an overview of general pharmacology...

1. General Pharmacology
Jehan Zeb Khan
Pharm.D

2. Pharmacology
• Greek “Pharmacon” – drug, “logos” – teaching
• The term "drug" means (A) articles recognized in the
official United States Pharmacopoeia, official
Homoeopathic Pharmacopoeia of the United States, or
official National Formulary, or any supplement to any
of them; and (B) articles intended for use in the
diagnosis, cure, mitigation, treatment, or prevention of
disease in man or other animals; and (C) articles (other
than food) intended to affect the structure or any
function of the body of man or other animals;
• (Mitigation means the action of reducing the severity, seriousness, or painfulness of something)

3. Pharmacology
• The study of substances that interact with
living systems through chemical processes,
especially by binding to regulatory molecules.
• Medical pharmacology is the science of
substances used to prevent, diagnose and
treat disease.

4. Sources of Drugs
• Natural sources (mainly plants)
– Atropa belladonna …atropine,
– Ginkgo biloba.. (Ginkgo)
– Digitalis lanata- digoxin
• Human and animals: such as epinphrine, insulin and
adrenocoticotrpoic hormone.
• Synthetic
 Sulfanilamide, acetaminophen, zafirlukast
• Minerals:
 as iron, iodine and zinc
• Biotechnology
– Smallpox vaccine, GH, Insulin..

5. Routes of Administration, Classification
 Classification:
I. Enteral (any form of administration that involves any part of the GIT): desired effect is systemic
(non-local). Drug is given via the digestive tract
II. Parenteral: desired effect is systemic. Drug is given by injection
III.Topical: desired effect is local. Drug is applied directly where its action is desired
I. Enteral:
I. by mouth (orally): many drugs such as tablets, capsules, liquids
 Widely used, convenient
 Some capsules and tablets contain sustained release drugs, which dissolve over an extended period
of time.
 Administration of oral drugs is relatively easy for patients who are alert and can swallow (can not
be used in unconscious patients).
 Certain drugs are given by the sublingual (placed under the tongue) route. These drugs must not
be swallowed or chewed and must be dissolved completely before the patient eats or drinks.
Nitroglycerin is commonly given sublingually.
II. by gastric feeding tube: many drugs and for enteral nutrition
III.Rectally: various drugs in suppository or enema form
 The effect of digestive enzymes is avoided
 Useful for unconscious patients and in vomiting cases

6. Routes of Administration, Classification
II. Parenteral:
 The most common routes of parenteral drug administration the subcutaneous (SC), intramuscular
(IM), intravenous (IV), or intradermal routes.
 The most common routes of parenteral drug administration the subcutaneous (SC), intramuscular
(IM), intravenous (IV), or intradermal routes.
 Rapid response obtained
 Useful in emergencies, vomiting, and unconsciousness
 The drug should be in a sterile dosage form

7. Routes of Administration, Classification
III. Topical:
 epicutaneous (application onto the skin), e.g. allergy testing, antifungal creams
 inhalational, e.g. asthma medications
 enema, e.g. contrast media for imaging of the bowel
 eye drops (onto the conjunctiva), e.g. antibiotics for conjunctivitis
 ear drops - such as antibiotics and corticosteroids for otitis externa
 intranasal route (into the nose), e.g. decongestant nasal sprays
 vaginal, e.g. antifungals creams

8. Routes of Administration, Summary

9. Drug Transport
• Drugs must reach and interact with or cross the
cell membrane to stimulate or inhibit cellular
function.
• 'A drug will not work unless it is bound‘
• These critical binding sites are often referred
to as 'drug targets'

10. Pharmacology Concepts
Pharmacology comprise of 2 processes
 Pharmacokinetics (PK) -
 PK describes how the body affects a specific drug
after administration
 Or What body does to a drug
 Pharmacodynamics (PD) –
 PD describes how a drug affects the body system
after administration
 Or What drug does to the body
 Or drug action
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11. General Concepts
Drug Dose
Administration
Drug Effect
or Response
Pharmaceutical
Pharmacokinetics
Pharmacodynamics
Pharmacotherapeutics
Disintegration
of Drug
Absorption/distribution
metabolism/excretion
Drug/Receptor
Interaction

12. Pharmacokinetics
• Involves drug movement through the body to
reach sites of action, metabolism, and
excretion.

13. Pharmacokinetics
• Processes of Pharmacokinetics
• The ADME scheme
– A- Absorption
– D- Distribution
– M- Metabolism
or Biotransformation
– E- Excretion
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14. Pharmacokinetics…
Absorption-process that occurs from the time a drug enters the body to
the time it enters the bloodstream to be circulated.
• Factors affecting absorption include: lipid solubility, degree of
ionization, solubility of drugs, dosage form, route of administration,
blood flow to the site of absorption, gastrointestinal function,
presence of food or other drugs.
• Sites: GIT (oral mucosa, intestinal mucosa, stomach), Skin,
Muscles, Vaginal mucosa.
• Bioavailability is the portion of a dose of a drug that reaches the
systemic circulation and is available to act on body cells.
• IV administration is 100% bioavailable
• Subcutaneous administrations has more rapid absorption than does
the oral route
• Mucous membranes allow for rapid and direct absorption into the
bloodstream

