Final exam Flashcards
(408 cards)
1
Q
HIV drug selection strategy:
A
Varying mechanisms, toxicities, patient symptoms, drug interactions, and adherence/administration convenience
2
Q
How do supplements differ from drugs and OTC medications?
A
they are legally considered food supplements used for health maintenance even if they’re really “drugs”
3
Q
What drugs can cause jaundice?
A
Macrolides/Ketolides,
4
Q
Efavirenz
A
HIV drug, NNRTI that causes conformational change to HIV-1 reverse transcriptase. P450 inducer, *great half-life, can cause vivid dreams
5
Q
What drugs can cause crystalluria?
A
Sulfonamides
6
Q
Moa: inhibits protein and RNA synthesis in trypanosomiasis
A
Benznidazole. Tx Chagas disease
7
Q
Rifampin AE:
A
Uncommon Nausea, vomiting, rash. Orange feces, urine, and tears. Increase p450 metabolism
8
Q
What are the 3 approaches of developing a new drug?
A
New drug targets, new drugs based on receptor structure, modification of known molecule
9
Q
Metronidazole
A
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.
10
Q
Ginseng
A
Botanical/Herbal. used as an upper: increased NT in CNS. anti-inflammatory, anti-cancer
11
Q
What supplement has antibiotic effects?
A
Echinacea, Garlic
12
Q
Rimantadine
A
Respiratory flu drug. inhibits viral uncoating. Blocks viral membrane matrix protein M2 so viral and host membrane can’t fuse.
13
Q
What do Trophozoites do?
A
Entamoeba histolytica trophozoites multiply and invade intestinal mucosa or feed on intestinal bacteria
14
Q
What treats pneumonia in immunocompromised patients?
A
Cotrimoxazole (Trimethoprim + Sulfamethoxazole)
15
Q
Ofloxacin
A
*2nd line antimycobacterial and 2nd Gen Fluoroquinolone. Enters bacteria via diffusion; uses dual mechanism to inhibit DNA gyrase and topoisomerase IV. *inexpensive
16
Q
What is the resistance of aminoglycosides?
A
Resistance not severe when topical
17
Q
Which malaria drug has a very long half-life?
A
Mefloquine
18
Q
Itraconazole
A
*Antifungal, Azole. Inhibits P450 enzyme that converts lanosterol to ERGOSTEROL, disrupting fungal membrane. *Tx histoplasmosis, take with food (needs acid)
19
Q
What are the two forms of
Entamoeba histolytica?
A
Cyst and Trophozoite (survives in body)
20
Q
How long do drug patents last? What is the average effective patent life of a drug?
A
20 years but includes approval time. Average effective patent life for major pharmaceuticals is around 11 years
21
Q
What causes dysentery?
A
Entamoeba histolytica
22
Q
AE Linezolid:
A
Thrombocytopenia, Anemia, Optic and peripheral neuropathy. Caution with MAOIs and SSRIs
23
Q
Which drugs are the luminal Amebicides
A
Iodoquinol and Paromomycin (think IodoParo luminal)
24
Q
What supplement is used for decreasing blood pressure?
A
Garlic
25
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.
26
Which rifamycin has the longest half-life?
Rifapentine
27
What is the resistance of Amphotericin B?
Infrequent
28
What is the commonly diagnosed intestinal parasite in the U.S?
Giardia lamblia
29
Posaconazole
*Antifungal, Azole. Inhibits P450 enzyme that converts lanosterol to ERGOSTEROL, disrupting fungal membrane. *the most broad spectrum azole
30
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
31
Which amebicide is actually an aminoglycoside antibiotic?
Paromomycin (luminal amebicide)
32
Darunavir
HIV protease inhibitor. inhibits HIV aspartyl protease to prevent viral maturation. MANY drug-drug interactions.
33
Which drug class causes vestibular problems?
Tetracyclines
34
MOA: Inhibits many enzymes involved in energy metabolism of Trypanosomiasis
Suramin (Trypanosomiasis)
35
Amikacin
PSI Aminoglycoside. Binds to 30s ribo subunit preventing protein synthesis initiation AND cause misreading of mRNA causing wrong AA insertion.
36
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
37
Linezolid
PSI, "other". binds to 50s subunit to inhibit ribosome complex formation.
38
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
39
AE for Amphotericin B:
It has a low therapeutic index. , Fever/Chills, Muscle spasm, Vomiting, Headache, Hypotension. Cumulative: renal impairment
40
AE of tetracyclines:
Gastric discomfort w/ Ca++ Food. Severe sunburns. Vestibular problems. Pseudotumor cerebri
41
What supplement is used as antidepressant?
St. John’s Wort
42
What portion of the world is exposed/infected with Tb?
1/3
43
What drugs are neuraminidase inhibitors?
Oseltamivir and Zanamivir (OselZana)
44
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
45
Which antimycobacterial involves prodrugs?
Isoniazid and Ethionamide
46
What are the phases of new drug?
Drug discovery, screening, preclinical testing, human testing, clinical trials, (phase 1-4)
47
Which Fluoroquinolone is bad systemically but good for UTIs and GI disease?
Norfloxacin
48
What drug class competes with dihydropteroate synthetase and inhibit folate production?
