Lecture 2. pharmakokinetic pptx

Objectives
Pharmacology & Toxicology
• Describe the pharmacokinetic
implications of various Routes of
Administration
• Understand the advantages and
disadvantage of various Routes of
Administration from a PK point of view
Routes

Definition
Definition:
To produce a pharmacological effect it is very
important for the drug to reach the site of action.
Route of administration is the path by which a
drug, fluid, poison or other substance is brought
into contact with the body.

PRINCIPLES OF DRUG
ADMINISTRATION
To provide safe drug administration, the
nurse should
practice the “rights” of drug administration.
They are:
• The right client
• The right drug
• The right dose
• The right time
• The right route

Cont.’
Experience indicates that five additional rights
are essential to
professional nursing practice;
• The right assessment
• The right documentation
• The client’s right to education
• The right evaluation
• The client’s right to refuse

Cont.’
A route of administration in pharmacology and
toxicology is the path by which a drug, fluid,
poison, or other substance is taken into the
body.
• Most of the drugs can be administered by
different routes.
• The choice of appropriate route in a given
situation depend both on drug as well as
patient related factors.

DETERMINANT OF THE ROUTE
OF ADMINISTRATION
1.Physical and chemical properties of the drug (solid/
liquid/gas; solubility, stability, pH, irritancy).
2. Site of desired action—localized and approachable or
generalized and not approachable.
3. Rate and extent of absorption of the drug from different
routes.
4. Rapidity with which the response is desired (routine
treatment or emergency).
5. Accuracy of dosage required (i.v. and inhalational can
provide fine tuning).
6. Condition of the patient (unconscious, vomiting)

Main division of Routes
(a) Local action
It is the simplest mode of administration of a drug at the site
where the desired action is required. Systemic side effects are
minimal.
(b) Systemic action.
Drugs administered by this route enter blood and produce
systemic effects. Enteral Routes It includes (i) Oral
route, (ii) Buccal or Sublingual route and (iii) Rectal route.

LOCAL ROUTES
• These routes can only be used for localized
lesions at accessible sites.
• Drugs whose systemic absorption from these
sites is minimal or absent.
• High concentrations are attained at the
desired site without exposing the rest of the
body.
• Systemic side effects or toxicity are
consequently absent or minimal.

Drug administration

TOPICAL:
• This refers to external application of the drug to the
surface for localized action.
• More convenient as well as encouraging to the
patient.
• Sites: Skin, oropharyngeal/ nasal mucosa, eyes, ear
canal, anal canal or vagina
Dosage form: lotion, ointment, cream, powder, rinse,
paints, drops, spray, lozengens, suppositories or
pesseries

Advantages and Disadvantages of
the Topical Route
 Advantages
- Used in children.
- Little first pass effect.
- Can be given in vomiting.
- Can be given in unconscious patient.
- Higher therapeutic concentrations of drug are achieved
rapidly in rectum.
- For rapid evacuation of bowel, usually during gut
sterilization before any surgical or radiological procedure.
 Disadvantages
- Inconvenient.
- Drug absorption is slow and erratic.
- Irritation or inflammation of rectal mucosa can occur.

Example of Topical
a) Oral cavity: As a suspension, e.g. nystatin; as a troche, e.g.
clotrimazole (for oral candidiasis); as a cream, e.g. acyclovir (for
herpes labialis); as ointment and jelly, e.g. 5% lignocaine
hydrochloride (for topical anaesthesia); as a spray, e.g. 10%
lignocaine hydrochloride (for topical anaesthesia).
b) b) GI tract: As tablet that is not absorbed, e.g. neomycin (for
sterilization of gut before surgery).
c) c) Rectum, Vaginal and anal canal:
- As an enema (administration of drug into the rectum in liquid
form):
- Evacuant enema (for evacuation of bowel): For example, soap
water enema—soap acts as a lubricant and water stimulates the rectum.
– Retention enema: For example, methylprednisolone in ulcerative
colitis.

DEEPER TISSUES
• Certain deep areas can be approached by
using a syringe and needle.
• Drug should be in such a form that systemic
absorption is slow
• e.g: Intra-articular injection (hydrocortisone
acetate in knee joint), infiltration around a
nerve or intrathecal injection (lidocaine),
retrobulbar injection (hydrocortisone acetate
behind the eyeball)

SYSTEMIC
The drug administered through
systemic routes is intended to be
absorbed into the blood stream and
distributed all over, including the site
of action through circulation

1. ENTERAL ROUTE:
Enteral route is through the
alimentary canal.
It might be:
• Oral
• Sublingual
• Per rectum

Administration

ORAL ROUTE

FACTORS AFFECTING ABSORPTION ON
ORAL ADMINISTRATION:
• Gut content
• Gastro-intestinal motility
• Splanchnic blood flow
• Surface Area for Absorption
• Particle size and formulation
• Physicochemical factors, drug
interactions

Advantages:
 Advantages:
- Convenient - portable, safe, no pain, can be self-
administered.
- Cheap - no need to sterilize (but must be
hygienic of course)
- Variety of dosage forms available - fast release
tablets, capsules, enteric coated, layered tablets,
slow
release, suspensions, mixtures
- Convenient for repeated and prolonged use.

