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229 Cards in this Set
- Front
- Back
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What is adjuvant therapy?
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It is treatment given to a patient to prevent recurrence of a cancer as well as preventing any unknown metastasis.
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What is growth %?
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The percentage of cells in a tumor that are actively dividing. Tumors with a low growth % are harder to treat.
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Cisplatin
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Anti-cancer drug based on DNA cross-linking(phase non-specific) with high renal toxicity. Phase NON-specific.
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Bleomycin. What is important about it's toxicity?
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Anti-cancer drug based on free radical damage. This is accomplished by an iron ion within the complex that bonds with oxygen and converts it into superoxide radicals. Due to the need for oxygen as well as the lack of amino hydrolase which inactivates it in other tissues, it has a high pulmonary toxicity. It is notably not toxic in bone marrow. It is PHASE SPECIFIC to G2 and M unlike other DNA damaging agents.
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Doxorubicin
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Anti-cancer drug based on free radical generation as well as topoisomerase II disabling activity causing DNA breaks. It is primarily toxic in cardiac tissue due to the increase in enzymes that activate doxorubicin in the heart that cause an accumulation of free radicals without enough anti-oxidants in cardiac muscles to compensate.
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Describe the entry of tetrahydrofolate from the blood to the cell.
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THF is monoglutamated form in the blood and when they get into the cell they become polyglutamated which keeps them in the cell. The polyglutamated form prevents them from leaving the cell while simulataneously activating them.
Tetrahydrofolate enters through the folic acid pump |
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Methotrexate
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Anti-cancer drug that works by being a purine and pyrimidine synthesis inhibitor as well as slowing certain amino acid synthesis. It does this by inhibiting thymidylate synthase(dUMP to dTMP) and dihydrofolate reductase(Tetrahydrofolate synthesis)
Major toxicity is in bone marrow and it is S-phase specific. Does not normally cross BBB. Can be given in low dose form or high dose form. In high dose form, another drug Leucovorin is simultaneously administered to counter the effects of methotrexate in normal tissue.(Some/most cancerous tissue will be unable to transport the leucovorin to save themselves) |
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Discuss methods of administering a drug to the CNS that normally does not cross the BBB
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It can be administered intrathecally which is either intraventricular with the use of an Ommaya Reservoir or intraspinally where it is injected into the CSF.
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mechlorethamine
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Nitrogen mustard that is a DNA damaging agent. Causes crosslinking due to the nucleophilic nature of compound after releasing chloride ion.
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Cyclophosphamide
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nitrogen mustard that yields two active metabolites and one byproduct, Mechanism of action is DNA cross linking. The byproduct, Acrolein, causes bladder toxicity.
Mesna is a drug that accumulates in the bladder and helps mediate Acrolein induced toxicity. |
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Mesna
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Administered in an inactive dimer form that monomerizes in the bladder and helps reduce Acrolein toxicity.
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6-Mercaptopurine
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Purine analog which is incorporated by the rescue pathway for purines when an unpaired base is present. This incorporation causes DNA strand breaks. In addition, it induces feedback inhibition of the normal purine pool. Hypoxanthine Guanine Phosphoribyl Transferase mutations can cause resistance.
It is phase S-phase specific and has bone marrow suppression as the major toxicity.. |
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5-Fluorouracil
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Pyrimidine analog that is notably Phase non-specific despite the mechanism of action being associated with DNA synthesis. It works by inhibiting thymidylate synthase which prevents the production of dTMP and the imbalance of nucleotides causes the activation of endonucleases.
It has a major toxicity in bone marrow. |
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Paclitaxel
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It functions by being an inhibitor of mitosis through binding to tubulin and preventing normal formation of microtubulin and formation of the mitotic spindle.
It is M-Phase specific and has neutropenia as the major toxicity. |
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What is one possible mechanism of varying forms of action in different tissue types for tamoxifen?
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The varying presence of coactivators and corepressors
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Describe the H-P-A axis
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The hypothalamus secretes GnRH and CRF to the hypothalamus which releases LH, FSH which goes to the gonads to release androgens/estrogens and the hypothalamus also secretes ACTH which goes to the adrenal cortex to release androgens and glucocorticoids
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Tamoxifen
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A estrogen hormone based anti-cancer drug. It has anti-estrogen effects on breast tissue and estrogenic effects on bone and uterine tissue.
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Raloxifene
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An alternative to Tamoxifen which doesn't have the uterine estrogenic effects.
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Why is letrazole not useful in pre-menopausal women?
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Because it is a competitive inhibitor for an enzyme in the estrogen synthetic pathway(aromatase) and there is a very large amount of estrogen in the ovaries that can overcome any competitors.
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What drugs do you use for pre-menopausal women? Why?
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Tamoxifen and Raloxifene are used on premenopausal women. They are antagonist to breast and agonist on bone. Raloxifene is antagonist to endometrial tissue but is also fetotoxic. Tamoxifene is the only non-fetotoxic anti breast cancer drug
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What drugs do you use for post menopausal women? Why?
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Letrozole and Fulvestrant are both used in post-menopausal women. These are not effective in premenopausal women because too much estrogen is produced in the ovaries. They are both fetotoxic. They work by inhibiting aromatase activity which is necessary to convert androgens into estrogens. They also have an antagonist activity in bone and can cause osteoporosis. In addition, Tamoxifen and Raloxifene are not used because they increase clotting and likelihood of strokes.
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What two chemotherapeutic drugs classically used to treat metastatic disease in prostate cancer?
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Paclitaxel and doxorubicin
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Leuprolide
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GnRH superagonist that downregulates GnRH receptors in the pituitary gland which prevents downstream upregulation of androgen production due to negative feedback from reduction of androgen production from other drugs.
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Flutamide
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Antagonist to the androgen receptor preventing testosterone from binding in prostate. Testosterone would normally promote growth and is now blocked. However, this tends to cause androgen mediated feeback inhibition of LH/FSH which then causes more of LH/FSH to be secreted. As such is given with Leuprolide, a GnRH superantagonist to prevent those effects.
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Aminoglutethimide
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Blocks first step of steroid synthesis involving cholesterol in the adrenal cortex thereby blocking androgen synthesis. However also blocks all minerocorticoids and glucocorticoids which are necessary for survival so these must be supplemented.
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Diethylstilbestrol(DES)
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synthetic estrogen. Guys have estrogen receptors in brain that can cause negative feedback to the pituitary resulting in reduction of LH/FSH secretion.
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Prednisone
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Acts on glucocorticoid receptors that upregulate apoptotic genese(caspases?). Glucocorticoids also promote gluconeogenesis and can have fat mobilization.
This drug is good for leukemias to pair with other drugs because it doesn't cause bone marrow suppression. It acts on circulating lymphocytes and not on precursors in bone marrow. The most dangerous side effect is acute tumor lysis syndrome. Leukemia patients have a large number of white blood cells which when broken down can cause an excess of a lot of crap which can end up in renal failure. |
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What are high risk drugs for developing secondary cancers? low risk?
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High risk are DNA damaging agents and DNA cross linkers
Low risk are metabolic analogues |
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Gleevec
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Binds to the ATP domain in the Tyrosine Kinase protein Bcr-Abl that is pathological in CML patients(Chronic Myelogenous Leukemia)
This drug is fetotoxic since it works on the inside of the cell and can cross the placental barrier. |
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Herceptin
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Antibody to HER2 gene, a transmembrane receptor with the EGFR protein and has tyrosine kinase activity. Not fetotoxic since it is an antibody mediated response on the outside of the cell.
Peculiar cardiac sideeffect which causes CHF and decreased left ventricular fraction. |
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Tykerb
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Binds to the ATP domain of the HER1 and HER2 gene products which are EGFR1 and EGFR2 in a fashion similar to Gleevec and as such is also fetotoxic.
It is hepatotoxic. Also has peculiar cardiac sideeffect which causes CHF and decreased left ventricular fraction similar to Herceptin. |
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Define MIC, MBC and PAE
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Minimum Inhibitory Concentration - lowest concentration of drug that inhibits growth.
Minimum Bacterial Concentration - lowest concentration of drug that kills bacterium PostAntibiotic Effect - an effect where drug still works even after it is removed from body/organism. |
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Slide 25 in Lecture 12 Memorized
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Huh
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What's an example of synergistic drug effects?
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Penicillin and Aminoglycosides.
Aminoglycosides are polar and cannot normally penetrate cell membrae to inhibit protein synthesis. However, with simultaneous administration of penicillin which makes cell wall more permeable, aminoglycoside can do work. |
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is Penicillin an L alanine or a D alanine?
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it is a D alanine
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What two methods of antibacterial resistance is specific to gram negative bacteria?
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Efflux resistance and porin based resistance
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What is penicillins mechanism of action?
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Penicillin binds to certain PBP by mimicing d-alanine which are either low MW carboxypeptidases or high MW transpeptidases and blocks the crosslinking of the cell wall which leads to the eventual osmotic lysis.
The carboxypeptidases are involved in cleaving the terminal D alanine residue of the peptide chain. |
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List the forms of bacterial resistance
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Bacteria produces beta lactamase which destroys antibiotic
Modified penicillin binding proteins which prevents binding of drug Modified porins(gram negative only) which prevents entry of drug Effluc(gram negative only) where bacteria pumps drug out of the cell. |
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Slide 12 in lecture 13
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Huh.
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What is the major/minor determinant in penicillin allergies?
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In a major determinant the most important antigenic intermediate of penicillin breakdown products act as haptens after attachment to proteins. In minor determinants you have intact penicillin and penicillanic acid derivatives.
You break open the ring and attach penicillin to an amino acid that causes an allergic response. In a minor determinant, you lose the R group but keep ring structure and attach to proteins also causing allergic response. |
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Which penicillins reach high concentrations in the CSF?
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Ampicillin, Oxacillin, Cloxacillin
Keep in mind in normal conditions none of the penicillins can penetrate the BBB. Only during meningitis like inflammation which causes increased permeability can certain drugs pass through the BBB. |
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Penicillin G
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must be IV and is used for gram +
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What makes the most difference in determining whether a drug can be given orally?
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Its acid sensitivity, not absorption.
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Penicillin V
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Can be taken orally and is only for gram +. especially for gram + cocci strep pneumoniae
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Ampicillin
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IV, IM. PO
short half life. Reaches effective concentrations in CNS during inflammation and if drug of choice to treat listeria meningitis(gram positive bacilli) in old people. Is effective in both gram positive and negative bacteria.Short half life makes IV administration more common. |
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Amoxicillin
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IV, IM, PO
drug of choice for ear infections and upper respiratory infections in children(H. influenza which is gram negative rod). Does not reach CNS and is effective for both gram negative and positive bactera. |
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Beta lactamase resistant penicillins
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Methicillin, Cloxacillin, Oxacillin,
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Methicillin
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No longer used clinically
Beta lactamase resistant |
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Cloxacillin
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IV, PO
Beta lactamase resistant, and is drug of choice for penicillin(because of PO) resistant bacteria like beta lactamase producing Staph. Aureus. NOT used for gram negative bacteria and MRSA. |
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Oxacillin
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IV, IM
Beta lactamase resistant with spectrum similar to Cloxacillin. As such, NOT used for gram negative and is useless against MRSA. |
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Piperacillin
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IV, IM Extended Spectrum
Drug of choice for pseudomonas aeruginosa and complicated gram negative respiratory infections which is not handled well by other penicillins. It is Beta lactamase SENSITIVE so it is now usually used with a beta lactamase inhibitor such as Tazobactam. Is not generally used for typical gram + bacteria as other penicillins are better for that. |
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Name common drug combinations of penicillins.
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Penicillins and Macrolides and penicillins and aminoglycosides
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What is the penicillin combined with aminoglycosides commonly used to treat? Why is this synergistic?
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Staphylococcus Aureus.
Because the penicillin makes the cell wall permeable enough for the aminoglycoside to be effective. |
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What contributes to the stability of penicillin the gut?
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the GI pH.
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Which cephalosporins penetrate into the CSF?
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Cefotaxime, Ceftriaxone(drug of choice), and Cefepime
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Cephalexin
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PO, 1st gen
Good against both gram + and - but effectiveness is limited by short half life and later generation drugs more commonly used. Cannot reach CSF. |
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Cefoxitin
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IV, IM, 2nd gen
Only cephalosporin effective against anaerobic bacteria(B fragilis most common anaerobic infection). Is good for most aerobic gram negative shit but NOT used for Staph due to MRSA. |
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Cefaclor
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PO, 2nd gen
Most active against gram - bacteria(especially H influenza). Also treats Staph. Aureus. Is also used to treat pneumonia and throat infections. |
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Cefotaxime
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IV, IM, 3rd gen
can penetrate CNS has Broad spectrum properties, enterobacter and P aeruginosa, Meningitis of various causes(N meningitis, H influenza, S pneumoniae), penicillin resistant S. pneumonia, |
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Cefotriaxone
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IV, IM 3rd gen
longer half life than Cefotaxime so this is preferred Primary use is for non-listeria meningitis. Is also useful for Enterobacteria and pseudomonas aeruginosa and penicillin resistant Staph. Aureus. Also useful for ear infections. |
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Cefepime
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IV, 4th gen
Especially good against enterobacteria and P. aeruginosa(especially difficult to treat types). Only cephalosporin resistant to beta lactamases but that is slowly changing. |
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Beta Lactamase inhibitors
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Clavulanic Acid, bromopenicillanic acid, Tazobactam, Sulbactam
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Aminoglycosides are important cause...
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useful against Lifethreatening gram negative infections
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General aminoglycoside information
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Very polar, will never penetrate into CNS, excreted in kidney completely unchanged(has high renal toxicity), used topically(neosporin), IV or IM. Is also bacteriosidal as opposed to bacteriostatic(tetracyclines)
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Describe mechanism of aminoglycoside.
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They bind to 30S subunit and cause high error rate transcription. Also inhibits translocation of ribosome.
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Describe Thabes model of aminoglycoside penetration.
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He says first one a minute amount of drug enters cell, causes malformed proteins to be created which makes cell wall more permeable which lets larger amount of drugs in.
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Source of aminoglycoside resistance?
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It is altering the hydroxyl groups on the aminoglyoside thereby inactivating it. You have various enzymes at work simultaneously.
Altered ribosome binding site and altered uptake is also possible. |
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Side effects/toxicity of aminoglycosides
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Nephrotoxic(very important), ototoxic(can be permanent), neuromuscular blockers(drug interactions), allergic skin reactions.
Of note: cannot be directly mixed with beta lactams due to acid-base interactions. |
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Risk factors to ototoxicity in AGS...
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Dose, duration, repeated exposure, use of loop diuretics, use of vancomycin, hypovolemia, liver dysfunction and age.
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Risk factors to nephrotoxicity in AGS...
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Use of diuretics(reduces volume), radiographic contrast exposure, hypovolemia, use of ACE inhibitors, use of NSAIDS, use of other nephrotoxic medications(amphotericin, cisplatin)
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Streptomycin
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2nd line drug(AGS) for tuberculosis but can cause optic nerve damage and has problems with resistance
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Nitilmicin
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IV, AGS
Not available in US. less toxic and less susceptible to resistance and is used as backup. |
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Neomycin and Kanamyccin
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Topical use only. AGS
Is the absolute most toxic AGS. However due to extreme toxicity it is not used systemically. It is only used topically. |
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Gentomicin
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IV, AGS
Most commonly used aminoglycoside. This is the most nephrotoxic systemically administerred drug and is used for serious systemic infections. Streptococci and Pneumococci along with anaerobes and fungi are resistant. |
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Tobramycin
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IV, AGS
Simiar to gentamicin, but more effective against pseudomonas aeruginosa and is less nephrotoxic. |
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Amikacin
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IV, AGS
It is good to use against AGS resistant bugs like streptomycin resistant m. tuberculosis because it is subject to only 2 of the 9 enzymes that can attack gentomicin. It is the broadest spectrum. |
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Tetracycline general properties
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Highly bound to proteins, eliminated with both elimination and biotransformation, well absorbed orally and well distributed including CNS and bone, cannot be given with certain antacids or milk due to chelation, bacterioSTATIC, cannot be given to pregnant women or children without permanent teeth, resistance via efflux pump.
Tetracyclines are very broad spectrum affecting gram +, gram -, anaerobic bugs and fungal bugs. |
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Tetracycline mechanism of action
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binds to 30s ribosomal subunit and prevents binding of tRNA
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What sort of diseases would you use tetracyclines for?
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First choice drug: Rickettsial infection, Mycoplasma pneumoniae, Chlamidia, Brucellosis, Cholera, Plague, Lyme Disease
Doxycycline is the most common tetracycline used. |
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Side effects of tetracyclines
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Hypersensitivity, GI, Renal, Hepatic, Phototoxicity, Brown discoloration of teeth, Suprainfections
most common suprainfection is due to destroying normal flora allowing bacteria like clostridium dificil to take over. These are also commonly drug resistant variants. |
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Which tetracycline can pass the BBB? Which one is most phototoxic? Which one is most used?
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Minocycline can cross BBB. Demecycline has unique phototoxicity. Doxycycline most commonly used.
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Chloramphenicol treats....
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Broad use, it is a drug of last resort for gram -(typhoid, meningitis, B fragilis, rickettsia, brucella)
Note: It is static for everything EXCEPT H. influenza for which it is bacterioCIDAL |
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Chloramphenicol General Properties. What is mechanism? How is resistance gained?
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PO
Binds to the 50S ribosome subununit and prevents peptide bond formation. Mostly bacteriostatic EXCEPT for H. influenza to which it is bacteriocidal. Distributes to CNS and is absorbed very well orally. Eliminated mostly by glucuronidation. Resistance is gained by R factor from bacterial conjugation and/or induction of bacterial acetyltransferase which inactivates chloramphenicol. |
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What causes gray baby syndrome?
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Chloramphenicol when given to neonates due to lack of hepatic development causing lack of glucuronidation(phase II)
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Chloramphenicol side effects
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Hypersensitivity, aplastic anemia, neonatal toxicity. Inhibits P450 which is important for drug interactions
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Sulfonamide
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Broad spectrum antibiotic effective against gram + and gram -, fungi, some yeasts and is well distributed including CNS, and eye, metabolically altered in liver but excreted in urine, BacterioSTATIC,
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What is sulfonamides mechanism of action?
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Sulfonamide functions by inhibiting the first enzyme in folic acid synthesis(dihydropteroate synthetase) by being a competitive inhibitor of PABA. Humans do not possess dihydropteroate synthetase.
Notably, therapy is only evident AFTER latent period while folic acid becomes depleted. |
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Describe methods of sulfonamide resistance
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Altered formed of dihydropteroate synthetase and overproduction of PABA(para amino benzoic acid) which is a metabolic precursor for folic acid synthesis.
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Describe side effects of sulfonamide
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Hypersensitivity response(Stevens-Johnson syndrome), renal crystalluria(metabolites precipitate problematic in older drugs), hematopoietic system disorders(hemolytic anemia, aplastic anemia), kernicturus in neonates when given during pregnancy
G6PD in blacks and Mediterranean population as well as HIV increases likelihood of aplastic anemia. |
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What is Stevens-Johnson syndrome?
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An allergic response to sulfonamide where all the mucosal lining in your body becomes inflamed.
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What is kernicterus?
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A side effect of giving sulfonamide to pregnant women causing brain problems due to high levels of unconjugated bilirubin.
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What is the major use for sulfonamides?
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Urinary Tract infections
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Sulfadiazine
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PO, topical, Sulfonamide
must be monitored for adverse kidney side effects(crystallurea) Mostly used to treat UTIs. Another major use is to administer it topically to chemical or thermal burns as a broad spectrum antibiotic ointment. It can be used with pyrimethamine to treat toxoplasmosis in immunocompromised. |
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Sulfisoxazole
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PO, topical, sulfonamide
More soluble so less chance of crystallurea. Treatment for UTI, ear infections and alternate amoxicillin therapy(sometimes paired with erythromycin) |
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Sulfacetamide
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Eyedrops, topical, Sulfonamide
Gram +, Gram -. Used as eyedrops for common eye infection. Also sometimes used as ointment to help alleviate acne. |
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Sulfasalazine
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Poorly absorbed, Sulfonamide
Used to treat Crohn's Disease as it reduces synthesis of inflammatory mediators. Is not used as an antibacterial drug. |
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Trimethoprim method of action
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It blocks the third step of folic acid synthesis.
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Trimethoprim general properties
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Oral, IV, excreted in urine, and distributes well to all tissues including CNS. Almost always used synergistically with sulfamethoxazole
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Trimethoprim-sulfmethoxazole
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Oral,
active against gram +, gram -, but inactive against anaerobes which are generally the cause for superinfections. Used for UTI, middle ear infections like other sulfur drugs but notably used for long lasting/recurring bronchitis in adults. Has similar side-effects to sulfonamides and so is contraindicated in pregnant ladies. Pseudomonas Aeruginosa is RESISTANT |
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(Fluoro)quinolones general properties
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Oral, IV, quinolone
Very rapidly absorbed in GI, bioavailability almost 1 meaning peak serum reached with oral is almost same as IV. Used to be limited to treating gram - bacteria. Newer fluoroquinolones are more broad spectrum and can do gram + as well. But still particularly effective against gram -, especially Pseudomonas aeruginosa. Excreted in urine unchanged(not metabolized) and is well distributed throughout including CNS and is used for meningitis. It is BacterioCIDAL. |
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Quinolone mechanism of action
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inhibits DNA gyrase which unwinds DNA thereby preventing DNA synthesis. Not known why this mechanism causes bacterioCIDAL activity versus bacteriostatic.
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Methods of quinolone resistance
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alter DNA gyrase(major), Decrease membrane permeability, development of efflux.
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Quinolone Side effects
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GI effects, CNS effects, Phototoxicity, athropathy
contraindications: Cannot take with tricyclic antidepressants, Class I antiarrythmics, Na channel blockers due to long QT. and cannot give to children under 18 due to uncertain joint issues |
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Ciprofloxacin. What is it used for? Where does it distribute? What is resistant to Ciprofloxacin?
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PO, IV, 2nd gen quinolone
increased gram - activity, some gram + and atypical pathogen coverage. Broadly used for GI, UTI, STDs and skin infections Also good penetration into bone so can be used for osteomyelitis. But a major use is lower respiratory tract infection. Notably Streptococcus Pneumoniae is RESISTANT. Also notably Ciprofloxacin is the MOST POTENT fluoroquinolone against Pseudomonas Aeruginosa. |
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Oxofloxacin
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another 2nd gen fluoroquinolone functions similarly to Ciprofloxacin
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Levofloxacin. What is it active against/used for? When is it worse the Cipro? What are you at risk for with this drug?
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3rd/4th gen fluoroquinolone
Expanded gram + coverage compared to older fluoroquinolones. Is active against penicillin resistant bacteria and can be used for bacterial meningitis(especially H influenza). However, it is less active than Ciprofloxacin against pseudomonas aeruginosa. Used for infections almost anywhere including bone, skin, lungs, etc. Have more risk for phototoxicity and long QT syndrome than 2nd gen. |
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gatifloxacin
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3rd/4th gen fluoroquinolone similar to levofloxacin
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name Macrolides and mechanism of action
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Erythromycin, Clarithromycin, Azithromycin.
Function by binding to 50S subunit of ribosome and preventing binding of tRNA similar to chloramphenicol. |
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Clarithromycin. Where does it distribute(CNS?)? What is it metabolized by? What is it effective/not effective against?
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Oral, IV, macrolide
Wide distribution, but poor CNS penetration. Metabolized by P450 and so has drug interactions. Effective against Gram +(Strep), and slightly with gram -, NOT effective with anaerobes, Enterococcus or Staphylococcus Aureus. |
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Side effects of Clarithromycin
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mild nausea, GI problems, may increase QT.
notably NOT responsible for headaches and reversible hearing loss |
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When would you use Azithromycin over Clarithromycin?
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Azithromycin is not metabolized with P450 so when drug interactions are a problem, you may choose Azithromycin. Also does not increase QT as a side effect.
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Clindamycin. Mechanism? Distribution? Excretion? When is it useful?
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Oral, IV, topical
inhibits transcription by binding to 50s ribosome. Does not reach CNS, mostly excreted in feces/bile, It is useful against most gram + bacteria both anaerobic and aerobic with the exception of enterococci and clostridium difficil. It is also effective against some gram - anaerobes but all aerobic gram - are resistant. |
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Major side effects associated with Clindamycin
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Antibiotic Associated Pseudomembranous Colitis due to C Difficil's resistance and overwhelming of normal flora.
Neuromuscular blockade and as such should not be paired with non depolarizing muscle relaxants. |
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Anaerobic Gram + bacteria
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Clostridium perfringen, Lactobacillus sp, bifidobacterium, clostridium difficil
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Differences between Clindamycin and Clarithromycin(Macrolides)
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Clindamycin has a mechanism similar to the macrolides and so there is cross resistance. Also, in contrast to macrolides it IS active against methicillin resistant staph.
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Synercid(Quinupristin/dalfopristin). How is it secreted? What is it used for? mechanism? What's important side effect?
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IV,
secreted hepatically, does not penetrate CNS, and is commonly used for drug resistant bacteria. Both bind to 50S ribosome meaning they have the same mechanism as macrolides and clindomycin. (Effective against gram + aerobes. It is not effective against gram - species or anaerobes. Also NOT effective against enterococcus faecalis. Is Dangerous for pregnant women.) |
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Side effects of Synercid(Quinupristin/dalfopristin)
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Bone/Joint pain is biggest concern.
Dangerous for pregnant women. |
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Which bacteria are susceptible to Synercid(Quinupristin/dalfopristin)?
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BacterioCIDAL to gram + aerobes. It is not effective against gram - species or anaerobes. Also NOT effective against enterococcus faecalis but IS effective against Enterococcus faecium. Commonly used against drug resistant bacteria.
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Linezolid. Mechanism? Distribution? What is it used for?
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oral, IV
Unique mechanism of action that prevents ribosome assembly so no cross resistance, widely distributed and DOES penetrate CNS. Is used against MDR bugs and VAE(specifically Enterococci Faecium). Not effective against gram - aerobe or anaerobes. (Notable side effect: due to CNS effect(it is an MAOI if given with SSRI, you have the risk of serotonin syndrome and increases risk of hypertensive crisis in people taking sympathomimetic agents.) |
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What major side effects do you look out for with Linezolid?
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Notable side effect: due to CNS effect(it is an MAOI if given with SSRI, you have the risk of serotonin syndrome and increases risk of hypertensive crisis in people taking sympathomimetic agents.
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Which kinds of viruses are more prone to creating escape mutants?
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RNA viruses because RNA dependent polymerase do not have proofreading mechanism.
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Acyclovir and Gancyclovir mechanism of action
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Pro drugs, need to be phosphorylated by thymidine kinase before they are active. They lack the 3' OH on ribose necessary for chain elongation of DNA. Both drugs also have higher affinity for viral thymidine kinase than cellular version of enzyme. In addition, viral DNA polymerase also have higher affinity for phosphorylated drug than the host cell. Resistance occurs when the higher affinity for both of these enzymes is altered.
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Acyclovir is used to treat..
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Used to treat Herpes 1(cold sores) and 2(genital herpes) as well as Varicella Zoster(shingles) as well as immunodeficient people where latent HSV/VZV reactivates.
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Gancyclovir is used to treat...
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used to treat CMV. Notably, CMV does not have a thymidine kinase but CMV works with cellular machinery to make monophosphate and then cell makes triphosphate of gancyclovir which has higher affinity for viral DNA polymerase.
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Acyclovir analogues
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Famicyclovir, Valacyclovir.
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Acyclic Nucleoside Phosphonates
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Cidofovir, Adefovir, Tenofovir,
are analogues for cytidine, adenine etc, have a phosphate moiety, substrates for DNA polymerase when triphosphorylated, bioavailability can be increased when lipid moieties added. Sometimes, rarely, two bases can be added before chain termination(mostly for pox viruses) |
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Cidofovir
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Comes in monophosphorylated via endocytosis and becomes triphosphorylated by cellular enzymes and gets added to DNA chain by viral DNA polymerase thereby ending it.
Approved for use against CMV and is stockpiled to fight smallpox but is used off label for molluscum contagiosum, adenovirus,HPV, BK virus, JC virus. It is POORLY bioavailable and is NEPHROtoxic |
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Tenofovir
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Phosphorylated similarly to Cidofovir and is a substrate for HIV reverse transcriptase leading to chain termination.
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Ribavirin
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Guanosine analog
Used to treat Hepatitis C Virus with pegylated interferon alpha, Influenza and respiratory synctial with or w/o monoclonal Antibody to RSV. |
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Ribavirin mechanism
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Has multiple possilble mechanisms of action. Stimulates Th1 response, inhibits IMDPH which produces GTP as a monophosphate, inhibits RNA replication and causes DNA mutagenesis as a triphosphate.
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(Foscarnet)Phosphonoformic Acid
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Similar to pyrophosphate which binds to the pyrophosphate binding site on DNA polymerase. Has higher affinity for viral DNA polymerase, but accumulates in bone and is too toxic for regular use.
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Enfuvirtide(Fuzeon)
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A peptide corresponding to COOH terminus of gp41 which inhibits fusion of HIV with cell membrane.
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Maravioc(Selezentry)
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Small molecule inhibitor of HIV envelope binding protein to CCR5 chemokine receptor
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Substrate Analogue for Reverse Transcriptase
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Azidothymidine(AZT) - A substrate analogue for reverse transcriptase phosphorylated by thymidine kinase that causes chain termination. It is 100 times more effective against reverse transcriptase than DNA polymerase and resistance arises when RT mutates.
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Non-nucleoside inhibitors of reverse transcriptase
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Not analogues of DNA bases, rather allosterically binds to RT to inhibit activity.
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non-Peptitomimetic Protease Inhibitors
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Tipranavir
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Which 5 classes of drugs are used in HAART?
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Protease inhibitors, Nucleoside Reverse Transcriptase Inhibitors, Non-Nucleoside Reverse Transcriptase Inhibitors, Nucleotide Reverse Transcriptase Inhibitors, Chemokine Receptor Inhibitors/Fusion inhibitors
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Amantadine/Rimantadine
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Used against influenza A, blocks the M2 channel so that the fusion protein cannot get out of the endosome and allow viral contents into cell.
Influenza B does not have M2 receptor so is immune. |
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Zanamivir/Oseltamivir(Tamifu)
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Look very similar to Sialic acid and as such inhibit neuraminidase activity by competitive inhibition and reduces release of both influenza A and B viruses from cell. Hard for resistant mutant to develop because mutations are lethal. Also are inactive against cellular neuraminidases.
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Interferon Info. used to treat?
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Two types Type 1 - alpha beta and type 2 - gamma
In interferon alpha/beta you have a foreign substance that depresses the genes leading to interferon production which turn cells into an anti-viral state Mechanism is such that interferon activates certain pathways that activate endonucleation of all RNA(2-5A) or inhibits protein synthesis(eiF-2) treats HCV with ribavarin, other viruses, hairy cell leukemia, CML, non-hodgkin's, Kaposi Sarcoma |
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Trichomonas Vaginalis
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infections can persist for long time, treatment is tinidazole which acts by generating superoxide radicals which kill the cell.
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Tinidazole
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PO
used to treat Trichomonas Vaginalis and giardia lamblia. Mechanism of action is free radical destruction, eliminated by P450(Cyp3A4) with primary excretion in urine. It is widely distributed including CSF, but doesn't generally make it past small intestine. Side effects are nausea, vomiting, and in rare cases neutropenia, leukopenia and neuropathy. Notable drug interaction -- inhibits aldehyde dehydrogenase which disallows the consumption of alcohol. |
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Giardia Lamblia
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Large percentage of asymptomatic infections. Found in SMALL intestine, common bile duct and gallbladder. Passes through contaminated drinking water.
Can be treated with Tinidazole which is drug of choice. Second choice is a drug called Metronidazole which is also used to treat C Difficil. |
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Metronidazole
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Used to treat C Difficil or second drug of choice for Giardia Lamblia(second to Tinidazole).
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Entamoeba Histolytica
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Resides primarily in large intestine but can become systemic if it passes through large intestine into circulation to get to lungs/liver. Can use Tinidazole for systemic infection but it doesn't reach small intestine. To treat large intestine infection you give a luminal drug called Paromomycin.
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Paromomycin
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PO,
Luminal drug which means it is poorly absorbed(but some does enter CNS, see side effects) and as such only acts on the luminal surface of the GI tract. Excreted unchanged in feces. Mechanism of action is inhibition of protein synthesis via binding of 30S ribosome. Side effects: GI problems, rare cases you have nephrotoxicity and ototoxicity. |
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African Trypanosomiasis
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There are two forms
1.) Trypanosoma Brucei Gambiense - Slow form, takes almost two years to develop into active disease 2.) Trypanosoma Brucei Rhodesiense - Can cause rapid CNS infection and death early stage of both diseases you get parasite in blood/lymph and later it moves to CNS where you get headaches and sleepiness. Causes really intense itching |
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Suramin
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IV
The mechanism of action is inhibition of energy metabolism. This drug does NOT distribute to CNS so is only used for early stage of disease. Suramin associated with high toxicity causing renal damage and/or neuropathy. This drug has high failure rate so it is used with pentamadine to treat T.b. gambiense and T.b. rhodesiense |
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Pentamadine
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IV
Is used to treat T.b. gambiense/rhodesiense and its mechanism of action is it interacts with DNA and causes cleavage of it in parasites, possibly effecting topoisomerases. Cannot give to pregnant patients(fetotoxic). Does not distribute to CNS. Also significantly toxic in that it causes renal damage and sometimes even pancreatic damage which can cause diabetes. |
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What do you use to treat T.b Gambiense
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before CNS infection:
a combo of suramin and pentamidine during CNS infection: Melarsoprol. Will NOT respond to second treatment, must use different drug Eflornithine |
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What do you use to treat T.b. rhodesiense
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before CNS infection:
Only Suramin as Pentamadine is NOT effective. after CNS infection: melarsoprol. Usually will respond to repeat treatment. |
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What drug do you use when T.b. enters the CNS?
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Melarsoprol
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Melarsoprol
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IV
Extremely painful drug that reacts with sulfhydryl groups thereby inactivating enzymes like pyruvate kinase. Also, it inhibits trypanothione reductase making cell unable to maintain reduced environment. Side effects are (peripheral) encephalopathy, hypotension, myocardial damage. Notably can cause hemolytic anemia in patients with glucose 6 phosphate dehydrogenase deficiency. It is used to treat CNS infections of Trypanosoma Brucie Gambiense/Rhodesiense. |
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Eflornithine
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IV, PO
Mechanism of action is to inhibit ornithine decarboxylase which makes precursors that are critical for DNA synthesis. Has much milder side effects than Melarsoprol. Will be used to treat T.b. gambiense on recurrent infection but will also work against rhodesiense. Widely distributed and does reach CNS. Apparently it also keeps hair from growing on womens chin so sometimes used in US. Cost prevents widespread use in Africa. |
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American Trypanosomiasis
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Caused by Trypanosoma Cruzi and also called Chagas disease.
Two stages: Stage when it's in blood/lymph and then there is a stage where it is intracellular. Therefore acutely in body fluids, chronically it is in many types of cells which causes death(untreatable). Acute phase is treated Nifurtimox. Chronic phase is currently untreatable. |
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Niifurtimox
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PO
Mechanism of action is generating oxygen free radicals that the parasite cannot get rid of. Side effects are CNS(memory loss, sleep disorders) and anorexia, vomiting. Again, this drug CANNOT be used against chronic Chagas disease when parasite is intracellular. |
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Leishmania
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live inside macrophages with several subspecies. Treated with sodium stibogluconate.
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Sodium Stibogluconate
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IV, IM
Mechanism of action is inhibiting energy metabolism. Side effects are nausea, joint pain. Can be used to treat all forms of Leishmania. |
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Malaria
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Biggest problem for malaria is resistance. Caused by Plasmodium vivax, ovale, falciparum and malariae.
In P ovale and vivax not all organisms leave liver(chronic exoerythrocytic), while other two they do all leave liver. Notably, tetracycline and doxycycline can be used to treat chloroquine resistant malaria. Thought to work by inhibiting protein translation. Sometimes used prophylactically or in conjunction with other malarial meds. |
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Which Plasmodium is most deadly? Why?
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Plasmodium Falciparum because it can infect all forms of RBCs while other species are restricted to certain phases of RBCs.
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Chloroquine
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PO
Rapidly distributes to liver, spleen and kidneys where malaria. Safe in pregnant patients. The mechanism of action is such that it renders the parasites ability to detoxify heme useless.(blocks Haem polymerase). Resistance is a problem in Africa where not enough chloroquine is taken up. Side effect: hemolysis in patients with G6PD. Should not be taken with drugs that also prolong QT |
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Mefloquine
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PO
You can use Mefloquine over chloroquine because it has a different mechanism of entry. Side effects: Should not use with drugs the prolong QT as they can be additive. Also has CNS effects(vivid dreams, seizures, etc.) |
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Pyrimethamine and Sulfadoxine
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PO,
Widely distributed including CNS Similar to Trimethoprim-Sulfamethoxazole. Mechanism is Sulfadoxine(similar to Sulfamethoxazole) inhibits dihydropteroate synthase and Pyrimethamine(similar to trimethoprim) inhibits Dihydrofolate Reductase(DHFR) which is third step of tetrahydrofolate synthesis. Side effects: allergic reactions(Steven johnsons), hemolytic anemia in patients with G6PD, other sulfa drug side like bone marrow suppression. |
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Atovaquone and Proguanil
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PO
Atovaquone is a selective inhibitor of parasite mitochondrial electron transport. Proguanil's active metabolite is a dihydrofolate reductase inhibitor. It is NOT good for pregnant women. |
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Primaquine
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inhibits pyrimidine synthesis and affects mitochondrial electron transport and can cause hemolytic anemia as a side effect. It is the ONLY drug used for extra-erythrocytic malarial infections.
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This set of drugs can cause hemolytic anemia in patients with G6PD.
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Mefloquine, Chloroquine, Primaquine, Pyrimethamine, Sulfadoxin
Many Children Playing Piano Softly |
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Which protozoan drugs are renotoxic? Fetotoxic? QT?
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Pentamadine, Suramin are renotoxic.
Pentamadine and Malarone(Atovaquone and proguanil) are fetotoxic QT are Chloroquine and Mefloquine |
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Mebendazole
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Poorly absorbed, used to treat many nematode infections in GI NOT drug of choice for E. Vermicularis or T Spiralis(but will work, atleast on GI aspect of spiralis). The mechanism of action is oxy phos decoupling, inhibition of glucose uptake and blocking of microtubule polymerization. Causes immobilization and death of parasite.
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Albendazole
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Good absorption, widely distributed and does reach CNS.
Specificity is drug of choice for T. Spiralis in GI and cysticercosis due to Taenia Solium drug interaction: When taken with Praziquantel which causes mean concetration to go up significantly. |
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Pyrantel Pamoate
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PO,
Poorly absorbed in GI, causes paralysis of worm by persistent activation of nicotinic Ach receptors. Worms removed by peristalsis of GI. Used as drug of choice for E Vermicularis. Side effects: normally mild. BUT if overdose than you could have neuromuscular blockade. Drug interactions: should not be given with Piperazine which is an atagonist of the same receptor. |
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Which drugs used to treat GI nematode infections?
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Mebendazole, Albendazole and Pyrantel Pamoate
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Diethylcarbamizine
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PO,
Absorbed readily and distributes well. Mechanism of action is unknown but may be by hyperpolarization. Seems to recruit macrophages. This drug used to treat systemic filarial infections W. Bancrofti(w/ Albendazole) and O vulvulus. The primary side effect to watch out for is the inflammatory response that causes lysis of macrophages engulfing nematode that releases cellular contents. This is called the Mozzotti reaction. The reaction can be treated with antihistamines and glucocorticoids. |
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What can the Mazotti reaction be treated with?
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Antihistamines and glucocorticoids.
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Ivermectin
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Well absorbed, used to treat systemic filarial infections W bancrofti(w/ albendazole), O volvulus and S. Stercoralis. The mechanism of action is activation of GABA and Glutamate gated chloride ion channels only in invertebrates which causes paralysis of parasites.
Side effects: This recruits macrophages like Diethylcarbamizine which can lead to a similar Mazotti reaction. Also at high doses and damaged BBB can lead to CNS toxicities. |
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Which drug treat systemic infections of nematodes?
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Diethylcarbamizine and Ivermectin
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Which cestode(tapeworm) has a tissue phase(cysticercosis)?
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Taenia Solium, the rest are only GI.
Diphyllobothrium Latum Taenia Saginata Hymenolepis Nana |
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When would you not treat a cysticercosis with a drug?
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When it is an infection in the eye, you would not use Albendazole or Praziquantel because it can lead to inflammation that causes blindness. Treatment is with surgery.
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Niclosamide
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Poorly absorbed, mechanism of action is decoupling of ox pho and inhibition of glucose uptake which renders worm inactive and lets you excrete it. Notably, it CAN be given to pregnant patients(not fetotoxic). Not used for Taenia Solium or Hymenolepis Nana. Used for D Latum, T Saginata and E Vermicularis.
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Praziquantel
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Very well absorbed, metabolized by liver. Mechanism is increasing permeability of membrane to calcium causing severe muscular contractions. Does not kill worms, but causes them to be passed out with feces. Useful against all cestodes, Taenia Solium(alternative to Albendazole and it treats both GI and systemic), Diphyllobothrium Latum, Taenia Saginata, and Hymenolepis Nana.
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Name all Trematodes and name which drug you use to treat them.
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Schistosoma Haematobium
Shistosoma Mansoni Shistosoma Japonicum Chlonorcis Sinensis Paragonimus Westermani You use Praziquantel to treat any of these worms. |
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What drug can be used to treat Ascaris Lumbricoides? What type of worm is it?
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It is a nematode and can be treated with Mebendazole or Albendazole
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What drug treats Trichuris Trichiura? What type of worm is it?
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It is a nematode. You use Mebendazole
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What drug treats Enterobius Vermicularis? What type of worm is it?
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It is a nematode. You use Pyrental Pamoate.
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What drug treats Ancylostoma Duodenale and Necator Americanus? What type of worm are they?
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They are nematodes. You use mebendazole or albendazole.
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What drug treats Strongyloides Stercoralis? What type of worm is it?
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It is a nematode. You use Ivermectin.
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What drug treats ONLY the GI phase of Trichinella Spiralis? What drug treats both systemic and GI? What about when the T spiralis is in muscle? What type of worm is it?
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It is a nematode. You use albendazole to treat the GI portion and Praziquantel to treat systemic and GI.
NO DRUG CAN TREAT MUSCULAR LARVAL INFECTION. |
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What drug treats Wuchereria Bancrofti? What type of worm is it?
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It is a nematode. Ivermectin and albendazole or Diethylcarbamazine plus albendazole.
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What drug treats Onchocerca Volvulus? What type of worm is it?
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It is a nematode. You use Ivermectin.
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What drug treats Paragonimus Westermani? What type of worm is it?
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It is a trematode. You use Praziquantel.
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What drug treats Clonorchis Sinensis? What type of worm is it?
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It is a trematode. You use Praziquantel.
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What drug treats the Schistosoma infections? What type of worm is it?
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It is a trematode. You use Praziquantel.
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What drug treats Taenia Saginata? What type of worm is it?
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It is a cestode. You use Praziquantel and niclosamide secondarily.
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What drug treats Diphyllobothrium Latum? What type of worm is it?
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It is a cestode. You use Praziquantel and niclosamide secondarily.
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What drug treats Hymenolepsis Nana? What type of worm is it?
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It is a cestode. You use Praziquantel.
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What drug treats Taenia Solium? What type of worm is it?
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It is a cestode. You use Praziquantel.
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Name the most common to least common fungal infections.
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Cutaneous, Mucocutaneous(GI, perianal, oral), Systemic
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Name the common opportunistic fungal infections? non-opportunistic?
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Opportunistic - Aspergillus, Candida, Cryptococcus
Non-opportunistic - Blastomyces, Coccidioides, Histoplasma |
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Fungi use something other than cholesterol in their cell membrane which allows for some selective toxicity, what is it?
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Ergosterol
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Name all the anti fungal drugs for systemic infection.
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Amphotericin B(Polyene), Ketoconazole, Miconazole, Itraconazole, Fluconacole(Azoles), Flucytosine, Caspofungin(Echinocandins)
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Systemic antifungal drugs for mucutaneous infections
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Griseofulvin, Terbinafin
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Topical Antifungal Therapy
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Nystatin
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Discuss mechanism of all antifungal drugs
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Terbinafine inhibits early step in ergosterol synthesis, Azoles inhibit later step in ergosterol synthesis, Amphotericin B and Nystatin create pores in cell membrane, Caspofungin interferes with beta glucans integration into cell wall and Flucytosine inhibits DNA/RNA synthesis and binds to tubulin.
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Amphotericin B
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IV, oral(for infection in GI)
Binds to ergosterol and creates pores causing electrolyte leakage. Active against almost all fungal species and is usually reserved to treat life threatening infections. Resistance is rare but does occur. It is fungacidal. It is highly nephrotoxic and is usually used to decrease fungal load and then chronically you replace with another drug. You can reduce toxicity by surrounding the Amphotericin by lipids. |
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Ketoconazole
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PO
Effective against most fungi. It inhibits P450 enzyme so there are relevant drug interactions(Cyclosporine, Phenytoin, Tolbutamide, Warfarin). Functions by inhibiting ergosterol synthesis(late step) |
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Fluconazole
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PO
It is well absorbed and widely distributed in the CNS. This drug is fungoSTATIC. Resistance does develop. Given to AIDS patients to prevent relapse. Mostly used against Candida Albicans, Cryptococcus Neoformans, Coccidiodes Immitus, and hisoplasma capsulatum. |
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Voriconazole
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IV, PO
Newer Azole effective against Candida, Aspergillus. Good bioavailability, reaches CNS. |
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Miconazole, Clotrimazole
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Too toxic for anything but topical use.
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Itraconazole
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PO
No CSF penetration, treats Histoplasma, Sporothrix, Aspergilus |
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5-fluorocytosine(flucytosine)
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PO
Used in conjugation with AmB because you get very high rates of resistant strains when used alone. Mechanism is it inhibits Thymidylate synthetase which inhibits DNA/RNA synthesis and is selective because it is only taken up by fungal cells. It is effective against Candida, Cryptococcus, Aspergillus. Side effects: can cause bone marrow suppression, anemia, live problems |
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Caspofungin
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It is relatively new that inhibits cell wall biosynthesis. Effective against Aspergillus and Candida with few side effects
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Grisans, Griseofulvins
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PO
Inhibits microtubule function and prevents mitosis. Deposits in Keratin and is effective against dermatophytes even though they are given orally. Side effect: bone marrow suppression |
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Nystatin
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Topical, swish and swallow
Effective against Candida, not absorbed in GI so can be taken orally but too toxic to be given IV. Also effective against Thrush. |
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How is Azole resistance generated?
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Change in expression of efflux pumps.
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Are Azoles bacteriostatic or bacteriocidal?
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Bacteriostatic
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How do mycobacteria differ from normal bacteria?
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They have mycolic acid in their cell wall which has pharmacological importance
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Isoniazid, Pyrazinamide, Ethambutol mechanism...
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Mechanism of action is blocking mycolic acid synthesis
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Rifampin, Rifabutin mechanism...
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Mechanism is to block transcription and production of mRNA via DNA dependent RNA polymerase.
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Clofazimine mechanism...
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Mechanism is blocking DNA template function meaning it can block RNA for transcription, cell division, etc.
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Dapsone mechanism...
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It is a sulfonamide that inhibits Dihydropteroate synthase.
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Isoniazid
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Mechanism is blocks mycolic acid synthesis. Can be both bacterioCIDAL or bacterioSTATIC. Well spread and reaches CNS. Metabolized by liver and is excreted through kidney in either non acetylated or acetylated form. Non acetylated form produces ammonia and causes toxicity, acetylated form does not cause these problems.
IMPORTANT - This can cause problems in treatment with slow and fast acetylators as slow acetylators will have increased toxicity. IMPORTANT - Side effect is hepatotoxicity(increased with simultaneous Rifampin treatment) and dose adjustment is necessary with liver failure/problems(monitor AST and ALT, especially people over 35 traveling in regions with known TB infections) |
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What is the cause of CNS problems with isoniazid? What are predisposing factors? How is this alleviated?
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It inhibits Pyridoxine kinase and therefore pyridoxine phosphate formation which is necessary for synthesis of neurotransmitters.
More common in diabetics, alcoholics, slow acetylators. It is alleviated with the cocommitant administration of Vitamin B6 |
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Rifampin, Rifabutin
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PO
Well distributed, reaches CNS. Both drugs metabolized in liver. Rifampin eliminated via hepatic secretion and Rifabutin eliminated via urine. Rifabutin is a semisynthetic derivative of Rifampin. Mechanism of action is blocking transcription. They don't differ in mechanism but differ in their ability to induce P450. Drugs used to treat all forms of mycobacteria(tuber.,marinum,kansasii,leprae, MAC as well as gram + gram -(Staph Aureus and Neiserria Meningitis) and are bactericidal. IMPORTANT - Side effect: They impart an orange/red color in the urine. Minor CNS effects. Rifampin can lead to hepatitis in patients receiving Isoniazid or are alcoholics. |
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When would you use Rifabutin of Rifampin?
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Differ in their ability to induce P450.
Rifampin is a strong inducer of Cyp3A4 as well as other isoforms which causes lots of drug interactions. Rifabutin is not as big of an inducer. Big interaction is HIV protease inhibitors which reduces levels by 80% when taken with Rifampin and would be switched to Rifabutin. |
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Ethambutol
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PO
Inhibits mycolic acid synthesis. Does not distribute to CNS. It is BacterioSTATIC. IMPORTANT - dose adjustment in renal failure. First line drug to treat mycobacterium tuberculosis, kansasii, avium complex, and marinum. IMPORTANT - Side effect: Optical neuritis, loss of ability to distinguish red and green. |
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Pyrazinamide
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PO
It is BacterioCIDAL. Mechanism similar to isoniazid, interferes with mycolic acid synthesis. Distributes well and reaches CSF. First line drug to treat Mycobacterium Tuberculosis Pyrazinamide is only used for 6 months due to hepatotoxicity. Cannot be taken longer unlike Isoniazid. IMPORTANT - Should not be given to patients with liver problems. |
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Difference between Isoniazid vs Pyrazinamide
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Isoniazid you would give it to someone and monitor liver function as you go along and the Pyrazinamide you would just not give to someone with liver problems
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Clofazimine
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PO
It is well distributed including CNS and is excreted in feces. Very little excreted in urine. The mechanism is to bind to DNA and block RNA production, Long been used to treat leprosy. Side effect: it is a dye so in patients you see pink/brownish discoloration in skin/cornea/retina/urine. IMPORTANT - It is also NOT recommended for pregnant patients(fetotoxic) and also possible to pass through breast milk. |
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Dapsone
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PO
Widely distributed including CNS. Hepatic metabolism and consequent excretion in urine. Mechanism is it inhibits dihydropteroate synthase which inhibits tetrahydrofolate synthesis.(same as other sulfadrugs) first line treatment for leprosy IMPORTANT - Side effects: same as other sulfa drugs, allergic effects(steven johnson), hemolytic anemia in G6PD patients, sulfone syndrome |
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What drug treatments used to treat M. tuberculosis?
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Isoniazid + rifampin + or - pyrazinamide + ethambutol or streptomycin
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