Antimalarials

Definitions & Key takeaways

Antimalarials are a class of drugs used to treat or prevent malaria. Malaria is caused by parasites belonging to the plasmodium species, and can be deadly if not treated quickly. Antimalarial drugs work by killing these parasites that cause the disease. There are different types of antimalarials usually taken as pills or injections. Common brands include artemisinin, chloroquine, quinine sulfate, doxycycline, and quinine. Antimalarial drugs are effective at treating malaria, but they can have various side effects depending on the drug.

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Introduction0:00–0:48

Malaria is an infection that can be caused by a few different types of Plasmodium species which are single celled parasites that are spread by mosquitoes.
There are 100s of types of plasmodium species, but the five that cause malarial disease in humans are Plasmodium falciparum, plasmodium vivax, plasmodium, Malai, plasmodium ovale and plasmodium knowlesi.
Once the plasmodium gets into the bloodstream, it infects liver cells and red blood cells which causes a variety of symptoms and sometimes even leads to death.
We rely on groups of medications commonly known as antimalarials in order to prevent and treat malaria. Now, malaria is transmitted when a Plasmodium infected female of the anopheles mosquito hunts for a blood meal in the evening and throughout the night, they're kind of like tiny flying vampires with the mosquito being drawn to carbon dioxide that gets breathed out as well as bodily smells like foot odor.

Pathology0:48–5:27

At this point. The plasmodium is in a stage of development called a sporozoite waiting patiently in the mosquito's salivary gland.
When a mosquito bites a person with its proboscis, the worm like sporozoites spill out of the mosquito saliva and make it into the bloodstream.
The sporozoites then travel to the liver where they invade hepatocytes. There they begin asexual reproduction, also known as schizogony.
Over the next 1 to 2 weeks. Plasmodium falciparum, plasmodium malai and plasmodium knowlesi sporozoites multiply asexually and mature into merozoites.
While host hepatic parenchymal cells die. In contrast, plasmodium vivax and plasmodium ovale sporozoites enter into a dormant hepatic phase where they're called hypnozoite.
They can remain in this dormant phase for months to years until they wake up and begin schizogony. In both cases, when the merozoites are released into the blood, they enter the erythrocytic phase where they invade red blood cells once inside the red blood cell.
Plasmodium feeds on hemoglobin via a process called endocytosis where the parasite wraps its membrane around the hemoglobin.
In order to bring the hemoglobin inside itself, the plasma membrane forms a bubble called a food vacuole where hemoglobin can be broken down.
Plasmodium uses the globin proteins to fuel their growth, but the heme is toxic to them. So they're converted into insoluble hemozoin crystals.
As the parasite feeds, it undergoes mitosis and differentiates into lots of merozoites which then burst out of the red blood cell and enter back into the circulation.
Now, instead of going into the erythrocytic phase again, some of the merozoites undergo gatto agony which is where they divide and give rise to gametocyte, which are little sausage shaped sexual forms that can be either male or female.
These gametocyte remain inside the red blood cell and can get sucked up by another female mosquito that bites the same malaria carrier.
The gametocyte can then fuse together inside the mosquito to form a zygote. This part of the plasmodium life cycle is called sporogony.
And that is sexual reproduction as opposed to the schizogony or a sexual reproduction that happened in the liver and in the red blood cells, the zygote then goes on to develop further.
It becomes an oe kin and then an oa cyst that ruptures in the mosquito's gut, releasing thousands of sporozoites which navigate their way into the mosquito's salivary gland in order to repeat the cycle all over again.
Symptoms of malaria correspond to the reproductive cycle. Thats unique for each plasmodium species when the red blood cells burst at the end of the erythrocytic phase, tumor necrosis factor alpha and other inflammatory cytokines are released, which causes high fevers that typically occur in paroxysms or short bursts.
For example, in plasmodium malai fevers happen every 72 hours and is called quartan fever. While for plasmodium vivax and Plasmodium ovale fevers happen every 48 hours and these are called tertian fevers.
Now, since red blood cells are destroyed when merozoites are released. Malaria also causes hemolytic anemia with symptoms like extreme fatigue, headaches, jaundice and splenomegaly.
Now, many of the antimalarial medications are quinoline derivatives like quiNINE, which is one of the earliest antimalarial medications derived from the bark of South American Sino trees.

