Final exam Flashcards
HIV drug selection strategy:
Varying mechanisms, toxicities, patient symptoms, drug interactions, and adherence/administration convenience
How do supplements differ from drugs and OTC medications?
they are legally considered food supplements used for health maintenance even if they’re really “drugs”
What drugs can cause jaundice?
Macrolides/Ketolides,
Efavirenz
HIV drug, NNRTI that causes conformational change to HIV-1 reverse transcriptase. P450 inducer, *great half-life, can cause vivid dreams
What drugs can cause crystalluria?
Sulfonamides
Moa: inhibits protein and RNA synthesis in trypanosomiasis
Benznidazole. Tx Chagas disease
Rifampin AE:
Uncommon Nausea, vomiting, rash. Orange feces, urine, and tears. Increase p450 metabolism
What are the 3 approaches of developing a new drug?
New drug targets, new drugs based on receptor structure, modification of known molecule
Metronidazole
Mixed Amebicides AND tx Giardiasis. Moa form cytotoxic compounds that bind to proteins and DNA. *AE metallic taste, rare neurological disorder. resistance not a problem. Tx of choice for Giardiasis.
Ginseng
Botanical/Herbal. used as an upper: increased NT in CNS. anti-inflammatory, anti-cancer
What supplement has antibiotic effects?
Echinacea, Garlic
Rimantadine
Respiratory flu drug. inhibits viral uncoating. Blocks viral membrane matrix protein M2 so viral and host membrane can’t fuse.
What do Trophozoites do?
Entamoeba histolytica trophozoites multiply and invade intestinal mucosa or feed on intestinal bacteria
What treats pneumonia in immunocompromised patients?
Cotrimoxazole (Trimethoprim + Sulfamethoxazole)
Ofloxacin
*2nd line antimycobacterial and 2nd Gen Fluoroquinolone. Enters bacteria via diffusion; uses dual mechanism to inhibit DNA gyrase and topoisomerase IV. *inexpensive
What is the resistance of aminoglycosides?
Resistance not severe when topical
Which malaria drug has a very long half-life?
Mefloquine
Itraconazole
*Antifungal, Azole. Inhibits P450 enzyme that converts lanosterol to ERGOSTEROL, disrupting fungal membrane. *Tx histoplasmosis, take with food (needs acid)
What are the two forms of
Entamoeba histolytica?
Cyst and Trophozoite (survives in body)
How long do drug patents last? What is the average effective patent life of a drug?
20 years but includes approval time. Average effective patent life for major pharmaceuticals is around 11 years
What causes dysentery?
Entamoeba histolytica
AE Linezolid:
Thrombocytopenia, Anemia, Optic and peripheral neuropathy. Caution with MAOIs and SSRIs
Which drugs are the luminal Amebicides
Iodoquinol and Paromomycin (think IodoParo luminal)
What supplement is used for decreasing blood pressure?
Garlic
What are the limitations to pre-clinical testing?
Time-consuming and expensive (can take up to 6 years), Large numbers of animals needed to obtain valid data, Animal to human toxicity data not always predictive, and Rare adverse effects are not likely to be identified.
Which rifamycin has the longest half-life?
Rifapentine
What is the resistance of Amphotericin B?
Infrequent
What is the commonly diagnosed intestinal parasite in the U.S?
Giardia lamblia
Posaconazole
*Antifungal, Azole. Inhibits P450 enzyme that converts lanosterol to ERGOSTEROL, disrupting fungal membrane. *the most broad spectrum azole
Chloroquine
Systemic Amebicides AND tx Malaria. Prevents malaria from digesting Hb; pH increases, heme accumulates, parasite AND rbc lyse! rapidly oral, cure in 4 days. Tx erythrocytic form. AE: minimal, can cause bull’s-eye maculopathy. Malaria resistance become a problem–combo therapy resolves. ALSO tx inflam disease like rheumatoid arthritis and lupus
Which amebicide is actually an aminoglycoside antibiotic?
Paromomycin (luminal amebicide)
Darunavir
HIV protease inhibitor. inhibits HIV aspartyl protease to prevent viral maturation. MANY drug-drug interactions.
Which drug class causes vestibular problems?
Tetracyclines
MOA: Inhibits many enzymes involved in energy metabolism of Trypanosomiasis
Suramin (Trypanosomiasis)
Amikacin
PSI Aminoglycoside. Binds to 30s ribo subunit preventing protein synthesis initiation AND cause misreading of mRNA causing wrong AA insertion.
5 classes of HIV drugs:
1 Nucleoside/tide reverse transcriptase inhibitors (NRTIs), 2 Nonnucleoside reverse transcriptase inhibitors (NNRTIs), 3 Protease inhibitors, 4 Entry inhibitors, 5 Integrase inhibitors
Linezolid
PSI, “other”. binds to 50s subunit to inhibit ribosome complex formation.
Abacavir
HIV drug, NRTI, nucleoside/tide integrates into DNA, terminating DNA elongation. *good for renal failure patients. can cause a fatal allergic reaction upon second exposure
AE for Amphotericin B:
It has a low therapeutic index. , Fever/Chills, Muscle spasm, Vomiting, Headache, Hypotension. Cumulative: renal impairment
AE of tetracyclines:
Gastric discomfort w/ Ca++ Food. Severe sunburns. Vestibular problems. Pseudotumor cerebri
What supplement is used as antidepressant?
St. John’s Wort
What portion of the world is exposed/infected with Tb?
1/3
What drugs are neuraminidase inhibitors?
Oseltamivir and Zanamivir (OselZana)
Ganciclovir
Cytomegalovirus drug. Guanosine analog gets incorporated into viral DNA via DNA poly. avoid in pregnancy, and renal failure. Available in ocular preparation (Zirgan). Easy dosing but expensive
Which antimycobacterial involves prodrugs?
Isoniazid and Ethionamide
What are the phases of new drug?
Drug discovery, screening, preclinical testing, human testing, clinical trials, (phase 1-4)
Which Fluoroquinolone is bad systemically but good for UTIs and GI disease?
Norfloxacin
What drug class competes with dihydropteroate synthetase and inhibit folate production?
