Tuberculosis Drugs, Antivirals,
Antiretrovirals, Antifungal and
Anti-Parasitics
Felix Hernandez, M.D.
Antituberculosis Drugs
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Isoniazid
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Rifampin
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MOA: blocks the beta subunit of bacterial RNA polymerase thus
stopping bacterial RNA synthesis
Side Effects: urine and sweat turn red, induces P450, hepatitis
Pyrazinamide
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MOA: inhibits mycolic acid synthesis in the wall
Side Effects: peripheral neuropathies (prevent with treatment
with pyridoxine), hepatitis, hepatotoxicity
MOA: nicotinamide analog with unknown mechanism
Side Effects: hepatitis, hyperuricemia with gouty arthritis.
Is never used alone because of rapid resistance
Ethambutol
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MOA: inhibits mycolic acid synthesis in bacterial cell wall
Side Effects: reversible retrobulbar neuritis, loss of central vision
Antiviral Drugs (DNA and RNA)
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Acyclovir
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MOA: inhibits DNA polymerase and incorporates itself
into viral DNA
Clinical Use: herpes simplex 1 and 2 and Varicella
zoster
Side Effects: skin irritation and burning, crystalline
nephropathy with rapid infusion
Ganciclovir
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MOA: same as Acyclovir
Clinical Uses: CMV retinitis and severe systemic CMV
infections in immunocompromised patients
Side Effects: granulocytopenia, anemia,
thrombocytopenia, renal dysfunction
Antiviral Drugs (DNA and RNA)
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Foscarnet
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MOA: analog of pyrophosphate and competes with it
in viral DNA polymerase and reverse transcriptase
therefore inhibiting DNA synthesis
Clinical Uses: CMV retinitis in immunocompromised
patients and acyclovir resistant HSV
Side Effects: renal toxicity, seizures, hypocalcaemia,
anemia
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Is deposited in bone and teeth.
Hydrate patient to protect the kidneys
Amantadine
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MOA: prevents virus from entering susceptible cells
Clinical Uses: treatment/prophylaxis of Influenza A in
the elderly
Side Effects: depression, CNS toxicity, CHF, orthostatic
hypotension, urinary retention
Rimantadine is used for prophylaxis in children
Antiviral Drugs (DNA and RNA)
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Ribavirin
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MOA: unknown
Clinical Uses: RSV in children
Side Effects: decreased pulmonary function,
teratogenic in animals
Is given via aerosol but is absorbed
systemically
Oseltamivir
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MOA: analog of adenosine monophosphate
Clinical Uses: chronic hepatitis B
Side Effects: HA, asthenia (weakness and loss
of strength)
Antiretroviral Therapy
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Zidovudine, Didanosine, Lamivudine
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MOA: nucleoside HIV reverse transcriptase
inhibitor
Clinical Uses: HIV in combination therapy
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Zidovudine is used in the prevention of maternalfetal transmission
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Mom takes it prenatally then infant takes it for 6 weeks
Side Effects: peripheral neuropathy,
pancreatitis, myelosuppression with
Zidovudine
Antiretroviral Therapy
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Ritonavir, Indinavir
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MOA: protease inhibitor (cleaves gag-pol) that
results in immature virus formation
Clinical Uses: HIV in combination therapy
Side Effects: weakness, anorexia,
parasthesias, indinavir has an increased risk
of kidney stones
Antiretroviral Therapy
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Nevirapine, Efavirenz
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MOA: non-nucleoside inhibitor of HIV reverse
transcriptase
Clinical Uses: HIV  never as monotherapy
due to rapid resistance
Side Effects: severe skin rash
Nevirapine crosses the placenta
Pneumocystis carinii Agents
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Trimethoprim-Sulfamethoxazole (Bactrim)
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Pentamidine (Pentam)
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MOA: inhibits folate synthesis pathway
Clinical Uses: Oral is DOC for PCP prophylaxis in
immunocompromised patients. IV is DOC for PCP
infection
MOA: unknown
Clinical Uses: nebulized form used as an alternative
for prophylaxis, IV is alternative for treatment
Side Effects: Bronchospasm
Atovaquone (Mepron)
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MOA: unknown
Clinical Uses: treatment for TMP-SMZ resistant strains
Antifungal Drugs
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Polyenes
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Amphotericin B
MOA: disrupts the plasma membrane of fungal
cells
 Clinical Uses: DOC for systemic fungal infections,
fungal meningitis and fungal UTI
 Side Effects: is toxic at therapeutic doses,
nephrotoxicity, hypokalemia, thrombophlebitis,
anemia
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Nystatin
MOA: same
 Clinical Uses: DOC for intestinal Candida or thrush
