Antimalarial Flashcards
1
Q
What are sulfonamides and sulfones classified as?
A
Slow-acting blood schizonticides
They are more active against P. falciparum than P. vivax.
2
Q
What is the mechanism of action of sulfonamides?
A
They are p-aminobenzoic acid analogues that competitively inhibit Plasmodium dihydropteroate synthase.
3
Q
What enhances the antimalarial action of sulfonamides?
A
Combination with an inhibitor of parasite dihydrofolate reductase.
4
Q
What genetic mutations confer resistance to sulfadoxine?
A
Several point mutations in the dihydropteroate synthase gene.
5
Q
What is the consequence of combining sulfadoxine resistance mutations with mutations of dihydrofolate reductase?
A
Greatly increased likelihood of sulfadoxine-pyrimethamine treatment failure.
6
Q
When is sulfadoxine-pyrimethamine routinely administered during pregnancy?
A
Intermittently during the second and third trimesters.
7
Q
What is a potential benefit of intermittent preventive treatment strategies?
A
They may also benefit infants.
8
Q
What is the expected trend for the use of antimalarials without novel anti-folates?
A
Continued decline in the use for either prevention or treatment.
9
Q
Which antibiotics are useful in malaria treatment?
A
Tetracycline, doxycycline, and clindamycin.
10
Q
What type of action do tetracycline and doxycycline have in malaria treatment?
A
Slow-acting blood schizonticides.
11
Q
Which antibiotic is recommended for malaria chemoprophylaxis?
A
Doxycycline.
12
Q
What mechanism leads to the delayed death of malaria parasites treated with antibiotics?
A
Inhibition of protein translation in the parasite apicoplast.
13
Q
What is a consequence of the slow mode of action of tetracyclines?
A
Ineffectiveness as single agents for malaria treatment.
14
Q
What are the restrictions on tetracycline use?
A
Should NOT be given to pregnant women or children younger than 8 years.
15
Q
What recent technological developments may revolutionize mosquito control?
A
Engineering resistance to infection by P. falciparum in mosquitoes.
16
Q
What does the gene editing technology CRISPR/cas9 offer for mosquito control?
A
High-efficiency expression of resistance genes.
17
Q
What is a ‘mutagenic chain reaction’ in the context of CRISPR/cas9?
A
It spreads a mutation from one chromosome to its homologous chromosome.
18
Q
How can CRISPR/cas9 gene drive technology affect mosquito populations?
A
By introducing antiplasmodium effector genes into the germline.
19
Q
What factors influence the success of gene drive technology for vector control?
A
Choice of suitable promoters, phenotype of disrupted genes, robustness of the nuclease, ability to generate compensatory mutations.
20
Q
Have CRISPR/cas9 gene drives been released into the wild?
A
No, they have not yet been released.
21
Q
What must be understood before using gene editing techniques in the field?
A
Ecological consequences and ethical and regulatory issues.
22
Q
4 of 13
A
23
Q
Artemisinin and Its
A
24
Q
Derivatives
A
25
Mechanism of Action
26
• The activity seems to result from cleavage
27
of the drug's peroxide bridge by reduced
28
heme-iron
produced inside the highly
29
acidic digestive vacuole of the parasite as
30
it digests hemoglobin
31
• activated artemisinin might in turn generate
32
free radicals that alkylate and oxidize
33
macromolecules in the parasite.
34
ADME
35
• semisynthetic artemisinins:
36
Oral (dihydroartemisinin
artesunate
37
Intramuscular (artesunate and artemether)
38
Intravenous (artesunate)
39
Rectal (artesunate)
40
• Blay siati ater ora dosing 30 or shins and in 2-6 h with intramuscular artemether
41
• Both artesunate and artemether have modest levels of plasma protein binding
ranging from 43% to 82%
42
• These derivatives are extensively metabolized and converted to dihydroartemisinin
Which has a plasma 4/2°1 1-2 h
43
• Drug bioavailability via rectal administration is highly variable among individual patients
44
• With repeated dosing
artemisinin and artesunate induce their own CYP-mediated metabolism
45
• primarily via CYPs 2B6 and 3A4
which may enhance clearance by as much as 5-fold.
46
• Artemisinin and its three major semisynthetic derivatives in clinical use
dihydroartemisinin
47
artemether
and artesunate
48
• are potent and fast-acting antimalarials
49
• optimized for the treatment of severe P. falciparum malaria
50
• also effective against the asexual erythrocytic stages of P. vivax
51
• Increasingly
the standard treatment of malaria employs artemisinin-based combination
52
therapies (ACTs) to increase treatment efficacy and reduce selection pressure for the emergence
53
of drug resistance
54
• P. falciparum artemisinin "resistance" do not indicate true resistance but reflect delayed
55
parasite clearance time on the order of hours
56
• mutations in the P. falciparum gene P 13 encoding the kelch13 propeller protein have been
57
associated with these delayed parasite clearance times
58
• mechanism of kelch13 propeller protein mediates delayed parasite clearance remains unknown
59
• True resistance to artemisinin has not been reported
60
• no infection from this parasite has been reported to survive ACT due to delayed clearance times
61
• Moreover
in the presence of mutations that confer resistance to partner drugs (e.g.
62
partner drug piperaquine)
clinically significant ACT failure is substantial
63
rates reported to exceed 50%
64
• Resistance of non-P. falciparum malaria parasites to artemisinin class drugs has not been
65
reported.
66
• Artemisinins cause a significant reduction of the parasite burden
67
• with a 4-log10 reduction in the parasite population for each 48-h cycle of intraerythrocytic
68
invasion
replication
69
• Only three to four cycles (6-8 days) of treatment are required to remove all the parasites from
70
the blood
71
• In addition
artemisinins possess some gametocytocidal activity
72
malarial parasite transmission.
73
Therapeutic Uses
74
• rapid and potent activity against even multidrug-
75
resistant parasites
76
• the artemisinins are valuable for the treatment of
77
severe P. falciparum malaria
78
• generally are not used alone because of their
79
limited ability to eradicate infection completely
80
• highly effective for the first-line treatment when
81
combined with other antimalarials
82
• should NOT be used for chemoprophylaxis
83
because of their short ty/2 values
84
Toxicity and Contraindications
85
• Preclinical toxicity studies have identified the
86
brain (and brainstem)
liver
87
marrow as the principal target organs.
88
• no systematic neurological changes have
89
been attributed to treatment in patients 5
90
years of age or older
91
• may develop dose-related and
92
REVERSIBLE DECREASE in reticulocyte
93
and neutrophil counts and INCREASE in
94
transaminase levels
95
• About 1 in 3000 patients develops an
96
• Although studies during the first trimester
97
have found no evidence of adverse effects on
98
• it is recommended that ACTs NOT be used
99
during the FIRST trimester of pregnancy or
100
for the treatment of children 5 kg or less
101
What are the criteria for choosing partner drugs for ACT?
Potency and t1/2 that substantially exceeds that of the artemisinin partner
102
List the primary ACT regimens well tolerated in adults and children 5 kg or more.
* Artemether-lumefantrine
* Artesunate-amodiaquine
* Dihydroartemisinin-piperaquine
103
Which drug is probably the drug of choice for all malaria cases if oral drug treatment is appropriate?
Artemether-lumefantrine
104
Is Pyronaridine licensed for use?
No, it remains in clinical trials and is not licensed.
105
What structural similarities does Lumefantrine share?
It shares structural similarities with mefloquine and halofantrine
106
What is Lumefantrine's role in malaria treatment?
Highly effective for the treatment of uncomplicated malaria and is the most widely used first-line antimalarial across Africa
107
What are the pharmacokinetic properties of Lumefantrine?
* Large apparent volume of distribution
* Terminal elimination t1/2 of 4-5 days
108
How does food affect the absorption of Lumefantrine?
Administration with a high-fat meal significantly increases absorption
109
What formulation of Artemether-lumefantrine has been approved for children?
A sweetened dispersible formulation
110
What type of compound is Piperaquine?
A potent and well-tolerated bisquinoline compound
111
What is the Tmax of Piperaquine after a single dose?
2 hours
112
What is the terminal plasma t1/2 of Piperaquine?
5 weeks
113
What has been reported regarding the efficacy of Piperaquine in Cambodia?
Reduced efficacy primarily associated with mutations leading to piperaquine resistance
114
How quickly does fever resolve with Piperaquine treatment?
1-2 days
115
What is the clearance time for parasites with Piperaquine treatment?
