chuka_lis

Какие же на современном этапе развития медицины у нас есть лекарства, чтобы бороться с лихорадкой Эбола?
Есть несколько препаратов (преимущественно экспериментальных), и несколько подходов, с различной степенью эффективности.

Многоoбещающие препараты -

GS-5734, вещество, представляющее собой нуклеотидный аналог, производимоей фарм-компанией Гилеад (США), сначала показало хороший результат " в пробирке" (в культуре)-
GS-5734 was discovered as part of Gilead’s program to screen compounds in its libraries for activity against a range of potential emerging viruses, including Ebola. In collaboration with the Centers for Disease Control and Prevention (CDC) and the United States Army Medical Research Institute of Infectious Diseases (USAMRIID), the company identified GS-5734 in vitro activity against the Ebola virus.
а затем прекрасно себя зарекомендовало в экспериментах на макаках -100% инфицированных лихорадкой Эбола обезьян вылечились после приема этого препарата на 3 день. Компания "отчиталась" об этом в октябре 2015 года "Gilead Sciences, Inc. (NASDAQ:GILD) today confirmed that the company fulfilled a request for compassionate access to GS-5734, a novel nucleotide analogue in development for the potential treatment of Ebola Virus Disease (EVD)";
так же лондонская пациентка получила это лекарство и выздоровела. Эта компания занимается разработкой противовирусных препаратов "исторически", выпустила на рынок лекарства от гриппа, СПИДа, гепатита. Компания планирует проводить первую стадию клинических испытаний препарата (общей безопасности и фармакокинетики для человека). Надежда на хороший препарат есть, хотя, как видим, это очень раннее лечение, "при первых симптомах".

Зидмапп (Zmapp) - представляющий из себя смесь трёх моноклональных антител против вируса, производимых 2мя лабораториями- 2 антитела the Public Health Agency of Canada's National Microbiology Laboratory (NML), и третье- and the third at the U.S. Army Medical Research Institute of Infectious Diseases; the cocktail was optimized by Dr. Gary Kobinger, the recently-departed branch chief of the NML and is undergoing further development under license by Mapp Biopharmaceutical.
с 27 февраля 2015 они вроде бы проходят клинические испытания в США и Либерии. Эти иммуноглобулины помогли 2мамериканским врачам, заразившимся вирусом в ходе спасательной миссии в Африке, но оказались бессильны в борьбе за жизнь либерианского доктора и испанского пастора (это из того, что известно публике). То, что их исследования продолжа.тся, обнадеживает- значит, они пока перспективны. Однако, этот коктейль из антибиотиков является чоень дорогой штукой и проивзодство нескольких "доз" его занимает продолжительное время.

Препарат BCX4413, РНК ингибитор РНК-полимеразы,
has demonstrated broad-spectrum activity in vitro against more than 20 RNA viruses in nine different families, including filoviruses, togaviruses, bunyaviruses, arenaviruses, paramyxoviruses, coronaviruses and flaviviruses. BioCryst is developing BCX4430 in collaboration with U.S. Government Agencies following the Animal Rule regulatory pathway. BioCryst is developing BCX4430 in collaboration with U.S. Government Agencies
который разрабатывает компания BioCryst из Северной Каролины, США, the Biomedical Advanced Research and Development Authority (BARDA) within the U.S. Department of Health and Human Services' Office of the Assistant Secretary for Preparedness and Response (ASPR) has awarded BioCryst a contract for the continued development of BCX4430 as a potential treatment for diseases caused by RNA pathogens, including filoviruses.
- еще одна надежда.
Клинические испытания первой фазы начались в декабре 2014 года, по результатам пока не отчитались, хотя предполагали в конце 2015го, но на обезьянах (не человекообразных) препарат себя зарекомендовал хорошо.

Препараты и способы, которые показали спорную эффективность, тоже есть.
Разумеется, отчасти эта эффектиность является спорной потому, что не было проведено "заранее" масштабных научных исследований и испытаний, как из-за высокой опасности вируса, так и из-за экономической бесперспективности подобных разработок (так было актуально до последней эпидемии, когда лихорадка Эбола и прочие филовирусные заболевания изредка поражали жителей Африки, исконно бедных стран).
Да, не смотря на то, что вирус лихорадки Эбола является высокосмертельным, лекарство от него было не то чтобы востребовано на медрынке.
Потому, когда случилась беда, использовали "то, что под рукою", с переменным успехом.
И что же было под рукою?

Как известно, в Африке многие лечатся от СПИДа, потому лекарства борьбы с ВИЧ там есть.
Lamivudine , Ламивудин- антиретровирусный препарат, нуклеозидный аналог ингибитора обратной транскриптазы (это чтоб РНК переводить в формат ДНК, чтоб вирус мог "работать" в клетке), был использован либерийским врачом, чтобы спасать своих пациентов, и из 15 принимавших ламивудин, выжило 13, в то время как в среднем болезнь уносила жизни более чем полвины заболевших.
Dr. Gorbee Logan reasoned that the two viruses, Ebola and HIV, share some similarities in the way they replicate and spread throughout the body.He told CNN in September of 2014 that he'd given the drug to 15 Ebola patients and all but two survived -- this during a time when 70% of Ebola patients were dying in West Africa.
Но, ВОЗ не приняла в расчет его успехи, по какой-то причине,The world's leading experts on Ebola dismissed Logan's experience. About six weeks after CNN's story, WHO issued a statement that "lamivudine has no antiviral activity against [Ebola] and should therefore not be administered for the treatment of Ebola."
В одной из лабораторий попытались проверить эффективность ламивудина против вируса ин витро - с негативным результатом. Далее, другая группа попыталась доказать его активность ин витро и преуспела в этом, однако ВОЗ опять таки отнеслось скептически, эксперты заявили, что, дескать, в таком случае, можно и гомеопатией и змеиным ядом лечить.
История какая-то темноватая, непрозрачная, и, похоже, там какие-то подводные течения, затрагивающие чьи-то интересы, либо научных или медицинских "школ", либо финансовых потоков:

"Stephen McCarthy, a graduate student in the department of laboratory medicine and pathobiology at the University of Toronto. Last spring, McCarthy tried lamivudine in the lab and found that it worked against the Ebola virus. Since he didn't have access to one of the world's few top-level biosafety labs, he had to use a toned-down version of the virus that wasn't infectious and wouldn't get humans sick.

Experts at the NIH and WHO were skeptical of McCarthy's findings, since he didn't use the actual Ebola virus but McCarthy was not deterred.

He and his supervisor, Donald Branch, managed to secure access to Canada's BSL-4 lab, where infectious Ebola can be used. Their new study, published Monday in PLOS Neglected Tropical Diseases, suggests that lamivudine does work against Ebola in the laboratory.

Their study found the drug works even better when paired with another HIV medication, called AZT, or with interferon beta, used to treat multiple sclerosis. The combination of all three drugs was the most effective against Ebola.

The study was co-authored by Thomas Hoenen, an NIH virologist who specializes in hemorrhagic fever viruses such as Ebola, and by Gary Kobinger, a widely respected Ebola researcher who led the animal research on Zmapp.

But leaders at the WHO and NIH were unenthusiastic, because not only did lamivudine not work in the NIH's lab, it also didn't work when they gave it to 12 guinea pigs infected with Ebola. In science, as a general rule, animal studies trump lab studies, but the NIH researchers themselves called their animal work "a small pilot study."

McCarthy said he still thinks lamivudine is worth further study, especially since it's inexpensive, already available in Africa, and has been used safely for decades.

He added that as an HIV researcher, he doesn't understand why authorities continue to study single drugs, rather than combinations. "The greatest success in HIV therapy is combination therapy. No one in HIV would give one drug," he said.

But Hensley and Friede say in their opinion there's no reason at this point to continue studying lamivudine. Friede puts lamivudine in the same category as countless other Ebola "remedies" that people latched onto during the horrific outbreak.

"If we should do further studies on lamivudine, then we should also have done them on homeopathy and snake venom and ozone injections," he said.

я с его заявлением (McCarthy), пожалуй, соглашусь.

Далее, например, противогриппозный и противолихорадочный Фавиправир (Favipiravir), Т-705 или Авиган, дериват пиразинкарбоксамида, производства Toyama Chemical Японии. Он показал себя эффективным против вируса желтой лихорадки, лихорадки Западного Нила, Долины Рифта, энтеровируса ( заболевание ног -рта), альфамирусов, буньявирусов,
флавивирусов, аренавирусов - то есть, довольно широкой группы РНК содержащих вирусов. так почему б не попробовать бороться с филовирусами, тоже РНК? Механизм его работы- тоже блокировка вирусной РНК-зависимосй РНК полимеразы (как и BCX4413).
На мышиной модели он себя неплохо показал, возможно, помог выздороветь французской медсестре, но клинические испытания, проведенные во время вспышки лихорадки Эбола в Гвинее, показали, что у пациентов с лихорадкой средней тяжести и тяжелых, эффекта сниженяи смертности нет. Впрочем, некоторое снижение смертности было в группе "легких" пациентов, или тех, кто начал лечиться пораньше.

