The mosquito's body should be effective in preventing the spread of malaria in the community.
Mechanism of action
The two drugs will inhibit two enzymes at two different stages in the parasite's folic acid synthesis process the parasite cannot synthesize DNA and RNA (see sulfamide section)
Pharmacokinetics : well absorbed through the digestive mucosa, 90% bound to plasma proteins, t/ 2 about 170 hours with sulfadoxine and 80 - 110 hours with pyrimethamine.
Undesirable effects
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+ Allergy: Itching, hives….
+ Blood disorders (hemolysis, granulocytopenia, macrocytic anemia)
+ Digestive disorders, kidney dysfunction, central nervous system
+ Long-term use to prevent diseases causing serious skin reactions: erythema, Stevens-Johnson syndrome, epidermal necrolysis..., risk of death.
Apply treatment
+ Indication
Treatment of chloroquine-resistant P. falciparum malaria (usually combined with quinine because of its slow action)
Prophylaxis for people entering malarial areas for long periods.
+ Contraindications and precautions
Do not use for people who are allergic to the drug, have megaloblastic anemia due to folate deficiency. People with severe blood, liver, or kidney diseases.
Caution: breastfeeding women, children under 2 months old, pregnant women (especially the last 3 months because sulfamide has a long half-life and can pass through the placenta, causing kernicterus in newborns)
+ Usage and dosage
Use a single dose, if you want to repeat the dose, it must be 8 days apart.
• Stop malaria:
Over 15 years old: take 3 pills or inject 2 tubes intramuscularly. Children under 1 year old: take 1/4 - 1/2 pill
Children 1 - 5 years old take 1 tablet
Children 5 - 12 years old take 2 tablets
• Malaria prevention: adults take 1 tablet/week
• Pyrimethamine is also used to treat Toxoplasma disease: adults start with 50 - 75 mg/day + 1 - 4 g sulfonamide for 1 - 3 weeks (dose adjusted according to the patient). Then reduce the dose of each drug by 1/2 for 4 - 5 weeks.
Tablets contain sulfadoxine 0.5g + Pyrimethamine 0.025g. 2ml tube contains: sulfadoxine 0.4g + Pyrimethamine 0.02g
2.1.4. Mefloquine (eloquin, lariam, mephaquin)
Synthetic drug derivative of 4-quinoline – methanol
Effect
+ Strong effect on asexual forms in red blood cells of P.falciparum, P.vivax.
+ Cannot kill gametocytes of P. falciparum and liver forms of P. vivax
+ Highly effective on parasites that are multi-resistant to other antimalarial drugs (chloroquine, proguanil, pyrimethamine...)
Mechanism of action : currently unknown
Pharmacokinetics
+ Absorbed through the digestive mucosa. In the blood, the drug is concentrated in red blood cells, lungs, liver, lymphocytes and central nervous system. In red blood cells with parasites, the drug concentration is twice the concentration in plasma.
+ Metabolized in the liver and loses its effect. Excreted mainly through feces and bile, the drug passes through the placenta, very little through milk. t/2 about 10 - 33 days.
Undesirable effects (related to dosage)
+ Digestive disorders: nausea, vomiting, abdominal pain, diarrhea
+ Neuropsychiatric disorders: headache, dizziness,...
+ Premature contractions, leukocytosis, ...
+ High dose: visual disturbances, psychosis...
Apply treatment
+ Indication
Treatment of chloroquine-resistant and multidrug-resistant P. falciparum malaria. Prophylaxis for travelers to malaria-endemic areas.
+ Contraindications : history of mental illness, epilepsy, arrhythmia, drug allergy, children < 3 years old, severe liver - kidney failure.
+ Caution: people operating machinery (because it causes dizziness even after stopping the drug)
How to use and dosage
+ Treatment of multidrug-resistant P. falciparum malaria:
Adults and children > 2 years old take 15mg/kg/day, maximum 1000mg/day divided into 2 times 6-8 hours apart, take after meals with plenty of water.
