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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
what are the 2 types of viral infection?
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
26
infectious agent consisting of only protein
prions
27
infectious agent consisting of RNA genome w/o any protein components
viroids
28
clinical feature so distinctive that by itself allows for correct ID
pathognomonic ex: comma shape = Vibrio cholerae
29
component of a microbial cell or virus which enhances its ability to cause disease
virulence factor
30
purpose of flagella; what protein is it made of?
movement of cell; chemotaxis | composed of flagellin protein
31
purpose of pili (fimbriae)
appendages composed of pilin proteins that allow cells to adhere to host cells (or other bacterial cells)
32
what are endospores? what are they rich in?
heat-resistant, dehydrated multi-layered cells rich in calcium dipicolinate germinate into growing cells when adverse conditions wane
33
functions of the bacterial cell envelope
``` structural rigidity permeability barrier metabolic uptake energy production (ETC) attachment to host cells escape from immune recognition antibiotic target ```
34
steps of Gram stain
1) stain w/ CV 2) treat w/ mordant/fixing dye (iodine) 3) wash w/ alcohol 4) counterstain w/ safranin
35
Difference in Gram + vs Gram - cell wall structures
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
36
Where is peptidoglycan found?
only in bacteria!
37
what is the structure and function of LPS? What clinical effects may be seen?
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
38
most drug receptors are what type of macromolecule?
proteins! can also be membrane lipids, nucleic acids
39
_____ is the ability w/ which the drug binds to the specific receptors on the cell membrane; strength of interaction between drug and receptor
affinity
40
inherent property of drug to impart a cellular response
intrinsic activity
41
do agonists have affinity or intrinsic activity?
both
42
do antagonists have affinity or intrinsic activity?
affinity; binds to but does not stimulate a receptor
43
agents that are only partly as effective as agonists no matter the amount employed
partial agonist
44
agents which stabilize the receptor in its inactive conformation
inverse agonist
45
what are the largest family of receptors with intrinsic enzymatic activity?
protein kinases, ex: tyrosine kinases-majority
46
what is the largest family of physiological receptors?
GPCRs
47
what types of receptors are enzymes?
protein kinases; protein kinase-associated receptors; guanylyl cyclase (activates cGMP & PKG)
48
what are the different types of drug receptors?
enzyme receptors, ligand-gated ion channels, transcriptional-related receptors, GPCRs
49
what is a PC? what does greater or less than 1 mean?
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
what is the Henderson-Hasselbach equation?
pH= pK + log [base form]/[acid form]
51
what is the primary site for absorption of all drugs?
small intestine; mostly by passive diffusion
52
what is the primary route of administration for drugs?
oral (a type of enteral)
53
what are 2 ways drugs can enter general circulation first and bypass the liver?
sublingual and rectal
54
how do most drugs cross the BBB?
passive diffusion
55
what is ion trapping? ex of where this happens
prostatic fluid pH= 6.4; basic drugs enter by passive diffusion and become protonated, cannot diffuse out, become "trapped"
56
what is the major CYP?
CYP34A
57
how do you determine bioavailability?
F= AUC oral/ AUC iv F iv = 1
58
what is the 4 half-lives rule?
when drug dosing is stopped, it takes 4 half-lives to essentially eliminate the drug from the body
59
how many half lives does it take to attain steady state concentration?
four
60
what chemical compound is rich in endospore formed bacteria?
calcium dipicolinate
61
this is a product of peptidoglycan degradation in the host; acts as an adjuvant, mitogen, pyrogen, & somnagen
muramyl dipeptide- MDP
62
what enzyme is involved in converting codeine to morphine?
