3. Pharmacodynamics Flashcards
What are drug interactions and the 4 types of them?
A situation in which a substance affects the activity of a drug
Interactions between 2 drugs- drug-drug interaction between 2 drugs metabolized by same CYP isoform
Between a drug and a food item- drug-food interactions are metabolized by CYP enzymes and grapefruit juice for example
Between drug and herbs- drug-herb interactions metabolized by CYP and St. John’s wort for example
Other interactions- with blood electrolytes for example
Slides 67-70 general principles
What are pharmacodynamic drug-drug interactions?
What are pharmacokinetic drug-drug interactions?
Pharmacodynamic- 2 drugs affecting the same system
Ex: 2 sedative drugs will produce more sedation, alcohol and a sedative drug
Pharmacokinetic- one drug changes the absorption, distribution, metabolism, excretion (ADME) of another
Ex: absorption- antacids reduce absorption of tetracycline
Distribution- competition for plasma protein binding by non-steroidal anti-inflammatory drugs
Metabolism- one drug affecting the metabolism of another drug is most common reason for drug drug interactions
What is the most common metabolizing enzyme responsible for drug-drug interactions?
Two drugs metabolized by the same enzyme can compete for the enzyme CYP3A4
Why is it important to check for liver and kidney diseases before administering a drug?
Liver and kidney affect the metabolism and excretion and plasma levels of many drugs
Doses of drugs with high hepatic extraction ratio have to be reduced in chronic liver and kidney disease (ex: antidepressants)
What are the 4 cases to watch out for drug-drug interactions (DDIs) in?
The elderly
Receiving more than 2 drugs
Receiving warfarin, NSAIDs
New signs/ symptoms after starting a new drug
What is a receptor?
What is affinity?
Receptor- macromolecule whose biological function changes when a drug binds to it
Drug receptor binding triggers signal transduction
Affinity- measure of propensity of a drug to bind receptor; the force of attraction between drug and receptor
What happens if we put 2 drugs acting at the same receptor?
They will compete for the receptor due to the transient binding
The drug with higher concentration will have a greater chance at binding
Slide 82 general principles
What is Kd and it’s equation?
Kd- concentration of a drug that occupies 50% of the total number of receptors at equilibrium
Kd=K2/K1
The lower the Kd, the more affinity the drug has for the receptor
Slide 83 general principles
What can be derived from dose response and quintal curves graphs?
What is efficacy?
Slide 84 graph of % contraction over dose of drug (mg)
Emax- maximal effect produces by a drug. It is a measure of efficacy of a drug
EC50- dose or concentration of a drug that produces 50% of maximal response
Efficacy (intrinsic activity)- ability of a bound drug to change the receptor in a way that produces an effect; some drugs possess affinity but not efficacy
What is an agonist?
What is a partial agonist?
What is an antagonist?
Agonist- drug that binds to the receptor and produces an effect
Affinity and intrinsic activity
Partial agonist- has affinity for a receptor but less intrinsic activity (lower efficacy and lower Emax compared to an agonist acting at the same receptor)
Antagonist- drug which binds (competes for binding against other ligands) but does not activate the receptor
Has affinity but no intrinsic activity
Can be competitive or non competitive
Slides 87-88
How does a partial agonist work?
What’s a clinical example?
Partial agonist produces less than full effect when given alone
Partial agonist acts as an antagonist in the presence of a full agonist (blocks the full effect of an agonist)
Antagonist properties of a partial agonist can be useful; they provide some agonist activity and at the same time block them endogenous full agonists
Pindolol for high blood pressure and abnormal heart rhythms (reduces excessive stimulation due to norepinephrine in a person with high sympathetic nervous system activity)
What is competitive antagonism?
Slides 92-93 general principles
In presence of a competitive (reversible) antagonist a higher dose of agonist is required to produce the same effect
When the agonist is alone a lower dose can produce maximal effect
What is non-competitive (irreversible) antagonism?
Slides 94-95 general principles
In the presence of an irreversible (non-competitive) antagonist even a higher dose of agonist cannot produce maximal effect
When the agonist is alone, a lower dose can produce maximal effect
What is inverse agonist?
Some receptors have intrinsic (constitutive) activity even when no ligand is bound to them
When a ligand binds to them, their basal activity is reduced, these are inverse agonists
Are like competitive antagonists but on their own they reduce receptor activity whereas competitive antagonists have no effect on their own
Slide 97 general principles
What is allosteric interaction?
What is an example?
Slides 98-100 general principles
When a ligand B binds to a site close to the site of an agonist A on a receptor, it can affect the binding and/or response to agonist A, this is allosteric interaction
Benzodiazepine drugs potentiate the response to gama aminobutyric acid (GABA) when they bind to GABAa receptor
What is the quantal dose response curve?
What are the 2 types?
Indicates sensitivity of a given population to the doses of a drug for a given effect
Frequency distribution- each bar shows number of people responding to dose, excludes people responding to lower doses
Cumulative frequency- each bar shows the number of people responding to that dose and to lower doses
Slides 101-102
What is the therapeutic index?
Therapeutic index= TD50/ED50 or LD50/ED50
TD50- toxic dose in 50% of people
ED50- effective dose in 50% of people
LD50- lethal dose in 50% of people
Higher the ratio, safer the drug
What is the therapeutic window?
The difference between the minimum effective concentrations for a desired response and an adverse response
Reflects plasma concentration range that provides efficacy without unacceptable toxicity
What’s the difference between. An dose-(concentration)-response curve and a quantal dose curve?
Dose-(concentration)-response curve shows graded responses in a single individual, produced by increasing concentrations of a given drug
Quantal dose-response curve shows a specific response (quantal-all or none, present or absent) in a group of individuals produced by a drug
What are the 4 signal transduction mechanisms?
- G protein coupled receptor systems (GPCRs, metabotropic receptors)
Half of all known drugs work through GPCRs - Ion-channel receptors (ionotropic receptors)
- Enzymes as receptors- tyrosine kinase, serine/threonine kinase
- Nuclear receptors
Slides 107-108
What are enzyme receptors?
Receptor is a pair of protein molecules (monomers) that are separate when inactive
Agonist causes them to interact and form a diner
The interaction phosphorylates tyrosines in the intracellular region of the receptor and the receptor becomes an active enzyme
What are ion channel receptors?
The receptor is a protein with a channel in the centre. An agonist causes the channel to open and allows specific ions to cross the cell membrane to the other side
What are nuclear receptors?
These receptors are mostly in the cell cytosol
Agonist enters the cell and binds to the receptor
Drug-receptor complex then enters the nucleus and stimulates gene transcription
This leads to synthesis of new proteins and enzymes
Slide 111 general principles
How do receptors get desensitized?
Agonists tend to desensitize receptors- frequent stimulations of a receptor by its agonist results in a decreased response (desensitization)
