Leprosy Treatment Flashcards
What drugs are used to treat Leprosy?
Drugs used to treat leprosy are: Dapsone, Rifampin, Clofazimine
Treatment of Adverse Disease effects are: Clarithromycin, Minocycline, Ofloxacin
Dapsone
• disease contraindications?
• Toxic metabolites? side effects?
• Drugs that may interfere?
Dapsone is contraindicated with G6PD deficiency. CYP3A and CYP2C9 in liver act on Dapsone to make Hydroxylamine a toxic metabolite responsible to G6PD def. hemolysis and Methemoglobinemia. Rifampin induces CYPs increasing the buildup of hydroxylamine. Trimethoprim interacts with Dapsone to increase serum concentration of BOTH DRUGS.
What are some symptoms to look for when starting someone on Dapsone?
• why?
Look for Cyanosis in the nail beds, lips, and check O2 sats. if possible.
**Note: people with COPD etc. may be very susceptible to this
What drugs can reduce Dapsone associated toxicity?
Cimetidine (H2 antagonist) and Omerprazole (PPI)
What is the MOA of Dapsone?
• is this agent bacteriostatic or cidal?
- PABA (p-aminobenzoic acid) analogue that inhibits dihydopteroate synthetase.
- Inhibition of 2nd messenger neutrophil chemotaxis
***DAPSONE IS BACTERIOSTATIC (only inhibits enzyme, doesn’t mess with cell structure***
What is Dapsone Syndrome?
• break this up into key organs affected.
Dapsone Syndrome:
Maculopapular Rash - could progress to SJS
Oxidation of Hbg (Hemolysis, Methemoglobinemia)
Myelosuppression (Leukopenia, Agranulocytosis)
Hepatitis/Cholestatic Jaundice (looks like mono, LOW SERUM ALBUMIN), Periphepheral Neuropathy
Psychosis
What are some markers that Dapsone Syndrome is occuring?
• is this reversible?
- Elevated Enzymes in LFTs = ALP/ALT/AST
- Increased Billirubin
- Low RBCs
****It takes weeks, but DAPSONE SYNDROME IS REVERSIBLE***
Dapsone
Administration
MOA
INDICATION
SIDE EFFECTS
CONTRAINDICATIONS
_Administration -_Oral
MOA
Analogue of PABA (p-aminobenzoic acid) Inhibition of Dihydropteroate Synthetase (like SMX)
Inhibition of 2nd messenger pathways of neutrophil chemotaxis
INDICATION
Acne Vulgaris, Dermatitis Herpetiformis, Leprosy
SIDE EFFECTS
Hydroxylamine (after Dapsone is metabolized by CYP3A and 2C9)
Rifampin induces CYPs leading to more Hydroxylamine
Trimethprimincreases Serum levels of Dapsone and TMX
Dapsone Syndrome: Maculopapular rash on FACE (may progress to SJS), Oxidation of Hbg (Hemolysis, Methemoglobinemia), Myelosuppression (Leukopenia, Agranulocytosis), Hepatitis/Cholestatic Jaundice (looks like mono, LOW SERUM ALBUMIN), Periphepheral Neuropathy and Psychosis
CONTRAINDICATIONS
G6PD deficiency
T or F: Rifampin is active against both rapidly and slowly dividing organisms?
True
MOA of Rifampin?
Inhibtion of the Beta subunit of DNA-dependent RNA pols
Due to its hydrophobicity Rifampin is great at crossing membranes and as a result can cross inflammed meninges into CNS.
• what are some problems with this permeability?
- Gets into Breast milk
- Crosses the Placenta
- Gets into glands like lacrimal glands and stains contacts
Why is there variability in the the amount of CYP induction across people taking rifampin?
Variability in PXR and RXR protein in people (targets for rifampin in CYP upregulation)
People may also have differences in the intrinsic activity of their CYP enzymes
What are the side effects of Rifampin?
Liver Toxicity: MAJOR inducer of CYPs (1A2, 2B6, 2C19, 3A) – variable degree of side effects based on RXR and PXR genomic targets and the activity of CYPs in people
Complicates management of Diabetes
Discoloration of Body Fluids
2 or more times a week: Hemolysis, Blood in urine, Renal dysfunction, Flu-like symptoms
What is the MOA of Clofazimine?
• why does this work?
Preferential binding to guanine in mycobacterial spp. (NOT intercelator)
This is effective because GC pairs are much more common in the mycobacterial genome
What should you do before starting therapy for Leprosy?
• what monitoring should you do chronically?
Before Starting Therapy:
• CBC/LFTs/BUN/Creatinine
• Bilirubin/G6PD
During Therapy:
• CBC’s and LFTs
What drugs can be used in cases where Clofazimine is contraindicated?
• what are their MOAs?
• Use in pregnancy?
Drugs can be used in the treatment of adverse reactions to TB therapy?
*Key features of these reactions?
Primary TB reactions involve dermatologic inflammation and peipheral neuropathies
Take note of Clofazimine and Thalidomide