Так же, есть еще несколько лекарств, которые, возможно, эффективны.
есть статья 2012 года, где описаны потенциальные подходы к лечению геморрагических лихорадок, включая Эбола:
Viral hemorrhagic fevers: advancing the level of treatment
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325866/

далее, это
интерферон (interferons) -
Исследования показали, что интерферон препятствует, нарушает воспроивзедение и размножение вируса Эбола (впрочем, и ряда других возбудителей болезней- тоже, работа унего такая, стимулировать иммунный ответ и бороться таким образом с врагами), потому у вируса выработалась специальная система блокировки сигналов зараженной клетки на выработку интерферона (и довольно успешно защищается).
"a protein called Ebola Viral Protein 24 (eVP24) stops the interferon-based signals from ramping up immune defenses. With the body's first response disabled, the virus is free to mass produce itself and trigger the too-large immune response that damages organs and often becomes deadly as part of Ebola virus disease (EVD)."
Так вот, в итоге интерферон не вырыбатывается, борьба с вирусом запаздывает, он размножается, пока не убивает своего хозяина. Если добавить интерферона извне, шансы побороть инфекцию растут.
В связи соп соледней эпидемией лихорадки, учеными были задействованы попытки по использованию интерферона в лечении, и на данном этапе, на сколько известно, результаты по 9 больным обрабатываются и готовятся к публикации.
есть еще
FGI-106 - противо-РНКвирусный препарат широкого спектра действия (bunyavirus, flavivirus and filovirus families), показал эффективность против возбудителей различных геморрагических лихорадок (Денге, Конго-Крымской, Долины Рифта, Хантавирусной). Был опробован на мышиной модели против вируса Эбола как профилактическое и лечебное средство. Но на сколько дело в исследованиях далее- не известно. Вероятно, финансы запели романсы, так как работа про Эбола- 2009 года, до вспышки. Кроме того, даже на мышах, это был скорее профилактических препарат, так как лечить начинали через 1 день после инфицирования.
Кроме того,
Есть опубликованные данные, что пациенты, заболевшие лихорадкой Эбола, которые принимали противомалярийный препарат Артезунат-амодиаквин (Artesunate/Аmodiaquine), препарат группы артемизинов, выживали чаще, чем пациенты, принимавшие другие противомалярийные препараты.
Это тоже, "полевой опыт", так как многие симптомы лихорадки Эбола похожи на малярию в тяжелой форме, то, пока не сделали анализ и не пришли результаты, больные могли получать противомалярийное лечение (впрочем, малярия у них вполне могла быть сама по себе, это Африка, где высокий процент заболевших малярией).
Однако, с уверенностью сказать, помогал ли этот препарат, или другие препараты усугубляли картину, нельзя. Шанс же, что артемизин эффективен не только против паразитов крови, но и против РНК-вирусов, есть. было бы неплохо, если бы как то продолжили исследования в этой области.

Я, кроме того, считаю, что вполне вероятна помощь от донорской крови или плазмы, полученных от переболевших. Они содержат антитела против вируса ( поликлональные), которые могут работать против возбудителя в кровеносной системе и тканях реципиента.

Разумеется, должна быть совместимость по группе крови, и, наверняка играет роль степень поражения, тяжесть течения заболевания у реципиента, как, собственно, и титр антител в крови донора.
Много факторов, которые играют роль в эффективности. Потому, никаких гарантий.
И этот способ был использован в ряде случаев, в попытках спасти заболевших, правда, в итогом 50/50.
В США был отмечен успех:
Infusing an Ebola patient with blood products from an Ebola survivor was a treatment that met with great fanfare and publicity in the United States. Dr. Kent Brantley, the first American Ebola patient, received a transfusion from a Liberian boy, and then donated his own plasma to at least four others: fellow charity worker Dr. Rick Sacra, Dallas nurses Nina Pham and Amber Vinson, and NBC videographer Ashoka Mukpo. Another charity worker, Nancy Writebol, donated her plasma to Dr. Craig Spencer in New York City.
Однако англйиские исследования данных по 84 больным показали неэффективность:
New England Journal of Medicine, which looked at 84 patients who received plasma donations, found it didn't help save lives.

