Chapter 54 Chemotherapy of Protozoal Infections Flashcards
1
Q
Best agents for treating sleeping sickness and chronic Chagas disease
A
None existent
2
Q
Problems with antiprotozoal drugs
A
most are toxic at therapeutic doses and increasing drug resistance of parasites
3
Q
Prevalence of Amoebiasis
A
10% or Worlds population about 50 million people and mortality rate of 100,000 annually
4
Q
Amoebiasis is commonly seen in:
A
individuals living in poverty, crowded conditions and in areas with poor sanitation
5
Q
what are the three morphologically identical Entamoebas?
A
E. histolytica, E. dispar and E. moshkovskii
6
Q
the recently discovered Entamoeba that may be pathologic
A
E. bangladeshi
7
Q
Entamoeba that requires treatment
A
E. histolytica
8
Q
The third leading cause Of mortality by parasitic infection
A
E. histolytica
9
Q
Route of transmission of Entamoebas?
A
fecal-oral, ingestion of cysts (infective stage)
10
Q
Outcome of E. histolytica infection
A
Most are asymptomatic, but when trophozoites invade the colonic mucosa, it may cause colitis and bloody (amebic) diarrhea; trophozoites may also travel to the liver causing amebic liver abscess (ALA)
11
Q
the cornerstone of therapy for amebiasis is
A
metronidazole or its analogue tinidazole
12
Q
T/F: Metronidazole is effective against entamoeba cysts?
A
False. Thats why you should add luminal agents (paromomycin or iodoquinol) together with metronidazole to eradicate the entamoeba especially in individuals with amebic colitis or amebic liver abscess
13
Q
A drug that is used primarily for treatment of kf cryptosporidiosis and giardiasis that showed effectivity against E. histolytica
A
nitazoxanide
14
Q
Is the most common reported intestinal protozoan infection in the US
A
Giardiasis
15
Q
Giardiasis is caused by
A
flagellated protozoan G. intestinalis
16
Q
giardiasis infection is via
A
ingestion of cyst form of the parasite found in fecally contaminated water or food, or through anal sex (male homosexuals)
17
Q
Hosts of entamoeba parasites?
A
Only humans
18
Q
Giardiasis infection may result to?
A
asymptomatic carrier state, acute self-limited diarrhea, and chronic diarrhea with signs of malabsorption (steatorrhea) and weight loss
19
Q
Treatment for giardiasis?
A
metronidazole, 5-7 days may be repeated or prolonged or
tinidazole, single dose (may be superior to metronidazole) or
nitazoxanide for adults and immune-competent children <12 Y.O
20
Q
treatment of giardiasis in pregnant women?
A
paromomycin to avoid mutagenic effects of other drugs
21
Q
this organism inhabits the genitourinary tract where it causes vaginitis in women and urethritis in men
A
T. vaginalis
22
Q
The most common nonviral sexually transmitted disease
A
trichomoniasis
23
Q
what form of the parasite is seen in infected secretion in trichomoniasis?
A
Trophozoite forms
24
Q
DOC for trichomoniasis?
A
Metronidazole, but Tinidazole is better tolerated and can be used to treat metronidazole-resistant T. vaginalis
25
is a zoonotic infection caused by an obligate intracellular protozoam T. gondii
toxoplasmosis
26
the natural host of T. gondii
Cats and other feline species (showing tissue cyst/bradyzoites which are also seen in other mammals)
27
routes of infection of toxoplasmosis in humans:
ingestion of undercooked meat with tissue cysts,
ingestion of contaminated vegetable matter containing infective oocytsts,
Direct contact with the faces of cat shedding oocysts,
Transplacental fetal infection with tachyzoites from acutely infected mothers
28
Tissue cyst of T. gondii
bradyzoites
29
form of T. gondii that causes transplacental fetal infection
tachyzoites
30
T/F acute illness of toxoplasmosis requires immediate treat & intervention?
False, the disease is usually self-limiting and doesn't require treatment
31
most common finding of congenital toxoplasmosis
chorioretinitis
32
primary treatment for toxoplasmic encephalitis
1. antifolates (pyrimethamine) + sulfadiazine + folinic acid (leucovorin)
but is toxic due to the SULFA compound
2. pyrimethamine+clindamycin is comparable but with substantial toxicity
3. alternative regimens combi drug (azithromycin + clarithromycin+ atovaquone or dapsone) is less toxic but less effective
33
drug for preventing toxoplasma transmission to the fetus, used in early pregnancy
spiramycin
34
treatment for fetal toxoplasmosis infection?
antifolates (pyrimethamine) + sulfadiazine + folinic acid (leucovorin) to the mother (after 12-14 weeks of gestation) and postnatally given to the newborn for 1 year
35
caused by coccidian protozoan parasite that causes diarrhea
cryptosporidiosis
36
cryptosporidia species accountable to almost all infections in humans
C. parvum and C. hominis (newly named)
37
Mode of infection of cryptosporidiosis?
ingestion of infectious oocyst in feces spread by human to human contact or by contaminated water
38
form of cryptosporidia parasite that invade host epithelial cells?
sporozoites
39
cryptosporidiosis is usually ________ in immunocompetent individuals
self-limiting
40
treatment of cryptosporidiosis and immunocompetent children and adults
Nitazoxamide
41
treatment of cryptosporidiosis and immunocompromised patients
restoration of immune function
42
causes african sleeping sickness or trypanosomiasis
T. brucei,
west african type: gambiense causing later CNS involvement and long-term course
east african type: rhodesiense causing progressive and rapidly fatal CNS involvement with terminal cardiac failure
43
vector for T. brucei
Tsetse flies of genus Glossina
44
trypanosomiasis is restricted to
sub-Saharan africa, causing serious infection and may also cause protein malnutrition by threatening the livestock (nagana)
45
Stage 1 of trypanosomiasis
earliest stage, replicating parasites is seen in the bloodstream or lymph without CNS involvement
46
Stage 2 of trypanosomiasis
characterized by CNS involvement with symptoms including febrile illness, lymphadenopathy, splenomegaly and occasional myocardiris
47
treatment for early stage of trypanosomiasis west african type?
pentamidine, parenteral for long periods but ineffective against late-stage disease
48
treatment for early stage of trypanosomiasis east african type?
suramin, parenteral for long periods but ineffective against late-stage disease
49
traditional treatment of trypanosomiasis with CNS involvement
melarsoprol, but causes fatal reactive encephalitis
50
only agent for late stage of trypanosomiasis
eflornithine (inhibitor or ornithine decarboxylase, a key enzyme for polyamine metabolism) but is only effective against T. brucei gambiense early and late stages of the disease with less side effects than melarsoprol
but INEFFECTIVE monotherapy against T. brucei rhodisiense
51
treatment of choice for late-stage T. brucei gambiense
NECT (Nifurtimox+Eflornithine)Combination Therapy with good efficacy and less side effects than melarsoprol
52
also known as American trypanosomiasis
Chagas Disease
53
a zoonotic infection caused by T. cruzi
Chagas disease
54
Chagas' disease is primarily confined to
Latin America
55
common vector to chagas disease
bloodsucking triatomid bugs
56
other route of transmission of Chagas disease?
blood transfusion and organ transplantation
57
chronic form of Chagas disease causes
cardiomyopathy,
megaesophagus,
megacolon,
death
58
Chagas heart disease follows what guidelines?
ACC and AHA for treatment of heart failure (using ACE inhibitors and beta adrenergic blockers, with downward adjustment-but still debated)
59
treatment for Chagas disease
Either of the two nitroheterocyclic drugs- nifurtimox ans benznidazole.
Both can suppress parasitemia and cure acute phase Chagas disease, and also deemed beneficial to intermediate and late stages of Chagas disease.
Both are TOXIC and must be taken for long periods
60
a complex vector-borne zoonotic disease caused by 20-species of intramacrophage protozoa of genus Leishmania
Leishmaniasis
61
reservoir of leishmania
small mammals and canines
62
vector of leishmania
female phloebotomine sandflies
63
transformation cycle of leishmania
flagellated free PROMASTIGOTES from infected feeding sandflies is regurgitated and enter the human host where they are engulfed by macrophage and then becomes AMASTIGOTES then multiply within the phagolysosomes until the macrophages burst and the amastigotes invades more macrophages and taken up by feeding sandflies where they transform back to promastigotes
64
Classification of Leishmaniasis in increasing order of systemic involvement and severity
1. Cutaneous - (self-limiting, cured after 3-18 months but can leave dysfuguring scars)
2. Mucocutaneous
3. Diffuse Cutaneous
4. Visceral (Kala Azar) - (fatal unless treated)
2-4 don't resolve without therapy
65
the leishmaniasis disease syndrome manifested depends on?
