¡GoConqr estrena diseño! Cuéntanos qué te parece.

Regístrate gratis

Fichas

aug 25

Shylla T Inglés 148 fichas

Fichas del conjunto (148)

  1. 1PRIMARY organ of drug metabolism.LIVER
  2. 2most important EXTRA-HEPATIC site.intestines that are part of the gastrointestinal tract
  3. 3most enzymes involved in drug metabolism are located within thelipophilic membranes of the smooth endoplasmic reticulum (SER) and some in the cytosol.
  4. 4CYP3A(4/5) AND UGTs combined by themselves metabolize>75% of drugs in use.
  5. 5CYP2D6accounts for about 5% of total human liver CYP450 content yet metabolizes about 25% of prescribed drugs.
  6. 6CLINICAL INHIBITORSGrapefruit juice(S)
    Clarithromycin(S)
    Ketoconazole(S)
    Diltiazem(S)
  7. 7CLINICAL INDUCERSSt. John's Wort(S)
    Carbamazepine(S)
    Rifampin(S)
    Phenytoin(S)
  8. 8CLINICAL SUBSTRATESNisoldipine
    Simvastatin
    Sildenafil
    Saquinavir
  9. 9CLINICAL SUBSTRATESDesipramine
    Metoprolol
  10. 10CLINICAL INHIBITORSFluoxetine(S)
    Terbinafine(S)
  11. 11CLINICAL SUBSTRATESCelecoxib
    S-Warfarin
  12. 12CLINICAL INHIBITORSFluconazole(M)
    Piperine(M)
  13. 13CLINICAL INDUCERSRifampin(M)
    Carbamazepine
  14. 14.Caffeine
  15. 15.Fluvoxamine
    Oral contraceptives(
  16. 16.Phenytoin(M)
    Smoking
  17. 17.Omeprazole
  18. 18.Fluvoxamine
  19. 19.Rifampin(S)
    Phenytoin.
  20. 20Phase I pathwayPhase I pathway is also known as functionalization reactions because these reactions often modify or
    remove existing functional groups from substrate molecules.
    As a general rule in drug metabolism,
    drug substrates often loose pharmacological activity when metabolized and become water soluble for
    faster excretion. Addition of functional groups to the drug does very little to increase the water
    solubility but can dramatically alter the biological properties of the drug.
  21. 21Phase II pathwayalso known as conjugation or synthetic reactions because the substrates often
    undergo adduct formation with molecules like sugars. The metabolic end products are highly water soluble (hydrophilic or polar) and are readily excreted via urine or feces. However, there is an exception where phase II metabolites can become relatively non-polar which has its own clinical implications. (We will review that in later section.)
  22. 22Indirect conversion of Phase I metabolite to phase II adductThe metabolic end product of phase I reaction can sequentially feed into phase II conjugation reactions forming polar adducts. However, it is not unusual for the parent drug substrates to undergo Phase II reaction directly.
  23. 23Excretion of polar species from phase 1 and 2 pathwaysMetabolites formed from either phase 1 or phase 2 metabolic pathways can get excreted in the urine as they are polar, water soluble molecules and cannot be reabsorbed from the kidneys
  24. 24Excretion of Adducts via Biliary RouteMost adducts formed via phase II conjugation pathways are polar metabolites that are excreted easily
    from the body. However, acetylation conjugation reaction sometimes render the metabolites relatively non-polar compare to the parent molecule hence have a particular interest b/c they are not very water soluble
  25. 25examplesulfanilamide (a sulfonamide antibacterial) often undergoes acetylation reaction
    making acetyl conjugates that have poor water solubility and can cause acute renal toxicity
  26. 26Aromatic HydroxylationHydroxylation reactions are typically very common reactions for compounds that have at least one aromatic ring in their chemical structures.
    Therefore, hydroxy-derivatives are quite ommonly seen in nature for both drugs and xenobiotics. e.g. Phenytoin
  27. 27Aliphatic HydroxylationHydroxylation reactions are also observed for some aliphatic substrates. e.g. side aliphatic chain is hydroxylated in secobarbital
  28. 28N-DealkylationThis metabolic reaction involves removal of an alkyl functional group (e.g. methyl or ethyl) attached to a Nitrogen atom. Example: Diazepam to Nordiazepam
  29. 29Oxidative DeaminationThis reaction is very common with stimulant drugs like amphetamine. The reaction involves removal of
    -NH2 functional group attached to a carbon on the side chain.
    Remember, this particular oxidative
    deamination reaction is very dierent from enzymatic oxidative deamination that occurs with neurotransmitters.
  30. 30Other Oxidation ReactionsO-dealkylation
    S-dealkylation
    N-oxidation
    Epoxidation
  31. 31ReductionReduction is the addition of a hydrogen or removal of an oxygen atom. Example azo (-N=N-) or nitro groups (-NO2) lead to formation of amines (-NH2
  32. 32HydrolysisThese types of metabolic reactions involve esterases that act on drug molecules that have an ester linkage. The reaction causes breakdown of the ester linkage producing a carboxylic acid and an
    alcohol
  33. 33Hydrolysis of peptide bondsWithin a
    peptide the cleavage can occur at the N-terminus by aminopeptidase or at the C-terminus by carboxypeptidase liberating amino acids. Endopeptidase are responsible to break the internal peptide
    bonds in proteins to form shorter peptides.
  34. 34Glucuronidationmost common conjugation reaction in our body.
    The liver synthesizes uridine diphosphate-glucuronic acid (UDPGA) from glucose-1-phosphate. UDPGA serves as a donor of glucuronic acid to various acceptors (i.e. drugs/metabolites).
    Enzymes mediating this process are called UDP-glucuronosyl transferases (UGTs)
  35. 35part 2Natural substrates include bilirubin and thyroxine. Aliphatic alcohols and phenols are commonly conjugated with glucuronide. Thus, hydroxylated metabolites can be conjugated, for example
    morphine
  36. 36SulfonationSecond most important conjugation reaction.
    An important dierence between sulfate and glucuronide conjugation is that sulfate conjugation reactions are saturable when substrate concentration increases. This reaction is catalyzed by sulfotransferases (SULTs) in the cytosol of the liver and other organs.
  37. 37part 2The sulfate donor for the reaction is an activated form of the sulfate known as 3'-
    phosphoadenosine-5'-phosphosulfate (PAPS) and depletion of this cofactor can result in the saturability of the activity of the sulfotransferases.
    In humans, at least 11 sulfotransferase isoenzymes are involved in drug metabolism.
  38. 38N-acetylationIs catalyzed by N-acetyltransferases {a cytosolic enzyme found in many tissues (e.g. liver, intestine, blood, kidney)}.
    The acetyl donor is acetyl-CoA. The acetyl group can be transferred to an acceptor (e.g. an aromatic amine).
  39. 39MethylationS-adenosylmethionine serves as the methyl donor.
    There are a number of methyltransferase enzymes e.g. catechol O-methyltransferase
    (COMT) which catalyzes the transfer of a methyl group to a phenolic OH- of catecholamines. COMT is found in a variety of tissues including the liver and brain. (In cytosol)
  40. 40Glutathione ConjugationGlutathione-s-transferases (GSTs) catalyze the transfer of glutathione to reactive electrophiles.
    Glutathione performs a variety of important physiological and metabolic functions in all mammalian cells, including the detoxication of free radicals, metals, and other electrophilic compounds.
    It is involved in the biotransformation of acetaminophen (Tylenol)
  41. 41Glutathione ConjugationOver 20 GSTs occur in humans and are divided into two subfamilies: cytosolic and microsomal forms. Cytosolic forms have more importance in drug metabolism whereas microsomal GSTs are important in endogenous metabolism.