+ Prevention: only used in places where parasites are resistant to many drugs:
Adults take 1 tablet of 250mg/week on a certain day, take 1 week before entering a malarial area and continue for 4 weeks after leaving the malarial area. If entering a severe malarial area for a short time: the first week take 1 tablet of 250mg/day, take for 3 consecutive days, then 1 tablet/week.
Children in the first week take 15mg/kg divided into 3 days, then: children 3 - 23 months: 1/4 tablet/week, 2 - 7 years old: 1/2 tablet/week, 8 - 13 years old: 3/4 tablets/week, > 14 years old: 1 tablet/week
Tablets: 250mg mefloquine hydrochloride 228mg mefloquine base
2.1.5. Artemisinin and derivatives
Isolated from Artemisia annua L, Asteraceae family.
Effect
+ Destroys asexual stages in red blood cells of 4 types of malaria parasites, including chloroquine-resistant P. falciparum.
+ No effect on the liver stage, on sporozoites and gametocytes of malaria parasites.
Mechanism of action : not completely clear
Pharmacokinetics
+ Rapidly absorbed through the digestive mucosa and rectal mucosa. Distributed widely to the liver, lungs, brain, blood, kidneys, heart muscle, and spleen.
+ Metabolism for 4 substances that are no longer effective
+ 80% of the dose is excreted in the user's feces and urine, t/2 is 4 hours.
Undesirable effects
+ In general, the drug is low in toxicity so it is relatively safe to use.
+ Unwanted effects are usually mild and transient: digestive disorders, headache, dizziness, lightheadedness (common when taking).
+ Some people may experience mild heart depression, slow heart rate. After rectal placement, burning pain, abdominal pain, diarrhea.
Apply treatment
+ Indication : is a commonly used drug in Vietnam
Treatment of mild to moderate malaria caused by 4 types of parasites.
Treatment of severe malaria due to multidrug-resistant P. falciparum or severe malaria. It is particularly effective in cerebral malaria.
+ Contraindications : should not be used for pregnant women in the first 3 months, unless they have cerebral malaria or complicated malaria and in areas where P. falciparum is multidrug resistant.
+ Usage and dosage
• Artemisinin:
First day take 20mg/kg/time/day Second - 5th day take 10mg/kg/time/day
• Artesunate:
First day take 4mg/kg/day Second - 5th day take 2mg/kg/day
Artemisinin tablets: 250mg Artesunate tablets: 50mg
2.1.6. Halofantrine (halfane)
Is a synthetic drug
Effect
+ Destroys asexual forms in red blood cells of P. falciparum
+ No effect on liver stage, sporozoites and gametocytes of malaria parasites
Mechanism of action : not completely clear
Pharmacokinetics : poorly absorbed through the digestive mucosa, fat in food increases drug absorption. Metabolized through the liver to form metabolites that are still effective. Excreted mainly through the feces, t/2 about 10 - 90 hours.
Undesirable effects : nausea, vomiting, abdominal pain, diarrhea (diarrhea occurs on the 2nd or 3rd day of taking the drug). Prolonged treatment or high doses can cause electrocardiogram changes and ventricular arrhythmia.
Apply treatment
+ Indication : treatment of malaria caused by chloroquine-resistant and multidrug-resistant P. falciparum.
+ Contraindications: pregnant women, breastfeeding women, history of cardiovascular disease. Use mefloquine 2-3 weeks before (because t/ 2 is long from 13-33 days). Do not combine with drugs that are toxic to the cardiovascular system. Do not use to prevent malaria.
+ Usage and dosage : adults and children > 40kg take 24mg/kg/day divided into 3 times every 6 hours.
Tablets: 250mg
45ml bottle of 5% oral suspension
2.2. Gametocidal drug “Primaquin”
Synthetic drug derivative of 8 amino – quinoline
Effect
+ Effective against the initial exoerythrocytic form in the liver of P. falciparum and the late exoerythrocytic form (dormant form, schizont form) of P. vivax; P. ovale, thus preventing recurrence
+ Kills gametocytes of 4 types of plasmodium in the patient's blood, so it has the effect of preventing the spread of the disease.