1. species or subspecies of infecting parasite
2. distribution of infected macrophages
3. host immune response
66
Classic therapy for all species of Leishmania is
Pentavalent antimony compounds (sodium stibogluconate or sodium antimony gluconate),
67
FDA-approved first orally active agent for treatment for cutaneous, mucocutaneous, and visceral leishmaniasis
miltefosine but TERATOGENIC, also should promising results as treatment for animal reservoirs like dogs
68
alternative drug for miltefosine in treating visceral leishmaniasis
liposomal amphotericin B, highly effective agent
69
used with some success as a parenteral agent for visceral leishmaniasis
Paromomycin
70
drug with topical formulations used in cutaneous leishmaniasis
paromomycin
71
babesiosis, a tick-borne zoonotic disease, is caused by
B. microti or B. divergens
72
babesiosis resembles what parasite
malaria, invading the RBCs
73
babesiosis presents with
febrile illness, hemolyis and hemoglobinuria, is usually mild and self-limiting but may be severe or fatal un ASPLENIC and severely immunocompromised
74
therapy for severe babesiosis
Combi of Clindamycin + Quinine
75
therapy for mild to moderate babesiosis
combi of Azithromycin + Atovaquone
76
Balantidiasis is an infection of LARGE INTESTINE is caused by what parasite
B. coli, ciliated protozoan
77
Theraphy for balantidiasis
Tetracycline
78
a coccidia that causes self-limited diarrhea in normal hosts or
prolonged diarrhea in immunocompromised patients
Cyclospora cayetanensis
79
a coccidia that causes diarrhea in patients with AIDS
Cycloisospora belli, formerly known as Isospora belli
80
treatment for Cyclospora and Cycloisospora infections?
trimethoprim-sulfamethoxazole
81
a spore-forming, unicellular, eukaryotic organisms that were once considered to be parasites
Microsporidia
82
A drug that is highly effective against visceral leishmaniasis (90% cure rate) and used for antimonial-resistant cases, can be also be used for cutaneous and mucosal leishmaniasis,
effective for immunocompromised patients
Amphotericin B, lipid preparations have reduced toxicity but costly and difficult to administer
83
Leishmania has similar _______ composition to fungi
sterol
84
MOA of Amphotericin B
forms complexes with ergosterol precursors forming pores in the cell membrane allowing ions to enter
85
typical regimen for visceral leishmaniasis using Amphotericin B
10-20 mg/kg total dose over 10-20 days by IV infusion (95% cure rate)
86
FDA recommendation regimen for VISCERAL leishmaniasis using Amphotericin B
21 mg/kg total dose
| given in 3 mg/kg IV on first 1-5 days, day 14 and day 21
87
FDA recommendation regimen for CUTANEOUS leishmaniasis using Amphotericin B
at least 21 mg/kg total dose
| given in 3 mg/kg/d IV for 7-10 days
88
these are molecules that are required for cell division that is inhibited by eflornithine
polyamines (putrescein, spermidine, and spermine)
89
irreversible catalytic (suicide) inhibitor of ornithine decarboxylase
eflornithine (DFMO)
90
the enzymes that catalyzes the first and the rate-limiting step in polyamine biosynthesis
ornithine decarboxylase
91
a polyamine that is required in the synthesis of trypanothione
spermidine
92
trypanothione is a conjugate of
spermidine and glutathione that replaces that function of glutathione in trypanosomes
93
eflornithine is transported into the cell via
amino acid transporter (Tb AAT6)
94
NECT (Nifurtimox+ Eflornithine Combi Therapy) is the DOC for
late-stage West African (Gambian) Trypanosomiasis
95
is a cytostatic agent that depletes polyamine
eflornithine, given IV
96
T/F: both human and parasite enzymes are susceptible to eflornithine?