    Saturable at higher substrate levels
  42. 42Some factors that can alter metabolism are:Enzyme induction/inhibition
    Age: With aging, the liver’s capacity for metabolism through the CYP450 enzyme system is reduced by ≥ 30% because hepatic volume and blood flow are decreased.
    Disease
    Diet
    Genetic polymorphism
  43. 43Enzyme InductionSome of the chemically dissimilar P450 substrate drugs, on repeated administration, induce P450 expression by enhancing the rate of its synthesis or reducing its rate of degradation.
    Induction results in accelerated substrate metabolism and usually in a decrease in the pharmacologic action of the inducer and also of co-administered drugs
  44. 44ageConjugation pathways are poorly developed in the fetus and unconjugated bilirubin from the maternal side can pass through the placenta and raise serum bilirubin concentration in the fetus, raising the risk for bilirubin-induced neurologic dysfunction (BIND).
    The bilirubin can cross the blood-brain barrier, bind to the brain tissue and then cause neurotoxicity and the condition is often called kernicterus.
  45. 45UGT (UGT1A1)most important in the metabolism of bilirubin. Bilirubin clearance is decreased in newborns, mainly due to the deficiency of the enzyme UDP- glucuronosyltransferase (UGT)
  46. 46diseaseAcute or chronic diseases that affect liver architecture or function markedly affect hepatic metabolism of some drugs.
    Such conditions include alcoholic hepatitis, active or inactive alcoholic cirrhosis, hemochromatosis, chronic active hepatitis, biliary cirrhosis, and acute viral or drug-induced hepatitis. Depending on their severity, these conditions may significantly impair hepatic drug-metabolizing enzymes, particularly microsomal oxidases, and thereby markedly affect drug elimination.
  47. 47diet and environmental factorsDiet can affect the rate of drug metabolism. Charcoal-broiled beef can induce hepatic microsomal enzyme CYP1A2 reduce plasma concentration of drugs that are substrates to this isoenzyme. Grapefruit juice inhibits CYP3A4 enzymes in the gut wall and can increase plasma concentration of drugs such as benzodiazepines like midazolam and triazolam and caffeine.
  48. 48part 2Cigarette smokers metabolize certain drugs more rapidly than nonsmokers b/c of enzyme induction. Industrial workers exposed to certain pesticides also metabolize certain drugs more rapidly. Such differences make it very difficult to determine effective and safe doses of drugs with narrow therapeutic indices.
  49. 49genetic polymorphGenetic differences (pharmacogenetics) can affect drug metabolism
  50. 50N-acetylation polymorphisman cause patient to acetylate (i.e. addition of acetyl function) isoniazid either slowly or rapidly. Chronic treatment of slow acetylators can cause isoniazid neurotoxicity due to isoniazid-induced vitamin B6 deficiency, whereas fast acetylators might have problems achieving adequate plasma levels of isoniazid. Approximately 45% of whites and blacks in the US (and some Northern Europeans) are slow acetylators.
  51. 51part 2Warfarin (anticoagulant) is metabolized mainly by CYP2C9 in the liver to inactive hydroxylated metabolites. The VKORC1 gene is the site involved in genetic resistance to warfarin. However, depending on the VKORC1 haplotype, patients can be more or less sensitive to warfarin and might require an increase or decrease in dose accordingly. The presence of different haplotypes of VKORC1 in different patients appears to account for the 25–30% variance in the required warfarin maintenance dose.
  52. 52CYP450 InductionThe primary mechanism of of P450 enzyme induction is an increase in the expression of the enzyme chiey through increased transcription.
  53. 53mechanismNumerous drugs and environmental compounds (like industrial
    hydrocarbons, pollutants, pesticides) enter the hepatocytes where they bind and activate the PXR receptor (pregnane receptor), the complex is translocated to the nucleus, where it binds to the
    promoters of various biotransformation enzymes leading to increased expression of the CYP450
  54. 54Competitive InhibitionReversible inhibition is perhaps the most common mechanism of drug-drug interactions.
