Pneumonia and TB Review Flashcards
What drugs can you treat outpatient CAP with? (in general)
Macrolide > Azithromycin or Clarithromycin(acute hypersensitivity reactions)
Respiratory fluoroquinolone > Levofloxacin, Moxifloxacin
3rd generation cephalosporin > cefotaxime, ceftriaxone, cefpodoxime;
A beta-lactam > Amoxicillin; amoxicillin-clavulanate; Ampicillin
Doxycycline (which is a tetracycline)
What type of organisms typically cause CAP?
Strep pneumoniae
Mycoplasma pneumoniae.
Chlamydia pneumoniae
What medication would you give to previously healthy patients who have not taken antibiotics within the past 3 months? (to treat outpatient pneumoniae with CAP)
- Macrolide (azithromycin or clarithromycin)
2. Doxycyline
What medications would you prescribe to patients with comorbid medical conditions or use of antibiotics within the previous 3 months. (Outpatient CAP)
- Levofloxacin, moxifloxacin
- 3rd generation Cephalosporin
- Macrolide plus a beta-lactam
What are all the drugs you can use to treat inpatient pneumonia with for treatment of CAP?
Antipneumococcal beta-lactam > cefotaxime, ceftriaxone, or ampicillin-sulbactam, aztreonam
Antipseudomonal beta-lactam > piperacillin-tazobactam, imipenem, meropenem
Aminoglycoside > Amikacin
Azithromycin
Levofloxacin, Moxifloxacin, as a single agent
Vancomycin
Linezolid
What drugs are used to treat inpatient CAP who are allergic to beta-lactam antibiotics?
Moxifloxacin or Levofloxacin plus aztreonam
What are some drugs used to treat inpatient s with CAP for patients that are at risk for Psudomonas infection?
An antipneumococcal cephalosporin
Antipseudomonal beta-lactam (piperacillin-tazobactam, imipenem, meropenem
Ciprofloxacin
What are drugs used to treat inpatient CAP in cases were you need to treat ventilator-associated pneumonia (VAP)
Imipenem or Meropenem, piperacillin/tazobactam or cefepime;
Gentamicin; and
Vancomycin or linezolid (MRSA)
Be able to reproduce this chart.
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Be able to reproduce this chart. Fluoroquinolones
Reproduce this chart
What is the MOA of Anti pneumococcal agents like Penicillins and cephalosporins?
Bind penicillin-binding proteins(PBPs)
Prevent transpeptidation
Inhibit cross-linking of bacterial cell wall
Give the mechanism by which there is resistance to penicillin and cephalosporins
Degradation by bacterial penicillinases (beta lactamases)
Mutation of PBP
Down regulation of porins channel(gram –ve)
Upregulation of efflux channels
What are the adverse effects of Penicillins and cephalosporins?
Adverse effect:
Hypersensitivity reactions,
Cross reactivity rxns
GI distress and maculopapular rash (ampicillin)
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Reproduce chart.
Be able to reproduce this chart.
Know things in red
Give MOA, characteristic of drug and AE charted out in these drugs.
Reproduce charts
What is the way to treat nosocomial pneumonia in which there is a low risk for multiple drug-resistant pathogens?
Ceftriaxone, Gemifloxacin, Moxifloxacin, Levofloxacin, Ciprofloxacin, Ampicillin-sulbactam, piperacillin-tazobactam, Ertapenem
What is a way to treat nosocomial pneumonia in which there is a higher risk for nosocomial pneumonia?
- Antipseudomonal coverage
Cefepime, Imipenem, meropenem, piperacillin-tazobactam,
Penicillin –allergic patients>aztreonam - A second antipseudomonal
Levofloxacin, gentamicin, tobramycin, amikacin - Coverage for MRSA
Vancomycin or linezolid
What are the medications of choice of anaerobic pneumonia and lung abscess?
Clindamycin or amoxicillin-clavulanate.
Penicillin (amoxicillin) or penicillin G plus metronidazole
What are some signs that may show that a patient may have a history of predisposition to aspiration?
poor dentition
foul-smelling purulent sputum (in many patients)
Infiltrate in dependent lung zone, with single or multiple areas of cavitation or pleural effusion
Who should a polyvalent pneumococcal vaccine be given to?
Age 65 years or older or any chronic illness that increases the risk of CAP
How does having a polyvalent pneumococcal vaccine benefit a patient with pneumonia?
contains common strains of S pneumoniae and has the potential to prevent or lessen severity of majority of pneumococcal infections in immunocompetent patients
How is the seasonal influenza vaccine beneficial?
effective in preventing severe disease due to influenza virus.
