Integration Flashcards
0
Q
Pelvic inflammatory disease caused by
A
Neisseria gonnorhea and
Chlamydia trachomatis
1
Q
infectious and inflammatory disorder of the upper female genital tract, including the uterus, fallopian tubes, and adjacent pelvic structures
A
Pelvic inflammatory disease
2
Q
What is the biochemical mechanism of action of the quinolone
A
Inhibits DNA gyrase
3
Q
Enzymes that assist in formation of superhelicesand regulate the breaking and rejoining of the DNA chain
A
Topoisomerase
4
Q
interfere with bacterial DNA synthesis
A
Fluoroquinolones
5
Q
blocks relaxation of supercoiledDNA
A
topoisomeraseII (DNA gyrase) in gram-negative organisms
6
Q
interferes with the separation of replicated chromosomal DNA during cell division
A
Topoisomerase IV in gram positive
7
Q
usually bactericidal against susceptible organisms •exhibit postantibioticeffect
A
Fluoroquinolones
8
Q
1st generation
A
Nalidixicacid,
Cinaxacin,
Rosoxacin
9
Q
2nd generation
A
Ciprofloxacin,
Ofloxacin,
Norfloxacin
10
Q
3rd generation
A
Levofloxacin,
Sparfloxacin,
Grepafloxacin
11
Q
3rd generation
A
Levofloxacin,
Sparfloxacin,
Grepafloxacin
12
Q
4th generation
A
Moxifloxacin,
Trovafloxacin,
Gemifloxacin,
Gatifloxacin
13
Q
urinary tract infections
A
1st generation
14
Q
gram negatives, gonococci, gram positive cocciand Mycoplasma
A
2nd generation
15
Q
less gram negative and more gram positive activity, streptococci and enterococci
A
3rd generation
16
Q
broad spectrum, including anaerobes–with increasing generation, increasing gram positive activity
A
4th generation
17
Q
increasing generation leads to increasing gram negative activity
A
Cephalosporin
18
Q
Inhibits DNA replication bybinding to DNA gyraseand topoisomerase IV. Bactericidal
A
Ciproploxacin
19
Q
Ciprofoxacin toxicity
A
Tendinitis and tendon rupture
20
Q
FloroquinoLONES hurt attachment to your
A
Bones
Cartilage damage
21
Q
As the two strands of the double helix are separated, a problem is encountered, namely
A
Positive super coils
Supertwist
22
Q
Theaccumulating positive supercoils interfere with further unwinding of the
A
Double helix
23
Q
If the cord is twisted in the direction of tightening the coils, the cord will wrap around itself in space to form
A
Positive super coils
24
If the cord is twisted in the direction of loosening the coils, the cord will wrap around itself in the opposite direction to form
Negative supercoils
25
which are responsible for removing supercoils in the helix
DNA topoisomerase
26
These enzymes reversibly cut one strand of the double helix
DNA topoisomerase 1
27
Nuclease and ligase
Strand cutting
| Strand resealing
28
DNA topoisomerase 1 They do not require ATP, but rather appear to store the energy from the
Phopodiester bond
29
Type I topoisomerasesrelax negative supercoils in ________, and both negative and positive supercoils in ____________
E. coli
| Eukaryotic cell
30
These enzymes bind tightly to the DNA double helix and make transient breaks in both strands
DNAtopoisomearse 2
31
The enzyme then causes a second stretch of the DNA double helix to pass through the break and, finally, reseals the break
DNA topoisomerase 2
32
Type II DNA topoisomerasesare also required in both prokaryotes and eukaryotes for the separation of interlocked molecules of DNA following
Chromosomal replication
33
a Type II topoisomerase found in bacteria and plants, has the unusual property of being able to introduce negative supercoils into relaxed circular DNA using energy from the hydrolysis of ATP
DNA gyrase
34
Bacterial DNA gyraseis a unique target of a group of antimicrobial agents
Quinolones
35
A typical human cell contains 46 chromosomes, whose total DNA is approximately
1m long
36
interaction of DNA with a large number of proteins, each of which performs a specific function in the ordered packaging of these long molecules of DNA