    Reversible inhibition implies that the eect of a competing drug C on the enzyme metabolizing the object drug D is the result of mutually exclusive competition between the competing drug C and the
    object drug D for binding to the enzyme.
  55. 55This competition is a function of:concentration of the two-drugs at the enzyme,
    relative binding anities of the two drugs for the enzyme-binding site.
    The timing of the onset and oset of the inhibition is dependent upon the half-life of the competing drug (in this case drug C).
  56. 56part 3Any two drugs that have the same metabolic (enzyme) pathway can display competitive inhibition.
    The interaction is of concern when the concentration and the binding anity of one drug is high enough to prevent the other drug to access the enzyme.
  57. 57Irreversible InhibitionInvolves the formation of a stable complex, between a drug and the metabolizing enzyme, is one mechanism that can result in irreversible inhibition. The rate of inhibition is rapid if involves the
    parent drug or is delayed if a drug metabolite that forms the complex with the enzyme.
    An example of delayed inhibition involves erythromycin.
  58. 58part 2Unlike competitive inhibition, the oset of irreversible inhibition is based on the formation rate of new enzyme. CYP450 enzyme half-life in humans is about 36 hours; thus, 3 to 5 days may be required for enzyme function to return to baseline following the discontinuation of an irreversible inhibitor.
  59. 59Drug ExcretionExcretion is the process by which drugs and their inactive metabolites are removed from the body.
    Excretion of drugs can occur through via urine, feces, exhaled air via lungs, saliva, sweat or tears.
    In many cases excretion of drugs/metabolites occur via urine and feces, however some drugs can be
    excreted via other specialized routes mentioned above.
  60. 60Drug EliminationDrug elimination refers to the irreversible removal of drug from the body by all
    routes of elimination. The declining plasma drug concentration observed after systemic drug absorption shows that the drug is being eliminated from the body but does not necessarily dierentiate between distribution and elimination, and does not indicate which elimination processes are involved.
    Elimination usually includes metabolism and excretion.
  61. 61Biliary Excretionan important route for the elimination of many drugs (e.g. most antimicrobials)
    and drug metabolites in man. The factors which determine elimination via the biliary tract include characteristics of the drug such as chemical structure, polarity and molecular size as well as characteristics of the liver such as specic active transport sites within the liver cell membranes
  62. 62Fecal excretionMost drugs that do not get absorbed are often excreted via the fecal route.
    Drugs/metabolites excreted
    via biliary route are often excreted via feces in signicant amounts.
  63. 63Excretion in breast milkMany drugs are present in mother's blood can be detected in her milk. Remember, lipophilicity which is the most important physiochemical characteristic that drugs should possess to cross the
    biological membranes;
    Fick's law that explains the importance of concentration gradient for
    ecient drug transfer occur across biological membranes; degree of ionization that controls the relative proportions of lipophilic and hydrophilic counterparts for a drug/metabolite; plasma
    protein binding that only allows the free fraction to cross the membranes. All these factors can be interrelated with drug excretion in breast milk.
  64. 64Pulmonary excretionA minor route of excretion. Drugs that are used as volatile anesthetics are primarily excreted via exhaled air.
  65. 65Salivary excretionAnother minor route for excretion of drugs. Drugs with high saliva to plasma ratios would indicate elimination via salivary route
  66. 66Clearancemeasure of drug elimination from the body without identifying the individual mechanism or process. Clearance (also known as systemic clearance or as total body clearance) considers the entire body as a drug-eliminating system from which many elimination processes may occur.
  67. 67Total or systemic clearancesum of clearances from various major eliminating organs
    or we can say that total or systemic clearance can be represented by:
  68. 68Factors Affecting Enterohepatic Recycling of Drugs..
  69. 69Liver disease or injurycholelithiasis, liver cirrhosis) may impair bile secretion thereby aecting elimination
    of certain drugs via biliary
    route.