2-3 days
116
What is Amodiaquine a congener of?
Chloroquine
117
Why is Amodiaquine no longer recommended in the U.S. for chemoprophylaxis?
Due to toxicities (hepatic and agranulocytosis)
118
What is the plasma t1/2 of monodesethyl-amodiaquine?
9-18 days
119
What is the peak concentration of monodesethyl-amodiaquine after oral administration?
About 500 nM 2 hours after administration
120
What are the clearance rates for Amodiaquine?
Vary widely among individuals (78-943 mL/min/kg)
121
What is atovaquone used for?
Malaria chemoprophylaxis and treatment of uncomplicated P. falciparum malaria in adults
## Footnote
A fixed combination of atovaquone with proguanil hydrochloride is available in the U.S.
122
What is the mechanism of action of atovaquone?
Inhibits electron transport in the parasite's mitochondrial cytochrome bc1 complex
## Footnote
Atovaquone binds at the Q site of cytochrome bc1, collapsing the mitochondrial membrane potential.
123
Why does atovaquone show selective toxicity for Plasmodium?
Structural differences in the amino terminal regions of plasmodial and human cytochrome b
## Footnote
This allows atovaquone to target the parasite without affecting the human host.
124
Against which malaria stages is atovaquone highly active?
P. falciparum asexual blood-stage parasites and liver stages
## Footnote
Not active against P. vivax liver-stage hypnozoites.
125
What is the significance of proguanil in combination with atovaquone?
Enhances the mitochondrial toxicity of atovaquone
## Footnote
This synergy reduces the frequency of resistance.
126
What side effects may atovaquone cause?
Abdominal pain, nausea, vomiting, transient elevations of serum transaminase or amylase
## Footnote
Readministration within an hour of vomiting may still be effective.
127
How is atovaquone absorbed and excreted?
Slow and variable absorption; excreted in bile, >94% recovered unchanged in feces
## Footnote
Absorption improves with a fatty meal.
128
What is the elimination half-life of atovaquone in adults?
2-3 days
## Footnote
In children, the half-life is 1-2 days.
129
What is the fixed dose of atovaquone and proguanil hydrochloride in the tablet?
250 mg atovaquone and 100 mg proguanil hydrochloride
## Footnote
Taken orally for treating mild-to-moderate attacks of resistant P. falciparum malaria.
130
What precautions should be taken when using atovaquone?
Evaluate in children <11 kg, pregnant women, and lactating mothers
## Footnote
Atovaquone may compete with certain drugs for plasma protein binding.
131
True or False: Atovaquone is metabolized significantly in humans.
False
## Footnote
Humans do not significantly metabolize atovaquone.
132
Fill in the blank: Atovaquone may compete with certain drugs for binding to _______.
plasma proteins
133
What impact does rifampin have on atovaquone therapy?
Reduces plasma levels of atovaquone substantially
## Footnote
The mechanism of this effect is not clear.
134
What is the effect of coadministration with tetracycline on atovaquone?
40% reduction in plasma concentration of atovaquone
135
What was a primary treatment for uncomplicated P. falciparum malaria?
Sulfadoxine-pyrimethamine
## Footnote
Especially effective against chloroquine-resistant strains.
136
Why is sulfadoxine-pyrimethamine no longer recommended for uncomplicated malaria?
Due to widespread resistance.
137
How long does it take for oral pyrimethamine to reach peak plasma levels?
2-6 hours.
138
What percentage of pyrimethamine is bound to plasma proteins?
About 90%.
139
What is the half-life (ty/2) of pyrimethamine?
85-100 hours.
140
For how long do suppressive concentrations of pyrimethamine remain in the blood?
About 2 weeks.
141
What is a therapeutic use of pyrimethamine-sulfadoxine despite resistance?
Intermittent preventive treatment of malaria in pregnancy.
142
What type of drug is pyrimethamine classified as?
A slow-acting blood schizontocide.
143
What does pyrimethamine inhibit in Plasmodium?
Folate biosynthesis.
144
How does the efficacy of pyrimethamine against hepatic forms of P. falciparum compare to proguanil?
It is less effective.
145
True or False: Pyrimethamine can eradicate P. vivax hypnozoites.
False.
146
What metabolic steps do pyrimethamine and sulfonamides inhibit in folate biosynthesis?