Histones
37
Eukaryotic DNA is associated with tightly bound basic proteins, called
Histones
38
DNA into basic structural units
Nucleosomes
39
The complex of DNA and protein found inside the nuclei of eukaryotic cells is called
Chromatin
40
5 classes of histones
H1, H2A, H2B, H3, and H4
41
5 classes of histones These small proteins are positively charged at physiologic pH as a result of their high content of
Lysine
| Arginine
42
antibiotics target bacterial DNA gyrase
Quinolones
43
controlled by topoisomerases which later the topology of the circular DNA but not its covalent structure
Super coiling
44
relax DNA from negative supercoils formed
Type 1 topoisomerase
45
change DNA by creating double break strands in DNA
Type 2 topoisomerase
47
abundant proteins associated with eukaryotic DNA and are a family of basic proteins rich in the positvelycharged amino acids lysine and arginine which interact with the negative charges of DNA
Histones
48
RNA is a polymer composed of alternating units of
Ribonucleotides
49
RNA is a polymer composed of alternating units of ribonucleotides connected through a
3-5 phospodiesterase bond
53
Histones, along with positively charged ions such as _________ help neutralize the negatively charged DNA _____________
Magnesium
| Phosphate group
54
HIV affects cells of the immune system, called
CD4 cells or T cells
55
most likely was transmitted to humans and mutated into HIV when humans hunted these chimpanzees for meat and came into contact with their infected blood
Simian Immunodeficiency Virus, or SIV from chimpanzees in west Africa
56
HIV family and subfamily?
Family Retroviridae-Subfamily Lentivirus
57
HIV 1
chimpanzees; pan troglodytes
58
HIV2
sootey mangabeys, more related to SIV 2
59
Retroviridaeis a single stranded RNA virus that has______________, which converts singlestranded RNA viral genome into doublestranded viral DNA
Reverse transcriptase
60
This new DNA is then incorporated into the host cell genome by an
Integrase enzyme
61
contains enhancer and promoter regions of HIV
LTR or long terminal repeat
62
encodes structural proteins which help in packaging RNA of the virus to generate new virus particles
Gag
63
encodes reverse transcriptase and integrase
Pol gene
64
codes for envelope proteins, along with the host plasma membrane complete the virus particle that buds off from the cell
Env
65
Regulatory proteins
Nef(negative factor), Tat(transactivator of transcription) and Rev (regulator of viral gene expressionresponsible for switching early to late HIV gene located in the 3’ end of envgene
66
catalyzes the insertion of viral DNA into the host genome to establish infection
Integrase
67
packaged in a capsidand buds out of the plasma membrane
Assembly and budding
68
Early stage–Within 2-4 weeks, many experience flu-like symptoms, often described as the “worst flu ever” also known as
Acute retroviral syndrome orprimary HIV infection
69
the first FDA-approved test that independently distinguishes results for HIV-1 p24 antigen and HIV antibodies in a single test
HIV-1/2 Ag/Ab
70
helpful in closing the window period (the time between HIV infection and appearance of antibodies to HIV
HIV antigen-antibody combination assay
71
People who are infected with HIV experience no HIV-related symptoms, or only mild ones
Asymptomatic HIV infection” or “Chronic HIV infection
72
Asymptomatic HIV infection” or “Chronic HIV infection
Clinical latency stage
73
Terminates elongation process–Zidovudine, didanosine, stavudine, lamivudine, abacavir–Prevent acute infection of susceptible cells
Nucleoside reverse transcriptase inhibitors
74
binds to the active site induces conformational change and inhibiting enzyme function–Delaviridine, nevirapine, efavirenz–Easily metabolized by cytoP450 system and prone to drug interaction
