- Artemisinin
- Chloroquie
- Mefloquine
- Primaquine
- Pyrimethsmine
- Quinine/quinidine
| Artemisinin |
| Availability: injection, lyophilized powder for reconstitution ,110mg/via |
| Indication & dosage : Malaria :2.4 mg/kg IV at 0, 12, and 24 hr, THEN qDay until able to tolerate PO antimalarial therapy |
| Mechanism of Action : Artemisinin derivative; rapidly metabolized to active metabolite, dihydroartemisinin (DHA) Artesunate and DHA, like other artemisinins, contain an endoperoxide bridge that is activated by heme iron leading to oxidative stress, inhibition of protein and nucleic acid synthesis, ultrastructural changes, and decreased parasite growth and survival |
| Contraindications Known serious hypersensitivity (eg, anaphylaxis) |
| Metabolism & Elimination: Primary pathway :Artesunate: Blood esterases :DHA: Glucuronidation Metabolite •Artesunate: DHA •DHA: alpha-DHA-beta-glucuronide Elimination Excretion: Unknown Half-life •Artesunate: 0.3 hr •DHA: 1.3 hr |
Side effects
- Headache, seizures, blurred vision, difficulty focusing
- CN VIII dysfunction (quinine and chloroquine)
- Cinchonism: nausea, vomiting, tinnitus, vertigo (↑ quinine or primaquine)
- Hypotension, heart block, asystole, syncope, QT prolongation
- Hypoglycemia (quinine)
- Nausea, vomiting, cramps, anorexia
- Pancytopenia
- Fatigue
- Pruritus, eczema, skin eruptions
Nursing consideration
- Check for allergies
- Contraindicated in patients hypersensitive to drug and in those with retinal or visual field changes
- Use cautiously in patients with severe GI, neurologic, or blood disorders; hepatic disease or alcoholism; or G6PD deficiency or psoriasis
- Take with food to prevent GI upset
In severe or resistant cases, artesunate IV may be prescribed
| Chloroquine |
| Availability: tablet,500mg NOTE: Chloroquine phosphate 16.6 mg is equivalent to 10 mg chloroquine base |
| Indication & dosage : suppression/Prophylaxis of Malaria PO (Adults): 300 mg once weekly, starting 2 wk prior to entering endemic areas and for 8 wk afterward. If suppressive therapy is not initiated prior to entering endemic area, initial dose should be 300 mg followed by another 300 mg dose 6 hr later, followed by the usual dose regimen. PO (Children): 5 mg/kg once weekly, starting 2 wk prior to entering endemic areas and for 8 wk afterward (not to exceed 300 mg/day). If suppressive therapy is not initiated prior to entering endemic area, initial dose should be 5 mg/kg followed by another 5 mg/kg dose 6 hr later, followed by the usual dose regimen. |
| Treatment of Acute Attack of Malaria PO (Adults): 600 mg initially, then 300 mg at 6–8 hr, 24 hr, and 48 hr after initial dose. PO (Children): 10 mg/kg initially (not to exceed 600 mg), then 5 mg/kg at 6 hr, 24 hr, and 48 hr after initial dose (not to exceed 300 mg/day). |
| Extraintestinal Amebiasis PO (Adults): 600 mg once daily for 2 days, then 300 mg once daily for at least 2–3 wk (in combination with other antiprotozoals). PO (Children): 10 mg/kg (not to exceed 300 mg/day for 2–3 wk. |
| Rheumatoid Arthritis/Systemic Lupus Erythematosus PO (Adults): 150 mg once daily; ↓ dosage following maximal response. |
| Mechanism of Action Active against erythrocytic forms of Plasmodium vivax & P. malariae and most strains of Plasmodium falciparum Precise mechanism not known |
Metabolism & Elimination:
Metabolism: Partially in liver
Elimination: Half-life: 3-5 days
Excretion: urine (~70% as unchanged drug); acidification of urine increases elimination
Small amounts may be present in urine months following discontinuation of therapy
Contraindications
Hypersensitivity to chloroquine, 4-aminoquinolones
Psoriasis, porphyria, retinal or visual field changes
Cautions
- Acute extrapyramidal disorders may occur; reactions usually resolve after treatment discontinuation and/or symptomatic treatment
- Not effective in most areas; CDC recommends mefloquine or atovaquone/proguanil – check CDC traveler information for specific recommendations for region
