Antimalarial Drugs - From a different Perspective!!

Antimalarials: The Harem

Once upon a time in a parallel Universe, there was a swampy kingdom ruled by King Medico. So, the story goes that once the kingdom was attacked by an epidemic of Malaria (Attack of the Plasmodia). The King (who is you in this story) decided to send his Queens out to destroy Malaria (much like in Chess: the Queen goes out to destroy, the King sits at home and watches ESPN!) He had 10 queens (including one eunuch), a mafia couple, a cyclist-warrior, a new warrior, and a CIA agent.

Chloe-Queen (Chloroquine).
Right, so…Chloe the Queen was a pretty effective warrior; she fought fast and long.
The parasites had occupied the Temples of the Red Corpuscles and were trying to degrade the sacred substance Heme, but she complexed with Heme and together their combined forces destroyed the plasmodial membranes. She could kill most of the erythrocytic schizonts (Bloody schizos!), but couldn't kill the resting forms in the liver (where they had set up their base camp).

She did manage to kill a few vivax babies (gametes), though, but not enough to prevent relapses.
Her strategy of complexing with Heme was so effective that other queens (Queen-9, Mufflo-Queen, Mepacrine) also used it (with variable success).
When plasmodial resistance to her increased, the King sent a spy called Viru Tamil (Verapamil) who penetrated the evil plasmodial defenses and allowed Chloe to do her job. Later in the war, a mafia couple (Sulfa-Pyri) took su-pyri to do the job.

She was useful in other Wars too:
1. Killed E. histolytica and Giardia
2. The Great War of RA (Rheumatoid Arthritis)
3. DLE
4. Lepra reactions
5. She also gave symptomatic relief to the King after he got Infectious Mononucleosis from kissing a teenage chambermaid.

Chloe the queen had the adverse effects of a typical woman:
• got under your SKIN (high affinity for melanin) and gave you an itch.
• got deep into the core of your being (high affinity for nuclear chromatin)
• aur aankhon mein bas gayi ( retinal accumulation). Love is Blind.
She gave the King headache and uneasiness, loss of hearing, blindness, mental disturbances and graying of hair. (damn typical woman!)
She did get pregnant though, and gave birth to a normal heir (no teratogenicity).
When the King drank himself to liver damage, she caused him to have seizures.
Being named after Chloro (Latin for green) she was a jealous queen, and the King could not be seen in the company of Mufflo-Queen, Amiodarone and other girls who could stop your heart from fluttering (antiarrhythmics).
She completely rid the kingdom of Falciparum (except some resistant forms), but vivax and ovale kept coming back. If the King went to an endemic area, he had her by his side for a week before and 10 weeks after.

Amodia-Queen (amodiaquine)
She was the African twin of Chloe; ditto on all counts but only called upon in time of war. Once the King took her on an endemic area junket, she almost killed him from toxic hepatitis and agranulocytosis. Known to be less toxic than Chloe, though – caused less of an itch.

Mufflo-Queen (mefloquine)
Mufflo came along to help Chloe get the falciparums that got away. She was very effective, fighting fast (though not as fast as Chloe) and long, but couldn't kill vivax babies. She was more toxic than Chloe. She was called Mufflo because she muffled and shuffled about (disturbed sense of balance, ataxia, errors in operating machinery), yes indeed, she was quite the Klutz of the palace (strange dreams, anxiety, hallucinations). She tends to get lost in the bile circulation. Safe in pregnancy, but the first trimester is always a time to avoid her. She was also quite the heart stopper and a bitter kisser, like Queen-9, and was only allowed to come out in very resistant attacks (kinda like Kumbhkarna, only female, and prettier). Allowed to go on trips ( a week before and 3 weeks after) to endemic areas but you gotta bring her back and not leave her there for the locals.

Mepacrine
He was the palace eunuch, tried to act like Chloe, but was quite ineffective, very toxic, caused the King to vomit and go mad (psychosis). Was banned and thrown out of the Kingdom. Keeps cryin' all the time – hence called Mepa-crine.

