Anti Tuberculosis Flashcards
What are the first line agents for anti-tuberculosis drugs
First-line agents
• Rifampin
• Isoniazid (INH)
• Pyrazinamide
• Ethambutol
ISONIAZD
Mechanism of action:
Resistance:
Pharmacokinetics:
Mechanism of action:
• prodrug and must be activated by bacterial catalase peroxidase
(KatG).
• inhibits synthesis of mycolic acids
Resistance:
• under expression of enzyme (KatG) required for activation
Pharmacokinetics:
• Metabolism - acetylation by liver N-acetyltransferase
-genetically determined
-rapid acetylators – decreased plasma conc
-slow acetylators - increased plasma conc
ISONIAZID Adverse Reactions
Hepatitis
• Drug-induced systemic lupus erythematosus
• Peripheral neuropathy
- relative pyridoxine deficiency
- more likely to occur in slow acetylators
• Sideroblastic anemia
Rifampin
MOA
Resistance
Pharmacokinetics
Adverse Rxn
MOA: *Binds to the β subunit of bacterial DNA-dependent RNA polymerase *Inhibits RNA synthesis
Resistance:point mutations in the gene
for the β subunit of RNA polymerase. *reduced binding of rifampin
to RNA polymerase.
Pharmacokinetics:
• Strong inducer most cytochrome P450 isoforms (CYP1A2,2C9, 2C19, 2D6, and 3A4)
Adverse Reactions:
• imparts a harmless orange color to urine, sweat, and tears
• cholestatic jaundice and occasionally hepatitis
• light-chain proteinuria
• a flu-like syndrome characterized by fever, chills, myalgias,
anemia, and thrombocytopenia.
• acute tubular necrosis
Ethambutol
MOA
Resistance
Adverse Rxn
MOA: Inhibits mycobacterial
arabinosyl transferases
• Inhibits polymerization
reaction of arabinoglycan,
an essential component of
the mycobacterial cell wall
Resistance:
Resistance• mutations resulting in
overexpression of gene for
arabinosyl transferases
Adverse Rxn:retrobulbar neuritis
- The most common serious adverse event
- loss of visual acuity and red-green color blindness
PYRAZINAMIDE (PZA)
MOA
Resistance
Adverse Rxn
Mechanism of Action:
• Pyrazinamide is converted to pyrazinoic acid—the active
form of the drug—by mycobacterial pyrazinamidase
• Pyrazinoic acid disrupts mycobacterial cell membrane
metabolism and transport functions.
Resistance:
• impaired uptake of pyrazinamide
• mutations in pyrazinamidase that impair conversion of PZA to its active form
Adverse Reactions:
• hepatotoxicity
• hyperuricemia
What’s the treatment protocols for active infection in the intensive phase?
Two months of Rifampin: PLUS Isoniazid , Pyrazinamide ,
and Ethambutol
What’s the treatment protocols for active infection in the continuation phase?
Four months of Rifampin: PLUS Isoniazid
❑Adjuvant treatment
• Pyridoxine
What’s the treatment protocols for active infection in the latent infection phase?
isoniazid for 9 months
Second-line drugs for tuberculosis
• Streptomycin
• Amikacin
• Capreomycin
• Aminosalicylic acid
• Clofazimine
• Cycloserine
• Ethionamide
• Levofloxacin
• Moxifloxacin
• Linezolid
• Rifabutin
• Rifapentine
Used if strains are resistant to first-line agents?
