Pharmacology

PHARMACOLOGY

• PHARMACOLOGY: It is the science which deals with the complete study of drugs, particularly the action of drug on various system of the body

• PHARMACOLOGIST: is a doctor, who teaches pharmacology at medical colleges

• PHARMACIST: is a technical person, who looks after the manufacture of formulations in the industry

• DRUG: It is defined as any substance used for the purpose of diagnosis, prevention, relief or cure of disease

PHARMACOLOGY• PHARMACY: It is branch of science of identification, selection, preservation, standardisation, compounding & dispersing of medicine

• PHARMACOKINETICS: It is defined as study of the absorption, distribution, metabolism & excretion of drugs & their relationship to Pharmacologic response (What the body does to the drug)

• PHARMACODYNAMICS: Which is the quantitative study of the biological & therapeutic effects of drugs (What the drug does to the body)

• PHARMACOPOEIA: It is an official code containing a selected list of established drugs & medicinal Preparations Eg. BNF, NF(Indian)

ABSORPTION

• Passive diffusion (aqueous or lipid environment):

most common

• Active transport: important for some drugs,

particularly larger molecules

Aqueous diffusion 

• Within large aqueous components (e.g.,interstitial

space, cytosol)

ABSORPTION

•Across epithelial membrane tight junctions across

endothelial blood vessel lining

• Through aqueous pores: allows diffusion of

molecules with molecular weights up to 20,000 --

30,000

• Driving force: drug concentration gradient

ORAL ADMINISTRATION

• Most convenient, most economical

DISADVANTAGES:

emesis (drug irritation of the gastrointestinal mucosa)

digestive enzymes/gastric acidity destroys the drug

unreliable or inconsistent absorption due to food or

other drug effects

metabolism of the drug by gastrointestinal flora

ORAL ADMINISTRATION

Factors determining rate of drug effect

onset

Primary factor:

• Rate & absorption extent by GI tract

• Absorption Site: mainly small intestine because of large

surface area

DRUG IONIZATION• Non ionized (lipid-soluble) forms favor absorption

• Weak acids may be highly ionized in the alkaline intestinal pH (not favoring absorption) but this effect is counterbalanced by the large surface-area effect

• Drugs which are weak acids are readily absorbed in the stomach

• Uncharged form: lipid-soluble

• Charged form: aqueous-soluble, relatively lipid-insoluble (does not pass biological membranes easily)

FIRST-PASS EFFECT

• Drugs absorbed from the GI tract passes through

the  portal venous system then through the liver &

finally into the systemic circulation, when drugs

interact with receptors in target tissues.

• Extensive hepatic metabolism/extraction result in

minimal drug delivery to the systemic circulation for

certain agents

FIRST-PASS EFFECT• Drugs with large first pass effect exhibit significant differences in pharmacological effects comparing oral vs. IV administration,Examples:

• Propranolol

• Lidocaine

Avoiding the first-pass effect:

• sublingual (e.g. nitroglycerin)-- direct access to systemic circulation

• transdermal

FIRST-PASS EFFECT

Avoiding the first-pass effect:

• use of suppositories in the lower rectum {if

suppositories move upward, absorption may occur

through the superior hemorrhoidal veins, which lead

to the liver}

• inhalation: first-pass pulmonary loss by excretion or

metabolism may occur

PARENTERAL ADMINISTRATION

• Ensures active drug absorption

• Sub-cutaneously intramuscular injection: more

rapid/predictable than oral administration route

• only route of administration acceptable for:

uncooperative patients

unconscious patients

PARENTERAL ADMINISTRATION

Advantages of IV administration

1. rapid/precise blood drug levels obtained (e.g.,

no first-pass effect)

2. Irritant drugs: more comfortably administered

(blood vessels relatively insensitive); drug

rapidly diluted (particularly if administered

into large forearm vein)

BIOAVAILABILITY

BIOAVAILABILITY: It indicates a measurement of the

rate & extent (amount) of therapeutically active drug

which reaches the general circulation (The amount of

drug available in the blood for action)

BIOEQUIVALENT: It means pharmaceutical equivalents

or whose rate & extent of absorption do not show a

significant difference when administered at the same

molar dose of the therapeutic moiety under similar

experimental conditions, either single dose or multiple

dose

AUC

AUC

Area Under the Curve AUC: It is a measure of the

bioavailability of the drug, AUC gives the extent of

absorption

C max: It is the peak concentration of the drug

reached in the plasma

T max: It is the time required to reach C max after

administration of the drug

Plasma Half-life(t1/2): It is the time taken by the

drug in the plasma to reduce to 50%(half) from its

peak concentration at a particular dosage form

HALF- LIFE

HALF-LIFE

Half-life: (t1/2): It is the time required to decrease the

amount of drug in body by 1/2 during elimination (or

during a constant infusion)

• Useful in estimating time to steady-state

• Useful in estimating time required for drug removal

from the body

• means for estimation of appropriate dosing interval

ORAL & IV

DRUG RECEPTORS

DRUG RECEPTORS: Cell functions are regulated by means of

messages substances involved in the transfer of information.

These messengers recognized & bind to specific sites on the

cell member called as receptors. They are macromolecules

proteineous substances, mostly present on the surface of the

cell membrane

Specific drugs have specific receptors to combine, this

combination is known as Drug- Receptor Complex

DRUGS RECEPTORS

PAETIAL AGONIST: It is a drug with an affinity equal to or

less than that of the agonist but less intrinsic activity

AGONIST: If the drug is binding to the receptor & initiating a

certain activity in the cell then the drug is called as Agonist,

E.g Beta receptor agonist – Salbutamol

ANTAGONIST:If the drug is binding to the receptor but not

initiating any action in the cell then the drug is called

Antagonist, E.g Ondensetron – 5 HT3