Study sets, textbooks, questions
Upgrade to remove ads
Terms in this set (48)
What are Mycobacteria?
-bacteria that are located INTRACELLULARY
-resistant to most ABX (ie like MDR-TB)
-quickly develop resistance
-therapy takes months/years
-it has a slow growing phase
-Need combo therapy to treat
-it is increasing bc of immunocompromised people
-Infects the LUNGS/UG tract/skeletal/meninges
-division time= 16-20 hrs
-1/3 of worlds pop is infected
(and the issue is that the drugs can ONLY attack them WHEN they are dividing...which they are only doing once a day when they are latent; when it is active it can replicate fast & attack ANY organ)
-can be LATENT or ACTIVE
-goes to the APEX of the lungs= greatest ventilation
What are the LINES of drugs for TB?
-Most Common (1st Line): Isoniazid, Rifampin (RNA Polymerase Inhibitor)
-NOTE: Rifatutin= 1st Line for patients with BOTH TB & HIV
*MDR= is resistant to Isoniazid & Rifampin
*TDR= is resistant to Isoniazid & Rifampin & some 2nd line drugs
-2nd Line Drugs are mostly drugs that are used to treat OTHER bacteria (ie like Streptomycin & Amikacin (Aminoglycosides)/Levofloxacin (Fluoroquinolones)
What are the GOALS of TB Therapy?
1) Kill the TB bacilli
2) Prevent Drug Resistance (as well as Travellers carrying TB)
3) Eliminate the PERSISTENT bacilli from the host's tissues (ie to prevent relapses; ie we want to eliminate the )
*You need to take lots of drugs for a long time to achieve this= need to kill the Latent stuff
-Give 3-4 drug COMBO
-You need to also do ABX susceptibility testing
What is Direct Observed Therapy (DOT)?
These are regimens that you need to use for NON-COMPLIANT patients (ie the ones that cannot keep up with their TB treatment...ie like the INCENTIVE thing in Bangladesh)
...OR for RESISTANT Strains of TB
-Usually TB meds will be given ORALLY to be taken at home
...BUT if they are difficult patients...we put them in a TB ward and watch them actually taking the drugs each day
What is LATENT TB?
People who are at HIGH RISK for developing TB are put into 2 categories (and will receive prophylaxis/treatment):
1) People who HAVE been recently infected with TB:
-people in close contact with people with TB (ie like us in a Hospital; great)
-people who have immigrated from an area with TB
-children who are under 5 who have a POSITIVE TB TEST
-groups with high rates of TB transmission
2) People with MEDICAL CONDITIONS that weaken the Immune System (ie IMMUNOCOMPROMISED):
-HIV (most common cause of TB in an Immunocompromised person)
-organ transplants (that is b/c we need to put them on immunosuppressive therapy)
-severe kidney disease
What does the Mycobacteria Cell Wall look like?
-they have MYCOLIC ACIDS
-they DO NOT gram stain (you need to use an ACID-FAST stain)
-Synthetic Pyridoxine Analog (ie B6 Analog)
-MOST POTENT ANTI-TB
*Targets the enzymes used for MYCOLIC ACID SYNTH
*Specifically used for TB
*HOWEVER, if it is used ALONE= run the risk of RESISTANCE
A) Active TB Infection= Used in COMBO with other drugs
B) Latent TB Infection= SOLE DRUG used
*ONLY USED FOR TB
-Pro-drug that is activated by the MYCOBACTERIAL Catalase-Peroxidase (KatG)
-After it is activated...it targets the enzymes for Mycolic Acid Synth: 1) Enoyl Acyl Carrier Protein Reductase (InhA), 2) B-ketoacyl-ACP Synthase (KasA)
-Oral, IV, IM
-Diffuses into ALL body fluids/cells/caseous material (ie it can kill TB ANYWHERE in the body)
What is the ABX Spectrum of Isoniazid?