American doctors treating patients in the U.S. all said they could not attribute the recovery of their patients to a single or combination of treatments, and would never know what worked. That several Americans survived after receiving plasma is generally chalked up to the fact that their disease was caught early and they were kept well hydrated, a key factor in surviving Ebola.

тут, впрочем, та же загвоздка, что и с Зид маппом (моноклональные антитела)- он тоже помог не всем, эффективность лечения зависит от стадии и тяжести поражения.

Кроме того, возможно, комбинации противовирусных препаратов разной напрвленности могут оказаться эффективны, так что надежды получить эффективное средство борьбы- есть.

и, в конце,
что пока считается не эффективным в лечении и предотвращении лихорадки Эбола
Бринцидофовир Brincidofovir- противовирусных препарат, эффективный в отношении ДНК вирусов, оказался эффективным в 1 случая заражения и неэффективным во втором, но, в итоге, в средине 2015 были начаты клинические испытания второй фазы в Либерии, к сожалению, то есть к счастью, там эпидемия ка краз подошла к концу, и больных не оказалось, затем попытались довести в Сьерра Леоне, однако производитель счел неэффективным тратить средства и прекратил испытания. Впрочем, там была своя "непрозрачная история".

Mukpo, the NBC camerman, was given Brincidofovir. The experimental drug has worked for some patients with various viral infections, but a study on brincidofovir and Ebola ended abruptly last year.Chimerix, the U.S. company that makes it, withdrew its drug from the trial without clearly explaining why, according to Martin Friede, who leads the World Health Organization's coordination of Ebola treatment research.The cancellation of the much-heralded study was "embarrassing," Friede said. But he added that it taught the research world a lesson: Don't start studies with human beings based on thin evidence that the drug might work. "The trials were started based on a single piece of data, and one piece of data isn't sufficient," he said.

ТКМ-Эбола, показавший результаты в моделях, разрешенный ко второй фазе клинчиеских испытаний, в Африке, но показавший себя неэффективным для лечени ялюдей ввиду чего испытания прекратили.
TKM-Ebola is an experimental antiviral drug for Ebola disease being developed by Arbutus Biopharma (Former name: Tekmira Pharmaceuticals Corp.) in Vancouver, Canada. It was formerly known as Ebola-SNALP

ДжейК-05 китайского производства, JK-05 is a broad-spectrum antiviral drug developed by the Chinese company Sihuan Pharmaceutical along with the Chinese Academy of Military Medical Sciences.

Триазавирин Triazavirin российского производства (пока только исследуется на потенциальную эффективность против клещевого энцефалита, лихрадки Ласса, лихорадки Эбола)

Caffeine or 1,3,7-Trimethyl-1H-purine- 2,6(3H,7H)-dione, or 1,3,7-trimethylxanthine, or Guaranine, or Methyltheobromine, or Theine (C₈H₁₀N₄O₂) is consumed by up to 90% of people in the world in one form or another, but mostly in beverages. It is a naturally occurring substance found in the leaves, seeds, and fruits of more than 60 plants, including:

Coffee

Guarana

Tea leaves

Mate

Kola nuts

Cocoa beans

Caffeine is a central nervous system stimulant of the methylxanthine class.

Routs of administrations are oral, insufflation, enema, rectal, intravenous.

Caffeine that is taken orally is absorbed by the small intestine within 45 minutes of ingestion and distributed throughout all bodily tissues, it passes quickly into the brain.
It does not collect in the bloodstream or get stored in the body.
It leaves the body in the urine only many hours after it has been consumed. Caffeine's strongest effects are felt for about an hour after taking it, but some effects last 4 to 6 hours .

Biological half life is - 3-7 hr for adults, 65-130 hr - neaonates.

Some people are more sensitive to caffeine than are others.

How you react to caffeine may be determined in part by how much caffeine you're used to drinking. People who don't regularly drink caffeine tend to be more sensitive to its negative effects. Other factors may include body mass, age, medication use and health conditions such as anxiety disorders. Research also suggests that men may be more susceptible to the effects of caffeine than are women.

In the U.S., the average person drinks 200 milligrams a day (about two 8 ounce cups of coffee).

