renal tubules, so their excretion is slow.

Plasma half-life (t1/2) is the time taken for the plasma

Minimum dose is the smallest dose required to produce desired therapeutic effect
Maximum dose is the largest dose that can be safely given to a patient without
harmful effect
Toxic dose drug dose which produces undesirable effects in majority of the
patient
Lethal dose drug dose which can cause death

Pharmacodynamics
 is the study of actions of the drugs on the body and their mechanism of
action. To know what drugs, do and how they do it.
  Drugs produce their effects by interacting with the physiological system of
the organism. By such interaction drugs can only modify the rate of
function of various systems.
 e.g., drugs may increase or decrease the secretions, but they cannot change
the basic function of any physiological system.
Drugs act by:
1. Stimulation
2. Depression
3. Irritation
4. Replacement
5. Anti-infective or cytotoxin action
6. Modification of the immune status

Site and mechanism of drug action:

Sites: drugs may produce their effects by locally or systematically.
Local: drugs may act at the site of application e.g., antibiotics, antifungal agent

Fundamental mechanism of drug action may be:

1. Through receptor
2. Through enzymes and pumps
3. Through ion channel
4. By physical action
5. Chemical interaction
6. Altering metabolic processes

Factor modifying the drug action:

1. Body weight
2. Age
3. Sex
4. Species and race
5. Diet and environment
6. Route of administration
7. Genetic factor
(Acetylation of drugs and G6PD deficiency)
8. Dose
9. Diseases
10.Repeated dosing
(Cumulative, tolerance and trachy phylaxis)
11.Physiological factor
12.Presence of other drugs