A) Bacteriostatic= when it is used against bacilli that are in their STATIONARY PHASE (ie NOT rapidly dividing)
B) Bactericidal= when it is used against RAPIDLY DIVIDING bacilli
*WORKS AGAINST BOTH INTRACELLULAR & EXTRACELLULAR
*Shouldn't really be used in isolation (ie ALONE AS MONOTHERAPY)= causes RESISTANCE
*ONLY use it by itself for for LATENT TB
Ways to get chromosomal mutations that cause Isoniazid resistance:
1) Mutation of deletion of KatG= you can't turn Isoniazid from a pro-drug to a real drug (ie you inhibit the enzyme that converts it to it's active form)
2) mutations of Acyl Carrier Proteins= alter the TARGET of Isoniazid (ie the enzymes that SYNTH MYCOLIC ACID= increased mycolic acid without TB attack it)
3) Overexpression of InhA= TOO MUCH of the enzymes that Synth Mycolic Acids (ie Isoniazid can't keep up)
*NOTE: Isoniazid DOES NOT have Cross-Resistance with other Anti-TB drugs (ie if the TB is resistant to Isoniazid...it is ONLY resistant to Isoniazid)
What are the AE of Isoniazid?
1) Peripheral Neuritis (which is corrected by PYRIDOXINE B6 supplementation...usually in PREG)
-this is b/c B6 is a co-factor for neurotransmitters
-isoniazid looks a lot like it...and will OUTCOMPETE (antagonize it) and thus you wont be able to make NT's
2) THE MOST Hepatotoxicity= hepatitis/idiosyncratic
3) CYP P450 INHIBITOR
4) Lupus-Like Syndrome (but RARE)
-this is b/c it can accumulate in SLOW ACYTLATERS= Lupus
(ie b/c the drug is metabolized via acytlation)
*NOTE: Isoniazid is SAFE in PREG (HOWEVER, you need to supplement it with PYRIDOXINE B6 in order to avoid Hepatitis)
Is Isoniazid safe in PREG?
YES...HOWEVER, you need to supplement it with PYRIDOXINE in order to avoid Hepatitis
What are the two Rifamycins?
2) Rifabutin (TB+HIV)
-BOTH FIRST LINE
(basically given if Isoniazid is NOT possible)
-Active TB= COMBO THERAPY
-LATENT TB= SOLE DRUG (2nd Line...ie after Isoniazid)
-BOTH Antimicrobial AND Antimycobacterial
-Resistance occurs RAPIDLY
-USED AS COMBO THERAPY
*RNA POLYMERASE INHIBITOR (B-Subunit; Bacterial)
*THUS, YOU CAN USE IT FOR OTHER BACTERIA OTHER THAN TB
*Used for MORE bacteria than just TB
*MONOTHERAPY= causes resistance
-BLOCKS TRANSCRIPTION by binding the to B-Subunit of RNA-POL= stops RNA synthesis
-Well distributed (including in the CSF)
-Excreted by FECES
-Strong CYP P450 INDUCER (along with Carbemazipine & Phenobarbital)
-if you give it along with Isoniazid...the Rimapin wins (inducer)
What is the ABX Spectrum fo Rifampin?
1) Bactericidal for Intracellular/Extracellular Mycobacteria= M.TB & M.Kansasii (ie it is NOT specific JUST for TB)
2) Used against BOTH Gram+ & Gram-
3) USED TO FIGH MRSA
1) Point Mutations in the rpoB gene (ie the gene for the B subunit of RNA Polymerase)= basically you will get DECREASED AFFINITY of bacterial RNA POL for the drug (ie the Drug will NOT be able to attach to the RNA POL b/c of the point mutation in the rpoB gene...which will cause the B-Subunit to become MUTATED)
2) Decreased permeability of the drug
What are the Clinical Applications of Rifampin?
1) Active TB infections
2) Latent TB infections (in patients who are INTOLERANT to Isoniazid)
3) Leprosy= delays resistance to dapsone
4) Prophylaxis for MENINGITIS EXPOSURE (ie if your roommate gets meningitis...they'll put you on Rifampin; along with Cipro, ceftriaxone)
5) Prophylaxis for people around kids who have H. Influenza Type b (ie you'll give it to their parents/teachers and stuff)
6) Treat MRSA (along with Vancomycin)
What are the AE of Rifampin?