True, but mammalian enzymes are turned over rapidly while parasite enzymes is stable-SELECTIVE TOXICITY
97
minimum eflornithine CSF concentration for parasite clearance
50 μM
98
T/F: eflornithine binds well with plasma proteins and doesn't penetrates the CSF
False, eflornithine does not bind to plasma proteins and well-distributed and penetrates into the CSF
99
half-life of eflornithine and renal clearance
3-4 hours, renal clearance 2 ml/min/kg ( >80% of unchanged drug)
100
NECT vs Eflornithine alone
higher cure rate, easier to administer
101
NECT dosing for late-stage West African Trypanosomiasis
Nifurtimox (oral)
15 mg/kg/d
divided doses every 8 hours for 10 days
+
Eflornithine (IV infusion)
200 mg/kg IV every 12 hours by 2-hour infusion for 7 days
with coadministration of substantial volumes of IV fluid leads to limitation of use posed by fluid overload
102
Eflornithine adverse reactions are generally reversible on drug withdrawal including
abdominal pain and headache - chief complaints
local reactions at injection site
fever peaks , seizures and diarrhea - most severe reactions
hearing loss (reversible) after prolonged therapy
103
luminal agents for E. histolytica in amebic colitis and amebic liver abscess
1. halogenated 8-hydroxyquinolines:
iodoquinol (diiodohydroxyquin) SAFER than clioquinol and
clioquinol (iodochlorhydroxyquin)
2. paromomycin - preferred since less adverse-effects
104
most important toxic reaction to clioquinol
subacute myelo-optic neuropathy
105
Administration of iodoquinol in children with chronic diarrhea may cause
optic neuropathy and permanently vision loss
106
less severe manifestation of neurotoxicity of hydroxyquinolines
Peripheral neuropathy
107
dosing of iodoquinol in adults
650 mg/day oral, 3 times daily for 20 days
108
dosing of iodoquinol in children
30-40 mg/kg/d (not exceeding 1.95 g/d)
| divided three times daily for 20 days
109
drug that is supplied as a 3.6% solution in PEG for slow IV administration (since drug is intensely irritating)
melarsoprol
110
only drug effective against late-stage (CNS) East African Trypanosomiasis,
also effective against late-stage (CNS) West African Trypanosomiasis
melarsoprol
111
the active drug of melarsoprol
melarsen oxide,
| melarsoprol is rapidly metabolized (<30 minutes) to melarsen oxide
112
melarsen oxide binds with
trypanothione resulting in adduct formation and inhibition of tryoanothione reductase
113
resistance to melarsoprol is due to
defects linked to aquaglyceporin pore-forming protein
114
terminal half-life of melarsen oxide
43 hours
115
fatality rate for untreated East African (Rhodesian) Trypanosomiasis
~100% fatality rate
116
T/F: for T. brucei rhodesiense relapse, you can still use melarsoprol as second course
True
117
T/F: for T. brucei rhodesiense uncured with melarsoprol, you can still use melarsoprol as second course
False, use eflornithine instead
118
Melarsoprol dosing
2.2 mg/kg/d IV for 10 days
119
what is employed/added throughout the treatment course to reduce the prevalence of encephalopathy caused by melarsoprol?
prednisolone
120
most often adverse reaction to melarsoprol?
febrile reaction after drug administration, especially if parasitemia is high
121
most serious complication of melarsoprol, occuring in 5-10% of patients after 9-11 days of treatment
reactive neuropathy
122
adverse effects of melarsoprol such us vomiting and abdominal colic is reduced by?
slow IV injection, with patient supine and fasting
123
melarsoprol administration in leprous patient may cause?
the precipitation of erythema nodosum
124
contraindications in melarsoprol use
influenza epidemics and G6PD deficiency (causing hemolytic anemia)
125
T/F: melarsoprol can be given to pregnant patients?
True
126
Metronidazole had especially high activity in vivo or in vitro against anaerobic protozoans
T. vaginalis and E. histolytica
127
Oral doses of metronidazole imparted____ activity to semen and urine with high cure rate of the disease ____.
trichomonacidal activity, trichomoniasis
128
1-( beta-hydroxyethy)-2-methyl-5-nitroimidazole
metronidazole
129
True or False
Metronidazole had extremely useful clinical activity against a variety of anaerobic pathogens both gram (-) and gram (+) bacteria including the protozoan _____
True
| G. lamblia
130
Other clinically effective 5-nitroimidazoles closely related in structure and activity to metronidazole
tinidazole
| ornidazole
131
Metronidazole has potent amebicidal activity against
E. histolytica
132
phase of life cycle in G. lamblia that is affected by metronizadole at ____ concentrations
Trophozoites
| 1-50microgram/mL (in vitro)
133
studies in drug-sensitive and drug-resistant protozoan parasites indicates that the nitro group on __of metronidazole is essential for activity and substitution at the ___ enhance the resonance conjugation of the chemical structure increases protozoal activity
C5
| 2 position
134
What will happen if 2 position is substituted by an acyl group of metronidazole?
