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ROUTES OF DRUG
ADMINISTRATION AND
TRANSPORT OF DRUGS ACROSS
CELL MEMBRANE.
DR BUSARI. A.A
(MB.BS, M.Sc., MMCP, FWACP)
Dept. of Pharmacology, Therapeutics and
Toxicology
OBJECTIVES
• At the end of the period of lecture, the
student should be able to;
• List various routes of administration of drug.
• Select or make a choice of route of a drug
depending on clinical condition of patient.
• Vividly describe advantages and disadvantages
of various routes of drug administration
• Various methods of drug transport processes
across the cell membrane.
INTRODUCTION
• To administer a drug is to make the drug
accessible to the patient’s body where the effect
is desired.
• For this to occur, the drug must come in contact
with the tissues of organs and cells of tissues by
one way or the other, the way the drug comes in
contact or is made accessible to the tissue fluids
tissues, cells, extracellular and intra cellular fluids
is the route of administration of drug.
INTRODUCTION
• A route of administration in pharmacology is
the path by which a drug and other substance
is taken into the body.
• Routes of administration are generally
classified by the location at which the
substance is applied.
Choice of Route of Administration
• This is based on the way the drug is preferred for
administration i.e.
1. based on the drug dosage forms.
• Drugs are administered in various dosage forms:
• As solid – e.g. oxytetracycline capsule, Paracetamol
tablet ,Dimenhydrinate pill,
• As solution - codeine syrup,
• As suspension – insulin, penicillin procaine,
• Aerosol - beclomethesone ,
• Volatile liquid - halothane or nitrous oxide ,
• As ointments, lotions, pastes etc.
Choice of Route of Administration
2.Based on the nature of the drug - oil based,
organic, Polar, non polar solvent etc.
3. The desired bioavailability.
4. Desired onset of action - how fast the therapist
wants to see the manifest effect of the drug. This
is important, especially in life threatening
conditions or circumstances that require
immediate onset of action are shock, circulatory
collapse,
5. Based on the nature of the disease or location of
the disease
Choice of Route of Administration
6. Duration of action – If a duration is required
to be long; the drug is administered 2-4 times
daily.
• This could be done in a depot form, as a patch
on the skin.
• The long acting oxytetracycline, which is
designated for slow absorption over 4-5 days.
Classification
Routes of drug administration:
• The routes of drug administration into two
major groups:
1. Systemic route and
2. Local route.
Routes of drug administration:
• The routes of drug administration for systemic
effect may be divided into two major groups:
1. Oral (enteral) and
2. Parenteral (systemic).
Routes of drug administration:
• Enteral - means to do with the GI tract and includes
oral, buccal, and rectal.
• Parenteral – means not through the alimentary canal
and commonly refers to injections such as IV, IM, and
SC; but could also include topical and inhalation.
• We can also distinguish IV from the rest, as with all
others at least one membrane must be crossed, thus
an absorption process is involved in the administration
and the pharmacokinetic model.
Enteral Administration Of Drug
• Oral ingestion is the most ancient method of drug
administration.
• Another organ where the substance or drug to be
administered is placed is the rectum.( Intrarectally).
• The drug could be placed in the mouth, under the
tongue, that is (sublinqual).
• The drug could be administered directly into the
stomach using intragastric tube.
Oral route
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Advantages:
1-Safe
2-Sterility is no required
3-Danger of acute drug reaction is minimal
4. Convenient - portable, no pain, easy to take.
5. Variety of dosage forms available - fast release
tablets, capsules, enteric coated, layered tablets,
slow release, suspensions, mixtures
Oral route
Disadvantages:
• 1-Ingestion of drug could cause gastric
irritation.
• 2-Nausea
• 3-Vomiting
• 4-Complexes formed with ingested drug could
prevent the drug absorption
Oral route
Disadvantages:
• 5-The drug could be destroyed by low gastric
Ph (acidic medium)
• 6. First-pass effect - drugs absorbed orally are
transported to the general circulation via the
liver. Thus drugs which areextensively
metabolized will be metabolized in the liver
during absorption.
Oral administration
First Pass Effect
Oral administration
Typical Plot of Cp versus Time after Oral Administration Fast and Slow
Release Dosage Forms
Parenteral Administration
• Parenterally “par” means beyond “enteral”
means intestinal.
• This is the route of administration of drug
without crossing the intestinal mucosa.
• This is possible when the drug is directly into
the blood or tissue fluid using syringes and
needles.
Parenteral Administration
• The most important and most frequently used
parenteral routes are
• I.V. (intravenous route),
• IM (intramuscular route) and
• SC (subcutaneous route respectively.
Parenteral Administration
Showing IV, IM, and SC Injection
Other Less Frequent
Parenteral Routes Are:
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Tissue infiltration
Intra articular
Intradermal
Epidural
Subarachnoid
Intra-arterial
Intrathecal
Other Less Frequent
Parenteral Routes Are:
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Intrathoracic
Intracardiac
Intramedullary
Intratesticular
Intralesional
Subconjuctival
Intramammary
Advantages of Parenteral route of drug
administration
• Bioavailability is faster and more predictable.