* Utilization of p-aminobenzoic acid
* Reduction of dihydrofolate to tetrahydrofolate.
147
What may affect the therapeutic response to antifolates?
Dietary p-aminobenzoic acid or folate.
148
What causes resistance to pyrimethamine?
Mutations in dihydrofolate reductase.
149
What is a common toxicity associated with antimalarial doses of pyrimethamine?
Occasional skin rashes and reduced hematopoiesis.
150
Excessive doses of pyrimethamine can produce what condition?
Megaloblastic anemia.
151
What combination may cause birth defects in humans?
Trimethoprim-sulfamethoxazole.
152
What severe reactions can result from the combination of pyrimethamine and sulfadoxine?
* Erythema multiforme
* Stevens-Johnson syndrome
* Toxic epidermal necrolysis.
153
Who should pyrimethamine-sulfadoxine be contraindicated for?
* Individuals with previous reactions to sulfonamides
* Lactating mothers
* Infants less than 2 months of age.
154
What adverse effect has been associated with the combination of pyrimethamine and dapsone?
Agranulocytosis.
155
What is the active metabolite of proguanil responsible for its antimalarial activity?
Cycloguanil
## Footnote
Cycloguanil is a cyclic triazine metabolite structurally related to pyrimethamine.
156
What enzyme does cycloguanil selectively inhibit in plasmodial species?
Bifunctional dihydrofolate reductase-thymidylate synthetase
## Footnote
This enzyme is crucial for parasite de novo purine and pyrimidine synthesis.
157
In drug-sensitive P. falciparum malaria, what stages does proguanil act against?
Both primary liver stages and asexual red blood cell stages
## Footnote
This action helps control the acute attack and usually eradicates the infection.
158
True or False: Proguanil is effective against the latent tissue stages of P. vivax.
False
## Footnote
Relapses may occur after proguanil is withdrawn because these latent stages are unaffected.
159
What effect does proguanil have on gametocytes?
Does not destroy gametocytes
## Footnote
However, oocytes in the mosquito gut can fail to develop normally.
160
What is the consequence of amino acid changes near the dihydrofolate reductase-binding site?
Causes resistance to cycloguanil, pyrimethamine, or both
## Footnote
This resistance affects the efficacy of these antimalarial drugs.
161
Is the presence of Plasmodium dihydrofolate reductase required for the intrinsic antimalarial activity of proguanil?
No
## Footnote
The molecular basis for this alternative activity is unknown.
162
What is the effect of proguanil on atovaquone's action against P. falciparum?
Accentuates the mitochondrial membrane-potential-collapsing action
## Footnote
Proguanil does not display this activity by itself.
163
What is the absorption characteristic of proguanil from the GI tract?
Slowly but adequately absorbed
## Footnote
Peak plasma concentrations are attained within 5 hours after a single oral dose.
164
What is the mean plasma elimination half-life of proguanil?
About 180-200 hours or longer
## Footnote
This indicates a prolonged duration of action.
165
What enzyme family is involved in the activation and metabolism of proguanil?
CYP2C subfamily
## Footnote
About 3% of whites are deficient in this oxidation phenotype, contrasting with about 20% of Asians and Kenyans.
166
What percentage of absorbed proguanil is excreted in urine?
40%-60%
## Footnote
This is excreted either as the parent drug or as the active metabolite.
167
What are common adverse effects of proguanil at chemoprophylactic doses?
Occasional nausea and diarrhea
## Footnote
Large doses may lead to more severe side effects.
168
True or False: Proguanil is safe for use during pregnancy.
True
## Footnote
It is also safe when used in conjunction with other antimalarial drugs.
169
What is the chief alkaloid of cinchona?
Quinine
## Footnote
Quinine and its derivatives have been used for malaria treatment for centuries.
170
How do asexual malarial parasites thrive in host erythrocytes?
By digesting hemoglobin
## Footnote
This process generates free radicals and iron-bound heme as by-products.
171
What is hemozoin?
Insoluble, chemically inert malarial pigment
## Footnote
Formed by the sequestration of heme.
172
What do quinolines interfere with in malaria treatment?
Heme sequestration
## Footnote
Failure to inactivate heme is thought to kill the parasites via oxidative damage.
173
What is chloroquine and how does it function in treating malaria?
