PHARMACOLOGY

Sanjaya K Shrestha
Definitions
• Pharmacology – study of drugs
• Drug (WHO 1966 definitions)
Drug is any substance or product that is used to modify or explore
physiological systems or pathological states for the benefit of the recipient.

- also used to mean addictive / abused substance

- it is an unfortunate degradation of a time honored term

• Pharmacology - 2 divs. - Pharmacodynamics

- Pharmacokinetics
Pharmacodynamics

• What drug does to body

• Includes physiological and biological effects
of drugs and their mechanism of action at
macromolecular / subcellular/ organ system
levels
eg., Adrenaline interaction with
adrenoceptors G-protein mediated
stimulation of cell membrane bound
adenylyl cyclase ed intracellular cyclic
3’,5’AMP cardiac stimulation
hepatic glycogenolysis (hyperglycemia)

preparation for activity

Pharmacokinetics

• What body does to the drug

• Includes absorption, distribution, binding,
localization, storage, biotransformation
and excretion of drug
eg., Digoxin 70% absorbed orally; 25% bound to
plasma proteins; localized in heart, skeletal
muscle, liver and kidney; widely distributed; a
small fraction is metabolized in liver to inactive
products and is primarily excreted unchanged by
kidney; has a total body clearance of about 150
ml/min, and a plasma half life of about 40 h
Drug nomenclature – 3 categories of names:
1. Chemical name - it describes a substance
chemically, eg., 1-(isopropylamino)-3-(1-
naphthyloxy) propan-2-ol----- cumbersome and not
suitable for prescribing----generic name is flumazenil
2. Non-proprietary name (Generic name) – a name
accepted by a competent scientific body such as U.S.
Adopted Name (USAN) Council, eg., phenothiazine,
tricyclic antidepressant,etc.
3. Proprietary (Brand) name – a name assigned by the
manufacturing company which is its property or
trademark
- one drug may have multiple
brand names, eg., Altol, Atecard, Atecor, Aten,
Betacard, Tenolol, etc. for atenolol
• Pharmacotherapeutics – application of
pharmacological knowledge to cure , prevent, or alliviate a
disease process
• Clinical Pharmacology – scientific study of drugs in
man; includes pharmacokinetics and pharmacodynamic
investigation in healthy volunteers and patients
• Chemotherapy – treatment of infection or malignancy
with drugs that have selective toxicity for infecting organism
or malignant cell, but no or minimal toxicity to the host cells
• Pharmacy – science of compounding and dispensing
drugs; it includes collection , identification, purification,
isolation, synthesis, standardization, and quality control of
medicinal substances
• Toxicology – study of poisonous effect of drugs and other
chemicals, along with detection, prevention, and treatment
of poisonings
Brand names are designed to be
catchy, short, easy to remember and
often suggestive of its action, eg.,
Lopresor suggesting drug for
lowering blood pressure
Routes of Drug Administration
• Local routes
- systemic absorption – minimal or absent
- high conc at desired site

1. Topical – surface
a) skin – ointment, cream, lotion, paste, powder, dressing, spray,
etc
b) mucous membrane –
- mouth and pharynx – paints, lozenges, gargles
- eyes, ears, nose – drops, ointments, spray
- GIT – as non-absorbable drugs – Mg(OH)2, sucralfate,
neomycin
- bronchi, lungs – inhalations, aerosols,
- urethra – jelly, irrigating soln
- vagina – pesseries, vaginal tablets, inserts, cream, powder,
douches
- anal canal – ointment suppositories
2. Deeper tissues
- approached by needle and syringe
- systemic absorption is low
eg., intra-articular inj (hydrocortisone)
intrathecal inj (lignocaine, amphotericin B)
retrobulbar inj (hydrocortisone)

3. Arterial supply
- contrast media in angiography
- anticancer drugs - infused in femoral or brachial
arteries
• Systemic routes
- absorbed into blood

1. Oral – safe, convenient, non-invasive, painless,cheap

- no sterilization needed
- solid – powder, tablet ,capsule
- liquid – syrup
2. Sublingual or buccal
- rapid absorption – rapid action
- liver bypassed – drugs with high 1st pass metabolism
3. Rectal – suppositories, retention enema – liver bypassed
4. Cutaneous – ointment – liver bypassed
- transdermal patches
5. inhalation – alveoli – rapid action
6. Nasal
7. Parenteral – rapid action in emergencies
- sterilized preparation, expensive, painful
• Subcutaneous (s.c.) slower absorption
• Intramuscular (i.m.) faster than s.c.
• Intrvenous (i.v.) immediate effect
• Intrdermal (i.d.) eg., BCG vaccine
Pharmacokinetics
• Quantitative study of drug movement in
and out of the body
• All pharmacokinetic processes involve
transport of drug across biological
membranes – bilayer of phospholipids
• Drug transported across membrane by
- passive diffusion and filtration
- specialized transport
• Passive diffusion

- most drugs – weak electrolytes – ionization is pH dependant

- lipid soluble non-electrolytes – readily cross biological
membranes – pH independent
- strong electrolytes – completely ionized in acidic as well as in
alkaline pH
- weakly acidic drugs – form salts with cations – ionize more at
alkaline pH
- Weakly basic drugs - “ anions - “
acidic pH

Ions being lipid insoluble, do not diffuse and a pH difference

across a membrane can cause differential distribution of
weakly acidic and weakly basic drugs on the 2 sides of the
biological membrane
• Implication

- acidic drug – aspirin – largely unionized at acidic

gastric pH - absorbed from stomach

- basic drug- atropine – largely ionized “

pH – absorbed from intestine

- lipid soluble nonelectrolytes, eg., ethanol, diethyl

ether cross biological membrane readily.
• Filtration – passing through aqueous pores in membrane
- influenced by hydrostatic and
osmotic pressure and MW of the drug

• Specialized transport

- carrier mediated – active transport

- facilitated diffusion
- pinocytosis - by formation of vesicles
- proteins and big molecules
• Absorption
- except when given i.v., drugs have to move to cross
biological membrane
- influenced by –
- above described principles
- aqueous solubility –poor water soluble – poor
absorption
- concentration gradient – passive diffusion
- area of absorbing surface
- vascularity of absorbing surface
- route of absorption
- oral – mucosal barrier
- s.c. /i.m.
- topical – cornea, skin – depends on lipid
solubility
• Bioavailibility
- it is a measure of the fraction of administered
dose of a drug that reaches the systemic circulation
in the unchanged form
- it is 100% for i.v. drugs
- it is lower for oral drugs
- incomplete absorption
- 1st pass metabolism
• Distribution
- blood stream ---- other tissue
- depends on – lipid solubility, ionization,
pH, extent of plasma protein binding,
regional blood flow

- Lipid insoluble drugs do not enter cells

- Extensive binding to plasma protein –
restricted to vascular compartment
• Penetration into brain and CSF
- capillary endothelial cells of brain have tight junctions
---- blood brain barrier
limit entry of non-lipid soluble drugs ----- only lipid soluble
drugs are able to penetrate and have action on CNS
• Plasma protein binding
- most drugs bind to plasma protein
acidic drugs – plasma albumin
basic drugs – alpha 1 acid glycoprotein

- bound fraction is not available for action----- it is in

equilibrium with free drug in plasma
• Tissue storage
some drugs---- accumulate in certain tissues --- toxicity
eg., tetracycline on bone and teeth
chloroquin in retina
• Biotransformation (metabolism)
- chemical alteration of drug in body
- make lipid soluble drugs – insoluble ---- so not
reabsorbed in renal tubules ---- excreted in urine
- sites of metabolism -----liver, kidney, intestine,
lungs, plasma