Mechanism of action : unknown
Pharmacokinetics : rapidly absorbed when taken orally, easily distributed into tissues. Completely metabolized in the liver, rapidly excreted in urine within 24 hours, t/ 2 is 3 – 8 hours.
Undesirable effects
+ Rare: hypertension, arrhythmia, agranulocytosis
+ Common: therapeutic doses can cause abdominal pain, epigastric discomfort, headache, high doses cause nausea and vomiting.
+ Toxicity: bone marrow suppression, hemolytic anemia, metHb
Apply treatment
+ Indication
Radical treatment and prevention of relapse of malaria due to P. vivax and P. ovale (usually in combination with erythrocytic asexual killers).
Preventing community transmission of malaria, especially chloroquine-resistant P. falciparum
+ Contraindications : bone marrow disease, liver disease, history of granulocytopenia, metHb, pregnant women, children < 3 years old.
Must stop taking the drug when there are signs of hemolysis.
+ Usage and dosage
• For radical treatment of malaria caused by P. vivax and P.ovale. Take Primaquin base 0.5mg/kg/day x 5 consecutive days (take with meals to reduce stomach irritation)
• To kill P. falciparum gametocytes and prevent transmission, take 0.5 mg/kg/day (1 day). Tablets 13.2 mg primaquine phosphate (7.5 mg primaquine base
Tablets 26.3 mg primaquine phosphate (15 mg primaquine base)
3. Drug-resistant parasites
3.1. Definition
According to WHO, drug resistance is "the ability of a parasite strain to survive and grow despite the patient having been treated and absorbed a certain amount of drug, or even the patient's blood having a concentration of drug that previously prevented and killed that type of malaria parasite."
Resistance can be relative (higher doses tolerated by the host still kill the parasite) or complete resistance (maximum doses tolerated by the host have no effect on the parasite).
3.2. Classification of antimalarial drug resistance
Antimalarial drug resistance is divided into two types:
– Natural resistance: the parasite has drug resistance before exposure to the drug, due to natural mutations in the parasite's genes, drug resistance is inherited through chromosomes. Parasites can be cross-resistant to drugs, for example: P.falciparum resistant to chloroquine can also be resistant to amodiaquine.
– Acquired resistance: parasites that are sensitive to drugs after a period of exposure become insensitive, due to chromosomal mutations, receiving resistance genes from the outside via plasmids or transposons
3.3. Drug resistance mechanism : unknown
4. Treatment principles
Treatment should be initiated as soon as possible, immediately after symptoms appear (children within 12 hours, adults within 24 hours).
Treatment with the right medicine, right dose, right duration.
Closely monitor treatment results to have timely and appropriate treatment measures.
5. Complications of malaria
People with malaria who are repeatedly untreated or treated incorrectly may experience complications such as:
Hepatitis, cirrhosis
– Spleen
– Glomerulonephritis, nephrotic syndrome.
– Swelling in legs, face…
– Other complications: anemia, iron deficiency, hypoglycemia, neuritis…
VALUATION
1. Describe the relationship between the biological cycle of malaria parasites and the use of drugs to treat malaria?
2. Describe the effects, mechanisms, indications, contraindications and dosage of antimalarial drugs.
3. Distinguish the differences in the effects of anti-convulsant drugs, anti-relapse drugs, and anti-malarial drugs.
ANTI-WORM DRUGS
Target:
1. Describe the effects, mechanisms of action and therapeutic applications of anthelmintics.
2. Describe the effects, mechanisms of action and therapeutic applications of anthelmintics.
Vietnam is a tropical country with a hot and humid climate, so the rate of worm infection is quite high. The types of worms with high infection rates are roundworms, whipworms, pinworms, hookworms, helminths and filariasis. Fluke diseases are often caused by flukes (small liver flukes, lung flukes, and tapeworms).
caused by intestinal tapeworms (beef tapeworm, pork tapeworm, etc.).