Sulfa drugs
49
Coenzyme Q10
Purified Supplements. used for hypertension, improving output in heart failure, prevents statin-induced myopathy
50
Resistance for tetracyclines:
Widespread
51
Sulfacetamide
Antifolate. Prohibits bacterial production of folate because drug is PABA analogue and competes with dihydropteroate synthetase.
52
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,
53
Emetine
Systemic Amebicides. inhibits protein synthesis. Via IM; oral might cause vomiting. Can concentrate in liver for a month
54
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
55
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
56
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.
57
How are macrolides/ketolides administered?
Oral is good. Erythromycin should NOT be given IV
58
Which trypanosomiasis drug is recommended
| as prophylaxis in hematopoietic stem cell transplant recipients?
Benznidazole
59
What can cause ototoxicity?
Aminoglycosides, macrolides (esp erythromycin), Capreomycin (2L antimycobacterial)
60
What is the spectrum of Aminoglycosides?
Gram - (including pseudomonas) , some +
61
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
62
Which malaria drug is reserved for severe/resistant cases?
Quinine
63
What is the treatment of choice for Giardiasis?
Metronidazole for 5 days
64
What supplement is used for cartilage nutrient?
Glucosamine (purified supplement)
65
What drugs interact with bacterial RNA polymerase to block transcription?
Rifamycins (1L antimycobacterial)
66
Which are the drugs that prohibit viral uncoating?
Rimantadine and Amantadine
67
Which NRTI has a conveniently long half-life?
Tenofovir
68
What can cause bull's eye maculopathy?
Chloroquine (systemic amebicide and malaria drug) and Primaquine (Malaria drug)
69
What drugs are used to treat MRSA?
Vancomycin, Bacitracin, Ceftaroline (5th gen) (kinda Telavancin, kinda Daptomycin). Linezolid [PSI](except in MRSA bacteremia), Cotrimoxazole (antifolate)
70
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
71
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
72
Demeclocycline
PSI, Tetracycline. reversibly binds to 30s ribo. subunit preventing tRNA binding--translation stops.
73
Rifampin
*First-line antimycobacterial. inhibits RNA polymerase to prevent transcription. induces P450, ORANGE POOP
74
Tetracycline
PSI, Tetracycline. reversibly binds to 30s ribo. subunit preventing tRNA binding--translation stops.
75
What 1st line antimycobacterial is preferred for HIV patients?
Rifabutin
76
Which Fluoroquinolone have the longest half-lives?
Levofloxacin and moxifloxacin
77
AE: cinchonism: Nausea, Vomiting, Tinnitus, Vertigo
Quinine (malaria drug)
78
What drugs are bad with antacids?
Quinine (malaria drug),
| Fluoroquinolones and Tetracyclines (PSI)
79
Between acyclovir,
| Valacyclovir, and Famciclovir, which is safest in pregnancy?
Famciclovir (anti-herpes)
80
What is the oral mouthwash for thrush?
Nystatin
81
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)
82
Melatonin
Purified Supplements. used for jet lag, insomnia, and improving sleep
83
HIV treatment now consists of suppressing HIV replication, allowing for restoration of ___ cells and immunocompetence
CD4 or T Helper Cells
84
Benznidazole
tx Trypanosomiasis. alternative for Chagas disease. Moa: inhibits protein and RNA synthesis. Recommended as prophylaxis in hematopoietic stem cell transplant recipients.
85
What is the second-line antifungal if amphotericin B or azole fails?
Caspofungin (Echinocandin)
86
Milk Thistle
Botanical/Herbal. used for treating liver disease, anti-cancer, promotes lactation
87
What drug causes squalene to build up to toxic levels?
Terbinafine (antifungal)
88
Ethambutol
First-line antimycobacterial. interferes with cell wall synthesis *EOM pain primary complaint with red/green color deficiency and optic neuritis
89
Which of the Amebicides can cause optic neuritis?
Iodoquinol.
90
Etravirine
HIV drug, NNRTI that causes conformational change to HIV-1 reverse transcriptase. P450 inducer,
91
How are Sulfonamides metabolized and excreted?
Liver metabolized kidney excreted
92
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)
93
Macrolides/Ketolides contraindications:
Hepatic dysfunction, arrhythmia
94
What drug can cause vivid dreams?
Efavirenz (NNRTI)
95
What is clinically equivalent to acyclovir but have longer half lives?
Valacyclovir, Famciclovir (anti-herpes)
96
Spectrum of Rifamycins:
+/-, mycobacteria, Leprosy
97
St. John’s Wort
Botanical/Herbal. used as antidepressant, antiviral and anticarcinogenic
98
Pharmacokinetics for tetracyclines:
Avoid calcium, iron, antacids (reduces plasma concentration). Do not give to children, can cross placenta. Bile secreted.
99
AE for Trimethoprim:
Folic acid deficiency (leads to anemia, Leukopenia, Granulocytopenia)
100
Which amebicide is effective against both trophozoite and cyst forms?
Iodoquinol (luminal)
101
Adverse Effects:, Hypersensitivity (acute and delayed), GI problems (sometimes severe), Peripheral neuropathy
Nifurtimox (trypanosomiasis)
102
What is the most potent Tb medication?
Isoniazid
103
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
104
How is one typically infected by Giardia lamblia?
Contaminated water (or food). Fecal-oral route
105
Which anti-viral is given intranasally?
