Pharmacology Basics Flashcards
actions of the biological system on the drug
What the body does to the drug
Pharmacokinetics
Pharmacokinetics describes:
What the body does to the drug
study of the undesired effects of chemicals on biological systems
Toxicology
action of drugs on the biological system
What the drug does to the body
Pharmacodynamics
Pharmacodynamics describes:
What the drug does to the body
Molecules whose interaction with receptor causes cellular responses
Agonists
Molecules whose interaction with receptor does not cause cellular response
Antagonists
But can prevent action of an agonist
Difference between agonists and antagonists
Agonists cause cellular responses; antagonists do not
Type of drug-target binding that is rare for drug-receptor interactions and irreversible
Covalent bonds
Drug-target binding for aspirin
Aspirin forms covalent (irreversible) bond with cyclooxygenase
Aspirin forms this type of bond with cyclooxygenase
Covalent (irreversible)
Aspirin forms covalent (irreversible) bond with this
Cyclooxygenase
Type of drug-target binding that is the primary electrostatic attractor
Ionic bond
Type of drug-target binding that is the secondary attractor; increased influence with better “fit”
Hydrogen and/or Van der Waals bonds
Opiate stereoisomers that are analgesic
L opiates
(D opiates are not)
Opiate stereoisomers that are antitussive
Both L and D opiates
Do stereoisomers require a symmetric or asymmetric center?
Asymmetric
proteins that bind with specificity and selectivity but are not receptors
No activity change with binding
Acceptors
Is there activity change with binding of acceptors?
No
Acceptors can affect pharmacodynamics by binding the drug and preventing:
Prevent drug interaction with the receptor
Drugs binding to acceptors is also referred to as this
Nonspecific protein binding
Nonspecific protein binding refers to this
Drugs binding to acceptors
Part of the dose response curve that is a measure of drug effectiveness or efficacy
Emax or the ceiling
Part of the dose response curve that is an indicator of binding affinity (strength) for the drug
Steepness of curve
Part of the dose response curve that is a measure of drug potency
Dose at 50% = effective dose 50% (ED50)
Emax or the ceiling of the dose response curve is a measure of this
Drug effectiveness / efficacy
Steepness of the dose response curve is an indicator of this
Binding affinity (strength) for the drug
Effective dose 50% (ED50; dose at 50% response) is a measure of this
Drug potency
Comparison of dose at a single level of effect
Does not allow comparison of effectiveness, merely dose at each drug’s half maximal response
Potency
Potency is this
Comparison of dose at a single level of effect
(dose at each drug’s half maximal response)
Does potency increase or decrease as the dose response curve shifts left?
Increases
Measure of maximal response effect
Does not compare dose at maximal effect
NOT a dose
Efficacy (aka intrinsic activity)
Efficacy (intrinsic activity) measures this
Maximal response effect
Does efficacy increase or decrease as dose response curve shifts down?
Decreases
Does potency or efficacy measure dose?
Potency
Intrinsic activity is also referred to as this
Efficacy
Efficacy is also referred to as this
Intrinsic activity
Describes when fewer than the total number of receptors are required to be occupied to achieve a maximal response
Receptor reserve (“spare receptors”)
Receptor reserve (“spare receptors”) describes when:
Fewer than the total number of receptors are required to be occupied to achieve a maximal response
Type of antagonism that binds the receptor but does not activate
Prevents other molecules from binding the receptor
Receptor antagonism
Type of antagonism that is a direct chemical interaction between agonist and antagonist, that renders agonist inactive
Chemical antagonism
Type of antagonism that involves two agonists with opposing effects
Functional antagonism
A receptor antagonist does this
Binds receptor but does not activate
Prevents other molecules from binding the receptor
A chemical antagonist does this
Directly chemically interacts with agonist and renders it inactive
Functional antagonism involves this
2 agonists with opposing effects
Type of antagonism where the agonist and inhibitor compete for access to binding site
Maximal effect maintained; potency reduced
Competitive
Type of antagonism with two major types: irreversible (covalent binding) and allosteric antagonists
Reduces efficacy
Noncompetitive antagonism
Competitive antagonism reduces this
Potency
Competitive antagonism has no effect on this
Maximal effect / efficacy
Noncompetitive antagonism reduces this
Efficacy
Allosteric antagonists mimic the dose response curve of this
Noncompetitive antagonism
Allosteric ______ enhance effect of primary receptor activation
Allosteric agonists
Allosteric _____ reduce the effect of primary receptor activation
Allosteric antagonists
Allosteric agonists has this affect on dose response curve
Opposite of competitive = increase potency, shift left
Allosteric antagonist has this affect on dose response curve
Mimic non-competitive = lower curve
Type of agonists that when added to a full agonist, may reduce the maximal activity achieved with only the full agonist by blocking the full agonist’s access to the active receptor
Partial agonists
Type of agonists that have intrinsic activity opposing agonist activity
Some receptors are normally ‘active’ and require an agonist to turm them “off”
Inverse agonists
Type of agonist that lowers the activity from that of full agonist, but still remains more active that constitutive activity
Partial agonist
Type of agonist that decrease activity below that of the constitutive activity level
Inverse agonist
state of decreased responsiveness to a drug (describes loss of response to drugs)
Desensitization
rapid desensitization due to repeated exposure to the same drug concentration
Tachyphylaxis
Desensitization that is rapid and receptors are usually retained
Tachyphylaxis
Type of desensitization that is not dose dependent
Tachyphylaxis
Tachyphylaxis describes this
rapid desensitization due to repeated exposure to the same drug concentration
reduced response to drug exposure over a long time frame, usually involving reduced receptor numbers
Tolerance
Type of desensitization involving changes in receptor number and/or function due to drug exposure
Tolerance
4 mechanisms of desensitization
Uncoupling of the receptor from downstream signaling
Endocytosis
Degradation
Down regulation
Uncoupling of the receptor, endocytosis, degradation, and down regulation are mechanisms of this
Desensitization
processes that reduce the number of receptor in a cell membrane
Occurs following continuous exposure to agonist or endogenous ligand, dictated at least in part by negative feedback
Mechanisms may include decreased gene transcription or increased mRNA degradation
Down regulation
2 mechanisms of down regulation
Decreased gene transcription
Increase mRNA degradation
Occurs when:
The cell is continuously exposed to an antagonist, decreasing exposure to agonist, Disease reduces concentration or availability of endogenous ligand
Genetic amplification
Up regulation
Drug that induces up-regulation of opioid receptors
Naloxone
exaggerated receptor response resulting from chronic reduction of receptor stimulation
Usually due to prolonged lack of exposure
Supersensitivity
Supersensitivity describes this:
Exaggerated receptor response resulting from chronic reduction of receptor stimulation
