Transcript over the counter drugs

OTC DRUGS
• ANALGESICS
• ANTI-HISTAMINES
• HERBALS
OVER THE COUNTER DRUGS
SELF MEDICATION IS AN INTEGRAL PART OF HEALTH CARE
TODAY. PEOPLE LIKE TO MEDICATE
THEMSELVES. HOWEVER, SELF MEDICATION IS BEING
PRACTICED TODAY WITH THE DEGREE OF SOPHISTICATION
THAT BELONGS TO THE DARK AGES.
BY DEFINITION, OVER THE COUNTER DRUGS (OTC
DRUGS), ARE THOSE THAT ANYONE CAN BUY WITHOUT A
PRESCRIPTION. THEY ARE SELF PRESCRIBED, AND SELF
ADMINISTERED FOR THE RELIEF OF SYMPTOMS OF A
SELF DIAGNOSED ILLNESS.
ONE ESTIMATE IS THAT EVERY 3 OUT OF 4 INDIVIDUALS
HAVE THE SYMPTOMS OF AN ILLNESS EACH MONTH, BUT
ONLY 1 OF THESE 3 SEEK PROFESSIONAL HELP.
THAT MEANS THAT OTC COMPOUNDS ARE FREQUENTLY
BEING TURNED TO FOR RELIEF.
• OTC PACKAGES MUST CARRY AT LEAST
THE COMMON OR GENERIC NAMES AND
QUANTITIES OF THEIR ACTIVE
INGREDIENTS, AS WELL AS THE AMOUNT
OF ALCOHOL, IF ANY, THEY CONTAIN.
• THE LABELS MUST ALSO INCLUDE
INSTRUCTIONS FOR USING THE DRUG,
INCLUDING SIMPLE DIRECT WARNINGS AND
LIMITATIONS ON THEIR USE, SUCH AS
"DISCONTINUE USE IF PAIN PERSISTS AND
CONSULT A PHYSICIAN."
• THE DIFFERENCE BETWEEN AN OTC DRUG AND
PRESCRIPTION DRUG:
• (FROM FDA) "A DRUG SHALL BE PERMITTED FOR
OTC SALE AND USE BY THE LAITY UNLESS,
BECAUSE OF ITS TOXICITY OR OTHER POTENTIAL
FOR HARMFUL EFFECT OR BECAUSE OF THE
METHOD NECESSARY TO ITS USE, IT MAY BE
SAFELY SOLD AND USED ONLY UNDER A
PRACTITIONERS PRESCRIPTION."
• USUALLY THIS TRANSLATES TO MEAN THAT THE
ONLY DIFFERENCE BETWEEN AN OTC AND A
PRESCRIPTION PRODUCT IS THE GREATER
AMOUNT OF AN ACTIVE INGREDIENT IN THE
PRESCRIPTION DOSE.
• IN 1962, FOOD, DRUG, AND COSMETIC ACT STATED
THAT ALL DRUGS MUST BE EVALUATED FOR
EFFECTIVENESS AS WELL AS BEING SAFE.
• THE PROBLEM WITH ENFORCING THIS ACT IS THAT
NO ONE KNOWS HOW MANY OTC PRODUCTS ARE
ON THE MARKET.
• THE FDA ALSO DOES NOT REQUIRE THE
MANUFACTURER TELL ANYONE, INCLUDING THE
CUSTOMER OR THE FDA, WHEN THERE IS A
CHANGE IN THE INGREDIENTS OR IN THE AMOUNT
OF AN INGREDIENT IN A PRODUCT.
THE FDA ALSO DECIDED ON ANOTHER REGISTRATION CALLED:
GENERALLY RECOGNIZED AS HONESTLY LABELLED: WHICH
STATED THAT LABELLING SHALL BE CLEAR AND TRUTHFUL IN
ALL RESPECTS, AND MAY NOT BE FALSE OR MISLEADING IN
ANY PARTICULAR.
• THE LABEL MUST STATE THE INTENDED
USES AND RESULTS OF THE PRODUCT,
AND ADEQUATE DIRECTIONS FOR PROPER
USE AND WARNINGS AGAINST UNSAFE
USE, SIDE EFFECTS, AND ADVERSE
REACTIONS.
How are we protected? The FDA and its history
In 1929 the US. Post office forced pharmacist Harold Watkins to stop
promoting his lucrative weight loss formula.
Harold was jobless after the stock market crash and throughout the
depression.
He was eventually hired by the S.E.. Massengill company Bristol,
Tennessee. In July 1937 Harold was asked to find a solvent for the new
anti-biotic sulfanilamide.
The drug was very effective against gonorrhea, meningitis and strep
throat. However the tablets were too big and difficult to swallow,
especially for children.
Harold was instructed, as the company's chief chemist, to make it into a
liquid.
Harold chose the solvent diethylene glycol, a sweet syrupy liquid.
Sometimes used as anti-freeze
Harold held a degree in pharmaceutical chemistry but was not aware that this
solvent could be a deadly poison at certain doses.
Harold added to the solution saccharin, caramel, amaranth, raspberry extract.
Harold tasted the concoction himself and with no further tests sent it to the
manufacturing laboratories.
By September 1937 the lab had shipped 240 gallons of "elixir sulfanilamide." By
October of the same year almost 12 gallons had been prescribed.
In that year, 107 children died after taking the elixir.
Samuel E. Massengill insisted his company was blameless, but fired Watkins
anyway. The government could only charge Massengill and his company with
improper labeling since the nation's food and drug law was so feeble at that
time.
Within months the food drug and cosmetic act had cleared both houses and in
June 1938 president Franklin D. Roosevelt signed it into law.
This act is still enforced today and requires drug makers to prove all new
products safe and effective.
On January 10, 1939 Samuel E. Massengill was elected president of the Bristol
chamber of commerce. Watkins, morose at this time, retreated to his home
and read of the election of Massengill. A brief notice appeared in the Bristol
Herald Courier a week later.
"Harold Cole Watkins, 58, retired chemist, was found dead Tuesday morning
in the kitchen of his home, a discharged 38 caliber automatic pistol lying
near his body. He had been shot once through the heart."
DRUG ADVERTISING TENDS TO PRESENT A PAIN, PILL, PLEASURE
MODEL WHICH FUNCTIONS TO VALIDATE AND ENFORCE VALUES,
ATTITUDES, AND BEHAVIOR THAT ENCOURAGE THE MISUSE AND
ABUSE OF SUCH DRUGS.
WHERE IS PAIN?
Kong, J. et al. J. Neurosci. 2006;26:381-388
Copyright ©2006 Society for Neuroscience
• CLASSIFICATION OF PAIN GOES INTO TWO
TYPES DEPENDING ON PLACE OF ORIGIN.
• VISCERAL PAIN, SUCH AS INTESTINAL
CRAMPS, ARISES FROM NONSKELETAL
PORTIONS OF THE BODY.
• NARCOTICS ARE EFFECTIVE IN REDUCING
PAIN OF THIS TYPE.
• SOMATIC PAIN, ARISING FROM MUSCLE OR
BONE, INTENSIFIED BY SPRAINS,
HEADACHES, AND ARTHRITIS, IS REDUCED
BY THE SALICYLATES (ASPIRIN).
• ONE CAN ALSO CATEGORIZE PAIN RELATED TO
TYPES OF NEURONS THAT CARRY THE SIGNAL.
• BRIGHT, SHARP PAIN IS MEDIATED BY LARGE FAST
NEURONS THAT SEEMS TO ACTIVATE THE
INDIVIDUAL, UNTIL ACHING PAIN WHICH
DEPRESSES THE PERSON AND CAUSES ANXIETY
IS MEDIATED BY SMALL, SLOW UNMYLENATED
NEURONS.
•
EXAMPLES TO DIFFERENTIATE THESE TWO: HIT
YOUR THUMB WITH A HAMMER. THE INITIAL
SENSATION IS BRIGHT PAIN, WHEREAS THE
THROBBING EXPERIENCE THAT SOON FOLLOWS IS
DULL PAIN.
• THIRD CLASS OF PAIN EXPERIENCE IS LABELLED
BURNING PAIN. NEURONS INTERMEDIATE IN SIZE
AND SPEED PRODUCE THIS PAIN.
Pain
• THE EXPERIENCE OF PAIN IS
INCREASED WITH FATIGUE, ANXIETY,
FEAR, BOREDOM, AND ANTICIPATION
OF MORE PAIN.
• INTROVERTS ARE GENERALLY FOUND
TO HAVE LOWER PAIN THRESHHOLDS
THAN EXTROVERTS.
• REDHEADS ARE MORE SENSITIVE TO
PAIN THAN BLONDES, WHO ARE MORE
SENSITIVE THAN BRUNETTES.
• Melanocortin-1 receptor
Aspirin
SALICYLATES ARE THE MOST WIDELY USED CLASS OF
INTERNAL ANALGESICS. THE NAME IS DERIVED FROM
THE LATIN SALIX, MEANING WILLOW (FILIPENDULA
ULMARIA).
2400 YEARS AGO, THE GREEKS USED EXTRACTS OF
WILLOW AND POPLAR BARK OR CORIANDER
(CORIANDRUM SATIVUM) IN THE TREATMENT OF PAIN,
GOUT, AND OTHER ILLNESSES.
ARISTOTLE COMMENTED ON SOME OF THE CLINICAL
EFFECTS OF SIMILAR PREPARATIONS.
THESE REMEDIES FELL INTO DISREPUTE WHEN
ST. AUGUSTINE DECLARED THAT ALL DISEASES OF
CHRISTIANS WERE THE WORK OF DEAMONS, AND
THUS THE PUNISHMENT OF GOD.
• THE AMERICAN INDIANS USED A TEA
BREWED FROM WILLOW BARK TO REDUCE
FEVER.
• THE SALICYLATES WERE NOT
REDISCOVERED IN EUROPE UNTIL ABOUT
1763, WHEN AN ENGLISHMAN, REV. EDWARD
STONE, PREPARED AN EXTRACT OF
WILLOW BARK AND GAVE THE SAME DOSE
TO 50 PATIENTS WITH VARYING ILLNESSES
AND FOUND THE RESULTS TO BE
“UNIFORMLY EXCELLENT.”
• IN THE 19TH CENTURY, ACTIVE
INGREDIENTS IN THESE PREPARATIONS
WAS ISOLATED AND IDENTIFIED AS
SALICYLIC ACID.
Aspirin
• IN 1838, SALICYLIC ACID WAS
SYNTHESIZED, AND IN 1859 IT
WAS MADE IN BULK
PRODUCTIONS. AT THAT TIME, IT
WAS PRIMARILY USED FOR THE
TREATMENT OF ARTHRITIS.
• IN 1890, AT BAYER
LABORATORIES IN GERMANY, A
CHEMIST, DR. HOFFMANN
TREATED HIS FATHER FOR
RHUMATORY ARTHRITIS.
• HOWEVER, THE DRUG
PRODUCED GREAT GASTRIC
DISCOMFORT.
• HOFFMANN IN 1898 SYNTHESIZED
ACETYLSALICYLIC ACID. THIS AGENT
PRODUCED RELIEF FROM PAIN WITHOUT
STOMACH UPSET.
• THIS AGENT HAD BEEN ACTUALLY
SYNTHESIZED SOME 45 YEARS EARLIER,
BUT WAS NEVER TESTED CLINICALLY.
• THE COMPOUND WAS TESTED, PATENTED,
AND RELEASED FOR SALE AUGUST 10, 1897
UNDER THE NAME ASPIRIN.
• IN 1915, THE BAYER ASPIRIN APPEARED
FOR THE FIRST TIME, AND ASPIRIN BECAME
A NONPRESCRIPTION ITEM.
• TODAY THERE ARE OVER 300 ASPIRIN
CONTAINING PRODUCTS ON THE
AMERICAN MARKET.
THERAPEUTIC USE
ASPIRIN HAS 3 MAIN EFFECTS:
1. ANALGESIC: BLOCKS SOMATIC PAIN IN THE
MILD TO MODERATE RANGE.
2. ANTIPYRETIC: REDUCES BODY
TEMPERATURE WHEN ELEVATED BY FEVER.
3. ANTI-INFLAMMATORY: REDUCES
INFLAMATION IN AN INJURED AREA. THIS
ACTION IS THE BASIS FOR ITS USE IN
ARTHRITIS.
Mechanism of Action of
Aspirin
ASPIRIN MODIFIES THE CAUSE OF PAIN.
WHEN CELL MEMBRANES ARE DAMAGED OR INJURED,
PROSTOGLANDINS ARE LOCAL HORMONES THAT ARE
RELEASED.
THESE AGENTS ACT ON THE ENDINGS OF NEURONS
THAT MEDIATE PAIN IN THE INJURED AREAS.
PROSTOGLANDINS SENSITIZE THE NEURONS TO
MECHANICAL STIMULATION AND TO STIMULATION BY
HISTAMINE
Mechanism of Action of
Aspirin
ASPIRIN BLOCKS THE SYNTHESIS OF PROSTAGLANDINS.
PROSTOGLANDINS ARE STORED BUT ARE RAPIDLY
SYNTHESIZED AND RELEASED FROM CELLS WHEN INJURY
OCCURS. THEY SENSITIZE NEURONS TO PAIN AND TO OTHER
LOCAL HORMONES.
• THEREFORE NERVE IMPULSES ARE NOT
INITIATED IN THE PAIN PATHWAYS BY
BRADYKYNINS OR HISTAMINE.
• ASPIRIN DOES NOT BLOCK PAIN
PRODUCED BY INJECTIONS OF
PROSTAGLANDINS.
• ASPIRIN'S ANALGESIC EFFECTS ARE ONLY
ON TISSUES WHERE PROSTAGLANDIN
FORMATION OCCURS
• ASPIRIN'S REDUCES BODY TEMPERATURE
(FEVER) BY BLOCKING SYNTHESIS OF
PROSTOGLANDINS IN THE ANTERIOR
HYPOTHALAMUS.
• THE THERAPEUTIC DOSE IS USUALLY
CONSIDERED TO BE BETWEEN 600 TO 1,000
MG; 300 MG. IS USUALLY MORE EFFECTIVE
THAN A PLACEBO OF 600 MG., CLEARLY
EVEN MORE EFFECTIVE.
• ABOVE 600 MG, THE ANALGESIC ACTION OF
ASPIRIN DOES NOT SEEM TO INCREASE,
ALTHOUGH THIS QUESTION HAS NOT BEEN
RESOLVED.
• OLDER PATIENTS NEED LESS ASPIRIN TO
OBTAIN THE SAME BLOCK OF PAIN.
DISTRIBUTION
ASPIRIN CAN BE ABSORBED FROM THE STOMACH,
BUT IS MUCH FASTER FROM THE INTESTINE.
THEREFORE, ANYTHING THAT DELAYS THE
MOVEMENT OF ASPIRIN FROM THE STOMACH
WOULD EFFECT ABSORPTION TIME.
MEALS TEND TO DELAY EMPTYING OF THE
STOMACH, AND THEREFORE MAY DELAY THE
ONSET OF ACTION.
A WATER SOLUTION OF ASPIRIN IS MORE RAPIDLY
ABSORBED THAN THE TABLET FORM, THUS GIVING
HIGHER AND EARLIER EFFECTIVE BLOOD LEVELS
OF THE DRUG.
BUT RAPID ABSORPTION DOES NOT CORRELATE
WITH RAPID ANALGESIA.
METABOLISM
ASPIRIN, WHICH IS ACETYLSALICYLIC
ACID, IS CONVERTED EITHER IN THE
GASTROINTESTINAL TRACK OR IN
THE BLOODSTREAM TO ITS ACTIVE
FORM, SALICYCLIC ACID.
TAKEN ORALLY, ASPIRIN IS MORE
POTENT AN ANALGESIC THAN
SALCYLIC ACID, SINCE ASPIRIN
IRRITATES THE STOMACH LESS AND
IS ABSORBED MORE RAPIDLY.
METABOLISM
• IT IS INTERESTING TO COMPARE TWO
COMPOUNDS INTRODUCED BY BAYER
LABORATORIES IN GERMANY AT THIS
TIME.
• BOTH ARE RAPIDLY TRANSFORMED TO
THEIR ORIGINAL FORM AFTER
ABSORPTION. HEROIN, WHICH IS
DIACETYLMORPHINE, AND ASPIRIN, WHICH
IS ACETYLSALICYLIC ACID, ARE
CONVERTED EITHER IN THE
GASTROINTESTINAL TRACK OR IN THE
BLOODSTREAM TO THEIR ACTIVE FORMS.
• TAKEN ORALLY, ASPIRIN IS MORE POTENT
AN ANALGESIC THAN SALCYLIC ACID,
SINCE ASPIRIN IRRITATES THE STOMACH
LESS AND IS ABSORBED MORE RAPIDLY.
Acetylsalicylate - Aspirin
LATENCY OF ONSET
INGESTION OF 650 MG TABLET OF ASPIRIN,
HEADACHE AND POSTPARTUM PAIN WERE NOT
REDUCED SIGNIFICANTLY FROM PLACEBO UNTIL
45 MIN HAD ELAPSED.
MAXIMUM RELIEF WAS OBTAINED AFTER 60
MIN. AFTER 4 HRS., PAIN LEVELS WERE
EQUIVALENT IN DRUG AND PLACEBO GROUPS, I.E.,
ANALGESIA WAS GONE.
AT 45 MIN TO 4 HR THE LEVELS OF SALICYLATE IN
THE BLOOD WAS THE SAME. IT WAS DETERMINED,
THEREFORE, THAT THE BLOOD LEVEL OF 30 UG/ML
IS THE THRESHHOLD FOR ANALGESIA.
MAXIMUM RELIEF IS OBTAINED AT 40 UG/ML.
EFFECTIVENESS
ASPIRIN DOES NOT BLOCK ALL TYPES OF PAIN.
IT IS ESPECIALLY EFFECTIVE AGAINST HEADACHE
AND MUSCULO-SKELETAL ACHES AND PAINS,
LESS EFFECTIVE FOR TOOTHACHE AND SORE
THROAT, AND MOST USELESS IN VISCERAL PAIN
AS WELL AS IN TRAUMATIC OR ACUTE PAIN.
ANTIPYRETIC ACTIONS
ASPIRIN DOES NOT LOWER THE TEMPERATURE OF A
NORMAL INDIVIDUAL. ONLY WORKS IN PERSON
WITH FEVER, I.E. LAW OF INITIAL VALUE.
ASPIRINS WORK ON THE TEMPERATURE REGULATING
AREA OF THE HYPOTHALAMUS TO INCREASE HEAT
LOSS THROUGH PERIPHERAL MECHANISMS.
THIS IS ATTAINED PRIMARILY BY INCREASED
VASODILATION OF PERIPHERAL BLOOD VESSELS
AND INCREASED PERSPIRATION.
HEAT PRODUCTION IS NOT CHANGED, BUT HEAT
LOSS IS FACILITATED.
Thermo-regulation of body temperature
Involves autonomic nervous, endocrine, and
skeletomotor systems
Body temperature detectors
Peripheral: skin, spinal cord, viscera
Central: anterior hypothalamus
Body temperature effectors
Heat retention or generation:
posterior hypothalamus
Heat dissipation: anterior hypothalamus
• Heat dissipating mechanisms
– Dilation of blood vessels in the skin
– Inhibition of shivering
• Heat conserving mechanisms
– Vasoconstriction of blood vessels in the
skin
– Shivering
– Increased secretion of thyroxin
Response to Cold
Response to Heat
Aspirin enhances the loss of heat from the body
ADVERSE SIDE EFFECTS
ASPIRIN INCREASES BLEEDING TIME BY INHIBITING
BLOOD PLATELET AGGREGATION. 2 OR 3
ASPIRINS CAN DOUBLE BLEEDING TIME. THIS
EFFECT MAY LAST 4 TO 7 DAYS.
THE RELATIONSHIP BETWEEN ASPIRIN USE AND A
DECREASE IN HEART ATTACKS WAS ORIGINALLY
OBSERVED IN A GROUP OF RHUMATORY
ARTHRITIS PATIENTS.
THESE PATIENTS HAD ABOUT 1/5 AS MANY HEART
ATTACKS AS WOULD BE EXPECTED.
THIS FEATURE OF ASPIRIN HAS BOTH GOOD AND
BAD SIDE EFFECTS. GENERALLY, HOWEVER,
ASPIRIN IS NOT RECOMMENDED 7 TO 10 DAYS
BEFORE UNDERGOING SURGERY.
