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 MOTTO AND VISION
• To impart evidence based
research oriented medical
education
• To provide best possible patient
care
• To inculcate the values of mutual
respect and ethical practice of
medicine

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 FOUNDATION MODULE

ABSORPTION OF DRUGS

Sources:
 Bertram G. katzung Basic & Clinical Pharmacology 15th Edition
 Goodman and Gilman’s The Pharmacological Basis of Therapeutics
13th edition.

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 PROFESSOR UMAR MODEL OF INTEGRATED
LECTURE

1%
HORIZONTAL
96%
INTEGRATION
CORE SUBJECT
Physiology
biochemistry

0% 0%
VERTICAL VERTICAL
INTEGRATION INTEGRATION
Clinical Pathology
integration pharmacology

3%
VERTICAL
INTEGRATION
Research,
professionalism
Ethics
Digital library

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 Learning Objectives

 Define Drug Absorption .

 Identify different sites of drug absorption.
 Recall transport processes utilized by the drug
for absorption across different sites.

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 Horizontal integration

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 ABSORPTION OF DRUGS
Core subject

• Absorption is the movement of drug from its site of

administration into the circulation.
• The rate of absorption affects the onset , duration
and intensity of drug action.

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 Drugs are transported across the membrane by:

1. Passive transport:
a. Simple diffusion
b. Filtration/ aqueous diffusion
c. Bulk flow

2. Active transport:
d. Primary active transport
e. Secondary active transport
f. Endocytosis:
1. Phagocytosis
2. Pinocytosis
3. Transcytosis
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 Simple diffusion

Most of the drugs are absorbed by simple diffusion ,

which is the movement of molecules down the
concentration gradient i.e. from higher
concentration to lower concentration.
• This type of transport occurs mostly for the lipid
soluble drugs.
• Non-specific: no carrier proteins are required.
• Energy expenditure:
no energy is required for this type of transport.

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 Factors Affecting Diffusion

1. Concentration Gradient Across Membrane:

• Fick’s law of diffusion

• Flux (molecules/unit time) =

(C1-C2) x Area x Permeability coefficient
Thickness

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 Factors Affecting Diffusion
CONT--

2. Molecular/ Particle Size

3. Membrane Surface Area

4. Lipid :Aqueous Partitian Coefficient

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 CONT--

5. Ionization of Drugs
• Most of the drugs are either weak acids or weak
bases. Therefore they are part ionized and part
unionized. The ionized portion is charged , which
attracts water molecules , thus forming large
complexes. These complexes cannot cross the
membranes because they are less lipid soluble. This
is why the ionized part of the drug cannot cross the
membrane.
• Drugs are better absorbed in
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unionized form. 13
 Acidic drugs
CONT--

• AH A- + H+ (eq 1)
• Acidic drugs on dissociation give anion and proton.
Basic drugs
• B + H+ BH+ (eq 2)
• Basic drugs on combining with a proton become a cation.
• The existence of drugs as neutral or charged particles depends on the
pH.

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 Acidic medium
• In acidic medium , lots of protons are present.
Therefore , greater amount of acidic drug is
unionized (shift towards left of eq 1). Thus in acidic
medium acidic drug is present more in unionized
form , which increases its absorption. This is why
acidic drugs are better absorbed from stomach.
• Basic drugs get ionized in acidic medium ( right shift
of eq 2) , thus this form is poorly absorbed. Aspirin ,
an acidic drug is unionized in acidic medium of
stomach , so is easily absorbed.

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 Basic medium

• The opposite is true in case of basic medium. Acidic drugs are poorly
absorbed while the basic drugs are well absorbed. Quinidine and
pyrimethamine are antimalarials and basic , so are ionized in stomach
and unionized in intestines , from where they are absorbed.

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 Protonated/Unprotonated form

• Protonated form of acidic drugs is well absorbed while the protonated

form of basic drugs is poorly absorbed , due to the reasons given above.

• When the Ionization constant pKa of a drug is equal to pH of the

medium, then 50% of the drug will be ionized and 50% will be non-
ionized.

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 Henderson Hasselbalch Equation

• This can be stated as :

pKa – pH = log[P/UP]
• Where P is the protonated form while UP is the unprotonated form.
• If pH is lower than pKa the value will be positive indicating that the protonated form is
more than the unprotonated form.
For acidic drugs
pKa – pH = log [AH/A-]
• If pH is lower than pKa , AH will be more.
For basic drugs
pKa – pH = log [BH+/B]
• If pH is lower than pKa , BH+ will be more.
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 Drugs in intestines
• For acidic drugs A- is more , so the drugs are present
in ionized form in the intestines , thus are less
absorbed.
• For basic drugs , B is more , thus are present in
unionized form in the intestines and are absorbed in
a much greater quantity.
• In short , we can say that acidic drugs are better
absorbed in the acidic medium while basic drugs
are better absorbed in the basic medium.

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 Ion trapping
• Most of the drugs are reabsorbed from the kidneys.
Acidic drugs are better reabsorbed from acidic urine.
This is an important fact , which can be manipulated
to get desired results , as is the case of poisoning
with acidic drugs. If we make the urine alkaline (by
administering sodium bicarbonate) , decreased
reabsorption of acidic drugs take place , a
phenomenon known as ion trapping.

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 Cont--

• In case of poisoning with basic drug , urine can be

made more acidic ( by administering ammonium
chloride) , by virtue of which the basic drug becomes
ionized and is not reabsorbed , with the result that
more of it excreted out.

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 Filtration

• Filtration involves the aqueous channel or pores through which

hydrophilic drugs can pass. Filtration occurs in the jejunum and proximal
tubules of kidneys.
• Only certain ions like Na+ and drugs of low molecular weight , like
ethanol and glycerol can undergo filtration.

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 Bulk flow
• The drug in this process passes through the pores
between capillary endothelial cells. The passage is
independent of water and lipid solubility.
• Bulk flow is the phenomenon mostly seen with the
intra muscular and subcutaneous injections.
• This type of transport is independent of pH and pKa.
Bulk flows does not occur in brain because of
absence of pores.
• However , bulk flow is dependent on the flow , more
the blood flow , more rapid is the absorption.

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 Active Membrane Transport
• Active membrane transport is for the drugs which cannot
cross the lipid membrane and require transport proteins.
Their structure is similar to the endogenous substances
undergoing active transport like amino acids , sugars ,
neurotransmitters , which have the transport proteins.
• Active transport is the carrier mediated transport.
• The drug moves against the concentration gradient. Energy
in the form of ATP is required for the process to occur.
• Different drugs bind different proteins , thus their
absorption is selective from different areas , as well as
their distribution.
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Cont---
• Some drugs directly affect the brain like the Levo
Dopa , which utilize amino acid transporting
mechanism. Other examples include methyl dopa for
hypertension and fluorouracil which is anticancer
drug.
• Active transport mechanism is saturable and can be
inhibited by competing drugs.

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 Primary Active Transport

When the substance moves against the concentration gradient by the

expenditure of energy , the process is called primary active transport .
Secondary Active Transport
When the substance moves against the concentration gradient by the
energy stored by a substance moving down the concentration gradient ,
the process is called secondary active transport.
It is of 2 types:
1.Antiport
2.Symport
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 Facilitated Transport
• Facilitated transport involves the drugs moving down the concentration
gradient by the help of transport proteins.
• No energy expenditure is required.
• This type of transport is also specific and saturable.
• The main objective is that lipid insoluble drugs become lipid soluble by
combining with the carrier. E.g . Iron binds with apoferritin and certain
catecholamines enter the nerve cells by this process.

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 BIOETHICS

• Protect and promote the health of patients and the public

• Provide a good standard of practice and care –
• Keep your professional knowledge and skills up to date
• Recognize and work within the limits of your competence

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 HOW TO ACCESS DIGITAL LIBRARY

1. Go to the website of HEC National Digital Library.

2. On Home Page, click on the INSTITUTES.
3. A page will appear showing the universities from Public and
Private Sector and other Institutes which have access to HEC
National Digital Library HNDL.
4. Select your desired Institute.
5. A page will appear showing the resources of the institution
6. Journals and Researches will appear
7. You can find a Journal by clicking on JOURNALS AND
DATABASE and enter a keyword to search for your desired
journal.

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FURTHER READING
 Further Reading
• Shinde, A.A., Velhal, A.B., Jadhav, P.D. and Redasani,
V.K., 2022. Improvement of Topical Absorption of Drug.
Asian Journal of Research in Pharmaceutical Science,
12(4).
• Farjadian, F., Ghasemi, A., Gohari, O., Roointan, A.,
Karimi, M. and Hamblin, M.R., 2019.
Nanopharmaceuticals and nanomedicines currently on
the market: challenges and opportunities.
Nanomedicine, 14(1), pp.93-126.
• Chou, W.C. and Lin, Z., 2023. Machine learning and
artificial intelligence in physiologically based
pharmacokinetic modeling. Toxicological
Sciences, 191(1), pp.1-14.
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 END OF LECTURE ASSESSMENT

• Q1. absorption is the movement of the drug from the site of

administration into the:
a) Muscles
b) Kidneys
c) Heart
d) Lungs
e) Circulation
• Q2. Fick’s law of diffusion is inversely proportional to:
a) Concentration gradient
b) Area
c) Permeability co-efficient
d) Flow of blood
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e) Thickness of membrane. 36