B1: Pharmacology Flashcards

Question

Active Transport (2 ex.)

Answer 1

- REQ energy (Na/K ATPase) 1. P glycoprotein: ATP binding cassette Carrier; binds to lipophilic drugs that entered cell via passive diffusion so mediates EFFLUX from cell; acts to limit oral absorption of drugs by transpotring them back to GI tract 2. Secondary active transport: uses electrochemical energy stored in a gradient to transport another molecule against its concentration gradient

Answer 2

Fraction of the dose that reaches the systemic circulation - IV drug F=1 - oral drugs F

Answer 3

Drug passes through liver where metabolism can occur. | -if metabolism by liver is large, F is reduced, and low potency of drug

Answer 4

Two drugs prepared w/ same active ingredients at same amounts and delivered by same route are bioequivalent if EXTENT and RATE of drug delivery to the circulation are the same.

Answer 5

- passive absorption (favors unionized state --acid HA form, base B form) - upper intestine

Answer 6

ADV: reduced frequency of admin, more stable drug concentrations in body, logical for short half life drugs DIS: greater inter patient variability, if dosage form fails large amounts of drug are dumped into blood thus toxic.

Answer 7

- venous drainage from mouth to SVC, avoids liver / 1st pass effect - lipophilic drugs (pass through membranes; normally would be inactivated in liver)

Answer 8

- epidermis is lipid barrier, ONLY lipophilic drugs absorbed this route - hydrated skin more permeable

Answer 9

- drug solubility in interstitial fluid | - area of capillary bed in vicinity

Answer 10

- blood flow to muscle (enhanced by exercise) | - fat content in muscle

Answer 11

- regional blood flow (initially the highly perfused get most of drug- liver, heart, kidney, brain) - capillary permeability of the drug (loose endothelial junctions=rapid diffusion into interstitial space)

Answer 12

Albumin (lots of pos. Charges)

Answer 13

Alpha 1-acid glycoprotein (lots of neg charges)

Answer 14

- severe liver disease = hypoalbuminemia (reduces protein binding for acidic drugs) - crohn's or arthirits --> immune activation = increase alpha 1 acid glycoprotein (thus need to increase drug dose)

Answer 15

- fat | - bone (tetracyclines and other divalent metal chelating agents)

Answer 16

Drug action is TERMINATED because the drug redistributes from its site of action to other tissues -factor for: highly lipid soluble drugs, site of action in brain or cardovascular sys, admin via iv or inhalation

Answer 17

- Who: patients suffer severe HYPOtension following admin of anti hypertensive debrisoquine - Drug: debrisoquine - Poor metabolizer (can be homo or heterozygous - homo = more severe); results in increased concentrations and decreased metabolism of debrisoquine - Ultrafast metabolizer: gene duplication of NORMAL allele up to 13 times (more duplications = faster processing); more rapid drug clearance - Metabolizes 25% drugs; including ANTIDEPRESSANTS

Answer 18

- ANTI CONVULSANTS (phenytoin) = poor metabolizers have increased drug levels and side effects - PPIs (omeprazole) = poor metabolizers have higher drug levels higher gastric pH, and better control of GERD **this case the poor metabolizers have a better short term outcomes - ANTI PLATELET DRUGS (clopidogrel) = activated by CYP2C19; those with even 1 slow allele have less active drug and >50% increase in MI and stroke; omeprazole decreases activation of clopidogrel, increasing risk for cardiac events

Answer 19

Two functions: 1) Binds drugs (or ligands, L) 2) Transduces binding into a response. Many drugs produce their effects via receptors, because they are

Answer 20

- POOR metabolizer: 2 variants *2 and *3 (*1=normal) - Warfarin (anticoagulant) cleared by CYP2C9 * 3 much larger impact on warfarin clearance and dosing than *2 - *2 and *3: decrease warfarin clearance, increase warfarin half life, increase risk of bleeding, need lower maintainance doses - no ultrafast variant

Answer 21

- VKORC1: required for clotting factor maturation; warfarin is a competitve inhibitor - haplotypes and clades of VKORc1 = predictors of warfarin dose (10 common SNPs) - Genetic Variants: A clade=(haplotypes H1, H2) need less drug, lower VKORC1 expression; B clade=(haplotypes H7,H8,H9)need more drug, increased VKORC1 levels

Answer 22

- Variant responses to SUCCINYLCHOLINE (depol. Muscle relaxant) due to reduced activity of pseudocholinesterase - atypical patients experience apnea and paralysis for 2-3 hours (due to decreased activity of pseudocholinesterase)