  70. 70Ageon both ends of continuum (neonate v/s
    geriatric)
  71. 71Chronic administration of certain drugs likephenobarbital can augment the rate of bile flow or by metabolic enzyme induction.
  72. 72Co-administration of drugs like ion exchange resinsbind to drugs like antibiotics and
    estrogens disrupting their enterohepatic recycling leading to their fecal elimination. (ion exchange resins are used for lowering cholesterol)
  73. 73Pulmonary Excretion of DrugsAny drug that is volatile in nature and is circulating in the vasculature would undergo excretion via pulmonary route.
  74. 74Factors that aect drug loss via pulmonary routeRespiration rate
    Pulmonary blood ow
    Aqueous solubility (low water solubility promote rapid gaseous exchange in alveoli)
    Increased cardiac output has greater eect on removal of poorly soluble
    gases
    Highly soluble volatile drugs slow removal via lungs (e.g. ethanol)
  75. 75Factors that can aect excretion of drugs in lactating mother's milk.Drug concentration in maternal blood
    Drug's plasma protein binding
    Lipid solubility of the drug
    Ionization constant (pKa) of the drug in maternal blood.
  76. 76Excretion of Drugs via Sweat and SalivaMinorroute of excretion.
    Excretion dependent upon diffusion of non-ionized drug species (pH and pKa).
    Some drugs that partition in saliva can be tasted in the mouth even afteri.v. administration
  77. 77PHARMACODYNAMICSBiochemical & physiological effects of Drug
    Drug + Receptor Effect(s)
  78. 78Receptors are found onproteins, glycoproteins, proteolipids
  79. 79Covalent bondsharing a pair of electrons
    long lasting
    nitrogen mustard, phenoxybenzamine
  80. 80Ionic bondelectrostatic attraction Forces between charged ions can be separated under physiological conditions
  81. 81.A Selective b receptor Agonist
    Stimulates b1 and b2 receptors
  82. 82.A Selective b receptor Antagonist (more correctly an inverse agonist) blocks b1 and b2 receptors
  83. 83Ionotropic receptorsReceptors coupled to ion channels
    Ion Conductance:
    Voltage gated
    Ligand gated 2nd messenger regulated
  84. 84Metabotropic Receptors IReceptors coupled to G-Proteins (Indirect coupling)
  85. 85Enzyme-linked receptorsGrowth factors
    Cytokines
    Insulin
    Tyrosine kinases (often)
    Tyrosine phosphatases
  86. 86Type 1 Receptorin cytosol- Sex hormones, glucocorticoids, mineralocorticoids
  87. 87G-proteinsTransduce extracellular stimuli intracellular Responses
    a change in [2nd messenger molecule]
    Involved in signaling, membrane vesicular transport, cytoskeletal assembly, protein synthesis
  88. 88Most G-Proteins are heterotrimersa b gamma
  89. 89Multiple forms of each subunit existsa binding & hydrolyzing Interacts with Receptors & Effecter proteins
    by hydrophobic anchors G-protein holoenzyme Signaling
    G-Proteins are freely diffusible
  90. 90Small G-Proteins-monomeric- belong to the Ras superfamily of small GTPases
    Signaling
    posses GTPase activity
    Cycles through GDP/GTP exchange
  91. 91Some targets of G-proteinsAdenylyle cyclases- multiple types
    Guanylyl cyclases (membrane bound type 1; Soluble type 2)
    Phospholipase C (PLC) (multiple types)
    Phospholipase A (A1 and A2)
    Ion channels
  92. 92Third” messengersProtein kinases
    PKA, PKC, PKG
  93. 93G-protein familiesGs, Gi, Gq, G12/13
  94. 94GTPase activating proteins (GAPs)Promote hydrolysis of GTP to GDP
    Thus, they increase GTPase activity of the a-subunit
    inhibit G-protein function
  95. 95GTPase inhibitory proteins (GIPs)Suppress hydrolysis of GTP to GDP
    They decrease GTPase activity of the a-subunit
    Promote G-protein function
  96. 96Receptor subtypes:are different in Amino Acid sequence
    can have different signal transduction systems
  97. 97exserotonin
    5-HT2A can use Gq/PLC
    5-HT3 receptor uses ion channel
  98. 98Drugs & Neurotransmitters will have different affinity for them can be found in same tissue But sometimes one subtype dominatesDrugs & Neurotransmitters will have different affinity for them
    can be found in same tissue But sometimes one subtype dominates
  99. 99At the Receptor levelPersistent agonist stimulation
    down-regulate Receptor # or Density
    subsensitivity
    Chronic deprivation of Receptor excitation
    up-regulate Receptor # or Density
    supersensitivity
  100. 100A brief exposure to an agonist or a reversible competitive antagonist usually does not alter Receptor affinity or its density.
