Objectives of General Pharmacology

@ the end of this session you will be able to: answer the following question.

1. What Pharmacology is?

2. What do you meant by drugs?

3. What are the different source of drugs.

4. Difference between Pharmacokinetics and Pharmacodynamics.

5. Principles of Pharmacokinetics & Pharmacodynamics.

Before knowing or studying Pharmacology you must aware or know about basic

processes of human life like;

 Physiology: The branch of biology that deals with the normal functions of
living organisms and their parts.

The way in which a living organism or bodily part functions.

Example : Physiology of Brain, heart, stomach etc…………

 Biochemistry : The field of science that deals with the study of chemical
processes in plants and animals.

OR

The chemistry of biology, the application of the tools and concepts of

chemistry to living systems.
 What is Pharmacology?

PHARMACOLOGY
means:
“THE SCIENCE OF DRUGS”
 DRUG
• A French word ‘Drogue’ which means dry herb.

• Any substance that brings about a change in biologic function through its chemical
action.

• Alters state in the body: = can’t create new function but alter existing function.

• Are poisons if they used irrationally.

• Poisons are drugs that have almost exclusively harmful effects. However, Paracelsus
famously stated that;

"the dose makes the poison,“

• Poisons in small doses are the best medicines; and useful medicines in too large doses
are poisonous.

“Every drug is a medicine but every medicine is not a drug!!!”

 Basic Areas of Pharmacology
• Two main Branches of Pharmacology are; Pharmacokinetics & Pharmacodynamics

• Pharmacokinetics: deals with absorption, distribution, biotransformation & excretion

of drugs.

• Pharmacodynamics: study of biochemical & physiological effects of drugs & their

MOA.

• Pharmacotherapeutics: use of drugs in prevention & treatment of disease.

• Chemotherapy: effect of drugs upon microorganisms, parasites and neoplastic cells

living & multiplying in living organism.

• Toxicology: branch of pharmacology which deals with the undesirable effects of

chemicals on living systems.

• Pharmacogenomics: relationship of individual’s genetic makeup to his/her response to

specific drugs.
 Application of pharmacology
• To control speed of onset, intensity of the drug‘s effect, and duration of
action. Hence decide on route of administration, the amount and
frequency of each dose, and the dosing intervals.

• To identify the possible side effect, and withdrawal symptoms of drugs and
take measures to manage.

• To avoid adverse effects from drug interaction and contraindicated

drugs.

• To avoid adverse effects in special populations like geriatrics, paediatrics,

pregnant and lactating mothers.

• To avoid treatment failure due to tolerance & resistance.

• To control misuse of drugs by the patient & health professionals.

 DRUGS

• Drugs mostly interact with a specific molecule in a biologic system that

plays a regulatory role [receptor].

• Clinically, drugs are used for;

– Diagnosis: Barium salts

– Prevention: Vaccines, chemoprophylaxis

– Treatment: Anti-inflammatory drug against inflammation

– Cure: Antibiotics

– Alteration of physiological processes:

Hormones & their derivatives (insulin, GH, contraceptives….)

– Global effect: General anesthetics

 Source of Drugs
• Drugs are obtained from various sources.

• Drugs may be synthesized within the body (hormones) or not. i.e. xenobiotics

 According to sources they are classified as;

1. Natural drugs

A. Plants :- Digoxin from Digitalis purpurea, Atropine from Atropa belladonna

B. Animals:- Insulin from pork/beef, Cod liver oil from Cod fish liver.

C. Minerals: Iron, Iodine, Potassium salts etc…

D. Micro – organisms: Penicillin from penicillium notatum, Chloramphenicol

from Actinomycetes
2. Synthetic drugs: prepared by chemical synthesis in pharmaceutical
laboratories.

Examples: Sulphonamides, quinolones, barbiturates etc…

3. Semi-synthetic drugs: prepared by chemical modification of natural drugs.

Examples: Ampicillin from penicillin G, Dihydroergotamine from

ergotamine.