Disadvantages:
- Sometimes inefficient :- high dose or low solubility drugs may
suffer poor availability, only part of the dose may be absorbed.
Griseofulvin was reformulated to include the drug as a micronized
powder. The recommended dose at that time was decreased by a
factor of two because of the improved bioavailability.
- First-pass effect :- drugs absorbed orally are transported to the
general circulation via the liver. Thus drugs which are extensively
metabolized will be metabolized in the liver during absorption. e.g. the
propranolol oral dose is somewhat higher than the IV, the same is true
for morphine. Both these drugs and many others are extensively
metabolized in the liver.

First pass effect
 The first-pass effect is the term used for the hepatic metabolism of a
pharmacological agent when it is absorbed from the gut and delivered to the
liver via the portal circulation.
 The greater the first-pass effect, the less the agent will reach the systemic
circulation when the agent is administered orally

SUBLINGUAL ROUTE OR
BUCCAL
• The tablet or pellet containing the drug is
placed under the tongue or crushed in the
mouth and spread over the buccal mucosa.
• Medication is absorbed directly by the blood
vessels under the tongue or in the lining of the
mouth which provide fast action and Bypasses
first-pass effect
• Only lipid soluble and non-irritating drugs
can be so administered.

ADVANTAGES & DISADVANTAGES
advantages
 economical
 quick termination
 first-pass avoided
 drug absorption is quick
disadvantages
 unpalatable & bitter drugs
 irritation of oral mucosa
 large quantities not given
 few drugs are absorbed

BUCCAL ROUTE

RECTAL ADMINISTRATION
• Drugs can be given in the form of solid or liquid.
- Suppository: It can be used for local (topical) effect as well as systemic effect,
e.g. indomethacin for rheumatoid arthritis.
- Enema: Retention enema can be used for local effect as well as systemic
effect. The drug is absorbed through rectal mucous membrane and produces
systemic effect,
e.g. diazepam for status epilepticus in children.
 Site: Through Rectum
• Drug are absorbed via external haemorrhoidal veins.
Advantages:
• Can be given to patient having nausea and vomiting
• First pass metabolism is relatively less.
• Useful for gastric irritant drugs also

DISADVANTAGES
• Chances of rectal inflammation
• Absorption is unreliable
• Inconvenient and embarrassing to the patient
Example:
For local effect: Bisacodyl and glycerine
suppositories, enemas and ointments
For systemic effects:
aminophylline(bronchodilator),
indomethacin( anti-inflammatory agent),
Paracetamol suppositories.

2. PARENTERAL ROUTE
• Routes other then enteral are called
parenteral routes of administration.
• The administration of drug by injection, by
topical application to the skin or by
inhalational through lungs are all parenteral.

ADVANTAGES
• Action is more rapid and predictable than oral
administration
• These routes can be employed in an unconscious or
uncooperative patient
• Gastric irritants can be given parenterally and therefore
irritation to the gastrointestinal tract can be avoided
• It can be used in patients with vomiting or those unable to
swallow
• Digestion by the gastric and intestinal juices and the first
pass metabolism are avoided.

parenteral routes of administration

INJECTION
1. Intravenous:
Site: Through the lumen of the vein, mainly the antecubital
vein.
Advantages:
• The drug enters the systemic circulation directly, by passing
the first pass degradation (100% bioavalabilty).
• Quick onset of action
• Lesser dose is required to achieve desired plasma
concentration

Cont.’
• Hypertonic solutions and GIT irritant drugs can
also be infused by this route.
• Large volume of fluid can be infused at a uniform
rate by this route
• Amount of drug can be controlled with an
accuracy.
• Can be given to even to unconscious,
uncooperative, even those having nausea,
vomitting, diarrhoea

DISADVANTAGES
• Strict aseptic condition condition are needed
• Patient has to depend on others for giving an injection
• It is painful, and risky because once the drug injected it
cannot be recalled.
• Introduction of any particulate matter or air may produce
embolism which may prove fatal.
• Drugs in suspension or oily drugs cannot be administered
by this route
• Venous thrombosis, thrombophlebitis and necrosis around
the site of injection of injection if extravasation occurs.