Answer 23

- if TPMT polymorphism then not as much 6Mercaptopurine is inactivated as anticipated, thus more 6MP active = bone marrow toxicity - Low activity allele has 2 SNPs in TPMT gene (normal/normal-(phenotype)norm risk bone marrow supression; normal/slow-elevated risk; slow/slow-high risk)

Answer 24

- OATP1B1: organic anion transporter that imports many drugs and endogenous compounds blood to liver - Low activity variants in SLCO1B1 gene=decreased drug uptake into the liver, thus higher drug levels in the plasma - strongest genetic evidence to date is for SIMVASTATIN (drug used to inhibit cholesterol biosyn) - Low activity variants have increased simvastatin blood levels and increased risk for skeletal muscle toxicity - some drugs are strong inhibitors of OATP1B1, thus increasing the risk for simvastatin toxicity (such inhibitors can further enhance the risk in those with low activity alleles)

Answer 25

Example - Tylenol 3 w/codeine - CYP2D6 activates a portion of codeine to morphine - 2D6 poor metabolizers will not get the expected pain relief - ultrafast metabolizers generate too much morphine from codeine

Answer 26

Drugs that are converted to their active form by metabolic enzymes

Answer 27

Oxidation, reduction, dealkylation, hydrolysis Often introduce or reveal a functional group *Not necessarily first Enyzmes usually in smooth ER

Answer 28

Conjugation of the drug or drug metabolite to an endogenous substrate molecule Most enzymes are cytosolic Makes metabolites usually more polar (easier to excrete), inactive/less toxic Some enzymes inducible, Vmax limited by conventional enzyme kinetics and conjugant supply

Answer 29

Applies to ORALLY administered drugs Portal venous system transports drugs to liver; significant metabolism (hepatic or intestinal) can occur prior to reaching circulation Can greatly reduce oral bioavailability of a drug (F)

Answer 30

-Phase I: hemeprotein, major catalyst -Anchored to the cytoplasmic face of smooth ER -Many isoforms (~10-20 P450s per every P450 Reductase) -CYP2B10: Cytochrome P450; 2=gene family (>40%); B=gene subfamily (>55%); 10=isoform -18 families; 3 involved in drug metabolism - CYP1, CYP2, CYP3 -Broad substrate specificity - each isoform can have several to hundreds of drug substrates CYP3A - 50% of drugs CYP2D6 - 25% CYP2C9 - 15% CYP1A2, CYP2E1, CYP2A6, CYP2C19 -

Answer 31

Flavoprotein Electron source in the P450 catalytic cycle (gets electrons from NAPDH) One isoform

Answer 32

S + O2 + 2e- + 2H --> SO + H2O S=substrate (drug) Reaction in P450 catalytic cycle

Answer 33

- Localized in smooth ER - Catalyzes monooxygenation reactions, primarily of soft nucleophiles (S, N, Pe, Se); primarily N-oxidation and S-oxidation reactions - hundreds of potential substrates, more polar and less toxic/active - required components: FMO, NADPH (electron source), O2, drug - 5 isoforms (FMO1-5); FMO3 major liver isoform - NOT significantly induced or inhibited - so fewer drug-drug interactions!

Answer 34

- UDP-glucuronosyl transferases (UGT) - UDP-glucuronic acid - HIGH conjugation capacity - HIGH abundance * *enzyme is on the lumenal face of the ER (an exception to the usual phase II enzyme cytosolic location)

Answer 35

- N-acetyltransferases (NAT) - Acetyl-coA - Variable conjugation capacity - Variable abundance

Answer 36

- Sulfotransferases (SULT) - Adenosine-3'-phosphate-5'-phosphosulfate (PAPS) - LOW conjugation capacity - LOW abundance

Answer 37

- Glutathione S-transferases (GST) - Drug itself: arene, oxides, epoxides, etc - LOW conjugation - LOW abundance **some ER enzyme, but mostly cytosolic

Answer 38

Exposure to drugs/environmental chemicals that markedly upregulates enzyme amount and/or activity MOST cytochrome P450s are inducible *CYP2D6 not as inducible as others Environmental inducers: tobacco smoke (1A), St John's Wort (3A), ethanol (2E1) Induction increases or decreases drug effects : - decrease when metabolites are inactive - increase for drugs that are activated by induced enzyme *Inducers may or may not be substrates How fast to act? 1-2 days max

