Flashcards in L72 – Drugs for the Treatment of Tuberculosis and Influenza Deck (96):
What is the genus and family of Mtb?
Organs that Mtb can spread to after lung infection?
80% of all cases infects the lungs (can also affect
bones, kidneys, brain)
Transmission route of TB ?
Cough, sneeze >> droplet nuceli contain bacteria
What contains the Mtb after primary tuberculosis?
form granuloma >> bacteria contained within calcified tubercle
What are the objective, identifiable signs of active TB?
blood cough (hemoptysis),
fever, scarring of lungs, fatigue, chest pain
What are the changes to lungs in CXR of active TB?
>> lungs cannot expel pathogen/ breathe properly
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
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
Result from tuberculin skin test is taken how long after injection of PPD?
What is the WHO classification of the TB situation in Hong Kong ?
"intermediate tuberculosis burden with good
What are the primary agents for TB? Presi
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
Effectiveness and toxicity of second line agents?
No more/ less effective
More toxic than 1st line
Full name of Isoniazid?
Route of admin of isoniazid?
Oral (tablets) / IV
How is isoniazid metabolized?
Acetylated in the liver (+ CH3CO) to acetyl-isoniazid
What determines response and efficacy of isoniazid?
Acetylation rate depends on **amount of N- acetyltransferase in liver**(genetic background)
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
Enzyme to activate isoniazid?
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
Isonizid can kill Mtb in which states?
-actively growing intracellular (e.g. penetrate through tubercule)
-extracellular (e.g. spreaded)
Can isoniazid inhibit dormant TB ?
Can inhibit growth of dormant TB in macrophages or TB lesions
Common side effects of Isonizid?
Mild GI disturbance
Severe Isoniazid side effects?
Hepatotoxicity/ liver injury >> hepatitis or elevated liver enzymes ALT/ AST
Peripheral neuropathy (numbness and tingling in limbs)
What drug is used with isoniazid to minimize its side effect on peripheral neuropathy?
Treatment with Vitamin B6 (pyridoxine)
What is the overall inhibition of Rifampicin?
Inhibit the synthesis of
ribonucleic acid (RNA) >> produce defective,
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,
Rifampcin route of admin and kills which type of TB?
Intracellular AND extracellular (like isoniazid)
Oral or IV
Adverse effects of Rifampicin?
Harmless red- orange discoloration of body secretions
GI disturbance, skin rash, hepatitis
How does Rifampicin interact with other drugs?
strong inducer of drug metabolizing enzymes >> affects efficacy of other drugs
What is Rifabutin? Used against what type of TB?
Derivative drug of rifampicin
Used against both intracellular and extracellular pathogen
Which is better: Rifabutin or Rifampicin?
-same side effects but less severe
-Just as effective in treating TB but less drug reaction with anti-HIV drug
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
Ethambutol is effective against which types of TB?
Intracellular AND extracellular
What is the major side effect of ethambutol?
>> inflammatory, demyelinating disorder of the optic nerve
What are the consequences of optic neuritis?
Decrease visual acuity
Lose ability to tell green from red
Ethambutol is not used for which patients?
Children under 5
MoA of pyrazinamide?
Inhibits cell wall biosynthesis:
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
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
Pyrazinamide is effective against which type of TB?
potent intracellular bactericidal activity
against extracellular Mtb
Side effects of Pyrazinamide?
Streptomycin is effective against which type of TB?
cannot penetrate macrophages or TB lesions (unlike Isoniazid)
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
Route of admin. for Streptomycin? One side effect?
What is contained in combo drug RifaMATE?
What is contained in combo drug RifaTER?
Name all 5 of the secondary agents for TB? KLACO
Adverse effect of Cycloserine?
Allergic reactions, numbness of hands and feet, skin rash, tremors, headache, dizziness,
Adverse effect of Amikacin?
Kidney damage, hearing loss
Adverse effect of Kanamycin?
Tinnitus, loss of hearing, kidney damage, allergic reactions
Adverse effect of Levolfoxacine and Oflaxacine?
CNS and tendon toxicity, tendon rupture, cardiac arrhythmia, hypoglycemia
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
What is another regimen for treating B (not the most common one)?
2 drugs regime: INH + rifampin for 9 months
What is the drug regime for MDR-TB?
** Individualized according to susceptibility reports**
5- / 6-drugs regime
contains at least 4 anti-tubercular drugs
Duration of MDR-TB regime?
1-2 years after cultures become negative the organism is susceptible to
Precaution when taking MDR-TB regime?
Daily administration and strict compliance is a must
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
What is considered adequate drug therapy for TB?
Improvement within 2 to 3 weeks
Decreased fever and cough
Improved well-being, x-rays
How to avoid resistant strains development?
Use drugs in combination
Increase use of short course regime
Genetic material of influenze virus?
8 segment ssRNA
The 3 types of influenza is divided by?
M2 (ion channel)
Divided into Influenza A,B,C
The SUBtypes of influenza A is divided by?
NA (N1- N11)
potential 198 different subtypes of Influenza A
What are the seasonality of influenza in HK?
Jan to Mar
July to Aug
Number of deaths from influenza per year?
Natural reservoir of influenza A?
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
Benefit of emerging new strains of influenza A?
New variants able to escape host defense (vaccinated or not)
Subtypes, reservoir of influenza B?
Reservoir = human and seals
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
Which influenza type causes pandemics?
Reservoirs of influenza C?
(though infection is not very symptomatic)
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
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)
Transmission of influenza virus?
Aerosols containing the virus
Direct contact with bird droppings
Contact with contaminated surfaces
How to distinguish flu from common cold by symptoms?
Flu is distinguished by HIGH FEVER with SUDDEN ONSET
and extreme fatigue
What is the normal recovery of influenza in normal people vs poor immune people?
Normal people =2-7 days
Poor immunity = serious respiratory illness
What are the nasopharynx and respiratory symptoms of influenza?
Nasopharynx: runny / stuffy nose, sore throat, aches
Respiratory: coughing, sneezing, breathing difficulties
What are the gastric and joints symptoms of influenza?
Gastric: vomiting, loss of appetite
What are the central and muscular symptoms of influenza?
Muscular: extreme fatigue (sudden onset, usually more severe)
When are antiviral drugs given?
Effective in treating influenza ONLY IF given at an early stage of infection
What strain is H5N1?
Avian > infection of birds is the major host
Only infect small number of humans > species barrier still significant
What are the combined genes in H1N1 (swine flu)?
Combined genes from human, pig, bird flu
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
What structure of influenza is used for internalization, attachment and budding during the replication cycle?
Attachment = Haemagglutinin
Internalisation = M2 ion channel
Budding = Neuraminidase
Name the antivirals that affects the M2 protein of Influenza A?
Rimantidine - methyl derivative of Amantadine
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
Toxic effects of influenza?
Name 3 antivirals that interacts with neuraminidase?
Which viruses are affected by Tamiflu and Relenza?
Both type A and B
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
What is the MoA of peramivir and route of admin?
Similar to Oseltamivir and Zanamivir
IV admin, single dose
When is peramivir used?
For patients with difficulty with inhaled or oral medicines
Common and rare side effects of Peramivir?
Diarrhea (<2% patients)
Serious skin reactions
MoA of Baloxavir?
Inhibit polymerase acidic endonuclease > impairs mRNA synthesis
>> Prevent viral replication
Baloxavir is effective against which influenza? Net effect?
Against both A and B
Single dose to significantly shorten duration of flu symptoms