PowerPoint Presentation
Semester 1 2020
• Welcome to BIOL 122 !
•Human Biological Science 2
•Introduction to Unit
•Week 1- Lecture A
• Important information about the BIOL122
• will be given at the lecture
• Not to be missed!
XXXXXXXXXXSemester 1 2020
Pharmacokinetics - Dr Hemant Mehta
20/02/2020
1
Pharmacokinetics
BIOL 122 Dr H Mehta
Pharmacokinetics
• Study of the absorption, distribution, metabolism, and
excretion of drugs, “ie. what the body does to the drug”
• Movement of drug inside the body – how the body
handles the drug (influenced by the route of
administration)
Drug absorption: the process of drug transport from
site of administration to systemic circulation by crossing
iological mem
ane.
Drug transport processes:
• Passive transport
Most drugs transport by simple diffusion
(movement from high to low concentration; no ca
ier
protein; no energy required)
• Specialised transport
- Active transport
- Facilitated diffusion
- Endocytosis
- Exocytosis
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Bioavailability: the rate and amount of drug that is
abso
ed from a given dosage form and reaches the
systemic circulation.
1st pass hepatic metabolism: metabolism of drugs upon
first passage through the liver (can inactivate drug molecule
efore reaching the systemic circulation)
The mode of entry of a drug into the body determines
the character, speed, dose and degree of action.
Absorption and hepatic first pass determine the bioavailability of
a drug to produce a therapeutic effect.
Factors affecting drug absorption & bioavailability
• Physico-chemical properties of drug (molecular size,
solubility, pH)
• Nature of the dosage form (eg. particle size,
disintegration and dissolution of drug)
• Physiological factors (eg. GI transit time, surface area,
lood supply to site of absorption, rate of gastric
emptying, peristaltic activity)
• Disease states (Absorption and first pass metabolism
may be affected in conditions like malabsorption, liver
ci
hosis)
Drug absorption depends on chemical structure of drug
and nature of the abso
ing surface
Drug molecular weight: the smaller in size, the more
absorption
• Many drugs are abso
ed by simple diffusion
• small molecules diffuse more rapidly than large
molecules
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Drug solubility:
Drug solubility determines the degree and time taken to cross cell
mem
anes.
- non-ionised (ie. non-polar) drugs are lipid soluble; these
lipophilic substances diffuse across cell mem
anes easily
and rapidly. Lipid-soluble drugs are abso
ed effectively.
- ionised (polar) drugs are water soluble; (hydrophilic
substances don’t cross cell mem
anes readily)
The more lipid soluble the drug … more absorption
The more water soluble the drug … less absorption
pH:
• Drugs are weak acids or weak bases, and tend to dissociate
in body fluids depending on pH of local environment. GIT is
a major site of drug absorption; it has a variable pH
(stomach: pH 3 & duodenum: pH 8).
• Acidic drugs (eg. aspirin) are better abso
ed in the
stomach
• Basic drugs (eg. morphine) are better abso
ed in the
small intestine.
Physiological factors affecting drug absorption
• Rate of gastric emptying: Rapid gastric emptying rate →
faster drug absorption
• Peristaltic activity: Slow peristaltic activity → slower but
more complete absorption of drugs.
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Nature of abso
ing surface
Number of cell layers: rapid absorption across thin respiratory
mem
ane than across skin (multiple cell layers)
Surface area of the administration site is also important:
a large surface area results in greater & rapid absorption.
Absorption of orally-taken drugs usually mainly takes place in
the small intestines.
Respiratory medication is best given by inhalation, as
the large surface area of lungs (thin respiratory mem
ane)
lead to rapid, effective absorption into pulmonary
loodstream.
Blood supply to site of absorption
High blood flow: facilitates drug absorptive process;
poor blood flow: impedes absorption.
Drugs administered into highly vascular tissues (eg. muscle,
or directly into circulation) are readily abso
ed.
Drugs administered into less vascularised tissues
(eg. subcutaneous layer) are poorly abso
ed.
Circulatory disorders (such as shock) significantly ↓drug
absorption.
Dosage forms and routes of administration
Ointment A medical preparation applied topically (to the skin)
that has an oil base (a cream is water-soluble).
Capsule A gelatinous casing enclosing a dose of a drug.
Tablet A small solid form of medication intended for oral use.
Drug suspension A preparation of drug suspended in a liquid.
Enteric coated A waxy coating applied to oral medication that
prevents release until the small intestine is reached.
Nebuliser A pump to administer medication in the form of
mist to the lungs.