• Gastric irritation and vomiting are not provoked.
• Parenteral routes could be used in unconscious,
uncooperative and vomiting patient.
• There are no chances of interference by food or
digestive enzymes.
• Liver enzymes are by-passed.
• It essential sometimes in the absorption of the
active form of the drug.
Disadvantages of Parenteral routes
•
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It is generally more risky
The preparation must be sterile
The technique is intensive and painful.
Drug administered by all routes except intraarterial might still be eliminated by first pass
elimination in liver prior to distribution to the
rest of the body.
Intravenous Route:
• The drug is injected slowly, sometimes it could
be infused rapidly as bodies. This method
provides accurate, reliable dosage of drug
directly into the circulation.
• It means that the biovailability of drug is 100%
when administered intravenously.
Intravenous IV route
Typical Plot of Cp versus Time
after IV Bolus Administration
Typical Plot of Cp versus Time during an
IV Infusion Administration
Advantages of IV intravenous route
• This route is often used in drug administration
in life threatening situations.
• The drug would have rapid onset of action.
• Irritating and non-isotonic solutions can be
administered intravenously, since the intima
of the vein are insensitive.
Disadvantages of IV intravenous route
• The drugs administered by this method have
short duration of action.
• Thrombophlebitis of veins
• Necrosis of adjoining tissue.
• Severe adverse effect especially when organs
such as liver, heart, brain are involved in
toxicity.
Intramuscular (Im)
• The drug is injected deep in the belly of a
large skeletal muscle.
• The muscles that are usually used are detoid,
triceps, Gluteus maximus, rectus, femurs
depending on the species of animal.
• The muscle is less richly supplied with sensory
nerves, hence injecting a drug IM is less
painful.
Advantages of IM intramuscular route
• It is convenient route in administering drugs in
animals that are difficult to restrain.
• It is used in administering aqueous or
oleaginous suspensions or solutions.
• Muscles are highly vascularized thus, the drug
could be absorbed haematogenously or
through the lymphatic fluid.
Disadvantages of IM intramuscular
route
• Disadvantages
• Intramuscular injection into fascia might lead
to erratic absorption of the drug.
• There is a possibility of improper deposition of
drug preparation in nerves, fats, blood vessels
or between muscle bundles in connective
sheaths.
Subcutaneous (SC)
• The drug is deposited in the loose
subcutaneous tissue that is richly supplied
with nerves but less vascular.
• The rate of absorption is slower than the
intramuscular route.
Advantages and disadvantages of
subcutaneous route(SC)
• Advantages:
• It is a good route of administration especially
in skin infections.
• It is relatively safer than I.M. and I.V.
• Absorption is slower thus, it is a good route of
a prolonged effect is to be achieved.
Disadvantages subcutaneous route
(SC)
• Disadvantages:
• If the drug is irritating it might cause the
sloughing off of the skin epithelial tissue.
Other forms of subcutaneous route
include
• Pellet implantation – The drug dosage form of
the drug is in solid pellet and is implanted
subcutaneously suing a trochar and cannula
under the skin.
Other forms of subcutaneous (SC)
route include
• Dermoject: In this method, needle is not
used, rather a high velocity jet of drug
solution is projected from a microfine orifice
of gun-like implement.
• The solution passes through the superficial
layer of the skin and gets deposited in the
subcutaneously. This method is used in Mass
innoculation.
Intra-arterial Route
• Drugs and diagnostic agents are administered
via this route.
• The diagnostic media e.g. (Contrast media in
angiography) is injected directly into the
artery.
• This is also of great use in treatment of limb
malignancies.
Intra-arterial Route
• Advantages:
• - The first pass and cleansing effects are bypassed.
• - Bioavailability is 100%.
• - It is of great clinical value in administering
anticancer drugs for
• example, in limb malignancies, the drug is
administered into the
• brachial artery or femoral artery.
Intra-arterial Route
• Disadvantages:
• Intra arterial injection requires great and
expertise
• If the drug is of adverse effect there might be
great danger.
Intraperitoneal
• The peritoneum possess a cavity that offers a
large absorptive area for drugs. The perioneum is
highly vascularized. This route is used in
laboratory animals administration and large
animal practice for administration of large
volumes of fluid. The injection is made via the
sub-lumbar fossa.
• Disadvantages:
• - Irritating compounds may produce peritonitis or
adhesion.
Intrathecal
• This is a route of administration of drug in
which the effects of the drug is desired in the
C.N.S. The blood brain barrier and the bloodcerebrospinal fluid barrier often slow the
entrance of drug into the C. N. S.
Intrathecal
• The drug will be accessible to the meninges
and cerebrospinal axis. The injection made in
the lumbar area or in the cisterna magna.
• These routes are primarily for diagnostic
procedures (e.g. Myelography) and treatment
of meningoencephelitis. Local anaesthetics
are sometimes administered intrathecally to
produce region or spinal anaethesia.
