Summary of Pharmacology and Nutrition HNH-23306_2019_2. Including all lectures, tutorials (pharmacokinetics, behavioral pharmacology, receptor pharmacology guinea pig, inflammation pharmacology), the syllabus, the clinical cases, graphs, tables, drawings and images.
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HNH23306_2019_2
PHARMACOLOGY
AND NUTRITION
2019
,Index
Lecture 1 ................................................................................................................................................ 3
Assignment 1 .......................................................................................................................................... 7
Lecture 2 ................................................................................................................................................ 7
General pharmacology ..................................................................................................................................... 7
Lecture 3 Pharmacokinetics .................................................................................................................. 11
Lecture 4 pharmacokinetics .................................................................................................................. 16
Lecture 5 .............................................................................................................................................. 18
Lecture 6 Drug interactions ................................................................................................................... 22
Effects of nutrition and diet on effects and side-effects of drugs...................................................................... 22
Drug – nutrient interactions ........................................................................................................................... 24
Lecture 7 Pharmacology of the autonomous nervous system (ANS) ....................................................... 26
Effects of the ANS .......................................................................................................................................... 27
Antagonistic control ................................................................................................................................................................ 27
Tonic control = basic activity ................................................................................................................................................... 27
Tutorial Pharmacokinetics .................................................................................................................... 37
Problem 2 : Basic pharmacokinetic calculations ..................................................................................................................... 38
Problem 3 : Area under the curve ........................................................................................................................................... 39
Problem 4 : Multiple dosing .................................................................................................................................................... 40
Tutorial Behavioral Pharmacology ........................................................................................................ 41
Lecture 8 Pharmacology of weight management and complications of obesity ...................................... 50
Overweight: What are the options? ................................................................................................................ 50
Specific dietary products ......................................................................................................................................................... 50
Medical .................................................................................................................................................................................... 50
GLP-1 agonists ............................................................................................................................................... 51
CB1-receptors .......................................................................................................................................................................... 52
,Tutorial: Inflammation Pharmacology + lecture 10 ................................................................................ 60
Important mediators ...................................................................................................................................... 62
Treatment of inflammation ............................................................................................................................ 62
Diseases ........................................................................................................................................................ 63
Nutrition and inflammation............................................................................................................................ 63
Lecture 11 Drug discovery and development ......................................................................................... 64
............................................................................................................................................................ 65
Syllabus pharmacokinetics .................................................................................................................... 65
Passive diffusion ............................................................................................................................................ 65
Zero-order elimination ................................................................................................................................... 66
One-compartment model ............................................................................................................................... 66
Volume of distribution ................................................................................................................................... 67
Binding to plasma- or tissue proteins .............................................................................................................. 67
Area under the curve (AUC) ............................................................................................................................ 67
Clearance....................................................................................................................................................... 67
Two (and more-) compartment models .......................................................................................................... 68
Administration by routes other than IV .......................................................................................................... 68
Bioavailability ................................................................................................................................................ 68
Pharmacokinetics after oral administration .................................................................................................... 69
Intravenous infusion ...................................................................................................................................... 70
Repeated dosing ............................................................................................................................................ 70
Clinical cases ........................................................................................................................................ 71
Case 1 Myasthenia gravis ............................................................................................................................... 71
Case 2 Asthma ............................................................................................................................................... 71
Case 3 narcotic analgetic ................................................................................................................................ 72
Case 4 propranolol ......................................................................................................................................... 73
Case 5 Acenocoumarol ................................................................................................................................... 73
Case 6 Ginkgo biloba ...................................................................................................................................... 73
Lecture 12 recap ................................................................................................................................... 74
Compound A .................................................................................................................................................. 74
Compound B .................................................................................................................................................. 74
Compound C .................................................................................................................................................. 74
Compound D .................................................................................................................................................. 74
Compound E .................................................................................................................................................. 75
Compound F .................................................................................................................................................. 75
Compound G.................................................................................................................................................. 75
2
,Lecture 1
Pharmacology is the study of the effects of drugs in living systems aiming to improve their function. The
drugs are also called medicines, bio-actives or chemicals. The main goals of nutrition are to maintain health
and there are functional foods & supplements which are used for prevention. Pharma focusses on
prevention and therapy.
Statins are used to lower the cholesterol level in the body.
Becel pro-activ and oatmeal can do the same.
The primary aim is: To study and evaluate effects on
bio-active compounds in the diet with the purpose of improving health and
preventing- or curing disease. The secondary aims are: The study the relation
and interaction between food and drugs from a clinical and public perspective
and to translate expertise, models and techniques between the two
disciplines.
Vragen? Pharmanut.hn@wur.nl
Example of drugs;
1) Naproxennatrium (almost the same as ibuprofen)
OTC means over the counter (buy it in the etos or kruidvat).
- What is a drug? (you do not have to replicate the definition)
- What are the indications? (reasons to use it)
Headaches, toothaches, menstrual cramps, muscular pain, backache, relief of the signs and pain in
influenza and after vaccination
Medicines need approval. This is done by the national authorities (CBG in the Netherlands) or European
(EMA). How can you recognize a drug? Each medicine allowed to be sold in NL should have a unique
registration code;
3
,Nationally approved: RVG code
Homeopathic medicines: RVH code
European registration: EU code
The original compound is an acid
and if you dissolve the compound it
will be a base. At a low pH it is able
to pass membranes, at a high pH it is
not possible to pass membranes.