- May cause hemolysis in glucose-6 phosphate dehydrogenase (G-6-PD) deficiency; blood monitoring may be needed as hemolytic anemia may occur, in particular in association with other drugs that cause hemolysis
- Experimental data showed a potential risk of inducing gene mutations; there are insufficient data in humans to rule out an increased risk of cancer in patients receiving long-term treatment
- Cases of cardiomyopathy resulting in cardiac failure, in some cases with fatal outcome, have been reported in patients treated during long term therapy at high doses with chloroquine; monitor for signs and symptoms of cardiomyopathy and discontinue chloroquine if cardiomyopathy develops to prevent life-threatening complications
- May cause conduction disorders (eg, bundle branch block / AV heart block) are diagnosed; if cardiotoxicity is suspected, prompt discontinuation of chloroquine may prevent life-threatening complications
- Monitor knee and ankle reflexes in patients on long-term therapy to detect any evidence of muscular weakness; if weakness occurs, discontinue therapy
- A number of fatalities have been reported following the accidental ingestion of chloroquine; advise to keep medication out of the reach of children because they are especially sensitive to the 4-aminoquinoline compounds
- Use in patients with psoriasis may precipitate a severe attack of psoriasis; may be exacerbated condition when used in patients with porphyria; do not use in these conditions unless the benefit to the patient outweighs the potential risks
- Shown to cause severe hypoglycemia including loss of consciousness that could be life-threatening in patients treated with or without antidiabetic medications; patients should be warned about risk of hypoglycemia and associated clinical signs and symptoms; patients presenting with clinical symptoms suggestive of hypoglycemia during treatment with chloroquine should have blood glucose level checked and treatment reviewed as necessary
- Administer with caution in patients with preexisting auditory damage; discontinue therapy immediately in case of any defects in hearing; observe patient closely
- Caution with hepatic disease, alcoholism, and coadministration with other hepatotoxic drugs
- May provoke seizures in patients with history of epilepsy
- Chloroquine does not treat hypnozoite liver stage forms of Plasmodium and will therefore not prevent relapses of malaria due to P. vivax or P. ovale; additional treatment with an anti-malarial agent active against these forms, such as an 8-aminoquinoline, required for treatment of infections with P. vivax and P. ovale
Adverse Reactions/Side Effects
CV: ECG changes (T-wave abnormalities, QRS prolongation), cardiomyopathy, hypotension
Derm: alopecia, dermatoses, photosensitivity, pigmentary changes, pruritus, skin eruptions, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, urticaria
EENT: corneal opacities (reversible), hearing impairment, retinopathy, tinnitus, visual disturbances
GI: ↑ liver enzymes, abdominal cramps, anorexia, diarrhea, hepatitis, nausea, vomiting
Hemat: AGRANULOCYTOSIS, APLASTIC ANEMIA, LEUKOPENIA, thrombocytopenia
Neuro: agitation, anxiety, confusion, delirium, depression, extrapyramidal reactions, hallucinations, headache, insomnia, neuromyopathy, peripheral neuritis, personality changes, polyneuritis, psychosis, SEIZURES, weakness
Patient/Family Teaching
- Instruct patient to take medication as directed and continue for full course of therapy, even if feeling better. Take missed doses as soon as remembered, except with regimens requiring doses more than once a day, for which missed doses should be taken within 1 hr or omitted. Do not double doses.
- Review methods of minimizing exposure to mosquitoes with patients receiving chloroquine prophylactically (use insect repellent, wear long-sleeved shirt and long trousers, use screen or netting).
