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Antimalarial Drugs

Malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria, a vector-borne parasitic disease caused by Plasmodium spp., is transmitted via injection of sporozoites or immature forms of the parasite into a person's bloodstream. Sporozoites then infect the hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy and differentiate into schizonts Schizonts Multinucleate cells or a stage in the development of sporozoan protozoa. It is exemplified by the life cycle of Plasmodium falciparum in the malaria infection cycle. Plasmodium/Malaria, which subsequently rupture, and merozoites Merozoites Uninuclear cells or a stage in the life cycle of sporozoan protozoa. Merozoites, released from ruptured multinucleate schizonts, enter the bloodstream and infect the erythrocytes. Plasmodium/Malaria invade red blood cells Red blood cells Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology. As such, pharmacotherapy for malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria targets exoerythrocytic and erythrocytic forms of schizonts Schizonts Multinucleate cells or a stage in the development of sporozoan protozoa. It is exemplified by the life cycle of Plasmodium falciparum in the malaria infection cycle. Plasmodium/Malaria. Collectively, these agents are classified as schizonticides.

Last updated: 17 Dec, 2020

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Plasmodia Life Cycle and Prophylaxis

Plasmodium life cycle antimalarial drugs

Plasmodium life cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation

Image by Lecturio.

The treatment of malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria is targeted at different stages of the Plasmodium life cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation:

  • Human liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy stage: targeted with tissue schizonticides
  • Human blood stage: targeted with blood schizonticides
  • Gametocyte stage: targeted with gametocides 
  • Human liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy dormant stages: Hypnozoites Hypnozoites Plasmodium/Malaria can form in P. ovale P. ovale A species of protozoan parasite causing malaria. It is the rarest of the four species of Plasmodium infecting humans, but is common in West african countries and neighboring areas. Plasmodium/Malaria and P. vivax P. vivax A protozoan parasite that causes vivax malaria. This species is found almost everywhere malaria is endemic and is the only one that has a range extending into the temperate regions. Plasmodium/Malaria infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease and are targeted with primaquine or tafenoquine.

Treatment consists of 3 steps:

  1. Identification Identification Defense Mechanisms of the infecting Plasmodium species
    • P. falciparum P. falciparum A species of protozoa that is the causal agent of falciparum malaria. It is most prevalent in the tropics and subtropics. Plasmodium/Malaria is the most severe; can cause anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types and cerebral malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria
  2. Identification Identification Defense Mechanisms of drug susceptibility of the infecting Plasmodium
    • Determined by geographic origin of infection
  3. Patient’s clinical status
    • Avoid the same drug for treatment if it was used prophylactically

Malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria prophylaxis Prophylaxis Cephalosporins and prevention

  • Centers for Disease Control and Prevention (CDC) prophylactic regimens are based on a traveler’s geographic region.
  • Travelers should consult local guidelines (will vary from country to country and with seasons)
  • Principles of prevention
    • Chloroquine: first choice in areas without resistant P. falciparum P. falciparum A species of protozoa that is the causal agent of falciparum malaria. It is most prevalent in the tropics and subtropics. Plasmodium/Malaria
    • Mefloquine: first choice in areas with chloroquine-resistant P. falciparum P. falciparum A species of protozoa that is the causal agent of falciparum malaria. It is most prevalent in the tropics and subtropics. Plasmodium/Malaria
    • Doxycycline or Malarone® (atovaquone + proguanil): in areas with multidrug-resistant malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria
    • Primaquine: in terminal prophylaxis Prophylaxis Cephalosporins of P. vivax P. vivax A protozoan parasite that causes vivax malaria. This species is found almost everywhere malaria is endemic and is the only one that has a range extending into the temperate regions. Plasmodium/Malaria and P. ovale P. ovale A species of protozoan parasite causing malaria. It is the rarest of the four species of Plasmodium infecting humans, but is common in West african countries and neighboring areas. Plasmodium/Malaria