Zanamivir
106
Voriconazole
*Antifungal, Azole. Inhibits P450 enzyme that converts lanosterol to ERGOSTEROL, disrupting fungal membrane. *inhibits P450, increasing warfarin conc
107
What leprosy drug also has anti-inflammatory activity?
Clofazimine
108
Which macrolide has a good half-life and high Vol of distribution?
Azithromycin
109
What supplement is used for increasing wbc?
Echinacea
110
AE Isoniazid (1L antimycobacterial):
Hepatitis and idiosyncratic hepatotoxicity, Peripheral neuritis, Mental abnormalities, convulsions, Optic neuritis, Hypersensitivity
111
Nystatin
*Antifungal, Polyene Antibiotic. binds to ergosterol in membrane making ion pore > death. *Tx topical Candida and Thrush mouthwash
112
Which NRTI has many antiretroviral drug interactions?
Tenofovir
113
Antibacterial spectrum for tetracyclines:
Considered broad spectrum, Gram(-) and Gram(+), Also against other organisms
114
What supplement is used for lowering cholesterol?
Garlic
115
What are the malaria drugs?
Chloroquine, Mefloquine, Primaquine, Quinine (think qui-quine). Chloroquine is also a systemic amebicide
116
Enfuvirtide
HIV drug, entry inhibitor that binds to viral transmembrane glycoprotein, preventing the conformational change that allows entry in cell.
117
What supplement used as an upper: increased NT in CNS?
Ginseng
118
AE Methenamine:
GI distress, formaldehyde reacts with Sulfonamides
119
What drug colors feces, urine, and tears ORANGE?
Rifampin (1L antimycobacterial)
120
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.
121
Streptomycin
Second-line antimycobacterial aminoglycoside. MoA not given.
122
Tx fungal infections of nails?
Terbinafine (antifungal)
123
What drug interferes with the synthesis of B-glucan, causing lysis and cell death?
Echinocandins
124
Which antiviral has few side effects?
Lamivudine (anti hep/NRTI) .(rarely headaches/dizziness)
125
What is the mechanism of HIV protease inhibitors?
They inhibit HIV aspartyl protease to prevent the maturation of viral particles, making noninfectious virions
126
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
127
What drugs can cause GI disturbances?
Chloramphenicol (PSI), methenamine and nitrofurantoin (UTI tx), Flucytosine (antifungal), Ethionamide (2L antimycobacterial), HIV protease inhibitors, Nifurtimox (trypanosomiasis)
128
What drugs are bad to have with Zinc?
Fluoroquinolones
129
Which drug can cause tinnitus and vertigo?
Quinine (malaria drug)
130
What inhibits fungus until skin sloughs off?
Griseofulvin
131
What supplement is used for treating BPH (inflamed prostate)
Saw Palmetto
132
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
133
How is the resistance in Cotrimoxazole?
Not frequent because bacteria needs to resist both drugs (Trimethoprim + Sulfamethoxazole)
134
Rifapentine
*First-line antimycobacterial. inhibits RNA polymerase to prevent transcription. *has long half-life
135
Flucytosine
Antifungal, "Other". drug enters fungal cell and is converted into the antimetabolite 5-FU
136
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.
137
Emtricitabine
HIV drug, NRTI, nucleoside/tide integrates into DNA, terminating DNA elongation * has NO significant drug interactions.
138
What drugs can cause optic neuritis?
Isoniazid (Antimycobacterial), Ethambutol (1L antimycobacterial), Ethionamide (2L antimycobacterial), Iodoquinol (luminal amebicide)
139
Moa:
| Prevents malaria from digesting Hb; pH increases, heme accumulates, parasite AND rbc lyse!
Chloroquine (also systemic amebicide )
140
What drug can cause hepatitis?
Isoniazid (1L Antimycobacterial)
141
Macrolides
Second-line antimycobacterial and PSI. Binds to 50s ribo. subunit (can inhibit its formation) to block peptidyl transferase center to prevent AA elongation.
142
Food impairs absorption of what drug?
Isoniazid (1L antimycobacterial)
143
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.
144
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
145
Nitazoxanide
Tx Giardiasis
146
Sulfadiazine
Antifolate. Prohibits bacterial production of folate because drug is PABA analogue and competes with dihydropteroate synthetase. *COMBINED with pyrimethamine in toxoplasmosis tx.
147
What drugs can cause changes in glucose and lipid metabolism?
HIV protease inhibitors
148
What drugs can cause connective tissue problems?
Fluoroquinolones
149
Cotrimoxazole (Bactrim)
Antifolate. Trimethoprim + Sulfamethoxazole. Tx UTIs, Respiratory tract infections, Pneumocystis jiroveci pneumonia in immunocompromised patients
150
Tipranavir
HIV protease inhibitor. inhibits HIV aspartyl protease to prevent viral maturation. MANY drug-drug interactions. *cause severe and fatal hepatitis, rare intracranial hemorrhages
151
Which Fluoroquinolone is poor against pseudomonas and not good for UTIs?
Moxifloxacin
152
What disease causes some to be asymptomatic, others to have serious diarrhea (esp. in immunocompromised patients)?
Giardiasis (Giardia lamblia)
153
Which HIV protease inhibitor can cause diarrhea and is NOT boosted by Ritonavir?