Fluoroquinolones
Levofloxacin
Moxifloxacin
Used in combination with other second- line drugs for
multidrug-resistant strains
Linezolid
Penetrates cells poorly and is active mainly against
extracellular tubercle bacilli
• Site of action is the ribosome subunit 30S
• Interferes with the synthesis of ribosomal proteins
• Ototoxic - Vertigo and hearing loss
• Nephrotoxic
Streptomycin
• Indicated for streptomycin-resistant or multidrug-resistant
strains
• Nephrotoxic
• Ototoxic - tinnitus, deafness, and vestibular disturbances
Capreomycin
Amikacin
• Indicated for streptomycin-resistant or multidrug-resistant
strains
Cycloserine
• a structural analog of D-alanine
• inhibits cell wall synthesis
Adverse effects:
• Peripheral neuropathy
• Central nervous system dysfunction
• Pyridoxine ameliorates neurologic toxicity
Ethionamide
• Blocks the synthesis of mycolic acids
• Hepatotoxic
• Neurologic symptoms may be alleviated by pyridoxine
Aminosalicylic Acid (PAS)
• structurally similar to p-amino-benzoic acid (PABA)
• folate synthesis antagonist
• very high concentrations in the urine can result in crystalluria
RIFAMYCINS
Rifabutin
• Bacterial RNA polymerase inhibitor
• Both substrate and inducer of cytochrome P450 enzymes
• Less potent inducer than Rifampin
• Often used in place of rifampin for treatment of tuberculosis in
patients with HIV infection on antiretroviral therapy
• Similar rates of hepatotoxicity compared to rifampin
Rifapentine
• Potent inducer of cytochrome P450 enzymes
• Combined with isoniazid is an effective short-course treatment for
latent tuberculosis infection
Bedaquiline
• inhibits adenosine 5′-triphosphate (ATP) synthase in
mycobacteria
• risk of QTc prolongation
Pretomanid
acts as a respiratory poison following nitric oxide release
Rifapentine
• Potent inducer of cytochrome P450 enzymes
• Combined with isoniazid is an effective short-course treatment for
latent tuberculosis infection
Rifabutin
• Bacterial RNA polymerase inhibitor
• Both substrate and inducer of cytochrome P450 enzymes
• Less potent inducer than Rifampin
• Often used in place of rifampin for treatment of tuberculosis in
patients with HIV infection on antiretroviral therapy
• Similar rates of hepatotoxicity compared to rifampin
Nasal Decongestants
Phenylephrine
• postsynaptic α-receptor stimulant
• Nasal spray to act as a decongestant in
hay fever & the common cold
Pseudoephedrine
Nasal Decongestants
Pseudoephedrine
• Similar to ephedrine - has both an
alpha and beta agonist properties
• Alpha receptor mediated
vasoconstriction in the respiratory
mucosa shrinks swollen nasal mucous
membranes
• Relief of nasal congestion or eustachian
tube congestion
Xylometazoline
α1 and α2 adrenergic agonist
• Faster acting
Nasal decongestant
Oxymetazoline
Oxymetazoline
• Long- Acting Topical Nasal
Decongestant
• Direct acting alpha agonist (1 &
2A)
• For the temporary relief of nasal
congestion or stuffiness caused
by hay fever or other allergies,
colds, or sinus trouble
Cough Suppressants (Antitussives)
Dextromethorphan
• Opioid derivative NMDA blocker
• Decreases the sensitivity of cough receptors
• Interrupts the transmission of cough impulses
by depressing the medullary cough center
• Reported to be free of addictive potential
• Produces less constipation compared to codeine
Cough Suppressants (Antitussives)
Benzonatate
• Non-narcotic
• Anesthetizes the stretch receptors and thereby
reducing the cough reflex at its source
• Symptomatic relief of cough
N-acetylcysteine?
Mucolytics (Expectorants)
opens disulfide bonds, reducing the viscosity of
mucous
• Dilution of thick mucus makes it easier to cough
up, or drain
• To reduce congestion related to sinusitis,
bronchitis, asthma
• Used to ease congestion in pneumonia and
other chronic respiratory diseases
Guaifenesin
Guaifenesin
• increases the volume and reduces the viscosity
of secretions in the trachea and bronchi.
Drugs for Cystic Fibrosis
❑Dornase alfa
• Mucolytic agent
• Recombinant human deoxyribonuclease I
• Cleaves the extracellular DNA from invading neutrophils to decrease
mucus viscosity.
❑Ivacaftor & Lumacaftor
❑Ivacaftor & Lumacaftor
• These are effective only in people with certain mutations - G551D
• Ivacaftor increasing chloride ion transport by increasing the channel-
open probability (or gating) of the CFTR protein
❑Acetyl cysteine
SH groups
❑Bosentan
Pulmonary Hypertension
Levels of ET-1 peptide are increased 10-fold in pulmonary arterial
hypertension (PAH)
❑Epoprostenol
Pulmonary Hypertension
-PGI analogue
❑Sildenafil
Pulmonary Hypertension
PDE5 antagonist
What drugs will you use for non tb Mycobacterium for a prophylaxis for 1 year?
Macrolide – Azithromycin, Clarithromycin, Erythromycin
• Rifabutin
• Ethambutol
What drug will you use for your patient with leprosy
Clofazimine
You have a patient that has Group a Streptococcus and has pharyngitis. What will you prescribe?
PCN to reduce the rates of acute rheumatic fever
Benzathine PCN G IM -weekly/monthly
If allergic to PCN please give Cephalosporing, clindamycin and macrolides
What organism affects sinusitis
S aureus
S pneumoniae
H influenza
Moraxella catarrhalis
Streptococcus pyogenes
What is the initial empirici tx for sinusit
Amoxicillin or amoxicillin-clavulanate blocks beta lactam
Third generation oral cephalosporin(cefixime or cefpodoxime) prescribed with or without/o clindamycin<——(Gram +)
PCN allergic pt levofloxacin or moxifloxacin
Metronidazole—-anaerobic
Tazobactam—-pseudomonas
Imipenem—-G-ve
Gentamicin G-ve
Tobramycin G-ve
What is the most common organism for acute otitis media
Strep Pneumonia
H Influenza
Moraxella cattarrhalis
What is the first line of therapy for acute otitis media
Amoxicillin-clavulanate
Alt
• Cefdinir
• Cefpodoxime
• Cefuroxime
• Ceftriaxone
• Doxycycline
• Azithromycin
• Clarithromycin
Otitis Externa
• most common causative bacteria
Otitis Externa
• most common causative bacteria are Pseudomonas species
Staphylococcus species, and anaerobes and gram-negative
organisms.
Otitis Externa Tx?
• The topical fluoroquinolones ofloxacin and ciprofloxacin provide coverage against both pathogens.
• Topical Polymyxin B and neomycin.
• Polymyxin B is effective against P. aeruginosa, while
neomycin is effective against S. aureus.
• Topical aminoglycosides (eg, tobramycin and gentamicin) are
also effective against both S. aureus and P. aeruginosa.
Community-Acquired Pneumonia (CAP) organism?
❑S pneumoniae
❑H influenza
❑M catarrhalis
CAP treatment
• Amoxicillin/clavulanate
• Cefpodoxime
• Macrolide
• Doxycycline
• Moxifloxacin, Levofloxacin
• In patients with penicillin allergy: a respiratory fluoroquinolone AND
aztreonam
• If MRSA is suspected, vancomycin or Linezolid
Atypical Pneumonias organism?
Atypical Pneumonias
• Mycoplasma pneumoniae
• Chlamydia pneumoniae
• Chlamydia psittaci
• Legionella pneumophila
Chlamydia pneumoniae tx?
Chlamydia pneumoniae
Macrolides (Azithromycin)
Alt: Tetracyclines (Doxycycline)
Fluoroquinolones
Mycoplasma pneumoniae tx?
Macrolides (Azithromycin):
Children and adults
ALT: Tetracyclines (Doxycycline):
Older children and adults
Fluoroquinolones: Adults
Chlamydia psittaci tx?
Chlamydia psittaci
Tetracyclines (Doxycylcine)
Alt: Macrolides (Azithromycin)
Legionella pneumophila tx?
