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Definition
| the study of substances and chemicals that interact with living, biological systems through chemical processes and alter biologic function or response. |
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Definition
| a branch of pharmacology, the study of the harmful effects of chemicals on living systems |
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Definition
| a substance or chemical that is foreign to the human body |
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Definition
| an inacive form of a drug that requires metabolic activation inside the body |
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Definition
| the component of a cell or organism that interacts with a drug and initiates the chain of biochemical events leading to the drug's observed effects |
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Definition
| reference to the actions of the drug on the human body. Mechanism of action, relationship b/t effect and concentration, etc |
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Definition
| literally means "the movement of a drug" ; refers to the actions of the human body on the drug |
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| ADME properties stand for... |
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Definition
| Absorption, Distribution, Metabolism/Excretion and refers to pharmacokinetics of the drug |
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Definition
| the study of the genetic variations among humans that cause differences in pharmacodynamics and pharmacokinetics. |
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| Acid-Base drug properties can greatly influence _____ |
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Definition
biodistribution and partitioning characteristics of a drug.
pH differences of the body may alter the degree of ionization |
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Term
| What determines the best route of administration of a drug? |
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Definition
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Definition
| the site of action of the drug |
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| Drug-Receptor Complex --> pharmacological response |
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| Drug Selectivity is also called |
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Definition
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Term
| What does selective binding/drug selectivity refer to? |
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Definition
| the number of receptor types or subtypes that the drug binds to in the body |
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Term
| What is used to measure drug selectivity? |
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Definition
| binding affinities of the drug to different receptor types and subtypes |
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Term
| What does "binding affinity" refer to? |
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Definition
| The ability of the drug to fit into and bind to the receptor pocket. |
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Term
| What does Drug Specificity refer to? |
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Definition
| The number of effects, whether beneficial or not, that the drug is capable of producing |
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Term
| What is a purely specific drug capable of? |
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Definition
| the production of a single, specific effect |
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Term
| What contributes to a drug's inability to be specific? |
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Definition
the likelihood of binding to more than one type of receptor in the body, and
postreceptor processes that are controlled usually take place in multiple cell types |
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Term
| Are drugs able to be "selective" or "specific" |
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Definition
| They are only selective in their actions |
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Term
| What can drug selectivity be attributed to? |
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Definition
drugs bind to one or a few receptor types or subtypes more tightly than others
receptors control discrete cellular processes that result in distinct effects |
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Term
| What is the best molecular weight range for a drug to selectively bind? |
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Definition
| a weight between 100 and 1000 |
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| Name the three major types of drug-receptor bonds? |
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Definition
covalent
electrostatic
hydrophobic |
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Term
| Which bonds are the strongest? |
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Definition
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| What bonding is irreversible? |
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Definition
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| Drugs that are considered highly reactive molecules are bonded by what bond type? |
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Definition
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| Which is more common in binding? Electrostatic or covalent |
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Definition
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| Name some electrostatic bond types? |
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Definition
ionic bonds
hydrogen bonds
van der Waals forces |
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Term
| Hydrophobic bonds are weak or strong? |
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Definition
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Term
| Where are hydrophobic bonds most important? |
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Definition
in the interactions of highly lipophilic drugs with the phospholipid bilayers of cell membranes.