• SECOND POINT, INJESTION OF ASPIRIN IN DOSES
OF 1 TO 3 GM PER DAY WILL INDUCE ACULT
GASTROINTESTINAL BLEEDING IN ABOUT 70% OF
NORMAL SUBJECTS.
• THIS AMOUNTS TO 5 ML OF BLOOD PER DAY,
WHICH IS 5 TIMES THE NORMAL LOSS OF BLOOD
VIA THE GASTROINTESTINAL TRACK.
• IN SOME PEOPLE, THIS BLOOD LOSS MAY BE
GREAT ENOUGH TO CAUSE ANEMIA.
• BASIS FOR THIS FACT IS BELIEVED TO BE A
DIRECT ERODING BY ASPIRIN ON THE GASTRIC
MUCOSA LAYER. THEREFORE, DRINK LOTS OF
WATER WHEN TAKING ASPIRIN. BETTER YET,
CRUSH THE ASPIRIN AND TAKE THEM IN ORANGE
JUICE OR OTHER LIQUID.
• THIRD POINT, ASPIRIN USE INCREASES THE
NUMBER OF VIRUSES PRODUCED IN SUFFERERS
OF THE COMMON COLD.
• WHAT THIS MEANS IS THAT ASPIRIN IS MORE
LIKELY TO LEAD TO THE SPREAD OF GERMS OR
FOR THE USER TO REINFECT HIMSELF THAN AS A
NON-ASPIRIN USER.
• FOURTH POINT, ASPIRIN IS THE NUMBER ONE
CAUSE OF ACCIDENTAL POINSONING DEATH IN
CHILDREN UNDER 5 YEARS OF AGE.
• HOUSEHOLD PLANTS AND HOUSEHOLD SOAPS
ARE FIRST AND SECOND CAUSES OF NON-FATAL
ACCIDENTAL POISONING IN YOUNG
CHILDREN. ASPIRIN IS THE FIRST CAUSE OF
MORTALITY IN THE YOUNG.
• USUALLY, THE POISONING AGENT IS "BABY
ASPIRIN."
ANTI-INFLAMMATION
• THIS IS THE MAJOR USE FOR ASPIRIN IN THE
NATION. PATIENTS WITH RHUMATORY ARTHRITIS
MAY CONSUME 3,000 MG TO 4,000 MG PER DAY.
LATENCY OF ONSET
• WHEN BUYING ASPIRIN TABLETS, ONE MUST
CONSIDER THAT THE TABLETS DEVELOP A HARDER
EXTERNAL SHELL THE LONGER THEY SIT.
• THIS DOES NOT EFFECT OR CHANGE THE AMOUNT
OF ACTIVE INGREDIENT, BUT IT DOES MAKE THE
ACTIVE INGREDIENT LESS EFFECTIVE BECAUSE
DISINTEGRATION TIME IS INCREASED.
• ALSO, MOISTURE AND HEAT SPEED DECOMPOSITION
OF ACETYLSALICYLIC ACID INTO SALICYLIC ACID
WHICH CAUSES GASTRIC DISTRESS, AND ACETIC
ACID.
• WHEN ASPIRIN BOTTLES SMELL LIKE VINEGAR, THEY
SHOULD BE DISCARDED.
• ACETAMINOPHEN (TYELNOL) IS
EQUIPOTENT WITH ASPIRIN AS AN
ANALGESIC
MECHANISM OF ACTION
• THE ANTIPYRETIC AND ANALGESIC
MECHANISM IS SIMILAR TO THAT OF
ASPIRIN, I.E. BY INHIBITION OF
PROSTAGLANDIN SYNTHESIS.
• ACETAMINOPHEN IS NOT
ANTI-INFLAMMATORY AND THUS IS OF
MINIMAL VALUE IN ARTHRITIS, GOUT,
ETC.
• ACETAMINOPHEN ACUTE TOXICITY CAN
OCCUR IN ADULTS TAKING 7 GM. 14 GM
CAUSE REVERSABLE DAMAGE TO THE
LIVER. MORE THAN 14 GM MAY LEAD TO
HEPATIC COMA, AND POSSIBLY TO DEATH.
• IBUPROFEN IS AN NSAID, OR NONSTEROIDAL ANTI-INFLAMMATORY
DRUG.
• BLOCKS CYCLOOXYGENASE ACTIVITY
- INHIBITION OF PROSTAGLANDIN
SYNTHESIS. EXACT MECHANISM
UPON COX ENZYME IS NOT KNOWN.
• ACTIONS OF ALL NSAIDS
• THEY SUPPRESS THE NOCTURNAL SURGE
IN MELATONIN SYNTHESIS.
• THEY ALSO ATTENUATE THE NIGHTTIME
DECREASE IN BODY TEMPERATURE.
• THESE ALTERATIONS MAY INFLUENCE
SLEEP PATTERNS.
• THEY PRODUCE ADVERSE REACTIONS IN
GI TRACT, E.G. BLEEDING AND
PERFORATION OF BOWELS.
• NEXT GENERATION OF NSAIDS TARGETED
ONLY THE TYPE II CYCLOOXYGENASE
WHICH SHOULD HAVE AFFECTED
INFLAMMATION BUT NOT THE GI TRACT.
COX-2 selective inhibitors are associated with
an increased incidence of serious adverse
events as compared to non-selective NSAIDs.
Anti-Histamines
Histamine containing neurons are a part of
the Brain’s Ascending Arousal Systems
Histamine
Origin: tuberomammillary nucleus of hypothalamus projects widely.
Functions: sleep-wake cycle, arousal.
Antihistamine medications used to treat allergies are thought to cause
drowsiness by blocking CNS histamine receptors.
During NonREM sleep, GABA neurons inhibit histamine
neurons. This reduces histamine activation of forebrain and
reduces activation of cholinergic neurons (like scopolamine).
-leading to sleep.
-Anti-histamines therefore lead to sleepiness.
Many OTC anti-histamines
also block acetylcholine
muscarinic receptors in the
brain.
– also leading to sleepiness.
HERBALS
Gingko: The Single Most Popular
Brain-specific Nutrient.
The theory: as we age, tissue damaging free
radicals become more prevalent and cause
age-related loss of neurons.
• Ginkgo may neutralize these chemicals.
• Gingko may increase function of acetylcholine
neurons.
• Three good research studies with doubleblind design.
• Two smaller studies found that gingko slightly
improved memory.
Gingko: The Single Most Popular
Brain-specific Nutrient.
Patients had significant memory problems
caused by mild to moderate AD or strokerelated dementia.
Almost two-thirds of patients did not
complete the first study. If all the subjects
had completed the study the authors
speculated that the effects would have
washed out.
Overall, the improvement in cognitive
function scores are small, variable and
required 4-6 weeks to appear.
• Use of Ginkgo Biloba can be traced back
centuries in Chinese traditional medicine
• Most widely-used herbal treatment for
cognitive functions – memory, learning,
alertness
• Approved in Germany for dementia
treatment
• NIH is supporting a clinical trial of Ginkgo
Biloba in Alzheimer's
• Typical dose (used in many experiments) is 120
milligrams of dried extract in two or three oral
doses.