Blood Schizonticides, Tissue Schizonticides, and Gametocides

Blood schizonticides

  • Chloroquine
    • Mechanism of action: prevents polymerization of heme and intracellular heme is toxic to the parasite
    • Mechanism of resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing:
      • Plasmodia develop membrane transporters to eject intracellular heme.
      • P. falciparum P. falciparum A species of protozoa that is the causal agent of falciparum malaria. It is most prevalent in the tropics and subtropics. Plasmodium/Malaria develops a transporter for chloroquine itself, coded by the P. falciparum P. falciparum A species of protozoa that is the causal agent of falciparum malaria. It is most prevalent in the tropics and subtropics. Plasmodium/Malaria chloroquine transporter (pfcrt) gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics.
    • Side effects at low doses:
      • Gastrointestinal (GI) disturbances ( nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, cramping, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea)
      • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions rash Rash Rocky Mountain Spotted Fever
      • Headaches
    • Side effects at high doses:
      • Severe skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions reactions
      • Peripheral neuropathies Neuropathies Chédiak-Higashi Syndrome, toxic psychosis, retinal and auditory damage
      • Myocardial depression
      • May precipitate porphyria attacks
  • Quinine
    • Mechanism of action: combines with dsDNA, prevents strand separation, blocks replication and transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription
    • Used in chloroquine-resistant P. falciparum P. falciparum A species of protozoa that is the causal agent of falciparum malaria. It is most prevalent in the tropics and subtropics. Plasmodium/Malaria
    • Often combined with doxycycline or clindamycin Clindamycin An antibacterial agent that is a semisynthetic analog of lincomycin. Lincosamides, used to shorten the duration and limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation toxicity Toxicity Dosage Calculation
    • Toxicity Toxicity Dosage Calculation:
      • Cinchonism (GI distress, headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, vertigo Vertigo Vertigo is defined as the perceived sensation of rotational motion while remaining still. A very common complaint in primary care and the ER, vertigo is more frequently experienced by women and its prevalence increases with age. Vertigo is classified into peripheral or central based on its etiology. Vertigo, blurred vision Blurred Vision Retinal Detachment, tinnitus Tinnitus A nonspecific symptom of hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, and other noises in the ear. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. Cranial Nerve Palsies)
      • Hemolysis in G6PD G6PD Pentose Phosphate Pathway deficient patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
      • Blackwater fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever ( intravascular hemolysis Intravascular hemolysis Hemolytic Anemia)
  • Mefloquine
    • Chemically related to quinine
    • Mechanism of action: creates toxic heme particles in food vacuoles
    • First-line agent: taken weekly (4 weeks before and 1 week after)
    • Toxicity Toxicity Dosage Calculation:
      • GI distress, skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions rash Rash Rocky Mountain Spotted Fever, headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome)
      • Nightmares
      • May cause cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) conduction defects and seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures at high doses

Tissue schizonticides

  • Primaquine  
    • Tissue schizonticide and gametocide
    • Used in conjunction with a blood schizonticide
    • Mechanism of action: forms quinoline-quinone metabolites that act as oxidants
    • Eliminates dormant liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy stages ( hypnozoites Hypnozoites Plasmodium/Malaria) of P. vivax P. vivax A protozoan parasite that causes vivax malaria. This species is found almost everywhere malaria is endemic and is the only one that has a range extending into the temperate regions. Plasmodium/Malaria and P. ovale P. ovale A species of protozoan parasite causing malaria. It is the rarest of the four species of Plasmodium infecting humans, but is common in West african countries and neighboring areas. Plasmodium/Malaria
    • Toxicity Toxicity Dosage Calculation:
      • GI distress, headaches
      • Methemoglobinemia Methemoglobinemia Methemoglobinemia is a condition characterized by elevated levels of methemoglobin in the blood. Methemoglobin is the oxidized form of hemoglobin, where the heme iron has been converted from the usual ferrous (Fe2+) to the ferric (Fe3+) form. The Fe3+ form of iron cannot bind O2, and, thus, leads to tissue hypoxia. Methemoglobinemia, toxicity Toxicity Dosage Calculation in G6PD-deficient patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (hemolysis)
      • Contraindicated in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care

Gametocides

  • Kill sexual stages and prevent transmission to mosquitoes

Gametocidal + schizonticidal:

  • Quinine: gametocidal against P. vivax P. vivax A protozoan parasite that causes vivax malaria. This species is found almost everywhere malaria is endemic and is the only one that has a range extending into the temperate regions. Plasmodium/Malaria and ovale 
  • Primaquine: gametocidal against P. falciparum P. falciparum A species of protozoa that is the causal agent of falciparum malaria. It is most prevalent in the tropics and subtropics. Plasmodium/Malaria, malariae, ovale, and vivax