  101. 101At Post-receptorc-AMP
    Desensitization
    tachyphylaxis
    Tolerance
  102. 102DesensitizationOccurs via phosphorylation
    Protein Kinase
    Protein Phosphatase
    Receptor Protein
    Homologous: agonist-dependent
    Heterologous: agonist-independent
  103. 103Homologous: agonist-dependentrequires 2 types of proteins
    G -Protein-coupled receptor kinases (GRKs) 7 types
    only phosphorylate agonist occupied Receptors
    initially minimal desensitization
    But receptor affinity for arrestin(s)
    Maximal desensitization
  104. 104Heterologous: agonist-independent2nd messenger-dependent kinases
    PKA & PKC
    agonist-stimulated & other Receptors 40-50%
  105. 105Arrestinscan initiate their own signaling to produce specific effects
  106. 106LigandNonspecific term
  107. 107Full agonistA Ligand that binds to the orthosteric binding site of a receptor and produces a maximal effect
  108. 108Partial agonistProduces a smaller maximal Effect following binding to the orthosteric site of the receptor
  109. 109part 2need to occupy all Receptors to produce a
    Maximal Effect
    No spare receptors
    antagonize the effects of full agonists
    have lower efficacy than full agonists
    can be more potent than a full agonist
    can have a greater affinity than a full agonist
  110. 110Inverse agonistBinds the orthosteric receptor site and produces an effect opposite to agonists
  111. 111AntagonistBinds the orthosteric site but does not produce a direct effect by itself (Modern name silent/neutral antagonist). An antagonist prevents the effects of agonists or inverse agonists
  112. 112Allosteric modulatorBinds the allosteric site
    of the receptor and modulates agonist’s
    affinity and/or efficacy
  113. 113Efficacy ability of a DrugMaximal Effect
  114. 114part 2Full agonists efficacy = 1
    Partial agonists efficacy = > 0 < 1
    Full inverse agonists efficacy = -1
    Partial inverse agonists efficacy = > -1 < 0
    Antagonists (Neutral) efficacy = 0
  115. 115EfficacyIntrinsic Efficacy / total [Receptors]
  116. 116Intrinsic Efficacy (activity)amount of stimulus a Drug applies to a Receptor does not vary among tissues stimulant property of a Drug
    Efficacy Varies......... dependent upon Receptor #
  117. 117Constitutively active Receptors IA small % of some receptor (R) populations elicit responses in the absence of agonists
  118. 118Full agonists preferentially bindR* maximally enrich R* & maximally increase effecter activity
  119. 119Partial agonists showa weaker preference for R* & shift the equilibrium to a smaller extent
  120. 120Inverse agonists preferentially bindR & reduce basal activity
  121. 121Silent Antagonists do notaffect the equilibrium since they bind equally to R* & R
  122. 122Constitutively active Receptors IIIAntagonists of 5-HT3R and 5-HT4R suppress gastrointestinal motility (GI)
    This suggests that endogenous serotonin (5-HT) increases GI motility
    However, such antagonists still block GI motility when all of intestinal 5-HT is depleted by gene deletion or other means
    Thus, inhibitory effects of these antagonists are independent of 5-HT
  123. 1235-HT3R and 5-HT4R present in the gut are constitutively active. Thus, their “antagonists” are really acting as inverse agonists.
