Drug Interactions Flashcards
Define Pharmacology
The study of the effects of drugs
Define Pharmakinetics
How the body affects the drug; Absorption, Distribution, Metabolism and Excretion
Define Pharmacodynamics
How the drug affects the body
Name two neurotransmitters
Each
Serotonin
What are auto acids
Local Hormones
Name two auto acids
Cytokines
Histamines
Name two hormones
Testosterone
Hydrocortisone
How do ligand-gated ion channels function
Binding of AcetylCholine opens pores and allows cations to move into cell
Give an example of a ligand-gated ion channels
Nicotinic ACh receptors
How do G protein-coupled receptors function
- M3 receptor couples with Gq and Phospholipase C
- Second Messenger IP3 or DAG
- Beta-2-adrenoreceptor couples with Gq and Adrenal Cyclase to give cAMP
What do kinase-linked receptors respond to
Growth Factors
What is a kinase
Another word for phosphorylation
Define protein dimerisation
Where two molecules join together via covalent or non-covalent bonds
How do kinase-linked receptors function
- Extracellular lingand binding causes dimerisation
- Allows tyrosine in cytoplasm to be trans-phosphorylated, spreading signal through plasma membrane
- Tyrosine residue creates binding site for SH2 and PTB (phosphotyrosine binding proteins)
- Initiates signal transduction pathways
How do cytosolic receptors function
Modify gene transcription
What are messenger molecules for cytosolic receptors
Steroids
What is the role of zinc fingers
Recognise discrete regions of DNA
What is a zinc finger
They bind different parts of the DNA together to modify gene transcription (the sequence)
How does an allergy effect histamine levels
Increased levels
How does Parkinsons effect dopamine
Decreased
How does myasthenia graves effect receptors
Loss of nicotinic ACh receptors
What is Mastocytosis
Increase in C-kit receptors
Define receptor potency
Measure of how well a drug works
What is an EC50
Concentration that gives half the maximal response
Define agonist
A compound that binds to a receptor and activates it
How can we compare drug potencies on a graph
If compound A is further to the left of the graph than compound B, it is more potent
How do we distinguish between a full agonist and a partial agonist
On a graph, a full agonist hits 100% whilst a partial hits a peak/plateau lower than 100%
We refer to this as ‘efficacity’ in exams (e.g. Compound A is more efficacious than B)
Formula for intrinsic activity
Emax of partial agonist / Emax of full agonist
Define antagonist
A compound that reduces the effect of an agonist
What does activity of receptor depend on after being bound to by an antagonist
The affinity
Name an antagonist\agonist to MAChR (Muscarinic ACH receptor)
Atropine - Antag
Muscarine - Agon
Name the antagonist/agonist for NAChR
Curare - Antag
Nicotine - Agon
How much of all genes express G coupled receptors
4%
How many drugs target G could receptors
30%
Examples of ligands
Light
Energy
Lipids
Proteins
When are G protein couples receptors activated
When bound to GDP
When are G protein coupled receptors not active
When bound to GTP
Binding to a H1 receptor does what
Inflammation
Binding to a H2 receptor does what
- Contraction of Ileum
- Gastric acid secretion from parietal cells
Binding to a H3 receptor does what
CNS disorders
What does binding to H4 receptors do
Inflammation
What is the antagonist to H2 receptors
Mepyramine
How does Mepyramine effect H2 receptors
- Reversed contraction of ileum
- No effect on acid secretion
Define affinity
How well a ligand binds to a receptor
Define efficacy
How well a ligand activates a receptor
What is the efficacy of antagonists
Zero because the receptor is not activated
What is the irreversible antagonist of beta adrenoreceptors
BAAM
How does receptor reserve differ from full and spare agonists
Full - can have receptor reserve as maximal response seen with less than 100% occupancy
Partial - Maxmal response not seen even with 100% occupancy
What factors effect drug action (4)
- Affinity
- Efficacy
- Receptor number
- Signal amplification
What happens during allosteric modulation
Binding of ligand to allosteric site
What is the orthosteric site
Where agonists usually bind to
What is the consequence of continuous, repeated and high conc. of an agonist
Increased tolerance and desensitisation
What is isoprenaline
Non-selective Beta adrenoreceptor agonist
What is the selective agonist to beta adrenoceptor
Salbutamol
What is the result of salbutamol
Opens up medium and large airways for the lungs
When is isoprenaline used
For bradycardia and heart block (NOT asthma)
What is desensitisation of receptors
- Become uncouples (no interaction with G protein)
- Receptor internalised in vesicle of cell
- Receptor is degraded
Where are G-protein coupled receptors found
EUKARYOTES
