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MBBS I CPRS > L72 – Drugs for the Treatment of Tuberculosis and Influenza > Flashcards

L72 – Drugs for the Treatment of Tuberculosis and Influenza Flashcards

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1
Q

What is the genus and family of Mtb?

A

 Genus: Actinobacteria

 Family: Mycobacteriaceae

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2
Q

Organs that Mtb can spread to after lung infection?

A

80% of all cases infects the lungs (can also affect

bones, kidneys, brain)

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3
Q

Transmission route of TB ?

A

Cough, sneeze&raquo_space; droplet nuceli contain bacteria

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4
Q

What contains the Mtb after primary tuberculosis?

A

form granuloma&raquo_space; bacteria contained within calcified tubercle

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5
Q

What are the objective, identifiable signs of active TB?

A 
blood cough (hemoptysis),
fever, scarring of lungs, fatigue, chest pain
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6
Q

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

A

Healed cavitation,
fibrosis,
distorted architecture

> > lungs cannot expel pathogen/ breathe properly

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7
Q

What are the 3 categories in Tuberculin skin test results?

A

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

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8
Q

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

A

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

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9
Q

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

A

48-72 hours

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10
Q

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

A

“intermediate tuberculosis burden with good

health infrastructure”

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11
Q

What are the primary agents for TB? Presi

A 
Pyrazinamide 
Rifampicin 
Ethambutol 
Streptomycin 
Isoniazid 
(+Rifabutin)
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12
Q

When are secondary agents for TB used?

A

for patients who cannot
tolerate primary drugs

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

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13
Q

Effectiveness and toxicity of second line agents?

A

No more/ less effective

More toxic than 1st line

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14
Q

Full name of Isoniazid?

A

isonicotinylhydrazine,

INH

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15
Q

Route of admin of isoniazid?

A

Oral (tablets) / IV

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16
Q

How is isoniazid metabolized?

A

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

inactive

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17
Q

What determines response and efficacy of isoniazid?

A

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

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18
Q

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

A

Slow and Fast Acetylators

Slow is more likely to accumulate to toxic concentration

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19
Q

Enzyme to activate isoniazid?

A

Catalase peroxidase

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20
Q

MoA of isoniazid?

A

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

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21
Q

Isonizid can kill Mtb in which states?

A

Both:

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

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22
Q

Can isoniazid inhibit dormant TB ?

A

Yes

Can inhibit growth of dormant TB in macrophages or TB lesions

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23
Q

Common side effects of Isonizid?

A

Diarrhea

Mild GI disturbance

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24
Q

Severe Isoniazid side effects?

A

Hepatotoxicity/ liver injury&raquo_space; hepatitis or elevated liver enzymes ALT/ AST

Peripheral neuropathy (numbness and tingling in limbs)

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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

MBBS I CPRS (78 decks)

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