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PHAR0007: Summary of Drugs and Mechanisms of Action
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Nutrition And Health / Voeding En Gezondheid
HNE-23306 Pharmacology And Nutrition
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PHARMACOLOGY AND NUTRITION // LECTURE 1: WELCOME
TO PHARMACOLOGY AND NUTRITION
Pharmacology = “The study of the effects of drugs on living systems, aiming to improve
their functioning “
A drug can be medicines, Bio-actives (compounds present in food which have no
nutritional purpose, but do something with your health) or chemicals
→ Nutrition works in the area of maintaining health and prevention
→ Food supplements look like drugs, but are regulated as food
→ Pharma works in the area of prevention and therapy
What are the main differences?
→ Common: They’re healthy, middle is a statin, they lower cholesterol
→ Pro-activ contains a vitosterol which competes with cholesterol in your GI tract for the
absorption thereby lowering the uptake → The effect is less than just the pill
→ Oats binds cholesterol and has a proven/small cholesterol lowering effect
→ A drug, functional food and just a food product
Pharmacology and nutrition
primary aim: To study and evaluate effects of bio-active compounds in the diet with
the purpose of improving health and preventing- or curing disease
secondary aims:
- To study the relation and interactions between food and drugs from a clinical and
public health perspective
- To translate expertise, models and techniques between the two disciplines
Course objectives
To provide an introduction to pharmacology (+ pharmacy and drug therapeutics), in order
to...
Be able to apply this in a clinical- or general health care profession
Understand how compounds work in health and disease
Integrate /use this knowledge in nutritional science
Be able to apply this in an industrial profession (Food or Pharmaceutical)
Intended for:
Students Nutrition and Health (BSc, 2nd year)
Others (Minor programs, MSc, BSc Biotechnology)
It’s about the mechanisms and principles
,Status : Drug, OTC ? Generic vs brands How does it work ? Dosage form ? Indications What
is the dose, and why ?
→ Naproxennatrium / Naproxensodium
→ Never say pills, use tablets
→ OTC: Over The Counter → You can buy it without a prescription
Naproxen-sodium is clearly a “medicine” (drug)
Legal definitions : Drug = “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”
Substantie of samenstelling van substanties, welke is bestemd te worden gebruikt
of op enigerlei wijze wordt aangeduid of aanbevolen als zijnde geschikt voor:
1°. het genezen, lenigen of voorkomen van enige aandoening, ziekte, ziekteverschijnsel,
pijn, verwonding of gebrek bij de mens,
2°. het herstellen, verbeteren of wijzigen van het functioneren van organen bij de mens,
3°. het stellen van een medische diagnose door toediening aan of aanwending bij de
mens;
→ You don’t have to remember the exact definition
→ Naproxen is acting against headaches
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
Indications:
An indication is a formally stated condition for which the drug may be used, in this case:
Headaches
Toothaches
Menstrual cramps
Muscular pains
Backache (lumbago)
For relief of the signs and pain in influenza and after vaccination
NB : official [approved] indications may differ per registration
→ Implications are necessary to put on the packet, even for the “kinderparacetamol”
Medicines need approval: by national authorities (= CBG in NL) or European (EMA)
Each medicine allowed to be sold in NL should have a unique registration code
Nationally approved : RVG code
Homeopathic medicines : RVH code
European registration : EU code
→ If you’re European registration you are approved in different countries
→ There’s a different root for supplements and you need to know what is going where and
what’s the difference
,→ If you look at naproxen in the data base you will see that there are many products
containing naproxen which all have a RVG code, in this case 91 other products → Some are
sleeping and some have an active product on the market
→ So what is a brand name and what is a generic name?
→ The active ingredient is naproxen sodium → Once here we have Aleve which is exactly
the same, but 5 times more expensive → There’s a certain average time that a compound
can keep a patent on a product → E.g. the covid vaccines are patent
→ It could be that they have better technology, because it doesn’t say anything about how
it’s packed
Naproxen-sodium
Nonsteroidal anti-inflammatory drug (NSAID)
Analgesic and antipyretic properties.