Sulfa drugs
Coenzyme Q10
Purified Supplements. used for hypertension, improving output in heart failure, prevents statin-induced myopathy
Resistance for tetracyclines:
Widespread
Sulfacetamide
Antifolate. Prohibits bacterial production of folate because drug is PABA analogue and competes with dihydropteroate synthetase.
Which drugs are dangerous for pregnant women?
Tetracyclines, Trimethoprim (antifolate), Fluoroquinolones, Isoniazid (first line), Inhibitors of viral uncoating (caution), Ribavirin (Hepatitis), Ganciclovir (cytomeg and corneal herpes), Antiprotozoal agents,
Emetine
Systemic Amebicides. inhibits protein synthesis. Via IM; oral might cause vomiting. Can concentrate in liver for a month
Nifurtimox
tx Trypanosomiasis, acute Chagas.MOA: oxygen radicals toxic to both host/parasite but human enzymes fix damage. Adverse Effects:, Hypersensitivity (acute and delayed), GI problems (sometimes severe), Peripheral neuropathy
What is the goal of phase 1 clinical trials?
Determine the probable limits of the safe clinical dosing range. Absorption, half-life, and metabolism are also often studied in this phase
What ophthalmic drug causes lots of irritation? Which is easy on the eye?
The inexpensive Trifluridine irritates and requires frequent dosing. The more expensive Ganciclovir is easier on the eye and has easier dosing.
How are macrolides/ketolides administered?
Oral is good. Erythromycin should NOT be given IV
Which trypanosomiasis drug is recommended
as prophylaxis in hematopoietic stem cell transplant recipients?
Benznidazole
What can cause ototoxicity?
Aminoglycosides, macrolides (esp erythromycin), Capreomycin (2L antimycobacterial)
What is the spectrum of Aminoglycosides?
Gram - (including pseudomonas) , some +
AE of NRTI:
Mainly due to inhibition of mitochondrial DNA polymerase; Can include peripheral neuropathy, pancreatitis, and lipoatrophy; All have been associated with potentially fatal liver toxicity
Which malaria drug is reserved for severe/resistant cases?
Quinine
What is the treatment of choice for Giardiasis?
Metronidazole for 5 days
What supplement is used for cartilage nutrient?
Glucosamine (purified supplement)
What drugs interact with bacterial RNA polymerase to block transcription?
Rifamycins (1L antimycobacterial)
Which are the drugs that prohibit viral uncoating?
Rimantadine and Amantadine
Which NRTI has a conveniently long half-life?
Tenofovir
What can cause bull’s eye maculopathy?
Chloroquine (systemic amebicide and malaria drug) and Primaquine (Malaria drug)
What drugs are used to treat MRSA?
Vancomycin, Bacitracin, Ceftaroline (5th gen) (kinda Telavancin, kinda Daptomycin). Linezolid PSI, Cotrimoxazole (antifolate)
What is included with an Investigational New Drug (IND)?
Composition, chemical/manufacturing info, animal studies data, clinical trial plans, names and credentials, relevant data for humans
What’s the difference between acute, subacute, and chronic toxicity?
Acute is determined of maximum dose, subacute is long-term dose toxicity (weeks to months), and Chronic toxicity is even longer
Demeclocycline
PSI, Tetracycline. reversibly binds to 30s ribo. subunit preventing tRNA binding–translation stops.
Rifampin
*First-line antimycobacterial. inhibits RNA polymerase to prevent transcription. induces P450, ORANGE POOP
Tetracycline
PSI, Tetracycline. reversibly binds to 30s ribo. subunit preventing tRNA binding–translation stops.
What 1st line antimycobacterial is preferred for HIV patients?
Rifabutin
Which Fluoroquinolone have the longest half-lives?
Levofloxacin and moxifloxacin
AE: cinchonism: Nausea, Vomiting, Tinnitus, Vertigo
Quinine (malaria drug)
What drugs are bad with antacids?
Quinine (malaria drug),
Fluoroquinolones and Tetracyclines (PSI)
Between acyclovir,
Valacyclovir, and Famciclovir, which is safest in pregnancy?
Famciclovir (anti-herpes)
What is the oral mouthwash for thrush?
Nystatin
What is the goal in phase 4 post marketing?
Monitor the safety of the new drug under actual conditions of use in large numbers of patients. Requires reporting by all physicians using the medications (because some adverse effects may become apparent only after chronic dosing)
Melatonin
Purified Supplements. used for jet lag, insomnia, and improving sleep
HIV treatment now consists of suppressing HIV replication, allowing for restoration of ___ cells and immunocompetence
CD4 or T Helper Cells
Benznidazole
tx Trypanosomiasis. alternative for Chagas disease. Moa: inhibits protein and RNA synthesis. Recommended as prophylaxis in hematopoietic stem cell transplant recipients.
What is the second-line antifungal if amphotericin B or azole fails?
Caspofungin (Echinocandin)
Milk Thistle
Botanical/Herbal. used for treating liver disease, anti-cancer, promotes lactation
What drug causes squalene to build up to toxic levels?
Terbinafine (antifungal)
Ethambutol
First-line antimycobacterial. interferes with cell wall synthesis *EOM pain primary complaint with red/green color deficiency and optic neuritis
Which of the Amebicides can cause optic neuritis?
Iodoquinol.
Etravirine
HIV drug, NNRTI that causes conformational change to HIV-1 reverse transcriptase. P450 inducer,
How are Sulfonamides metabolized and excreted?
Liver metabolized kidney excreted
Mefloquine
Malaria drug. *tx erythrocytic form. Has very long half life. good for pregnant. AE: Nausea and vomiting, Dizziness, Disorientation and depression, Cardiac arrest possible if taken concurrently with quinine or (quinidine)
Macrolides/Ketolides contraindications:
Hepatic dysfunction, arrhythmia
What drug can cause vivid dreams?
Efavirenz (NNRTI)
What is clinically equivalent to acyclovir but have longer half lives?