Answer 39

Drug or environmental chemical may inhibit the metabolism of several drugs - usually activity decreases Types of inhibition: - competitive (most common) - non-competitive (disrupt function, bind heme of CYPs) Extent of inhibition variable (CYP2D6 can be decreased to near zero) Onset: rapid/immediate Grapefruit juice: inhibits intestinal CYP3A -> increases bioavailability of CYP3A substrates

Answer 40

Genetically controlled variations in drug response Genetic factors can alter an individual's response to a drug - genetic polymorphisms - less common genetic variants

Answer 41

Specific genes vs expression of genotype

Answer 42

Mendelian trait that exists in the population in at least two phenotypes - neither of which is rare (represents greater than 1% of total)

Answer 43

Change in a single base pair in the DNA that differs from wildtype

Answer 44

Closely linked genetic markers on a chromosome that tend to be inherited together (often within gene or closely linked genes)

Answer 45

Cluster of SNPs that occur together in an individual (and are of interest to a phenotype) -useful for categorizing individuals to understand how clusters of SNPs contribute to phenotype

Answer 46

1=p2 + 2pq + q2 p: proportion of wild type alleles q: proportion of variant alleles

Answer 47

N-Acetyltransferase-2 is a phase II enzyme responsible for metabolism of the anti-TB drug isoniazid -Fast vs Slow acetylators - autosomal recessive trait "slow" = homozygous for "slow" allele Ethnic variations Slow acetylator phenotype has been associated with: - increased neuropathy (due to isoniazid) - arylamine-assoc bladder cancer - hypersensitivity to sulfonamides - higher incidence of lupus

Answer 48

Ligand is a substance that forms a complex with a biomolecule. A ligand that binds to a receptor, alters the function of the receptor to trigger a physiological response, is called an agonist.

Answer 49

= k2/k1 or =[L]* ([R]/[LR]) Equilibrium dissociation constant, and also describes the "goodness of fit" between ligand and receptor. Inversely related to the affinity of ligand for the receptor. Units: concentration

Answer 50

Tendency of a molecule to associate with another. I.e. the affinity of a drug = ability to bind to its biological target (receptor, enzyme, transport system, etc). Frequency with which the drug will reside at a position of minimum free energy within the force field of that receptor.

Answer 51

(α) Measure of the ability of the LR complex to elicit the effect being measured Ratio of the Emax of the ligand of interest to the Emax of a full agonist. AKA efficacy

Answer 52

α=0 (zero intrinsic activity)

Answer 53

Partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. alpha is less than 1 but greater than 0.

Answer 54

Increases the sensitivity of the cell to a low concentration of ligand. Together with the normally low affinity of endogenous agonists, the presence of spare receptors allows for high sensitivity without long activation time.

Answer 55

The goal of drug therapy; it is the concentration of the drug in the body that needs to be maintained to produce the desired effect with minimum toxicity. Above therapeutic window can be toxic. Below are ineffective.

Answer 56

A measure of the apparent space in the body available to contain the drug. Assumption: concentration of drug throughout body is same as its concentration in plasma/serum.

Answer 57

Rate of elimination/concentration in respect to blood, plasma, or serum depending upon the concentration that is used. Unit: liter/min Clearances are additive: CL renal + CL liver For most drugs, processes involved in elimination are not saturable in range of drug concentrations used, so clearance is constant.

Answer 58

Directly proportional to the drug concentration. =Vmax * (C/(Km +C)) or =CL * Concentration

Answer 59

T1/2 = 0.69/ke1 T1/2 = (0.69* Vd)/CL Time required to decrease the concentration of the drug by one half. It is constant in first-order kinetic drugs. Also, the time required to change the amount of drug in the body by one-half. Dependent on volume of distribution and clearance.

Answer 60

Larger dose of the drug that allows for therapeutic levels to be achieved immediately. Usually administered once, and then followed up with maintenance dose. =(Vd * C0)/F C0= desired therapeutic concentration Useful for very long half-life drugs, or antibiotic therapy.

Answer 61

= ((Css * CL)/F) * Interval Maintains therapeutic effectiveness after loading dose.