Non nucleoside inhibitor
75
inhibits HIV protease which activates precursors of gag-pol–binds to the active site of HIV protease and blocks viral maturation–Saquinavir, ritonavir, indinavir, nelfinavir–Side effects: nausea, vomiting, diarrhea
Protease inhibitor
76
2 Reverse transcriptase inhibitor, 1 protease inhibitor
HAART
| Highly active antiretroviral therapy
77
12,241 cases, of which 93 percent—or 11,520—acquired the virus through sexual contact •85 % involved males having sex with other males (MSM) •Age group 15 to 24 was also notable in most new cases •11 patients with full-blown Aids at the time of reporting •Metro Manila accounted for more than half of the new cases (55%) while Calabarzonhad 14% •Other regions cited were: Central Visayas, 7%; Central Luzon, 3% and Davao region, 5
Nice to know
78
Timothy Brown also known as the “Berlin patient” •Diagnosed with HIV in 1995 •After controlling the virus for many years with antiretroviral therapy, Brown was diagnosed with acute myeloid leukemia (AML) and in 2007, destruction of his immune system and a stem cell transplantionwas done from a donor with a rare genetic mutation (homozygous CCR5∆32) that resists HIV infection •Nearly four years after his transplant, Brown remains free of both his cancer and readily detectable HIV
Nice to know
79
Lyme disease
spirocheteBorrelia burgdorferi
80
Three shape of spirochete
cocci(spheres)–bacilli(rods)–spirochetes(spirals
81
Weakly staining, gramnegative spirochetes largest medically important bacteria Stains well with aniline dyes (Giemsaor Wright
Borreliaburgdorferi
82
Borreliaburgdorferi curtured on
BarbourStoenner-Kelly medium
83
Transmission of lyme disease
bite from deer tick Ixodes scapularis
84
Once in the skin, the spirochete can:–Be eliminated by host defense mechanisms–Remain viable and localized in the skin where it
Erythema migrans
85
Characteristic expanding rash (target lesion) at the site of the tick bite 7-14 days after the tick is removed
Erythema migrans
86
Erythemamigrans is an example of
Erythema mutiforme
87
Dark center of small papule, vesicle, or bulla •Pale intermediate zone •Peripheral rim of erythema
Erythema mutiforme
88
Atrophy and skin as thin as cigarette paper
Acrodermatitischronicumatrophicans
89
Occurs within 30 days of Erythema migrans Fatigue, myalgias , bite arthralgias , headache, fever, chills, and neck stiffness
Early lyme disease
90
Occurrs weeks to months after the bite. Musculoskeletal and neurologic symptoms are the most common Cardiac and dermatologic
Early disseminated lyme disease
91
Months to years after infection Musculoskeletal (mainly joints) and neurologic systems are most commonly affected
Later or chronic lyme disease
92
A tetracycline drug that inhibits bacterial protein synthesis by binding to and interfering with ribosomes
Doxycycline
93
Cell wall inhibitors
Penicillin
| Cephalosphorin
94
DNA synthesis inhibitors
Quinolones
95
Metabolic inhibitors
Folate inhibitor
96
50 + 30 = 70
Prokaryotic ribosomes
97
Protein synthesis inhibitor
Aminoglycosides Tetracylcines Macrolides Lincosamides Chlolamphenicol Linezolid
98
act on the ribosomesto inhibit translation
Protein synthesis inhibitor
99
Cell wall
Peptidoglycans
100
Unit
-10 to the minus 30
101
60+40=80
Eukaryotes ribosomes
102
bind to 30 s, preventing the binding of amiono acyl tRNAto heriosomes.
Tetracyclines
103
work against 30Ssub unit, stored the structure in iniation of protein synthesis stop.
- a suicide antibioticor bomb shell antibiotics, stop initiation of translation, incorporation of, prematurely termination of translation.
- example, gentamycin, streptomycin
Aminoglycosides
104
inhibit the formation of initiation complex of 30s and 50 s.