they are important in the interaction of drugs with the active site or 'pocket' of the receptor |
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Term
| Drugs which bind through weak bonds to their receptors are considered more/less selective than drugs which bind through stronger bonds? |
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Definition
| they are more selective in binding |
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Term
| What is attributable to the selectivity of weaker binding drugs? |
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Definition
| the very precise fit of the drug in the active pocket |
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Term
| Most drugs, relating to stereochemistry, are.... |
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Definition
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Definition
| 50/50 mix of optical isomers or enantiomers |
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Term
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Definition
| drugs that bind to and activate the receptor, bringing about pharmacological effect, either directly or indirectly |
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Term
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Definition
| a component of a signal transduction pathway that produces a biologic effect after the receptor is activated by an agonist. |
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| How do some drugs mimic the effect of a receptor agonist? |
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Definition
| by inhibiting the molecules responsible for terminating the action of an endogenous agonist |
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Term
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Definition
| drugs that can active the receptor-effector system to the maximum extent of which the system is capable when administered at a sufficiently high concentration. |
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Term
| high intrinsic efficacy are what type of agonist? |
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Definition
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Term
| What are Partial Agonists? |
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Definition
| Drugs that bind and activate the receptor; the evoked response or effect is not as high as the effect obtained by full agonist. |
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Term
| In the presence of a full agonist, a partial agonist can act as... |
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Definition
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Term
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Definition
| drugs that bind to the receptor and stabilize it in its inactive conformation |
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Term
| Allosteric Agonists are also known as |
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Definition
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Term
| What do allosteric agonists do? |
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Definition
| They enhance the efficacy/binding affinity of the receptor agonist by binding to allosteric sites on the receptor molecule |
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Term
| What are Pharmacological Antagonists, also known as blockers, or receptor specific antagonists capable of? |
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Definition
| they bind to the same binding site of the agonist on the receptor molecule without activating the receptor. This prevents activation of the receptor. |
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Term
| Allosteric Antagonists/Allosteric Inhibitors are also called two more names... |
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Definition
Receptor-Specific Allosteric Antagonists
Noncompetitive Allosteric Antagonists |
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Term
| What do Allosteric Inhibitors do? |
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Definition
| they inhibit or reduce the efficacy/binding affinity of the receptor agonist by binding to allosteric sites on the receptor molecule |
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Term
| Are allosteric antagonists competitive? |
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Definition
| No, Noncompetitive, may bind either reversibly or irreversibly |
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Term
| Modern concepts of drug-receptor interactions consider the receptor to have how many conformations? |
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Definition
| at least 2, inactive and active |
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Term
| In the active conformation, the receptor can do what? |
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Definition
| activate effectors and produce an effect, even in the absence of a ligand. |
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Term
| What is "Constitutive Activity"? |
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Definition
| It is the effect produced in the absence of an agonist. This is a small observable effect. |
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Term
| In the absence of a ligand, the receptor exists in a state of _________. |
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Definition
| Equilibrium between the inactive and active forms |
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Term
| In the absence of any ligand, which conformation is favored? |
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Definition
| The inactive conformation |
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Term
| In the absence of an agonist, receptor systems in humans exhibit ______ |
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Definition
| a low level of constitutive activity |
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Term
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Definition
| have much higher affinity for binding to the Ra conformation and are able to fully stabilize it. |
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Term
| Full agonists can cause a shift of the receptor pool to the _____ |
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Definition
| Ra-D pool, when administered at sufficiently high concentrations |
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Term
| In the presence of a full agonist, a partial agonist acts as what? |
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Definition
| an antagonist, or blocker |
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Term
| Pharmacologic Antagonists have what level of affinity for Ri and Ra forms? |
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Definition
| intermediate affinity for binding, with slightly greater affinity for the Ra form |
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Term
| Inverse Agonists prefer to bind to the |
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Definition
| inactive form of the receptor molecule and stabilize it. |
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Term
| What is the difference between a receptor and an inert binding site? |
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Definition
| a receptor is usually endogenous, regulatory molecule and must be selective in binding to ligands. It must change it's function on activation. Inert molecules will not alter biological function or response. |
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Term
| Most receptors are ______ |
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Definition
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Term
| What do regulatory proteins do? |
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Definition
| mediate the actions of endogenous chemical signals such as neurotransmitters, autocoids, and hormones |
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Term
| What types of molecules may act as drug receptors? |
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Definition
regulatory proteins
enzymes
transport proteins
structural proteins |
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Term
| What are the three practical consequences of the "receptor concept"? |
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Definition
1) Receptors are responsible for establishing the quantitative relationship between dose or concentration of the drug and its pharmacologic effect
2) Receptors are responsible for selectivity of drug action.