Nelfinavir
154
Azithromycin (Zithromax, Zpak)
PSI, Macrolide/Ketolide. Binds to 50s ribo. subunit (can inhibit its formation) to block peptidyl transferase center to prevent AA elongation.
155
What drugs are best acidic?
Methenamine, nitrofurantoin.
156
Who should not take tetracyclines?
Kidney deficient (Doxycycline is ok), motherly women, children under 8, warfarin takers
157
What is the goal of neuraminidase inhibitors?
Decrease the intensity and duration of symptoms within 1-2 days of infection.
158
Antibacterial spectrum of Macrolides/Ketolides:
Similar to penicillin G (gram +)
159
What supplement is used for increasing blood flow and vasodilation?
Ginkgo
160
Methenamine
Urinary Tract Antiseptic. Makes formaldehyde at low 5.5 pH
161
Maraviroc
HIV drug, entry inhibitor that blocks binding of viral membrane to host cell on CCR5 receptor
162
Which drugs have a dual mechanism against bacteria?
Fluoroquinolones
163
Interferon
Viral Hepatitis drug. MoA poorly known: inhibit viral RNA translation
164
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
165
What is the goal of phase 2 clinical trials?
determine efficacy
166
Drug resistance of NRTIs:
Only between same analog class
167
What drugs are used prophylactically in patients exposed to meningitis
Rifampin (1L antimycobacterial)
168
What is used prophylactically for sleeping sickness?
Suramin (trypanosomiasis)
169
Which drug class causes phototoxicity?
Tetracyclines, Fluoroquinolones
170
What is the drug of choice for histoplasmosis?
Itraconazole
171
What causes Chagas disease
American: trypanosomiasis via insect feces
172
Famciclovir
Herpesvirus drug. ?Guanosine analog gets incorporated into viral DNA via DNA poly. safest in pregnancy
173
Who is involved in phase 3 clinical trials?
larger numbers of patients with the target disease (usually thousands of patients)
174
Pyrazinamide
First-line antimycobacterial. Inhibits growth by lowering intracellular pH *can cause precipitate gout
175
Who is involved in phase 2 clinical trials?
100-200 subjects with target disease.
176
Which trypanosomiasis drugs treat American Chagas disease?
Nifurtimox and Benznidazole (alternative)
177
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.
178
What NRTI is best taken when fasting?
Didanosine
179
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)
180
How is Linezolid administered?
Oral is completely absorbed (IV also available)
181
Tx UTI:
Methenamine and nitrofurantoin (UTI antiseptics), Norfloxacin (fluoroquinolone),
182
MoA: interferes with heme polymerization.
Quinine (malaria drug)
183
What are the different types of amebicidal drugs?
Luminal, systemic, or mixed (both)
184
Tobramycin
PSI Aminoglycoside. Binds to 30s ribo subunit preventing protein synthesis initiation AND cause misreading of mRNA causing wrong AA insertion.
185
Which HIV protease inhibitor is a CYP450 inhibitor?
Ritonavir
186
What has been shown to block (dry) ARMD in mice? Through what mechanism?
NRTI (HIV drug), NRTIs block inflammation
187
Trimethoprim + Sulfamethoxazole makes
Cotrimoxazole
188
What phase of clinical trials has the highest failure rate?
Phase 2 with only 25% of drugs passing.
189
Ethionamide
Second-line antimycobacterial. Prodrug gets converted and blocks mycolic acid production
190
Clindamycin
PSI, "other". Binds to 50s ribo. subunit (can inhibit its formation) to block peptidyl transferase center to prevent AA elongation.
191
Sulfamethoxazole
Antifolate. Prohibits bacterial production of folate because drug is PABA analogue and competes with dihydropteroate synthetase.
192
Clofazimine
Antimycobacterial, Leprosy drug. binds to DNA to prevent using it as a template for replication. Has anti-inflammatory properties good for skin lesions
193
Isoniazid
*First-line antimycobacterial. Prodrug gets converted and blocks mycolic acid production. *most potent Tb medication. Absorption impaired w/ food
194
Summarize the forms of malaria
Sporozoite > cyst > merozoites released > trophozoite in RBC > gametocytes > repeat. Spock Cycles Mel's Trophy Game
195
What is the most broad spectrum azole?
Posaconazole
196
What drug can bacteria NOT form resistance to?
Methenamine (UTI antiseptic) because it makes formaldehyde
197
What causes sleeping sickness? Disease and vector
Africa: trypanosomiasis via tsetse fly
198
Mitochondrial DNA is susceptible to what drug class?
NRTI (HIV drug)
199
What can cause EOM pain as a primary complaint?
Ethambutol causing optic neuritis
200
Which drugs are the mixed Amebicides?
Metronidazole, Tinidazole (think MetronTin mixed). They are also part of Giardiasis tx.
201
What is an antiviral and HIV treatment?
Tenofovir and Lamivudine (anti hep and NRTI)
202
Azoles should not be used with ___
Amphotericin B
203
What is a treatment for erythrocytic forms of malaria?
Chloroquine (also systemic amebicide) is drug of choice, Mefloquine, Quinine
204
Suramin
tx Trypanosomiasis. moa:Inhibits many enzymes involved in energy metabolism. used prophylactically for sleeping sickness.
