Principles Of Pharmacology 1 Flashcards
What is the need for receptors?
Signalling molecules or hormones in the blood reaching a large no. Of cells
Do all cells respond to receptors?
Specificity is applicable where only specific cells have receptors for that chemical.
What is the receptor concept?
Chemicals produce and effect by combining to specific receptor - lock and key model.
What is affinity?
The strength of a drug receptor interaction
What are receptors?
Proteins with specific binding site that has both affinity and receptive to ligand
Receptor locations
Name different receptor locations
What are the four types of receptors?
Ion gated channels, g protein couples receptors, kinase linked receptors, nuclear receptors
How to ion gated channels work?
Hyperpolarisation/ depolarisation affects ion gates whether they open or close
How do G PC receptors work?
Upon activation by a ligand, the receptor binds to a partner heterotrimeric G protein and promotes exchange of GTP for GDP
How do kinase linked receptors work?
play an important role in protein phosphorylation, gene transcription, protein synthesis and cellular effect
How do nuclear receptors work?
Change what type of gene is expressed or depressed
List transmitters?
Hormones, neurotransmitters, autocoids, neuropeptides, neuromodulators
What are hormones?
Released from one cell to an extracellular cell to travel to new site if action
How are neurotransmitters released?
By exocytosis
Name types of neurotransmitter degradation and recovery
Diffusion- away from synapse /reuptake- nt reenter presynaptic axon terminal/ enzymatic degradation - in cytosol or synaptic cleft
Give types of neurotransmitters:
Acetylcholine, monomanies such as noradrenaline and dopamine/ amino acids such as GABA and GLUTAMATE/ neuropeptides such as endorphins/ purines such as ATP / soluble gases such as nitric acid
Give amino acid types of neurotransmitters and their functions?
GABA- 40% inhibit
GLUTAMATE- 50% excite
Whats the difference between a hormone and neurotransmitter?
N- diffused from presynaptic cleft into extracellular space to act in adjacent neurones
H- chemical released by an organ to be transportd in blood to reach targetted organ/tissue
Difference between adrenaline and noradrenaline
Adrenaline is a hormone released in blood for fight or flight and noradrenaline is a neurotransmitter
Recall types of receptors based on ligand
Cholinoreceptors- muscarinic and nicotinic
Histamine- h1/h2h3
Adrenoreceptors- alpha and beta
What are the different acetylcholine receptors
Muscarinic and nicotinc
Tell me more about nicotinc receptors
Ligand gated ion channels permeable to na+ ions and are excitatory
They are pentaremic and have 5 sub units alpha beta etc.
Tell me more about muscarinic recrptors
G protein coupled receptors, with 5 subtypes, M1/3/5 excite and M2/4 inhibit
What are gluttamate receptors
Theyre both ionotropic and metabotropic
What are ionotropic receptors?
Receptors that open cation channels
Talk about Gaba receptors
Gaba a- ionotropic- chloride channel
Gaba b - metabotropic - stop voltage gated ca channels and open k channels
What are G coupled protein receptors
Muscarinic alpha beta receptors work by turning on transducer proteins specifically guanine
Structural motifs
7 hydrophobic channels, single polypeptide chain with extracellular n terminus and intracellular c terminus
What does an active g protein interact with
Ion channel to allow influx of ion or enzyme to produce a substance that helps to make another thing known as second messenger
Whats the role of an agonist
Cellular response
Whats the role of an antagonist
No response
Explain the role of a pharmacological agonist
Combines with receptor and produces a response so has efficacy and affinity
Explain the role of an antogonist
Combines with receptor does not cause a response but prevents agonist binding
Has affinity but no efficacy
Whats the difference between blocker and modulator?
Blocker permeation is blocked whereas modulator increased/ decreased probability of opening
What effect does a substrate have on enzyme?
Normal reaction =normal metabolite produced
What effect does inhibitor have on enzyme?
Normal reaction inhubitted
What effect does false substrate have on enzyme
Abnormal metabolite produced
What does effect does prodrug have on enzyme
Active drug produced
How do you study the effects of a drug on a receptor?
Use an isolated tissue preparation within an organ bath and investigatethe effects of the addition of the drug
OR
Use an animal/human and give them an increasing dose of the drug and monitor particular effect
What information does the EC50 provide to us?
If drug had low EC50, drug has high affinity
If drug has high EC50, drug has low affinity
How should a drug with different affinity be used in terms of dosage
If a drug has high affinity it should only be used in low concs and if a drug has low affinity it should be used in high concs
How do you determine EC50?
By looking at the drug response at 50 and noting down the antilog
Define EC50
The affinity of an agonist for its receptor
In humans do we use affinity or potency
Potency
Define potency
The required amount of drug to gain particular effect in an intact animal
What is the amount of drug in relation to effect?
Some drugs have different potency but will have same efficacy
On a graph, how do you know that all receptors have bound?
Maximum response of curve has levelled off
What are the different types of agonist
Partial
Full
What does 100% occupancy mean
100% effect
What is drug efficacy
The ability of drug to produce a therapeutic effect
What is the intrinsic activity equation
Maximum response to TESTagonist/maximal response to FULL agonist
How do you calculate intrinsic activity
Small h/H
What are the theee types on antagonist
Chemical, physiological, pharmacological
What is a chemical antagonist?
A drug that counters the effects of another by binding the agonist drug (not the receptor)
What is a physiological antagonist
Where the effect of the drug starts a reaction opposite to what is currently happening
Does not act at same receptor site
Usually pharmacological agonist
What is a pharmacological antagonist?
Agonist meets receptor to stop action of agonist DOES NOT CAUSE A RESPONSE
What is a irreversible antagonist
Binds in irreversible manner by covalent bond modification, causing irreversible effects= agonist cannot bind
Adding more agonist WILL NOT FIX THIS
WILL HAVE TO MAKE NEW RECEPTORS VIA PROTEIN SYNTHESIS
What are non comp antagonists?
Binds to allosteric site, CANNOT BE OVERCOME BY ADDING MORE AGONIST
May not impair binding of ligand to make complex but will cause a conformational change= response