3) Receptors mediate the actions of both agonists and antagonists |
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Term
| What is the graded dose response curve? |
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Definition
the relationship between drug concentration and effect:
(Emax x C)/(C + EC50) = E
E = effect observed at C
Emax= max response produced by the drug
EC50=concentration of drug producing 50% of the maximal effect |
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Term
| What is the graded dose binding curve? |
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Definition
The relationship between drug bound to receptor molecules and concentration of free drug
B=(Bmax x C)/( C+Kd) |
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Term
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Definition
| drug efficacy; if Emax is low, efficacy is low |
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Term
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Definition
| drug potency; if EC50 is low, drug potency is high |
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Term
| Kd characterizes the drug's |
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Definition
| affinity for receptor binding; if Kd is low, binding affinity is high |
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Term
| How is dose response/ dose effect data usually presented? |
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Definition
| as a function of the logarithm of the dose or concentration |
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Term
| Why are sigmoidal curves preferred? |
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Definition
| Because you can see better the relationship between concentration and drug receptors. |
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Term
| What is meant by drug potency? |
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Definition
| the less drug required to produce the desired effect, the more potent the drug is considered to be. |
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Term
| What is Coupling, or Occupancy-Response Coupling? |
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Definition
| the transduction process between occupancy of receptor molecules and drug response |
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Term
| What determines the efficiency of the coupling process? |
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Definition
1) Initial Conformation Change in the receptor
2) Biochemical Events that transduce receptor occupancy into a cellular response and how efficient these events are. |
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Term
| What are Spare Receptor Molecules? |
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Definition
| for a pharmacologic response, spare receptor molecules are present when the maximal effect or response can be produced by an agonist at a concentration not resulting in complete receptor saturation |
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Term
| If Emax is obtained at less than Bmax, then... |
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Definition
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Term
| If EC50 is lower than Kd, then |
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Definition
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Term
| If EC50 is the same as Kd, then |
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Definition
| spare receptors do not exist |
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Term
| What mechanisms result in spare receptors? |
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Definition
the duration of the activation of the effector may be greater than the duration of drug-receptor interactions
the number of receptor molecules may exceed the number of effector molecules |
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Term
| The sensitivity of a cell or tissue to a particular concentration of the agonist depends on both: |
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Definition
1) affinity of the receptor for binding to the agonist
2) the degree of spareness of the receptor |
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Term
| What is "the degree of spareness"? |
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Definition
| the total number of receptor molecules present compared to the number of receptor molecules needed to elicit maximum response |
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Term
| a high degree of spareness will lead to |
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Definition
| considerable increase in tissue sensitivity |
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Term
| Pharmacologic Antagonists are divided into two classes: |
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Definition
| competitive and non-competitive |
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Term
| Competitive Antagonists... |
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Definition
| bind to the same binding site of the agonist on the receptor in a reversible way, without activating the effector system for that receptor. |
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Term
| Competitive Antagonism is... |
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Definition
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Term
| How can competitive antagonism be overcome? |
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Definition
| a considerable increase in agonist concentration will result in a decrease in antagonistic effect of a blocker. |
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Term
| What do Noncompetitive, irreversible pharmacologic antagonists do? |
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Definition
| they bind to the receptor without activating it, at the same binding site of the agonist on the receptor. |
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Term
| What causes an antagonist to bind irreversibly? |
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Definition
| they either form covalent bonds, or they have an extremely high affinity for binding to their receptor sites. |
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Term
| What is different about irreversible antagonists from competitive antagonists? |
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Definition
| the effects of irreversible antagonists can not be overcome by increases in agonist concentrations. |
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Term
| What does the duration of action of an irreversible antagonist depend on? |
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Definition
| the rate of turnover of receptor molecules |
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Term
| What is a disadvantage of using an irreversible antagonist as a therapeutic agent? |
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Definition
| the need to antagonize excess effects of the antagonist in cases of overdose |
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Term
| What is a disadvantage of using an irreversible antagonist as a therapeutic agent? |
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Definition
| the need to antagonize excess effects of the antagonist in cases of overdose |
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Term
| What contributes to the inability of a partial agonist to produce a maximal effect at full receptor occupancy? |
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Definition
its mode of interactions with the receptor
low intrinsic efficacy at the receptor site
its inability to stabilize the Ra form of the receptor as fully as full agonists. |
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Term
| Partial agonists competitively inhibit full agonists, and can therefore be used as... |
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Definition
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Term
| What is chemical antagonism? |
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Definition
| this occurs when one drug binds to, and blocks the actions of, a second drug. |
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Term
| what antagonist does not depend on interactions with the agonist receptor? |
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Definition
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Term
| What are three chemical antagonists? |
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Definition
protamine
dimercaprol
pralidoxime |
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Term
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Definition
| a chemical antagonist of heparin |
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Term
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Definition
| a chemical antagonist of lead and some other toxic metals |
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Term
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Definition
| is a chemical antagonist of organophosphate cholinesterase inhibitors. |
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Term
| a physiological antagonist |
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Definition