Valacyclovir, Famciclovir (anti-herpes)
Spectrum of Rifamycins:
+/-, mycobacteria, Leprosy
St. John’s Wort
Botanical/Herbal. used as antidepressant, antiviral and anticarcinogenic
Pharmacokinetics for tetracyclines:
Avoid calcium, iron, antacids (reduces plasma concentration). Do not give to children, can cross placenta. Bile secreted.
AE for Trimethoprim:
Folic acid deficiency (leads to anemia, Leukopenia, Granulocytopenia)
Which amebicide is effective against both trophozoite and cyst forms?
Iodoquinol (luminal)
Adverse Effects:, Hypersensitivity (acute and delayed), GI problems (sometimes severe), Peripheral neuropathy
Nifurtimox (trypanosomiasis)
What is the most potent Tb medication?
Isoniazid
Primaquine
Malaria drug. perhaps toxic metabolites. *treats EXOerythrocytic forms, including in liver, gametocytic forms. can cause bull’s-eye maculopathy. AE: can aggravate lupus/arthritis
How is one typically infected by Giardia lamblia?
Contaminated water (or food). Fecal-oral route
Which anti-viral is given intranasally?
Zanamivir
Voriconazole
*Antifungal, Azole. Inhibits P450 enzyme that converts lanosterol to ERGOSTEROL, disrupting fungal membrane. *inhibits P450, increasing warfarin conc
What leprosy drug also has anti-inflammatory activity?
Clofazimine
Which macrolide has a good half-life and high Vol of distribution?
Azithromycin
What supplement is used for increasing wbc?
Echinacea
AE Isoniazid (1L antimycobacterial):
Hepatitis and idiosyncratic hepatotoxicity, Peripheral neuritis, Mental abnormalities, convulsions, Optic neuritis, Hypersensitivity
Nystatin
*Antifungal, Polyene Antibiotic. binds to ergosterol in membrane making ion pore > death. *Tx topical Candida and Thrush mouthwash
Which NRTI has many antiretroviral drug interactions?
Tenofovir
Antibacterial spectrum for tetracyclines:
Considered broad spectrum, Gram(-) and Gram(+), Also against other organisms
What supplement is used for lowering cholesterol?
Garlic
What are the malaria drugs?
Chloroquine, Mefloquine, Primaquine, Quinine (think qui-quine). Chloroquine is also a systemic amebicide
Enfuvirtide
HIV drug, entry inhibitor that binds to viral transmembrane glycoprotein, preventing the conformational change that allows entry in cell.
What supplement used as an upper: increased NT in CNS?
Ginseng
AE Methenamine:
GI distress, formaldehyde reacts with Sulfonamides
What drug colors feces, urine, and tears ORANGE?
Rifampin (1L antimycobacterial)
Dolutegravir
HIV integrase inhibitor that inhibits final step of integration of viral DNA into host DNA. NO P450 interactions. *extensive liver metabolism once or twice dosing (twice if previous treatment with other integrase inhibitors.
Streptomycin
Second-line antimycobacterial aminoglycoside. MoA not given.
Tx fungal infections of nails?
Terbinafine (antifungal)
What drug interferes with the synthesis of B-glucan, causing lysis and cell death?
Echinocandins
Which antiviral has few side effects?
Lamivudine (anti hep/NRTI) .(rarely headaches/dizziness)
What is the mechanism of HIV protease inhibitors?
They inhibit HIV aspartyl protease to prevent the maturation of viral particles, making noninfectious virions
Elvitegravir
HIV integrase inhibitor that inhibits final step of integration of viral DNA into host DNA. NO P450 interactions. *only in combination with Tenofovir/Emtricitabine/Elvitegravir/Cobicistat
What drugs can cause GI disturbances?
Chloramphenicol (PSI), methenamine and nitrofurantoin (UTI tx), Flucytosine (antifungal), Ethionamide (2L antimycobacterial), HIV protease inhibitors, Nifurtimox (trypanosomiasis)
What drugs are bad to have with Zinc?
Fluoroquinolones
Which drug can cause tinnitus and vertigo?
Quinine (malaria drug)
What inhibits fungus until skin sloughs off?
Griseofulvin
What supplement is used for treating BPH (inflamed prostate)
Saw Palmetto
Goals for HIV treatment
Maximally and durable suppress viral load, replication, Restore and preserve immunologic function, Reduce HIV-related morbidity and mortality, Improve quality of life
How is the resistance in Cotrimoxazole?
Not frequent because bacteria needs to resist both drugs (Trimethoprim + Sulfamethoxazole)
Rifapentine
*First-line antimycobacterial. inhibits RNA polymerase to prevent transcription. *has long half-life
Flucytosine
Antifungal, “Other”. drug enters fungal cell and is converted into the antimetabolite 5-FU
What is the mechanism of NRTIs?
Nucleoside/tide reverse transcriptase inhibitors are analogs that are incorporated into viral DNA by viral reverse transcriptase (once drug is phosphorylated). This terminates DNA chain elongation.
Emtricitabine
HIV drug, NRTI, nucleoside/tide integrates into DNA, terminating DNA elongation * has NO significant drug interactions.
What drugs can cause optic neuritis?
Isoniazid (Antimycobacterial), Ethambutol (1L antimycobacterial), Ethionamide (2L antimycobacterial), Iodoquinol (luminal amebicide)
Moa:
Prevents malaria from digesting Hb; pH increases, heme accumulates, parasite AND rbc lyse!
Chloroquine (also systemic amebicide )
What drug can cause hepatitis?
Isoniazid (1L Antimycobacterial)
Macrolides
Second-line antimycobacterial and PSI. Binds to 50s ribo. subunit (can inhibit its formation) to block peptidyl transferase center to prevent AA elongation.
Food impairs absorption of what drug?
Isoniazid (1L antimycobacterial)
Why are supplements not more widely accepted by the medical community?
Clinical studies are poorly designed and Do not account for placebo effect. Most studies not peer reviewed.
Clarithromycin
*PSI, Macrolide/Ketolide. Binds to 50s ribo. subunit (can inhibit its formation) to block peptidyl transferase center to prevent AA elongation. *also Tx H influenzae
Nitazoxanide
Tx Giardiasis
Sulfadiazine
Antifolate. Prohibits bacterial production of folate because drug is PABA analogue and competes with dihydropteroate synthetase. *COMBINED with pyrimethamine in toxoplasmosis tx.