Queen-9 (Quinine)
Holy mo'fo' big bad mamma. Queen-9 was like Chloe in the War, killing vivax babies and bloody schizos, but slightly slower to act (and shorter) and very very toxic. "Very bitter kisser," said the King, "makes my stomach turn she does, the irritating bitch. Makes me deaf and blind, stimulates then depresses my brain. Sometimes I swear I can hear a ringing in my ears, did so the first time I met her – she said they were wedding bells! She is damn pretty though, quite the heart-stopper, and caused nausea, hypoglycemia, heavy breathing, fever, weakness in the legs and collapse in many of her suitors. Some even died. She aborted her babies, and killed my sperm, the bitch. She is a relief in varicose veins and when I get leg cramps at night though, and then she's the typical wife. I reserve her for the times when falciparum attacks the palace (brain). She's an effective killer when she teams up with the mafia Supyri, and the small time killers tetra and doxy.
In this scenario she is sometimes supported by Mufflo's team with Arti-Sunita the Chinese Queen.

Progu-Anil Cyclewala (proguanil)
Progu-Anil got on his cycle (cycloguanil) and went to kill the bloody schizos too. This he accomplished by inhibiting DHFRase, a strategy also employed by the mafia couple Sulfa-Pyri. He was kinda slow like Queen-9, but fought longer. His major achievement was getting into the enemy base camp (got his inspiration from Prima-Queen!) and killing the sleeping falciparums and some vivaxes too. He didn't kill any babies but didn't let them grow up. He was much less toxic than the queens - caused the King some tummy upset, and almost caused him some loss of hair. He was safe to hang around in pregnant times but mostly went along with Chloe to swampy battlegrounds that didn't agree with Chloe very much (not just to give her company!)

Prima-Queen (primaquine)
She didn't kill any bloody schizos, but she killed the babies, and all the sleeping ones in the base camp. They gave her the Prima title then
Terrible effects in G6PD deficient people. Roots out relapsing malaria.

Bula-Queen
Indian twin sister of prima, safe in G6PD.

Sulfa-Pyri
Pyri (pyrimethamine) was the female Sulfa-Pyri mafia team. She could kill the enemy by inhibiting DHFRase directly (without getting on her cycle). Also didn't let the babies grow up, like Anil. Sulfadoxine was her mate, he blocked the enemy a step ahead of Pyri. Together, these slow to act, but durable fighters exhausted the vivaxes in a strategy similar to the Septran Gang (trimethoprim-sulfamethoxazole).

PABA ---X-----> Folate ----X---->THFA
Sulfa Pyri/Trim

This gang took the su-pyri to kill the enemy when Chloe was ineffective. They took along Tetra and Doxy in their gang.

Tetra and Doxy
Small time killers. Slow, short acting, assist the Sulfa-Pyri gang to kill bloody schizos, and some falci sleepers.

The Chinese Queens
Very fast acting (like the Chinese playing ping-pong or like Jackie Chan) and short acting. Arti-Sunita (Artesunate) and Arti-Mathur (Artemether) killed the enemy babies. (These names are not real, guys). Used only for acute attacks of MDR falci. These beautiful ladies are heart stoppers too (QT prolonged, first degree A-V block), but they are kept secure in the palace. Ar-teeth-er (Arteether) (yes she's got the typical Chinese teeth!) only for institutional use in cerebral malaria.

Halofantrine is a last resort (like a CIA agent used for assassination) and acts like Mufflo-Queen, also cross-reacts with her. May cause VT. Toxic fellow.

Atovaquone is a new warrior that teams up with Progu-Anil to kill bloody schizos. Also fights P. carinii and Toxoplasma gondii (Pyri was in the latter fight too)

Disclaimer: My apologies for all the sexist, racist remarks in this story. It is fictional like Star Wars, but more palpable. No offense is meant to female humans, schizophrenics, eunuchs, Chinese, Parsis, Tamilians, Africans, Klutzes, womanizers, and the characters are not intended to look like real people, only fairy tale chumps.

Welcome to the Medical World! - For Freshers!

Few agonies and ecstasies of life compare with the rich variety and depth of experience, the pain and the peril shared by medical students in their voyage of metamorphosis from raw, ex-school kid ducklings to qualified doctors in all their swan-like white-coat glory. In the initial heady euphoria of qualifying for a premier medical institution, most bright-eyed youngsters do not realize that they are setting themselves up for a trial by fire. The selection process sieves brilliant students habituated to being frontrunners, and brings them together as equals. From being the `brain' of his class at school, the fresher student is immediately demoted to being just one of the guys'! Thus begins the medical student's long and arduous journey, where small victories are hard won and few, and every triumph just wins him the right to work harder.

