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Pharmacology- Anti Malarial Drugs MADE EASY!

Plasmodium is a parasite that infects

the red blood cells and liver cells of

the human body

they're about over hundreds of species

of Plasmodium but the five most common

that cause disease in the humans are

Plasmodium falciparum plasmodium vivax

plasmodium malaria Plasmodium Overlea

and Plasmodium Alesi now there are some

blood disorders that naturally give a

person or the patient advantage by

protecting from Plasmodium or malaria

infection they are thalassaemia mainly

the alpha type g6pd deficiency because

we know that g6pd protects against

oxidative stress and Plasmodium also

depends on it and also in sickle cell

anemia now the sickle cells do not have

specific receptors which are needed for

the Plasmodium vivax to bind to it and

enter the RBC

now we'll briefly review the life cycle

of Plasmodium to understand the anti

malarial drugs better all of this starts

with the bite of a female Anopheles

mosquito which carries with it in its

cell every plant the sporozoite form of

the Plasmodium when this mosquito takes

a blood meal it injects the sporozoites

into the bloodstream

now these poor results will find their

way into the liver cells the hepatocytes

and start an asexual cycle or squids

organy there what they will do is they

will invade the hepatocytes and start

producing mira Zoids this mira soy

production or the asexual cycle is

typical for Plasmodium falciparum

plasmodium malaria and Plasmodium Milesi

which form these me results and cause

symptoms within one to two weeks at this

stage another thing that can happen

besides the asexual cycle is that the

sporozoites that have been injected in

the hepatocytes remain dormant there and

do not multiply and thus

get converted into the hypnosis form

this process is typical for the

Plasmodium vivax and plasmodium ovale

these hippo no soy forms are responsible

for the relapses now after let's say

we're dealing with the other three

plasmodia and they undergo the asexual

cycle and form mero soit's what happens

is that these merozoite

will invade the RBC's Plasmodium

falciparum in which RBC's of all ages

Plasmodium vivax is particular for

reticulocytes which are young RBC's and

immature and Plasmodium malaria and

Milesi are more specific for older RBC's

after invading the RBC's what they will

do is they will undergo the asexual

cycle again and form more mera soils

which will then be released into the

blood by bursting the RBC now some of

these me resorts can undergo gamete

Ogoni

that means they will form gamma 2 sites

both male and female and these chemita

sites can then be ingested by a female

Anopheles mosquito again in the gut of

the mosquito both of these gametes will

fuse leading to the formation of a

zygote and then an assist which will

rupture in its gut and thus release

sporozoites which will then go and

colonize the celebrity land and thus

repeat the cycle from this cycle we can

see that we have many targets to kill

the Plasmodium and there are many drugs

that are used for this purpose

first we'll classify them on the basis

of the stage of the Plasmodium that they

affect and secondly we will classify

them on the basis of the clinical

indication or their use or utility

depending upon the stage of Plasmodium

that these drugs affect they can be

divided into the tissue susan to sidle

agents the blood Shazahn to sidle agents

and the give me to sidle agents now the

tissue is on to sidle agents will act on

the form of the plasmodia which which

enters the liver and has not yet

affected the RBC's or that form that is

converted into the hypno so it form in

vivax and Ovalle that's why they can be

converted into the primary tissue forms

and the latent tissue forms the primary

tissue forms being the pre electrostatic

stage that is in the liver and has not

yet affected the RBC and the latent

tissue forms which are the hypnosis of

the vivax and Valley the primary tissue

form affecting drugs are sulfur dock

scene and pyrimethamine frog Juan el a

toga cone and prema queen while those

acting on the latent tissue forms or the

Hypnose ID form mainly of the WebEx and

Ovalle our primer Queen and death no

Queen coming to the blood sit on to

sidle which will act on the blood forms

of the parasite they can be divided into

the rapid acting with high efficacy and

slow acting with low efficacy the rapid

acting being chloroquine artemisinin

derivatives quenon mefloquine Etobicoke

n-- mo dire queen and lumefantrine while

the slow acting with low efficacy are

proven el pyrimethamine and sulfur dog

scene and clindamycin all of these have

to be used with a rapid acting agent the

gamete acetyl agents are artemisinin

primer queen for all the species of

plasmodia chloroquine and queen in for

vivax all of these will decrease the

transmission to mosquitoes and thus help

prevent spread of the disease now coming

to the classification that depends on

the clinical indication or utility they

can be divided into those that are used

for

prophylaxis causal prophylaxis for

suppressive prophylaxis clinical cure to

prevent relapses and to decrease the

transmission to mosquitoes and prevent

spread of disease

one thing to remember is that we don't

have a drug for the sporozoite form of

the Plasmodium for causal prophylaxis we

use the drugs for three electrostatic

stages of Plasmodium in the liver these