• Extract in German product is named EGb 761,
manufactured by Schwabe Pharmaceuticals.
• The extract contains
– flavonoids and biflavonoids, a large group of natural
plant products
– terpenes (active ingredients in catnip and marijuana)
• Dozens of clinical trials have examined the
cognitive effects of gingko in humans.
• Great majority of studies have involved
subjects with mild to moderate impairment,
usually an early diagnosis of Alzheimer's.
• Most experiments test learning and
memory; less often attention, motivation or
anxiety.
• Most subjects were selected and tested long after they
began using gingko, typically several months, so their
cognitive level before using gingko is unknown.
• This may introduce a bias, if those with better cognitive
abilities are more likely to take gingko.
• For example, higher scores on the memory and learning
tests may come from subjects who could read and
understood articles suggesting gingko might help them,
or who were better able remember to take the drug.
• Researchers need to give tests both before and after the
patients start taking gingko, or else the experiment
results are suspect.
• Another recent, large, well-controlled
clinical trial of EGb 761 sponsored by its
manufacturer involved patients with mild or
moderate dementia.
• The results showed no "systematic and
clinically meaningful effect of gingko" on
any of the cognitive tests used.
Improvement in ADAS-cog
Efficacy of Ginko Biloba
4
3
2
1
0
-1 0
12
26
39
52
-2
-3
-4
Weeks of Double-Blind Medication
Le Bars et al. JAMA: 1327, 1997
Placebo (n=157)
24 mg (n=131)
Solomon et al., JAMA, Aug, 2002
Is gingko safe?
• Few health risks at typical doses (120 to
240 milligrams per day)
• Some complications have occurred in
people taking gingko:
– subdural hematomas (blood clots between
skull and brain)
– gastrointestinal problems
– nausea and vomiting
Scientific American, April, 2003
Potatoes, tomatoes &
Eggplants
Contain two solanaceous glycoalkaloids:
a-Solanine and α-chaconine
Inhibit acetylcholinesterase and
butyrylcholinesterase leading to an elevation of
synaptic levels of acetylcholine.
GINSENG
Widely used to improve overall energy
and vitality, particularly during times of
fatigue or stress.
While there is not much clinical
evidence to support an energy
boosting effect, there are studies
showing its potential value in
normalizing glucose levels after meals
in diabetics, stimulating immune
function and symptoms of attention
deficit-hyperactivity disorder (ADHD)
in children.
Ginsenosides may underlie ginseng's
bioactivity.
Polluted and Diluted
2003 studies: A high amount of the pesticide
hexachlorobenzene — a potential human
carcinogen — was found in one of five products
labeled as containing "Korean Ginseng."
Levels of two other pesticides, quintozene and
lindane — were also above acceptable levels.
"Chinese Ginseng" labeled "EXTRA STRENGTH"
contained less than 10% of the expected
ginsenosides.
Single doses of Panax ginseng (G115) reduce blood
glucose levels and improve cognitive performance during
sustained mental activity. J Psychopharmacol, 2005; 19: 357
- 365.
Numerous potential mechanisms of action upon a variety of
neural systems, e.g. acetylcholine, bioamines, nitric oxide,
calcium channels and steroids.
The lack of unanimity in the research (on Ginseng use in
humans) can be explained on the basis of various
methodological problems such as inadequate sample size
and lack of double-blind, control and placebo paradigms.
Report to NIH in 2000.
Vinpocetine: Extract From the
Periwinkle Plant
May increase blood flow and circulation in
the brain and increase neuronal glucose
transport and uptake.
• May stimulate the acetylcholine neural
activity.
• May reduce the loss of neurons due to
decreased blood flow (ischemia).
Vinpocetine: Extract From the
Periwinkle Plant
Two good studies:
• Older adults with memory problems
associated with either circulation problems
or mild-moderate dementia.
• Patients given vinpocetine showed modest
to very modest (3 points over 13 wks on the
Mini-Mental) vs placebo for tests measuring
attention &memory.
Vinpocetine: Extract From the
Periwinkle Plant
• In a larger study, 16 wks of therapy gave
patients just a one point gain in memory and
concentration vs. placebo.
• Evidence for cognitive benefits of
vinpocetine is similar to that for Gingko.
Statistically significant improvements in a
only few studies with benefits that are very
modest at best and tend to disappear in
larger studies.
NADH
• NADH is abundant in meat, less so in fruits & vegs.
• NADH levels tend to decrease slightly with aging.
• Open label trial, 17 AD. No controls. 8-12 wks, 10
mg/day, p.o., by Jorg Birkmayer, MD, Austria.
• WEB Site: Within 2 wks, “noticeable improvements
in cognitive function, increased production of
norepinephrine and dopamine.” “remarkable
improvements in cognition” “No negative sideeffects.”
• 1996 Publ: “This represents a pilot study from
which no definitive conclusion can be drawn.”
Patent Holder? Dr. Jorg Birkmayer.
Fava Beans
BBB
L-DOPA is a precursor to
the production of
Dopamine in the brain
OTC Strategies for
Enhancing Cognition Via
Neuroprotectants
• Anti-Oxidants to protect
us from the consequences
of breathing oxygen
Probability of dying from any cause
Data for 1,000,000 people
OXYGEN: A Pro-Aging Molecule
• The risk is simply being alive, e.g.
breathing, eating, exercising…
• 2% of oxygen used in energy metabolism
forms oxygen free radicals that are toxic
and may damage DNA.
• The complement of anti-oxidant systems
your species possesses is directly related
to how long your species lives.
Effect of Caloric Restriction
Fewer cancerous tumors among those on restricted
diets
50
Normal Diet (control group)
Caloric Restrictions
45
40
30
20
15
11
9
10
2.1
0
Hepatoma
1
Lymphoma
All Tumors
Degenerative Diseases
Control Rats vs. Restricted Rats
% Degenerative Disease
100
95
Normal Diet (control group)
Caloric Restrictions
80
75
80
55
60
35
40
25
19
18
20
0
Kidney
Muscle
Heart
Disease Type
Vascular
Vitamin E
Vitamin E is an anti-oxidant that easily
crosses the Blood Brain Barrier.
• The theory: by neutralizing chemicals
that kill neurons, vitamin E may slow
memory decline due to aging or brain
diseases.
• Beneficial Effects of Vitamin E. The
largest and best study on vitamin E
investigated patients with moderate AD.
Vitamin E
• 2000 IU/day delayed by about 9 months
the entry into a nursing home. Patients
did not lose daily living skills as rapidly as
patients given the placebo.
• Vitamin E did not halt the speed of
memory decline!
• FDA has not approved use of vitamin E
for treatment of AD because it did not
slow cognitive and memory decline.
Effects of Vitamin-E and Selegiline on
Institutionalization, Loss of ADLs, StageChange or Death
Percent Event-Free
120
100
80
Placebo
Selegiline
Vitamine E
60
40
20
0
0
100
200
300
400
Days of Study
500
600
700
CAFFIENE
CAFFIENE
(1,3,7-TRIMETHYLXANTHINE) SIMILAR TO PURINE.
COFFEE, CHOCOLATES AND TEA.
IMPORTS INTO USA, CRUDE COFFEE 3,000,000,000
LBS/YR.
HISTORY
USED IN CHINA FOR MEDICAL AND RELIGIOUS
PURPOSES FOR MANY CENTURIES.
THE HISTORY OF COFFEE AND CAFFEINE CONTAINING
BEVERAGES IN THE WESTERN WORLD PROVIDES A
WONDERFUL EXAMPLE ON HOW SOCIETY AND
MEDICINE RESPOND TO MILDLY PSYCHOACTIVE
SUBSTANCES. THE STIMULANT EFFECTS OF CAFFEINE
WERE CALLED A PANACEA AND THE SOLUTION FOR
MAN'S MENTAL STRESS BY MANY; BUT WERE
DENOUNCED BY OTHERS.
WORLDWIDE USE OF CAFFEINE:
S. AMERICANS PREPARE DRINKS FROM MATE LEAVES,
YOCO, AND GUARANA.
W. AFRICANS CHEW ON KOLA NUTS.
IN 1800'S ALL OF THESE WERE FOUND TO CONTAIN
CAFFEINE.
DAILY INTAKE: U.S. 2.5 MG/KG BODY WEIGHT;
EUROPEANS 3.5 MG/KG
OR ABOUT 165 MG/DAY IN U.K.; 246 MG/DAY IN U.S.; OR
465 MG/DAY IN FINLAND.
TODAY, COFFEE COVERS 44 PERCENT OF THE
PERMANENT ARABLE CROPLAND IN NORTHERN LATIN
AMERICA.
INTERPLANETARY: THE APOLLO 11 ASTRONAUTS WERE
DRINKING COFFEE 3 HOURS AFTER LANDING ON THE
MOON.
SOURCE:
CAFFEINE IS FOUND IN AT LEAST 63 PLANT SPECIES,
BUT 54% OF WORLD'S CONSUMPTION DERIVES FROM
TWO DIFFERENT BEANS OF COFFEA ARABICA AND
COFFEA ROBUSTA AND 43% FROM THE TEA PLANT
Camellia sinensis.
C. MAURITIANA AND C. HUMBOLTIANA HAVE NO
CAFFEINE.
DOSE: 1 MG/KG AVERAGE CUP OF COFFEE
INSTANT COFFEE HAS 60-70 MG; BREWED HAS 100 MG; ESPRESSO
(100 MG); DRIP HAS 150 MG; DECAF (2-4 MG).
MINIMUM STIMULANT DOSE IS BETWEEN 85 AND 250 MG.
TEA: BUDS HAVE GREATEST CAFFEINE CONTENT.
BLACK TEA HAS ABOUT 40 MG; GREEN TEA ABOUT 35 MG. DEPENDS
METHOD OF PREPARATION AND VARIETY OF TEA USED. ICED TEA
HAS ABOUT 70 MG. WHITE TEA (STEAMED RATHER THAN
FERMENTED OR ROASTED) MAY CONTAIN MORE.
CHOCOLATE (1 OZ BAR) CONTAINS 75-150 MG OF
METHYLXANTHINE (90% AS THEOBROMINE). HAS LOW LIPID
SOLUBILITY SO WEAK CENTRAL ACTIONS.
EXPRESSO HAS LESS CAFFIENE THAN PEPSI COLA
DUE TO WAY ITS PREPARED AND DRANK
JOLT COLA (100 MG); SUGAR-FREE MR. PIBB (59 MG);
MELLOW YELLOW (52 MG); MOUNTAIN DEW(53 MG),
COKE (45 MG); PEPSI (36 MG).
Coffee is rich in biologically active substances such as trigonelline,
quinolinic acid, tannic acid, pyrogallic acid and, of course, caffeine.
Niacin in particular is formed in great amounts from trigonelline during
the coffee-bean roasting process (Czok, 1977; Casal et al. 2000). The
amount of niacin can vary from 2 to 80 mg/100 g coffee.
Coffee is a rich source of antioxidants (caffeic, chlorogenic, coumaric,
ferrulic and sinapic acids). A by-product of coffee-bean roasting,
silverskin, has marked antioxidant activity.
The caffeine content of caffeinated coffees ranges from 58 to 259
mg/dose. In one study, the mean caffeine content of brewed specialty
coffees was 188 mg for a 16 oz cup. Variability is high. McCusker et al.
(2003) reported a wide range of caffeine concentration (259–564
mg/dose) in the same coffee beverage
obtained from the same outlet on six consecutive days.
EFFECTS ON SLEEP
2 CUPS WILL DOUBLE SLEEP LATENCY WITH 150 MG
DOSES (I.E. A SINGLE CUP OF COFFEE).
100 MG IS MINIMUM DOSE TO DETECT AN EFFECT OF
CAFFEINE.
HEAVY DRINKERS ARE IMMUNE TO THIS SLEEP
LATENCY EFFECT.
CAFFEINE INCREASES STAGE 2 SLEEP TIME,
DECREASES STAGES 3 & 4 SLEEP.
NO EFFECT ON REM (DREAM) SLEEP
Effects of major xanthine derivatives
Major Source
CNS
Heart
Diuretic
Theophylline
Tea
Moderate
Potent
Potent
Caffeine
Coffee
Potent
Moderate
Moderate
Slight
Minimum
Slight
Theobromine Coco nut
Elements found in tea leaves
Aluminum, arsenic, boron,
calcium, copper, iron,
flourine, mercury, iodine,
manganese, molybdenum,
sodium, nickel,
phosphorus, lead,
potassium, selenium,
silicon, sulfur & zing.
Cellular Defense and
Carcinogenesis Section
CH3 O
HO
OCH33
CH=CHCOCH22COCH=CH
Kaempferol, Quercetin
OH
Curcumin, DBM
Galangin
Resveratrol
Diosmetin, Diosmin
CAFFEINE PASSES VERY QUICKLY INTO THE
BRAIN.
BRAIN UPTAKE INDEX (BMI)
NICOTINE
ETHANOL
COCAINE
WATER
CAFFIENE
HEROIN
PHENOBARBITAL
MORPHINE
ASPIRIN
131 (ONLY ONE PUFF)
104
100
100
90
68
22
2.6
1.8
80% OF CAFFIENE IS REMOVED BY BRAIN IN SINGLE
PASS.
CAFFEINE IN CSF REACHES 1/2 ITS PLASMA LEVELS IN 48 MINUTES.
BRAIN LEVELS REMAIN STABLE FOR 1 HOUR.
2 GROUPS OF PEOPLE IN US. 80% WHO USE COFFEE
AND 20% WHO AVOID IT. HIGH CONSUMERS AND LOW
CONSUMERS. RESPOND VERY DIFFERENTLY TO
CAFFIENE.