What drugs can cause changes in glucose and lipid metabolism?
HIV protease inhibitors
What drugs can cause connective tissue problems?
Fluoroquinolones
Cotrimoxazole (Bactrim)
Antifolate. Trimethoprim + Sulfamethoxazole. Tx UTIs, Respiratory tract infections, Pneumocystis jiroveci pneumonia in immunocompromised patients
Tipranavir
HIV protease inhibitor. inhibits HIV aspartyl protease to prevent viral maturation. MANY drug-drug interactions. *cause severe and fatal hepatitis, rare intracranial hemorrhages
Which Fluoroquinolone is poor against pseudomonas and not good for UTIs?
Moxifloxacin
What disease causes some to be asymptomatic, others to have serious diarrhea (esp. in immunocompromised patients)?
Giardiasis (Giardia lamblia)
Which HIV protease inhibitor can cause diarrhea and is NOT boosted by Ritonavir?
Nelfinavir
Azithromycin (Zithromax, Zpak)
PSI, Macrolide/Ketolide. Binds to 50s ribo. subunit (can inhibit its formation) to block peptidyl transferase center to prevent AA elongation.
What drugs are best acidic?
Methenamine, nitrofurantoin.
Who should not take tetracyclines?
Kidney deficient (Doxycycline is ok), motherly women, children under 8, warfarin takers
What is the goal of neuraminidase inhibitors?
Decrease the intensity and duration of symptoms within 1-2 days of infection.
Antibacterial spectrum of Macrolides/Ketolides:
Similar to penicillin G (gram +)
What supplement is used for increasing blood flow and vasodilation?
Ginkgo
Methenamine
Urinary Tract Antiseptic. Makes formaldehyde at low 5.5 pH
Maraviroc
HIV drug, entry inhibitor that blocks binding of viral membrane to host cell on CCR5 receptor
Which drugs have a dual mechanism against bacteria?
Fluoroquinolones
Interferon
Viral Hepatitis drug. MoA poorly known: inhibit viral RNA translation
Norfloxacin
*2nd line antimycobacterial and 2nd Gen Fluoroquinolone. Enters bacteria via diffusion; uses dual mechanism to inhibit DNA gyrase and topoisomerase IV. *Tx GI disease and UTIs
What is the goal of phase 2 clinical trials?
determine efficacy
Drug resistance of NRTIs:
Only between same analog class
What drugs are used prophylactically in patients exposed to meningitis
Rifampin (1L antimycobacterial)
What is used prophylactically for sleeping sickness?
Suramin (trypanosomiasis)
Which drug class causes phototoxicity?
Tetracyclines, Fluoroquinolones
What is the drug of choice for histoplasmosis?
Itraconazole
What causes Chagas disease
American: trypanosomiasis via insect feces
Famciclovir
Herpesvirus drug. ?Guanosine analog gets incorporated into viral DNA via DNA poly. safest in pregnancy
Who is involved in phase 3 clinical trials?
larger numbers of patients with the target disease (usually thousands of patients)
Pyrazinamide
First-line antimycobacterial. Inhibits growth by lowering intracellular pH *can cause precipitate gout
Who is involved in phase 2 clinical trials?
100-200 subjects with target disease.
Which trypanosomiasis drugs treat American Chagas disease?
Nifurtimox and Benznidazole (alternative)
What’s the difference between first and second line antimycobacterials?
Second line drugs are no more effective than first line agents but toxicities may be more serious.
What NRTI is best taken when fasting?
Didanosine
What is the goal of phase 3 clinical trials?
Establish and confirm safety and efficacy; designed to minimize errors caused by placebo effects and disease variations; Usually performed in settings similar to what is anticipated for the ultimate use of the drug (hospitals, clinics, etc)
How is Linezolid administered?
Oral is completely absorbed (IV also available)
Tx UTI:
Methenamine and nitrofurantoin (UTI antiseptics), Norfloxacin (fluoroquinolone),
MoA: interferes with heme polymerization.
Quinine (malaria drug)
What are the different types of amebicidal drugs?
Luminal, systemic, or mixed (both)
Tobramycin
PSI Aminoglycoside. Binds to 30s ribo subunit preventing protein synthesis initiation AND cause misreading of mRNA causing wrong AA insertion.
Which HIV protease inhibitor is a CYP450 inhibitor?
Ritonavir
What has been shown to block (dry) ARMD in mice? Through what mechanism?
NRTI (HIV drug), NRTIs block inflammation
Trimethoprim + Sulfamethoxazole makes
Cotrimoxazole
What phase of clinical trials has the highest failure rate?
Phase 2 with only 25% of drugs passing.
Ethionamide
Second-line antimycobacterial. Prodrug gets converted and blocks mycolic acid production
Clindamycin
PSI, “other”. Binds to 50s ribo. subunit (can inhibit its formation) to block peptidyl transferase center to prevent AA elongation.
Sulfamethoxazole
Antifolate. Prohibits bacterial production of folate because drug is PABA analogue and competes with dihydropteroate synthetase.
Clofazimine
Antimycobacterial, Leprosy drug. binds to DNA to prevent using it as a template for replication. Has anti-inflammatory properties good for skin lesions
Isoniazid
*First-line antimycobacterial. Prodrug gets converted and blocks mycolic acid production. *most potent Tb medication. Absorption impaired w/ food
Summarize the forms of malaria
Sporozoite > cyst > merozoites released > trophozoite in RBC > gametocytes > repeat. Spock Cycles Mel’s Trophy Game
What is the most broad spectrum azole?
Posaconazole
What drug can bacteria NOT form resistance to?
Methenamine (UTI antiseptic) because it makes formaldehyde
What causes sleeping sickness? Disease and vector
Africa: trypanosomiasis via tsetse fly
Mitochondrial DNA is susceptible to what drug class?
NRTI (HIV drug)
What can cause EOM pain as a primary complaint?
Ethambutol causing optic neuritis
Which drugs are the mixed Amebicides?