| binds to a different receptor molecule, producing an effect opposite to that produced by the drug it antagonizes |
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Term
| the effects of physiological antagonists |
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Definition
| are less specific and more difficult to control |
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Term
| Name three physiologic antagonists |
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Definition
insulin
epinephrine
glucagon |
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Term
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Definition
| antagonizes the hyperglycemic effects of glucocorticoids |
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Term
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Definition
| antagonizes the bronchoconstrictor action of histamine |
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Term
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Definition
| antagonizes the cardiac effects of Bblockers |
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Term
| What are the five basic mechanisms of transmembrane signalling? |
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Definition
intracellular receptors for lipid-soluble agents
ligand-regulated transmembrane enzymes
cytokine receptors
ligand-gated ion channels
g proteins and second messengers |
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Term
| Explain an intracellular receptor for lipid soluble agents. |
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Definition
| a lipid soluble ligand, or drug, crosses the plasma membrane and acts on an intracellular receptor |
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Term
| name the intracellular receptor for lipid soluble agents |
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Definition
| nitric oxide, corticosteroids, sex hormones, thyroid hormones, vitamin d |
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Term
| what are ligand gated transmembrane enzymes? |
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Definition
| these are transmembrane proteins consisting of extracellular ligand binding domains and a cytoplasmic enzyme domain. these domains are connected by a hydrophobic segment of the polypeptide that crosses the lipid bilayer |
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Term
| name the ligand regulated transmembrane enzymes |
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Definition
insulin
epidermal growth factor
platelet derived growth factor
transforming growth factor B
trophic hormones |
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Term
| Describe the receptor tyrosine kinase signaling pathway |
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Definition
| ligand binding to the receptor's extracellular domain, which results in conformation change. this causes receptor molecules to bind to one another. the tyrosine kinases are now enzymatically active, and phosphorylate each other and downstream proteins |
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Term
| What is the difference in the cytokine receptors and the tyrosine kinase? |
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Definition
| in the cytokine receptors, the protein tyrosine kinase activity is not intrinsic to the receptor molecule. a seperate protein from the JAK binds to the receptor. |
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Term
| what are examples of ligands that activate cytokine receptors |
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Definition
growth hormones
interferons
other regulators of growth and differentiation |
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Term
| ligand gated ion channels are |
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Definition
| a class of receptors that are opened or closed by the binding of a ligand |
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Term
| name examples of ligands that regulate the flow of ions |
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Definition
acetylcholine
serotonin
y-aminobutyric acid
excitatory amino acids |
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Term
| Receptors that are coupled to G proteins belong to a family of proteins called |
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Definition
| Serpentine Receptors or 7transmembrane receptors |
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Term
| for cAMP, the effector enzyme is... |
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Definition
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Term
| Gs stimulates adenylyl cyclase after being activated by ligands, such as |
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Definition
| catecholamines, b adrenoceptors, histamine, vasopressin, glucagon, fsh, lh, thyrotropin, parathyroid hormone |
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Term
| Receptors are dynamically |
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Definition
| regulated in number, location, and sensitivity |
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Term
| What causes desensitization? |
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Definition
frequent or continuous exposure of the receptor to the agonist over a short period of time
rapid and reversible process that desensitizes tissue to further receptor-agonist interaction |
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Term
| Internalization of receptor molecules |
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Definition
occurs following frequent or continuous exposure of the receptor to the agonist over a relatively short period of time.
Receptors are recycled, intact, to the plasma membrane via endocytic vesicles |
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Term
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Definition
occurs after prolonged or repeated exposure of cells to the agonist over a LONG period of time
decreases the number of receptor molecules present in the cell or tissue and is less readily reversible |
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Term
| How is down-regulation reversed/recovered? |
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Definition
| it requires the biosynthesis of new receptor molecules for recovery |
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Term
| What causes relative drug tolerance? |
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Definition
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Term
| What does tolerance refer to? |
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Definition
| the decrease in intensity of the response to a given dose of a drug as a consequence of continued drug administration |
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Term
| Why might tolerance occur? |
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Definition
| depletion of essential substrates required for downstream effects in the signal transduction pathway following continuous activation of the receptor-effector system |
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Term
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Definition
| when receptor activation is blocked for long periods of time by pharmacologic antagonists or by denervation |
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Term
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Definition
| the ability of the drug to accomplish a specified effect |
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Term
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Definition
| the amount of drug required to cause an effect |
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Term
| Potency of a drug depends on |
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Definition
the affinity of the drug for binding to the receptor
the efficiency of the occupancy response coupling process |
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Term
| Clinical Effectiveness depends on |
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Definition
| maximal therapeutic efficacy and its ability to reach its site of action |
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Term
| Quantal Dose-Response Curve |
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Definition
| represents the percentage of individuals or lab animals under study who exhibit a specified drug effect, plotted as a function of log drug dose |
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Term
| What does a quantal dose response curve illustrate? |
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Definition
| the potential variability of responsiveness to the drug among a population |
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Term
| The therapeutic index is defined, in ratio, as |
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Definition
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Term
| The Therapeutic Window of a drug |
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Definition
| describes the dosage range between minimum effective concentration and minimum toxic concentration |
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