Answer 62

Monospecific antibodies and specific because they are produced by 1 type of immune cell that are all clones of a single parent cell. - highly specific - high affinity - long half life in vivo

Answer 63

- Admin--subcu/intramuscular: 24-95% bioavail; 7-8 days peak serum conc.; absorbed slowly by convective absorption through lumph vessels and by diffusion into blood vessels; limited by volume that can be injected at these sites - extracellular distribution - does not cross BBB

Answer 64

Intracellular receptors for small hydrophobic signaling molecules such as steroid hormones, thyroid hormones, retinoids and vitamin D are ligand-activated transcription factors. 2 unique features: 1. Receptors are intracellular and bind ligands in cytoplasm or nucleus 2. Receptors are ligand-activated transcription factors Contains a hormone binding site, a DNA binding domain, and a transcription activating domain.

Answer 65

Composed of multiple subunits which may have arisen from common gene family. Receptor directly gates ion channel. Major target for drugs. Rapid signaling.

Answer 66

Multi component system, GPCRs comprise a large family of common receptors (~1000) that mediate effects of: neurotransmitters, light, odorants, hormones, and other extracellular messengers. A GPCR is a single protein that passes through the plasma membrane SEVEN times (has seven transmembrane domains).

Answer 67

Guanine nucleotide binding proteins. Link the ligand-activated GPCR to effector enzymes. Receptor provides specificity, and the heterotrimeric G protein is the transducer. Effector provides the catalytic component to generate the second messenger. Switch between two states: GDP-bound (inactive) --> GTP-bound (active) Contain three different proteins: G(alpha): binds GTP, binds effectors, acts as a GTPase G(beta and gamma- together form the beta-gamma dimer): anchor to membrane and has its own effector

Answer 68

G(alpha): binds GTP, binds effectors, acts as a GTPase Three types of G alpha protein, used for classification: Ga (s)- stimulates adenylyl cyclase Ga (i) - inhibits adenylyl cyclase Ga (q) - stimulates phospolipase C

Answer 69

Diverse group of receptors with different enzymatic activities, includes: Tyrosine kinase linked receptors, serine/threonine kinase linked receptors, protein phosphatase linked receptors, guanylyl cyclase linked receptors

Answer 70

Aka. Receptor-linked tyrosine kinases or receptor-associated tyrosine kinases. Structure: Single protein with one TM domain which dimerizes upon ligand binding - OR tetramer composed of two extracellular subunits and two TM subunits. Mechanism: The extracellular domain/subunits bind the ligand. Cytoplasmic domain has tyrosine-specific protein kinase activity, but can also bind tyrosine-specific protein kinases or proteins with other enzymatic activities. Ligand binding will lead to: dimerization, activation by cross-phosphorylation (intermolecular auto-phosphorylation), binding of intracellular signaling molecules. Function: regulate cell proliferation and differentiation in response to hormones (like insulin), growth factors (like epidermal growth factor), and play important roles in oncogenesis.

Answer 71

EGF receptor is a type of protein kinase, specifically a tyrosine-specific protein kinase. Mutations in the EGF receptors or in the Ras occur in several types of tumors. These mutations cause abnormally high activity of this pathway and may promote tumorigenesis and metastasis. See: Gefitinib and Erlotinib

Answer 72

DNA binding proteins that regulate transcription of specific genes. Examples) CREB, Myc, Fos, Jun, etc. Signal transduction cascades regulate many properties of TFs, including their nuclear translocation and ability to bind DNA. Once activated, TFs induce transcription by activating RNA polymerase, resulting in transcription from mRNA from the target gene.

Answer 73

Some TFs are activated when they are phosphorylated by protein kinases, and inactivated when they are dephosphorylated by protein phosphatases.

Answer 74

Function: Catalyze addition of phosphate group to side chain of amino acids of proteins and peptides. Classified according to the type of amino acid which is modified: - serine/threonine specific protein kinases: PKA, PKC, Calmodulin-depdendent protein kinase, MAP kinases - tyrosine specific protein kinases: EGF receptor and other tyrosine kinase linked receptors - dual specificity protein kinase: phosphorylate both threonine and tyrosine (MAP kinase kinase, such as MKK1)

Answer 75

Function: catalyze cleavage of phosphate group from side chain of amino acids of proteins and peptides. Also classified into different groups but less variety than protein kinases.