Metronidazole, Tinidazole (think MetronTin mixed). They are also part of Giardiasis tx.
What is an antiviral and HIV treatment?
Tenofovir and Lamivudine (anti hep and NRTI)
Azoles should not be used with ___
Amphotericin B
What is a treatment for erythrocytic forms of malaria?
Chloroquine (also systemic amebicide) is drug of choice, Mefloquine, Quinine
Suramin
tx Trypanosomiasis. moa:Inhibits many enzymes involved in energy metabolism. used prophylactically for sleeping sickness.
What is the life cycle of malaria?
Injected sporozoites from mosquito migrate through the blood to the liver to form cysts. Merozoites released and invade RBC and becomes trophozoite. Some trophozoites become gametocytes and get picked up by mosquitos.
Atazanavir
HIV protease inhibitor. inhibits HIV aspartyl protease to prevent viral maturation. MANY drug-drug interactions. *can cause slow heart rate
What disease is attracted to the macula?
toxoplasma gondii
What Parasite grows in blood and eventually invades CNS?
trypanosomiasis via tsetse fly causes Sleeping sickness (in Africa)
Quinine
Malaria drug. *interferes with heme polymerization. reserved for severe/resistant cases. AE: cinchonism: Nausea, Vomiting, Tinnitus, Vertigo
Which NNRTI has a long half-life and is the most preferred?
Efavirenz
What supplement is anti-pathogen?
Echinacea
What is the mechanism of NNRTIs?
They cause conformational change to HIV-1 reverse transcriptase and does not need to be activated by cellular enzymes. They don’t affect the host cells.
What drugs can cause liver toxicity?
Isoniazid (1a Antimycobacterial) Ethionamide (2L Antimycobacterial), NRTI (HIV drug),
What is often given with
Amphotericin B?
Flucytosine
AE Sulfonamides:
Crystalluria, allergies, anemia, increase warfarin levels by inhibiting p450.
Which anti-CMV needs to be activated by viral enzyme?
Ganciclovir
Cidofovir
Cytomegalovirus drug. cytosine analog inhibits DNA synthesis wo/ need of viral enzymes. *Tx cmv-induced retinitis in AIDS patients
Which trypanosomiasis drugs treat African sleeping sickness?
Pentamidine and Suramin (prophylaxis)
Chloramphenicol
PSI, “other”. binds to 50s ribo subunit to inhibit peptide bond formation.
Tx acute Chagas
Nifurtimox (trypanosomiasis)
What supplement is used for increasing cognition and concentration?
Ginkgo
Which integrase inhibitor is only available in combination?
Elvitegravir. With Tenofovir/ Emtricitabine/ Elvitegravir/ Cobicistat
How is Leishmaniasis transmitted?
Through sandfly bites
Cycloserine
Second-line antimycobacterial. Inhibits cell wall synthesis. *Exacerbates epileptic seizures
What drug can cause folic acid deficiency?
Trimethoprim (antifolate drug)
Which malaria drug is good for pregnant people?
Mefloquine (malaria drug)
Spectrum of chloramphenicol?
Very strong Broad spectrum
What is the treatment of choice for HSV encephalitis?
Acyclovir (anti-herpes)
What drug class binds to tissues undergoing calcification (children under 12)
Tetracycline
Which anti-viral would you not want to give to COPD or asthma people?
Zanamivir
What can be used to treat pneumonia in HIV patients?
Dapsone (leprosy drug)
Tigecycline
**PSI, “Tetracycline”; actually a glycylcycline. reversibly binds to 30s ribo. subunit preventing tRNA binding–translation stops. *Extended spectrum. Tx MRSA, resistant s. Pneumoniae. NOT Tx pseudomonas
What supplement used as an anti-cancer?
Ginseng , Milk Thistle, and St. John’s Wort
Zidovudine (AZT)
HIV drug, NRTI, nucleoside/tide integrates into DNA, terminating DNA elongation. *can be used for prophylaxis and is toxic to bone marrow
Which amebicide is also used for malaria and arthritis/lupus?
Chloroquine
Which antiviral is particularly bad for people with renal failure?
Amantadine (uncoating inhibitor), high dose Acyclovir (anti-herpes), Cidofovir (anti-CMV)
What drugs bind to the 50s ribosomal subunit?
Chloramphenicol, Clindamycin, Linezolid, Macrolides/Ketolides.
Which anti-CMV doesn’t need to be activated by viral enzyme?
Cidofovir
Viruses that cause the flu contain the enzyme _____
Neuraminidase
How is resistance for macrolides/ketolides?
It’s becoming a problem. Drug has decreased 50s affinity in resistance
Acyclovir
Herpesvirus drug. Guanosine analog gets incorporated into viral DNA via DNA poly. *tx HSV encephalitis
Nelfinavir
HIV protease inhibitor. inhibits HIV aspartyl protease to prevent viral maturation. MANY drug-drug interactions. *can cause diarrhea and is NOT boosted by Ritonavir
Rilpivirine
HIV drug, NNRTI that causes conformational change to HIV-1 reverse transcriptase
Lopinavir
HIV protease inhibitor. inhibits HIV aspartyl protease to prevent viral maturation. MANY drug-drug interactions.
Pyrimethamine
tx Toxoplasmosis, combined with sulfadiazine.
Doxycycline
**PSI, Tetracycline. reversibly binds to 30s ribo. subunit preventing tRNA binding–translation stops. *liver excreted
Amantadine
Respiratory flu drug. inhibits viral uncoating. Blocks viral membrane matrix protein M2 so viral and host membrane can’t fuse. *can cross BBB, bad for kidney failure people
What antifungal induces p450 activity?
Griseofulvin (“other”)
What drugs can cause skin rash?
Cotrimoxazole (antifolate) and rifampin, rifabutin (1L antimycobacterial) (NOT rifapentine)
Which NRTI can be used for prophylaxis and is toxic to bone marrow?
Zidovudine (AZT)
Which HIV protease inhibitor can cause severe and fatal hepatitis, rare intracranial hemorrhages?
Tipranavir
Echinacea
Botanical/Herbal. used for increasing wbc, anti-inflammatory, and anti-pathogen
Preclinical testing is finding out what toxicities?