There are many types of anthelmintics, arranged according to the general morphology of the parasite.
1. Anti-worm medicine
1.1. Mebendazole (BD: fugacar, vermox, mebutar, nemasole)
Effect
+ The drug is highly effective on the adult and larval stages of roundworms, pinworms, whipworms, hookworms, and whipworms.
+ Kills eggs of roundworms and whipworms.
+ High doses have the effect of killing cysticercosis
Mechanism of action :
The drug binds to the parasite's tubules, inhibiting the polymerization of tubules into microtubules (which are essential components for normal parasite function).
Decreased glucose uptake, depleted glycogen reserves, decreased ATP. As a result, the parasite becomes immobile and dies.
Pharmacokinetics : little absorption through the digestive tract, absorption will increase when eaten with fatty foods. Metabolized in the liver to form inactive metabolites. Mainly excreted through feces, only a small amount excreted through urine (5 - 10%). t/2 about 1 hour.
Undesirable effects
+ Digestive disorders, mild headache.
+ High doses (therapeutic doses for cysticercosis) can cause bone marrow suppression, hair loss, hepatitis, nephritis, fever and exfoliative dermatitis.
Apply treatment
+ Indication
Treatment for infection with one or more types of worms such as roundworms, pinworms, whipworms, hookworms, whipworms, etc.
Treatment of hydatid cysts when albendazole is not available.
+ Contraindications : hypersensitivity, pregnant women, children < 2 years old (because the dose for children < 2 years old has not been studied), liver failure.
+ Usage and dosage : adults and children > 2 years old
Pinworm infection: take a single dose of 100mg, repeat after 2 weeks (because pinworms are prone to reinfection).
Hookworm, roundworm, whipworm, pinworm and multiple worm infections: take 100mg/time, twice daily (morning and evening), for 3 days or take a single dose of 500mg.
Strongyloidiasis: take 200mg/time, 2 times/day, for 3 days
Hydatid disease: 40 mg/kg/day orally, for 1 – 6 months (if no albendazole)
Tablets: 100mg, 500mg Oral solution 20mg/ml Oral suspension: 20mg/ml
1.2. Albendazole
BD: Albenza, eskazole, zeben, zentel
Effect
+ Effective against many types of worms such as roundworms, pinworms, hookworms, whipworms, strongyloides, trichinosis and tapeworms.
+ Effective on both adult and larval stages of parasitic worms and flukes in the digestive tract.
+ Kills roundworm and whipworm eggs.
Mechanism : similar to mebendazole
Pharmacokinetics
Albendazole is poorly absorbed through the gastrointestinal mucosa (5%).
Metabolized in the liver to the active metabolite (albendazole sulfoxide), which crosses the blood-brain barrier and the concentration in the cerebrospinal fluid = 1/3 of the concentration in plasma. Excreted mainly through the kidneys, a small amount is excreted in the bile, t/ 2 is 9 hours.
Undesirable effects : digestive disorders (abdominal pain, diarrhea...), pain
headache, dizziness, fatigue, insomnia.
Apply treatment
+ Indication
Infection with one or more types of worms such as roundworms, pinworms, whipworms, hookworms, whipworms, and strongyloides.
Treatment of cysticercosis and cysticercosis with brain damage (drug of choice for the treatment of cysticercosis).
+ Contraindications : pregnant women, people with severe liver disease
+ Usage and dosage
Can be chewed, swallowed or crushed and mixed with food, no need to fast, no need to use laxatives.
Roundworm, pinworm, whipworm and hookworm infections: adults and children > 2 years old take a single dose of 400mg/day, can be treated again after 3 weeks. Children < 2 years old take a single dose of 200mg (retreat after 3 weeks).
Cutaneous larva migrans: adults take 400mg/day for 3 days. Children take 5mg/kg/day for 3 days.