205
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.
206
Atazanavir
HIV protease inhibitor. inhibits HIV aspartyl protease to prevent viral maturation. MANY drug-drug interactions. *can cause slow heart rate
207
What disease is attracted to the macula?
toxoplasma gondii
208
What Parasite grows in blood and eventually invades CNS?
trypanosomiasis via tsetse fly causes Sleeping sickness (in Africa)
209
Quinine
Malaria drug. *interferes with heme polymerization. reserved for severe/resistant cases. AE: cinchonism: Nausea, Vomiting, Tinnitus, Vertigo
210
Which NNRTI has a long half-life and is the most preferred?
Efavirenz
211
What supplement is anti-pathogen?
Echinacea
212
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.
213
What drugs can cause liver toxicity?
Isoniazid (1a Antimycobacterial) Ethionamide (2L Antimycobacterial), NRTI (HIV drug),
214
What is often given with
| Amphotericin B?
Flucytosine
215
AE Sulfonamides:
Crystalluria, allergies, anemia, increase warfarin levels by inhibiting p450.
216
Which anti-CMV needs to be activated by viral enzyme?
Ganciclovir
217
Cidofovir
Cytomegalovirus drug. cytosine analog inhibits DNA synthesis wo/ need of viral enzymes. *Tx cmv-induced retinitis in AIDS patients
218
Which trypanosomiasis drugs treat African sleeping sickness?
Pentamidine and Suramin (prophylaxis)
219
Chloramphenicol
PSI, "other". binds to 50s ribo subunit to inhibit peptide bond formation.
220
Tx acute Chagas
Nifurtimox (trypanosomiasis)
221
What supplement is used for increasing cognition and concentration?
Ginkgo
222
Which integrase inhibitor is only available in combination?
Elvitegravir. With Tenofovir/ Emtricitabine/ Elvitegravir/ Cobicistat
223
How is Leishmaniasis transmitted?
Through sandfly bites
224
Cycloserine
Second-line antimycobacterial. Inhibits cell wall synthesis. *Exacerbates epileptic seizures
225
What drug can cause folic acid deficiency?
Trimethoprim (antifolate drug)
226
Which malaria drug is good for pregnant people?
Mefloquine (malaria drug)
227
Spectrum of chloramphenicol?
Very strong Broad spectrum
228
What is the treatment of choice for HSV encephalitis?
Acyclovir (anti-herpes)
229
What drug class binds to tissues undergoing calcification (children under 12)
Tetracycline
230
Which anti-viral would you not want to give to COPD or asthma people?
Zanamivir
231
What can be used to treat pneumonia in HIV patients?
Dapsone (leprosy drug)
232
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
233
What supplement used as an anti-cancer?
Ginseng , Milk Thistle, and St. John’s Wort
234
Zidovudine (AZT)
HIV drug, NRTI, nucleoside/tide integrates into DNA, terminating DNA elongation. *can be used for prophylaxis and is toxic to bone marrow
235
Which amebicide is also used for malaria and arthritis/lupus?
Chloroquine
236
Which antiviral is particularly bad for people with renal failure?
Amantadine (uncoating inhibitor), high dose Acyclovir (anti-herpes), Cidofovir (anti-CMV)
237
What drugs bind to the 50s ribosomal subunit?
Chloramphenicol, Clindamycin, Linezolid, Macrolides/Ketolides.
238
Which anti-CMV doesn't need to be activated by viral enzyme?
Cidofovir
239
Viruses that cause the flu contain the enzyme _____
Neuraminidase
240
How is resistance for macrolides/ketolides?
It's becoming a problem. Drug has decreased 50s affinity in resistance
241
Acyclovir
Herpesvirus drug. Guanosine analog gets incorporated into viral DNA via DNA poly. *tx HSV encephalitis
242
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
243
Rilpivirine
HIV drug, NNRTI that causes conformational change to HIV-1 reverse transcriptase
244
Lopinavir
HIV protease inhibitor. inhibits HIV aspartyl protease to prevent viral maturation. MANY drug-drug interactions.
245
Pyrimethamine
tx Toxoplasmosis, combined with sulfadiazine.
246
Doxycycline
**PSI, Tetracycline. reversibly binds to 30s ribo. subunit preventing tRNA binding--translation stops. *liver excreted
247
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
248
What antifungal induces p450 activity?
Griseofulvin ("other")
249
What drugs can cause skin rash?
Cotrimoxazole (antifolate) and rifampin, rifabutin (1L antimycobacterial) (NOT rifapentine)
250
Which NRTI can be used for prophylaxis and is toxic to bone marrow?
Zidovudine (AZT)
251
Which HIV protease inhibitor can cause severe and fatal hepatitis, rare intracranial hemorrhages?
Tipranavir
252
Echinacea
Botanical/Herbal. used for increasing wbc, anti-inflammatory, and anti-pathogen
253
Preclinical testing is finding out what toxicities?
Acute, subacute, and chronic
254
Iodoquinol
Luminal Amebicides. *effective against both trophozoite and cyst forms. can cause optic neuritis
255
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
256
What is the combo treatment for toxoplasma gondii?
pyrimethamine and sulfadiazine
257
Glucosamine
Purified Supplements. used for cartilage nutrient
258
Saquinavir
HIV protease inhibitor. inhibits HIV aspartyl protease to prevent viral maturation. MANY drug-drug interactions.