- Advise patients to avoid use of alcohol while taking chloroquine.
- Caution patient to keep chloroquine out of the reach of children; fatalities have occurred with ingestion of 3 or 4 tablets.
- Explain need for periodic ophthalmic exams for patients on prolonged high-dose therapy. Advise patient that the risk of ocular damage may be decreased by the use of dark glasses in bright light. Protective clothing and sunscreen should also be used to reduce risk of dermatoses.
- Advise patient to notify health care professional promptly if sore throat, fever, unusual bleeding or bruising, blurred vision, difficulty reading, visual changes, ringing in the ears, difficulty hearing, mental changes, or muscle weakness occurs or if diarrhea, anorexia, nausea, stomach pain, vomiting, or rash becomes pronounced or bothersome. Most adverse reactions are dose related.
- Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding.
- Rheumatoid Arthritis/Systemic Lupus Erythematosus: Instruct patient to contact health care professional if no improvement is noticed within a few days. Treatment may require up to 6 mo for full benefit.
| Mefloquine |
| Availability: Tablet,250mg |
| Indication & dosage : Acute Malaria Infections ,1250 mg PO once Malaria Prevention :250 mg PO qWeek |
| Mechanism of Action Structural analog of quinine; exact mechanism unknown, acts as a blood schizonticide May increase intravesicular pH in parasites |
| Metabolism & Elimination: Metabolism : Extensively metabolized in liver by CYP3A4 Metabolites: 2,8-bistrifluoromethyl-4-quinoline carboxylic acid is inactive Elimination : Half-life: 21-22 days Total clearance (hepatic): 30 mL/min Excretion: Mainly in bile and feces; urine (~1.5-9% as unchanged drug) |
| Contraindications Hypersensitivity to mefloquine, related drugs (eg, quinidine, quinine) Do not prescribe for prophylaxis in patients with active or recent history of depression, generalized anxiety disorder; history of psychosis, schizophrenia, other major psychiatric disorders, or convulsions |
Precautions
- Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).
- Before having surgery, tell your doctor or dentist about all the products you use (including prescription drug , nonprescription drugs, and herbal products).
- Mefloquine may cause live bacterial vaccines (such as typhoid vaccine) not to work well. Tell your health care professional that you are using mefloquine before having any immunizations/vaccinations
Adverse effects
CNS: Fever, dizziness, syncope, headache, psychotic changes, hallucinations, confusion, anxiety, fatigue, vertigo, depression, seizures, tremor, panic attacks
CV: chest pain, Edema
ENT: tinnitus, visual disturbances
GI: anorexia, vomiting, nausea, loose stools, diarrhoea, abdominal discomfort or pain, dyspepsia
Hematologic: leukopenia, thrombocytopenia
Skin: Rash
Nursing responsibility
- Take dose immediately before or after a meal on the same day each week to improve compliance
- Patient should not take drug on an empty stomach and always to take it with at least 8 ounces of water
- Patient should be careful when performing activities that require alertness and coordination because dizziness ,disturbed sense of balance, and neuropsychiatric reactions may occur
- Patient should notify prescriber is signs and symptoms of impending toxicity occur
- Women of childbearing age should use reliable contraception during treatment
- Call your doctor immediately if you are experiencing some uncommon side effects like tingling in your finger or toes, difficulty in walking , dark colored urine
| Primaquine |
| Availability: Tablets: 26.3 mg (15 mg base) |
| Indications and dosages To prevent or treat relapse of malaria caused by Plasmodium vivax Adults: 15 mg base P.O. daily for 14 days Children: 0.3 mg base/kg/day P.O. for 14 days, to a maximum of 15 mg base daily |