Chloroquine is a weak base that concentrates in the highly acidic digestive vacuoles of susceptible Plasmodium, where it binds to heme and disrupts its sequestration.
174
How does hydroxychloroquine compare to chloroquine in terms of effectiveness against P. falciparum malaria?
Hydroxychloroquine is essentially equivalent to chloroquine against P. falciparum malaria.
175
What is the primary cause of chloroquine resistance in P. falciparum?
Chloroquine resistance results from mutations in the polymorphic gene pfcrt that encodes a putative transporter in the membrane of the acidic digestive vacuole.
176
Which transporters may play a role in chloroquine resistance?
* PfCRT
* P-glycoprotein transporter encoded by pfmdr1
* P. falciparum multidrug resistance-associated protein (PfMRP)
177
What is chloroquine's therapeutic effectiveness against other Plasmodium species?
Chloroquine is highly effective against the erythrocytic forms of P. vivax, P. ovale, P. malariae, P. knowlesi, and chloroquine-sensitive strains of P. falciparum.
178
What is the agent of choice for chemoprophylaxis and treatment of infections caused by P. ovale and P. malariae?
Chloroquine remains the agent of choice.
179
What has largely replaced chloroquine for treating P. falciparum infections?
Artemisinin-based combination therapies (ACTs) have largely replaced chloroquine.
180
In which situations is chloroquine still effective?
Chloroquine is effective in chemoprophylaxis or treatment of acute attacks caused by P. vivax, P. ovale, and P. malariae, except in areas with resistant strains of P. vivax.
181
What is the role of primaquine in relation to chloroquine?
Primaquine can be given with chloroquine or used after a patient leaves an endemic area to prevent relapses in P. vivax and P. ovale infections.
182
How quickly does chloroquine control the symptoms of acute malarial attacks?
Chloroquine rapidly controls clinical symptoms and parasitemia, with most patients becoming completely afebrile within 24-48 hours.
183
What should be suspected if patients fail to respond within the second day of chloroquine therapy?
Resistant strains should be suspected.
184
What are the recommended alternative treatments if chloroquine is ineffective?
* Quinine plus tetracycline or doxycycline
* Atovaquone-proguanil
* Artemether-lumefantrine
* Mefloquine
185
What are the absorption characteristics of chloroquine?
Chloroquine is well absorbed from the GI tract and rapidly from intramuscular and subcutaneous sites.
186
What is the significance of chloroquine binding to plasma proteins?
Chloroquine binds moderately (60%) to plasma proteins.
187
What are the active metabolites produced by hepatic CYPs from chloroquine?
* Desethylchloroquine
* Bisdesethylchloroquine
188
What is the terminal half-life of chloroquine?
The terminal half-life ranges from 30 to 60 days.
189
What can cause acute chloroquine toxicity?
Acute chloroquine toxicity is most frequently encountered when therapeutic or high doses are administered too rapidly by parenteral routes.
190
What are some cardiovascular effects of chloroquine overdose?
* Hypotension
* Vasodilation
* Suppressed myocardial function
* Cardiac arrhythmias
* Cardiac arrest
191
What symptoms may result from chloroquine overdose?
* Confusion
* Convulsions
* Coma
192
What gastrointestinal side effects can occur with oral chloroquine therapy?
* GI upset
* Headache
* Visual disturbances
* Urticaria
193
What is the risk associated with high doses of chloroquine or hydroxychloroquine?
High daily doses (>250 mg) can lead to irreversible retinopathy and ototoxicity.
194
Which patient conditions should chloroquine not be prescribed for?
* Epilepsy
* Myasthenia gravis
* Psoriasis or other exfoliative skin conditions
* Porphyria cutanea tarda
195
What should be monitored in patients receiving long-term high-dose chloroquine therapy?
Patients should undergo ophthalmological and neurological evaluations every 3-6 months.
196
True or False: Chloroquine can interact with CYP2D6.
True
197
What effect does chloroquine have on the yellow fever vaccine?
Chloroquine attenuates the efficacy of the yellow fever vaccine when administered at the same time.
198
What are the FDA-approved uses of quinine and quinidine?
Treatment of uncomplicated P. falciparum malaria
## Footnote
Quinine and quinidine are specifically approved for uncomplicated malaria cases.
199
How does quinidine compare to quinine in terms of potency and toxicity?