Fluoroquinolones
(levofloxacin, moxifloxacin,
gemifloxacin)
Macrolides (azithromycin)
Alt:Tetracyclines (Doxycylcine
Tetracyclines
MOA
Drugs
Interaction/toxicities
• Doxycycline
• Minocycline
• Methacycline
• Tigecycline
MOA:Prevents bacterial protein synthesis
by binding to the 30S ribosomal subunit
Interaction
• divalent cations impair oral absorption
Toxicity:
• Gastrointestinal upset, hepatotoxicity,
photosensitivity, deposition in bone and
teeth
Prevents bacterial protein
synthesis by binding to the
50S ribosomal subunit? Interaction/toxicity
Erythromycin
• Azithromycin
• Clarithromycin
• cytochrome P450
inhibitor
Toxicity:
• Gastrointestinal
upset,
• QTc prolongation
FLUOROQUINOLONES
MOA
Toxicity
• Moxifloxacin
• Gemifloxacin
• Levofloxacin
Inhibits DNA replication by binding to DNA
gyrase and topoisomerase IV
• Toxicity: neurotoxicity, tendonitis
• Amphotericin B MOA
S/E
• Binds to ergosterol in the membrane
forming pores through which electrolytes
and other cell content leak
•Fevers, chills, and flu-like reaction
•Renal toxicity
• hydrate
• supplement potassium and
magnesium
•Anemia
• Flucytosine
• Flucytosine
• Converted by fungal enzyme cytosine
deaminase to 5-fluorouracil, which then
inhibits nucleic acid synthesis•Bone marrow suppression
Tx for histoplasmosis
Amphotericin B
Azoles/triazoles
Tx Coccidioidomycosis
Amphotericin B
Fluconazole/itraconazole
Tx Blastomycosis
Amphotericin B
Itraconazole
Tx Cryptococcosis
Amphotericin B
Fluconazole
Flucytosine + amphotericin B
Tx Aspergillosis
Voriconazole
Posaconazole
Echinocandins (Caspofungin)
Mucormycosis tx
Lipid amphotericin B
Echinocandins (Caspofungin)
Sporotrichosis TX
Itraconazole
Amphotericin B
Pneumocystis pneumonia Tx
Trimethoprim/sulfamethoxazole
Fungal infections of the respiratory system
• Coccidioides immitis
• Pneumocystis jeroveci
• Cryptococcus neoformans
• Aspergillus fumigatus
• Histoplasma capsulatum
• Mucor species
• Sporothrix schenckii
• Blastomyces dermatitidis
Azoles
MOA
S/E
•Inhibits 14-alpha-demethylase,
which is key in ergosterol
synthesis in fungi
•Fungistatic
•Anti-androgen effects
via inhibiting
testosterone synthesis
• gynecomastia (in
particular,
ketoconazole)
•Inhibits cytochrome
P450
Echinocandins
MOA
S/E
Echinocandins
•Disrupts cell wall
synthesis by inhibiting
beta-glucan synthesis
•Flushing
• mediated by histamine
❑OSELTAMIVIR & ZANAMIVIR
❑OSELTAMIVIR & ZANAMIVIR
competitively and reversibly
inhibit viral neuraminidase
• clumping of newly released
influenza virions to each other
and to the membrane of the
infected cell
• Oseltamivir – oral
• Zanamivir - inhalation
• Zanamivir can cause cough,
bronchospasm
❑PERAMIVIR
❑PERAMIVIR
• Neuraminidase inhibitor
• Activity against both influenza A and B viruses
• Treatment of acute uncomplicated influenza in adults – IV
❑AMANTADINE & RIMANTADINE
❑AMANTADINE & RIMANTADINE
• Block the M2 proton ion channel
• Inhibit uncoating of the viral RNA within infected host cells
• Active against influenza A only
• Central nervous system adverse effects (marked behavioral changes,
delirium, hallucinations, agitation, and seizures) less frequent with
rimantadine than with amantadine
• amantadine - Skin rash – livedo reticularis
BALOXAVIR MARBOXIL
BALOXAVIR MARBOXIL
• prodrug that is converted by
hydrolysis to the active baloxavir
• a cap-dependent endonuclease
inhibitor that interferes with viral
RNA transcription and blocks
virus replication
• activity against both influenza A
and influenza B.
