IASM 76 77 78: Drug Basics I Flashcards
GABA => Degraded (Under GABA-Transaminase)
What are the inhibitor of GABA-Transaminase?
Valproate
When plotting a graph for reaction rate against substrate amount, what is the shape of graph like
Think it inside head
Increasing with decreasing rate
Pain sensation are transmitted through sensory neurones to the brain
Name an Na+ channel blocker to prevent the sensation of pain
Lidocaine
Pharmacokinetics: Transport drugs with a _______ structure as the endogenous compound across the membrane
Pharmacodynamics: Drug binds to the transporter as an _________ for the transport of the endogenous compound
Pharmacokinetics: Transport drugs with a similar structure as the endogenous compound across the membrane
(KISS: KInetics Similar Structure)
Pharmacodynamics: Drug binds to the transporter as an inhibitor for the transport of the endogenous compound
Is Serotonin (5-HT) working by Pharmacokinetics (Transport drugs with similar structure) or Pharmacodynamics (Drug binds to transporter as an inhibitor) ?
Pharmacodynamics (Drug binds to transporter as an inhibitor)
In a receptor:
What is the recognition domain
What is the transduction domain
Recognition: Bind to ligands
Transduction: Signal into response and undergo functional conformational changes
What are true drug receptors
The known ________ are drugs, there is no ___________ for that receptor
What are true drug receptors
The known ligand are drugs, there is no endogenous ligand for that receptor
Cell Surface Protein Kinase
- Phosphorylation of the effector protein
- Which amino acid (s) do they phosphorylate on? Mainly on _____, also on _____ and _______
Cell Surface Protein Kinase
- Phosphorylation of the effector protein
- Which amino acid (s) do they phosphorylate on? Mainly on tyrosine, also on serine and threonine
Nuclear receptors are in _______ during inactive state. After activated by binding with specific ligands, they will be ________ to _________ and bind to DNA.
Nuclear receptors are in cytosol during inactive state. After activated by binding with specific ligands, they will be translocated to nucleus and bind to DNA.
Tamoxifen is the receptor of which molecule?
Estrogen
Compare the speed of certain kinds of receptors
- Ligand-gated ion channels
- GPCRs
- Kinase-linked receptors
- Nuclear Receptors
Which 2 of them have a higher speed? Why?
Compare the speed of certain kinds of receptors
- Ligand-gated ion channels
- GPCRs
- Kinase-linked receptors
- Nuclear Receptors
Ligand-gated ion channels and GPCRs are faster
They do not require protein synthesis
Just read:
Compare the orthosteric site and allosteric site of the receptor. Orthosteric site are binding sites for endogenous agonists, allosteric sties are binding sites conformationally linked to orthosteric site.
i.e. something binding to allosteric site will change conformation on orthosteric site
We have orthosteric agonist and allosteric agonists.
Positive Allosteric Modulator will increase the _______ and ________ of the orthosteric agonist.
Negative Allosteric Modulator will decrease the ________ and ________ of the orthosteric agonist.
Positive Allosteric Modulator will increase the efficacy and affinity of the orthosteric agonist.
Negative Allosteric Modulator will decrease the efficacy and affinity of the orthosteric agonist.
What are spare receptors and what’s the phenomenon
What should we do then
- Spare receptors= Receptors unbound
- Maximal drug response is obtained less than the maximal occupation of receptors
- We should reduce the concentration of the drug to reduce the toxic effect
What is the difference between drug tolerance and drug dependence
Tolerance: Reduced drug response with repeated doses, therefore need increased dose to maintain the same response
Dependence: Person needs the drug to function normally
For drug tolerance
There can be 3 ways for drug tolerance to occur
- Decrease in concentration of drug at the receptor
- Decrease in response at the receptor to the same concentration of drug
- Decrease in the number of receptors
Pharmacokinetics is the study of…
Pharmacodynamics is the study of…
Pharmacokinetics is the study of the drug movement into, around and out of body
Pharmacodynamics is the study of onset, intensity and duration of response of the drug
What do we call when:
A. Response increases when drug concentration increases
B. Response decreases when drug concentration increases
What do we call when:
A. Response increases when drug concentration increases- Stimulation
B. Response decreases when drug concentration increases- Repression
How to calculate the response based on the following 3:
Receptor occupancy
Efficacy
Receptor number
Receptor occupancy x Efficacy x Receptor number
When we say Drug A is more potent than B
For the same ____________, the concentration of drug A required is ______ than that of drug B.