  124. 124Biased agonistscan stabilize a receptor to one or more
    conformation(s) which could be coupled with different
    signal transduction system(s).
  125. 125Biased ligandscan have different affinity/efficacy (e.g. agonist, antagonist, or inverse agonist) for these different receptor conformations
  126. 126Affinityis the strength or ability of a drug to bind its receptor (R)
    Defines the relative onset and offset of the drug molecule to its receptor since affinity = K1/K-1
    It is unique for each drug for a given receptor
    A high affinity drug has a much greater tendency to bind the receptor
  127. 127Equilibrium Dissociation Constant (Kd):measure of concentration of a drug
  128. 128Inverse relationship between Kd and affinityif Kd = 0.1 nM then affinity is high = 10; if Kd = 100 nM then affinity is low = 0.01
    The smaller the Kd, then the greater the affinity of the drug for its R
    The greater the affinity of a drug, the less drug required to occupy 50% of its Rs
  129. 129Observed effect “E/Emax” is determined by[D] and its affinity (Kd). Thus, effect is related to the degree of receptor occupancy
  130. 130Observed “effect”dependent upon receptor occupancy and the propensity of the drug to activate its receptor “e = intrinsic efficacy”
  131. 131If Effect produced is directly proportional to the degree of drug binding its receptors, thenKd = ED50
  132. 132dose response relationshipCan determine EC50 and compare relative potency of different drugs
  133. 133Chemical Antagonismchelation Pb, arsenic, gold by dimercaprol
    not common
  134. 134Functional AntagonismAcetylcholine Heart Rate
    Norepinephrine Heart Rate
  135. 135Competitive AntagonismEquilibrium
    Nonequilibrium
  136. 1361-Equilibrium CompetitiveSurmountability of antagonism
    Change in antagonist occupancy
    Rightward parallel shift (//) in log agonist dose/response curve
    No reduction in maximal response
    No change in slope
    // rightward shift in D/R = dose ratio
  137. 137If antagonist dose versuss one agonist dose.
  138. 138Nonequilibrium competitiveIrreversible antagonism
    Dissociates slowly or not at all Covalent bond
    No change in antagonist occupancy
    occurs by large doses of agonist
    Antagonism is not surmountable
  139. 139Max Response & slope when [antagonist],
  140. 140Potencyrefers to the dose or [Drug] to produce a given effect
  141. 141Potency depends uponKd (affinity)
    receptor density
    drug’s efficacy
    Efficiency of Drug-Receptor interaction coupled with Response
  142. 142Efficacyreflects the limit of Dose/Response relationship on the response axis
  143. 143A partial agonist may have a greater potency, but never a higher efficacy than a full agonist.
  144. 144Spare ReceptorsMaximal Response occurs at a drug concentration that does not lead to full occupation of all Receptors
  145. 145SRs can be coupled to response Presence of SRs can be demonstrated by an irreversible antagonist (nonequilibrium competitive) e..
  146. 146EC50 is not always an accurate reflection of Kd since EC50 may not occupy 50 % of total receptor poolThus, Kd ( i.e. affinity) of an agonist
    can not be determined fro a D/R curve
  147. 147Therapeutic Index (TI)A measure of impunity with which an overdose can be given
  148. 148Has limitationsbased on animal toxicity data and not human some toxicities are idiosyncratic
    toxicity depends on clinical status
    ED50 is not often definable

Información

Descripción
Fichas sobre aug 25, creado por Shylla T el 25/08/2020.
Creado por
Shylla T
Visitas
0
Valoración

Escríbenos

¿Sobre qué es tu mensaje?

¿Qué te parece el nuevo diseño?

¿Te gusta?