drugs can include through Guanella which

is mainly for falciparum and tremor

Queen that is for all the species of

Plasmodium but it is toxic and that's

the reason that it is not that well used

in prophylaxis for suppressive

prophylaxis

we know that the RBC's have been

infected but we suppress the error

through setec phase so that the RBC's do

not burst and there are no clinical

symptoms or clinical disease does not

start these drugs are chloroquine

mefloquine and doxycycline in cases of

pregnancy we cannot use tetracycline so

we can use clindamycin for clinical cure

of active malaria infections

we also need to suppress the

electrostatic phase of the Plasmodium

because we know that the main clinical

symptoms and the disease actually is due

to the bursting of RBC's so in clinical

malaria our active malaria we use rapid

and slow blood serum to seidel agents

now we know that the relapses of malaria

are due to the hypnotoad form that is

present in the liver and it's mainly in

the infections by vivax and valley and

this is actually to prevent relapse we

do a radical cure and for that we use a

blood schisandra Seidel with primer

Queen which is tissue Susan recital as

well that is it will kill the Hypnose

form as well so that that's how we

prevent relapses of malaria and we do

know that spread of malaria is due to

the chemita sight the sexual cycle and

for that we need to use gamete or Seidel

agents so that there is no transmission

to the mosquitos and thus spread of

disease is inhibited the main drug that

can be used here for all all the

malarial types is prema Queen now we'll

study all of these drugs in detail but

with a slightly different classification

we will divide them into the Queenie

like drugs or the quinolone derivatives

the artemisinin s' and their derivatives

both semi synthetic and synthetic the el

alcohol derivatives antipholus and anti

microbials the first drug we'll discuss

from the Quinlan derivatives and the

Queenie light drugs is chloroquine this

is a blood schisandra seidel agent as

we've discussed previously its mechanism

of action is by being taken up in the

acidic vacuoles of the Plasmodium and as

it is a weak base it will get

concentrated in the acidic vacuoles of

the parasite and this parasite is

actually converting him into him as Owen

because heme is toxic to a Plasmodium

but this chloroquine will inhibit this

conversion of him into him as Owen and

thus this chloroquine him complex will

damage the Plasmodium cell membrane and

thus kill it

chloroquine also has anti-inflammatory

properties and it has been used in

rheumatoid arthritis chloroquine has

good oral absorption and as well as

parenteral administration it has strong

affinity for melanin containing tissues

it has extensive tissue binding and

therefore to in order to achieve an

effective therapeutic concentration we

need to administer a loading dose

it gets concentrated in various organs

such as liver spleen kidney lung skin

etc its metabolism is in the liver and

it is excreted slowly in the urine

regarding the side effects on IV

administration it can cause hypertension

confusion arrhythmias convulsions and

even cardiac arrest as I said it can be

used in rheumatoid arthritis that means

it will be used in a prolonged manner

that's why it can cause retinopathy and

ototoxicity in that case it should not

be given with epileptics because its own

side effect is conversions and it will

enhance that effect and it should also

not be given with mefloquine which also

precipitates seizures although it is

safe in pregnancy it is a drug of choice

for acute attack of malaria because it

is the blood schizandra seidel and it is

also used prophylactically with

primaquine

for radical cure of malaria the next is

Queenan and quinidine which is the

alkaloids of cinchona bark as we well

know apart from being a blood Siddhanta

Seidel it is also a gamete or Seidel in

Plasmodium vivax and thus can be used to

help prevent spread of Plasmodium it has

some effects depressive effects on

cardiovascular system in the GI t it

increases gastric acid secretion it

depresses skeletal muscle contraction

and it also has local anesthetic action

and if you remember it is also used as

an anti-arrhythmic it has good gut

absorption and on I M or IV

administration it has some side effects

that is I am injection will cause pain

and necrosis at the site while IV

injection will cause thrombophlebitis

both because these are alkaloids and

they are naturally irritant regarding

adverse effects a queen in a causes dose

dependent

accessories they can include synchronism

which is very well known hypoglycemia

and hypertension Quinlan also causes a

release of insulin increased release of

insulin and thus can lead to

hypoglycemia another hypersensitivity

reaction is Blackwater fever which is

characterized by hemolysis and then

ultimately hemoglobin emia and

hemoglobinuria this can also lead to

renal failure

it should also not be given with

mefloquine but for different reason that

is it will increase the risk of cardio

toxicity Queenan is mostly used used for

an acute attack of malaria but not for

prophylaxis because of its severe side

effects and is also safe in pregnancy

the next drug is a Tubba cone which

apart from being a blood schisandra

seidel agent is also effective against

the liver stages that is the pre

electrostatic forms of Plasmodium

