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POD > POD E1 > Flashcards

POD E1 Flashcards

1
Q

Equation for bioavailability.

A

F = AUC oral/ AUC iv

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2
Q

equation for half-life

A

t 1/2 = 0.693/ ke

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3
Q

equation for volume of distribution

A

Vd = dose (iv) / C0

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4
Q

equation for clearance

A

CL = Ke x Vd

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5
Q

equation for steady state concentration

A 
Css= MD/CL or
Css= (loading dose x F) / Vd
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6
Q

equation for loading dose

A

Ld = (Css x Vd)/ F

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7
Q

What is the difference btwn a primary and opportunistic pathogen?

A

primary- can cause disease in any host

opportunistic- can only cause disease in hosts w/ impaired or damaged defense mechanisms

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8
Q

_____ is the ability of an organism to cause disease

A

virulence

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9
Q

_____ is a state where infection exists with no clinical symptoms

A

asymptomatic carriage

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10
Q

What are common routes of microbial transmission?

A

Exogenous agents:

1) aerosols: respiratory or salivary
2) fecal-oral spread
3) venereal spread
4) biting arthropods (vector)
5) vertebrate reservoir
6) vector-vertebrate reservoir

Endogenous agents part of the normal flora; ex: gut contents leaking (causes: severe trauma, surgery)

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11
Q

____ are inanimate objects which harbor microorganisms

A

fomites

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12
Q

What are specific mechanisms of transmission?

A
  • spread by fomites
  • food and water
  • direct contact (often poor hygiene)
  • social ills
  • world travel
  • living conditions
  • nosocomial infections
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13
Q

What sites of the body are normally colonized by flora?

A

nose, mouth, pharynx, GI tract, skin

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14
Q

what body sites are considered sterile?

A

blood, deep tissue, alveoli

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15
Q

What is the role of normal microbial flora?

A

provide nutrients (vitamins, fatty acids)
occupy habitat–deter pathogens
produce toxic (antimicrobial) products
stimulate host immune response

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16
Q

what are host factors that lead to opportunistic infection?

A

age (newborn, early childhood, geriatric)
cancer
nutritional status
genetic factors
pharmacological agents
HIV
breach of host surfaces (cuts/wounds/surgery, burns, medical devices/valves/catheters)
antibiotics (can wipe out normal flora!!)

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17
Q

What are Koch’s postulates? What do they apply to?

A

show that a BACTERIA is responsible for a particular disease

1) bacterium should be found in all people who have the disease; bacterium or its products should be found in parts of the body affected by the disease
2) bacterium should be isolated from lesions of an affected person & able to be maintained in culture
3) the pure culture inoculated into another should reproduce the disease symptoms
4) same bacterium should be reisolated in culture from the newly infected person

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18
Q

2 broad classes of bacterial virulence factors:

A

1) promote colonization & survival within host

2) cause damage to host cells

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19
Q

What are limitations to Koch’s postulates?

A

1) ignores role of host; susceptibility & resistance can have genetic basis & reduce the extent of correlation expected in P#1
2) importance of being able to culture bacterium: some organisms harder to culture or cannot be cultured at all (P#2)
3) variability in virulence of single bacterial species; organisms can acquire new virulence traits by genetic exchange
4) ethical problems w/ P#4; cannot ethically inoculate humans
5) polymicrobial infections: some diseases caused by combination of pathogens

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20
Q

What are limitations to Koch’s postulates?

A

1) ignores role of host; susceptibility & resistance can have genetic basis & reduce the extent of correlation expected in P#1
2) importance of being able to culture bacterium: some organisms harder to culture or cannot be cultured at all (P#2)
3) variability in virulence of single bacterial species; organisms can acquire new virulence traits by genetic exchange
4) ethical problems w/ P#4; cannot ethically inoculate humans
5) polymicrobial infections: some diseases caused by combination of pathogens

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21
Q

differences btwn prokaryotes & eukaryotes:

A

Prokaryotes: no nuclear membrane, replicate by binary fission, DNA is genetic material; few introns; translation begins w/ N-formylmethionine; respiration in plasma membrane; includes eu- & archaebacteria

