Pharmacodynamics Flashcards
What is pharmacodynamics
The effects of drugs on the body
What happens when a drug binds to a receptor?
A change is brought about
Equation for receptor binding
L + R reversible LR
What is Kd?
Intrinsic factor in any pair of drug receptor complex. It varies with temperature.
The mass of action equation between bound and free receptors
Kd = (L)(R) / (LR)
As ligand concentration increases so does the concentration of…… (In diseases)
Bound receptors increase
As free receptor concentration increases so does……..
The receptor bound concentration does as well
Kd is defined as
50% of the available receptor occupied
Pharmacodynamics in relationship to dose response relationship curves
The relationship between the dose of the drug and the organisms response to the drug.
The response to a drug is proportional to……
Concentration of receptors that are. Bound by the drug.
What are the two types of dose responses curves?
Graded and quantum
Graded response curves
The effect of various doses on an individual
Quantal response curves
Effect of various doses of a drug on a population of individuals.
What are two important parameters that can be deduced from the graded response curve?
Potency and efficacy
What is the symbol denoted for potency?
EC 50
What is the symbol denoted for efficacy?
E max
What does the potency parameter mean?
Concentration at which the drug elicits 50% of its maximum response.
Agonist
If a drug-receptor binding results in the activation of the receptor.
Antagonist
Inhibits the drug from binding
In order for a drug to have a useful therapeutic effect to must?
Absorbed, distributed and eliminated
In order for drugs to have an effect they must.
Move for the site of administration to the site of action.
What is permeation?
Is the movement of drugs molecules from into and within the biological environment.
What are the four stages of permeation?
Aqueous diffusion
Lipid diffusion
Transport by special carrier
Endocytosis and pinocytosis
Aqueous diffusion
It is the movement of molecules through the watery extra cellular and intercellular spaces.
Lipid diffusion
Is the passive movement of molecules through the phospholipid membrane of cells and other lipid structures.
Special carriers
Drugs that do not readily diffuse through membeanes need endogenous substances to transport the molecules through the cells.
Endocytosis
The binding of the transported molecules to specialized components on the membrane(receptors) which cause the unfolding of the area of that membrane.
Endocytosis
Allows large proteins to get across membrane in the lipid form.
What was an example of endocytosis?
B12 and iron intrinsic factor
Exocytosis
The reverse process it is the expulsion of membrane encapsulated materials from the cells.
Frick’s Diffusion
Predicts the rate ochre movement of molecules across a barrier.
Receptors
Specific molecules in a biological system that drugs interact with to produce changes in the function of the system.
Receptor site
The binding region on a macromolecule and has relatively high and selective affinity for the drug.
Effectors
Molecules that translate the drug receptor integration into a change in a cellular activity.
Pharmacodynamics
Term used to describe the effects of a drug on the body.
Drug receptor binding
When a ligand binds to receptor a change is brought about .
Kd= koff/ kon
The intrinsic factor of any pair
What is the law of mass?
Kd
What are the two types of dose response ?
Graded and Quantal
Potency is
Concentration at which the drug elicits 50% of its maxiumum
What is efficacy?
The maximum response produced by the drug and additional drug would yield no better response
Spare receptor
When a drug does not use all its receptors but shows 100% maxiumum.
There are two types of antagonist. What are there?
Receptors and non receptors
Antagonist that bind to receptors are divided into two groups.
Active and allosteric
Antagonist that do not bind to receptors are called non receptors. What are the tow groups of receptors?
Chemical and physiological
What is a receptor antagonist?
A receptor antagonist bonds to either an active receptor or allosteric receptor.
Properties of antagonist
antagonists have affinity but no efficacy for their cognate receptors, and binding will disrupt the interaction and inhibit the function of an agonist or inverse agonist at receptors
What happen when an antagonist binds to an allosteric receptor?
antagonists have affinity but no efficacy for their cognate receptors, and binding will disrupt the interaction and inhibit the function of an agonist or inverse agonist at receptors
The function of a non receptor anatagonist
It does not bind to the agonist receptor but binds to an allosteric receptor and stops the agonist from binding.
How does non receptor work?
By inhibiting the agonist directly (antibodies) by inhibiting a downstream molecule in the activation pathway by activating a pathway that opposes the action of the agonist.
