Pharmacology and Nutrition
lecture notes
Lecture 1 - introduction
There are different process phases in pharmacology, which are
shown in the image.
Coated tablet: a coating protects the core in the stomach, it
prevents dissolution in the stomach (the stomach needs to be
protected from the active ingredient).
Biotransformation: a compound is metabolised by the liver to
make a compound more water soluble. This occurs in several
phases and results in conjugates.
The drug development process is shown in the
image, which usually takes 10-15 years.
However, during the covid pandemic, drugs and
vaccines were faster made.
Pharmacology: the study of the effects of drugs
on living systems, aiming to improve their
functioning.
Drugs: medicines, bio-actives and chemicals.
Critical concepts of drugs:
Drugs need to be absorbed and/or reach the target tissue
The drug molecule needs to interact with a receptor
This interaction should lead to a (measurable) effect on health, physiology etc.
Drug absorption is mostly in the duodenum (‘twaalfvingerige darm’) and the drug should be in a
dissolved state. Drug absorption usually occurs via passive diffusion and sometimes, active transport
is involved. Lipid soluble compounds will be absorbed better if you take it with
a fatty meal (containing a lot of lipids). Metabolism in the intestinal wall can be
considerable, meaning that the majority of the drug is already broken down
before the drug enters your bloodstream.
A tablet disintegrates into granules and further on into fine particles. Granules
and fine particles should be in a solution (more important for the fine particles).
MEC: minimal effective concentration.
MTC: minimal toxic concentration.
The room between the MEC and the MTC in a
graph is called the therapeutic window. The
graphs have been made following mathematical
rules (logarithms), which will be explained later
on in the course. Micronutrients behave
similarly, which also have similar curves.
Vitamins also have too high or too low doses.
,COX enzymes: convert arachidonic acids, present in the phospholipids of all cells, into PGH2 during
an inflammatory response (see image). Celecoxib is a selective COX-2 enzyme inhibitor. This blocks
the conversion to PGH2, which is indicated in the image
with the lightning bolt.
There is a big overlap between how drugs behave in the
body and how micronutrients behave in the body. This is
not only true for the graph, but also for the interaction
with receptors. Vitamin D from sunlight and diet enters
the bloodstream and has to be metabolised by the liver.
Then, it is transferred to the kidney, were it is again
metabolised into the active form (1,25(OH)2D). The active
form can bind to the vitamin D receptor (VDR) of a cell,
causing dimerization of the retinoid X receptor (RXR). The ligand-bound VDR-RXR complex binds to
structurally distinct vitamin D response elements (VDREs) in multiple,
widely spaced vitamin D responsive regions. This causes modification in the
recruitment of co-activators or co-repressors, which leads to positive or
negative transcriptional regulation of gene expression.
Medicines need approval to be allowed on the market. The Netherlands
has the CBG (college ter beoordeling van geneesmiddelen), and Europe has
the European Medicines Agency (EMA). Each medicine sold in the
Netherlands needs a unique registration code (RVG code). Homeopathic
medicines have a RVH code and an EU code is made for European registration.
Phytotherapy: studying and using medicinal plants. This is not the same as homeopathy!
Homeopathy: like-cures-like, uses extreme dilutions. The effectiveness and safety is very
controversial.
Our diet contains molecules that have biological activities that go beyond providing energy or
structure. For example caffeine is involved in neutrophil degranulation. Vitamin supplements should
only be taken when you have a deficiency, because these also have (negative) biological activities.
Legal definition of drugs: any substance or combination of substances which may be administered to
human beings with a view to making a medical diagnosis or to restoring, correcting or modifying
physiological functions in human beings.
Working definition: a drug is a substance of known structure, other than a nutrient or an essential
dietary ingredient, which when administered to a living organism, produces a biological effect.
Fake health claims on food products are forbidden.
Lecture 2 - receptors
The molecular action of a drug/bioactive can often be explained by-, and
predicted from a receptor concept. Receptors are macromolecules, including:
enzymes, transporters, structures on cell membranes, transcription factors,
nucleotides etc.
Receptors are mostly normal regulatory structures playing a role in the
physiology of the organisms. Ligands, such as neurotransmitters, hormones or
other signalling molecules can bind to receptors. Drugs either bind by
coincidence to receptors or by design. The types of receptors and their
interactions are shown in the image.
Ion channels: multi-subunit ion channels are located at the cell surface
, transmembrane. The binding of a ligand results in an ion flux, which has an effect on cell excitability.
Blocking of the ion channels can have an effect on permeability. An example of a ligand is GABA, the
GABA receptor can be inhibited by benzodiazepines medicines.