Eukaryotes: membrane bound nucleus & organelles; replicate by mitosis; DNA is genetic material; most genes have introns; translation begins w/ methionine; respiration in mitochondria

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22
Q

____ are eukaryotic organisms w/ well-defined nucleus, membrane bound cytoplasmic organelles, & a cell wall; includes yeasts, molds

A

fungi

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23
Q

intracellular parasites that lack cell structure; generally consist of nucleic acid genome surrounded by a protein coat; require cellular host for replication

A

virus

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24
Q

require living host for at least part of life cycle & cause disease to host

A

parasite;

resources argue whether it is only eukaryotes or if the definition can include prokaryotes & viruses

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25
Q

what are the 2 types of viral infection?

A

lytic cycle- one/few viruses infect cells, replicate & produce 1000s, then are released by lysing host cell
persistent/latent infection- host cell not lysed but harbors viral genome, allows replication of low # of viruses

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26
Q

infectious agent consisting of only protein

A

prions

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27
Q

infectious agent consisting of RNA genome w/o any protein components

A

viroids

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28
Q

clinical feature so distinctive that by itself allows for correct ID

A

pathognomonic

ex: comma shape = Vibrio cholerae

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29
Q

component of a microbial cell or virus which enhances its ability to cause disease

A

virulence factor

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30
Q

purpose of flagella; what protein is it made of?

A

movement of cell; chemotaxis

composed of flagellin protein

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31
Q

purpose of pili (fimbriae)

A

appendages composed of pilin proteins that allow cells to adhere to host cells (or other bacterial cells)

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32
Q

what are endospores? what are they rich in?

A

heat-resistant, dehydrated multi-layered cells rich in calcium dipicolinate
germinate into growing cells when adverse conditions wane

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33
Q

functions of the bacterial cell envelope

A 
structural rigidity
permeability barrier
metabolic uptake
energy production (ETC)
attachment to host cells
escape from immune recognition
antibiotic target
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34
Q

steps of Gram stain

A

1) stain w/ CV
2) treat w/ mordant/fixing dye (iodine)
3) wash w/ alcohol
4) counterstain w/ safranin

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35
Q

Difference in Gram + vs Gram - cell wall structures

A

Gram positive: thick, multilayered peptidoglycan; teichoic & lipoteichoic acids (LTA); pentaglycine bridging & crosslinking of PG molecules

Gram negative: contains outer membrane with LPS; thin PG layer; periplasmic space; inner (plasma) membrane; Braun’s lipoprotein & omp proteins also outer membrane structures; PG is crosslinked but no bridging, more porous; periplasmic space contains hydrolytic enzymes

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36
Q

Where is peptidoglycan found?

A

only in bacteria!

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37
Q

what is the structure and function of LPS?

What clinical effects may be seen?

A

LPS is found in the outer membrane of Gram negative bacteria only. It has…

Lipid A portion responsible for endotoxic activity; anchors molecules; disaccharide w/ esterified LCFAs

Core polysaccharide of 9-12 sugars w/ an unusual 8 carbon sugar 2-keto-3-deoxyoctulosonic acid (KDO)

O antigen- long linear polysaccharide attached to core, extends to exterior of cell; basis for serotypes

LPS shed into bloodstream during bacteremia & induces synthesis of IL-1, TNF & other cytokines; some pyrogenic; complement & coagulation cascades activated

sleep, fever, leukopenia, hypoglycemia, hypotension, shock, DIC, even death

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38
Q

most drug receptors are what type of macromolecule?

A

proteins!

can also be membrane lipids, nucleic acids

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39
Q

_____ is the ability w/ which the drug binds to the specific receptors on the cell membrane; strength of interaction between drug and receptor

A

affinity

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40
Q

inherent property of drug to impart a cellular response

A

intrinsic activity

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41
Q

do agonists have affinity or intrinsic activity?

A

both

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42
Q

do antagonists have affinity or intrinsic activity?

A

affinity; binds to but does not stimulate a receptor

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43
Q

agents that are only partly as effective as agonists no matter the amount employed

A

partial agonist

44
Q

agents which stabilize the receptor in its inactive conformation

A

inverse agonist

45
Q

what are the largest family of receptors with intrinsic enzymatic activity?