| -last resort antibiotic, cause its very expensive
Linezolid
105
anti 50 S drugs, inhibits translocation
Macrolides
106
the most common, arise in epithelial cells
Carcinoma
107
from connective tissue (e.g. bone, cartilage
Sarcomas
108
from white blood cells
Lukemia and lymphomas
109
The sequence of events that occurs in the proliferation of individual cells is known as the
Cell cycle
110
which controls progression through the cycle so that, once the cell passes G1, it is committed to divide
G1
111
DNA is synthesized and the original DNA duplicated
S phase
112
the chromosomes separate and move to the two ends of the cell
G2
113
the cell divides to produce two daughter cells
M phase
114
the tissue contains cells that proliferate continually to replace those that die or are lost (e.g. the skin, intestine, bone marrow). These cells are known as stem cells
Continual renewing
115
the tissue contains cells (stem cells) that can be stimulated to proliferate in response to an appropriate signal (e.g. liver after injury, lymphocytes during an infection
Conditionally renewing
116
the cells in the tissue never proliferate (e.g. nerve, muscle) Most primary tumours arise in continually renewing tissues (often epithelium
Non renewing
117
TUMOR SUPPRESSION GENE
P 53
118
The protein p21 can be induced by p53independent factors, including drugs known as
Statins
119
Statins are used to lower blood cholesterol by inhibition of its synthesis, via the enzyme
HMG CoA reductase
120
sequences of six-nucleotide repeats found at the ends of the chromosomal DNA strands
Telomeres
121
These are present at the ends of the strands to overcome a problem posed by the semiconservative mechanism of DNA replication, known as
The end replication problem
122
present at the end of the 3′ strand
TTAGGG
123
at the end of the 5′ strand
AATCCC
124
Replication of the ends of the chromosomes presents particular difficulties, since DNA polymerase can only elongate a pre-existing DNA strand (it cannot initiate DNA synthesis) and can only polymerise DNA in one direction (5′ to 3
Need to know
125
Since there is no complementary strand from which to synthesise primers at the ends of the DNA molecule, up to 200 base pairs of DNA
Would be lost
126
Problem in cancer
no complementary strand
127
Tom maintain the length of the telomeres
enzyme, telomerase, which adds on repetitive nucleotides
128
In a normal cell, telomere length is gradually lost during cell replication and, when it is completely lost and then coding sequences are lost, the cell dies via
Apoptosis
129
Tumour cells, however, have an enhanced activity of telomerase which maintains the length of the telomeres which contributes to their
Evasion of normal apoptotic mechanism
130
compound that is foreign to the body
Xenobiotic
131
It may include drugs, chemical carcinogens, and various other compounds •The xenobiotic may be excreted unchanged, or it may me metabolized by the body’s enzymes to other compounds
Xenobiotic
132
2 phases of xenobiotic metabolism
1. Hydroxylation / Biotransformation
| 2. Conjugation
133
Attachment of new functional groups,
Phase 1 biotransformation
134
Masking of an existing functional group
Conjugation
135
Catalyzed by cytochromeP450, a monooxygenase
Hydroxylation
136
Approximately 50% of the drugs humans ingest are metabolized by isoformsof
CYTOCHROME P 450
137
The reaction catalyzed by a monooxygenaseis as follows
RH + O2 +NADPH + H+→ R-OH + H2O + NADP
138
It is sometimes referred to as a Mixed Function Oxidase
Cytochrome P -450
139
Compounds produced in phase 1 are converted by specific enzymes to various polar metabolites by conjugation with glucuronic acid, sulfate, acetate, glutathione, or certain amino acids, or by methylation
Conjugation
140
UDP-glucuronic acid is the glucuronyl donor, and glucuronosyltransferases
•This is the most frequent conjugation reaction
Glucuronidation
141
Sulfate donor is adenosine 3-phosphate5-phosphosulfate (PAPS), called “active sulfate
Sulfation
142
tripeptideconsisting of glutamicacid, cysteine, and glycine
Glutathione
143
are conjugated to the nucleophilic GSH: R+GSH→R—S—G
Electrophilic xenobiotic
144
R+GSH→R—S—G •The enzymes catalyzing these reactions are called
Glutathione S transferase
145
X+Acetyl-CoA→Acetyl-X + CoA •Catalyzed by__________ present in the cytosol of various tissues, particularly the liver
acetyltransferases
146
used in the treatment of tuberculosis, is subject to acetylation
Isoniazid
147
Polymorphic types of acetyltransferases exist, resulting in individuals who are classified as slow or fast acetylators •Slow acetylators are more subject to certain •toxic effects of isoniazid because the drug persists longer in these individuals
Acetylation
148
Xenobiotic may be converted from an inactive to a biologically active compound
prodrug or procarcinogen
149
conjugation may increase the biologic activity of a xenobiotic
Very few cases
150
it is the conjugation reactions that convert the active products of phase 1 reactions to less active or inactive species, which are subsequently excreted in the urine or bile
Other cases
151
PROPERTIES OF HUMAN CYTOCHROME P450
Hemoproteins
Broad substrate specificity
Liver and other tissues
Mitochondria or ER enzyme
152
Warfarin
Cytochrome
| Phenobarbital
153
The preferred lipid in cytochrome P 450 is
phosphatidylcholine