4. Biosynthetic drugs: prepared by cloning of human DNA in to the bacteria

like E.coli.

Examples: Human insulin (humulin), human GH.

 Routes of Drug administration
• It is the path by which a drug, fluid, poison or other substance is brought into

contact with the body.

• Factors governing choice of Route

1. Drug characteristics

2. Ease of administration

3. Site of action

4. Onset of action

5. Duration of action

6. Quantity of drug administered

7. Liver and kidney diseases

Classification
 Local Routes

• These can only be used for localised lesions at accessible sites & for drugs
whose systemic absorption from these sites is minimal.

E.g. GTN applied as ointment

• High concentrations are attained at desired site without exposing rest of

body.

 The local routes are:

1. Topical

2. Deeper tissues

3. Arterial Supply
 Topical route
 This refers to external application of the drug to the surface for localized
action.

 Skin: Drug is applied as ointment, cream, lotion, paste, powder, dressing etc.
Mucous membrane: The dosage form depends on the site ;

a. Mouth and pharynx: Paints, lozenges, mouth washes, gargles.

b. Eyes, ears and nose: As drops, ointments, irrigation, nasal spray.

c. Gastrointestinal tract: As non-absorbable drugs given orally e.g. aluminium

hydroxide, kaolin, neomycin.

d. Bronchi and lungs: As inhalations, aerosols (nebulised solution or fine

powder) e.g. salbutamol, cromolyn sodium.

e. Urethra: As jellies e.g. lidocaine, irrigating solutions.

f. Vagina: As pessaries, vaginal tablets, inserts, cream, powders, douches.

g. Anal canal: As ointment, suppositories

 Deeper tissues
• Another local/ Parenteral route of administration though invasive. The drug is
in such state that absorption is slow and systemic absorption is minimal.

Example: Hydrocortisone acetate in knee joint/ retrobulbar injection

 Arterial Supply
• Local but Parenteral route attained by drug with minimal systemic absorption

Example: 1. Intra-arterial injection for contrast media in angiography.

2. Anti–cancer drugs in femoral artery/ brachial artery to localise

malignancies in limbs.
 Systemic Routes of Administration

1. Enteral Route

Enteral means - drugs placed directly in the GI tract.

2. Parenteral Route

Parenteral means - drugs placed other than GI tract.

3. Inhalation Route

Inhalation means – drugs are inhaled by mouth or nose to lungs.

 Enteral Route

Oral Sublingual Rectal

 Oral Route of administration
Oral - swallowing

ADVANTAGES
 Safe DISADVANTAGES
 Convenient  Slow absorption -----slow action
 Economical  Irritable and unpalatable drugs
 Usually good absorption  Un co-operative & unconscious pts.
 Can be self administered  Some drugs destroyed
 First-pass effect
 Sublingual Route
Sublingual - placed under the tongue
ADVANTAGES

 Economical DISADVANTAGES

 Quick termination  Unpalatable & bitter drugs

 Irritation of oral mucosa
 First-pass avoided
 Large quantities not given
 Drug absorption is quick
 Few drugs are absorbed
 Can be self administered
 Rectal Route
Rectal - absorption through the rectum
ADVANTAGES

 Used in children Vaginal Routes

 Little or no first pass effect Drug may be administered locally in the

vagina in the form of pessaries.
 Used in vomiting / unconscious
Example: 1. Antifungal vaginal pessaries
 Higher concentrations rapidly achieved
2. Steroidal pessaries

DISADVANTAGES
Inconvenient
Absorption is slow and erratic
Irritation or inflammation of rectal mucosa can occur
• Parenteral Route

Needle insertion for parenteral drug:

A. Intradermal injection @15⁰.
B. Subcutaneous injection @45⁰.
C. Intramuscular injection @90⁰.
D. Intravenous injection
 INTRADERMAL
 Drug injected into the layers of
skin raising a bleb
Example: BCG vaccine, allergy test
Disadvantage
• small amount of drug injected
• may be painful
SUBCUTANEOUS
 Reliable & Patients can be trained for
self-administration
Example: Insulin, Heparin
Disadvantages
• Irritant drugs can cause severe pain- due
to rich nerve supply.
• Less vascular tissue – slows absorption
& if vasoconstriction is there then further
decreases absorption.
• Repeated injections at same site
may lead into lipoatrophy and decreased
absorption
 Intramuscular Injection

 More reliable

 Highly vascular & ↑ absorption

 Irritants, depot preparations, suspensions, colloids can be injected

Disadvantages

• Painful

• Nerve liable to injury or irritation

• Local infection with necrosis

• Some drugs have decreased absorption by IM ( diazepam, phenytoin)

• Some drugs should be avoided (heparin)

 Intravenous injection
Injection by this route given as;

1. bolus- large dose dissolved in vehicle injected slowly e.g. Heparin

2. Slow injection- over 15-20 mins e.g. Aminophylline

3. Slow infusion- for constant plasma conc. About 1 litre solution infused for
about 3-4 hrs depending drug and patient conditions.
Advantages
 Immediate action ( useful in emergencies)
 100% bioavailability
 Large volumes can be given
 Irritants can be given
 Rapid adjustments possible

Disadvantages
• Irritation of veins cause thrombophlebitis
• Extravasations of drug can cause irritation
• Only aqueous solution can given IV
 Intrathecal
 Drug to be injected in the subarachnoid space for CNS action

example: spinal anesthetics

 Used for long duration surgeries to prevent complications from GA

 Direct and rapid action

Note: strict aseptic conditions are required.

 Inhalation

 Used for gaseous and volatile agents and aerosols.

Advantages

• Large surface area

• Serves as local route in lung diseases

• High blood flow

• Hepatic first pass met. Is avoided

• Small dose since direct delivery – less toxicity

• As result of that a rapid onset of action due to rapid access to

circulation.
• The ROA is determined by;

 Physical characteristics of the drug,

 Speed which the drug is absorbed and/or released,

 The need to bypass hepatic metabolism and achieve high conc. at particular
sites.

IMP NOTE: No single method of drug administration is ideal for all drugs
in all circumstances !!!!!!!!!!
Two main branches of PharmAcology
 Pharmacokinetics
Pharmacokinetics: (The life cycle of a Drug)
 Pharmakon: drug
 Kinesis: motion
• Action of body on drug/ how body handles drugs
• Pharmacokinetics: ADME
• Four pharmacokinetic properties determine the
• onset, intensity & duration of drug action.
• Using knowledge of pharmacokinetic parameters;
• clinicians can design optimal drug regimens;
• including the route of administration, dose,
• frequency & duration of treatment.
 Absorption
• Absorption is the process by which a drug enters the bloodstream without
being chemically altered

OR

• The movement of a drug from its site of application into the blood or
lymphatic system

• How drugs transfer form site of administration?

1. Filtration [aqueous diffusion]- Passage of drugs through aqueous pores.

Size should be less than size of pore

Has to be water soluble.

Example: Na+, glucose, caffeine.

2. Diffusion: drugs supposed to pass membrane.

• Drugs must be lipid soluble.

• High partition coefficient high absorption.

3. Carrier mediated absorption

a. Facilitated diffusion

- Passive but facilitated.

Example: levodopa & amino acid into brain.

b. Active transport

- Use ATP & carrier proteins.

- Against the concentration gradient.

Example: levodopa & methyldopa from the gut.

4. Phagocytosis & pinocytosis

 Process by which large molecules are engulfed by the cell membrane

forming a vesicle & releases them intracellularly.

Example: protein, toxin

 Drug absorption

• Transfer of a drug from its site of administration to the bloodstream.

• The rate and efficiency of absorption depend on the route of administration.

• – For IV delivery, absorption is complete; that is, the total dose of drug
reaches the systemic circulation.