→ You don’t have to learn/recognize this structure, but understand how this works
→ Right is the sodium salt → This was originally a carboxylic group
→ Is naproxen an acid or base? It’s an acid because it has a carboxylic group, a proton
dissociates and will add a sodium and then you have a sodium salt which better dissolves
→ If you put this in water the pH is going to be higher than 7 → It’s the conjugated base of
the original acid → If you put it in water it’s going to react as a base
→ The pH also determines the charge of the molecule
Pharmacology of Naproxen (and other NSAIDs)
Non-steroidal anti-inflammatory drugs bind to cyclo-oxygenase [= prostaglandin
endoperoxide H synthase (PGHS)]
→ They’re called non-steroidal, because there’s a large group of inflammatory drugs which
are the corticoid steroids
→ Steroids are the more potent anti-inflammatory compounds
→ These are the non-steroids and they bind to an enzyme named cyclo-oxygenase with the
formal name of prostaglandin endoperoxide H synthase (PGHS)
→ Never say aspirin, but acetyl salicylic acid (arachidonic acid)
→ These groups of drugs bind to an enzyme and what is that enzyme doing?
What are cyclo-oxygenases and what are they doing ?
→ This is the synthesis of prostaglandins (PG) and thromboxane (TxA2)
→ Prostaglandins are inflammatory mediators → Prostaglandins of different structure all
have a slightly different function
→ Thromboxane E2 is involved in platelet aggregation which is the cluttering of the blood
platelets and the formation of thrombus which is an important function in inflammation
, → PGE2 prostaglandin E2 is involved in fever, pain, etc.
→ They all have their different receptors
→ These compounds are formed from a fatty acid (arachidonic acid) which is an omega 6
poly unsaturated fatty acid which is a fatty acid with a number of unsaturated bonds and the
first one starting from the CH3 terminus is on the sixth position
→ You can’t make arachidonic acid yourself but have to get it from your diet → Normally it’s
connected to your phospholipids in your membrane
→ There’s always some activity of an enzyme PLE2 and during inflammation a bit
upregulated and then arachidonic is set free from the membrane and then there are 2
enzymes there, COX-1 and COX-2 (cyclo-oxygenase’s) which do the first step and make a
cycle and then the different prostaglandins are formed
→ The compound naproxen is acting on these enzymes COX-1 and COX-2
→ COX-1 is a so-called constitutive enzyme and is therefore always there and has a
background activity and makes the good guys which are the prostaglandins you need for
daily function
→ COX-2 is upregulated during fever and makes more the bad guys → However during
inflammation is no good and bad guy, because inflammation has a role → However the
feeling on inflammation is not nice, but even a headache has a role → So it’s difficult how
much you should inhibit
→ PGE2 gives the pain in the fever → So inhibiting COX-2 ,which is what naproxen does,
reduces PGE2 and reduces fever and pain, but the difficulty is that also COX-1 is inhibited in
this case → There’s one other good thing which is that also the formation of TxA2 is
inhibited and that’s being used to prevent blood clot formation in certain people → If you’re
at risk of getting MI you may get a low dose aspirin
→ If you inhibit COX-1 you also inhibit the formation of PGI2 which is the one that’s keeping
your stomach okay
NSAID GI toxicity
→ Cyclo-Oxygenase pathway
→ Arachidonic acid is transformed to inflammatory prostaglandins, but also to
gastroprotective prostaglandins
→ So if you inhibit them both you getting rid of your fever and pain, but at the same time
your protection of your stomach is getting less and you may suffer from stomach problems,
like bleeding
→ So selectivity is an issue
Schematic depiction
→ Schematic depiction of the structural differences between the substrate-
binding channels of COX-1 and COX-2 that allowed the design of selective inhibitors
→ I want to inhibit mainly COX-2 but not COX-1 too much because that’s gastro protective
→ The chemists were able to synthesize compounds that more selectively were able to go
into the COX-2 enzyme and had a preferred inhibition of COX-2
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