CYP2D6 gene deletions--poor metabolizers gene duplications--ultra metabolizers
63
for drug metabolizing enzymes, what does patient outcome depend on?
whether drug is a prodrug or active agent | change pharmacokinetics of drug
64
for drug transporters, what do patient outcomes depend on?
location of transporter important; polymorphisms change pharmacokinetics
65
polymorphisms in genes encoding drug targets result in changes in...
pharmacodynamics of drug (efficacy)
66
what is the reversible transfer of drug from one location in the body to another?
redistribution
67
what types of reactions occur in phase one biotransformation?
oxidation, reduction, hydrolysis
68
biliary excretion of drugs is for drugs of what MW?
MW of 300 and higher
69
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
synergism
70
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?
potentiation; curve shifts left for agonist classic example is cocaine making norepi more sensitive
71
what are epitope and paratope?
epitope is the portion of the antigen that binds to the paratope on the antibody, BCR, or TCR
72
which cells are of lymphoid origin? myeloid?
lymphoid: B&T cells, NK cells myeloid: granulocytes & agranulocytes (monocytes)
73
what are commonalities share by the skin, gut, lungs, and eye/nose/oral cavity?
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
what is the gamma delta TCR associated with?
mucosal surfaces/mucosal immunity
75
how are T cells that possess reactivity against self eliminated?
central tolerance induction
76
what are the hallmark signs of inflammation?
redness and swelling w/ heat and pain
77
what is an opsonin?
any molecule that enhances phagocytosis
78
what is a biomarker for inflammation?
IL6
79
what cytokines are primarily involved in cytokine storm?
IL-6 and TNF-alpha | however, both pro and anti-inflammatory cytokines are elevated
80
what cells express PRRs? PAMPs? DAMPs?
PRRs- all immune cells PAMPs- pathogens DAMPS- our own cells that are damaged
81
what is a danger signal?
the ligation of TLR to PAMP
82
what are the steps of the neutrophil response to get to site of infection?
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
what is the immediate innate response to viruses?
NK cells
84
if cytokine storm occurs in the lungs, it can result in this syndrome, and death...
vascular leak syndrome
85
what are properties of cytokines?
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
what chain of cytokine receptor determines specificity?
alpha chain; it is different for each
87
what is the difference in inflammatory and lymphoid chemokines?
inflammatory- not expressed in normal tissue; turned on by infection/insult lymphoid- expressed in lymphoid organs; constituitively expressed
88
what types of molecular forces are not involved in antigen-antibody binding?
covalent bonds are NOT involved
89
what genes are involved in somatic recombination?
RAG 1 and RAG 2
90
how do antibodies generate diversity
1) somatic recombination (both B and T cells do this) | 2) somatic hypermutation (T cells do not do this)
91
pathogen-induced down-regulation of key recognition molecules is known as
antigenic modulation
92
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
antigenic shift
93
_____ is a mechanism for variation in viruses that involves accumulation of mutations within the genes that code for antibody-binding sites
antigenic drift
94
what chromosome is HLA found on?
6
95
what are the types of antigen presenting cells?
dendritic cells macrophages B cells
96
what chromosome is beta 2 microglobulin on? which MHC class is it required for?
chrom 15; required for MHC 1
97
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
anchor residues
98
what is DiGeorge syndrome? what chromosome does it affect?
chrom 22; thymus fails to develop; T cells are absent, though B cells are made; no adaptive immune response; suffer from opportunistic infections
99
where are positive and negative selection in the thymus?
positive- cortex; if T cell does not bind, apoptosis | negative- medulla; if T cell has high affinity binding, apoptosis
100
what is AIRE? where is it expressed?
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
what do immature vs mature DCs secrete and what changes?
immature- IL10 | mature- IL12; also see increase in MHC proteins and costimulatory molecules as well as decrease in phagocytizing
102
what is the danger signal?
PRR binds to PAMP
103
what is the difference between MHC class 1 and 2 antigen processing?
``` class 1- Ag degraded in cytosol--intracellular class 2- Ag degraded in endocytic vesicles (low pH)--extracellular ```
104
what is TAP?
a transporter protein assoc w/ antigen processing; transports peptides into ER; MHC class 3 (on chrom 6)
105
what signals are required for activation of naive T cells?
``` 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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