16. Factors affecting absorption/systemic
availability
• Lipid solubility, like absorb like.. Lipophillic drugs absorb rapidly across
the cell membrane. Cell membrane is lipoid in nature, will readily absorb
Lipophillic substances.
• Degree of ionization, an unionized drug is lipid soluble and readily absorb
across the cell membrane while an ionized drug is not water soluble and
will not absorb.
• Solubility of drugs, for a drug to be absorbed from the mucosa into the
blood it must have sufficient water solubility to be solubilized at the site of
absorption.
• Dosage form, the physical form in which a drug is administered is called a
dosage from. For example syrups, tablets, capsules, parenterals, topical
creams, ointments e.tc. Absorption from different dosage forms varies.
Absorption from solution form is rapid than solid dosage form. The
absorption from tablets depends upon disintegration and dissolution time.
• Route of administration, absorption from oral route is slower than from
parenteral route. Absorption from inhaled route is faster than oral,
sublingual route gives full absorption by bypassing first pass effect.

17. Factors affecting absorption/systemic
availability
• Blood flow at the site of administration, increase
blood flow at the site of absorption will increase the
rate of absorption. --- local massage after IM injection.
• Gastrointestinal Tract, small intestine is the ideal
place for drug absorption due to large surface area.
Acidic drugs absorbed from acidic media while basic
drugs from basic media. e.g. aspirin from stomach,
phenobarbitone from intestines. Increased peristaltic
activity decrease the absorption of drugs
• Presence of food or other drugs, Vitamin C increases
absorption of iron from GIT, calcium containing food
interfere with the absorption of tetracycline antibiotics.

18. Pharmacokinetics…
Distribution Involves the transport of drug
molecules within the body.
• After the drug is absorbed into the
bloodstream, it is carried by the blood or tissue
fluids to its sites of action, metabolism and
excretion.
• Protein binding is an important factor in drug
distribution.
• Albumin is important carrier for many drugs.

19. Pharmacokinetics…
• Drug distribution into the CNS is limited
because of the blood-brain barrier.
• Blood-brain barrier is composed of capillaries
with tight walls which limits movement of
drug molecules into brain tissue.
• Only drugs that are lipid soluble or have a
transport system can cross the blood-brain
barrier and reach therapeutic concentrations in
brain tissue.

20. Pharmacokinetics…
Protein binding:
• Most drugs form a complex with plasma proteins,
mainly albumin, which act as carriers.
• Only the free or unbound portion of a drug acts on
body cells
• As unbound drug acts on cells, the decrease in
plasma drug level causes some of the bound drug
to be released
• Protein binding allows a part of a drug dose to be
stored and released as needed

21. Pharmacokinetics…
Metabolism:
• Method by which drugs are inactivated or
biotransformed by the body.
• Some drugs yield metabolites that are also active
and exert effects on the body until they are
excreted.
• Most drugs are lipid soluble which aids their
passage across the cell membrane.
• In metabolism lipid soluble drugs are converted
into water soluble forms.

22. Pharmacokinetics…
• Excretion usually is by kidneys. Need to be water
soluble for this to occur. Thus, one function of
metabolism is to convert fat soluble medications to
water soluble ones.
• Hepatic drug metabolism or clearance is a major
mechanism for terminating drug action and eliminating
drug molecules from the body
• Most drugs are metabolized by the cytochrome P450
enzymes in the liver
• Liver contains complex system of enzymes, three of
which are key in the metabolism of medications/drugs

23. Pharmacokinetics…
Excretion
• Refers to the elimination of a drug from the body.
• Excretion usually is by kidneys. Need to be water soluble
for this to occur.
• Most are excreted by the kidneys although some are
excreted in the bile.
• Kidneys: excretion is through Glomerular filtration, active
tubular secretion. Drugs having m.wt less than 300 are
excreted via GF.
• Bile: Drugs with a m.wt greater than 300 are excreted
through bile e.g. erythromycin, metoprolol.
• Other minor routes of excretion are breast milk, lungs e.tc.

24. Volume of distribution
• It is the volume into which the dose of a given drug appears
to have been dissolved. It is not a real but a hypothetical
voume. Calculated as
• Vd=dose/Cp
• It is measured in liters
• If the entire drug remains in the circulation the volume of
distrubtion will be around 5litrs, equal to volume of
vascular compartment. Some highly Lipophillic drugs
(amitryptyline) have a volume of distribution more than 250
liters which indicate that most of the drug is present in
tissue compartment.
• Drugs that are not lipid soluble have low volume of
distribution e.g. amikacin, gentamicin, aspirin.

25. Plasma Protein Binding
• Drugs after absorption into blood occurs in two forms
• Free fraction: moves freely without any complexation,
pharmacologically active, is able to be metabolized and excreted.
• Protein bound fraction: this fraction is bound to plasma protein
mainly albumin, pharmacologically inactive due to large complex
size, this binding is reversible.
• There is equilibrium between free and bound drug.
• Drugs which are highly protein bound are phenytoin, warfain.
• In renal and liver diseases the binding capacity of plasma protein is
reduced due to decrease in albumin synthesis. The concentration of
free drug increases which may lead to toxicity.