Beverage/Food	Serving Size	Average Amt. (mg)	Range (mg)
Brewed Coffee	8 ounce	85	65-120
Instant Coffee	8 ounce	75	60-85
Decaf, Brewed	8 ounce	3	2-4
Decaf, Instant	8 ounce	3	1-4
Espresso	Single 2 ounce	80	60-100
Cappuchino/Latte	2 ounce	80	60-100
Moccachino	2 ounce	90	70-110
Black Tea	8 ounce	40	30-60
Decaf Black Tea	8 ounce	4	<5
Green Tea	8 ounce	40	30-50
Iced tea mix, unsweetened	8 ounce	13
Iced tea, ready to drink	8 ounce	30
Cocoa beverage	5 ounce	5	2-20
Chocolate Milk	8 ounce	5	2-7
Dark chocolate, semi-sweet	1 ounce	20	5-35

The American Congress of Obstetricians and Gynecologists (ACOG) and the UK Food Standards Agency concluded that caffeine consumption is safe up to 200 mg per day in pregnant women.

For kids,
Health Canada recommends a maximum daily caffeine intake of no more than 2.5 milligrams per kilogram of body weight. Based on average body weights of children, this translates to the following age-based intake limits:

Age range	Maximum recommended daily caffeine intake
4–6	45 mg (slightly more than in 12 oz of a typical soft drink)
7–9	62.5 mg
10–12	85 mg (about ½ cup of coffee)

Caffeine is one of the most commonly used stimulants among athletes. Taking caffeine, within limits, is allowed by the National Collegiate Athletic Association (NCAA). Urine concentrations over 15 mcg/mL are prohibited. It takes most people about 8 cups of coffee providing 100 mg/cup to reach this urine concentration

The following doses have been studied in scientific research:

BY MOUTH:

For headache or improving mental alertness: 250 mg per day.

For tiredness: 150-600 mg.

For improving athletic performance: 2-10 mg/kg or more has been used. However, doses in excess of 800 mg per day can result in urine levels greater than the 15 mcg/mL allowed by the National Collegiate Athletic Association.

For weight loss: the ephedrine/caffeine combination products are commonly dosed 20 mg/200 mg three times per day.

For headache after epidural anesthesia: 300 mg.

For preventing gallstone disease: intake of 400 mg or more of caffeine per day.

For preventing Parkinson’s disease: men drinking 421-2716 mg of total caffeine daily have the lowest risk of developing Parkinson's disease, when compared to other men. However, men who drink as little as 124-208 mg of caffeine daily also have a significantly lower chance of developing Parkinson's disease. In women, moderate caffeine intake per day (1-3 cups of coffee per day) seems to be best.

One cup of brewed coffee provides from 95-200 mg of caffeine. An 8-ounce serving of black tea provides from 40-120 mg of caffeine. An 8-ounce serving of green tea provides 15-60 mg of caffeine. Soft drinks such as cola provide from 20-80 mg of caffeine per 12 ounce serving. Sports or energy drinks typically provide from 48-300 mg of caffeine per serving.

INTRAVENOUS:

Caffeine is given intravenously (by IV) by healthcare providers for breathing problems in infants and for headache after epidural anesthesia.

Caffeine is selled for medical use in tablets (No-Doz, Vivarin, etc), mints, dissolvable caffeine strips, lip balm, cream, powder(pouches), rectal suppositories.

Up to 400 milligrams (mg) of caffeine a day appears to be safe for most healthy adults. That's roughly the amount of caffeine in four cups of brewed coffee.

The caffeine molecule is structurally similar to adenosine, and is capable of binding to adenosine receptors on the surface of cells without activating them, thereby acting as a competitive antagonist at all adenosine receptor subtypes (A1, A2A, A2B, and A3 receptors).
Antagonism at these receptors stimulates the medullary vagal, vasomotor, and respiratory centers, which increases respiratory rate, reduces heartrate, and constricts blood vessels.
Adenosine receptor antagonism also promotes neurotransmitter release (e.g., monoamines and acetylcholine), which endows caffeine with its stimulant effects; adenosine acts as an inhibitory neurotransmitter that suppresses activity in the central nervous system. Heart palpitations are caused by blockade of the adenosine A1 receptor.

Caffeine is an inositol triphosphate receptor 1 antagonist and a voltage-independent activator of the ryanodine receptors (RYR1, RYR2, and RYR3). It is also a competitive antagonist of the ionotropic glycine receptor.
Caffeine, like other xanthines, also acts as a phosphodiesterase inhibitor. As a competitive nonselective phosphodiesterase inhibitor, caffeine raises intracellular cAMP, activates protein kinase A, inhibits TNF-alpha^[ and leukotriene synthesis, and reduces inflammation and innate immunity. Caffeine is also significantly implicated in cholinergic system where it e.g. inhibits enzyme acetylcholinesterase.

