What happens when a

drug enters the body

What happens when a drug enters the
body
Administration

When a drug reaches the stomach it

Dissolution dissolves in the acidic liquid of the
stomach

The drug moves from the intestine

absorption into the blood stream

The liver is the main organ of metabolism for

1 metabolism
st
drugs metabolism means the drug is broken down
into small molecules with use of.
enzymes(bilirubin, alkaline phosphatase )
 Injections , suppo, inhaled starts here

Distribution The drug leaves the blood stream and enters

the tissue where it exerts its effects

This usually in the liver but can be in

2nd metabolism
other organs ( kidney)

Removed from the body by kidney

Excretion
ADME

 ABSORPTION
 DISTRIBUTION
 METABOLISM
 EXCRECTION
ABSORPTION

 PASSAGE
OF DRUGS ACROSS
MEMBRANES:

A drug can enter into circulation and reach the

site of action only after absorption. The
absorption of a drug involves its passage
across cell membrane.
 Passage of drugs across the cell membrane:
they will pass through two process. They are:
1. passive transfer 2. specialized transport
a. simple diffusion a. active transport
b. filtration b. facilitate diffusion
c. pinocytosis
 simple diffusion: It is a bidirectional process.
Water soluble and lipid soluble substances can
be transported by this process.

 Filtration: only water soluble substance can be

transported by this process. Passage through
pores.

 Active diffusion : it is a selective process which

requires energy, also it requires a carrier and so is
called as carrier transport.
 Facilitated diffusion: it is very similar to
carrier transport, but does not require energy.

 Pinocytosis: proteins and macromolecules

are transported by this process . It is similar
to phagocytosis (ingestion of bacteria or
other material by phagocytes)
Factors modifying drug absorption

 Physical state: drugs in the form of liquids are

well absorbed than solids. Gases are quickly
absorbed through lungs.

 Particle size: smaller the particle size, better the

absorption.

 Solubility: an easy soluble drug is quickly

absorbed, and also form of solutions are quickly
absorbed than solids.
 Concentration:concentrated forms are
absorbed more than dilute one.

 Absorbing surface: greater the absorbing

surface , more the absorption.

 Circulation to site of absorption: increase

blood flow to area of absorption can increase
more absorption rate. can do by massage .
 Route of administration:based on route of
administration absorption varies.

BIOAVAILABILITY:
It is defined as the quantity of the drug that is
absorbed and reached systemic circulation
after administration of drug.
Presented by

Kishan
Aarudra
Distribution

After drug is absorbed , it is distributed to various body

tissues and fluids.

Drugs which easily pass through cell membrane achieve wide

distribution. Drugs which do not pass through cell
membrane are limited in their distribution.

The distribution of drugs to various tissues depends upon the

size of the organs, blood flow, solubility of the drug.
 Entry into central nervous system:
entry of drugs into central nervous system is
limited by BBB .

It is a hypothetical barrier which exists

between plasma and extracellular surface of
brain .
 This barrier is constituted by glial cells and
capillary endothelium in the brain.

 Only lipid soluble substance readily pass

through this barrier.

 This barrier protects most of the central

nervous system from substance which may
be circulating in the blood, such as drugs.
 The chemoreceptor trigger zone (CTZ) is one
example of an area which is not protected.

 Some drugs can destroy the BBB, PENICILLIN

DOES NOT NORMALLY ENTER THE csf, but it is
able to do so in patients with acute meningitis.

 The unwanted effects of drugs are caused due to

drug passage through BBB. For example ,
antihistamine drugs causes effects .
 Placental transfer of drugs:
it is important to consider medication use in
pregnancy seriously.

 Chemicals in the mothers circulation can harm

her baby through the placental transfer.

 The dose of the drug and the physicochemical

properties of the drug influence transfer
(molecular size, solubility)

of drugs across the placenta.

 Entry of drugs into placenta is restricted by
blood-placental barrier. It is barrier b/w
maternal & foetal circulation.

 It permits entry of only lipid soluble drugs.

 Mammary transfer of drugs:

Drugs can also enter the breast milk and be

passed to the suckling infant. Again lipid
solubility, protein binding and molecular size
are important.
 Redistribution:

Initial distribution mainly based on blood flow,

attachment to binding sites.

Redistribution occurs as drugs in peripheral

tissues is gradually retuned to the site of action.