Acute, subacute, and chronic
Iodoquinol
Luminal Amebicides. *effective against both trophozoite and cyst forms. can cause optic neuritis
How can a supplement be pulled from the market?
FDA has to prove that it is harmful before use can be restricted or removed from the market
What is the combo treatment for toxoplasma gondii?
pyrimethamine and sulfadiazine
Glucosamine
Purified Supplements. used for cartilage nutrient
Saquinavir
HIV protease inhibitor. inhibits HIV aspartyl protease to prevent viral maturation. MANY drug-drug interactions.
Ribavirin
Viral Hepatitis drug. guanosine analog causes dec guanosine triphosphate, blocking DNA/RNA synthesis.
Which malaria drug can cause depression?
Mefloquine
How much does it take to develop a drug?
$150 million to several billion
Ganciclovir has much less toxic with easier dosing than…_____
Trifluridine
Zanamivir
Respiratory flu drug. Inhibits neuraminidase, kills virus. via intranasal. not for COPD/asthma people
AE HIV protease inhibitors:
FAT REDISTRIBUTION, Paresthesias, GI disturbances, Changes in glucose and lipid metabolism
Micafungin
Antifungal, Echinocandin. lyses cell wall.
Melarsoprol
tx Trypanosomiasis. tx sleeping sickness or Chagas disease, perhaps?
Nevirapine
HIV drug, NNRTI that causes conformational change to HIV-1 reverse transcriptase. P450 inducer,
Which drugs hardly interact with P450?
Linezolid (PSI), Azithromycin (Macrolides)
What drug class inhibits the cytochrome P450 system?
Azoles (and Macrolides/Ketolides except Azith), this can increase Warfarin drug concentration
Which drugs are the systemic Amebicides?
Chloroquine, Dehydroemetine, Emetine, (Think Chlo-emetine system). Chloroquine is also part of malaria tx.
What drugs can cause Optic and peripheral neuropathy?
Linezolid (other PSI)
What is the distribution of Aminoglycosides?
Bad for systemic versions, they cross the placenta. High concentrations in inner ear and renal cortex
What supplement promotes lactation?
Milk Thistle
Which “tetracycline” has expanded spectrum?
Tigecycline.
What supplement is used for treating liver disease?
Milk Thistle
What can cause nephrotoxicity?
Aminoglycosides, Capreomycin (2L antimycobacterial)
Sodium stibogluconate
tx Leishmaniasis. orally poor. AE: Can cause pain at the injection site, GI upsets, and cardiac arrhythmias.
Fluconazole
Antifungal, Azole. Inhibits P450 enzyme that converts lanosterol to ERGOSTEROL, disrupting fungal membrane.
How is Amphotericin B administered? Eliminated?
SLOWLY through IV.
Excreted through BOTH kidney and liver
What kind of resistance can Trimethoprim encounter?
Gram (-) from altered enzyme
What is used to treat abdominal bacterial infections associated with trauma?
Clindamycin
AE for Cotrimoxazole:
Skin rash (esp in elderly), Nausea, vomiting, Anemia or thrombocytopenia
Saw Palmetto
Botanical/Herbal. used for treating BPH (inflamed prostate)
Where does Trimethoprim tend to accumulate?
In acidic environments because the drug is a weak base
Which drugs are P450 inducers?
NNRTIs (HIV drugs), Griseofulvin (antifungal), and Isoniazid, Rifampin, Rifabutin (1L antimycobacterial)
What is the drug of choice for erythrocytic forms of malaria?
Chloroquine (also systemic amebicide)
Which drugs are never given as a single agent?
Isoniazid (1L antimycobacterial), Rifamycins (1L antimycobacterial)
What can cause gray baby syndrome?
Chloramphenicol because baby can’t excrete the drug well
Can you use a different tetracycline for bacteria that is resistant to a tetracycline?
Nope!
What drugs bind to the 30s ribosomal subunit?
Tetracyclines, Aminoglycosides
MOA:
oxygen radicals toxic to both host/parasite but human enzymes fix damage.
Nifurtimox (trypanosomiasis)
AE nitrofurantoin:
Hemolytic anemia, GI disturbances, Neurological problems, Chronic use can result in interstitial pulmonary fibrosis
Which antiviral can cross the BBB?
Amantadine (uncoating inhibitor)
What is the treatment for EXOerythrocytic forms of malaria?
Primaquine
Paromomycin
Luminal Amebicides. *aminoglycoside antibiotic. it doesn’t get absorbed through GI and kills food source
Ritonavir
HIV protease inhibitor. inhibits HIV aspartyl protease to prevent viral maturation. MANY drug-drug interactions. *P450 inhibitor, boosts performance of other protease inhibitors
Elimination of Macrolides/Ketolides:
Kidney. They inhibit p450 enzyme system (Azithromycin does NOT inactivate P450 enzymes)
Dapsone
Antimycobacterial, Leprosy drug. Inhibits folate synthesis. concentrates in skin, Tx pneumonia in HIV patients
What is approved for treatment of cytomegalovirus induced retinitis in AIDS patients?
Cidofovir
How is Cotrimoxazole administered?
Orally
How do you administer interferons for hep tx?
IV or IM because it’s made of recombinant DNA
What class of drugs have tons of interactions?
HIV protease inhibitors
Capreomycin
Second-line antimycobacterial. Inhibits protein synthesis
Amphotericin B
Antifungal, Polyene Antibiotic. binds to ergosterol in membrane making ion pore > death.
Trimethoprim
Antifolate. Inhibits dihydrofolate reductase, preventing dihydrofolic acid to tetra
Which stage of Giardia lamblia is resistant to drugs?
The four-nucleate cyst (as opposed to the binucleate trophozoite)
What is the antifungal precursor to 5-FU?
Flucytosine
Which amebicide kills off the protozoal food source?
Paromomycin (luminal amebicide)
What is the pharmacokinetics of HIV protease inhibitors? (bioavailability, metabolism)
Poor oral bioavailability, P450 metabolized, good for renal impairment.
What drug can decrease glomerular filtration rate?