259
Ribavirin
Viral Hepatitis drug. guanosine analog causes dec guanosine triphosphate, blocking DNA/RNA synthesis.
260
Which malaria drug can cause depression?
Mefloquine
261
How much does it take to develop a drug?
$150 million to several billion
262
Ganciclovir has much less toxic with easier dosing than…_____
Trifluridine
263
Zanamivir
Respiratory flu drug. Inhibits neuraminidase, kills virus. via intranasal. not for COPD/asthma people
264
AE HIV protease inhibitors:
FAT REDISTRIBUTION, Paresthesias, GI disturbances, Changes in glucose and lipid metabolism
265
Micafungin
Antifungal, Echinocandin. lyses cell wall.
266
Melarsoprol
tx Trypanosomiasis. tx sleeping sickness or Chagas disease, perhaps?
267
Nevirapine
HIV drug, NNRTI that causes conformational change to HIV-1 reverse transcriptase. P450 inducer,
268
Which drugs hardly interact with P450?
Linezolid (PSI), Azithromycin (Macrolides)
269
What drug class inhibits the cytochrome P450 system?
Azoles (and Macrolides/Ketolides except Azith), this can increase Warfarin drug concentration
270
Which drugs are the systemic Amebicides?
Chloroquine, Dehydroemetine, Emetine, (Think Chlo-emetine system). Chloroquine is also part of malaria tx.
271
What drugs can cause Optic and peripheral neuropathy?
Linezolid (other PSI)
272
What is the distribution of Aminoglycosides?
Bad for systemic versions, they cross the placenta. High concentrations in inner ear and renal cortex
273
What supplement promotes lactation?
Milk Thistle
274
Which "tetracycline" has expanded spectrum?
Tigecycline.
275
What supplement is used for treating liver disease?
Milk Thistle
276
What can cause nephrotoxicity?
Aminoglycosides, Capreomycin (2L antimycobacterial)
277
Sodium stibogluconate
tx Leishmaniasis. orally poor. AE: Can cause pain at the injection site, GI upsets, and cardiac arrhythmias.
278
Fluconazole
Antifungal, Azole. Inhibits P450 enzyme that converts lanosterol to ERGOSTEROL, disrupting fungal membrane.
279
How is Amphotericin B administered? Eliminated?
SLOWLY through IV.
| Excreted through BOTH kidney and liver
280
What kind of resistance can Trimethoprim encounter?
Gram (-) from altered enzyme
281
What is used to treat abdominal bacterial infections associated with trauma?
Clindamycin
282
AE for Cotrimoxazole:
Skin rash (esp in elderly), Nausea, vomiting, Anemia or thrombocytopenia
283
Saw Palmetto
Botanical/Herbal. used for treating BPH (inflamed prostate)
284
Where does Trimethoprim tend to accumulate?
In acidic environments because the drug is a weak base
285
Which drugs are P450 inducers?
NNRTIs (HIV drugs), Griseofulvin (antifungal), and Isoniazid, Rifampin, Rifabutin (1L antimycobacterial)
286
What is the drug of choice for erythrocytic forms of malaria?
Chloroquine (also systemic amebicide)
287
Which drugs are never given as a single agent?
Isoniazid (1L antimycobacterial), Rifamycins (1L antimycobacterial)
288
What can cause gray baby syndrome?
Chloramphenicol because baby can't excrete the drug well
289
Can you use a different tetracycline for bacteria that is resistant to a tetracycline?
Nope!
290
What drugs bind to the 30s ribosomal subunit?
Tetracyclines, Aminoglycosides
291
MOA:
| oxygen radicals toxic to both host/parasite but human enzymes fix damage.
Nifurtimox (trypanosomiasis)
292
AE nitrofurantoin:
Hemolytic anemia, GI disturbances, Neurological problems, Chronic use can result in interstitial pulmonary fibrosis
293
Which antiviral can cross the BBB?
Amantadine (uncoating inhibitor)
294
What is the treatment for EXOerythrocytic forms of malaria?
Primaquine
295
Paromomycin
Luminal Amebicides. *aminoglycoside antibiotic. it doesn't get absorbed through GI and kills food source
296
Ritonavir
HIV protease inhibitor. inhibits HIV aspartyl protease to prevent viral maturation. MANY drug-drug interactions. *P450 inhibitor, boosts performance of other protease inhibitors
297
Elimination of Macrolides/Ketolides:
Kidney. They inhibit p450 enzyme system (Azithromycin does NOT inactivate P450 enzymes)
298
Dapsone
Antimycobacterial, Leprosy drug. Inhibits folate synthesis. concentrates in skin, Tx pneumonia in HIV patients
299
What is approved for treatment of cytomegalovirus induced retinitis in AIDS patients?
Cidofovir
300
How is Cotrimoxazole administered?
Orally
301
How do you administer interferons for hep tx?
IV or IM because it's made of recombinant DNA
302
What class of drugs have tons of interactions?
HIV protease inhibitors
303
Capreomycin
Second-line antimycobacterial. Inhibits protein synthesis
304
Amphotericin B
Antifungal, Polyene Antibiotic. binds to ergosterol in membrane making ion pore > death.