Artemisinins and Antifolate Drugs

Artemisinins

  • Blood schizonticides
  • Not used as monotherapy to prevent resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing
  • Only drugs effective against quinine-resistant strains
  • Mechanism of action: accumulate in protozoan food vacuoles, and once metabolized, release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology toxic free radicals Free radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Ischemic Cell Damage
    • Rare adverse effects of nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, and diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
    • No increase in congenital Congenital Chorioretinitis problems or stillbirths in women taking these drugs
  • Short half-lives and not used for malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria prophylaxis Prophylaxis Cephalosporins
  • Artesunate IV: treatment of severe malaria Severe malaria Plasmodium/Malaria
  • Artemether-lumefantrine: CDC recommended for uncomplicated malaria Uncomplicated malaria Plasmodium/Malaria treatment in adults and children weighing ≥ 5kg
  • Halofantrine: Active against all 4 plasmodium malarial species
  • Dihydroartemisinin-piperaquine: not available in the United States and not recommended by the CDC due to widespread resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing

Antifolate drugs

  • Prophylaxis Prophylaxis Cephalosporins and treatment for multidrug-resistant P. falciparum P. falciparum A species of protozoa that is the causal agent of falciparum malaria. It is most prevalent in the tropics and subtropics. Plasmodium/Malaria 
  • Mechanism of action: antimetabolites, block folic acid synthesis Synthesis Polymerase Chain Reaction (PCR)
  • Proguanil
  • Pyrimethamine
  • Sulfonamides Sulfonamides A group of compounds that contain the structure so2nh2. Sulfonamides and Trimethoprim
    • Mechanism of action: inhibit dihydropteroate synthase Dihydropteroate Synthase An enzyme that catalyzes the formation of dihydropteroate from p-aminobenzoic acid and dihydropteridine-hydroxymethyl-pyrophosphate. Sulfonamides and Trimethoprim
    • Adverse reactions: skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions rashes Rashes Rashes are a group of diseases that cause abnormal coloration and texture to the skin. The etiologies are numerous but can include irritation, allergens, infections, or inflammatory conditions. Rashes that present in only 1 area of the body are called localized rashes. Generalized rashes occur diffusely throughout the body. Generalized and Localized Rashes, GI upset, hemolysis, kidney damage
    • Sulfadoxine-pyrimethamine: not used in the United States
    • Dapsone Dapsone A sulfone active against a wide range of bacteria but mainly employed for its actions against Mycobacterium leprae. Its mechanism of action is probably similar to that of the sulfonamides which involves inhibition of folic acid synthesis in susceptible organisms. It is also used with pyrimethamine in the treatment of malaria. Antimycobacterial Drugs: rarely used
  • May combine pyrimethamine and sulfadoxine: synergistic effects through a sequential Sequential Computed Tomography (CT) blockade
  • Toxicity Toxicity Dosage Calculation:
    • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions rash Rash Rocky Mountain Spotted Fever, GI distress
    • Contraindicated in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care

Erythrocides and Miscellaneous Drugs

Erythrocides

  • Atovaquone
    • Malarone® (atovaquone + proguanil)
    • Used as treatment and as once-daily prophylaxis Prophylaxis Cephalosporins
    • Is an alternative treatment for P. jiroveci infection
    • Mechanism of action: disrupt mitochondrial electron transport
    • Toxicity Toxicity Dosage Calculation:
      • Abdominal pains
      • GI effects
  • Halofantrine
    • Active against erythrocytic forms of all 4 malarial organisms
    • Not used as a chemoprophylactic agent
    • High potential for cardiotoxicity: prolonged QT interval QT interval Electrocardiogram (ECG)
    • Embryotoxic: contraindicated in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care

Miscellaneous drugs

  • Doxycycline
  • Amodiaquine
    • Inexpensive
    • Used extensively in the developing world
    • Used in fixed dosing with artesunate
    • Toxicity Toxicity Dosage Calculation:
      • Agranulocytosis Agranulocytosis A decrease in the number of granulocytes; (basophils; eosinophils; and neutrophils). Lincosamides and aplastic anemia Aplastic Anemia Aplastic anemia (AA) is a rare, life-threatening condition characterized by pancytopenia and hypocellularity of the bone marrow (in the absence of any abnormal cells) reflecting damage to hematopoietic stem cells. Aplastic anemia can be acquired or inherited, however, most cases of AA are acquired and caused by autoimmune damage to hematopoietic stem cells. Aplastic Anemia