Also, caffeine is metabolized in the liver by the cytochrome P450 oxidase enzyme system, in particular, by the CYP1A2 isozyme, into three dimethylxanthines,^[128] each of which has its own effects on the body:

Paraxanthine (84%): Increases lipolysis, leading to elevated glycerol and free fatty acid levels in blood plasma.

Theobromine (12%): Dilates blood vessels and increases urine volume. Theobromine is also the principal alkaloid in the cocoa bean (chocolate).

Theophylline (4%): Relaxes smooth muscles of the bronchi, and is used to treat asthma.

Otherwise,
Caffeine works by stimulating the central nervous system (CNS). Caffeine causes increased neuron firing in the brain which the pituitary gland perceives as an emergency and therefore causes the adrenal glands to release adrenaline. Caffeine also increases dopamine levels -- the neurotransmitter that is affected by drugs like amphetamines and heroin. Obviously, it does this on a much reduced level from those drugs, but this may be the source of caffeine's addictive quality.
While caffeine is mildly addictive, it has not been shown to have a direct link with any serious health risks.
Caffeine is most commonly used to improve mental alertness, it is used to reduce physical fatigue and to prevent or treat drowsiness. It produces increased wakefulness, improved thought-processing, increased focus, and better general body coordination. Caffeine is a mild cognition enhancer. At normal doses, caffeine improves memory in learning and sleep deprived activities, but has both beneficial and harmful effects on the working memory depending on the nature of the task.

Caffeine can increase blood pressure and cause vasoconstriction, temporarely, but might not have this effect in people who use it all the time.

Caffeine can temporarily speed the heart rate afterwards, and stimulate muscles to work better.
It can affect gastrointestinal motility and gastric acid secretion,
increases basal metabolic rate in adults.

Caffeine is a diuretic. Caffeine prompts the body to lose water through urination (acutelly, but nor chronically). This increase is due to both a diuresis (increase in water excretion) and a natriuresis (increase in saline excretion); it is mediated via proximal tubular adenosine receptor blockade. But again, it may not have this effect in people who use caffeine regularly. Also, drinking caffeine during moderate exercise is not likely to cause dehydration.

Caffeine in low doses may cause weak bronchodilation for up to four hours in asthmatics.

Caffeine is effective for:

Migraine headache. Taking caffeine by mouth together with painkillers such aspirin and acetaminophen or ergotamine is effective for treating migraines. Caffeine is an FDA-approved product for use with painkillers for treating migraine headaches.

Headache following surgery. Using caffeine by mouth or intravenously (by IV) is effective for preventing headaches following surgery. Caffeine is an FDA-approved product for this use in people who regularly consume products that contain caffeine.

Tension headache. Taking caffeine by mouth in combination with painkillers is effective for treating tension headaches.

It is also used with painkillers for simple headaches and preventing and treating headaches after epidural anesthesia.

Likely Effective for:

Mental alertness. Research suggests that drinking caffeinated beverages throughout the day keeps the mind alert. Combining caffeine with glucose as an “energy drink” seems to improve mental performance better than either caffeine or glucose alone.

Possibly Effective for:

Asthma. Caffeine appears to improve airway function for up to 4 hours in people with asthma.

Athletic performance. Taking caffeine seems to increase physical strength and endurance and might delay exhaustion. It might also reduce feelings of exertion and improve performance during activities such as cycling, running, playing soccer, and golfing. However, caffeine does not seem to improve performance during short-term, high-intensity exercise such as sprinting and lifting.

Diabetes. Drinking beverages that contain caffeine is linked with a lower risk of developing type 2 diabetes. It appears that the more caffeine that is consumed, the lower the risk. Although caffeine might help prevent type 2 diabetes, it might not be effective in treating type 2 diabetes. Research on the effects of caffeine in people with type 1 diabetes is inconsistent. Some research shows benefit, while other research does not.

Gallbladder disease. Drinking beverages that provide at least 400 mg of caffeine daily seems to reduce the risk of developing gallstone disease. The effect seems to be dose-dependent. Taking 800 mg of caffeine daily seems to work best.

Low blood pressure after eating. Drinking caffeinated beverages seems to increase blood pressure in older people with low blood pressure after eating.

Memory. Taking 200 mg of caffeine by mouth daily seems to improve memory in some people with outgoing personalities and college students.

Breathing problems in infants. Caffeine given by mouth or intravenously (by IV) appears to improve breathing in infants born too early. It seems to reduce the number of episodes of shortness of breath by at least 50% over 7-10 days of treatment. However, caffeine does not seem to reduce the risk of premature infants developing breathing problems.

Pain. Research suggests that taking caffeine together with painkillers can reduce pain.

Parkinson’s disease. Some research suggests that people who drink caffeinated beverages have a decreased risk of Parkinson’s disease. However, this reduced risk is not observed in people who smoke cigarettes.

Headache after epidural anesthesia. Taking caffeine by mouth or intravenously (by IV) seems to help prevent headache after epidural anesthesia

Weight loss. Taking caffeine in combination with ephedrine seems to help reduce weight, short-term. Taking 192 mg of caffeine in combination with 90 mg of ephedra daily for 6 months seems to cause a modest weight reduction (5.3 kg or 11.66 pounds) in overweight people. This combination, along with limiting fat intake to 30 percent of calories and moderate exercise, also seems to reduce body fat, decrease “bad” low-density lipoprotein (LDL) cholesterol, and increase “good” high-density lipoprotein (HDL) cholesterol. However, there can be unwanted side effects. Even in carefully screened and monitored otherwise healthy adults, caffeine/ephedra combinations can cause changes in blood pressure and heart rate.

Caffeine creams are applied to the skin to reduce redness and itching in dermatitis.

Possibly Ineffective for:

Attention deficit-hyperactivity disorder (ADHD). Most research suggests that caffeine does not reduce ADHD symptoms in children. The use of caffeine in adolescents and adults with ADHD has not been studied.

Insufficient Evidence for:

Depression. Some research suggests that caffeine intake is linked with an increased occurrence of depression symptoms in children. However, other research suggests that caffeinated coffee intake is linked to a decreased occurrence of depression in adults.

Low levels of oxygen in the blood caused by exercise. Early research shows that taking caffeine may improve breathing during exercise, but does not affect blood levels of oxygen in athletes with low blood oxygen levels during exercise

Hepatitis C. Research suggests that higher intake of caffeine from coffee is linked to reduced liver scarring in people with hepatitis C.

Headaches while sleeping. Some early evidence suggests that drinking a cup of coffee before bed or upon waking up might help alleviate pain associated with headaches that occur during sleep.

Cramping due to narrowed arteries (intermittent claudication). Taking a single 6 mg dose of caffeine by mouth seems to improve walking and muscle strength in people with aching and cramping due to narrowed or blocked arteries.

Liver cirrhosis. Research suggests that drinking coffee might reduce the risk for liver cirrhosis. However, it is unclear if this effect is due to caffeine or other components of coffee.

Muscle soreness during exercise. Evidence on the effect of caffeine for muscle soreness during exercise is inconsistent. It seems that taking moderate doses of caffeine (10 mg/kg) can reduce muscle pain during exercise, while lower doses may not have this effect.

Obsessive-compulsive disorder (OCD). Early research shows that adding caffeine to conventional therapy seems to decrease the severity of OCD symptoms.

Stoke. Research shows that increased caffeinated or decaffeinated coffee intake is linked to a decreased risk of stroke in women. However, it is not clear if the effect is due to caffeine.

Skin irritation, redness, and itching.

Overdose.

Other conditions.

Caffeine is LIKELY SAFE for most adults when used appropriately.

Caffeine is POSSIBLY UNSAFE when taken by mouth for a long time or in fairly high doses. Caffeine can cause insomnia, nervousness and restlessness, stomach irritation, nausea and vomiting, increased heart rate and respiration, and other side effects. Caffeine can make sleep disorders in patients with acquired immunodeficiency syndrome (AIDS) worse. Larger doses might cause headache, anxiety, agitation, chest pain, and ringing in the ears.

Caffeine is LIKELY UNSAFE when taken by mouth in very high doses as it can cause irregular heartbeats and even death.

Special Precautions & Warnings:

Children: Caffeine is POSSIBLY SAFE when taken appropriately by mouth or intravenously (by IV), as well as when used in amounts commonly found in foods and beverages.

Pregnancy and breast-feeding: Caffeine is POSSIBLY SAFE in pregnant or breast-feeding women when used daily amounts of less than 200 mg. This is about the amount in 1-2 cups of coffee. Consuming larger amounts during pregnancy or when breast-feeding is POSSIBLY UNSAFE. When consumed in larger amounts during pregnancy, caffeine might increase the chance of miscarriage and other problems. Also, caffeine can pass into breast milk, so nursing mothers should closely monitor caffeine intake to make sure it is on the low side. High intake of caffeine by nursing mothers can cause sleep disturbances, irritability, and increased bowel activity in breast-fed infants.