305
Trimethoprim
Antifolate. Inhibits dihydrofolate reductase, preventing dihydrofolic acid to tetra
306
Which stage of Giardia lamblia is resistant to drugs?
The four-nucleate cyst (as opposed to the binucleate trophozoite)
307
What is the antifungal precursor to 5-FU?
Flucytosine
308
Which amebicide kills off the protozoal food source?
Paromomycin (luminal amebicide)
309
What is the pharmacokinetics of HIV protease inhibitors? (bioavailability, metabolism)
Poor oral bioavailability, P450 metabolized, good for renal impairment.
310
What drug can decrease glomerular filtration rate?
Amphotericin B
311
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
312
Gemifloxacin
2nd line antimycobacterial and 4nd Gen Fluoroquinolone. Enters bacteria via diffusion; uses dual mechanism to inhibit DNA gyrase and topoisomerase IV.
313
Spectrum of
| Fluoroquinolones:
Both +/- , including (-) like Pseudomonas, H. influenzae, Moraxella, Chlamydia
314
Terbinafine
*Antifungal, "Other". Squalene builds up because drug prevents conversion into ERGOSTEROL by inhibiting squalene epoxidase. *Tx nail infection
315
What inhibits the p450 enzyme lanosterol to ergosterol, disrupting membrane structure and function?
Azoles
316
What drug binds ergosterol in the plasma membrane and forms a pore for electrolytes?
Amphotericin B
317
Which HIV protease inhibitor can cause slow heart rate?
Atazanavir
318
AE for Flucytosine:
Neutropenia, Thrombocytopenia, Bone marrow depression--bad for immunocompromised, Caution in patients undergoing chemotherapy, GI disturbances common
319
Which antifolate drug is good against MRSA?
Cotrimoxazole
320
What is used for pre-CNS involvement of sleeping sickness?
Pentamidine (trypanosomiasis)
321
Griseofulvin
Antifungal, "Other". Inhibits fungal mitosis until skin sloughs it off.
322
Minocycline
PSI, Tetracycline. reversibly binds to 30s ribo. subunit preventing tRNA binding--translation stops.
323
Which tetracycline is good for people with renal disease?
Doxycycline
324
Dehydroemetine
Systemic Amebicides. inhibits protein synthesis. Via IM; oral might cause vomiting. Can concentrate in liver for a month
325
What drug is restricted to topical Candida infections
Nystatin because it's systemically toxic
326
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
327
What is often given with
| Flucytosine?
Amphotericin B
328
___ should not be taken with Sulfonamides because they cancel out
Methenamine
329
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
330
What supplement is anti-inflammatory?
Echinacea and Ginseng
331
Didanosine
HIV drug, NRTI, nucleoside/tide integrates into DNA, terminating DNA elongation *take when fasting, AE Pancreatitis and peripheral neuropathy
332
What drug combo can make HIV UNDETECTABLE in 60-95% of patients?
A protease inhibitor and two NRTIs
333
Spectrum of viral uncoating inhibitors:
Influenza A
334
What supplement is used for jet lag, insomnia, and improving sleep?
Melatonin (purified supplement)
335
Boceprevir
Viral Hepatitis drug. Bind to active site of HCV protease
336
Contraindications for Fluoroquinolones:
Pregnancy, nursing mothers, children under 18, arrhythmia
337
How are NRTIs excreted?
Kidney, except abacavir!
338
What supplement is used for hypertension, improving output in heart failure, prevents statin-induced myopathy.
Coenzyme Q10 (purified supplement)
339
AE of aminoglycosides:
Ototoxicity, nephrotoxicity, neuromuscular paralysis, bad allergic reactions
340
Which antivirals are antimetabolites?
Ribavirin (anti hep),
| Acyclovir (anti-herpes)
341
What is the drug of choice for chlamydia infections?
Azithromycin (z-pak)…. (Fluoroquinolones are also good)
342
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)
343
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.
344
What drugs cause epigastric distress?
Macrolides/Ketolides
345
Lepers who are allergic to ___ might also be allergic to Dapsone
Sulfa drugs
346
Why are mycobacterial resistant to most antibiotics?
Grow more slowly, Can be dormant, Cell wall impermeable to many drugs, can be intracellular
347
Fosamprenavir
HIV protease inhibitor. inhibits HIV aspartyl protease to prevent viral maturation. MANY drug-drug interactions.
348
What drugs should not get acidic?
Sulfonamides
349
Which NRTI does NOT affect mitochondrial DNA synthesis?
Lamivudine (has less side effects). Remember Emtricitabine has NO significant drug interactions
350
Only __% of marketed drugs return their R&D investments
20%
351
Rifabutin AE:
UVEITIS, Uncommon Nausea, vomiting, rash. (Orange feces, urine, and tears..?). p450 inducer
352
Raltegravir
HIV integrase inhibitor that inhibits final step of integration of viral DNA into host DNA. NO P450 interactions
353
Rifabutin
*First-line antimycobacterial. inhibits RNA polymerase to prevent transcription. *Good for HIV patients that need it. increase P450 metabolism. Can cause uveitis
354
Valacyclovir (Valtrex)
Herpesvirus drug.?Guanosine analog gets incorporated into viral DNA via DNA poly
355
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
356
What decreases testosterone and cortisol production?