A

protein kinases, ex: tyrosine kinases-majority

46
Q

what is the largest family of physiological receptors?

A

GPCRs

47
Q

what types of receptors are enzymes?

A

protein kinases; protein kinase-associated receptors; guanylyl cyclase (activates cGMP & PKG)

48
Q

what are the different types of drug receptors?

A

enzyme receptors, ligand-gated ion channels, transcriptional-related receptors, GPCRs

49
Q

what is a PC? what does greater or less than 1 mean?

A

PC= partition coefficient = [drug] in fat / [drug] in water; determines fat/water solubility of drugs

PC> 1 is lipophilic, hydrophobic
PC<1 is hydrophilic

50
Q

what is the Henderson-Hasselbach equation?

A

pH= pK + log [base form]/[acid form]

51
Q

what is the primary site for absorption of all drugs?

A

small intestine; mostly by passive diffusion

52
Q

what is the primary route of administration for drugs?

A

oral (a type of enteral)

53
Q

what are 2 ways drugs can enter general circulation first and bypass the liver?

A

sublingual and rectal

54
Q

how do most drugs cross the BBB?

A

passive diffusion

55
Q

what is ion trapping? ex of where this happens

A

prostatic fluid pH= 6.4; basic drugs enter by passive diffusion and become protonated, cannot diffuse out, become “trapped”

56
Q

what is the major CYP?

A

CYP34A

57
Q

how do you determine bioavailability?

A

F= AUC oral/ AUC iv

F iv = 1

58
Q

what is the 4 half-lives rule?

A

when drug dosing is stopped, it takes 4 half-lives to essentially eliminate the drug from the body

59
Q

how many half lives does it take to attain steady state concentration?

A

four

60
Q

what chemical compound is rich in endospore formed bacteria?

A

calcium dipicolinate

61
Q

this is a product of peptidoglycan degradation in the host; acts as an adjuvant, mitogen, pyrogen, & somnagen

A

muramyl dipeptide- MDP

62
Q

what enzyme is involved in converting codeine to morphine?

A

CYP2D6

gene deletions–poor metabolizers
gene duplications–ultra metabolizers

63
Q

for drug metabolizing enzymes, what does patient outcome depend on?

A

whether drug is a prodrug or active agent

change pharmacokinetics of drug

64
Q

for drug transporters, what do patient outcomes depend on?

A

location of transporter important; polymorphisms change pharmacokinetics

65
Q

polymorphisms in genes encoding drug targets result in changes in…

A

pharmacodynamics of drug (efficacy)

66
Q

what is the reversible transfer of drug from one location in the body to another?

A

redistribution

67
Q

what types of reactions occur in phase one biotransformation?

A

oxidation, reduction, hydrolysis

68
Q

biliary excretion of drugs is for drugs of what MW?

A

MW of 300 and higher

69
Q

the combination of 2 drugs induces an effect which is greater than the sum of the effects of the 2 drugs when administered individually is known as

A

synergism

70
Q

administration of a drug w/ little or no efficacy enhances the biological response induced by an agonist is known as what? what way does does-response curve shift?

A

potentiation; curve shifts left for agonist

classic example is cocaine making norepi more sensitive

71
Q

what are epitope and paratope?

A

epitope is the portion of the antigen that binds to the paratope on the antibody, BCR, or TCR

72
Q

which cells are of lymphoid origin? myeloid?

A

lymphoid: B&T cells, NK cells
myeloid: granulocytes & agranulocytes (monocytes)

73
Q

what are commonalities share by the skin, gut, lungs, and eye/nose/oral cavity?

A

all have…

1) epithelial cells joined by tight junctions
2) antimicrobial peptides (defensins– some have alpha, some beta–form pores in membranes)
3) normal microbiota

74
Q

what is the gamma delta TCR associated with?

A

mucosal surfaces/mucosal immunity

75
Q

how are T cells that possess reactivity against self eliminated?

A

central tolerance induction

76
Q

what are the hallmark signs of inflammation?

A

redness and swelling w/ heat and pain

77
Q

what is an opsonin?