HIGH CONSUMERS SHOW LESS EFFECT ON SLEEP THAN
LOW CONSUMERS.
PHYSIOLOGY:
ONLY NEED 5 UG/ML INCREASE IN BLOOD LEVEL TO
FEEL EFFECTS.
MOST DRINKERS TITRATE THEIR BLOOD LEVELS FROM
1-3 UG/ML OF CAFFIENE.
10 UMOLAR BRAIN CAFFIENE IS EXPERIENCED BY 80%
OF ALL N.AM PEOPLE FROM EMBRYO TO DEATH.
PEAK LEVELS IN 15-30 MIN AFTER DRINKING FIRST
SIP. I.E. BEFORE THE CUP IS FINISHED USUALLY.
LETHAL LEVEL IS 500 uM IN BLOOD.
LETHAL DOSE IS 5-10 GRAMS, ORAL OR IV. THIS IS
ABOUT 75 CUPS OF COFFEE.
SMOKING INCREASES CAFFIENE HALF-LIFE FROM 3
HRS (I.E. NORMAL) TO 6 HRS.
LITTLE PROTEIN BINDING.
TOLERANCE
DEVELOPS TO SOME PERIPHERAL SYMPTOMS;
SLOWER TO CENTRAL EFFECTS.
DOWNREGULATION OF ADENOSINE TYPE-2-a
RECEPTORS AND UPREGULATION OF ADENOSINE
TYPE-1 RECEPTORS IN AMYGDALA – THE EMOTIONAL
PART OF THE LIMBIC SYSTEM
WITHDRAWAL: HEADACHE - "WEEKEND TENSION
HEADACHES" MAY BE DUE TO LARGE COFFEE INTAKE
DURING WORKWEEK, THEN WITHDRAWAL ON WEEKENDS.
LARGE DOSES: MOOD CHANGES, NERVOUSNESS,
IRRITABILITY, LACK OF ALERTNESS.
1 GM (7-10 CUPS) CAFFIENE: INSOMNIA, WEARINESS,
ANXIETY, RESTLESSNESS, SENSORY DISTURBANCES
SUCH AS RINGING IN THE EARS, MUSCLE TENSENESS,
WEAKNESS, TREMOR, CARDIAC IRREGULARITIES,
EXACERBATION OF ULCERS, DIARRHEA, NAUSEA,
APATHY.
REPORT ON WOMEN WITH FIBROCYSTIC BREAST
DISEASE:
FINDING-- ABSTENTION FROM CAFFEINE RESULTED IN
DISAPPEARANCE OF SYMPTOMS.
PREGNANCY AND CHILDREN
ORAL CONTRACEPTIVES WILL DECREASE METABOLISM
OF CAFFIENE. LIVER P450 SYSTEM IS ESTROGEN
SENSITIVE.
HALF-LIFE FOR WOMEN IN LAST TRIMESTER IS 10.5
HOURS.
PREGNANT WOMEN ARE ESTIMATED TO CONSUME 144
MG/DAY.
BREAST FEEDING HAS INCREASED FROM 24.7% IN 1971
TO 55.3% IN 1980.
CAFFEINE IS RAPIDLY TRANSMITTED INTO BREAST
MILK.
BREAST MILK CAFFIENE IS SAME AS MOTHER'S PLASMA
LEVELS.
STUDY OF 6 HEALTHY LACTATING WOMEN (AGES 28 35): 100 MG DOSE OF CAFFEINE IN WATER ON EMPTY
STOMACH.
BLOOD AND BREAST MILK WAS SAMPLED FOR NEXT 24
HRS.
PLASMA PEAK TIME WAS 0.5 TO 1 HOUR. LEVELS WERE
3.6 TO 6.1 UG/ML.
BREAST MILK PEAK TIME WAS 0.75 TO 2 HR. LEVELS
WERE 2.0 TO 4.3 UG/ML.
IN A PRETERM INFANT WITHOUT LIVER FUNCTION, I.E.,
WITHOUT METABOLISM, THE HALF-LIFE WOULD BE 80 100 HOURS.
IT IS DIFFICULT TO FIND A NEWBORN BABY WITHOUT
CAFFEINE IN ITS BLOOD!
THEOPHYLLINE (IN TEA) HALF-LIFE IS 77 + 65 HOURS IN
PRETERM INFANTS.
FETAL LIVER CAN CONVERT THEOPHYLLINE TO
CAFFEINE!
BEGINNING IN 3RD TRIMESTER, BABY BRAIN REACTS TO
CAFFIENE JUST LIKE ADULT BRAIN. RECEPTORS MUST
BE THERE?
CAFFEINE AT VERY HIGH DOSES (80 CUPS/DAY) IS A
TERATOGEN.
XANTHINES HAVE A POSITIVE INOTROPIC EFFECT ON
THE HEART
XANTHINES ARE DIURETICS (BLOCKS NA+ AND K+
REABSORPTION, LOSS OF WATER IS PURPOSE OF
CAFFEINE IN OTC WEIGHT LOSS PILLS)
CAFFEINE IS USEFUL IN MIGRAINE HEADACHES
(CAFERGOT): INCREASES VASODILATION IN PERIPHERY,
DECREASES VASODILATION IN CNS, INCREASES
GLUCOSE UTILIZATION (INCREASED NEURONAL
ACTIVITY).
BENEFICIAL EFFECTS: ENHANCES MENTAL CLARITY,
ALLAYS FATIGUE.
CAFFEINE IS MOST EFFECTIVE IN IMPROVING
PERFORMANCE WHICH HAS BEEN DETERIORATING DUE
TO EXCESSIVE STRESS OR FATIQUE.
IT HAS LESS DRAMATIC EFFECTS ON WELL RESTED
SUBJECTS.
THIS IS DUE TO THE LAW OF INITIAL VALUE.
Coffee melanoidins showed higher antioxidant activity than melanoidins
isolated from beer (Morales & Jimenez-Perez, 2004).
Coffee is the main contributor of dietary antioxidant intake in the diet in the
USA (Svilaas et al. 2004).
There is an inverse association between coffee consumption and liver
cirrhosis (Tverdal & Skurtveit, 2003).
Total testosterone was positively associated with coffee consumption
in adult men.
The consumption of at least one cup of coffee per day was associated
with a higher prevalence of sexual activity in elderly women and with a
higher potency rate in elderly men.
Coffee consumption protects women from the development of diabetes
(Rosengren et al. 2004).
Long-term coffee consumption is associated with a statistically
significant lower risk of type 2 diabetes.
Regular caffeine use (250 mg twice daily) might have the potential to
reduce the risk of cardiovascular events in patients with longstanding
type 1 diabetes.
The combination of coffee and exercise elicited a higher lipolytic
response than exercise alone (Mougios et al. 2003).
A study of 87,000 registered female nurses found a strong inverse
association between coffee intake and risk of suicide.