Confusion amid contradiction dog him throughout his academic career. Hardly has he acclimatized to the feeling of achievement at having made it to the medical college, that he has to contend with failure - he has to get used to the idea of flunking in exams! But with the toughness and resilience peculiar to his breed, the medical student adapts readily to the changed scenario. He learns to grin and bear it all- the cadaveric gloom of the dissection hall and the equally gloomy, often menacing predictions regarding his future; the somnolent boredom of biochemical reactions and their changeable colours over the bunsen flame; the slimy frogs and sooty drums of physio-lab that leave him with dirty hands and weary spirits, wondering what he ever did to deserve all this! Tenaciously he clings on nevertheless , and masters the mysteries of the "normal" to cross the first hurdle of medical life and set up his date with disease.

The mind of the hapless medical student is a virtual battlefield of emotions, where the clerics of caution and restraint are locked in constant crusade with devils of his youth. He watches his school chums enviously as they celebrate the spring of their lives, while he struggles with microbial invasions and drug pharmacokinetics, forensic perversions and pathogenesis of syndromes. He feeds off carminative mixtures and rabbit ileum, broadens his horizons in the microscopic world of vague and nebulous life-forms, explores the grotesque architecture of pathological specimens, and uses his imposingly proportioned textbooks for mind and body building.

The students foray into the clinical arena and hospital wards is no less traumatic. One by one all his romantic illusions regarding the nobility of his chosen profession crash like waves on the stony shores of reality. On one hand he is inundated with theoretical facts, while on the other, he is increasingly demoralized by the futility of his inadequate tools in the face of human suffering. As all the immutable beliefs of his adolescent naivete disappear like dew in the harsh glare of the real world, his immature psyche and youthful personality struggle to keep pace with his expanding knowledge and graying experience of life.

As he grapples with his own tenuous adulthood, academic hawks wait at every step to quash his zeal and steamroll him into submission. He comes face to face with eternal contradindication: how in the world can he value the sanctity of life and dedicate his own life, to safeguard life, if the zest and passion for life itself are dead within him? Under siege from foes of his indefatigable spirit, the medical student learns to veil his enthusiasm but keeps the fire burning within, his courage bruised but never crushed. Skillfully like a nimble-toed ballet dancer, he where his way through the jungle of mammoth egos, where stalwarts await their prey with tentacles spread and claws unsheathed.

All that the majority of humanity learns about life in its most glorious and gory detail after the age of fifty, the medical student witnesses and internalizes before he turns twenty-five. For all those valiant survivors engaged in making sense of the mess and marvel of human existence, this tribute goes out from an ex-medical student and potential teacher to the present medical student and potential healer - just hang in there kiddo, and hats off to you!

A Doctor's Plight!

Comes the 12-1 lecture, and I am thoroughly disgusted,
It seems as if my cerebral hemispheres have been busted;
Our esteemed professors are the worst,
Whenever it comes to bewildering the mind first;
On they go about their accomplishments,
Never paying heed to our predicament;
Overdone gesticulations and histrionics galore,
Always fail to dispel the fact that they are a big bore;
God take me back to the time,
When biological cramming held neither reason nor rhyme;
When Physics numericals and Chemistry equations hadus by the neck,
But when compared to THIS monstrosity, they were but a small speck;
Now I am at my wit's end,
Trying to fathom what and how I can comprehend
Today, as I frequent theatres with unconcealed glee,
There always hangs the Damocles' sword of a supplee;
As I look up to the masters of this "noble" profession,
I realize I have to make a candid confession;
Whenever I gaze at an eminent urologist or cardiologist,
I get the portentous feeling I'll fare no better than being a philologist;
Sometimes, I dismiss these thoughts as being borne by youthful truancy,
But then again - truancy could hardly be an alibi for lunacy;
A lunatic asylum, the best in the state,
Would suit me, not as a doctor but as an inmate;
My psychiatric future looks a bit hazy,
But what the hell! All docs must be crazy!!!