Protein kinases: located at the cell surface transmembrane. They have a binding site on the outer site
of the cell and a catalytic site on the inside of the cell. Examples of ligands are growth factors, insulin
and peptide hormones which bind to the binding site.
Transcription factor: located in the cytoplasm. Examples of ligands are steroid hormones, thyroid
hormones and vitamin D. If the ligand binds to a transcription factor, the transcription factor
becomes activated and can bind to the DNA to regulate its expression (think about the vitamin D
receptor from lecture 1). Vitamin D has been found to be effective in the treatment of cancer or
other inflammatory diseases.
G-protein coupled receptors (GPCR): located at the cell surface (7 transmembrane).
Examples of ligands are acetylcholine and α- and β-adrenergic eicosanoids. Binding of
the ligand leads to a conformational change, which affects the G-protein. The G-
protein cycles between GTP and GDP and is a rapid
signalling process. The GPCR is one of the most important
targets of today’s drugs and it is a very large family of
regulatory proteins. Agonist bindings lead to a cell
signalling cascade, involving many chemical mediators.
In the image, the green blocks (α- and β-subunit) make up
the G-protein. The α-subunit binds to target 1, the β-
subunit binds to target 2. What happens next depends on
the target effector proteins. Examples:
Adenylyl cyclase: intracellular second messenger system.
Activated G-protein can activate adenylyl cyclase, which
results in the conversion of ATP to cAMP. cAMP can
activate protein kinase A as a second messenger. Protein
kinase A is used for conversion of glycogen to glucose (by
activating phosphorylase).
Phospholipase C/inositol phosphate pathway: The
activated G-protein results in binding of the α-subunit to
phospholipase C. Activated phospholipase C can form
inositol
triphosphate
(calcium release
into cytosol) and diacylglycerol (results into
activated protein kinase C). Protein kinase C can
result to phosphorylated proteins.
Phosphodiesterase can hydrolyse cAMP back to ATP, to
turn off the receptor signals. GTPase can convert GTP to
GDP, to inactivate the G-protein.
Receptor desensitization: inactivating the receptor signals.
Some receptors are phosphorylated via specific receptor kinases. The phosphorylated receptor may
then bind to a protein b-arrestin, that promotes removal of the receptor from the membrane by
clathrin-mediated endocytosis.
lecture notes
Lecture 1 - introduction
There are different process phases in pharmacology, which are
shown in the image.
Coated tablet: a coating protects the core in the stomach, it
prevents dissolution in the stomach (the stomach needs to be
protected from the active ingredient).
Biotransformation: a compound is metabolised by the liver to
make a compound more water soluble. This occurs in several
phases and results in conjugates.
The drug development process is shown in the
image, which usually takes 10-15 years.
However, during the covid pandemic, drugs and
vaccines were faster made.
Pharmacology: the study of the effects of drugs
on living systems, aiming to improve their
functioning.
Drugs: medicines, bio-actives and chemicals.
Critical concepts of drugs:
Drugs need to be absorbed and/or reach the target tissue
The drug molecule needs to interact with a receptor
This interaction should lead to a (measurable) effect on health, physiology etc.
Drug absorption is mostly in the duodenum (‘twaalfvingerige darm’) and the drug should be in a
dissolved state. Drug absorption usually occurs via passive diffusion and sometimes, active transport
is involved. Lipid soluble compounds will be absorbed better if you take it with
a fatty meal (containing a lot of lipids). Metabolism in the intestinal wall can be
considerable, meaning that the majority of the drug is already broken down
before the drug enters your bloodstream.
A tablet disintegrates into granules and further on into fine particles. Granules
and fine particles should be in a solution (more important for the fine particles).
MEC: minimal effective concentration.
MTC: minimal toxic concentration.
The room between the MEC and the MTC in a
graph is called the therapeutic window. The
graphs have been made following mathematical
rules (logarithms), which will be explained later
on in the course. Micronutrients behave
similarly, which also have similar curves.
Vitamins also have too high or too low doses.
,COX enzymes: convert arachidonic acids, present in the phospholipids of all cells, into PGH2 during
an inflammatory response (see image). Celecoxib is a selective COX-2 enzyme inhibitor. This blocks
the conversion to PGH2, which is indicated in the image
with the lightning bolt.
There is a big overlap between how drugs behave in the
body and how micronutrients behave in the body. This is
not only true for the graph, but also for the interaction
with receptors. Vitamin D from sunlight and diet enters
the bloodstream and has to be metabolised by the liver.
