L72 – Drugs for the Treatment of Tuberculosis and Influenza Flashcards Preview

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Flashcards in L72 – Drugs for the Treatment of Tuberculosis and Influenza Deck (96):
1

What is the genus and family of Mtb?

 Genus: Actinobacteria
 Family: Mycobacteriaceae

2

Organs that Mtb can spread to after lung infection?

80% of all cases infects the lungs (can also affect
bones, kidneys, brain)

3

Transmission route of TB ?

Cough, sneeze >> droplet nuceli contain bacteria

4

What contains the Mtb after primary tuberculosis?

form granuloma >> bacteria contained within calcified tubercle

5

What are the objective, identifiable signs of active TB?

blood cough (hemoptysis),
fever, scarring of lungs, fatigue, chest pain

6

What are the changes to lungs in CXR of active TB?

Healed cavitation,
fibrosis,
distorted architecture

>> lungs cannot expel pathogen/ breathe properly

7

What are the 3 categories in Tuberculin skin test results?

Cat. 1 = immunocompromised
Cat. 2 = Kidney disease, Diabetes, Health-care workers, Contact with TB
Cat. 3 = Normal immune system

8

What are the positive test results for 3 categories in tuberculin skin test?

5-9mm: positive if person is in category 1

10-14mm: positive if person is in category 2

>=15mm: positive if person is in category 3

9

Result from tuberculin skin test is taken how long after injection of PPD?

48-72 hours

10

What is the WHO classification of the TB situation in Hong Kong ?

"intermediate tuberculosis burden with good
health infrastructure"

11

What are the primary agents for TB? Presi

Pyrazinamide
Rifampicin
Ethambutol
Streptomycin
Isoniazid
(+Rifabutin)

12

When are secondary agents for TB used?

for patients who cannot
tolerate primary drugs

to treat mycobacterial infections resistant to 1st-line agents / primary drugs

13

Effectiveness and toxicity of second line agents?

No more/ less effective

More toxic than 1st line

14

Full name of Isoniazid?

isonicotinylhydrazine,
(INH)

15

Route of admin of isoniazid?

Oral (tablets) / IV

16

How is isoniazid metabolized?

Acetylated in the liver (+ CH3CO) to acetyl-isoniazid
(inactive)

17

What determines response and efficacy of isoniazid?

Acetylation rate depends on **amount of N- acetyltransferase in liver**(genetic background)

18

2 groups of patients with different genetic background and thus different amount of N-acetyltransferase in liver?

Slow and Fast Acetylators


Slow is more likely to accumulate to toxic concentration

19

Enzyme to activate isoniazid?

Catalase peroxidase

20

MoA of isoniazid?

inhibits enoyl-acyl carrier protein reductase (InhA)

InhA = important enzyme component of fatty
acid synthase II complex (FAS-II)

>> cannot synthesize LONG- chain mycolic acids

21

Isonizid can kill Mtb in which states?

Both:

-actively growing intracellular (e.g. penetrate through tubercule)
&
-extracellular (e.g. spreaded)

22

Can isoniazid inhibit dormant TB ?

Yes
Can inhibit growth of dormant TB in macrophages or TB lesions

23

Common side effects of Isonizid?

Diarrhea

Mild GI disturbance

24

Severe Isoniazid side effects?

Hepatotoxicity/ liver injury >> hepatitis or elevated liver enzymes ALT/ AST

Peripheral neuropathy (numbness and tingling in limbs)

25

What drug is used with isoniazid to minimize its side effect on peripheral neuropathy?

Treatment with Vitamin B6 (pyridoxine)

26

What is the overall inhibition of Rifampicin?

Inhibit the synthesis of
ribonucleic acid (RNA) >> produce defective,
non-functional bacterial
proteins

27

What is the MoA of Rifampicin?

Inhibit the synthesis of
ribonucleic acid (RNA):

directly binds to β-subunit
of RNA polymerase >>
inhibits mRNA transcription >> produce defective,
non-functional bacterial
proteins

28

Rifampcin route of admin and kills which type of TB?

Intracellular AND extracellular (like isoniazid)

Oral or IV

29

Adverse effects of Rifampicin?

Harmless red- orange discoloration of body secretions

GI disturbance, skin rash, hepatitis

30

How does Rifampicin interact with other drugs?

strong inducer of drug metabolizing enzymes >> affects efficacy of other drugs

31

What is Rifabutin? Used against what type of TB?