When we say Drug A is more potent than B
For the same degree of effect, the concentration of drug A required is less than that of drug B.
Refer to graphs on IASM 77
When we say Drug A has a higher efficacy than B
For the same ____________, drug A gives a higher ___________ than drug B.
When we say Drug A has a higher efficacy than B
For the same concentration, drug A gives a higher degree of response than drug B.
Refer to graphs on IASM 77
Do we always use more potent drugs
Why
no
Maximal effect of the more potent drug might be less than that of the less potent drug
Refer to graphs on IASM 77
Besides binding to the target receptor, drugs can also bind to other receptors. The best drugs are achieved when there is high affinity for the target receptor, but little or no affinity for the other receptors.
Do agonists and antagonists have affinity?
Do agonists and antagonists have efficacy?
Besides binding to the target receptor, drugs can also bind to other receptors. The best drugs are achieved when there is high affinity for the target receptor, but little or no affinity for the other receptors.
Do agonists and antagonists have affinity? Yes for both
Do agonists and antagonists have efficacy? Agonists have efficacy, antagonists don’t have efficacy
For drugs with the same maximal effect as the endogenous compound, what is the value of the efficacy?
1
or 100%
Partial agonists bind to the receptor to produce ________ effect, but ________ a full agonist.
Partial agonists bind to the receptor to produce submaximal effect, but antagonize a full agonist.
Inverse agonist (Inactive) <=> Agonist (Active) When more agonists bind to the active receptor, it will shift the equilibrium positive to the \_\_\_\_\_\_ site
Inverse agonist (Inactive) <=> Agonist (Active) When more agonists bind to the active receptor, it will shift the equilibrium positive to the active site
Specific binding of drugs to receptor and non-specific binding of drugs to receptor
Specific: Exert effects only upon a single receptor
Non-specific: Affects all receptors in the same way to denature the receptor portion of the protein (Irreversible)
There is only non-specific _________ but not non-specific ______.
Specific binding of drugs to receptor and non-specific binding of drugs to receptor
Specific: Exert effects only upon a single receptor
Non-specific: Affects all receptors in the same way to denature the receptor portion of the protein (Irreversible)
There is only non-specific inhibition but not non-specific stimulation.
Under specific and non-specific binding
There is reversible and non-reversible binding
Reversible binding has rapid _____ of drug receptor complex, while non-reversible dissociates very slowly.
Under specific and non-specific binding
There is reversible and non-reversible binding
Reversible binding has rapid dissociation of drug receptor complex, while non-reversible dissociates very slowly.
There is competitive and non-competitive binding of receptors. For competitive binding, drug binds to the ____ site as the endogenous ligand. For non-competitive binding, drug binds to a _____ site as the endogenous ligand which changes the _______ of the active site.
There is competitive and non-competitive binding of receptors. For competitive binding, drug binds to the same site as the endogenous ligand. For non-competitive binding, drug binds to a different site as the endogenous ligand which changes the conformation of the active site.
For competitive binding, increase the ligand concentration ____ (can/cannot) outcompete the binding of drug to the receptor.
For non-competitive binding, increase the ligand concentration ____ (can/cannot) outcompete the binding of drug to the receptor.
For competitive binding, increase the ligand concentration CAN outcompete the binding of drug to the receptor.
For non-competitive binding, increase the ligand concentration CANNOT outcompete the binding of drug to the receptor.
What is desensitization
When the dosage continues, the degree of response ________. The responses can _______ after an extended period.
What is desensitization
When the dosage continues, the degree of response decreases. The responses can recover after an extended period.
Homologous Desensitization: Need to switch to a drug that acts on another _______
Heterologous Desensitization: Need to switch to another _____ of drug completely ______ to the original drug
Homologous Desensitization: Need to switch to a drug that acts on another receptor
Heterologous Desensitization: Need to switch to another class of drug completely different to the original drug
Refer to graphs on IASM 77
How to calculate the Therapeutic Index
TD50/ED50
TD50= Dose of drug causing toxic response to 50% of population
ED50= Dose of drug therapeutically effective in 50% of population
Value should at least be larger than 1
What is the Lipid:Water Partition Coefficient?
What does a higher coefficient indicate
Ratio of drug in lipid : Drug in water
Higher coefficient= More drug in the cell membrane = Diffusion is faster speed
For a substance with pKa = 5.0
At pH 5.0, 50% of it will be ______, 50% of it will be _______.
Now the solvent is pH=7.0
How many percent (<50% or >50%) of the substance will be ionized?
Now the solvent is pH=3.0
How many percent (<50% or >50%) of the substance will be ionized?
The substance, in which form (ionized or non-ionized form) can they pass through the membrane?
For a substance with pKa = 5.0
At pH 5.0, 50% of it will be ionized, 50% of it will be non-ionized.
Now the substance is dissolved in a solvent with pH=7.0
How many percent (<50% or >50%) of the substance will be ionized? Answer: >50%
Now the substance is dissolved in a solvent with pH=3.0
How many percent (<50% or >50%) of the substance will be ionized? Answer: <50%
The substance, in which form (ionized or non-ionized form) can they pass through the membrane? Answer: Non-ionized
What is bioavailability
Fractional extent to which a dose of drug reaches the site of action
First pass effect occurs when…
Name the major organ that causes first pass effect
Drug is metabolized between the site of administration and the site of sampling
Organ: Liver
2 drugs are considered to be bioequivalent if…
In the concentration against time curve,
_______ concentration is the same
__________ is also the same
___________ is the same
(Superimposable)
2 drugs are considered to be bioequivalent if…
In the concentration against time curve,
Maximum plasma concentration is the same
Time to peak height is also the same
Area under curve is the same
(Superimposable)
What 3 factors affect the drug distribution
1.
2.
3.
What 3 factors affect the drug distribution
- Cardiac output
- Regional blood flow
- Tissue volume
Only unbound drugs can freely move from vessels to the interstitial space, other drugs bind to proteins.
What does acidic drugs bind to
What does basic drugs bind to
Once the drugs bind to these proteins, the drugs ________ (Can/ cannot) pass through the cell membrane
Only unbound drugs can freely move from vessels to the interstitial space, other drugs bind to proteins.
What does acidic drugs bind to: Albumin
What does basic drugs bind to: Alpha1-acid glycoprotein
Once the drugs bind to these proteins, the drugs CANNOT pass through the cell membrane
Drugs with small therapeutic window means…
A small difference in dose of drug can cause serious therapeutic failure
Most drugs accumulate in tissues, rather than blood and extracellular fluid. What about lipophilic drugs in obese people?
Most drugs accumulate in tissues, rather than blood and extracellular fluid. What about lipophilic drugs in obese people?
If they take too much lipophilic drugs, the drugs may bind to the lipid instead of going to tissues.
Consider Drug Displacement
- Class I Drug: Clinical dose is ____ (more/less) than the binding capacity, most drugs binds to _______ and the free drug concentration is ________
- Class II Drug: Clinical dose is ____ (more/less) than the binding capacity, most albumin are bound by drugs already, free drug concentration is _______
Which class of drug can be displaced by another? Causing rapid increase in its free form in plasma
Consider Drug Displacement
- Class I Drug: Clinical dose is LESS than the binding capacity, MOST drugs binds to albumin and the free drug concentration is LOW
- Class II Drug: Clinical dose is MORE than the binding capacity, most albumin are bound by drugs already, free drug concentration is HIGH
Class I can be displaced by Class II, causing rapid increase in Class I drug (free form) in plasma.
When Class I drug is displaced by Class II drug, what will result?
- Comment on the action
- Comment on the duration
Increase in action of Class I drug, due to increase in free form of drug in the plasma
Decrease in the duration of drug response, due to an increase portion of drug are available for elimination
Elimination half-life VS Redistribution half-life
- Drug gone out from the _____ VS Drug gone out from the _________
So they are very different
Elimination half-life VS Redistribution half-life
- Drug gone out from the body VS Drug gone out from the site of action
So they are very different