Amphotericin B
Ciprofloxacin (Cipro)
*2nd line ANTIMYCOBACTERIAL and 2nd Gen Fluoroquinolone. Enters bacteria via diffusion; uses dual mechanism to inhibit DNA gyrase and topoisomerase IV. *most potent against Pseudomonas
Gemifloxacin
2nd line antimycobacterial and 4nd Gen Fluoroquinolone. Enters bacteria via diffusion; uses dual mechanism to inhibit DNA gyrase and topoisomerase IV.
Spectrum of
Fluoroquinolones:
Both +/- , including (-) like Pseudomonas, H. influenzae, Moraxella, Chlamydia
Terbinafine
*Antifungal, “Other”. Squalene builds up because drug prevents conversion into ERGOSTEROL by inhibiting squalene epoxidase. *Tx nail infection
What inhibits the p450 enzyme lanosterol to ergosterol, disrupting membrane structure and function?
Azoles
What drug binds ergosterol in the plasma membrane and forms a pore for electrolytes?
Amphotericin B
Which HIV protease inhibitor can cause slow heart rate?
Atazanavir
AE for Flucytosine:
Neutropenia, Thrombocytopenia, Bone marrow depression–bad for immunocompromised, Caution in patients undergoing chemotherapy, GI disturbances common
Which antifolate drug is good against MRSA?
Cotrimoxazole
What is used for pre-CNS involvement of sleeping sickness?
Pentamidine (trypanosomiasis)
Griseofulvin
Antifungal, “Other”. Inhibits fungal mitosis until skin sloughs it off.
Minocycline
PSI, Tetracycline. reversibly binds to 30s ribo. subunit preventing tRNA binding–translation stops.
Which tetracycline is good for people with renal disease?
Doxycycline
Dehydroemetine
Systemic Amebicides. inhibits protein synthesis. Via IM; oral might cause vomiting. Can concentrate in liver for a month
What drug is restricted to topical Candida infections
Nystatin because it’s systemically toxic
Tenofovir
Viral Hepatitis drug. nucleotide analog inhibits viral reverse transcriptase.
HIV drug, NRTI, nucleoside/tide integrates into DNA, terminating DNA elongation. *long half-life, many antiretroviral drug interactions
What is often given with
Flucytosine?
Amphotericin B
___ should not be taken with Sulfonamides because they cancel out
Methenamine
Lamivudine
Viral Hepatitis drug. inhibits HBV DNA poly and HIV rev transcriptase. *Has few side effects.
ALSO HIV drug, NRTI, nucleoside/tide integrates into DNA, terminating DNA elongation. *does NOT affect mitochondrial DNA synthesis
What supplement is anti-inflammatory?
Echinacea and Ginseng
Didanosine
HIV drug, NRTI, nucleoside/tide integrates into DNA, terminating DNA elongation *take when fasting, AE Pancreatitis and peripheral neuropathy
What drug combo can make HIV UNDETECTABLE in 60-95% of patients?
A protease inhibitor and two NRTIs
Spectrum of viral uncoating inhibitors:
Influenza A
What supplement is used for jet lag, insomnia, and improving sleep?
Melatonin (purified supplement)
Boceprevir
Viral Hepatitis drug. Bind to active site of HCV protease
Contraindications for Fluoroquinolones:
Pregnancy, nursing mothers, children under 18, arrhythmia
How are NRTIs excreted?
Kidney, except abacavir!
What supplement is used for hypertension, improving output in heart failure, prevents statin-induced myopathy.
Coenzyme Q10 (purified supplement)
AE of aminoglycosides:
Ototoxicity, nephrotoxicity, neuromuscular paralysis, bad allergic reactions
Which antivirals are antimetabolites?
Ribavirin (anti hep),
Acyclovir (anti-herpes)
What is the drug of choice for chlamydia infections?
Azithromycin (z-pak)…. (Fluoroquinolones are also good)
What are confounding variables found in clinical trials?
Variable nature of most diseases, Presence of other diseases or risk factors, Subject and observer bias (Placebo effect)
Tinidazole
Mixed Amebicides AND alternative tx Giardiasis. Moa form cytotoxic compounds that bind to proteins and DNA. *shorter treatment, more expensive, used in other countries before US.
What drugs cause epigastric distress?
Macrolides/Ketolides
Lepers who are allergic to ___ might also be allergic to Dapsone
Sulfa drugs
Why are mycobacterial resistant to most antibiotics?
Grow more slowly, Can be dormant, Cell wall impermeable to many drugs, can be intracellular
Fosamprenavir
HIV protease inhibitor. inhibits HIV aspartyl protease to prevent viral maturation. MANY drug-drug interactions.
What drugs should not get acidic?
Sulfonamides
Which NRTI does NOT affect mitochondrial DNA synthesis?
Lamivudine (has less side effects). Remember Emtricitabine has NO significant drug interactions
Only __% of marketed drugs return their R&D investments
20%
Rifabutin AE:
UVEITIS, Uncommon Nausea, vomiting, rash. (Orange feces, urine, and tears..?). p450 inducer
Raltegravir
HIV integrase inhibitor that inhibits final step of integration of viral DNA into host DNA. NO P450 interactions
Rifabutin
*First-line antimycobacterial. inhibits RNA polymerase to prevent transcription. *Good for HIV patients that need it. increase P450 metabolism. Can cause uveitis
Valacyclovir (Valtrex)
Herpesvirus drug.?Guanosine analog gets incorporated into viral DNA via DNA poly
Moxifloxacin
*2nd line ANTIMYCOBACTERIAL and 4nd Gen Fluoroquinolone. Enters bacteria via diffusion; uses dual mechanism to inhibit DNA gyrase and topoisomerase IV. *Poor activity against pseudomonas, NO tx for UTIS because not concentrated in urine. Has long half-life
What decreases testosterone and cortisol production?
Azoles
___% of health care expense in the U.S. is on prescription drugs
10-12% of health care expense in the U.S. is on prescription drugs
AE chloramphenicol:
GI disturbances, Candida overgrowth, Anemia (can be fatal), Gray baby syndrome
Fidaxomicin
PSI, Macrolide/Ketolide. Binds to 50s ribo. subunit (can inhibit its formation) to block peptidyl transferase center to prevent AA elongation.