1) Light Chain Proteinuria
2) GI Distress
3) Sometimes: thrombocytopenia, rashes, nephritis, liver dysfunction
4) turns your body fluids ORANGE/RED
5) Strong CYP P450 INDUCER
*NOTE: it is SAFE in PREG
Can you use Rifampin for Preg?
(it is SAFE)
-DOC for TB+HIV
(this is b/c it has LESS CYP P450 INDUCTION than Rifampin)
-Used as a SUBSTITUTE for Rifampin (in people who are INTOLERANT)
-Hasn't been determined to be safe in Preg
-FIRST LINE for ALL forms of TB
-Specifically for M.TB & M.KANSASII
*Used in COMBO Therapy with Pyrazinamide, Isoniazid, Rifampin
*HOWEVER, should NOT be used along= may cause RESISTANCE
-Inhibits Arabinosyltransferase= DECREASED Carbohydrate Polymerization of Cell Wall (ie you are weakening the cell wall by stripping it of it's carbs)
*VISUAL DISTURBANCES (Dose Dependent)= Red/Green Colorblindness
-Thus, you CANNOT give it to children who are TOO YOUNG to receive sight tests
-Also causes headache, confusion, hyperuricemia, peripheral neuritis
*NOTE it is SAFE in PREG
Can you use Ethambutol in Preg?
(it is safe)
-FIRST LINE for TB
-Used iN COMBO with Isoniazid, Rifampin, Ethambutol
-Has to be enzymatically HYDROLYZED to it's ACIVE form (ie Pyrazinoic Acid)
-Resistant strains lack Pyrazinamidase/have increased EFFLUX of drug
-Well absorbed orally
-Well distributed into the CSF
-You may have to adjust the doses if the person has Renal/Hepatic Insufficiencies
-Non-Gouty Polyarthralgia (joint pain; just give them some pain relief)
-Acute Gouty Arthritis (rare)
-Hyperuricemia (ie it will just make Gout even worse)
-Hepatotoxicity, myalgia, GI irritation, porphyria, rash, photosensitivity
*NOTE: it CAN be used for PREGNANCY when the benefits outweigh the risks
Can you use Pyrazinamide for PREG?
(it is safe)
-2nd Line (b/c it has decreased activity against TB)
-Aminoglycoside (irreversibly inhibits the 30s)
*Used for DRUG-RESISTANT STRAINS of TB
-they usually have crappy PK's and they have a lot of AEs
Also used in DRUG COMBOs for treatment of LIFE-THREATENING TB:
2) Miliary Dissemination of TB (ie the WIDESPREAD Spread of TB via the Hematogenous Spread; Millet-Like SEEDING of TB in the lungs)
3) Severe Organ TB
*However it is becoming RESISTANT
-Only fights AEROBIC GRAM NEGATIVE RODS (Negative NAGS)
-Attaches to the 30S Ribosomal Subunit
*CANNOT BE USED FOR PREG (TOO HARSH)= TERATOGENIC
Can you use Streptomycin in PREG?
-It is an AMINOGLYCOSIDE= TOO HARSH
What are the 2nd Line Drugs used to treat TB?
*NOTE: ALL OF THESE ARE TERATOGENIC!!!
-Ethionamide= gynocopastia, hypothyroidism, hypogonadism
-A lot of them are INJECTABLE
What are the treatment options for LATENT TB?
FIRST LINE: ISONIAZID!!
SECOND LINE: RIFAMPIN!!
Isoniazid is used LONGER than Rifampin
What is the STANDARD EMPIRIC therapy for TB?
-Basically in the LONG-TERM CONTINUATION PHASE...you just stick with Isoniazid & Rifampin in the long run (ie these are the ones that will make sure that you do not have a LATENT TB that stays around forever)
*4 for 2 (initiation)
...2 for 4 (continuation phase)
What drugs do you use for DRUG-RESISTANT strains of TB?
