Quiz 2 Flashcards
What is an agonist?
Whats a full agonist?
A partial agonist?
An agonist is a substance which acts like a receptor to initiate a full response.
A full agonist is one whose maximal response is the largest a tissue is able to give e.g. drug which causes Emax of 100. Only a few receptors occupied for a maximal response.
A partial agonist- agonist whose maximal response is less than the full response. Ie all receptors are occupied and max response isn’t reached.
Affinity
The ability of a ligand to bind to a receptor. Applies to both agonists and antagonists and is measured by the equilibrium constant Kd
What is Kd?
Dissosiation constant- its an equilibrium for the dissociation of a complex into its components. Eg dissociation of a substrate from an enzyme. Its used to define the binding strength or affinity between the receptors and respective ligands.
whats Occupancy?
Were both drugs occupy the same number of receptors but have different responses.
The proportion of receptors occupied by ligand and is denoted by the expression
P= N/Ntot (occupied receptors/ total number of receptors for an agonist in a tissue)
Whats difference between dose- response and dose-binding?
Dose response: measure of biological effect
Dose-binding: measure of receptor binding sites
Concentration-Response Curves What do these values mean? ED50 (EC50): The concentration of dose of a drug Kd Spare receptors
ED50 (EC50): The concentration of dose of a drug that produces 50% of the mex possible biological response.
Kd:The concentration of a drug that results in binding to 50% of the receptors.
Spare receptors:
Receptors that don’t bind drug in order for max biological effect to be produced
Types of Drug antagonism
1. Competative (reversible and irreversible)
Competative:
Involves ability of an antagonist to compete for a ligand binding site on a receptor with an agonist. As concentration of the antagonist increases, receptor occupancy of agonist will decreases as they are displaced.
a) reversible: 2 drugs compete for the receptor.
- represented as a parallel shift in the agonist log-concentration curve
b) addition of enough agonist will displace the antagonist and a full response will occ.
b) Irreversible- little or no dissociation of antagonist from receptor
In competitive antagonist the potency decreases because the agonist and antagonist compete for the SAME receptors. The effect does not change because the same number of receptors are available for both. That is primarily why, if you increase the dose of the agonist, it will overcome the effects of competitive antagonist. Basically, you need a bigger dose (Potency) to get the same effect because with increased dose/concentration, it will bind more to the receptors than the competitive antagonist.
Types of Drug antagonism
2) Non-competative
1) A non-competitive antagonist works at a different receptor binding sites and alter the configuration of the actual receptors for the agonist. Therefore, it reduces the number of receptors available for the agonist and that reduces the effect (efficacy). Non-competitive antagonist DO NOT compete with the agonist for the receptors. That is why the Potency remains the same because both drugs (the agonist and the antagonist) work on different receptors. The same dose of the agonist can still cause the effect but it is a reduced effect due to lack of receptors.
Types of Drug antagonism
3)Chemical
• 2 substances combine in the solution and the active drug is los- ie by adding chemical you lose effect of drug eg the chelating agent, dimercaprol binds tightly to heavy metal ions (lead, cadmium) forming an inactive (and less toxic) complex.
Types of Drug antagonism
4) Pharmacokinetic
• Antagonists reduces the concentration of agonists at the site of access eg phenobarbitone reduces anticoagulant effect of warfarin by accelerating its hepatic metabolism
Types of drug Antagonist
5) Physiological
• Describes the interaction of 2 drugs whose opposing actions in the body cancel each other out eg noradrenaline raises arterial blood pressure acting on heart and peripheral vessels whilst histamine lowers arterial BP by causing vasodilation
Give examples of drugs that function through non-protein drug receptors i.e. lipid and DNA
Lipids
• General anaesthetics may act by dissolving the membrane lipid affecting the physical state of the membrane or increase membrane fluidity resulting in membrane disorder (halothane, nitrous oxide, xenon)
DNA
• Anti-tumor agents used in chemotherapy.
• Mitomycin-covalently binds to the DNA bases, preventing DNA replication & degrading DNA by free radical formation
• Idoxuridine (thymine analogue)- can be phosphorylated & incorporated into DNA. Used to inhibit viral replication (herpes, shingles etc)
• Ie drugs which target DNA
Proteins
• 4 classes of protein receptors a) enzymes, b) carrier molecules c) ion channels, d) classical receptors
List the 4 classes of transmembrane protein receptors and give examples of drugs that act as agonist and antagonists
- Ligand-gated ion channels
A) nicotinic Ach receptor
a- Acetylcholine
ant- tubocurarine
2. 7 Transmembrane receptors A) Muscarinic Ach receptor a- Acetylcholine ant- atropine B) Beta Adrenoceptor a- isoprenaline ant-propranolol
- Single transmembrane receptors
A) Insulin receptor
a-insulin
ant-unkown - Steroid/ Thyroid receptors
A) Oestrogen receptor
a- oestrodinol
ant- tamoxifen
List 2 Classes of protein receptors (enzymes and classical transmembrane receptors) and briefly outline the way that drugs can affect them and give examples of drugs that interact with each receptor.
- Enzymes:
a) They can be an INHIBITOR (substrate analogue acting as competitive or non-competitive inhibitor)
eg Neostigmine acting on ACH-esterase
eg2- Aspirin acting on cyclo-oxygenase (COX) signalling pathway
b) they can be a FALSE SUBSTRATE- were the drug undergoes chemical transformation tot orm abnormal product which puts of the normal metabolic pathway
eg DOPA–> adrenaline (normal substrate)
MethylDOPA–> Methylnoradrenaline (false substrate)
c) could act as a PRO-DRUG- conversion of inactive drug to active by enzyme, usually in liver i.e. it piggy backs on enzyme and uses it to activate drugs.
egCortisone–> Hydrocortisone
eg2 Azathioprine (immunosuppressant)–> Mercaptopurine.
- Transmembrane receptors
- ion channel modulation
- enzyme activation/ inhibition
- receptor tyrosine kinase
- DNA transcription
- Distinguish between the nicotinic and muscarinic acetylcholine receptors by their molecular structures
Nicotinic acetylcholine receptors (also known as ‘ionotropic’ acetylcholine receptors) are particularly responsive to nicotine. The nicotine Ach receptor is also a Na+ and K+ ion channel
Muscarinic acetylcholine receptors (also known as ‘metabotropic’ acetylcholine receptors) are particularly responsive to muscarine.
Comparison: Ionotropic receptors form an ion channel pore. In contrast, metabotropic receptors are indirectly linked with ion channels on the plasma membrane of the cell through signal transduction mechanisms, often G proteins. Hence, G protein-coupled receptors are inherently metabotropic.