Adverse Effects

Drug Adverse effects
Artemether-lumefantrine (Coartem®) Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome), anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics/ vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, weakness, arthralgia Arthralgia Pain in the joint. Rheumatic Fever, myalgia Myalgia Painful sensation in the muscles. Ion Channel Myopathy
Artesunate Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome), anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics/ vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
Atovaquone-proguanil (Malarone®) Abdominal pain Abdominal Pain Acute Abdomen, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics/ vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, cough in children
Chloroquine
  • GI upset, headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, exacerbation of psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis, retinal toxicity Toxicity Dosage Calculation, visual impairment
  • Blue-gray skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions pigmentation with long-term use
  • Cardiomyopathy Cardiomyopathy Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). Cardiomyopathy: Overview and Types and QT prolongation have been seen with long-term therapy
Hydroxychloroquine Hydroxychloroquine A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. Immunosuppressants GI upset, headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, rash Rash Rocky Mountain Spotted Fever, visual changes
Doxycycline Photosensitivity Photosensitivity Tetracyclines, GI upset (mitigated by taking with food), permanent tooth discoloration in children < 8 years
Mefloquine
  • GI upset, skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions rash Rash Rocky Mountain Spotted Fever, headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome)
  • Psychiatric effects: nightmares, anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder, depression
  • Cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) conduction defects
  • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures at high doses
Primaquine GI upset, headaches, methemoglobinemia Methemoglobinemia Methemoglobinemia is a condition characterized by elevated levels of methemoglobin in the blood. Methemoglobin is the oxidized form of hemoglobin, where the heme iron has been converted from the usual ferrous (Fe2+) to the ferric (Fe3+) form. The Fe3+ form of iron cannot bind O2, and, thus, leads to tissue hypoxia. Methemoglobinemia, hemolysis (due to G6PD G6PD Pentose Phosphate Pathway deficiency)
Quinidine Quinidine An optical isomer of quinine, extracted from the bark of the cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potentials, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission. Class 1 Antiarrhythmic Drugs (Sodium Channel Blockers)
  • Hemolysis ( G6PD G6PD Pentose Phosphate Pathway deficiency)
  • Cinchonism (syndrome of nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, tinnitus Tinnitus A nonspecific symptom of hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, and other noises in the ear. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. Cranial Nerve Palsies, and vertigo Vertigo Vertigo is defined as the perceived sensation of rotational motion while remaining still. A very common complaint in primary care and the ER, vertigo is more frequently experienced by women and its prevalence increases with age. Vertigo is classified into peripheral or central based on its etiology. Vertigo)
  • Hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia (quinine-induced insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology)
  • Blackwater fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever: uncommon anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types of massive hemolysis with “Coca-Cola”-colored urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat
Tafenoquine
  • Dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome), nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics/ vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
  • Psychiatric effects are rarely seen (in ≤ 3% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship): somnolence, anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder, abnormal dreams, depression