| Mechanism of Action: Unknown. Thought to disrupt parasitic mitochondria and bind to native DNA, leading to structural changes that disrupt metabolic processes and to inhibition of gametocyte and erythrocyte forms. Destroys some gametocytes and makes others incapable of undergoing maturation division. |
| Metabolism & Elimination: Metabolism: Hepatic to carboxyprimaquine (active) Elimination:Half-life: 3.7-9.6 hr Excretion: Urine (small amounts as unchanged drug) |
| Contraindications : ● Hypersensitivity to drug ● Concurrent use of quinacrine, other hemolytic drugs, or myelosup ● Systemic disease with history of or tendency to granulocytopenia (such as lupus erythematosus or rheumatoid arthritis) |
| Precautions : ● porphyria, methemoglobinemia, methemoglobin reductase deficiency, hemolytic anemia in G6PD deficiency (particularly in Blacks, Asians, and persons of Mediterranean descent), iodine deficiency, anemia ● pregnant patients. |
| Administration : Before giving, check prescription to see if dosage is written as mg or mg base. ● Start therapy during last 2 weeks of suppression course with chloroquine or comparable drug, or after suppression course ends. |
Adverse reactions
CNS: headache, dizziness, asthenia
CV: hypertension
ENT: blurred vision, difficulty focusing
GI: nausea, vomiting, diarrhoea, constipation, abdominal pain, epigastric distress
Hematologic: mild anaemia, leucocytosis, haemolytic anaemia, methemoglobinemia
Skin: pruritus, skin eruptions, pallor
Patient monitoring
- Monitor CBC. Watch for evidence of blood dyscrasias or hemolytic reaction (dark urine, chills, fever, chest pain, bluish skin). Stop drug and notify prescriber at once if these occur.
- Monitor blood pressure
Patient teaching
- Advise patient to take with food to minimize GI upset. Teach patient to recognize and immediately report signs and symptoms of haemolytic reactions.
- Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration, vision, and alertness.
- Instruct patient to complete entire course of therapy as prescribed, even after symptoms improve.
- As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.
| Pyrimethsmine |
| Availability :Tablets: 25 mg |
| Indications and dosages To control plasmodia transmission and suppress susceptible strains Adults and children ages 10 and older: 25 mg P.O. daily for 2 days, given with a sulfonamide |
| Toxoplasmosis Adults: Initially, 50 to 75 mg P.O. daily for 1 to 3 weeks, given with a sulfonamide. Depending on response and tolerance, reduce dosages of both drugs by 50% and continue therapy for 4 to 5 more weeks. Children: 1 mg/kg P.O. daily in two equally divided doses for 2 to 4 days, then reduced to 0.5 mg/kg/day for approximately 1 month. Alternatively, 2 mg/kg (up to 100 mg) P.O. daily in two equally divided doses for 3 days, then 1 mg/kg (up to 25 mg) in two equally divided doses for 4 weeks, given with sulfadiazine for 4 weeks. |
| Prophylaxis of malaria caused by susceptible plasmodia strains Adults and children older than age 10: 25 mg P.O. weekly Children ages 4 to 10: 12.5 mg P.O. weekly Infants and children younger than age 4: 6.25 mg P.O. weekly |
| Mechanism of Action: Inhibits reduction of dihydrofolic acid to tetrahydrofolic acid (folinic acid) by binding to and reversibly |
| Metabolism & Elimination: Metabolism: hepatic Half-life elimination: 80-95 hr Peak Plasma Time: 1.5-8 hr Excretion: urine (20-30% as unchanged drug) |
| Contraindications ● Hypersensitivity to drug ● Megaloblastic anemia caused by folate deficiency ● Concurrent folate antagonist therapy |
Precautions :
- Anemia, bone marrow depression, hepatic or renal impairment, G6PD deficiency
- History of seizures
- Patients more than 16 weeks pregnant
- Breastfeeding patients.
Administration
- Administer with meals.
- When giving tablets to young children, crush them and administer as oral suspension in water, cherry syrup, or sweetened solution.
- Know that because of worldwide resistance to pyrimethamine, its use alone to prevent or treat acute malaria is no longer recommended.