Chemical antagonist
Inactivates an agonist before it has an opportunity to act
Example of a chemical antagonist
Chemical neutralisation
Physiological effect
Causes a physiological effect opposite to that induced by the agonist.
Competitive receptor antagonist
Binds reversibly to the active site of a receptor. It does not stablises a conformation required for receptor activation.
Example of a competitive receptor antagonist
Pravastatin
Non competitive antagonist
Can bind to either the active site or allosteric site.
Are non competitive antagonist irreversible
Yes
Does high concentration of the agonist affect non competitive antagonist
No it does not
What is the role of a non competitive allosteric antagonist ?
Prevents an agonist from working even if the agonist is bound to the active site.
A receptor is bound to A Non competitive antagonist can it be useful again ?
No
What effect does a competitive receptor have on potency?
It reduces the potency
What effect does a non competitive receptor have on potency?
Nothing , non competitive receptors effect effacy and not potency
Example of a non competitive antagonist
Aspirin
How does aspirin work?
Irreversibly acetylates cyclo -oxygenase which generates thromboxane A2 in platelets . This prevents platelets from clotting.
How long does aspirin remains In the body?
7- 10 days
How long does it take to make platelets
7-10 days
The role of a chemical antagonist
Involves a direct chemical interaction between the agonist and the antagonist in a way which renders the agonist pharmacologically inactive.
What is an example of a chemical antagonist?
Protea mine binds stoichiomatically to the acidic heparin classes of anticoagulants.
What type of antagonist is Dimercaprol?
A chelator if lead and some other toxic metals. Is used to treat toxicity from mercury, arsenic or gold
What’s a physiological antagonist
Binds to a different receptor molecule producing an effect opposite to that produced by the agonist.
Example of a physiological antagonist?
Beta adrenergic antagonist used in the treatment
Specifity
Makes drugs selective to particular to certain tissues
Affinity
The tendency of a drug to bind to its receptor
Drug potency
Is when a drug has a high affinity for receptors and occupy a high
proportion of receptors at Low concentrations.
Partial agonist
Drugs with intermediate levels of efficacy with 100% receptor occupancy.
What are full agonist
Have sufficient efficacy to elicit maximal tissue response maximal tissue response
What does drug dose response relationships show?
They show that biological responses are graded and will continuously increase up to a maximum as the administered dose is continuously increased.
What is TD50?
Toxic dose which 50% of subjects showed a toxic response.
ED50
Effective dose which causes response in 50% of subjects and is used to determine the potency of drugs
LD 50
Lethal dose which causes death in 50% of cases
Therapeutic index
Ratio of TD50 and ED50
Which has a high therapeutic index Aspirin or Heparin
Heparin
What is reversible competitive antagonism?
When the combination of competitive antagonist and the receptor is loose.
What is irreversible competitive antagonism?
When the combination of the competitive antagonist and the receptor is covalent bonded
Non competitive antagonism
This involves the antagonist acting at a site beyond the receptor for the agonist.
Example of a non competitive antagonist
Hexamethonium and the nicotine acetylcholine receptor.
The effect of an antagonist on an agonist dose response relationship
Reduces the potency of the agonist without affecting the efficacy.
The effect of a non competitive antagonist on a drug dose curve
Does not effect the potency but effects the efficacy.
Pharmacokinetic antagonist
Reduces the effect of the active drug of action
Examples of drugs that exert a physiological antagonism effect
Histamine and salbutamol . Histamine constricts the respiratory airways while salbutamol relaxes it.
Describes the interaction of two agonist that act independently of each other but happen to cause opposite effects.
Tolerance
Developed when it becomes necessary to increase the dose of a drug to obtain an effect previously obtained with a smaller dose.
Tolerance can occur due to?
Change in receptors caused by desensitization
Loss of receptors by internalization of receptors
Exhaustion of mediators
Increased metabolic degradation of the drug.
Physiological adaptions
Active extrusions of drugs from the cells.
What is tachyphylaxis?
This is a quick onset of acquired tolerance following its initial administration. Usually due to quick lost of efficacy of the drugs at the receptors responsible for eliciting the effect upon a drug binding.