Answer 76

Small diffusible signaling molecules that are generated in response to ligand receptor binding and activate other downstream signaling molecules. Examples (and other notecards in this deck): cAMP, IP3, DAG

Answer 77

Generated by adenyl cyclase which is activated by the Ga (s) protein. Activates cAMP dependent kinases (ie PKA)

Answer 78

``` Generated when PLC cleaves PIP2 into DAG and IP3 Activates PKC (protein kinase C) ```

Answer 79

Generated when PLC cleaves PIP2 into DAG and IP3 | Binds to IP3 receptors on the ER, causing release of Ca2+ from the ER

Answer 80

Generated by opening of ion channels | Activates PKC and other protein kinases

Answer 81

1. Cyclic nucleotide pathways - cAMP pathway regulated by GPCRs coupled to Ga (s) - cAMP pathway regulated by GPCRs coupled to Ga (i) 2. Phospholipid hydrolysis pathway - inositol-lipid pathway 3. Monomeric G protein pathways (involving Ras, Rho, Rac, Rap, etc) - important participants in the MAP (mitogen activated protein) kinase signaling cascade

Answer 82

Aka small G proteins, small GTPases, small GTP-binding proteins, and p21 proteins. Recruited to receptor linked tyrosine kinases and turned on by GEF, and turned off by GAP. Important participants in the MAP Kinase Signaling cascade.

Answer 83

Heterotrimeric G proteins are activated by direct interaction with a GPCR. Monomeric G proteins are activated by direct interaction with a GEF.

Answer 84

Turns on monomeric G protein. Example) Sos is a GEF that activates Ras (prototypic monomeric G protein). Sos is activated when it is recruited to activated tyrosine kinase linked receptors by adaptor proteins (like GRB2). Ras + GEF = Ras-GDP releases bound GDP and binds to GTP, and thus forms ACTIVE Ras-GTP complex which then can activate other molecules.

Answer 85

Turns off monomeric G protein.

Answer 86

A MAP Kinase Kinase Kinase (MAPKKK) phosphorylates a Map Kinase Kinase (MAPKK) which then phosphorylates a Map Kinase (MAPK). Lol. So MAPKKK -> MAPKK -> MAPK. The final phosphorylated MAPK usually phosphorylates a TF, resulting in increased gene transcription.

Answer 87

Ras! Ras couples tyrosine kinase liked receptors to the MAPK Signaling cascade. Ligand binds to tyrosine-linked receptor, which dimerizes and cross-auto phosphorylates. The phosphorylated receptor binds to the adaptor protein called GRB2. GRB2 binds both the receptor and GEF (Sos) --> Sos activates Ras (via GDP release and binding GTP) --> Ras-GTP activates MAPKKK (Raf) --> Raf phosphorylates MAPKK (MKK1) --> MKK1 phosphorylates MAPK (ERK) --> ERK phosphorylates several TFs leading to more gene transcription.

Answer 88

Tyrosine kinase inhibitors target kinase domain of EGF receptor and inhibit signaling by the EGF receptor. Efficacy is enhanced by presence of mutations in the EGF receptors expressed by the tumor. These drugs decrease tumor burden in 80% of patients who have tumors with mutated EGF receptors. In contrast, drugs are effective inly ~10% of patients who have tumors without EGFRs. Detection of EGF Receptor mutations in tumors may identify patients who will benefit the most from these drugs.

Answer 89

Modulation of signals is possible by adaptation in response to the intensity and frequency of stimulation.

Answer 90

Type of adaptation: Regulates the number (amount) of receptors (which determines sensitivity for the ligand) and may promote degradation of both the receptor and ligand. In absence of ligands, receptors are not localized specifically. Upon binding of ligands, receptors migrate to coated pits and endocytosis occurs. Electron dense cage formed by structural protein clathrin. Vesicle pinches off and fuses with tubular-reticular structures termed CURL. Most of the dissociated ligands incorporation into vesicles which fuse with lysozymes, some may be recycled (retroendocytosis). Free receptor in CURL may recirculate to cell membrane or be sequestered or degraded (down regulation mechanism). Internalized ligand never enters cytoplasm.

Answer 91

- NT: Somatic motor nicotinic receptors (Nm); Autonomic preganglionic nicotinic receptors (Nn), postganglionic muscarinic receptors (M) - Synthesized from choline and Acetyl CoA (choline uptake into nerve terminals is rate-limiting step); enzyme – Choline acetyl transferase - Transported into vesicle, released into synaptic cleft by exocytosis (exocytosis inhibited by botulinum toxin)

Answer 92

