Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Chemotherapy intercalation > Lecture 9 Antibacterial drugs affecting nucleic acids/nucleic acid biosynthesis > Flashcards

Lecture 9 Antibacterial drugs affecting nucleic acids/nucleic acid biosynthesis Flashcards

1
Q

Give an example of drugs that inhibit tetrahydrofolate biosynthesis

A

sulphonamides

trimethoprim

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Give an example of drugs that inhibit bacterial DNA supercoiling and decatenation

A

Quinolones inc. fluoroquinolones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Give an example of drugs that cause bacterial DNA damage

A

nitroimidazoles and nitrofurans e.g. methronidazole, nitrofurantoin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Give an example of drugs that inhibit RNA synthesis

A

rifamycins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Why is tetrahydrofolate production important in bacteria

A

essential for the production of DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Which step in the pathway of tetrahydrofolate production does sulfonamides inhibit?

A

GTP to dihydropteroate

Inhibits dihydropteroate synthase by binding to the PABA binding site (analogue) at a higher affinity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Which step in the pathway of tetrahydrofolate production does trimethoprim inhibit?

A

Dihydrofolate to tetrahydrofolate

Inhibits dihydrofolate reductase enzyme (analogue)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the advantage of using trimethoprim and sulfonamides together?

A

used alone = bacteriostatic

Used together = bacteriocidal (synergistic effect)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How are sulfonamides selective to bacteria

A

Humans do also need tetrahydrofolate but the pathway of production is different
GTP to dihydropteroate does not exist in the human pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the clinical uses of trimethoprim and sulfonamides?

A

First line treatment/prophylaxis for pneumocystis jiroveci pneumonia in HIV
UTI
Sometimes resp and GI tract infections and malaria due to plasmodium falciparum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are side effects associated with sulfonamides

A

Hypersensitivity
Drug induced fever
Steven-Johnson syndrome
Haemolytic anaemia in patients with inherited glucose-6-phosphate deficiency in red blood cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are side effects associated with trimethorpim

A

rash
nausea
vomiting
hypersensitivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the mode of action of quinolones and fluroquinolones?

A

Target DNA gyrase (gyrA, gyrB) and topisomerase IV (parC, parE)
Specifically binds into the ‘quinolone binding pocket’ - where the staggered cuts have been made via base stacking = complex can no longer rejoin
Therefore supercoiling and decatenation does not occur

Blocks DNA replication/transcription therefore Bacteriacidal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the function of DNA gyrase?

A

Catalyses ATP dependent DNA double strand breakage/rejoining reactions
Cuts at 4 base pair staggered sites on the double stranded DNA - the enzyme then binds to the 5’ end via a tyrosine residue
-ve supercoiling - relax DNA is coiled so that it can be packaged in bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the function of topoisomerase IV?

A

Catalyses ATP dependent DNA double strand breakage/rejoining reactions
Cuts at 4 base pair staggered sites on the double stranded DNA - the enzyme then binds to the 5’ end via a tyrosine residue
Decatination - After replication of chromosome, the 2 daughter chromosomes interlink

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Name an example of a quinolone/fluroquinolone

A

Ciprofloxacin

17
Q

Explain the relationship between DNA gyrase/topoisomerase IV and gram +ve/-ve

A

Gyrase is the primary target for gram -ve

Topoisomerase IV is the primary target for gram +ve

18
Q

Why are quinolones/fluroquinolones specific?

A

humans do not have DNA gyrase

Humans have topoisomerase IV but it has a different structure

19
Q

What are the clinical uses of 1st generation quinolone/fluroquinolones?

A

UTI

sometimes oral infections

20
Q

What are the clinical uses of 2nd and 3rd generation quinolone/fluroquinolones?

A 
Most commonly used
UTIs
Prosatitis
STDs - gonorrhea/chlamydia
Skin and soft tissue infections
Bronchitis
Osteomyelitis
Enteric fever
Mycobacterial infections
21
Q

What are the clinical uses of 4th generation quinolone/fluroquinolones?

A

Same as 2nd/3rd generations (UTIs, Prosatitis, STDs - gonorrhea/chlamydia, Skin and soft tissue infections,, Bronchitis, Osteomyelitis, Enteric fever, Mycobacterial infections)
also includes intra-abdo infections
Pneumonia

22
Q

What are side effects that can occur from quinolone/fluroquinolones?

A 
Generally well tolerated
GI distubances
CNS toxicity
Phototoxicity
Hypotension
Tachycardia
Haematological changes
Drug interactions
Interference with caffeine metabolism
Tendonitis
23
Q

In what case arequinolone/fluroquinolones contraindicated?

A

arthopathy - erosion of cartilage in joints

Shown in young animals = contraindicated in pregnant woman, nursing mothers, adolescents

24
Q

What are the 2 main drugs used clinically from the nitrohetercyclic class?

A

Nitroimidazoles - metronidazole

Nitrofurans - nitrofurantoin

25
Q

Apart from bacteria, what other parasite does metronidazole effect?

A

Protazoa

26
Q

How is metronidazole used clinically?

A

Bactericidal action against most anaerobic bacteria (and protazoa)
Active against some facultative anaerobes (can switch from aerobic to anaerobic if the environment permits)

Intra-abdo infections, C.diff, H.pylori
Genital infections
Resp
Meningitis/brain abscesses 
Osteomylitis
Oral/dental infections
27
Q

What is the mechanism of action of metronidazole?

A

Enters the cell
Reduction activation - reduction of nitrate via pyruvate ferredoxin oxidoreductase enzyme
= DNA damage from product e.g. oxidation, strand breaks, helix destabilisation

28
Q

What are the side effects of metronidazole?

A 
Normally well tolerated
GI disturbances
CNS effects
reversible neutropenia
Enhancement of anticoagulant effects of warfarin
29
Q

When is use of metronidazole contraindicated?

A

Alcohol - disulfiram (used to treat alcoholism) like reaction where metronidazole blocks alcohol oxidation = accumulation of acetaldehyde in the blood stream
Pregnancy - teratogen

30
Q

What are the issues surrounding metronidazole and mutogenicity?

A

Weakly mutagenic under anaerobic conditions
Some reports in animals
No evidence in humans

31
Q

What is the mechanism of action of nitrofuran drugs?

A

reductively activated = DNA damage

Can be aerobic conditions

32
Q

How is nitrofurantoin used clinically?

A

Broad spectrum
UTI - treatment or prophylaxis for recurrent cases
Rapidly excreted

33
Q

What are the side effects of nitrofurantoin?

A

Nausea/vomiting
allergic reaction
Haemolytic anaemia - rare
Pulmonary reactions (acute/chronic) - rare
Mutagenicity/carcinogenicity - produces double stranded breaks in human DNA under anaerobic cells for older drugs, no evidence in humans now

34
Q

What is the mode of action of rifamycin?

A

Bacteriacidal effect in most bacteria

Binds to beta subunit of RNA polymerase = blocks the exit tunnel for RNA release, this is known as abortive initation

35
Q

How is rifamycin used clinically?

A 
combination treatment for:
TB
Leprosy
Penicillin resistant S. pneumoniae
S. aureus

All gram +ve

36
Q

What are the side effects of rifamycin?

A

Relatively non toxic

Urine turns a orange-red colour
Hepatits, skin reactions, febrile effects can occur
Immunosupressive effects seen in animal studies

Chemotherapy intercalation (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions