MG - infectious diseases and oncology 6

Tuberculosis, NTDs and worms

tuberculosis

pathogen can cause latent and active infections, in otherwise healthy it is latent.

only the active form is transmitted via aerosols

latently infected people can relapse into active disease progression even years after initial infection

lives mostly intracellular

Ziehl-neelsen staining is positive

has no outer membrane, then there is the outer cell membrane but the outer part of the cell wall is covered with long 60-90 carbon chain mycolic acid. inner part consists of peptidoglycan with high degree of crosslinking

mycolic acids

outer part of the cell wall is covered with this

very long fatty acid that is crosslinked that has unusual carbocycles and other funcitonal groups

isoniazid, rifampicin, pyrazinamide

first line treatment of tuberculosis for 6 months

isoniazid:

• MOA: mycolic acid synthesis inhibitor

• it is active on extra- and intracellular tuberculosis and is bactericidal for actively growing tbc

• toxicity: hepatits, peripheral neuropathy

• high incidence of toxicity, which is why there is coadministration

rifampicin

• MOA: inhibitor of RNA synthesis by binding b-subunit of DNA-dependent RNA polymerase

• effect: bactericidal against gram + and reaches intracellular tbc and otherwise difficult to access tissues

• good oral bioavailability

• SE: discoloration of secretions, CYP inducer

pyrazinamide

• MOA unknown

• mainly active on dormant, kills residual intracellular tb in combination therapy

• SE: hyperuricemia

ethambutol

alternative 1st line treatment

MOA: inhibitor of arabinosyl transferase

bacteriostatic, mostly effective against active extracellular tb

indications: tb meningitis and in case of isoniazid resistance with rifampicin, pyrazinamide and levofloxacin

bedaquiline

designed for multidrug resistant tb

targets the proton pump for ATP synthase

there should be close monitoring of liver enzymes(strong interactions) and monitoring of heart function(QT cycle prolongation)

pretomanid

anti-tb

prodrug which kills due to release of NO resulting in respiratory poisoning of the bacteria

beef tapeworm

transmission through infected meat

usually no symptoms

treatment with niclosamide

there should be differential diagnosis between the beef and pig tapeworm as the pig is more problematic

pinworms

roundworm

transmission through fecal smear (kids)

treatment with mebendazole

albendazole, thiabendazole, mebendazole

benzimidazole drugs

antihelminths

broad spectrum

• for luminal parasites should be taken on empty stomach

• for tissue parasites should be taken with greasy meals

MOA: inhibition of the microtubule synthesis

niclosamide

first line treatment for beef tapeworm, second line for others

salicylamide derivative

ivermectin

MOA: stimulation of ligand-gated ion channels in motorneurons resulting in the paralysis of the worm

broad spectrum antiparasitic medicine

adverse effects: fatigue, nausea, dizziness, vomiting, rashes, abdominal pain

concomitant use of GABA enhancing drugs should be avoided

not to be used during pregnancy

schistosomiasis

chronic worm infection

symptoms: fever, fatigue, head and muscle aches, rash, hoves, abdominal pain, diarrhea, blood in stool and urine

praziquantel treatment: racemic compound

• SE: gagging/vomiting due to bitter taste, discolored stool and urine, GI issues, mild neurological issues