Intrademal and intra-articular
• Intrademal: the drug is injected into the skin
raising a bleb. This route is used in diagnosis
of tuberculosis (tuberculin testing in human)
and (allergen sensitivity testing).
Intrademal and intra-articular
• Intra-articular: Intra-articular injection of
anti-inflammatory preparation (e.g. steroids)
may be justified in some forms of lameness
due to acute inflammation or trauma e.g.
(swollen bursa or tendon sheath)
• Other routes of drug injection include intramedullary, which is used for blood transfusion
directly into the bone marrow. This is done in
neonates when other is difficult.
Pulmonary Route (Inhalation)
• Gases, volatile liquids, and aerosols (fine
droplets ion air).
• Some drugs such as ventolin are administered
using a nebulizer or inhalers.
• Anaesthesia such as halothane, sevoflurane
are vaporized and made to be atomized by a
process atomization –
Pulmonary Route (Inhalation)
• This is delivered into the respiratory passages
with the aid of anaesthetic machine or
vapourizer.
• The vapourised anaesthesia is inhaled to
cause anaesthesia and thus is eliciting its
effect.
Route of administration
•DRUG
TRANSPORT
PROCESSES
DRUG TRANSPORT PROCESSES
• Principal mechanisms of transport of drug
molecules across the cell membrane are
• 1. Passive diffusion
• 2. Carrier mediated transport
• (a) Active transport
• (b) Facilitated transport
• 3. Vesicular transport
• (a) Pinocytosis (b) Phagocytosis
• 4. Pore transport
• 5. Ion pair formation
PASSIVE TRANSPORT
• PASSIVE TRANSPORT Passive diffusion is the
process by which molecules spontaneously
diffuse from a region of higher concentration
to a region of lower concentration. This
process is passive because no external energy
is expended. Mathematical expression Passive
diffusion is best expressed by Fick’s first law of
diffusion which can be expressed
mathematically
Fick’s first law of diffusion
CARRIER MEDIATED TRANSPORT:
• CARRIER MEDIATED TRANSPORT
• Some polar molecules cross the membrane more
readily than can be predicted from their
concentration gradient and partition coefficient
values.
• This suggests the presence of some specialized
transport mechanisms without which many
essential water-soluble nutrients like
monosaccharides , amino acids and vitamins will
be poorly absorbed.
CARRIER MEDIATED TRANSPORT:
• The mechanism is thought to involve a
component of the membrane called as the
carrier that binds reversibly or noncovalently
with the solute molecules to be transported.
• A) Active transport
• (b) Facilitated transport
Active Transport
• Active Transport The drug is transported from
a region of lower concentration to a region of
higher concentration, i.e. against the
concentration gradient Endogeneous
substances that are transported actively
include Sodium (Na+), potassium (K+), calcium
( Ca ++), iron (Fe++) in ionic state; certain
amino acids and vitamins like niacin,
pyridoxine and ascorbic acid .
Facilitated diffusion:
• Facilitated diffusion is also a carrier mediated
transport system but it moves along a
concentration gradient ( i.e from higher to
lower concentration) and hence it does not
require any energy.
• Facilitated diffusion is the process of
spontaneous passive transport of molecules
or ions across a cell's membrane via specific
transmembrane integral proteins.
Facilitated diffusion:
• Acetylcholine (ligand) binds to certain synaptic
membrane and opens Na+ channels and
initiate a nerve impulse.
• Gamma amino butyric acid (GABA) binds to
GABAA receptors and the chloride channel
opens.
• This inhibits the creation of a nerve impulse.
Facilitated diffusion:
VESICULAR TRANSPORT:
• VESICULAR TRANSPORT Vesicular transport is the
process of engulfing particles or dissolved
materials by the cell .
• Vesicular transport
• (a ) Pinocytosis ; the ingestion of liquid into a cell
by the budding of small vesicles from the cell
membrane. (cell drinking)
• b) Phagocytosis ; the ingestion of bacteria or
other material by phagocytes and amoeboid
protozoans. (cell eating)
VESICULAR TRANSPORT:
• Vesicular transport is the proposed process for
the absorption of orally administered Sabin
polio vaccine and large proteins.
• Transport of proteins, polypeptides like insulin
from insulin producing cells of the pancreas
into the extracellular space
PORE TRANSPORT:
• Very small molecules (such as urea, water, and
sugars) are able to rapidly cross cell
membranes as if the membrane contains
channels or pores. A certain type of protein
called transport protein may form an open
channel across the lipid membrane of the cell.
Drug permeation through aqueous pores is
used to explain the renal excretion of drugs
and the uptake of drugs into the liver.
ION PAIR FORMATION:
• ION PAIR FORMATION Strong electrolyte drugs
are highly ionized or charged molecules, such as
quaternary nitrogen compounds with extreme
pKa values. When ionized drugs is linked up with
an oppositely charged ion, an ion pair is formed
in which the overall charge of the pair is neutral.
This neutral drug-complex diffuses more easily
across the membrane . Examples: Propranolol , a
basic drug, forms an ion pair with oleic acid.
Quinine forms an ion pair with hexylsalicylate
•Thanks