Coffee (or caffeine from non-coffee sources), but not decaffeinated
coffee, has been associated with a low relative risk of Parkinson’s
disease (Ascherio et al. 2001; Ross et al. 2000).
However, this association is an inverse one for women using hormones
(Ascherio et al. 2003).
Coffee consumption was also associated with a slightly reduced risk
of Alzheimer’s disease (Lindsay et al. 2002; Heuser, 2003).
CAFFEINE AFFECTED THE MEMORY ABILITIES OF HIGHLY
IMPULSIVE PEOPLE MORE THAN LOW IMPULSIVE
PEOPLE. (PSYCHOPHARM. 1991; 105:137.)
INCREASES VIGILANCE, PREVENTS DECLINE IN
ATTENTION SEEN AFTER MEALS, IMPROVES
INFORMATION PROCESSING AFTER LUNCH.
RESPONSES ARE QUICKER - INTELLIGENCE IS NOT
AFFECTED.
WOMEN IN FIRST 5 DAYS OF MENTRUAL CYCLE HAVE
ENHANCED MEMORY WITH CAFFEINE DOSE.
DRINKING 2 CUPS (TYPICAL) OF COFFEE PER DAY MAY
SIGNIFICANTLY SHORTEN THE MENTRUAL CYCLE IN
SUSCEPTIBLE WOMEN.
CHRONIC CAFFEINE TREATMENT SIGNIFICANTLY REDUCED
NEURONAL DAMAGE AFTER 5 MINUTES OF BILATERAL CAROTID
OCCLUSION.
TEAS CONTAIN POWERFUL ANTI-OXIDANTS, ESPECIALLY WHITE TEA,
WHICH IS BETTER THAN GREEN TEA.
DRINKING TEAS OR COFFEE MAY REDUCE RISK OF COLON CANCER
(DASHWOOD ET AL., 2000).
COFFEE OR TEA DRINKING REDUCES THE RISK OF
PARKINSON’S DISEASE. DECAFFEINATED DOES NOT
HAVE SAME EFFECT. SEEN IN MEN BUT NOT WOMEN.
NEUROPROTECTANT EFFECT DOES NOT SHOW
TOLERANCE AFTER CHRONIC EXPOSURE (2002).
ESTROGEN OR ERT CAN PREVENT THE
NEUROPROTECTION IN WOMEN (2006).
CAFFEINE AND ATHLETES
450 mg CAFFEINE - NO EFFECT ON SIMPLE COORDINATION IN ADULT
MEN.
300-900 MG CAFFEINE - INDUCES ARM AND HAND TREMORS.
COFFEE DRINKING CAN EXACERBATE HAND TREMORS ASSOC. WITH
PARKINSON'S DISEASE AND LITHIUM THERAPY.
STIMULATES RELEASE OF ENDORPHINS AND MAY LESSEN PAIN
ASSOC WITH EXERTION WITH EXERCISE.
CAFFEINE DOES NOT MODIFY THE DELAY BEFORE
EXHAUSTION WITH EXERCISE, BUT IT DOES
ATTENUATE THE PERCEPTION OF THE EFFORT
REQUIRED.
CAFFEINE EFFECTS ARE MORE PRONOUNCED AT HIGH
ALTITUDES (2900 METERS), E.G. SKIING. AT HIGH
ALTITUDES, CAFFEINE DOES INCREASE DELAY TO
EXHAUSTION.
AT HIGH ALTITUDES, CAFFEINE INCREASES
ENDURANCE BY MOBILIZATION OF FATTY ACIDS.
ADVICE FOR ATHLETES:: ABSTAIN FROM CAFFEINE
FOR 4 DAYS PRIOR TO EVENT.
ABSORB THE CAFFEINE 2-3 HOURS PRIOR TO EFFORT,
SO THAT PLASMA FREE FATTY ACIDS, AND NOT
CAFFEINE, WILL BE AT PEAK DURING EVENT.
NEGATIVE SIDE EFFECTS
CNS: GRAND MAL CONVULSIONS CAN BE ELICITED
BY CAFFEINE AND THEOPHYLLINE.
INCREASES CORTICAL EEG ACTIVITY; DECREASES
THALAMIC EEF ACTIVITY: THIS MAY EXPLAIN SLEEP
DISTURBANCES.
HEART: PREMATURE VENTRICULAR CONTRACTIONS
AND SERIOUS ARRHYTHMIAS.
AT LOW DOSES, CAFFEINE CAN COUNTERACT THE
PSYCHOMOTOR DISTURBANCE OF ALCOHOL.
STIMULANT EFFECTS MAY BE MEDIATED BY
INHIBITION OF CNS ADENOSINE RECEPTORS
ANTAGONISM AT THESE RECEPTORS IMPROVES
MENTAL CLARITY AND MOOD.
(SCIENCE 263:689, FEB 1994)
PROPENSITY TO SLEEP AND INTENSITY OF DELTA
WAVES UPON FALLING ASLEEP ARE
PROPORTIONAL TO THE DURATION OF PRIOR
WAKEFULNESS.
RISE IN BRAIN TEMP INDUCES SLEEPINESS AND
INCREASED DELTA WAVE ACTIVITY.
MESOPONTINE CHOLINERGIC CELLS MAY
CONTROL CORTICAL EEG VIA THALAMUS.
ADENOSINE MAY MODULATE THE ACTIVITY OF THESE
NEURONS.
PRODUCTION AND RELEASE OF ADENOSINE IN BRAIN IS
LINKED TO NEURONAL METABOLIC ACTIVITY WHILE
AWAKE.
THEREFORE, ADENOSINE BUILDS UP WHILE BRAIN IS
ACTIVE DURING THE DAY AND INHIBITS CHOLINERGIC
MESOPONTINE NEURONS THAT ARE IMPORTANT FOR
AROUSAL.
THIS LEADS TO DECREASED EEG ACTIVITY IN FRONTAL
CORTEX, INCREASED DROWSINESS AND DELTA WAVE
SLEEP.
CAFFEINE AND THEOPHYLLINE ARE POWERFUL
BLOCKERS OF ADENOSINE RECEPTORS AND
THEREFORE OF THIS ADENOSINE DRIVEN SLEEP.
CHOCOLATE HAS MOSTLY THEOBROMINE (3,7DIMETHYLXANTHINE) WITH MUCH LESS CAFFEINE.
THEOBROMINE IS A CONSIDERABLY WEAKER CENTRAL
STIMULANT THAN CAFFEINE OR THEOPHYLLINE, WHICH
HAVE SIMILAR POTENCIES.
The Effects of Chocolate Upon
Cognition are Due to:
1. Presence of Xanthine
2. Fats induce the release of endogenous opiates
3. Presence of Amphetamine-like drug (PEA)
4. A Marijuana-like drug known as anandamide
5. Presence of Glucose
6. Presence of Estrogen-like compounds
7. Magnesium Salts for post-menopausal women
8. Anti-oxidants, flavonoids = 1 glass of red wine
THE END