• – Drug delivery by other routes may result in only partial absorption and,
thus, lower bioavailability.
 Factors affecting GI absorption

• PH of media & pKa of the drug

• Area of absorbing surface

• Particle size of the drug

• Formulation

• Gut motility

• GIT blood flow

• Gastric secretion

• Drug interaction

 A drug must be in solution to be absorbed, since most drugs are either weak
acids or weak bases, pH affects their solubility and hence absorption.

 Weak bases are absorbed more rapidly from the intestine than stomach.
• Small intestine is the major absorption site because:

 It has large surface area (microvilli 200M2)

 There is good blood supply (1L blood/min compared to 150mL/min stomach)

 Permeability to drugs is greater

• Bioavailability (F)

• Fraction of administered drug that reaches the systemic circulation in a

chemically unchanged form.

• Amount of drug available in the circulation/site of action. It is expressed in

percentage.

• It is 100% for drugs given IV.

• For example, if 100 mg of a drug is administered orally and 70 mg of this drug

are absorbed unchanged, the bioavailability is 0.7 or 70%.
• Factors affecting bioavailability

• – Extent of absorption

• – First pass effect

 The first-pass effect is the term used for the hepatic metabolism of a
pharmacological agent when it is absorbed from the gut and delivered to
the liver via the portal circulation.

 The greater the first-pass effect, the less the agent will reach the systemic
circulation when the agent is administered orally.
• Drug distribution

• Reversible movement of drug from bloodstream to interstitium

(extracellular fluid) and/or cells.

• Factors affecting drug distribution

1. Plasma protein binding

• – Albumin [acidic & hydrophobic drugs]

• – Glycoprotein [basic drugs]

2. Tissue uptake of drugs/tissue binding

 Adipose tissue [DDT]

 Bone [TTC]

 Liver [chloroquine]

 Thyroid gland [iodine]

3. Barriers –capillary permeability

 Blood brain barrier (BBB)

 Placental blood barrier (PBB)

 Cell membrane

4. Rate of blood flow

 Brain

 Kidney

 Liver & highly perfused

 Lung

5. Plasma concentration
 Drug metabolism

• Enzymatically mediated alteration in drug structure.

• Transforms lipophilic drugs into more polar readily excretable products.

• Liver - major site for drug metabolism, but specific drugs may undergo
biotransformation in other tissues, such as the kidney and the intestines.

• Note: Some agents are initially administered as inactive compounds

(pro-drugs) and must be metabolized to their active forms.
• Inducers

• The cytochrome P450 enzymes are an important target for pharmacokinetic

drug interactions.

• Certain drugs, most notably phenobarbital, rifampin, and carbamazepine,

are capable of increasing the synthesis of one or more CYP isozymes.

• This results in increased biotransformations of drugs.

1. Decreased plasma drug concentrations.

2. Decreased drug activity if metabolite is inactive.

3. Increased drug activity if metabolite is active.

4. Decreased therapeutic drug effect.

• Inhibitors

• Inhibition of CYP isozyme activity is also an important source of drug

interactions that leads to serious adverse effects.

• The most common form of inhibition is through competition for the same
isozyme.

• For example, omeprazole is a potent inhibitor of three of the CYP isozymes

responsible for warfarin metabolism.

• If the two drugs are taken together, plasma concentrations of warfarin

increase, which leads to greater inhibition of coagulation and risk of
hemorrhage and other serious bleeding reactions.

• CYP inhibitors are erythromycin, cimetidine, ketoconazole, and ritonavir,

because they each inhibits several isozymes.
• Inhibition of drug metabolism may lead to; - Increased plasma levels over time
with long-term medications.

• - Prolonged pharmacological drug effect.

• - Increased drug-induced toxicities.