Derivative drug of rifampicin

Used against both intracellular and extracellular pathogen

32

Which is better: Rifabutin or Rifampicin?

Rifabutin:

-same MoA
-same side effects but less severe
-Just as effective in treating TB but less drug reaction with anti-HIV drug

33

MoA of ethambutol?

Interferes with cell wall biosynthesis:

inhibits arabinose transferase (EmbB = membrane-associated enzyme)

>> cannot synthesize arabinogalactan

>> fail to make essential structural component of mycobacterial cell wall

34

Ethambutol is effective against which types of TB?

Intracellular AND extracellular

35

What is the major side effect of ethambutol?

Optic neuritis

>> inflammatory, demyelinating disorder of the optic nerve

36

What are the consequences of optic neuritis?

Decrease visual acuity

Lose ability to tell green from red

37

Ethambutol is not used for which patients?

Children under 5

38

MoA of pyrazinamide?

Inhibits cell wall biosynthesis:

pyrazinamidase (PncA)
converts pyrazinamide (= pro-drug) to pyrazinoic acid (= active form)

>>pyrazinoic acid binds to inhibit the fatty acid synthase I (FAS-I)

>> cannot synthesize SHORT chain mycolic acids

39

Compare the structures inhibited by pyrazinamide and Isoniazid?

isoniazid inhibits FAS-II, long chain myocolic acid synthesis

pyrazinamide: inhibit FAS-I and SHORT chain myocolic acid synthesis

40

Pyrazinamide is effective against which type of TB?

potent intracellular bactericidal activity

weakly bactericidal
against extracellular Mtb

41

Side effects of Pyrazinamide?

Hepatotoxicity

GI disturbances

42

Streptomycin is effective against which type of TB?

Only Extracellular

cannot penetrate macrophages or TB lesions (unlike Isoniazid)

43

MoA of streptomycin?

Binds to a ribosomal protein (= component of 30S subunit of ribosomal complex)

>> facilitates codon-misreading during translation of mRNA

>> inhibits synthesis
of mycobacterial proteins

44

Route of admin. for Streptomycin? One side effect?

Intramuscular injections

Hearing problems

45

What is contained in combo drug RifaMATE?

INH (isoniazid)
+
Rifampicin

46

What is contained in combo drug RifaTER?

INH
+
Rifampin
+
Pyrazinamide

47

Name all 5 of the secondary agents for TB? KLACO

Kanamycin

Levofloxacin

Amikacin

Cycloserine

Ofloxacin

48

Adverse effect of Cycloserine?

Allergic reactions, numbness of hands and feet, skin rash, tremors, headache, dizziness,
difficulty speaking

49

Adverse effect of Amikacin?

Kidney damage, hearing loss

50

Adverse effect of Kanamycin?

Tinnitus, loss of hearing, kidney damage, allergic reactions

51

Adverse effect of Levolfoxacine and Oflaxacine?

CNS and tendon toxicity, tendon rupture, cardiac arrhythmia, hypoglycemia

52

What is the most common regime for treating TB?

triple drug regime:

INH (isoniazid) + rifampin + pyrazinamide for 2 months

>> then INH + rifampin for 4 months

53

What is another regimen for treating B (not the most common one)?

2 drugs regime: INH + rifampin for 9 months

54

What is the drug regime for MDR-TB?

** Individualized according to susceptibility reports**

5- / 6-drugs regime

contains at least 4 anti-tubercular drugs

55

Duration of MDR-TB regime?

1-2 years after cultures become negative the organism is susceptible to

56

Precaution when taking MDR-TB regime?

Daily administration and strict compliance is a must

Very expensive

57

Initial drug therapy is based on factors such as?

 Extent of the disease
 Whether patient has previously received anti-TB drugs
 Whether MDR-TB are being isolated in the particular community

58

What is considered adequate drug therapy for TB?

Improvement within 2 to 3 weeks

 Decreased fever and cough
 Weight gain
 Improved well-being, x-rays

59

How to avoid resistant strains development?

Use drugs in combination

Increase use of short course regime

60

Genetic material of influenze virus?

8 segment ssRNA

61

The 3 types of influenza is divided by?

Difference in:
M1 (Matrix)
M2 (ion channel)
NP (Nuceloprotein)

Divided into Influenza A,B,C

62

The SUBtypes of influenza A is divided by?

HA (H1-H18)

NA (N1- N11)

potential 198 different subtypes of Influenza A

63

What are the seasonality of influenza in HK?

2 periods:
Jan to Mar

July to Aug

64

Number of deaths from influenza per year?

