Primaquine

Key takeaways

Primaquine belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Primaquine to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Primaquine from memory before moving on to harder problems.

Reference excerpt

Primaquine is a medication used to treat and prevent malaria and to treat Pneumocystis pneumonia. Specifically it is used for malaria due to Plasmodium vivax and Plasmodium ovale along with other medications and for prevention if other options cannot be used. It is an alternative treatment for Pneumocystis pneumonia together with clindamycin. It is taken by mouth. Common side effects include nausea, vomiting, and stomach cramps. Primaquine should not be given to people with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to the risk of red blood cell breakdown. It is often recommended that primaquine not be used during pregnancy. It may be used while breastfeeding if the baby is known not to have G6PD deficiency. The mechanisms of action are not entirely clear but are believed to involve effects on the malaria parasites' DNA. Primaquine was first made in 1946. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication.

Medical uses

Malaria Primaquine is primarily used to prevent relapse of malaria due to Plasmodium vivax and Plasmodium ovale. It eliminates hypnozoites, the dormant liver form of the parasite, after the organisms have been cleared from the bloodstream. If primaquine is not administered to patients with proven P. vivax or P. ovale infection, a very high likelihood of relapse exists for weeks or months (sometimes years). But it has been hypothesized that primaquine (and perhaps also the newer, related drug tafenoquine) might kill a proportion of non-circulating merozoites as well as hypnozoites, such as merozoites in bone marrow, thereby reducing the number of recrudescences (not only hypnozoite-mediated relapses) that take place. Clarity in this regard is expected to be forthcoming soon. Use of primaquine in combination with quinine or chloroquine each of which is very effective at clearing P. vivax from blood, improves outcomes; they appear to also potentiate the action of primaquine. As of 2016, the US Centers for Disease Control and Prevention recommends the use of primaquine for primary prophylaxis prior to travel to areas with a high incidence of P. vivax, and for terminal prophylaxis (anti-relapse therapy) after travel. A single dose of primaquine has rapid and potent ability to kill gametocytes (stage V) of P. falciparum and P. vivax in blood; it also kills asexual trophozoites of P. vivax in blood, but not of P. falciparum. Because of its action against gametocytes, the WHO recommends it for use in reducing transmission to control P. falciparum infections.

Pneumocystis pneumonia Primaquine is also used in the treatment of Pneumocystis pneumonia (PCP), a fungal infection commonly occurring in people with AIDS and, more rarely, in those taking immunosuppressive drugs. To treat PCP effectively, it is usually combined with clindamycin.

Special populations Primaquine has not been studied extensively in people 65 and older so it is not known if dosing should be adjusted for this population. Primaquine should not be administered to anyone with G6PD deficiency because a severe reaction can occur, resulting in hemolytic anemia. However, the WHO has recommended that a single dose of primaquine (0.25 mg/kg) is safe to give even in individuals with G6PD deficiency, for the purpose of preventing transmission of P. falciparum malaria. Primaquine is contraindicated in pregnancy, because the glucose-6-phosphate dehydrogenase status of the fetus would be unknown. Primaquine overdose can cause a dangerous reduction in various blood cell counts, and therefore should be avoided in people at risk for agranulocytosis, which include people with conditions such as rheumatoid arthritis and lupus erythematosus, and those taking concurrent medications that also decrease blood cell counts. Hemolytic reactions (moderate to severe) may occur in individuals with G6PD deficiency and in individuals with a family or personal history of favism. Areas of high prevalence of G6PD deficiency are Africa, Southern Europe, Mediterranean region, Middle East, South-East Asia, and Oceania. People from these regions have a greater tendency to develop hemolytic anemia (due to a congenital deficiency of erythrocytic G6PD) while receiving primaquine and related drugs.

Adverse reactions Common side effects of primaquine administration include nausea, vomiting, and stomach cramps. In persons with cytochrome b5 reductase deficiency, primaquine causes methemoglobinemia, a condition in which the blood carries less oxygen that it does normally. Overdosing can reduce the number of function of various kinds of blood cells, including loss of red blood cells, methemoglobinemia, and loss of white blood cells. Persons with glucose-6-phosphate dehydrogenase deficiency (G6PD) may develop hemolytic anemia from primaquine.

Pharmacology

Mechanism of action Primaquine is lethal to P. vivax and P. ovale in the liver stage, and also to P. vivax in the blood stage through its ability to do oxidative damage to the cell. However, the exact mechanism of action is not fully understood. Liver hypnozoites aside, primaquine can possibly eliminate P. vivax merozoites in bone marrow as a result of accumulation there of hydrogen peroxide.

Pharmacokinetics Primaquine is well-absorbed in the gut and extensively distributed in the body without accumulating in red blood cells. Administration of primaquine with food or grapefruit juice increases its oral bioavailibity. In blood, about 20% of circulating primaquine is protein-bound, with preferential binding to the acute phase protein orosomucoid. With a half-life on the order of 6 hours, it is quickly metabolized by liver enzymes to carboxyprimaquine, which does not have anti-malarial activity. Renal excretion of the parent drug is less than 4%.

Chemistry Primaquine is an analog of pamaquine which was the first drug of the 8-aminoquinoline class; tafenoquine is another such drug.

History Primaquine was first made by Robert Elderfield of Columbia University in the 1940s as part of a coordinated effort led by the Office of Scientific Research and Development in World War II to develop anti-malarial drugs to protect and treat soldiers fighting in the Pacific theater.

Society and culture It is on the World Health Organization's List of Essential Medicines.

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Primaquine

Start with the simplest possible case. Write down what Primaquine claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Primaquine before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Primaquine ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Primaquine

In research: Primaquine appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Primaquine in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Primaquine is common in secondary-school and first-year university syllabi. It links to neighbouring topics Antimalarial agents, CYP2D6 inhibitors, Phenol ethers, so understanding it makes those chapters shorter.
In everyday life: Look for Primaquine outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Primaquine in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Primaquine means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Primaquine out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Primaquine in simple terms?

Primaquine is a medication used to treat and prevent malaria and to treat Pneumocystis pneumonia. Specifically it is used for malaria due to Plasmodium vivax and Plasmodium ovale along with other medications and for prevention if other options cannot be used.

Why does Primaquine matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Primaquine?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Primaquine.