Microsomal enzyme inducers Microsomal enzyme inhibitors

 Phenobarbitone  Isoniazid
 Phenytoin  Disulfiram
 Rifampicin  Cimetidine
 Carbamazepine  Allopurinol
 Sulphonamides  Chloramphenicol
 St. John’s Wort  Erythromycin
 Cigarette smoking  Metronidazole
 Grape fruit juice
• Drug excretion

• Removal of a drug from the body occurs via a number of routes.

• The major routes of excretion include renal excretion, hepatobiliary

excretion & pulmonary excretion.

• The minor routes of excretion are saliva, sweat, tears, breast milk,
vaginal fluid & hair.

• The rate of excretion influences the duration of action of drugs.

• If the drug is excreted slowly, the concentration of drug in the body is

maintained and the effects of the drug will continue for longer period.
 Routes of drug excretion
a. Renal excretion
For water soluble and non volatile drugs.
The three principal processes that determine the urinary excretion of a drug.
– Glomerular filtration
– Active tubular secretion
– Passive tubular reabsorption
The function of glomerular filtration and active tubular secretion is to remove drug
out of the body, while tubular reabsorption retain the drug.

b. Hepatobiliary Excretion
The conjugated drugs are excreted by hepatocytes in the liver.
After excretion of drugs through bile to the intestine; certain amount of drug is reabsorbed
into the portal vein leading to an entrohepatic cycling which can prolong the action of drug.
Example: Chloramphenicol, estrogen.
What the drug does to the body
• It is the study of biochemical and physiological effects of drug and
their mechanism of action at organ level as well as cellular level.
Deals with

• Mechanism of action

– Organ system effects

– Adverse drug reaction

– Drug-receptor interactions

• Combined drug action

• Also Modification of action of one drug by another drug

• Study of action-effect of drugs and dose-effect relationship

 Principles of Drug action

• Do NOT impart new functions on any system, organ or cell

• Only alter the PACE of ongoing activity

1. Stimulation: ↑ing activity of tissues

2. Depression: ↓ing activity of tissues

3. Irritation: Counterirritant

4. Replacement: Insulin in DM

5. Chemotherapy: Antibiotics/anticancer drugs

 Mechanisms of drug action

• Non receptor mediated

&
• Receptor mediated Non receptor mediated actions
1. Physical
2. Chemical
3. Enzymatic
4. Ion channel
5. Alteration of metabolism
6. Placebo
 Non receptor mediated actions

1. Physical action:

– Mass of drug – Ispaghula husk

– Adsorptive property - char coal

– Osmotic activity - Magnesium sulfate

– Radio activity - I 131

– Oxidising property – KMnO4

2. Chemical action
Antacids neutralise gastric HCl
3. Through enzymes
• Stimulation
Pyridoxine acts as co factor for dopa
decarboxylase activity
• Inhibition
Aspirin inhibits Cyclo-oxygenase
• Through ion channels:
• Calcium channel blockers
• Sodium channel blockers
• Potassium channel openers
• 5. Altering the metabolic processes
• Sulfonamides –
• interfere with bacterial folic acid synthesis

• 6. Placebo effect ???

• •Inert substance which is given in the garb of medicine
– •Works by psychological rather than pharmacological
means
– •Often responses equivalent to the active drug
 4 major target of drug action

1. Enzymes

2. Ion channels

3. Transporters

4. Receptors
 Receptor mediated action
What is a receptor ???

• Macromolecule or binding site located on the surface or inside the

effector cell that serves to recognize the signal molecule/drug and initiate
response to it.

• Itself has no function

Functions of Receptors

 Recognition& binding of the ligand

 Propagation& integration of the message/signal

 Different terminologies

Affinity R

D
Intrinsic Activity

D RESPONSE
 Agonist

It has both affinity + IA R

D RESPONSE
 Antagonist

It has affinity but no IA R

D
NO
RESPONSE
Does not have any effect of its own
 Inverse agonist

Affinity + IA with negative sign

ANTI -
Agonist CONVULSANT
GABA-
RECEPTOR
Inverse
Agonist CONVULSANT

Example: ß-Carbolines