Heart and Circulatory system

Hypertension

high blood pressure, cause blood vessel damage, cause vision lost/ stroke/ heart attack/ kidney failure

Indian Snakeroot (Rauvolfia serpentina)

shrub, periwinkle (apocynaceae) family, native regions of India and southeast Asia, root used medically, tranquilizer, active agent inole alkaloid reserpine

historic use of Indian snakeroot

calming effect, treat mental disorders and agitations, soothe babies, written about in Charaka Samhita

reserpine

indole alkaloid, from indian snakeroot, used treat hypertension/psychos, prescription tranquilizer for anxiety

M. Greshoff

german chemist, reported Rauvolfia species had physiologically-active alkaloid

S and R. H siddiqui

indian chemist, chamical analysis of Snakeroot, demonstareted hypotensive activity (reduce blood pressure), discovered sedative effect

Reserpine mode of action

deplete stores of neurotransmitters (serotonin/norepinephrine/ epinephrine/dopamines), insight in role of brain amines (neurotransmitters) in mental disorders, not a cure must be taken regularly

combination with reserpine

thiazide diuretic, vasodilator

Cardiotonic

tonic (strengthing) effect on heart

Foxglove (Digitalis purpurea)

poisonous, leaf used medical, active agent cardiac glycosides digoxin/digotoxin

Dropsy

main caus eof death in europe, accumulation of bodily fluid (edema) in body cavity/limbs, grotesque swelling caused by weakened heart, compromised kidneys, leads congestive heart failure

William Withering

medical botanist, wrote Botanical arrangement of all vegetables naturally growing in great britain, develop clinical trails

folk history of foxgloves

spread by word of mouth, herbal only recognized as poisonous, william withering note female herbalist used leaves to treat dropsy

Digoxin and digitoxin

cardiac glycosides, from foxgloves, treat incurable disease of heart/circulatroy system, treat congestive heart failure caused by hypertension and arteriosclerosis, restore and maintain normal heart rhythm, increasing contractability/strength heart

Digoxin

widley prescribed cardiotonic drug

semi synthetic digital drugs

lanatoside C, acetyldigitoxin, delanoside

Digitalis drugs

provides temporary relief, taken regularly over lifetime, adverse side effects (nausea/excess salivation/headache/fatigue)

Quinine/ Peruvian bark (Cinchona calisaya)

genus Cinchona, tree, native south america and central america, used bark, active agent quinoline alkaloids Quinine

historic use of Quinine

bark used by peruvian, fever remedy

history of quinie use as anti malaria

known as Jesuits/Lugo powder, wasn;t use due to anti-caltholic rhetoric, Talbor used as secret ingredient, wide spread use upon talbor death/waning anti-catholic sentiment

John De Lugo

Spanish Jesuit Cardinal, popularized Cinochona bark as anti-malarial

Robert Talbor

treat malaria with secret recipe, cured king charles, agreement with king louis to release secret recipe upon his death, recipe was powdered quinine bark at correct does

Quinine production history

many plantation attempted to be established, most less then 3% concentrations, Dutch plantation in Java (indoesia) bought seed of 8-13% concentration quinine species from Charles Ledger (got from Manuel Incra Mamani), graft onto stronger roots, dutch monopoly(Kina Bureau) on until WW2

Charles Ledger

befriend Manuel Incra Mamani, bought high yielding Cinchonia tree, sold to dutch 

Manuel Incra Mamani

native Bolivain, sold charles ledger high-yeilding Cinochona tree see(illegal), died in jail

Kina Bureau

set global quotas and prices for quinine, run by Dutch

Why dutch lost quinine monopoly

insecticide DDT reduced malaria, synthetic anti-malarial drugs, independence of Java (from japanese invasion), United states established cinochona plantations

Mepacrine

synthetic anti-malarial drug, developed by bayer

Malaria life cycle

female Anopheles inject Plasmodium sporozoites into blood, invades liver cells and divide, rupture releasing merozoites into blood/invade RBC, produce gametocytes, misquito bites infected and carries parasite to next

Malaria symptoms

release merozoites every 12-60 hours, bouts of fever/chills/sweating,liver and spleen swollen, anemia may occur

Malaria

debilitating/deadly disease, caused by parasitic protozoans (genus Plasmodium) originated in Africa, 4 species (malariae, vivax, ovale, flaciparum), all but malaria exclusively affect humans, flaciparum most pathogenic, transmitted by female anopheles mosquitoes, often self limiting, deadly when invades CNS

Quinidine 

stereoisomer of quinine, quinoline alkaloid, anti-malarial drug, treat atrial fibrillation

semi synthetic quinolines

chloroquine, hydrochloroquinem lumefanterine, mefloquine

Chloroquine

semi synetheic quinolic alkaloids, higher activity and lower toxicity than quinine, resistant to it has developed

Hydrochloroquine

semi synthetic quinolines alkaloid, treat lupus erythematosus (auto immune disease)

lumenfantrine and mefloquine

synthetic anti malarial quinolines, very effective, unpleasant side effects, toxic to some

rtenusubub, Qinghao, sweet wormwood (artemisia annua)

annual herb, Aster (asteraceae) family, native southern asia and eastern europe, active agent sesquiterpenoid lactone artemisinin

Artenisinin

sesquiterpenoid lactone, from sweet wormwood, anti-malarial, highly effective at killing plasmodum but only last few hours

Artemsinin combination therapy (ACT)

combines artemisinin with longer acting synthetic quinoline lumefantrine, cure rate > 90% for treatment over 3 days, expensive

how attempting to make artemsinin less expensive

synthetic artemisinin using genetically engineered yeast to produce artemisinic acid (precursors)