Quinoline derivatives5:27–8:55

Other medications in this class include quiNIDine, chloroquine, mefloquine and primaquine. These medications work by entering the plasmodium and accumulating in their food vacuoles.
Here, they bind to heme and prevent it from being converted into hemozoin. Since heme is toxic to the plasmodium, this eventually leads to their death.
Chloroquine is one of the most commonly used antimalarial medications and it's an effective blood schizonticide, meaning it kills the plasmodium found in erythrocytes.
It's effective against all species of plasmodium. But its widespread use has caused plasmodium falciparum in many parts of South America, Africa and Asia to develop resistance via an efflux pump on their membrane that can remove this medication.
It's a little bit like the plasmodium is just spitting it back out in these regions. Mefloquine, quiNIDine and quiNINE can be used as the main schizonticidal medication for life threatening.
Plasmodium infections, quiNINE and quiNIDine are often combined with an antibacterial like doxycycline and clindamycin. Now, one problem is that most quinoline derivatives can't kill the dormant hypnozoite of plasmodium ovale and plasmodium vivax in the liver.
Primaquine is the exception because it's less effective at killing sporozoites in the blood, but more effective at killing hypnozoite and gametocyte.
For this reason, it should always be given along with chloroquine or another blood schizonticidal when treating plasmodium ovale and plasmodium vivax infections.
Common side effects of quinoline derivatives include gastrointestinal distress and headaches. Chloroquine can cause pruritus or itching and if used over long periods of time, it can cause retinopathy that's reversible.
If the medication is stopped, quiNINE and quiNIDine could cause synchronism, which includes symptoms like skin flushing, tinnitus or ringing in the ears, hearing problems, blurred vision and headaches.
These medications especially quiNIDine can cause arrhythmias and Long Qt syndrome. So they should be avoided in people with cardiac problems.
Mefloquine. On the other hand, can cause neuropsychiatric side effects like depression, anxiety, psychosis and seizures.
Finally, primaquine could cause life threatening hemolytic anemia. In people with G six PD deficiency where the red blood cells lack a specific enzyme that protects them from oxidative stress.
It also causes hemolysis in the fetus and newborns. So it's contraindicated during pregnancy.
Artemisinin derivatives are a class of antimalarials that have been used for over a millennium. In Chinese medicine.
This family of medications include artemisinin, artemether, artena and dihydro artemisinin. These medications are blood schizonticides that build up in the food vacuoles of the plasmodium where they bind to the iron found in heme and create free radicals that damage parasite proteins.

Artemisinin derivatives8:55–10:14

They're useful since they're effective against all Plasmodium species, including the strains that are resistant to chloroquine and other quinoline derivatives.
They are considered for chloroquine resistant malaria and for treating serious infections. Notably, they're often used in combination with other anti malarials to lessen the chance of resistance ever developing.
For example, artemetherum Mehan combination is used to treat individuals with uncomplicated malaria caused by plasmodium falciparum.
Their other advantage is the comparatively mild side effects which include nausea, vomiting and diarrhea. They are also safe for use during pregnancy.
Travelers going to countries endemic for malaria need prophylactic medication depending on the region they're traveling to chloroquine can be used for regions that don't have resistant strains of Plasmodium falciparum in regions that do mefloquine, doxycycline and antifolate medications like atovaquone, proguanil can be used artemisinin derivatives have a short half life of only a few hours.

Indications10:14–10:58

So they're not effective for prophylaxis for travelers. Going to regions endemic for Plasmodium vivax and Plasmodium ovale.
Primaquine should be given along with one of the other medications to kill hypnozoite in the liver. All right.
Now we're gonna make a mnemonic to help you memorize and retain all of these farm facts for the Quinoline derivatives. We'll have a group of queens.
First. We have a queen playing in a small swimming pool for Chloroquine.

Memory palace10:58–13:40

Next, there's a narcissistic queen on a parade float with the word me on it for mefloquine. There's a nine year old queen for quiNINE and her hungry older sister who's holding a bucket of chicken for dinner for quiNIDine.
Let's give these two little bows and arrows is they can take care of the serious infections. Finally, an opera singing.
Prima Donna Queen represents Prima queen. Her singing is the only thing that could disturb the sleeping hypnozoite in the liver for the side effects of these medications.
There's too much chlorine in the pool and the swimming queen is itching. She's playing Marco Polo and has a blindfold on representing retinopathy.
It's reversible retinopathy since she can take the blindfold off. Even with the float.
Not enough people are paying attention to mefloquine and it drove her crazy. She's shouting angry gibberish which represents the neuropsychiatric side effects.
Next. QuiNINE and quiNIDine sink broke representing synchronism.
The plumber they hired is flushed red because he's bad at his job. He's got big earrings that get in the way representing Tinnitus.
He's also got two pairs of glasses on for diplopia. There's a bandage on his head from when he bumped it earlier.
Representing headaches. Representing long Qt syndrome is a squirrel with a long tail.
That's a real cutie. This squirrel broke the sink by jamming acorns down the drain since primaquine is contraindicated for pregnancy.
Let's have her singing which wakes up a baby causing him to cry. The baby has a mobile above him with six letter GS hanging from it to help you remember, it should also be avoided in people with G six PD deficiency for artemisinin derivatives.
We'll use Artemis, the Greek goddess of hunting. Since she's a goddess, she can hunt down any species of Plasmodium with her big shiny bow and arrow.
This helps you remember it's also more effective for serious infections compared to the little bow and arrow used by quiNINE and quiNIDine.
Since it causes gastrointestinal side effects, one of her hunting hounds is throwing up after taking a bite out of a dead plasmodium.
All right. There's a quick recap.
Malaria is a life threatening mosquito transmitted infection caused by plasmodium parasites. These parasites feed and grow inside hepatocytes and red blood cells.
But some species may have dormant forms that can stay in the liver for years. Most quinoline derivatives are effective at treating the erythrocyte stage of plasmodium.

Review13:40–14:17

But primaquine can treat the dormant stages that remain in the liver. The artemisinin derivatives are used to treat Plasmodium species resistant to the quinoline derivatives.
But wait, there's more. Here's a mind map with all of the mnemonics from the video.
Go ahead and pause so you can test yourself and see what you remember. Stay tuned for the answers after the credits.

Mind map14:17–14:07