- Ligand gated ion channels; activation always causes rapid increase in cellular permeability to Ca and Na depolarization and excitement - Exists at NMJ (Nm), autonomic ganglia, adrenal medulla, CNS (Nn), some non-neuronal tissues

Answer 93

- All G protein-coupled receptors - M1, M3, M5 – Gq – depolarize – activate PLC, IP3, DAG (and thus Ca and PKC) - M2, M4 – Gi – hyperpolarize – inhibit AC (lower cAMP); activate potassium channels (hyperpolarize), and inhibit vg Ca channels

Answer 94

-Released upon depolarization -Removed from synaptic cleft by: • Reuptake into nerve terminals by norepinephrine transporter (NET) - MAJORITY • Diffusion from synaptic cleft • Uptake by extraneuronal transporters (ENT, OCT 2, OCT 3) -Degraded by monoamine oxidase (MAO) and catechol-0-methyltransferase

Answer 95

-Made from norepinephrine in the adrenal medulla

Answer 96

- Enzyme acting on the rate liming step in synthesis of dopamine, norepinephrine, and epinephrine) - TYROSINE –tyrosine hydroxylase DOPA DOPAMINE NOREPINEPHRINE EPINEPHRINE

Answer 97

-Blocks norepinephrine transporter (NET) resulting in more NE in the synapse

Answer 98

-Blocks the conversion of dopamine into norepinephrine

Answer 99

-Inhibits acetylcholine release into synaptic cleft

Answer 100

-Transports dopamine synthesized in nerve terminals into storage vesicles, where it is converted to norepinephrine (blocked by reserpine)

Answer 101

- Reuptakes norepinephrine from the synaptic cleft into the nerve terminals – blocked by cocaine - 87% of norepinephrine removal from synaptic cleft

Answer 102

- Oxidatively deaminates catecholamines - found on outer surface of mitochondria; located in adrenergic nerve terminals, but also widely distributed with highest amounts in liver and kidney - MAO-A and MAO-B - Eventually degrades norepinephrine into form excreted in urine

Answer 103

- Transfers a methyl group to the 3-hydroxy position of the phenyl ring - cytosolic enzyme widely distributed with high levels in liver and kidney * NOT found in adrenergic neurons - Eventually degrades norepinephrine into form excreted in urine

Answer 104

-Very rapidly hydrolyzes and inactivates acetylcholine

Answer 105

- Gq - Found in vascular and other smooth muscle, glands - Leads to contraction and secretion from glands - Activates PLC IP3 and DAG (increased Ca and PKC)

Answer 106

- Gi - Found in nerve terminals, glands, and vascular smooth muscle - Leads to decreased NE release, decreased secretion, and contraction - Inhibits AC (decreased cAMP)

Answer 107

- Gs - Found in cardiac muscle, glands - Leads to increased force and rate of contraction of heart, increased secretion from glands - Activates AC (increased cAMP)

Answer 108

- Gs - Found in vascular and other smooth muscle, skeletal muscle, and liver - Leads to relaxation of smooth muscle, glycogenolysis in skeletal muscle, and glycogenolysis and gluconeogenesis in liver - Activates AC (increased cAMP)

Answer 109

- Transfers passive immunity across placenta from mother to fetus; protects IgG from degredation, prolonging half life in serum. - espressed in: hepatocytes, endothelial cells, phagocytic cells, APCs, intestinal epithelium.

Answer 110

1-binds Fc region of IgG at ACIDIC pH (binding IgG1=IgG2=IgG4>>IgG3) 2-endocytosis into low pH endosomes--promotes IgG binding to FcRn 3-complex is resistant to lysosomal enzymatic degredation; free IgG degraded 4-complex returns to cell surface pH 7.4 IgG dissociates 5-recycles endocytosed IgG to cell surface or transmigration across cell layer (90% recycled) **antibody FRAGMENTS such as Fab lack the Fc region and do not bind FcRn

Answer 111

1-antagonism/neutralization: binding inactivates antigen; competitive inhibitor actions; decreases concentration of unbound soluble antigen in plasma 2-cell signaling inhibition: antibody binds cell surface signaling molecule which inhibits cell activation or signaling; antibody now functions as an agonist stimulating receptor; competitive inhibitor of cell surface protein either activating or inactivating path; promotes ADCC 3-Antibody dependent cellular cytotoxicity (ADCC)--explained on different card 4-Complement dependent cytotoxicity (CDC): antigen bound antibody induces lysis of target cell by activation of complement system

Answer 112

Antigen bound antibody induces lysis of a target cell by an activated NK cell, neutrophil, or macrophage - depends on Fc region - NK releases cytotoxins - Macrophage phagocytose target cell

B1: Pharmacology Flashcards

(136 cards)