it ablates the conjugation thus reduces antiprotozoal activity
135
True or false
Metronidazole manifests antibacterial activity against all anaerobic cocci and both anaerobic gram- and gram+ bacilli, including Bacteroides speciesand, anaerobic spore-forming gram+ bacilli and nonsporulating gram+ bacilli
False
| Nonsporulating gram+ bacilli are often resistant, as are aerobic and facultatively anaerobic bacteria
136
Metronidazole is clinically effective in infections such as
trichomoniasis, amebiasis, giardiasis and variety of infections caused by obligate anaerobic bacteria including Bacteroides, Clostridium, Fusobacterium, Peptococcus, Peptostreptococcus, Eubacterium, and Helicobacter
137
Metronidazole is clinically effective in microaerophilic bacteria such as
Helicobacter and Campylobacter species
138
Metronidazole may facilitate extraction of this parasite in but has no direct effect on the parasite
adult guinea worms in dracunculiasis
139
The selective toxicity of metronidazole toward anaerobic and microaerophilic pathogens derives from their____, this considers metronidazole as ____
metabolism
| prodrug
140
anaerobic and microaerophilic pathogens reactive to metronidazole contains electric transport component that have a sufficiently negative redox potential to donate electrons to the drug
ferredoxins (small Fe-S proteins)
141
What will happen to the action of metronidazole if there's an increasing levels of O2
high levels of O2 can both inhibit the action of metronidazole-induced toxicity (decreases the reductive activation) and increases recycling of the activated drug
O2 competes with metronidazole for electrons generated by energy metabolism
142
Anaerobic and microaerophilic organisms that are susceptible to metronidazole derive energy from
oxidative fermentation of ketoacids such as pyruvate
143
produces electrons that reduce ferredoxin and catalytically donates electrons to metronidazole or to biological electron acceptors
Pyruvate decarboxylation
144
Catalyst of Pyruvate decarboxylate
pyruvate:ferredoxin oxidoreductase
145
PFOR
mechanism in metronidazole metabolism
pyruvate:ferredoxin oxidoreductase
catalyzes pyruvate decarboxylate
pyruvate decarboxylate produces electrons that reduce ferredoxin and catalytically donates electrons to metronidazole or to biological electron acceptorsthat
146
Shows resistance to metronidazole
T. vaginalis
G. lamblia
E. histolytica
147
Two major types of abnormalities that lead to resistant strains of T. vaginalis to metronidazole
impaired oxygen-scavenging capabilities
| lowered levels of PFOR
148
Why infections with resistant strains to metronidazole responds to higher doses or prolonged therapy of the said drug?
PFOR and ferredoxin are not completely absent although lowered
149
in amebic trophozoites, metronidazole resistance is mediated primarily by increase expression of what enzymes
superoxide dismutase and peroxiredoxin
150
Bacteroides spp resistance in metronidazole is linked to what family of genes?
nitroimidazole(nim) resistance gene
| nimA, -B, -C, -D, -E, -F
151
The mean effective concentrations of metronidazole for most susceptible protozoa and bacteria
≤ 8microgram/mL
152
plasma concentration of a single 500mg dose of metronidazole after 0.25-4hrs
8-13microgram/mL
153
half-life of metronidazole in plasma
~8hrs
154
Less than 20% of metronidazole is bound to plasma proteins with the exception of the
placenta
155
metronidazole penetrates well into body tissues and fluids including
```
vaginal secretions
seminal fluids
saliva
breast milk
csf
```
156
Major oxidative metabolites of metronidazole
hydroxy and acetic acid
157
Preparations of metronidazole for administration
oral
iv
intravaginal
topical
158
The main site of metabolism of metronidazole and accounts for ___ of the systemic clearance
Liver
| 50%
159
___ of labeled metronidazole is pass in the urine after an oral dose and ___ is recovered as unchanged drug
75%
| 10%
160
metabolite of metronidazole that has a longer half-life of ___ and has ___ of antitrichomonal activity
hyroxy
~12hrs
~50%
161
Urine color of patients taking metronidazole
reddish brown
162
Oxidative metabolism of metronidazole is induced by drugs and compound such as (4)
phenobarbital
prednisone
rifampim
ethanol
163
this drug appears to inhibit hepatic metabolism of metronidazole
cimetidine
164
metronidazole preferred treatment regimen to genital infections with T. vaginalis in both m and fm
2-g single oral dose
165
this drug alternative has longer half-life than metronidazole and appears to have better response in curing genital infections
what is the dosing
tinidazole
| 2-g single dose
166
treatment regimen for patients who cannot tolerate a single 2-g dose or 1-g BID of metronidazole
250-mg TID or 375-mg BID for 7 days
167
treatment regimen for repeated courses or higher doses of metronidazole for uncured or recurrent infections
250-mg TID or 375-mg BID for 7 days with intervals of 4-6 weeks elapse between courses
168
should be considered prior to treating recurrent or uncured genital infections caused by T. vaginalis with metronidazole
leukocyte count
169
a measure used to successfully treat resistant strains of T. vaginalis
2-g dose to both patient and sexual partner
170
dose of topical gel and vaginal suppository given in addition to oral therapy of metronidazole that will increase the chance of drug concentration and beneficial in refractory cases.
