Lecture 1,2 Flashcards
Define pharmacology
investigatiing the function altering effect of several substances in living entiities
What is a pharmaceutical substance?
when a substance can be used for treatment
what does drug mean?
dry
dried out substance of plants
Define pharmacodynamics
Drugs affect on the body
Define pharmacokinetics
how the body acts on the drug, the behaviour and the movement
What is the principle of ADME?
- Absorption
- how it gets into the body
- Distribution
- where it goes
- transporters
- metabolism
- how it is broken down
- liver
- excretion
- how it leaves the body
What are some non-specific physical interaction drugs?
Give example for each of them:
Osmotic diuretics - mannitol
antacids - magnesium hydroxide
laxatives - magnesium sulfate
chelators - EDTA, deferoxamine
Some drugs have biochemical interaction, these are proteins, what groups do we divide them into?
With receptors
and
Without receptors
What are the the task of drugs that are without receptors?
Inhibition of enzymes: NSAIDs, ACE inhibitor, AChE inhibitors
DNA damage: anticancer drugs
Transporters: proton-pump inhibtors, diuretics
Ion channels: local anasthetics (lidocain, Na+ channel)
What are the task of drugs that are working with receptors?
they act on signaling mechanisms as acceptors - will bind to something
Name the four groups of receptors
- Ligand-gated ion channels
- G protein-coupled receptors
- Receptor-activated tyrosine kinases
- Intracellular nuclear receptors
How does ligand gated ion channels operate?
the ligand will bind to the receptor and there will be an influx. ex Na+ and there will be an effect
give an example of an ligand gated ion channel
nikotinic acetylcholine receptor
where can you find nicotinic acetylcholine receptor?
- neuromuscular junction
- autonomic ganglia
- CNS
What does it mean that a drug is orthosteric?
binds to the natural binding site of the receptor
what does it mean that a drug has an allosteric effect?
it will bind next to the binding site, enhance it
is propofol allosteric or orthosteric?
both
What is PAM an acronym for?
Positive Allosteric Modulator (allosteric agonist)
How many times does a G-coupled receptor cross the membrane, and what is the correct term for corssing the membrane?
Crosses 7 times
Transmembrane
What are the three types of G protein-coupled receptors?
Gas- coupled receptor: stimulatory
GaI - coupled receptors: inhibitory
Gq - coupled receptors
Give an example for an Gas - coupled receptor
-Beta-adrenoceptor
Ligand is adrenaline - Leads to phosphorylation
Where can the Gas-coupled receptors be found?
- Cardiac muscle cells
- Vascular smooth muscle cells
Give some examples of Gai-coupled receptors
- M2 Cholinergic receptors
- A2 receptors
Give some examples of Gq coupled receptors
A1- receptor
H1 receptors
Serotonin receptors
What happens when serotonin binds to a serotonin receptor?
GDP -> GTP
PLC activated
PIP2 -> IP3 + DAG
=
Ca2+ and PKC is activated
What happens when insulin binds to the insulin receptor (kinase activity)
- Serotonin binds
- Tyrosin is phosphorylated
- AKT is activated (phosphokinase b)
- multiple cellular effects
What happpens when cytokines binds to the cytrokine receptor
JAK causes phosphorylation
STAT binds
STAT: activated, goes inside the cell nucleus and stimulate DNA gene transcription
Protein synthesis: inflammation, allergy
What does JAK inhibitors primarly inhibit and give an example of a veterinary drug
inhibit redominately JAK-1 (kinase)
(JAK1 produce: IL-2, IL-4, IL-6. IL13
(allergy, inflammation) IL-31 (itching))
Drug: Oclacitinib
Give some examples of drugs that use intracellular nuclear receptors
Ligand - cortisol
HEat shock protein
CoA
RNA polymerase II
What is a ligand
a substrate that binds to the receptor - drug
what bonds are formed between the ligand and the receptor?
and what are their characterisitcs
Van der waals, hydrogen and ionic
- they are usually reversible
they cause altered confirmation leading to an effect
difference in the affinity
Is there some lignads that bind irreverisble? what bond?
covalent bond
omenprazol - proton pump
long lasting action
needs to be given once a day
What does a continous dose-response curve show?
the affect of a drug in an animal over time
if dose is increased the curve must be watched to see effect
What is EC50?
half maximum effective conencentration
What is meant by efficacy
the strength of the effect
what is meant by potency?
how fast a drug reacts in the animal
- Which drug is the most potent?
- Which drug has least efficacy?
- fentanyl is most potent (100x more than morphine)
- butorphenol
What does a quantal dose-response curve give information about?
Drug in a population
- about 100 dogs
Which parameters does a quantal dose-response curve give us?
Effective dose
toxic dose
lethal dose
When reading a graph giving therapeutic definitions what elese but efficancy and potency is important to look for?
the slope of the graph is also important
What is the therapeutic index and what does it mean?
LD50/ED50
It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity.
larger therapeutic index means the drug is safer
Range these drugs in their order of beeing safest
ethanol
digoxin
morphine
remifentanyl
atropine
from safest to unsafest
remifentanyl
morphine
ethanol
digoxin
atropine
What is the therapeutic window?
where the drug acts and is safe
between minimum toxic concentration and minimum effective concentration
What is an full agonist?
a drug that has high affinity to receptor
high efficancy
induces maximum response
binds to the receptor and will activate it
what is an full antagonist?
Drug that will bind to an receptor and keep the respons from happening
no efficacy
receptor will not be activated
what is a partial agonist?
drug that will induce a sub-maximal response
it has hig affinity
it has low efficacy
will bind to and partially activate the receptor
give example of a full agonist, full antagonist and partial agonist
Full agonist - fentanyl, morphine
Full antagonist - naloxone
Partial agonist - buprenorphine
What is an inverse agonist
a drug that causes the reverse action, such as antihistamine
What type of drug is A, B and C (agonist)
A) full agonist
B) partial agonist
C) partial agonist
Fill in the graph
What happens to the maximum efficcacy in presence of a competitive antagonist?
unchanged
what happens to the agonist potency in prescens of a competitive antagonist`?
decreases
What is meant by pharmacodynamic tolerance?
- Desensitization
- Agonist that continously binds to the receptor will cause inactivation, sequestration or down-regulation
what is pharmacokinetic tolerance?
induction of CYP450 enzymes
PL.phenobarbital, ethanol
often a consequence of the drug being an inducer or inhibitor of a specific metabolic enzyme or transporter system, resulting in a time-dependent decrease in presentation of the active moiety to the receptor biophase