Then, it is transferred to the kidney, were it is again
metabolised into the active form (1,25(OH)2D). The active
form can bind to the vitamin D receptor (VDR) of a cell,
causing dimerization of the retinoid X receptor (RXR). The ligand-bound VDR-RXR complex binds to
structurally distinct vitamin D response elements (VDREs) in multiple,
widely spaced vitamin D responsive regions. This causes modification in the
recruitment of co-activators or co-repressors, which leads to positive or
negative transcriptional regulation of gene expression.
Medicines need approval to be allowed on the market. The Netherlands
has the CBG (college ter beoordeling van geneesmiddelen), and Europe has
the European Medicines Agency (EMA). Each medicine sold in the
Netherlands needs a unique registration code (RVG code). Homeopathic
medicines have a RVH code and an EU code is made for European registration.
Phytotherapy: studying and using medicinal plants. This is not the same as homeopathy!
Homeopathy: like-cures-like, uses extreme dilutions. The effectiveness and safety is very
controversial.
Our diet contains molecules that have biological activities that go beyond providing energy or
structure. For example caffeine is involved in neutrophil degranulation. Vitamin supplements should
only be taken when you have a deficiency, because these also have (negative) biological activities.
Legal definition of drugs: any substance or combination of substances which may be administered to
human beings with a view to making a medical diagnosis or to restoring, correcting or modifying
physiological functions in human beings.
Working definition: a drug is a substance of known structure, other than a nutrient or an essential
dietary ingredient, which when administered to a living organism, produces a biological effect.
Fake health claims on food products are forbidden.
Lecture 2 - receptors
The molecular action of a drug/bioactive can often be explained by-, and
predicted from a receptor concept. Receptors are macromolecules, including:
enzymes, transporters, structures on cell membranes, transcription factors,
nucleotides etc.
Receptors are mostly normal regulatory structures playing a role in the
physiology of the organisms. Ligands, such as neurotransmitters, hormones or
other signalling molecules can bind to receptors. Drugs either bind by
coincidence to receptors or by design. The types of receptors and their
interactions are shown in the image.
Ion channels: multi-subunit ion channels are located at the cell surface
, transmembrane. The binding of a ligand results in an ion flux, which has an effect on cell excitability.
Blocking of the ion channels can have an effect on permeability. An example of a ligand is GABA, the
GABA receptor can be inhibited by benzodiazepines medicines.
Protein kinases: located at the cell surface transmembrane. They have a binding site on the outer site
of the cell and a catalytic site on the inside of the cell. Examples of ligands are growth factors, insulin
and peptide hormones which bind to the binding site.
Transcription factor: located in the cytoplasm. Examples of ligands are steroid hormones, thyroid
hormones and vitamin D. If the ligand binds to a transcription factor, the transcription factor
becomes activated and can bind to the DNA to regulate its expression (think about the vitamin D
receptor from lecture 1). Vitamin D has been found to be effective in the treatment of cancer or
other inflammatory diseases.
G-protein coupled receptors (GPCR): located at the cell surface (7 transmembrane).
Examples of ligands are acetylcholine and α- and β-adrenergic eicosanoids. Binding of
the ligand leads to a conformational change, which affects the G-protein. The G-
protein cycles between GTP and GDP and is a rapid
signalling process. The GPCR is one of the most important
targets of today’s drugs and it is a very large family of
regulatory proteins. Agonist bindings lead to a cell
signalling cascade, involving many chemical mediators.
In the image, the green blocks (α- and β-subunit) make up
the G-protein. The α-subunit binds to target 1, the β-
subunit binds to target 2. What happens next depends on
the target effector proteins. Examples:
Adenylyl cyclase: intracellular second messenger system.
Activated G-protein can activate adenylyl cyclase, which
results in the conversion of ATP to cAMP. cAMP can
activate protein kinase A as a second messenger. Protein
kinase A is used for conversion of glycogen to glucose (by
activating phosphorylase).
Phospholipase C/inositol phosphate pathway: The
activated G-protein results in binding of the α-subunit to
phospholipase C. Activated phospholipase C can form
inositol
triphosphate
(calcium release
into cytosol) and diacylglycerol (results into
activated protein kinase C). Protein kinase C can
result to phosphorylated proteins.
Phosphodiesterase can hydrolyse cAMP back to ATP, to
turn off the receptor signals. GTPase can convert GTP to
GDP, to inactivate the G-protein.
Receptor desensitization: inactivating the receptor signals.
Some receptors are phosphorylated via specific receptor kinases. The phosphorylated receptor may
then bind to a protein b-arrestin, that promotes removal of the receptor from the membrane by
clathrin-mediated endocytosis.