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Oral route
• Most drugs are administered by the oral route
Advantages:
- safest
- most convenient
- least expensive
Disadvantages:
- slower acting than other routes such as injectables
- oral route not suitable for those with GI intolerance or
‘nil by mouth’ status, or who are unconscious
• Give oral drug with caution to those who have difficulty
swallowing, eg. stroke (CVA) patient
Routes of drug administration
Sublingual • Under the tongue
• Drug diffuses through the
mucous mem
ane
eneath tongue and into
venous circulation
• Bypasses liver and hepatic
metabolism
eg. anginine (for
treatment of angina)
www.answers.com/topic/sublingual
Inhalational route
eg. nasal
espiratory
• Through the nose or
inhaled
• Drugs delivered directly
to lungs
• Have to be atomised
(small droplets in air)
Eg. Ventolin
• Also quickly abso
ed
into bloodstream through
mucous mem
anes
Eg. psychoactive drugs
www.buzzle.com/.../nasal-spray-side-effects.html
http:
www.answers.com/topic/sublingual
http:
www.buzzle.com/articles/nasal-spray-side-effects.html
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Transdermal
• Drugs are delivered
odywide through the
skin by wearing a skin
patch
• Continuous slow
absorption
• Useful for drugs that are
quickly eliminated from
the body
Eg. anginine, nicotine
publications.nigms.nih.gov/.../chapter1.html
Intravenous
• Injection into a vein
• Fastest way to deliver
liquids and medicines
• Immediate effect because
no ba
ier to absorption,
eg. morphine,
chemotherapeutic
agents…
• Use any identifiable vein
(arm most common)
Parenteral A route of administration that requires piercing
the skin or mucous mem
ane and bypasses the GIT.
Intravenous Drug injected directly into a vein to produce
apid action; can be given as bolus (eg. morphine, dopamine)
or as continuous infusion (eg. fluids during shock or
dehydration).
Intrathecal Injected into subarachnoid space of spinal cord,
eg. spinal anaesthetics.
Intra-articular Injected directly into a joint,
eg. hydrocortisone.
http:
publications.nigms.nih.gov/medbydesign/chapter1.html
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• Intradermal Injection into the layers of the skin,
eg. BCG vaccine.
• Subcutaneous Non-i
itant substances are given into
subcutaneous tissue, eg. insulin.
• Depot form of drug Drug formulation where drug is
injected i.m. or inserted under the skin and is slowly
eleased over a period of time (eg. vaccines). This drug
delivery method is mainly used for contraception and in
mental health.
Depot injection
• Subcutaneous or intramuscular injections
• Usually solid or oil-based
• Long acting, slow release drugs
• Reduction in frequency of dosing (helps with compliance)
Eg. Fluanoxal for schizophrenia
Subcutaneous • Under the skin
• Avoids gastric digestion
• Highly effective for
insulin
• Areas of injection are
outer area of upper arm,
above and below the
waist, front of thigh,
upper area of buttock
www.dana-fa
er.org/can/patient-instruction/h...
www.hghnews.us/p/175.html
www.answers.com/topic/injection
http:
www.dana-fa
er.org/can/patient-instruction/html/instructions-for-subcutaneous-injection.html
http:
www.hghnews.us/p/175.html
http:
www.answers.com/topic/injection
20/02/2020
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Intramuscula
- Injected into the muscle
• - Used for medicines
(soluble substances, mild
i
itants, suspensions, and
colloids) administered in
small amounts,
eg. vaccines, penicillin
• - Slow absorption
- Given in deltoid or
vastus lateralis muscles
www.answers.com/topic/injection
Pessary A drug delivery system that contains a drug and is
inserted into the vagina. Therapeutic pessaries may also be
used to support the pelvic floor.
Suppository A drug delivery system that is inserted into the
ectum. It is inserted as a solid and will dissolve in the body
to release the drug.
Rectal
• Insertion of suppositories into
ectum;
• drug is mixed with a waxy
substance that dissolves or
liquefies after it is inserted
into the rectum;
• rectum's wall is thin and its
lood supply rich so drug is
eadily abso
ed;
• prescribed for people who
cannot take a drug orally
ecause they have nausea,
cannot swallow, or have
estrictions on eating, as is
equired after many surgical
operations, eg. Stemetil
http:
en.wikipedia.org/wiki/File:Anorectum.gif
http:
upload.wikimedia.org/wikipedia/commons/c/ce/Suppositories_three_different_sizes_2.jpg
http:
www.answers.com/topic/injection
20/02/2020
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Drug distribution
After absorption of drug into blood circulation, it travels
to its site of action.
As the drug has to be lipophilic for absorption to take
place, solubility in plasma may be limited.
Many drugs become bound to plasma protein (“drug
eservoir”: prolongs drug presence in body).
Another drug reservoir in the body is the adipose (fat)
tissue.
Protein binding
• Bloodstream has a remarkable ability to transport
elatively insoluble substances (eg. sex hormones such
as androgens) which are lipophilic and yet are
transported efficiently in the blood. This is because
they are transported attached to blood proteins such
as albumin and globulins.
• Many drugs are highly (99.9%) protein-bound; only the
0.1% free (unbound) drug is pharmacologically active.
As the free form is used up, more is released from the
protein-bound form.
Protein binding acts as a temporary store of a drug
and tends to prevent large fluctuations in
concentration of unbound drug in the body fluids.
- High protein bound drugs are usually long acting
- Low protein bound drug: usually short acting
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Adipose tissue binding
Body fat deposits also bind drugs. Fat tissue is an important
eservoir for lipophilic drugs.
Lipid-soluble drugs are abso
ed into adipose tissue, and
slowly released into bloodstream, hence prolonging their
presence in the body.
Eg. Tetrahydrocannabinol (THC: active constituent in
marijuana) is lipophilic, and is readily taken up into body fat.
After