More potent as an antimalarial and more toxic than quinine.
200
What is the effect of quinine on skeletal muscle?
Increases tension response to maximal stimulus and increases refractory period, reducing tetanic stimulation response.
201
True or False: Quinine has a significant effect on hepatic forms of malarial parasites.
False.
202
What is a major reason quinine is not used for chemoprophylaxis?
Its toxicity and short half-life.
203
What factors contribute to the complexity of P. falciparum resistance to quinine?
Correlates with resistance to chloroquine, mefloquine, and halofantrine.
204
How is quinine absorbed in the body?
Orally absorbed mainly from the upper small intestine, >80% complete.
205
What is the typical time to reach maximum plasma levels after an oral dose of quinine?
3-8 hours.
206
What happens to the pharmacokinetics of quinine during severe malarial infection?
Apparent volume of distribution and systemic clearance decrease, increasing elimination half-life to 18 hours.
207
What is the fatal oral dose range of quinine for adults?
2-8 g.
208
What are the dose-related toxicities associated with quinine?
Cinchonism, hypoglycemia.
209
What are mild forms of cinchonism?
Tinnitus, high-tone deafness, visual disturbances, headache, dysphoria, nausea, vomiting, postural hypotension.
210
True or False: Quinine can cause hyperinsulinemia and severe hypoglycemia.
True.
211
What is 'blackwater fever'?
A rare hypersensitivity reaction to quinine therapy characterized by massive hemolysis, hemoglobinemia, and hemoglobinuria.
212
What is the therapeutic range for 'free' quinine?
0.2 to 2.0 mg/L.
213
What is the recommended initial dose of quinidine by the CDC?
10 mg salt/kg initially, followed by 0.02 mg salt/kg/min.
214
Fill in the blank: Quinine should be avoided in patients with _______.
Tinnitus or optic neuritis.
215
True or False: Quinine is considered safe in pregnancy.
True.
216
What can delay the absorption of quinine from the gastrointestinal tract?
Antacids that contain aluminum.
217
What effect does quinine have at neuromuscular junctions?
Enhances effect of neuromuscular blocking agents and opposes action of acetylcholinesterase inhibitors.
218
What is a potential interaction of quinine with cardiac glycosides?
Delays absorption and elevates plasma levels.
219
What serious cardiac complications can result from acute over-dosage of quinine?
Sinus arrest, junctional rhythms, atrioventricular block, ventricular tachycardia, and fibrillation.
220
What is Mefloquine and where did it emerge from?
Mefloquine is a drug that emerged from the Walter Reed Malaria Research Program as safe and effective against drug-resistant strains of P. falciparum.
221
What is the primary action of Mefloquine?
Mefloquine is a highly effective blood schizonticide.
222
With which substance does Mefloquine associate, suggesting similarities to chloroquine's mode of action?
Mefloquine associates with intraerythrocytic hemozoin.
223
What genetic factor is associated with reduced parasite susceptibility to Mefloquine?
Increased pfmdr copy numbers are associated with reduced parasite susceptibility to Mefloquine.
224
What does increased PfMDR1-mediated solute import suggest about Mefloquine's target?
It suggests that the drug's target resides outside the vacuolar compartment.
225
Which enantiomer of Mefloquine is associated with adverse CNS effects?
The (-)-enantiomer is associated with adverse CNS effects.
226
How does the (+)-enantiomer of Mefloquine differ in terms of side effects?
The (+)-enantiomer retains antimalarial activity with fewer side effects.
227
What combination can reduce the selection pressure for resistance when using Mefloquine?
Mefloquine can be paired with artesunate.
228
Why is Mefloquine taken orally?
Parenteral preparations cause severe local reactions.
229
How long does it take for plasma levels of Mefloquine to peak?
Plasma levels of Mefloquine rise to their peak in about 17 hours.
230
What is the half-life range of Mefloquine?
The half-life of Mefloquine ranges from 13 to 24 days.
231
What significant property contributes to the slow elimination of Mefloquine?
Its high lipophilicity and extensive tissue distribution.
232
How is Mefloquine primarily metabolized and excreted?
Mefloquine is extensively metabolized in the liver by CYP3A4 and excreted mainly by the fecal route.
233
What type of warning has the U.S. FDA added to Mefloquine labeling?
