Pharmacodynamics Flashcards
What is the difference between pharmacodynamics and pharmacokinetics?
Dynamics= How the drug interacts with the receptors in the body Kinetics= How the body interacts with the drugs ADME
How is drug concentration measured? What is the equation to figure out the concentration of a drug?
Molarity (moles per L)
grams/ litres) / Mr (RFM of drug) = Molarity (conc
What is the difference between an agonist and and antagonist?
agonist activates a receptor
antagonist prevents binding of endogenous agonist so prevent receptor activation
What is affinity?
How easily a drug will bind to a receptor
How can affinity be measured?
Using radioactively labelled ligand and distinguishing between the amount of free and bound ligand
What graph describes affinity of a ligand for a receptor? What is the name for the maximum binding capacity (how many receptors present) and the concentration of drug needed to fill 50% of the receptors?
A concentration- binding curve
Bmax is the maximum binding capacity- [drug] needed to bind to every receptor
Kd is dissociation constant, lower Kd means higher affinity
If there is 100,000 receptors, how many receptors will be filled at the Kd value? How many will be filled if there is only 10,000 receptors?
50,000 and 5,000 because at Kd conc 50% of the receptors will be filled no matter how many receptors there are
If the concentration- binding curve is sigmoidal what has happened?
The drug concentration has been put into logs.
What is the ligands efficacy? What governs a ligands efficacy?
The ability of a bound ligand to cause a response
Governed by intrinsic efficacy (ability to cause conformational change to activate receptor) and other cell/ tissue dependant factors
How many micro moles (uM) in a milli mole (mM)
1,000
Do antagonists have efficacy and affinity?
affinity only as they have no intrinsic efficacy
How can the ability of a drug to cause a response me measured?
Measure response (eg amount of secretion) at varying drug concentrations Draw concentration- response curve
What is the name for the maximum response and the drug concentration needed to give 50% response
Emax is maximum response
EC50 is [drug] needed for 50% response
What is EC50 an measure of?
Potency- ability of drug to cause response (affinity+ efficacy)
What is the pharmacological difference between dose and concentration of a drug?
Concentration refers to known concentration at site of action
Dose refers to amount of drug given, with conc at site of action unknown
What element of drug potency can change for the same drug and receptor?
Affinity and intrinsic efficacy are FIXED
Tissue dependant factors of efficacy can change however
How can drug efficacy be determined from a conc- binding and conc- response curve?
If Kd is high (low affinity) but EC50 is low (high potency) then it must have pretty good efficacy.
Why may two agonists with the same binding curve and the same intrinsic efficacies have different response curves?
One may have better efficacy, it is simply better at provoking a response
What is functional antagonism?
An agonist that blocks an endogenous ligands action by activating a different pathway/ receptor. Eg salbutamol
How are salbutamol and salmeterol selective to the B2 receptor in lungs?
Salbutamol- slightly higher affinity (lower Kd) to B2, but mainly by route of administration and selective efficacy
Salmeterol- much higher affinity to B2 than B1, no selective efficacy
Why can a full response (Emax) be bought about partial binding- for example at Kd concentration?
Because most cells have many spare receptors- there are more receptors on the cell than needed to evoke a full response
Receptors are energy consuming to make so why have spare ones?
Less ligand needs to be produced so saves energy long term
What can cause receptor numbers to change? What is clinical consequence of this?
If the receptor is rarely stimulated (low activity), the receptor is expressed more.
Therefor sensitivity to a drug will change the longer you’ve been on a drug/ the more times you’ve been on it
What is the difference between full and partial agonists?
Partial agonists have a lower intrinsic efficacy than full agonists because they cause a slow/ partial conformational change
Why do partial agonists also have a lower Emax (cant produce full response)?
Because all receptors are filled but lower intrinsic efficacy means response less strong
Why are partial agonists useful?
More controlled response
Work in absence of endogenous ligand
Act as antagonists if high levels of full agonists
Give an example of a partial agonist and how it can be a more effective pain management and drug detoxing?
Buprenorphine is partial agonist to u opiod receptors
More controlled pain relief than morphine and lower chance of respiratory depression also used on heroine addicts to make withdrawal symptoms less severe
How can partial agonists cause a full response (Emax) equivalent to a full agonist?
By having loads of spare receptors, it may take a higher conc of partial agonist for this to be achieved tho
What are the types of antagonists?
Reversible and irreversible competitive antagonists and non- competitive antagonists
If two drugs have equal responses (Emax) do they have equal efficacy?
Not necessarily, it make take more of one drug to cause a full response
This is because the maxiumum response is often limited
What is the name of the concentration of drug needed to inhibit the maximum response by 50%?
What is the name for affinity of a competitive inhibitor?
IC50 is conc antagonist needed for 50% inhibition
Kd is dissociation constant ([drug] needed for 50% binding)
Is inhibition of a competitive antagonist surmountable? What will a conc- response curve of a drug look like if competitive antagonist added?
Yes
It will be identical just shifted to the right
Give an example of a competitive antagonist
Naloxone- high affinity to u- opioid receptors. Used to reverse respiratory depression due to overdose
Is irreversible competitive antagonism surmountable? What is affect on conc- response curve of adding more?
Nope
Same but shifted to left at start (as spare receptors fill) and then Emax decreases as more antagonist added
Give an example or a irreversible competitive inhibitor.
Phenoxy benzamine- blocks a1 adrenoreceptors so less vesoconstriction so lower bloop pressure.
Used to treat tumors in adrenal glands because it will not be overcome but the massive quantities of adrenaline being produced
What is opposite of allosteric site?
orthosteric site
What is effect of non-competitive antagonism on conc- response curve?
Same as irreversible competitive:
Parrellel shift as spare receptors inactivated
Then Emax decreases as more is added becausenot enough receptors able to be activated to create full response no matter how much drug you add
Give an example of a non- competitive antagonist
Maraviroc acts on CCR5 which is used by HIV to enter cells. Therefor HIV cannot enter cells and spread (its an antiretroviral drug).