 Side Effects: few adverse effects
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Antifungal Drugs
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Imidazoles
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Ketoconazole
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MOA: impairs synthesis of ergosterol which is a principle
component of the fungal plasma membrane
Clinical Uses: DOC for thrush and chronic mucocutaneous
candidiasis
Side Effects: fetal hepatic necrosis, gynecomastia and breast
pain (due to inhibition of testosterone synthesis)
Fluconazole (Diflucan)
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MOA: inhibits fungal P450 and damages the plasma
membrane by inhibiting sterol demethylation which is an
integral step in plasma membrane synthesis
Clinical Uses: systemic histoplasmosis, candidal vaginitis and
esophagitis
Side Effects: rash, diarrhea
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Has no effects on testosterone synthesis
Antifungal Drugs
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Itraconazole
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Clotrimazole (Lotrimin)
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MOA: same as fluconazole
Clinical Uses: aspergillosis, histoplasmosis, local tinea
or candidal infections
Side Effects: edema, hepatitis
No testosterone effects
MOA: mechanism unknown
Clinical Uses: DOC for candida and dermatophyte
infections of the skin and vaginal candidiasis
Miconazole (Monistat)
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MOA: unknown
Clinical Uses: vaginal candidiasis
Side Effects: phlebitis, pruritis, rash
Antifungal Drugs
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Flucytosine
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Griseofulvin
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MOA: converted to 5-fluoro-uracil by the fungus and is
incorporated into the RNA where thymidilate synthetase is
inhibited
Side Effects: leukopenia, increased LFT, bone marrow
suppression
MOA: interferes with the synthesis of nucleic acids
Clinical Uses: dermatophytes of hair, skin and nail. May require
up to 6mo treatment
Side Effects: decreased memory and judgment, leukopenia,
photosensitivity, possible teratogen (CI in prego)
Terbinafine (Lamisil)
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MOA: inhibits squalene epoxidase a critical enzyme in ergosterol
synthesis
Clinical Uses: toe nail infection due to Trichophyton
Side Effects: neutropenia, skin reactions and ophthalmic toxicity
Antiparasitic Drugs
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Metronidazole (Flagyl)
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MOA: binds DNA and inhibits synthesis in
bacteria. In parasites it’s unknown
Clinical Uses: E. histolytica, Trichomonas,
Giardia
Side Effects: seizures, ataxia, Disulfiram-like
reaction
Lindane
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MOA: induces seizures in ectoparasites
Clinical Uses: Scabies and lice
Side Effects: seizures, CNS disturbance and
risk of arrhythmias
Antiparasitic Drugs
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Antihelminthic Drugs
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Mebendazole
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MOA: disrupts microtubules in worms
Clinical Uses: DOC for pinworm and is also effective against
roundworms
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Side Effects: GI pain
Praziquantel
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Pinworms is highly contagious and the entire family should be
treated
MOA: increases cell membrane permeability causing a loss of
calcium which results in paralysis of the worm and release
from host tissue
Clinical Uses: Schistosomiasis (single dose)
Side Effects: minimal, flu-like symptoms
Ivermectin
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MOA: Glutamate-gated channel antagonist that causes worm
paralysis
Clinical Uses: strongyloides and Onchocerca
Side Effects: pruritis
Antimalarial Drugs
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Chloroquine or Hydroxychloroquine
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MOA: Mechanism unclear and has wide resistance
(UK)
Clinical Uses: prophylaxis and acute attacks
Side Effects: irreversible retinal damage, hemolysis in
G6PD-deficient patients
Quinine
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MOA: not clear
Clinical Uses: treat chloroquine resistant P. falciparum
Side Effects: Cinchonism (flushed and sweaty skin,
ringing of the ears (tinnitus), blurred vision, impaired
hearing, confusion, reversible high-frequency hearing
loss), Most toxic antimalarial and should only be used
when all other fail, cardiac arrhythmias
Antimalarial Drugs
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Mefloquine
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Pyrimethamine
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MOA: structural analog of quinine
Clinical Uses: multidrug resistant malaria
Side Effects: well tolerated, benign sinus bradycardia
MOA: inhibits folate synthesis by inhibiting
dihydrofolate reductase
Clinical Uses: Malaria prophylaxis and used in
combination for acute attacks
Side Effects: Few and are very mild
Primaquine
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MOA: unclear but likely to involve crosslinking of
glutathione
Clinical Uses: chloroquine resistant Vivax malarias
Side Effects: hemolysis in patients with G6PD
deficiency