This compound is an acid. If you
dissolve it in water, the pH will be higher than 7.
This was an acid, which will lower the pH. However,
from a strong acid you can make a weak base and
from a weak acid a strong base. So if we dissolve
naproxen-sodium in water, the pH will above 7
since it’s now a strong base.
Nonsteroidal anti-inflammatory drug (NSAID) and
they are analgesic (lowering pain) and antipyretic
(lowering fever) properties.
The NSAID drugs bind to cyclo-oxygenase
(prostaglandin endoperoxide H synthase).
Arachidonic acid is an omega 6 acid. COX is an
enzyme which converts arachidonic acid to an
intermediate PGH2 (prostaglandin H2). The prostaglandin is converted into different compounds for
different target organs. Naproxen can inhibit PGH2 and can block pain with it. It blocks the pain, but it
does not take away the cause. There need to be a balance.
There is nutritious a side effect of NSAID. There are
two enzymes; COX I and COX II. COX I is a gastro-
protective prostaglandin, COX I is always present.
COX II is an inflammatory prostaglandin. You would
like to only inhibit COX II, but you cannot inhibit just
COX II. This causes the side effect of gastro problems.
Blocking COX 1 = not a good idea (side effects in the
stomach)
Blocking COX 2 = might be interesting
However, most medicines are not specific. So, they developed selective inhibitors, that only block COX2 so
people don’t suffer from the side effects of blocking COX1 on long term.
Blocking COX2 might also be preventive against cancer → in long term trials, they submitted COX2
inhibiters however on the long term the people suddenly suffered from cardio problems. So, they tried to
solve 1 problem, but made another.
COX2 selectivity increases your cardio risk, COX1 selectivity increases your GI risks.
4
,There were drugs
that could only block
COX II, but it turns
out that inhibiting
only COX II can
cause colon cancer
and it causes
cardiovascular
diseases. The gastro
problems were
decreased, but the
cardiovascular
problems were
increased. There
need to be a balans
between COX I and
COX II.
What about the dosage form?
Almost every drug is given in something, in
volume. You need a taste. Some drugs are
given in micrograms, so you need to fill the
tablet with something. It is about the
ingredients but also in the non-active
ingredients. Drug substances are rarely
administered alone, but as a part of a
formulation or dosage form. Formulation can
have varied and specialized pharmaceutical
function.
In this case the tablet was coated. It comes in
your stomach and the coating protects core in
the stomach. The drug released in the upper GI
tract after the stomach. The coating protects
the drug form being dissolved in the stomach.
The enteric coated tablet protects the stomach
from the drug, and it protects the drug from
the stomach.
We cannot put oral tablets for 100% in the site
of action. This only works when you use an
injection or a crème on the skin (if the target is
the skin).
There are different phases in pharma. In the
pharmaceutical phase you can affect the effect by the formulation etc. The pharmacokinetic phase refers
to absorption, distribution, metabolism and excretion. The pharmacodynamic phase refers to the
interaction with the molecular targets
5
,There are different routes of application.
If a drug is intended to work, it needs to be absorbed by the liver and excreted to the blood. You can also
inject direct to the blood. Then you avoid the first-pass effect. This can also be done via the lungs. Eye and
ear drops are used local.
Drug absorption is mostly done in the
duodenum. Drugs should be in dissolved state.
The absorption often goes by passive diffusion,
but sometimes active transport. Lipid soluble
compounds with lipids. Metabolism in
intestinal wall can be considerable.
The concentration needs to be between the MTC and MEC
(therapeutic window), else you will have no effect or side-
effect.
6
, In the liver there is biotransformation. We have enzymes in the liver which are
responsible for biotransformation.
We looked at the pharmacology; pharmacokinetics (ADME), pharmacodynamics
(action on COX).
Assignment 1
How does a leaflet look?
First, you always communicate with the generic name, because the name (brand name) of the product can
differ in different countries.
Lecture 2
In the 16th century they found out that a compound from a Salix alba (willow) could reduce pain. Later they
found out that the compound was (acetyl)salicylic acid. They call it Aspirin nowadays. They are still used as
herbs → white willow or salifyt. They are officially registered as ‘food supplements’, but you would rather
call them a drug, because they can reduce a disease.
A functional food is a food which a health claim or a content claim can be attributed to. A health claim is a
claim that something can contribute to your health and a content claim is a claim that it is low in some
compounds like; low in fat. Indirect claims are not allowed. Indirect claims are claims like ‘stophoest’, the
candy does not stop the coughing, so it is not allowed. In the Netherlands the NVWA makes sure that the
products follow the rules of the
claims.
Nutrition claims are claims about
something that is in de product or
not, like low in fat.
Health claims;
- Article 13 is based on scientific
data.
- Article 14 is based on reduction
of disease risk claims.
If you refer to a specific disease it
cannot be a food supplement. Then it
is a medicine.
General pharmacology
Some basic principles of pharmacodynamics;
1) The molecular action of a drug/ bioactive can often be explained by and predicted from a receptor
concept.
2) Receptors are macromolecules including enzymes, transporters, structures on cell membrane,
transcription factor, nucleotides etc. Antibodies are exceptions
3) Receptors are mostly normal regulatory structures playing a role in the physiology of the organism.
4) Natural ligands are neurotransmitters, hormones or other signaling molecules.
5) Drugs just bind by coincidence (back in the days) or by design to these receptors.
7
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