ANTI MALARIAL DRUGS

INTRODUCTION

• Malaria, a disease caused by parasites of the genus Plasmodium, continues to claim hundreds of thousands of lives every year.
• Infusions of Cinchona bark provided the first effective cure for malaria in the early 1600s and were used widely for centuries.
• Quinine, isolated from the Cinchona bark in 1820, was to become the first identified antimalarial drug.
• World War II led to the introduction of chloroquine, chloroguanide (proguanil), and eventually amodiaquine and pyrimethamine.
• The war in Vietnam brought mefloquine and halofantrine. These drugs are all we have available now to treat malaria..

DEFINITION

• Antimalarial medications are a type of anti- parasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria.

CLASSIFICATION

Based on the structure Anti-malarial drugs are classified as follows

• Aryl amino alcohols

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• • Quinine: Available as tablets and capsules containing 300 or 600 mg & as injections, containing 300mg /ml.
  • Quinidine: Available as tablets 200 mg; 300 mg; 275 mg & 324 mg; and Injection forms 80mg/ml
  • Mefloquine: Available as tablets 250mg
  • Halofantrine: Available as 250mg tablets
• 4-aminoquinolines
  • Chloroquine: Available as 250mg & 500mg tablets; and 50mg/ml Injectable form
  • Amodiaquine: Available as 150mg tablets per Oral administration
• 8-aminoquinolines
  • Primaquine: Available as 26.3 mg tablets per oral
• Folate Synthesis Inhibitors
  • Chloroguanide: Available as 100mg tablets administered per oral
  • Sulfadoxine+Pyrimethamine: used in combination with other drugs.
• Peroxides- Artemisinin derivatives
  • Artemether: Available as 80mg/ml Injection and 40mg per capsule
  • Arteether (Artemotil): Available as 150mg per 2 ml ampoule administered Deep IM
  • Artesunate:  Available as 50mg tablets and 60mg/ml injection
• Naphthoquinones
  • Atovaquone: Available as 250 mg tablets per Oral;
  • combination forms available as 250 mg atovaquone + 100 mg proguanil per tablet for adults and 62.5 mg atovaquone + 25 mg proguanil per tablet for children.

Mode of Action:

These drugs act on the primary tissue forms that initiate the erythrocytic stage of the plasmodia

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Inhibits the parasitic enzyme heme polymerase that converts the toxic heme into non-toxic hemozoin

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Accumulation of toxic heme within the parasite

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Interferes with the bio-synthesis of Nucleic acids within the parasites

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Blocks the further development of the parasites

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Terminates the clinical Attacks of malaria

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Ablates the transmission of Infection

 INDICATIONS:

• Uncomplicated malaria (Plasmodium falciparum)
• Chloroquine-resistant (Plasmodium falciparum, Plasmodium vivax)
• Malaria (prophylaxis)
• Prevention of relapse of Plasmodium vivax malaria
• Pneumocystis carinii pneumonia
• Amebiasis, extraintestinal
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Toxoplasmosis

PHARMACOKINETICS:

• Absorption: Around 90% of the drug is absorbed from G.I.T and rapidly absorbed from intra muscular and subcutaneous sites.
• Distribution: It has a large distribution volume due to extensive sequestration in tissues of liver, spleen, kidney, lung etc. Hence the need for a larger loading dose. Therapeutic blood levels persist for 6-10 days and elimination half-life is 1-2 months.
• Metabolism: Half of the drug is converted to active metabolites in the liver.
• Excretion: Half of the drug is excreted unchanged by the kidneys.

CONTRAINDICATIONS:

• Chloroquine should be used with caution in patients with hepatic disease, as it is distributed widely in the liver and is converted to active metabolites, severe gastro intestinal, neurological or blood disorders.
• Quinine derivatives exhibit Hypersensitivity in the form of rashes, angioedema, visual and auditory symptoms, hence contraindicated in patients with tinnitus and optic neuritis. It should be used with caution in patients with atrial fibrillation.
• Pyrimethamine can cause occasional skin rashes and depression of hematopoiesis. Excessive doses can produce megaloblastic anemia.
• Mefloquine should be avoided in first trimester of pregnancy and pregnancy should be avoided within 3 months of taking the drug.

DRUG TOXICITY:

• serious toxic effects include neutropenia, anemia, hemolysis, and elevated levels of liver enzymes.
• Neurotoxic effects like blurred vision, disturbed color perception, photophobia, diplopia, night blindness, and rarely, even blindness.

ADVERSE & SIDE EFFECTS:

• Dysphagia, Nausea, vomiting, anorexia, diarrhea & abdominal pain
• visual hallucinations, confusion, excitement, delirium and occasionally frank Psychosis
• dizziness, headache, diplopia, disturbed visual accommodation, malaise
• pruritus of palms, soles and scalp & allergic Reactions
• prolonged QT interval and sinus arrhythmias, Sinus bradycardia & Postural hypotension.

NURSING RESPONSIBILITY:

Acute malarial infection

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• • Monitor hyper sensitivity reaction and cinchonism.
  • Monitor vital signs & Electrocardiogram (ECG) regularly
  • Monitor the Glassgow coma Score (GCS) function & discontinue the drug in case of Neurotoxicity
  • Monitor for eye and ear function
  • Monitor blood test  - Complete Blood Count (CBC), Liver Function Tests (LFT) and Renal Function Tests (RFT)
  • Advise the patient to complete the course of treatment
  • Advise the patient to report any discoloration in cornea, nail and fingers
  • Drug should be taken only after meals
  • Advice the client to drink plenty of Oral fluids
  • Patient is advised to wear sun glasses while exposing to bright sunlight to prevent photophobia
  • Advise the patient that urine may change brown color due to drug administration
  • Avoid use of alcohol during drug therapy
  • Evaluate therapeutic response: treatment of malarial Infection.