How is seasonal influenza vaccine administered (frequency) and to what groups of people?
administered annually to persons at risk for complications of influenza infection
age 65 years or older,
residents of long-term care facilities,
patients with pulmonary or cardiovascular disorders etc
What are the drugs used to treat Influenza A and Influenza B
And Just influenza A
Influenza A and Influenza B -> Oseltamavir or Zanamavir
Influenza A -> Amantadine or Rimantadine
Reproduce this chart on TMP/SMX MOA, Dosage, clinical use, and adverse events.
Reproduce chart
Jeopardy Round. What type of pathogen is describe by the following characteristics?
1. Acid-fast bacilli Slow growing(intracellular), Can become dormant Rapidly active (wall of cavitary lesion).
- Mostly reside inside macrophage, not all drugs reach.
- Cell wall is made of mycolic acid, its impermeable to many drugs.
- Develop resistance (more if single or two drugs used).
- Combination therapy needed (usually 3-4 drugs).
- Slow response, treatment requires months to years (Usually 6 or 9 months, or up to 2 years for TB bones).
- Poor compliance due to prolonged treatment, cost & symptomatic relief.
What are some major characteristics of mycobacteria TB?
What are some first line anti-TB drugs?
Isoniazid(H)
Rifampin(R)
Pyrazinamide(Z)
Ethambutol(E)
TB+ HIV
Rifabutin
Less CYP Interaction
Rifapentine
What are some second-line anti-TB drugs?
Cycloserine
Ethionamide
Streptomycin(S)
Amikacin
Capreomycin
Clarithromycin
Ofloxacin
Levofloxacin
Moxifloxacin
What is the MOA of Isoniazid?
Prodrug activated by catalase-peroxidase (coded by Kat G).
Activated metabolite inhibits the enzyme ketoenoylreductase (coded by inh A), required for mycolic acid synthesis.
Blocks synthesis of Mycolic Acids for mycobacterial cell wall.
Is Isoniazid (INH) bacteriostatic or bactericidal? (explain.)
Bactericidal in growing cells, rapidly dividing and bacteriostatic against slow growing.
What are the clinical uses of Isoniazid?
Prophylaxis– Used alone for TB exposure, tuberculin convertors
Combination chemotherapy for TB– With ethambutol, rifampin, or pyrazinamide
ROA of Isoniazid?
oral admin
INH is acetylated in the liver why is this important to know?
Because there are fast acetylators and slow acetylators
Fast acetylators may require higher doses, “Fast” acetylators–50% of US Blacks and Whites, most Eskimos, Asians, Native Americans, t1/2 for “Fast acetylators < 1.5 hrs,
Slow acetylator are predisposed to toxicity(particularly peripheral neuritis) “slow” acetylators– t1/2 > 3 hrs
In what disease may you have to alter dosing in isoniazid. Which one will you not have to?
alter dosing in hepatic, not renal disease.
What are the adverse effects of Isoniazid?
Hepatotoxicity
Peripheral and central neuropathy
What can cause an individual to be resistant to treatment with Isoniazid?
deletion of KatG gene in mycobacterium
Why is B6 deficiency related to use of Isoniazid?
B6 is a cofactor for hepatic transaminase which is increased with INH therapy. Leads to B6 def which leads to decreased detoxification of ammonia causing neuropathies.
What is the MOA of Rifampin?
Inhibits bacterial RNA synthesis via DNA dependent RNA polymerase
Is Rifampin bactericidal or bacteriostatic/
cidal
What are the clinical uses of Rifampin?
Combination chemotherapy for active disease of TB
Single agent prophylaxis for INH-intolerant patients
A patient with tuberculosis develops bright orange-red urine and calls his physician in a panic because he is afraid he is bleeding into the urine. The patient has no other urinary tract symptoms. Which of the major 1st line TB medications is most likely to produce this side effect?
Rifampin
A 19 year old woman is diagnosed with TB before prescribing a drug regimen, you take a careful medication history because one of the drugs commonly used to treat TB induces microsomal cytochrome P450 enzymes in the liver. Which major 1st line TB drug is this?
rifampin
Rifampin induces cytochrome P450 enzymes, which cause a significant increase in the elimination of drugs
What are the adverse effects of rifampin?
Inducer of microsomal enzymes CYP450:
Hepatotoxic
“Flu-like” syndrome
Gives orange colour to body fluids
D/I of Rifampin?