- Be aware that fixed combination of pyrimethamine and sulfadoxine is available and has been used for uncomplicated mild to moderate malaria caused by chloroquine resistant Plasmodium falciparum and for presumptive self-treatment by travellers.
Adverse reactions
CNS: headache, light-headedness, insomnia, malaise, depression, seizures
CV: arrhythmias
ENT: dry throat
GI: nausea, vomiting, diarrhea, anorexia, atrophic glossitis
GU: hematuria Hematologic: megaloblastic anemia, leukopenia, pancytopenia, thrombocytopenia
Metabolic: hyperphenylalaninemia Respiratory: pulmonary eosinophilia
Skin: pigmentation changes, dermatitis, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome
Other: fever, anaphylaxis
Patient monitoring
- Monitor CBC. Watch for evidence of blood dyscrasias.
- Assess for signs and symptoms of folic acid deficiency.
- Closely monitor neurologic and cardiovascular status. Stay alert for seizures and arrhythmias.
- Watch for evidence of erythema multiforme, including sore throat, cough, mouth sores, rash, iritic lesions, and fever. Report early signs before condition can progress to Stevens Johnson syndrome.
Patient teaching
- Advise patient to take with meals.
- Tell patient to discontinue drug and contact prescriber at first sign of rash.
- Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
- As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.
| Quinine/quinidine |
| Availability: quinidine gluconate Injection: 80 mg/ml Tablets (extended-release): 324 mg quinidine sulfate Tablets: 200 mg, 300 mg Tablets (extended-release): 300 mg |
| Indications and dosages Test dose Adults: 200 mg sulfate P.O. as a single dose or 200 mg gluconate I.M. to check for idiosyncratic reaction |
| Premature atrial and ventricular contractions Adults: 200 to 300 mg sulfate P.O. three to four times daily, or gluconate (extended-release) given as 324 to 660 mg P.O. q 8 to 12 hours |
| Paroxysmal supraventricular tachycardia (PSVT) Adults: 400 to 600 mg sulfate P.O. q 2 or 3 hours until arrhythmia ends; or 324 to 660 mg (extended-release) P.O. q 8 to 12 hours. For parenteral use, 400 mg gluconate I.M., repeated q 2 hours if necessary; or 330 mg gluconate I.V. (up to 750 mg) in diluted solution, infused no faster than 1 ml/minute |
| To convert atrial fibrillation to sinus rhythm Adults: 200 mg sulfate P.O. q 2 or 3 hours for five to eight doses, increased daily until sinus rhythm returns or toxic effects occur; maximum daily dosage is 4 g. Or 300 mg sulfate (extended-release) P.O. q 8 to 12 hours, increased cautiously if necessary. Or 324 to 660 mg gluconate (extended-release) P.O. q 8 to 12 hours. For parenteral use, 800 mg gluconate I.V. in diluted solution, infused no faster than 0.25 mg/kg/minute. |
| Severe, life-threatening Plasmodium falciparum malaria Adults: Loading dose of 10 mg/kg gluconate I.V. diluted in 5 ml/kg of normal saline solution (or 250 ml of normal saline solution in otherwise healthy, 50-kg [110-lb] patient) by continuous infusion over 1 to 2 hours, then a continuous maintenance infusion of 0.02 mg/kg/minute for 72 hours or until parasitemia drops to less than 1% or oral therapy can begin. Or alternative loading dose of 24 mg/kg gluconate I.V. diluted in 250 ml of0.9% sodium chloride injection by intermittent infusion over 4 hours, followed by maintenance dosage of 12 mg/kg gluconate I.V. at 8-hour intervals, starting 8 hours after loading dose, infused over 4 hours for 7 days or until patient tolerates oral therapy |
| Mechanism of Action: Slows conduction and prolongs refractory period, reducing myocardial irritability and interrupting or preventing certain arrhythmias. As an antimalarial, acts primarily as intra-erythrocytic schizonticide |
Contraindications
- Hypersensitivity to drug or related cinchona derivatives
- Thrombocytopenia with previous quinidine therapy
- Myasthenia gravis
- Complete heart block
- Left bundle-branch block or other severe intraventricular conduction defects
- Aberrant ectopic impulses and abnormal rhythm
- History of prolonged QT interval or drug-induced torsades de pointes
- Digoxin toxicity
Precautions:
- potassium imbalance, renal or hepatic disease, heart failure, respiratory depression
- elderly patients
- pregnant or breastfeeding patients
- children.
Metabolism & Elimination:
Metabolism
Metabolism: Liver via hepatic P450 enzyme CYP3A4
Metabolites: 3-hydroxyquinidine and 2-quinidinone (some have antiarrhythmic effects)
Enzymes inhibited: CYP2D6
Elimination
Half-Life: 6-8 hr (adults); 3-4hr (children)
Clearance: 3-5 mL/min/kg (adults); 1-2.5 mL/min/kg (children)
Excretion: Urine (15-25%); feces (5%)
Dialyzable: HD: Yes; PD: No
Administration
- Before first dose, assess apical pulse and blood pressure. If patient has bradycardia or tachycardia, withhold dose and contact prescriber.
- If patient has atrial fibrillation, expect to give digoxin, calcium channel blocker, beta-adrenergic blocker, and possibly an anticoagulant before administering quinidine.
- If sinus rhythm isn’t restored after patient has received a total of 10 mg/kg quinidine gluconate, other means of cardioversion may be considered.
- Monitor blood pressure and ECG; titrate flow rate to correct arrhythmia.
- When giving large doses, monitor blood pressure and ECG continuously.
- Know that quinidine gluconate is the only parenteral cinchona alkaloid antimalarial commercially available in U.S. Because newer antiarrhythmics have replaced quinidine in many cardiac uses, it may not be readily available and prescribers may not be familiar with its use
Adverse reactions
CNS: vertigo, headache, ataxia, apprehension, excitement, delirium, syncope, confusion, depression, dementia
CV: ECG changes, hypotension, vasculitis, tachycardia, premature ventricular contractions, paradoxical tachycardia, ventricular tachycardia, ventricular fibrillation, ventricular flutter, ventricular ectopy, torsades de pointes, complete atrioventricular (AV) block, widened QRS complex, prolonged QT interval, asystole, aggravated heart failure, arterial embolism, vascular collapse
ENT: diplopia, blurred vision, mydriasis, abnormal color perception, scotoma, photophobia, night blindness, optic neuritis, decreased hearing, tinnitus
GI: nausea, vomiting, diarrhea, abdominal pain, increased salivation, anorexia
GU: lupus nephritis Hematologic: purpura, hemolytic anemia, hypothrombinemia, leukocytosis, shift to left in white blood cell differential, neutropenia, thrombocytopenia, thrombocytopenic purpura, agranulocytosis
Hepatic: hepatotoxicity Respiratory: acute asthma attack, respiratory arrest
Skin: rash, pruritus, urticaria, photosensitivity, angioedema
Other: fever, cinchonism, lupuslike syndrome, hypersensitivity reaction
Patient monitoring
- Monitor ECG and vital signs closely. Assess for worsening heart failure, especially with I.V. use.
- Assess CBC, kidney and liver function tests and quinidine blood level.
- Watch for signs and symptoms of blood dyscrasias.
- Closely monitor respiratory status. Stay alert for asthma attacks and impending respiratory arrest.
- Monitor for adverse GI effects, which may signify drug toxicity.
Patient teaching
- Advise patient to take with food to reduce GI upset.
- Instruct patient not to crush or chew extended-release tablets.
- Teach patient to recognize and immediately report signs and symptoms of toxicity, including tinnitus, nausea, headache, dizziness, and visual disturbances.
- Caution patient to avoid potassium supplements, licorice, and grapefruit juice. Tell him to maintain constant level of sodium intake.
- Advise patient to consult prescriber before taking herbs.
- As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.
REFERENCES
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