What disease causes a dendritic pattern on the cornea?
Herpetic Keratitis
AE Ethionamide:
GI irritation, Hepatotoxicity, Optic Neuritis, Peripheral neuropathies
Ginkgo
Botanical/Herbal. used for increasing blood flow and vasodilation; increasing cognition and concentration.
Which drugs bind to the 30s ribosomal subunit?
Tetracyclines, Aminoglycosides
What drug can cause some visual disturbances?
Terbinafine (antifungal)
What strategies can prevent mycobacterial resistance?
Use multiple drugs, LONG duration, increase compliance through directly observed therapy. (DOT)
What drugs can lead to fat redistribution?
HIV protease inhibitors
Methenamine should not be taken with __ because they cancel out
Sulfonamides
What drugs are bad to have with Ca++, Iron, Antacids?
Fluoroquinolones and Tetracyclines
Hepatitis __ and __ are the most common causes of chronic hepatitis, cirrhosis, and hepatocellular carcinoma
B and C
Erythromycin
*PSI, Macrolide/Ketolide. Binds to 50s ribo. subunit (can inhibit its formation) to block peptidyl transferase center to prevent AA elongation. *not via IV! oral is good
Tx Leishmaniasis
Sodium stibogluconate
What drug have flu-like AE?
Interferons (anti Hep)
Which amebicide inhibits protein synthesis?
Dehydroemetine and Emetine
Caspofungin
*Antifungal, Echinocandin. lyses cell wall. *second-line antifungal if amphotericin B or azole fails
Which Fluoroquinolone is most potent against pseudomonas?
Ciprofloxacin
What can cause precipitate gout?
Pyrazinamide (1L antimycobacterial)
What’s in a new drug application? How long does it take to get approval?
Full reports of all preclinical and clinical data. Can take months to years to gain approval, but If urgent need for the drug is perceived, the process of FDA review can be accelerated.
Oseltamivir (Tamiflu)
Respiratory flu drug. Inhibits neuraminidase, kills virus.
Nitrofurantoin
Urinary Tract Antiseptic. bacteria makes drug a toxic intermediate that damages their DNA
What foods/supplements should you avoid when taking tetracyclines?
Calcium (dairy) reduces bioavailability; avoid antacids or iron supplements
Which NRTI can cause a fatal allergic reaction upon second exposure?
Abacavir
Gentamicin
PSI Aminoglycoside. Binds to 30s ribo subunit preventing protein synthesis initiation AND cause misreading of mRNA causing wrong AA insertion.
What supplement is used as an antiviral?
St. John’s Wort
What was revealed in the Herpetic Eye Disease Study I and II?
“there really no point in treating herpetic keratitis with both topical and/or oral medication”. Oral (acyclovir) will work by itself for the corneal disease. Oral acyclovir given 400mg bid (twice a day) is effective in reducing the recurrence of herpetic eye disease by almost half
Who is involved in phase 1 clinical trials?
Small number (20-100) of healthy volunteers
What is the recommended HIV drug class combination?
Two NRTIs (w/ different mechanisms) and one other class (NNRTI, protease inhibitor, integrase inhibitor). For some reason entry inhibitors isn’t listed.
Levofloxacin (Levaquin)
*2nd line ANTIMYCOBACTERIAL and 3nd Gen Fluoroquinolone. Enters bacteria via diffusion; uses dual mechanism to inhibit DNA gyrase and topoisomerase IV. *Long half-life
Anidulafungin
Antifungal, Echinocandin. lyses cell wall.
Trifluridine (Viroptic)
Herpesvirus drug. Fluorinated pyrimidine nucleotide inhibits incorporation of thymide triphosphate into viral DNA ; drug also incoporates into viral DNA. Cheap but short half life
Which drugs inhibit P450?
Azoles, Macrolides/Ketolides (except Azithromycin)
Neomycin
PSI Aminoglycoside. Binds to 30s ribo subunit preventing protein synthesis initiation AND cause misreading of mRNA causing wrong AA insertion.
Telithromycin
PSI, “Ketolide”. Binds to 50s ribo. subunit (can inhibit its formation) to block peptidyl transferase center to prevent AA elongation.
What does the cell membrane of fungi contain?
Ergosterol
What drugs can cause peripheral neuropathy?
Didanosine and other NRTIs, Nifurtimox (trypanosomiasis), Linezolid (PSI), Ethionamide (2L Antimycobacterial)
Garlic
Botanical/Herbal. used for lowering cholesterol, decreasing blood pressure, antibiotic effects.
Which form of Entamoeba histolytica is infective?
The cyst form
Pentamidine
tx. Trypanosomiasis. used for pre-CNS involvement of sleeping sickness
Telaprevir
Viral Hepatitis drug. Bind to active site of HCV protease
AE Macrolides/Ketolides:
Epigastric distress, cholestatic jaundice, ototoxicity
Which malaria drugs in combination can cause cardiac arrest?
Mefloquine with quinine (malaria drug) or (quinidine).
What drugs can cause Anemia?
chloramphenicol and Linezolid (other PSI), nitrofurantoin (UTI antiseptic), Sulfonamides, and Cotrimoxazole and Trimethoprim (antifolates)
How are generic drugs approved? What’s required?
Through an abbreviated new drug application (ANDA). Must demonstrate equivalence.
WHO recommends what for treatment of leprosy? For how long?
The triple-drug regimen: dapsone, clofazimine, and rifampin for 6 to 24 months
Spectrum of Isoniazid (1L antimycobacterial):
M Tuberculosis, intracellular bacteria
Ketoconazole
*Antifungal, Azole. Inhibits P450 enzyme that converts lanosterol to ERGOSTEROL, disrupting fungal membrane. * more side effects, limited to topical
What drug class can cause pseudotumor cerebri?
Tetracyclines
Which antiviral should be avoided in pregnancy?
Ganciclovir (anti-CMV)
Which NRTI has NO significant drug interactions?
Emtricitabine. Remember Lamivudine does NOT affect mitochondrial DNA synthesis.
