Table of Contents
1-introduction ......................................................................................................................................... 2
2-taxonomy of vertebrates...................................................................................................................... 2
3-basic principles of pharmacodynamics ................................................................................................ 3
4.2-rodents and lagomorphs................................................................................................................... 6
5-embryology of lab animals................................................................................................................... 7
6-comparative physiology ..................................................................................................................... 10
7.1-anaesthesia ..................................................................................................................................... 12
7.2-analgesia ......................................................................................................................................... 14
8-diseases + disease control ................................................................................................................. 15
9-immunisation in lab animals .............................................................................................................. 16
10-Radiation protection + radiobiology ................................................................................................ 18
11-experimental techniques ................................................................................................................. 20
12-necropsy of lab animals ................................................................................................................... 20
13- nutritional needs of lab animals ..................................................................................................... 21
14-reproduction of lab animals............................................................................................................. 22
15-postoperative care ........................................................................................................................... 24
16-surgical principles ............................................................................................................................ 25
17-euthanasia of lab animals ................................................................................................................ 27
18-ethology and stress – welfare of lab animals................................................................................... 29
19.1-ethical commitees......................................................................................................................... 31
19.2-legislation – legal aspects ............................................................................................................. 32
20-good laboratory practice (GLP) ........................................................................................................ 32
21-animal ethics .................................................................................................................................... 33
22.1-bacterial and mycotic zoonoses .................................................................................................... 34
22.2-viral zoonoses ............................................................................................................................... 36
23-safety in working and care of lab animals ....................................................................................... 36
24-handling and transportation of lab animals..................................................................................... 37
25-housing of lab animals ..................................................................................................................... 38
26-statistics ........................................................................................................................................... 39
27-environmental enrichment .............................................................................................................. 40
28-alternatives for lab animals ............................................................................................................. 41
29.genetic standardization and transgenesis ........................................................................................ 41
30-disease prevention in lab animals.................................................................................................... 43
31-extrapolation of experimental data to man..................................................................................... 44
,1-introduction
Most used lab animals in order: rodents – chickens – zebrafish – farm animals – dogs and cats – primates
Rodent -mice, rats, guinea pigs
-small size
-low cost
-ease in handling
-good models: different genetic straints
-cancer research, ageing...
Pig -similarity to humans and size → organs
-CT scan development
-burn healing research
Guinea pig -nutritional studies
The three R’s: replacement- reduction – refinement
Replacement: look for replacement alternatives for animals, only use animals when really necessary
Reduction: if you use animals, use as little animals as possible by doing good study design, share or
reuse the animals if possible
Refinement: if you use animals, hurt them as little as possible → enhance welbeing; correct handling
+ enrichment
→ minimize suffering by determining
human endpoints
Non-technical summary (NTS)
= summary for general public, no jargon, explains goal, why no alternatives, and the animal enrichment
2-taxonomy of vertebrates
Vertebrates → spine, skull that encloses the brain, complex nervous system
-fish
-amphibians
-reptiles
-birds
-mammals
Taxonomy = giving a name to animals and trying to order/classify these animals based on evolution
and physical traits
Binomen = species name consisting out of a genus name and a specific name
Phylogeny = evolutionary history from a specific species. We assume that they all come from a
common ancestor. (based on homologies betw animals)
,Monophyletic taxon = always have a common ancestor and all the different species that derived from
this ancestor.
Polyphyletic taxon = they have (multiple) different ancestors.
Paraphyletic taxon = group of animals with a shared common ancestor, but we are not talking about
all derived animals from this ancestor.
→ moeten gwn op gelijke hoogte verbonden zijn
Vertebrates are a subgroup within the chordates: these have a lot of shared characteristics:
-heart, bloodcirculation
-neural tube
-notochord
-mouth, intestine...
However, vertebrates are more complex in: mobility, skeleton, CNS, intestinal system, breathing system,
circulatory system..