E+P >Contraceptive pills failure
Phenytoin> epilepsy
Methadone > withdrawal syndrome
Anti retroviral > treatment failure
MOA of Ethambutol. Bacteriostatic or cidal?
Inhibits synthesis of mycobacterial cell wall component arabinoglycan
Inhibition of arabinosyl transferase.
Bacteriostatic
What are the adverse effects of ethambutol?
Dose-dependent and reversible optic neuritis,
decreased visual acuity, central scotoma, loss of red-green differentiation
hyperuricemia
retrobulbar neuritis
What patients is ethamutol contraindicated in?
Children
Does Pyrazinamide act as a bacteriostatic or Bactericidal? What organisms does it act on?
Bactericidal; Acts only on intracellular mycobacteria
Effective against slowly replicating bacteria and in the acidic medium
MOA of Pyrazinamide?
unknown
AE of Pyrazinamide
Hyperuricemia
(common, major) gouty attack
porphyria, photosensitivity
When is Streptomycin used to treat TB? Is it used now?
biliary TB, severe organ TB
only for severe life-threatening cases, now used less frequently
Is Streptomycin bactericidal or static and what organisms is it most effective against?
Bactericidal, effective only against extracellular bacilli, i.m injection,
Adverse effects of Streptomycin.
adverse effects typical of aminoglycoside
Nephrotoxicity- renal failure
Ototoxicity
MOA of Rifabutin
Inhibits DNA-dependent RNA polymerase and interferes with DNA synthesis in M. tuberculosis.
Which is the less potent CYP450 inducer Rifabutin or Rifampin?
Rifabutin is a less potent CYP450 inducer
Which has the longest half-life? Rifabutin or Rifapentine?
Rifapentine
Rifabutin and Rifapentine main benefit. (What are they treating against) What type of bacteria is it most effective against?
Prevention and Treatment of disseminated atypical mycobacterial infection AIDS patients
More effective against Mycobacteriam avium complex (MAC).
Why are anti TB drugs that are considered second line in this category?
toxicity outweighs therapeutic effects except for highly resistant strains
Name some second-line anti-TB drugs.
Cycloserine Ethionamide Amikacin Capreomycin Clarithromycin Ofloxacin Levofloxacin Moxifloxacin Para-aminosalicylic acid
MOA Cycloserine
Inhibits cells wall synth
A/E Cycloserine
Most serious side effects during the 1st 2 weeks of treatment (25%) are peripheral neuropathy and CNS dysfunction, including depression and psychosis
Neurologic toxicity associated with Cycloserine is minimized by what drug?
pyridoxine
Ethionamide MOA? What drug is it chemically related to?
Chemically related to Isoniazid, blocks the synthesis of mycolic acid
A/E of Ethionamide?
Intense gastric irritation, neurologic symptoms (Pyridoxine given) and hepatotoxicity
What is the clinical use of Amikacin; Capreomycin?
MDR TB
What is the clinical use of clarithromycin related to TB?
non tubercular atypical mycobacteria
What is the clinical use of Ciprofloxacin and levofloxacin, moxicfloxacin related to this section specifically can be used to treat what?
MAC and HIV patient
What are Drugs used for Leprosy?
Sulfones and Dapsone
Sulfones MOA? Does it have bactericidal or static action?
inhibit the synthesis of folic acid by M. leprae, and exhibit a bacteriostatic action
What is the purpose of using Dapsone for treatment of leprosy?
used in combination with Rifampin, with or without clofazimine to prevent resistance
A/E Sulfones and Dapsone?
G.I.T. disturbances, Peripheral Neuropathy, Optic neuritis, Blurred vision, Proteinuria and Nephrotic syndrome, Lupus-like syndrome and Hematologic toxicity.
Patients with G-6-P Dehydrogenase deficiency may exhibit hemolytic anemia
What is the benefit of using Clofazimine that we discussed in this section?
Bacteriostatic against M. leprae, and is active against M. avium intracellulare.
Approved for use in combination with Dapsone and Rifampin for the treatment of Lepromatous leprosy.
Used often to Sulfone-resistant patients
MOA of Clofazimine?
The drug enhances the phagocytic activity of Neutrophils and Macrophages, and reduces the motility of Neutrophils and the ability of Lymphocytes to transform.
A/E Clofazimine
GIT disturbances such as anorexia
Photosensitivity, skin discoloration (ranging from re-brown to nearly black)
May elevate hepatic enzyme levels and may cause hepatitis