0.75% and 500-1000-mg
171
dose of oral preparation of metronidazole to adult and children infected with amebic colitis and amebic liver abscess
500-750-mg TID for 7 to 10 days for adults
| 35-50mg/kg/day given in 3 divided doses for 7 to 10 days for children
172
How many days is the standard recommendation for the duration of metronidazole therapy?
7-10 days
173
Period and duration of treatment for amebic liver using metronidazole or tinidazole?
short course, -2.4-g OD as single oral dose for 2 days
174
in patients with E. histolytica who recovered from acute amebiasis after metronidazole treatment, it is highly recommended that they should also be treated with what? give examples of such drugs.
luminal amebicide
diloxanide furoate
metronidazole is less effective in treating organisms that thrives in bowel lumen such as luminal amebiasis
175
First-line therapy against giardiasis aside from metronidazole that is yet to be approved in U.S for this infection, give the dosing
tinidazole single 2-g dose
176
Metronidazole also achieves clinically effective levels to this parts of the body
bones
joints
cns
177
appropriate IV dosing for metronidazole when oral administration is not possible
15mg/kg is followed by 6hrs later by a maintenance dose of 7.5/kg every 6hrs, usually for 7-10days
178
Metronidazole is used as a component of prophylaxis for ____ and is employed as a single agent to treat ____
colorectal surgery
| bacterial vaginosis
179
Metronidazole is also used in combination with other antibiotics and a proton pump inhibitor in regiments to treat this infection
H. pylori
180
Metronidazole is used as a primary therapy for infection to this spore-forming gram+ pathogen which is also the major cause of pseudomembranous colitis. Give the appropriate dosing
C. difficile
| 250-500 mg orally TID for 7-14days (or even longer)
181
This drug is an alternative treatment to C. diff. infection than oral vancomycin therapy because its efficacy and cost-saving. Give its downside effects comparted to oral vancomycin.
Metronidazole
reported cases on increase treatment failures and higher rates of disease recurrence
182
This antiprotozoal drug is also used in treatment for patients with Crohn's disease who have perianal fistulas, it can also help control colonic (but not small bowel) Crohn's disease. Give the drug and its dosing
metronidazole
(high doses) 750mg TID for prolonged periods may be necessary and neurotoxicity may be limiting
183
This antiprotozoal drugs can sentisize hypoxic tumor cells to the effects of ionizing radiation but are not used clinically for this purpose.
metronidazole and other nitroimidazoles
184
Most common side-effects of metronidazole
headache
nausea
dry mouth
metallic taste
185
Occasional side-effects of metronidazole
vomiting
diarrhea
abdominal distress
186
This side-effects to metronidazole may be associated with an exacerbation of candidiasis
furry tongue
glossitis
stomatitis
187
common and very rare neurotoxic effects from metronidazole
Common:
dizziness
vertigo
```
very rare:
encephalopathy
convulsions
incoordination
ataxia
```
188
cutaneous signs that are indicative of drug sensitivity to metronidazole that requires withdrawal of the treatment
urticaria
flushing
pruritus
189
What will happen if patient taking metronidazole imbibes alcohol within 3 days of therapy?
this drug has disulfiram-like effect and some patients experience abdominal distress, vomiting, flushing and headache
190
What will happen if metronidazole and any disulfiram-like or drugs are taken together? why.
confusional and psychotic states may occur
191
Metronidazole, although seen not teratogenic to humans, it is not advised to take this drug in what stage of pregnancy?
1st trimester
192
What will happen to patients taking metronidazole and coumadin at the same time?
prolonged PT
193
This drug can elevate plasma levels of metronidazole. Why.
Cimetidine
it inhibits hepatic microsomal metabolism
194
Does metronidazole linked to any forms of cancer to humans?
No current evidence but only carcinogenic in rodents (given high doses and prolonged periods)