3-basic principles of pharmacodynamics
Drug given to patient/animal:
→ body is exposed to the drug = pharmacokinetics
→ desired (doeleffect) and adverse effects (bijwerkingen) = pharmacodynamics
A drug has a target for drug action → receptor, ion-channel, enzyme, carrier
, Ligand gated ion channels G-protein coupled receptor Tyrosine kinase linked Nuclear receptor
receptor
Ligand binds → ion channel Neurotransmitter binds → Binding of insulin/growth Binding of steroid
opens or closes → influx ion channel opens or closes factors/cytokines → gene hormone → conformation
+ activation of kinase transcription and protein change of receptor (zinc
Sodium/Potassium/Calcium enzymes that (in)activate synthesis fingers) → goes inside
influx → muscle contraction other enzymes nucleus → gene
(excitatory) Even slower pathway transcription and protein
Chloride influx → inhibition Slow pathway synthesis
pain stimulation/reduce
nerve activation (inhibitory)
Receptor theory = key-keylock mechanism = a drug can only bind its receptor when the structure is
complementary.
If it easily binds, we say that it has high affinity. It all comes down to the molecular structure.
Quantitative pharmacology
Initially there is no effect, because the concentration of the agonist/antagonist is too low. If you keep
increasing the dose, the effect will increase as well until it reaches a plateau phase (ex. muscle can’t
exceed maximum contraction).
In log transformation of the dose we get a sigmoidal curve.
Efficacy =
[AR] = occupied receptors
0<alfa<1 → 0: antagonist, 1: full agonist
with a partial agonist (B, C), you will not reach the same response as the full agonist (A)
Affinity/potency =
EC50: the concentration at which the 50% of the maximum effect is enlisted.
If the EC50 of a drug is high, it means that we have a low affinity and low potency of that drug.
more to the right = less affinity and potency of the drug
, Antagonist types:
reversible → binds to the receptor, but it can be released from the
competitive receptor again
→ agonist has less affinity/potency than the antagonist
→ the effect of the antagonist can be overcome by increasing
the dose of agonist.
non-competitive → the effect of the antagonist cannot be overcome because
they do not compete for the same binding position (receptor
has 2 binding sites)
irreversible → antagonist irreversibly binds to the receptor → agonist
competitive cannot bind the receptor anymore so is forever excluded
→ agonist cannot reach its maximum effect anymore
functional → 2 agonists binding 2 different receptors, each causing an
antagonism effect that is opposite to eachother
pharmocokinetic → inhibition of a pharmacokinetic process by a
antagonism transformation
chemical → inactivation of agonist by a chemical binding to it
antagonism
Tolerance = the effect of a drug that decreases over time, caused by desensitization.
Desensitization = a receptor or molecular target becomes less susceptible for the drug
- conformation change of receptors (fosforylation)
- downregulation of receptors
- upregulation of receptors
- exhaustion of mediaters (mediators for releasing or vesicle forming)
- increased biotransformation (drug is broken down by enzymes)
- physiological adaptation (body compensates for effect of the drug with other pathways)
4.1-comparitive morphology
= throws similarities and differences into perspective to understand functional and evolutionary
traits
Homology: features that are derived from a common evolutionary ancestor and may have different
functions.
<> Homoplasy: features that are similar in function but do not share a recent common ancestry.
Integument Basic structure of the skin is the same between most vertebrates, with or without glands. Fish
have scales. Amphibian skin is a lot thinner than mammal skin.
Skeleton Skeleton in fish and reptiles is more complex than in mammals.
Amount of bones is larger in mammals.
Digestive Basic structure is the same.
system Different shapes of stomach.
In some fish the liver and pancreas is combined into a hepatopancreas.
All animals make gal, but not all have a galbladder.
Most vertebrates have homodont teeth, only mammals have heterodont teeth (different shapes).
- monophyodont = have 1 set of teeth, so these are directly permanent
- diphyodont = have 2 sets of teeth, so they fall out once
- polyphyodont = teeth continuously grow
→hyps(el)odont = teeth keep growing continuously throughout their life
→brachydont = teeth with limited growth period and stop growing after reaching a certain size
Respiratory Lungs are originally formed out of the digestive system in fish (=swimbladders to ascend and
system descend in water).
Some amphibians lost their lungfunction and breath through their skin.
Birds have a very efficient breathing system with air sacs.
Humans always have dead air because some air stays in the lungs, also not all oxygen is taken
from the air, it’s not as efficient.