A 'black box' warning noting the drug's potential to cause severe, possibly permanent, neurological and psychiatric adverse effects.
234
What are common short-term adverse effects of Mefloquine?
Nausea, vomiting, and dizziness.
235
What should be done if vomiting occurs within the first hour of taking Mefloquine?
The full dose should be repeated.
236
What symptoms can indicate CNS toxicity from Mefloquine?
Symptoms include seizures, confusion, acute psychosis, and disabling vertigo.
237
What are some mild-to-moderate toxicities associated with Mefloquine?
Disturbed sleep, dysphoria, headache, GI disturbances, and dizziness.
238
What contraindications exist for Mefloquine use?
History of seizures, depression, bipolar disorder, or adverse reactions to quinoline antimalarials.
239
What is the recommendation regarding pregnancy after using Mefloquine?
Pregnancy should be avoided for 3 months after Mefloquine use.
240
Is Mefloquine considered first-line treatment for malaria?
No, it is no longer considered first-line treatment of malaria.
241
For what specific cases should Mefloquine be reserved?
For the prevention and treatment of malaria caused by drug-resistant P. falciparum and P. vivax.
242
In what situations is Mefloquine especially useful?
As a chemoprophylactic agent for travelers spending weeks to years in endemic areas.
243
What is the benefit of using Mefloquine in combination with an artemisinin compound?
It is more effective in areas with multiply drug-resistant strains of P. falciparum.
244
What is the primary action of primaquine?
Acts on exoerythrocytic tissue stages of Plasmodium spp. in the liver to prevent and cure relapsing malaria.
245
What should patients be screened for before therapy with primaquine?
G6PD deficiency.
246
What is the mechanism of action of primaquine?
Not fully elucidated.
247
Against which stages of Plasmodium spp. does primaquine act?
Primary and latent hepatic stages.
248
What types of infections does primaquine prevent relapses in?
P. vivax and P. ovale infections.
249
What type of activity does primaquine display against P. falciparum?
Gametocytocidal activity.
250
Is primaquine active against asexual blood-stage parasites?
No, it is inactive.
251
What is the absorption rate of primaquine from the GI tract?
Approaches 100%.
252
When does peak plasma concentration of primaquine occur?
Within 3 hours.
253
What is the average half-life (t1/2) of primaquine?
7 hours.
254
What is the fate of primaquine after administration?
Rapidly metabolized; only a small fraction is excreted as the parent drug.
255
What enzyme does primaquine induce?
CYP1A2.
256
What is the major metabolite of primaquine?
Carboxyprimaquine, which is inactive.
257
For what purposes is primaquine primarily used?
Terminal chemoprophylaxis and radical cure of P. vivax and P. ovale infections.
258
When should primaquine regimens be initiated for terminal chemoprophylaxis?
Shortly before or immediately after leaving an endemic area.
259
What is required for a radical cure of P. vivax or P. ovale malaria?
Administration during an asymptomatic latent period or during an acute attack.
260
Is simultaneous administration of a schizonticidal drug plus primaquine more effective than sequential treatment?
Yes, it is more effective.
261
What are the common side effects of primaquine?
Mild-to-moderate abdominal distress, mild anemia, and leukocytosis.
262
How can abdominal distress caused by primaquine be alleviated?
Taking the drug at mealtime.
263
What serious condition can occur in individuals with congenital deficiency of NADH methemoglobin reductase when taking primaquine?
Methemoglobinemia.
264
What should be monitored if a daily dose of more than 30 mg primaquine is given?
Blood counts.
265
Should primaquine be given to pregnant women?
No, it should not be given.
266
What is tafenoquine a derivative of?
Primaquine.
267
How is tafenoquine absorbed after oral administration?
Slowly, with maximum plasma concentrations occurring about 12 hours after dosing.
268
What is the elimination half-life of tafenoquine?
About 14 days.
269
What are the common gastrointestinal side effects of tafenoquine?
Heartburn, gas, vomiting, and diarrhea.
270
Is there any reported QTc effect from tafenoquine?
No reported detectable QTc effects.
271
What possible serious side effects are associated with tafenoquine?
Methemoglobinemia, hemolytic anemia, and thrombocytopenia.
272
Has tafenoquine been tested in pregnant women or children?
No, it has not been tested.