Cont.’
• This route mainly systemic effect.
• Examples:
• Glucose, glucose normal saline,
dopamine,
norepinephrine drips for i.v infusion.
• Many antibiotics, barbiturate
anaesthetics, diazepam
etc. are injected by this route

ii) Intramuscular injection:
Site: Deltoid muscle.
Gluteal muscle
rectus femoris ( lateral surface of the thigh)
Advantages:
• Absorption is more predictable, less variable and
rapid compared to oral and subcutaneous route
• Depot injection can also be given by this route.

DISADVANTAGES
• Aseptic condition is needed
• Chances of abscess at the site of injection
• Chances of nerve damage leading to paresis of muscle
supplied by it.
• Large volume of drug cannot be administered (max- 5ml)
• This route provides mainly systemic effect.
• Examples:
• Various antibiotics, antiemetics
• Depot injection of testosterone and
neuroleptics(haloperidol)

iii) Intraperitoneal
• Site : into the peritoneal space
Advantages:
• Rapid absorption due to large surface
area
Disadvantage:
• Aseptic condition is needed
• Painful,
• Chances of adhesion and infection in the
peritoneal cavity

Intrathecal (intraspinal)
administration
• Site : Into the subarachnoid space
Advantage:
• The drug passes directly into subarachnoid
space
bypassing the blood brain barrier and blood CSF
barrier.
• The drug act directly on meninges and the
spinal cord
• Significant CSF level are achieved, not possible
by other route.

Disadvantages:
Disadvantages:
• Strict aseptic condition and expertise is required
• Painful and risky procedure
Examples:
• Many radiopaque contrast media for myelography
• Xylocaine injection for providing spinal anesthesia
( local effect)
• Antibiotics used to treat meningitis do provide
systemic effect when given by this route

INTAMEDULLARY
• Site: injection into the bone marrow of tibia or
sternal bone.
Advantages:
• Onset of action is very fast as vascular spaces
of bone marrow communicate directly with
large veins.
Disadvantages:
• Aseptic condition
• Skill is needed, Risky, Painful,

INTRA-ARTERIAL
• Site : Into the lumen of desired artery
Advantages:
Greater concentration of drug can be
delivered at the desired site of action.
Disadvantage:
• Aseptic condition
• Expertise is required

Cont.’
Examples:
• Peripheral vascular diseases,
• Radiopaque contrast media for
coronary angiography and cerebral
angiography
• Chemotherapy drug for malignancy

INTRA-ARTICULAR
• Site: Injection directly into the bone space
Advantage:
Higher concentration of drug in a localised area.
Disadvantage:
• Strict aseptic condition is needed.
• Painful procedure
• Repeated injection into the joint space may further
damage the joint

SUBCUTANEOUS ADMINISTRATION
Site: Injection into the subcutaneous tissue under
the skin
Advantages:
• Smooth but slower absorption for longer period
compared to intravenous or intramuscular.
• Depot injection or implants can also be made.
Disadvantages:
• Only small volume of drugs can be injected.
• Irritant drug cannot be administered – may lead to
sloughing and necrosis

Cont.’
Examples:
• Subcutaneous injection of local anesthetics( local
effect)
• Subcutaneous insulin, heparin for systemic effect
• Vaccines are also administered by this route
Other cutaneous related routes:
a) Intradermal
b) Dermojet injection
c) Pellet implants

A) Intradermal Route:
i. The drug is injected into the outer layer of skin
ii. Drug amount is small
iii. Absorption is slow
iv. Tuberculin syringe is used to administer
e.g – B.C.G vaccine, diagnostic test, allergic
sensitization
testing

B) Dermojet injection:
i.Subcutaneous needleless injection
of a drug by means of
a high velocity jet projected
through a microfined orifice
ii. Painless
iii. Useful for mass inoculation

INHALATIONAL ADMINISTRATION
• Site: Inspiration through nose or mouth
Advantages
• Almost instantaneous absorption of the drug is
achieved because of the large surface area of alveoli.
• Self administration is possible
• In pulmonary diseases, it serves almost as a local route
as the drug is delivered at the desired site making it
more effective and less harmful
• Hepatic first pass metabolism is avoided
• Blood levels of volatile anesthetics can be conveniently
controlled as their absorption and excretion through the
lungs are governed by the laws of gases.

Disadvantage
Disadvantage
• Irritant gases may enhance pulmonary
secretions and should be avoided by this route.
• This is an important route of entry of certain
drugs of abuse.
e.g :
• Oygen and general anesthetics ( systemic use)
• Salbutamol for treatment of bronchial asthma

TRANSDERMAL
ADMINISTRATION
• Transdermal administration is considered under
parentral route because the Patches, though apllied
topically provide systemic effect.
• Highly lipid soluble drugs can be applied over the skin
for slow and prolonged absorption,
Site: Adhesive patch containing drug is applied to chest,
upper abdomen or mastoid region.
Advantages:
• Slow but sustained release of the drug for several days
• Bypasses first pass metabolism

Summary

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Lecture 2. pharmakokinetic pptx

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