Anxiety disorders: Caffeine might make these conditions worse. Use with care.

Bipolar disorder: Too much caffeine might make this condition worse. In one case, a 36-year-old man with controlled bipolar disorder was hospitalized with symptoms of mania after drinking several cans of an energy drink containing caffeine, taurine, inositol, and other ingredients (Red Bull Energy Drink) over a period of 4 days. Use caffeine with care and in low amounts if you have bipolar disorder.

Bleeding disorders: There is concern that caffeine might aggravate bleeding disorders. Use caffeine with care if you have a bleeding disorder.

Heart conditions: Caffeine can cause irregular heartbeat in sensitive people. Use caffeine with caution.

Diabetes: Some research suggests that caffeine may affect the way the body uses sugar and might worsen diabetes. However, the effect of caffeinated beverages and supplements has not been studied. If you have diabetes, use caffeine with caution.

Diarrhea: Caffeine, especially when taken in large amounts, can worsen diarrhea.

Epilepsy: People with epilepsy should avoid using caffeine in high doses. Low doses of caffeine should be used cautiously.

Glaucoma: Caffeine increases the pressure inside the eye. The increase occurs within 30 minutes and lasts for at least 90 minutes after drinking caffeinated beverages.

High blood pressure: Consuming caffeine might increase blood pressure in people with high blood pressure. However, this effect might be less in people who use caffeine regularly.

Irritable bowel syndrome (IBS): Caffeine, especially when taken in large amounts, can worsen diarrhea and might worsen symptoms of IBS.

Weak bones (osteoporosis): Caffeine can increase the amount of calcium that is flushed out in the urine. If you have osteoporosis or low bone density, caffeine should be limited to less than 300 mg per day (approximately 2-3 cups of coffee). It is also a good idea to get extra calcium to make up for the amount that may be lost in the urine. Older women with an inherited disorder that affects the way vitamin D is used should use caffeine with caution. Vitamin D works with calcium to build bones.

Major interaction with Ephedrine

Moderate interaction with Adenosine, Quinolone antibiotics, Cimetidine, Clozapine, Dipyridamole, Disulfiram, Estrogens, Fluvoxamine, Lithium, Medications for depression (MAOIs), Medications that slow blood clotting (Anticoagulant / Antiplatelet drugs), Pentobarbital, Phenylpropanolamine, Riluzole, Stimulant drugs, Theophylline, Verapamil

Minor interaction with Alcohol, Birth control pills, Fluconazole, Terbinafine, Antidiabetes drugs, Mexiletine,

You may want to limit your caffeine intake if:

You are prone to stress, anxiety, or sleep problems.

You are a woman with painful, lumpy breasts.

You have acid reflux or stomach ulcers

You have high blood pressure that does get lower with medicine.

You have problems with fast or irregular heart rhythms.

You have chronic headaches.

Side Effects.
Caffeine can lead to:

A fast heart rate

Anxiety

Depression

Difficulty sleeping

Nausea

Restlessness

Tremors

Urinating more often

Vomiting

Stopping caffeine suddenly may cause withdrawal symptoms. These may include:

Drowsiness

Headaches

Irritability

Nausea

Vomiting

Caffeine overdose can result in a state of central nervous system over-stimulation called caffeine intoxication. This syndrome typically occurs only after ingestion of large amounts of caffeine (10 or more gram).
The symptoms of caffeine intoxication are comparable to the symptoms of overdoses of other stimulants: they may include restlessness, fidgeting, anxiety, excitement, insomnia, flushing of the face, increased urination, gastrointestinal disturbance, muscle twitching, a rambling flow of thought and speech, irritability, irregular or rapid heart beat, and psychomotor agitation.^[94] In cases of much larger overdoses, mania, depression, lapses in judgment, disorientation, disinhibition, delusions, hallucinations, or psychosis may occur, and rhabdomyolysis (breakdown of skeletal muscle tissue) can be provoked.
Massive overdose can result in death.
The LD₅₀ of caffeine in humans is dependent on individual sensitivity, but is estimated to be 150 to 200 milligrams per kilogram of body mass (75–100 cups of coffee for a 70 kilogram adult).
Treatment of mild caffeine intoxication is directed toward symptom relief; severe intoxication may require peritoneal dialysis, hemodialysis, or hemofiltration.

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