What drugs do you use if the TB is resistant to Rifampin?
Really your first choice is Isoniazid...and then the rest of them
What is Leprosy?
-it is caused by Mycobacterium LEPRAE/LEPROMATIS
-Armadillos have it naturally
-it is a GRANULOMATOUS DISEASE of the PERIPHERAL NERVES...as well as the UPPER RESPIRATORY TRACT
-70% of cases are in INDIA
What 2 systems does LEPROSY effect?
1) Peripheral Nerves
2) Respiratory Tract
What are the drugs used for Leprosy?
Combo Therapy of:'
3) Rifampin (for SEVERE form of Leprosy/Resistance; MOST POTENT; b/c it is NOT just for TB)
-Leprosy Drug (used in COMBO with Clofazimine & Rifampin)
-Structurally similar to SULFONAMIDES= it will INHIBIT FOLATE SYNTH
(ie by inhibiting Dihyropteroate Synthase)
-Can also be used in treatment of Pneumonia in HIV patients due to Pneumocystis Jiroveci
*SINCE IT IS SIMILAR TO SULFA DRUGS= DO NOT GIVE TO PREG/NEWBORNS B/C IT CAN CAUSE KERNICTERUS?
-well absorbed & distributed (high levels in SKIN= good for LEPROSY patients who have the bug attack their SKIN)
-Ace-dapsone= the REPOSITORY form of Dapsone (ie the LONG-EFFECT form of Dapsone)
1) Hemolysis (especially in people with G6PD deficiency)
2) Erythema Nodosum Leprosum (ie the Type 2 HS reaction that you see with the SPOTS in Leprosy)
*you can treat this with corticosteroids/thalidomide (which is DEFFFFFFF a NO NO FOR PREG= causes Meromelia)
3) CYP P450 INHIBITOR (just like sulfa drugs)
4) Other problems= GI irritation, fever, hepatitis, methemoglobinemia
What are the 2 diseases you use Dapsone for?
2) Pneumonia in HIV patients infected with Pneumocystis Jeroveci
-Leprosy drugs (given in conjunction with Dapsone & Rifampin)
*Binds to DNA and inhibits its replication (which will help kill the Leprosy bacteria and stop it from replicating)
*BACTERICIDAL to M. Leprae (and some activity against M.Avium-intracellulare complex)
-It has some redox properties= may generate CYTOTOXIC OXYGEN RADICALS (damage the proteins/DNA of the Leprosy)
-RED-BROWN discoloration of the SKIN
*NOTE: NO ERYTHEMA NODOSUM (b/c it is Anti-Inflamm)
Is Dapsone Bacteriostatic or Bactericidal?
Is Clofazimine Bacteriostatic or Bactericidal?
Does Dapsone cause Erythema Nodosum?
Does Clofazimine cause Erythema Nodosum?
(it is ANTI-inflamm)
What are the WHO treatment regimens for Leprosy?
What are ATYPICAL Mycobacteria?
-these are mycobacteria that are present in the Environment...BUT NOT COMMUNICABLE from person to person
-they are basically their own thing and susceptible to DIFFERENT drugs than M. TB
-you need to hit them with a COMBO THERAPY to avoid resistance
Treatment options for ATYPICAL Mycobacteria
Treatment options for M. Fortuitum (ie ATYPICAL Mycobacteria CONTINUED)
Is Rifampin a Cyp Inducer or Inhibitor?
Is Isoniazid a Cyp Inducer or Inhibitor?
Why do you use Rifabutin rather than Rifampin in HIV?
it is NOT an Inhibitor like Rifampin
Sets with similar terms
TB and Mycobacterium Treatment
N3083 Pharmacology Module 4 - Anti-Infective Drugs…
Pharm drugs for TB
Chapter 38 (309 test 2)
Other sets by this creator
Step 1: Kidney Stones
Step 1: Neuro-Embryo
STEP 1 Cell Bio: Lab Techniques
Step 1 Biochem: Lipid Drugs