Overview

Drug Classification Mechanism of action Usage Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation
Artemether-lumefantrine (Coartem®)
  • Blood schizonticide
  • Artemisinin-aryl alcohol combination
Metabolized in plasmodial food vacuole to toxic free radicals Free radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Ischemic Cell Damage
  • Treatment of uncomplicated P. falciparum P. falciparum A species of protozoa that is the causal agent of falciparum malaria. It is most prevalent in the tropics and subtropics. Plasmodium/Malaria malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship weighing ≥ 5 kg
  • Treatment of severe malaria Severe malaria Plasmodium/Malaria after the administration of IV artesunate
Artesunate
  • Blood schizonticide
  • Artemisinin
Metabolized in plasmodial food vacuole to toxic free radicals Free radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Ischemic Cell Damage
  • First-line treatment for severe malaria Severe malaria Plasmodium/Malaria in the United Sates (CDC recommended, not FDA approved)
  • 3-day treatment of 4 equal IV doses of 2.4 mg/kg
  • Followed by one of the following PO:
    1. Artemether-lumefantrine
    2. Atovaquone-proguanil
    3. Doxycycline
    4. Clindamycin Clindamycin An antibacterial agent that is a semisynthetic analog of lincomycin. Lincosamides
    5. Mefloquine (if no other options)
Known hypersensitivity to artemisinins
Atovaquone-proguanil (Malarone®)
  • Blood schizonticide
  • Tissue schizonticide
  • Quinone-folate antagonist
  • Prophylaxis Prophylaxis Cephalosporins in all areas
  • Taken with milk or fatty meal to aid absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption
Severe renal impairment (CrCl < 30 mL/minute)
Chloroquine
  • Blood schizonticide
  • 4-Aminoquinoline
Enters the food vacuoles of Plasmodia and disrupts heme polymerization Prophylaxis Prophylaxis Cephalosporins in areas with chloroquine-sensitive malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria
  • Retinal or visual changes
  • Caution in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with porphyrias Porphyrias Porphyrias are a group of metabolic disorders caused by a disturbance in the synthesis of heme. In most cases, porphyria is caused by a hereditary enzyme defect. The disease patterns differ depending on the affected enzyme, and the variants of porphyria can be clinically differentiated between acute and nonacute forms. Porphyrias, psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures, pre-existing hearing impairment Hearing impairment Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss
Hydroxychloroquine Hydroxychloroquine A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. Immunosuppressants Blood schizonticide Known hypersensitivity to 4-aminoquinolone derivatives
Doxycycline Inhibits protein synthesis Synthesis Polymerase Chain Reaction (PCR) in the plasmodial apicoplast
  • Children < 8 years old
  • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care or breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding
Mefloquine
  • Blood schizonticide
  • Quinoline methanol Methanol A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. Metabolic Acidosis
Enters the food vacuoles of Plasmodia and disrupts heme polymerization Prophylaxis Prophylaxis Cephalosporins in areas with chloroquine-sensitive malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria or chloroquine-resistant areas
  • History of seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
  • Psychiatric disorders
Primaquine
  • Forms quinoline-quinone metabolites that act as oxidants
  • Gametocidal against P. falciparum P. falciparum A species of protozoa that is the causal agent of falciparum malaria. It is most prevalent in the tropics and subtropics. Plasmodium/Malaria, malariae, ovale, and vivax
Prophylaxis Prophylaxis Cephalosporins in P. vivax P. vivax A protozoan parasite that causes vivax malaria. This species is found almost everywhere malaria is endemic and is the only one that has a range extending into the temperate regions. Plasmodium/Malaria predominant areas
  • Treatment for presumptive antirelapse therapy of P. ovale P. ovale A species of protozoan parasite causing malaria. It is the rarest of the four species of Plasmodium infecting humans, but is common in West african countries and neighboring areas. Plasmodium/Malaria and P. vivax P. vivax A protozoan parasite that causes vivax malaria. This species is found almost everywhere malaria is endemic and is the only one that has a range extending into the temperate regions. Plasmodium/Malaria
  • In conjunction with chloroquine (blood schizonticide)
  • Taken for 14 days after departing malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria area
  • G6PD G6PD Pentose Phosphate Pathway deficiency
  • Lupus erythematosus
  • Rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis (RA) is a symmetric, inflammatory polyarthritis and chronic, progressive, autoimmune disorder. Presentation occurs most commonly in middle-aged women with joint swelling, pain, and morning stiffness (often in the hands). Rheumatoid Arthritis
  • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care and breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding
Quinidine Quinidine An optical isomer of quinine, extracted from the bark of the cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potentials, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission. Class 1 Antiarrhythmic Drugs (Sodium Channel Blockers) IV
  • Blood schizonticide
  • Quinoline methanol Methanol A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. Metabolic Acidosis
Interferes with heme polymerization Discontinued in the United States
Quinine
  • Blood schizonticide
  • Quinoline methanol Methanol A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. Metabolic Acidosis
  • Interferes with heme polymerization
  • Gametocidal against P. vivax P. vivax A protozoan parasite that causes vivax malaria. This species is found almost everywhere malaria is endemic and is the only one that has a range extending into the temperate regions. Plasmodium/Malaria and P. ovale P. ovale A species of protozoan parasite causing malaria. It is the rarest of the four species of Plasmodium infecting humans, but is common in West african countries and neighboring areas. Plasmodium/Malaria
  • Treatment of uncomplicated chloroquine-sensitive malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria
  • Quinine sulfate oral PLUS either:
  • Prolonged QT interval QT interval Electrocardiogram (ECG)
  • Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis
  • Optic neuritis Optic neuritis Inflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as multiple sclerosis, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis). Cranial Nerve Palsies
Tafenoquine Interferes with heme polymerization Prophylaxis Prophylaxis Cephalosporins in all areas
  • Treatment of presumptive antirelapse therapy of P. ovale P. ovale A species of protozoan parasite causing malaria. It is the rarest of the four species of Plasmodium infecting humans, but is common in West african countries and neighboring areas. Plasmodium/Malaria and P. vivax P. vivax A protozoan parasite that causes vivax malaria. This species is found almost everywhere malaria is endemic and is the only one that has a range extending into the temperate regions. Plasmodium/Malaria
  • Administered as a single dose after departing malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria area
  • G6PD G6PD Pentose Phosphate Pathway deficiency
  • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care and breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding
  • Children < 16 years old
  • History of or active psychotic disorder

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