falciparum it is thus used for

prophylaxis of chloroquine resistant

falciparum malaria and also in the

treatment of some opportunistic

infections associated with HIV patients

that is Pneumocystis arrow etsy

pneumonia and also toxoplasmosis gandhi

i a Toa cone is contraindicated in

pregnancy the next drug is primaquine

which is also a clue quinolone

derivative it is not a blood stress

don't recycle agent unlike the previous

ones that we have discussed but it acts

on both the stages of the liver forms

and thus can be used for radical cure

because it will get rid of the hypnosis

as well it also has marked chemita

seidel activity and thus will help

prevent the spread of disease it is also

used in terminal prophylaxis of

Plasmodium vivax and avail because as i

said both of them have hypno so it forms

in the liver regarding its side effects

it can cause hemolytic anemia in g6pd

deficiency because of the oxidative

stress metamour globin emia and

also it is contraindicated in pregnancy

the next queen helene derivative is

mefloquine like winning it is also a

highly effective blood serum to side but

it does not have any effect on the

hepatic forms and also no gamete recital

activity its mechanism fraction is the

same as all queens it can be given

orally but not parentally because it is

an irritant it's half-life is very long

that's about three weeks because it

undergoes in Tara hepatic recycling

after being secreted in the bile it is

mainly used for prophylactic purposes of

chloroquine resistant of beef Elsa

Parham and also in vivax side effects of

mefloquine are mainly related to

neuropsychiatric symptoms and seizures

it is thus contraindicated in epileptic

patients and those with psychiatric

disorders although it is safe for use in

young children that are suffering from

malaria lastly we have deaf no Queen

which apart from being a blood Shazahn

to seidel agent also has activity

against the latent tissue forms that is

the hypnotoad form of py backs it also

has a great as has a long half-life

there is about 15 to 19 days and thus

can be used alone as a single anti

relapse agent

coming to the artemisinin sand their

derivatives first thing to remember is

that they are not used prophylactically

they have a short half-life that's why

and they should not be used alone as

monotherapy because they will they have

the risk of developing resistance

artemisinin x' are used in artemisinin

based combination therapy and it can be

used against uncomplicated p falciparum

malaria and also severe malaria which is

a medical emergency

these drugs are of two types one of the

artemisinin and it's semi synthetic

derivatives while the other are

synthetic derivatives the first type

include dye hydro artemisinin artem

ether artesunate and alte ether the dye

hydro artemisinin can be given orally

and has a short half-life of about two

hours altimeter can be given both orally

and I am artisan eight is given oral I M

IV and as well as by rectal root and RT

ether is given I am and has a long

half-life these artemisinin x' act on

the blood stages of the Plasmodium and

they are highly active they also have

chemita seidel activity but they do not

have any effect on the hepatic stages

and thus cannot be used alone to

eradicate the infection altogether the

mechanism of action by which they cause

this effects is by generating free

radicals in the acid vacuole of the

parasite which will then damage the

lipid and proteins and thus lead to the

cell death artesunate has a property of

auto induction and thus it will enhance

its own metabolism side effects are

usually mild GI disturbances neutropenia

and also prolongation of QT interval

leading to cardiac arrhythmias such as

tosod rhythm the synthetic derivative or

of artemisinin is arturo lane

which also acts on the S era through

civic stages of the parasite and it is

more important with the rapid onset and

a short duration of action it is usually

combined with purpura Queen and has been

found effective for the treatment of

Plasmodium falciparum malaria coming to

the era el alcohol derivatives we have

one drug that is lumefantrine and it is

active against the era through setec

stages of all species of malaria

parasite and it is usually given in the

treatment of p falciparum malaria in

combination with our Demeter

next we have the anti folates now we

have already discussed these in the

nucleic acid synthesis inhibitor

antibiotics

these are pyrimethamine sulphur Daxing

DEP zone if you remember from the

leprosy of video and prog 1l all of

these who are blood schisandra Seidel

agents coming to Prague one L or

chloroquine ID it is a prodrug

prog 1l for a pro drug and it is a

slow-acting blood Shanta side for all

those four species of plasmodia but also

has activity against the primary hepatic

stages of p falciparum it rarely causes

side effects so it is a wide margin of

safety and if it does they might be

hematuria and skin rashes coming lastly

to the anti microbials we have

tetracyclines and clindamycin among the

tetracyclines we can use doxycycline for

chemo prophylaxis of multi

drug-resistant strains of malaria and if

tetracyclines are contraindicated

because they are contraindicated in

pregnancy and children then we can use

clindamycin both of them are slow acting

blood issues on to seidel agents and do

not have any effect in the hepatic

stages they are usually used in

combination therapy that's all