300000-500000

65

Natural reservoir of influenza A?

Avian
Pigs
Humans

66

3 explanations for emergence of new strains of influenza A?

Mutation occurs at high rate (esp. on surface glycoproteins) (no proofreading)

Re-assortment of segmented genome of 2 parent viruses

Zoonosis

67

Benefit of emerging new strains of influenza A?

New variants able to escape host defense (vaccinated or not)

68

Subtypes, reservoir of influenza B?

No subtypes

Reservoir = human and seals

69

Give 2 reasons why influenza B does not generate new strains as much as inf. A?

Mutation rate is 2-3 times slower than Influenza A

Limited hosts = limited re-assortment

70

Which influenza type causes pandemics?

Only A

71

Reservoirs of influenza C?

Human

(though infection is not very symptomatic)

72

Survival of virus in 22°C, 0°C and in frozen material?

4 days at 22°C

>30 days at 0°C

frozen material: virus probably survives indefinitely

73

2 ways to kill viruses?

 Heat (56°C for 3 hrs; or 60°C for 30 min)

 Common disinfectants (e.g. formalin (37% formaldehyde), iodine compounds)

74

Transmission of influenza virus?

 Nasal secretions
 Aerosols containing the virus
 Direct contact with bird droppings
 Contact with contaminated surfaces

75

How to distinguish flu from common cold by symptoms?

Flu is distinguished by HIGH FEVER with SUDDEN ONSET

and extreme fatigue

76

What is the normal recovery of influenza in normal people vs poor immune people?

Normal people =2-7 days

Poor immunity = serious respiratory illness

77

What are the nasopharynx and respiratory symptoms of influenza?

 Nasopharynx: runny / stuffy nose, sore throat, aches

 Respiratory: coughing, sneezing, breathing difficulties

78

What are the gastric and joints symptoms of influenza?

 Gastric: vomiting, loss of appetite
 Joints: aches

79

What are the central and muscular symptoms of influenza?

 Muscular: extreme fatigue (sudden onset, usually more severe)

 Central: headache

80

When are antiviral drugs given?

Effective in treating influenza ONLY IF given at an early stage of infection

81

What strain is H5N1?

Avian > infection of birds is the major host

Only infect small number of humans > species barrier still significant

82

What are the combined genes in H1N1 (swine flu)?

Combined genes from human, pig, bird flu

83

What are the steps in viral replication cycle?

1. Attachment to cell membrane
2. Internalization/ Absorption
3. Fusion + uncoating
4. translation and transcription
5. Assembly + packaging
6. Release by budding

84

What structure of influenza is used for internalization, attachment and budding during the replication cycle?

Attachment = Haemagglutinin

Internalisation = M2 ion channel

Budding = Neuraminidase

85

Name the antivirals that affects the M2 protein of Influenza A?

Amantadine

Rimantidine - methyl derivative of Amantadine

86

What is the MoA of Amantadine and Rimantadine?

1) Inhibit uncoating of Influenza A virus:
Block pore function of M2 protein of Influenza A

2) Inhibit viral replication:
Prevent H+ entering/ acidification of virus core >> inhibit active viral RNA transcriptase

87

Toxic effects of influenza?

GI irritation
Dizziness
Ataxia
Slurred speech

88

Name 3 antivirals that interacts with neuraminidase?

Oseltamivir (Tamiflu)
Zanamivir (Relenza)

Peramivir (Rapivab)

89

Which viruses are affected by Tamiflu and Relenza?

Both type A and B

90

MoA of Tamiflu and Relenza?

Binds to inhibit influenza neuraminidase

>> prevents cleavage
of sialic acid residues in receptor

>> cannot release progeny
virions through budding from host

91

What is the MoA of peramivir and route of admin?

Similar to Oseltamivir and Zanamivir

Neuraminidase inhibitor

IV admin, single dose

92

When is peramivir used?

For patients with difficulty with inhaled or oral medicines

93

Common and rare side effects of Peramivir?

Common:
 Diarrhea (<2% patients)

Rare:
 Serious skin reactions
(e.g. Stevens-Johnson
syndrome, erythema
multiforme)

94

MoA of Baloxavir?

Inhibit polymerase acidic endonuclease > impairs mRNA synthesis

>> Prevent viral replication

95

Baloxavir is effective against which influenza? Net effect?

Against both A and B

Single dose to significantly shorten duration of flu symptoms

96

What is the primary mean to prevent and control flu outbreaks?

Yearly vaccination

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