A

any molecule that enhances phagocytosis

78
Q

what is a biomarker for inflammation?

A

IL6

79
Q

what cytokines are primarily involved in cytokine storm?

A

IL-6 and TNF-alpha

however, both pro and anti-inflammatory cytokines are elevated

80
Q

what cells express PRRs? PAMPs? DAMPs?

A

PRRs- all immune cells
PAMPs- pathogens
DAMPS- our own cells that are damaged

81
Q

what is a danger signal?

A

the ligation of TLR to PAMP

82
Q

what are the steps of the neutrophil response to get to site of infection?

A

1) marginate– roll slowly along blood vessel wall
2) sticking/adherence mediated by selectins and integrins, ICAMs
3) diapedisis- pass through gaps in endothelial cells
passage of cells from interior of blood vessels to extravascular space called extravasation

83
Q

what is the immediate innate response to viruses?

A

NK cells

84
Q

if cytokine storm occurs in the lungs, it can result in this syndrome, and death…

A

vascular leak syndrome

85
Q

what are properties of cytokines?

A

1) redundant- diff cytokines can have same effects; accomplished by sharing portions of receptors
2) pleiotropic- one cytokine can have different effects on diff cells
3) synergistic

86
Q

what chain of cytokine receptor determines specificity?

A

alpha chain; it is different for each

87
Q

what is the difference in inflammatory and lymphoid chemokines?

A

inflammatory- not expressed in normal tissue; turned on by infection/insult
lymphoid- expressed in lymphoid organs; constituitively expressed

88
Q

what types of molecular forces are not involved in antigen-antibody binding?

A

covalent bonds are NOT involved

89
Q

what genes are involved in somatic recombination?

A

RAG 1 and RAG 2

90
Q

how do antibodies generate diversity

A

1) somatic recombination (both B and T cells do this)

2) somatic hypermutation (T cells do not do this)

91
Q

pathogen-induced down-regulation of key recognition molecules is known as

A

antigenic modulation

92
Q

the process by which 2 or more different strains of a virus, or strain of 2 or more different viruses, combine to form a new subtype having a mixture of the surface antigens is

A

antigenic shift

93
Q

_____ is a mechanism for variation in viruses that involves accumulation of mutations within the genes that code for antibody-binding sites

A

antigenic drift

94
Q

what chromosome is HLA found on?

A

6

95
Q

what are the types of antigen presenting cells?

A

dendritic cells
macrophages
B cells

96
Q

what chromosome is beta 2 microglobulin on? which MHC class is it required for?

A

chrom 15; required for MHC 1

97
Q

only certain AAs in the peptide binding groove of MHCs are critical for a peptide to bind to an HLA molecule. these are known as

A

anchor residues

98
Q

what is DiGeorge syndrome? what chromosome does it affect?

A

chrom 22; thymus fails to develop; T cells are absent, though B cells are made; no adaptive immune response; suffer from opportunistic infections

99
Q

where are positive and negative selection in the thymus?

A

positive- cortex; if T cell does not bind, apoptosis

negative- medulla; if T cell has high affinity binding, apoptosis

100
Q

what is AIRE? where is it expressed?

A

thymic medulla; transcription factor, allows expression of tissue specific genes and for T cells to become tolerant of antigens that are expressed in the periphery

lack of AIRE= autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy

101
Q

what do immature vs mature DCs secrete and what changes?

A

immature- IL10

mature- IL12; also see increase in MHC proteins and costimulatory molecules as well as decrease in phagocytizing

102
Q

what is the danger signal?

A

PRR binds to PAMP

103
Q

what is the difference between MHC class 1 and 2 antigen processing?

A 
class 1- Ag degraded in cytosol--intracellular
class 2- Ag degraded in endocytic vesicles (low pH)--extracellular
104
Q

what is TAP?

A

a transporter protein assoc w/ antigen processing; transports peptides into ER; MHC class 3 (on chrom 6)

105
Q

what signals are required for activation of naive T cells?

A 
signal 1 (TCR--zeta) and signal 2 (CD28/B7) for T cell proliferation
CD28 is on T cell; B7 is on APC

POD (2 decks)

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