Azoles
357
___% 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
358
AE chloramphenicol:
GI disturbances, Candida overgrowth, Anemia (can be fatal), Gray baby syndrome
359
Fidaxomicin
PSI, Macrolide/Ketolide. Binds to 50s ribo. subunit (can inhibit its formation) to block peptidyl transferase center to prevent AA elongation.
360
What disease causes a dendritic pattern on the cornea?
Herpetic Keratitis
361
AE Ethionamide:
GI irritation, Hepatotoxicity, Optic Neuritis, Peripheral neuropathies
362
Ginkgo
Botanical/Herbal. used for increasing blood flow and vasodilation; increasing cognition and concentration.
363
Which drugs bind to the 30s ribosomal subunit?
Tetracyclines, Aminoglycosides
364
What drug can cause some visual disturbances?
Terbinafine (antifungal)
365
What strategies can prevent mycobacterial resistance?
Use multiple drugs, LONG duration, increase compliance through directly observed therapy. (DOT)
366
What drugs can lead to fat redistribution?
HIV protease inhibitors
367
Methenamine should not be taken with __ because they cancel out
Sulfonamides
368
What drugs are bad to have with Ca++, Iron, Antacids?
Fluoroquinolones and Tetracyclines
369
Hepatitis __ and __ are the most common causes of chronic hepatitis, cirrhosis, and hepatocellular carcinoma
B and C
370
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
371
Tx Leishmaniasis
Sodium stibogluconate
372
What drug have flu-like AE?
Interferons (anti Hep)
373
Which amebicide inhibits protein synthesis?
Dehydroemetine and Emetine
374
Caspofungin
*Antifungal, Echinocandin. lyses cell wall. *second-line antifungal if amphotericin B or azole fails
375
Which Fluoroquinolone is most potent against pseudomonas?
Ciprofloxacin
376
What can cause precipitate gout?
Pyrazinamide (1L antimycobacterial)
377
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.
378
Oseltamivir (Tamiflu)
Respiratory flu drug. Inhibits neuraminidase, kills virus.
379
Nitrofurantoin
Urinary Tract Antiseptic. bacteria makes drug a toxic intermediate that damages their DNA
380
What foods/supplements should you avoid when taking tetracyclines?
Calcium (dairy) reduces bioavailability; avoid antacids or iron supplements
381
Which NRTI can cause a fatal allergic reaction upon second exposure?
Abacavir
382
Gentamicin
PSI Aminoglycoside. Binds to 30s ribo subunit preventing protein synthesis initiation AND cause misreading of mRNA causing wrong AA insertion.
383
What supplement is used as an antiviral?
St. John’s Wort
384
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
385
Who is involved in phase 1 clinical trials?
Small number (20-100) of healthy volunteers
386
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.
387
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
388
Anidulafungin
Antifungal, Echinocandin. lyses cell wall.
389
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
390
Which drugs inhibit P450?
Azoles, Macrolides/Ketolides (except Azithromycin)
391
Neomycin
PSI Aminoglycoside. Binds to 30s ribo subunit preventing protein synthesis initiation AND cause misreading of mRNA causing wrong AA insertion.
392
Telithromycin
PSI, "Ketolide". Binds to 50s ribo. subunit (can inhibit its formation) to block peptidyl transferase center to prevent AA elongation.
393
What does the cell membrane of fungi contain?
Ergosterol
394
What drugs can cause peripheral neuropathy?
Didanosine and other NRTIs, Nifurtimox (trypanosomiasis), Linezolid (PSI), Ethionamide (2L Antimycobacterial)
395
Garlic
Botanical/Herbal. used for lowering cholesterol, decreasing blood pressure, antibiotic effects.
396
Which form of Entamoeba histolytica is infective?
The cyst form
397
Pentamidine
tx. Trypanosomiasis. used for pre-CNS involvement of sleeping sickness
398
Telaprevir
Viral Hepatitis drug. Bind to active site of HCV protease
399
AE Macrolides/Ketolides:
Epigastric distress, cholestatic jaundice, ototoxicity
400
Which malaria drugs in combination can cause cardiac arrest?
Mefloquine with quinine (malaria drug) or (quinidine).
401
What drugs can cause Anemia?
chloramphenicol and Linezolid (other PSI), nitrofurantoin (UTI antiseptic), Sulfonamides, and Cotrimoxazole and Trimethoprim (antifolates)
402
How are generic drugs approved? What's required?
Through an abbreviated new drug application (ANDA). Must demonstrate equivalence.
403
WHO recommends what for treatment of leprosy? For how long?
The triple-drug regimen: dapsone, clofazimine, and rifampin for 6 to 24 months
404
Spectrum of Isoniazid (1L antimycobacterial):
M Tuberculosis, intracellular bacteria
405
Ketoconazole
*Antifungal, Azole. Inhibits P450 enzyme that converts lanosterol to ERGOSTEROL, disrupting fungal membrane. * more side effects, limited to topical
406
What drug class can cause pseudotumor cerebri?
Tetracyclines
407
Which antiviral should be avoided in pregnancy?
Ganciclovir (anti-CMV)
408
Which NRTI has NO significant drug interactions?
Emtricitabine. Remember Lamivudine does NOT affect mitochondrial DNA synthesis.