Drug accumulation is also common with

repeated dosing in drugs that are redistributed.
Metabolism:

 Alteration of a drug in a living organism is

known as biotransformation/Metabolism.

 By this process drug may be either convert

into inactive or more active compound.
 Induction: stimulation of hepatic drug
metabolism by some drugs(phenobarbital).
enzyme inducers stimulate their own
metabolism and also accelerate metabolism
of other drugs.
 Inhibition: some drugs may decrease the
activity of hepatic drug-metabolizing
enzymes.

 Hereditary difference in activity of metabolic

enzymes.(genetic drugs)
Types of Metabolic reactions

 Conjugation: synthetic reaction combining

the parent drug with a sugar , amino acid or
other naturally occurred compound.

 Non- synthetic reactions: oxidation,

reduction, hydrolysis.
Results of metabolism

 The conjugated, oxidized, reduced or

hydrolyzed drug is usually more water soluble
and therefore more readily excreted.

 Drug metabolism often results in

detoxification or inactivation of drugs where
the metabolites are less active or inactive
compared to the parent drug.
 Some metabolites may be equally or even
more active than the parent drug.

 Prodrugs are drugs which are administered in

an inactive form and depend on metabolism
for their conversion to active form.
Enalapril,acyclovir, dopamine
 Some drugs can be metabolized to toxic
compounds.

 Drugs have more than one metabolite, some

are active , some inactive.
 First pass effect:
drugs absorbed from the GI tract enter the portal
circulation and are carried to the liver before entering
the systemic circulation.

 Some drugs are extensively metabolized in liver

known as 1st pass metabolism.

 So that’s the reason when drugs taken orally, the

dose may need to be much higher than when it is
given by injection.
EXCRECTION

 Drugs may be excreted from the body by

number of routes, exhaled air, sweat, saliva,
tears, urine, feces.

 Urine is the principle vehicle of drug excretion

in the body.
 Kidney has 3 types of mechanisms for
substance which passes through it

 1. glomerular filteration

 Tubular reabsorption

 Tubular secrection
 Glomerular filteration:
it is passive diffusion process where rate
of filteration directly proportional to the
concentration of the substance in the renal
blood and in the renal blood flow.
 The passing of blood through the glomeruli is
as follows.
 The plasma ions, sugar, amino acids,
hormones and other substance of molecular
weight less than 69M are filtered but plasma
protients , some lipids, substance are
excluded.

 Thus both toxic materials and essential ions

and nutrients are filtered at the glomerulus.
Excretion of drugs
 loading dose is an initial higher dose of a drug that may be
given at the beginning of a course of treatment before
dropping down to a lower maintenance dose.

 A loading dose is most useful for drugs that are eliminated

from the body relatively slowly, i.e. have a long systemic half-
life.
 Drugs which may be started with an initial loading dose
include digoxin, teicoplanin, voriconazole and procainamide.
Kinetics of elimination:
 Clearance(CL) : a quantitative measure of the rate at which a
substance is removed from the blood, as by the kidneys, the
liver, or hemodialysis; the volume of plasma cleared per unit
time. Symbol C.

 1st order kinetics (studying the rates of reactions) :

The rate of elimination is directly proportional to the drug
concentration, CL remains constant/Unit time
 Zero Order kinetics:
The rate of elimination remains constant irrespective of drug
concentration, CL decrease in increase of concentration of
drug is eliminated/Unit time.
 Factors influencing the
safety/effectiveness of drugs
 The drug response vary from individual to other.

 AGE: children are hyper reactive to certain drugs. The reasons

are immaturity of renal functions or poor developments of
enzymes. So less dose must be given to children.

Youngs for: AGE/AGE+12Xadult dose

dilling for: AGE/20X adult dose
 Body weight: body weight has influence on the concentration
of the drug at the site of action. So the dose of a drug must be
suitably adjusted in case of lean or obese individual.

 Sex: women are most susceptible to the effects of certain

drugs.
Morphine (used to relieve intense pain) produces more
excitation in women than in men.
 Route of administration: the rate of absorption of a drug
differ with the route of administration. The dose also varies
with the route of administration.

 Time of administration: this factor has a definite effect on

drug absorption.

 Physiological factors: body temperature and acid-base status

are some factors which modify drugs effects, salicylates lower
body temperature only in fever but not in normal individuals.
 Psychological factors: