This document provides a comprehensive overview of alkaloids, detailing their definitions, history, classification, and effects on humans and plants. It includes information on various specific alkaloids like nicotine and morphine, their chemical structures, uses, and potential side effects. The text also touches on the biosynthesis and methods for isolation and purification of alkaloids.

2. Presenter:
MAHEYA MIDHAT KHAN
Department Of Pharmacy
Jinnah University For women, Karachi.

3. the term “alkaloid” (alkali-like) is
commonly used to designate basic
heterocyclic nitrogenous
compounds of plant origin that are
physiologically active.

4. Deviation from Definition:
 Basicity: Some alkaloids are not basic e.g.
Colchicine, Piperine, Quaternary alkaloids.
 Nitrogen: The nitrogen in some alkaloids is not in
a heterocyclic ring e.g. Ephedrine, Colchicine,
Mescaline.
 Plant Origin: Some alkaloids are derived from
Bacteria, Fungi, Insects, Frogs, Animals

5. New Definition:
Alkaloids are cyclic organic compounds
containing nitrogen in a negative state of
oxidation with limited distribution among
living organisms.

6. ORIGIN AND HISTORY
 The term alkaloid was coined by Meissner, A German
Pharmacist, in 1819.
 The mankind has been using alkaloid for various purposes
like poisons, medicines, poultices, teas and etc.
 The French chemist, Derosne in 1803, isolated Narcotine.
 A significant contribution to the chemistry of alkaloids in
the early years of its development was made by the French
researchers Pierre Joseph Pelletier and Joseph Bienaimé
Caventou, who discovered quinine (1820)
and strychnine (1818).
 Several other alkaloids were discovered around that time,
including xanthine (1817), atropine (1819), caffeine (1820),
coniine (1827), nicotine (1828), and cocaine (1860).

7. Nomenclature:
Trivial names should end by "ine". These names may refer to:
From plant generic name (Atropine)
From specific plant species (Cocaine)
From the common name of Drug (Ergotamine)
From physiological activity (emetine)
From the name of discoverer (Pelletierine)
From the prominent Physical character (Hygrine)

8. Distribution and occurrence:
Rare in lower plants.
 Dicots are more rich in alkaloids
than Monocots.
 Families rich in Alkaloids:
Apocynaceae, Rubiaceae,
Solanaceae and Papaveracea.
 Families free from Alkaloids:
Rosaceae, Labiatae

9. Distribution in Plant:
All Parts e.g. Datura.
Barks e.g. Cinchona
Seeds e.g. Nux vomica
Fruits e.g. Black pepper
Latex e.g. Opium
Leaves e.g. Tobacco

10. Forms of Alkaloids:
• Free bases
• Salts with Organic acids e.g. Oxalic, acetic acids
• Salts with inorganic acids e.g. HCl, H2SO4.
• Salts with special acids:
e.g. Meconic acid in Opium
Quinic acid in Cinchona
• Glycosidal form e.g. Solanine in Solanum.

11. Function in Plants
• They may act as protective against insects and
herbivores due to their bitterness and toxicity.
• They are, in certain cases, the final products of
detoxification (waste products).
• Source of nitrogen in case of nitrogen deficiency.
• They, sometimes, act as growth regulators in certain
metabolic systems.
• They may be utilized as a source of energy in case
of deficiency in carbon dioxide assimilation.

12. EFFECTS OF ALKALOIDS ON HUMANS:
High Biological Activity
Produce Vary Degrees Of Physiological and
Psychological Responses – Largely by interfering
with Neurotransmitter
In large doses- highly toxic – fatal
In small doses – many have therapeutic value
Muscle relaxant, Pain killers, tranquilizers, Mind
altering drugs, Chemotherapy

13. Physical Properties:
I- Condition:
• Most alkaloids are crystalline solids.
• Few alkaloids are amorphous solids e.g. emetine.
• Some are liquids that are either:
Volatile e.g. nicotine and coniine, or
Non-volatile e.g. pilocarpine and hyoscine.
II- Color:
The majority of alkaloids are colorless but some are colored e.g.:
• Colchicine and berberine are yellow.
• Canadine is orange.
• The salts of sanguinarine are copper-red.

14. Physical Properties:
III- Solubility:
 Both alkaloidal bases and their salts are soluble in alcohol.
 Generally, the bases are soluble in organic solvents and
insoluble in water
Exceptions:
 Bases soluble in water: caffeine, ephedrine, codeine,
colchicine, pilocarpine and quaternary ammonium bases.
 Bases insoluble or sparingly soluble in certain organic solvents:
morphine in ether, theobromine and theophylline in benzene.
 Salts are usually soluble in water and, insoluble or sparingly
soluble in organic solvents.

15. Chemical Properties:
I- Nitrogen:
Primary amines R-NH2 e.g. Norephedrine
Secondary amines R2-NH e.g. Ephedrine
Tertiary amines R3-N e.g. Atropine
II- Basicity:
R2-NH > R-NH2 > R3-N

16. According to basicity Alkaloids are classified
into:
Weak bases e.g. Caffeine
Strong bases e.g. Atropine
Neutral alkaloids e.g. Colchicine

17. III- Oxygen:
 Most alkaloids contain Oxygen and are solid in nature e.g. Atropine.
 Some alkaloids are free from Oxygen and are mostly liquids e.g.
Nicotine, Coniine.
 Effect of heat:
Alkaloids are decomposed by heat, except Strychnine and caffeine.
 Reaction with acids:
1- Salt formation.
2- Dilute acids hydrolyze Ester Alkaloids e.g. Atropine
IV- Stability:

18. COOH
R-CHNH2 R-CH2NH2 RN=CH RNH-CH-R’ CH2R’’
Schiff Base Alkaloid
COOH Transamination R’-CHO
R’-CHNH2 -CO2
Alkaloid Biosynthesis
Mannich
Condensation
H-C-H
R”
carbonion
Amino Acids Schiff Base Alkaloid
-H2OCO2

19. Isolation of Alkaloids
• Process remained unchanged >1,000 years
Plant Material
Acid solution
EtOAc: neutral/weakly basic
alkaloids
1) Methanol
2) Concentrate
3) Partition EtOAc/2% acid
Petroleum ether extracts non-
polar fats and waxes
Residue: polar material
Wash with petroleum ether
Basic aqueous solution of
quaternary alkaloids
1) Ammonia
2) Partition with EtOAcEtOAc: basic alkaloids

20. Purification of Alkaloids
• Gradient pH as alkaloids are basic
• Volatile alkaloids: distillation
• Crystallisation
•Fractional or acid/base pair
• Chromatography
• HPLC, GC, TLC and CC

21. Precursors of Alkaloids:
Alkaloids
Ornithine
Tropane
Pyrrolidine
Pyrrolizidine
Tyrosine
Benzyl-iso-
Quiniline
Tryptophan
Indole
Quinoline
Lysine
Quinolizidine
Piperidine
N
N
CH3
nicotine
from
ornithine
N
O
N
O
strychnine
from
tryptophan
O
HO
N
CH3
HO
morphine
from
tyrosine
N O
H
H3C
Lycopodine
from
lysine

22. CLASSIFICATION OF
ALKOLOIDS

24. TRUE ALKOLOIDS
True alkoloids derived from amino acids
Heterocyclic ring with nitrogen
Highly reactive substances in low doses also
Bitter taste with white appeareance
Form water soluble salts
examples:
cocaine,morphine,nicotine,dopamine etc.

25. NICOTINE
Nicotine is a potent
parasympathomimetic
alkaloid found in the
nightshade family of plants (Solanaceae) and
a stimulant drug .
 It is made in the roots of and accumulates in the
leaves of the nightshade family of plants.

26. Nicotine is a hygroscopic, colorless oily liquid that is readily
soluble in alcohol, ether or light petroleum. It
is miscible with water in its base form.
nicotine forms salts with acids that are usually solid and
water soluble.
Nicotine is optically active, having two enantiomeric forms.
The naturally occurring form of nicotine is levorotatory (−)-
nicotine. The dextrorotatory form, (+)-nicotine is
physiologically less active than (–)-nicotine. (−)-nicotine is
more toxic than (+)-nicotine.
CHEMISTRY

27. SAR

29.  Initially causes nausea and vomiting by stimulating vomiting center
in brain stem and sensory endings in stomach. This becomes
tolerant.
 Stimulates hypothalamus to produce antidiuretic hormone, causing
fluid retention.
 Reduces activity coming in from muscles, producing relaxation.
 Increases heart rate, blood pressure and contractility; but carbon
monoxide in smoke combines with oxygen better than hemoglobin,
so it decreases oxygen carrying capacity (suffocates cells).
PHARMACOLOGICAL EFFECTS

30.  Nicotine is quickly and thoroughly distributed in the body, to brain, placenta, all body fluids
(including breast milk).
 Liver metabolizes 80–90 percent before excretion by kidneys.
 Elimination half-life is ~2 hours. The major metabolite of nicotine is cotinine, which is basis for
tests.

32. Uses:
The primary therapeutic use of nicotine is in treating
nicotine dependence in order to
eliminate smoking with the damage it does to
health.
Nicotine medicines release a sufficient amount of
nicotine into the body to help stop your craving to
smoke

33. Believe it!
smoking (almost certainly due to nicotine)
reduces risk of Parkinson’s disease
reduces risk of Alzheimers
schizophrenics on neuroleptics smoke in very large numbers –
why?
nicotine also can
be neuroprotective (against ETOH WD neurotoxicity for example)
suppress certain autoimmune diseases

34. Doses:
In lesser doses (an average cigarette yields about 2 mg of absorbed nicotine), it stimulant the
nicotinic receptor(cholinergic), while high amounts (50–100 mg) can be harmful and blocks
the receptors.

35. Side effects:
 Feeling sick (nausea)
 Being sick (vomiting)
 Indigestion (dyspepsia)
 Headache
 Dizziness
 Dry mouth
 Increase in saliva in the mouth
 Throat irritation
 Cough
 Rash
 Swelling (oedema)
 Nasal irritation
 Nose bleeds (epistaxis)
 Nasal irritation
 Watery eyes
 Feeling thirsty
 Stomach discomfort
 Ear sensations
 Inflammation of the blood vessels
(vasculitis)
 Nightmares
 Chest pain
 Shortness of breath (dyspnoea)
 Sweating

36. MORPHINE

37. MORPHINE
 Morphine is the most abundant opiate found
in opium, the dried latex extracted by shallowly
scoring the unripe seedpods of the Papaver
somniferum poppy. Morphine was the first active
principle purified from a plant source and is one
of at least 50 alkaloids of several different types
present in opium.
 Morphine is an opioid analgesic drug. Morphine
has a high potential
for addiction; tolerance and psychological dep
endence develop rapidly,
although physiologicaldependence may take
several months to develop.

38. Morphine was first isolated in 1804 by Friedrich
Sertürner, which is generally believed to be the
first ever isolation of a natural plant alkaloid in
history.
Sertürner originally named the
substance morphium after the Greek god of
dreams, Morpheus (Greek: Μορφεύς), for its
tendency to cause sleep

39. CHEMISTRY
 Morphine is a benzylisoquinoline alkaloid with two
additional ring closures. It has:
 A rigid pentacyclic structure consisting of a benzene ring
(A), two partially unsaturatedcyclohexane rings (B and C),
a piperidine ring (D) and a tetrahydrofuran ring (E). Rings A,
B and C are the phenanthrene ring system. This ring system
has little conformational flexibility.
 Two hydroxyl functional groups: a C3-phenolic OH (pKa
9.9) and a C6-allylic OH
 An ether linkage between C4 and C5,
 Unsaturation between C7 and C8,
 A basic, 3o-amine function at position 17,
 5 centers of chirality (C5, C6, C9, C13 and C14) with
morphine exhibiting a high degree of stereoselectivity of
analgesic action.

40. Structure activity relationship

46. USES
Relief of pain caused by heart attack or
myocardial infarction.
Relief of the severe bone and joint pain
associated with sickle cell crisis.
Pain relief before, during and after surgery.
General anesthsia to sedate a patient.
A cough suppressant in cases where cough is
severe enough.

47. MECHANISM OF ACTION
 Opioid receptors
 As morphine binds to opioid receptors, molecular signalling activates the
receptors to mediate certain actions.
 There are three important classes of opioid receptors and these are:
 μ receptor or Mu receptors - There are three subtypes of this receptor, the μ1, μ2
and μ3 receptors. Present in the brainstem and the thalamus, activation of these
receptors can result in pain relief, sedation and euphoria as well as respiratory
depression, constipation and physical dependence.
 κ receptor or kappa receptor - This receptor is present in the limbic system, part
of the forebrain called the diencephalon, the brain stem and spinal cord.
Activation of this receptor causes pain relief, sedation, loss of breath and
dependence.
 δ receptor or delta - This receptor is widely distributed in the brain and also
present in the spinal cord and digestive tract. Stimulation of this receptor leads
to analgesic as well as antidepressant effects but may also cause respiratory
depression.

48. ADR
dizziness
drowsiness
nausea
vomiting
stomach pain and
cramps
diarrhea
loss of appetite
weight loss
dry mouth
sweating
weakness
headache
agitation
nervousness
mood changes
confusion

49. PROTO-ALKALOIDS

50. 1. ADRENALINE
General Characteristics Features:
• Have no nitrogen as part of heterocyclic ring
• Derived from amino acids like Phenylalanine, Tyrosine
• Physiologically active compounds
• Examples: Adrenaline, Ephedrine, Colchicines, Mescaline

51. SHIKIMATE PATHWAY

52. SHIKIMATE PATHWAY
Shikimic Acid Chorismic Acid Prephenic Acid
Phenylalanine
Tyrosine
Proto-Alkaloids
E.g. Ephedrine, Epinephrine
etc.

53. Adrenaline is a hormone and
a neurotransmitter
• As a hormone it is synthesized by
adrenal medulla of kidney
• As a neurotransmitter it is
released by some sympathetic
nerve endings.

54. Adrenaline is one of a group
of monoamines called the
catecholamines. It is
produced in some neurons of
the central nervous system,
and in the chromaffin cells of
the adrenal medulla from
the amino acids
phenylalanine and tyrosine
(R)-4-(1-Hydroxy-2-
(methylamino)ethyl)benzene-1,2-
diol

56. “Fight” OR
“Flight”
Response of
ADRENALINE
Blood flow to
skeletal
muscles
increases
Intestinal
muscle
relax
Breathing
rate
increases
Heart rate
increases
Pupil
dilate
Blood
pressure in
arteries
increases
Blood sugar
level
increases

57. Clinical Use
of
ADRENALINE
Anaphylaxis
Cardiac
Arrest
Asthma
Local
Anesthetics

58. HO
OH
OH
HN
R

59. HO
OH
OH
HN
R
CATECHOL

60. HO
OH
OH
HN
R
AMINE

61. HO
OH
OH
HN
R
ALKYL
GROUP

62. HO
OH
OH
HN
R
OH
OH
HO
HN
H
ADRENALINE
NORADRENALINE

63. HO
OH
OH
HN
R
OH
OH
HO
HN
CH
ADRENALINE ISOPRENALINE
CH3
CH3

64. HO
OH
OH
HN
R
OH
OH
OH
HN
C
ADRENALINE SALBUTAMOL
CH3
CH3
CH3

66. Ephedrine
A phenethylamine found in EPHEDRA
SINICA. PSEUDOEPHEDRINE is an isomer.
It is an alpha- and beta-adrenergic
agonist that may also enhance release
of norepinephrine. It has been used for
asthma, heart failure, rhinitis, and
urinary incontinence, and for its central
nervous system stimulatory effects in the
treatment of narcolepsy and
depression.

67. 2D structure of Ephedrine

68. 3D structure of Ephedrine

69. Chemical properties of Ephedrine
Chemical Names Ephedrine,
2-(methylamino)-1-phenylpropan-1-ol; Benzyl
alcohol, alpha (1-methylaminoethyl)
Formula: C10H15NO
Molecular Weight 165.2322 g/mol
Boiling Point 260 deg C at 745 mm Hg
Melting Point 38.1 deg C
Solubility In water, 56,900 mg/L at 25 deg C ; 63,600
mg/L at 30 deg Celcius
Density 1.0085 g/cu cm at 22 deg C

70. Chemistry of Ephedrine
Ephedrine exhibits optical isomerism and has two chiral
centres, giving rise to four stereoisomer. By convention,
the pair of enantiomers with the stereochemistry (1R, 2S
and 1S,2R) is designated ephedrine, while the pair of
enantiomers with the stereochemistry (1R,2R and 1S,2S) is
called pseudoephedrine. Ephedrine is a substitute
amphetamine and a structural
methamphetamine analogue. It differs from
methamphetamine only by the presence of
a hydroxyl (OH).

72. SAR
 Ephedrine and pseudo ephedrine are the diastereomers
 Among the optical isomers of ephedrine and pseudo ephedrine only
D(-) ephedrine can significantly block the adrenergic receptors there by
lowering blood pressure.
5/9/2015Stucture-activity relationship

73. On R1 -substitution on Amino Nitrogen= CH3 (the activity of both alpha and beta
receptor is maximal when R1 is Methyl.)
On R2- Substitution alpha to basic Nitrogen to Carbon 2 = CH3 (such substitution
slows metabolism by MAO but has little over all effect on duration of action)
On R3- Substitution on Aromatic Ring = H, (provides excellent receptor activity on
both alpha and beta receptor)
Receptor Activity= on alpha and beta adrenergic receptors
ephedrine is less polar than the other
compounds, and crosses the blood brain
barrier far better than the catecholamine
do.
Because of its ability to penetrate the
CNS, ephedrine has been used as a
stimulant, and exhibits side effects
related to its actions in the brain.

74. Mechanism of Action
Ephedrine is a sympathomimetic amine - that is, its
principal mechanism of action relies on its direct and
indirect actions on the adrenergic receptor system,
which is part of the sympathetic nervous system.
Ephedrine increases post-synaptic noradrenergic
receptor activity by (weakly) directly activating post-
synaptic α-receptors and β-receptors, but the bulk of its
effect comes from the pre-synaptic neuron being
unable to distinguish between real adrenaline or nor
adrenaline from ephedrine.

75. Uses
Diseases of the respiratory tract with mild
bronchospasms in adults and children over
the age of six.
Spinal anesthetics during delivery
Used for breathing problems, asthma and
nasal swelling/congestion caused by a cold
or allergies.

76. Ephedrine is the active ingredient in ephedra or
huang. It belongs to a class of medications
called sympathomimetics. It works like a
naturally occurring substance (adrenaline) that
your body makes when it thinks it is in danger.
It is a central nervous system stimulant that
increases your heart rate/blood pressure,
narrows your blood vessels (vasoconstriction),
and opens up the lungs (bronchodilation).

77. Side effects
 Nervousness
Headache
 Confusion
 Delirium
 hallucination,
 Pallor
 hypertension
 tachycardia,
 Palpitation
 Sweating, vomiting
 Anorexia
 Restlessness
 Anxiety
 Tension
 Tremor
 Weakness
 Dizziness
 Vertigo

78. Nervous system
Nervous system side effects associated with large doses of
ephedrine have included nervousness, insomnia, vertigo, and
headache.
Cardiovascular
Cardiovascular side effects associated with large doses of
ephedrine have included tachycardia and
palpitation. Hypertension, stroke, and myocardial infarction.
Gastrointestinal
Gastrointestinal side effects have included nausea, vomiting,
and anorexia.

79. Genitourinary
Urinary retention has mainly been reported in male
patients with prostatism.
Genitourinary side effects have included dysuria and
urinary retention.
Psychiatric
Psychiatric side effects associated with prolonged abuse of
ephedrine have included symptoms of paranoid
schizophrenia. Suicide and psychotic episodes have also
been reported.

81. Caffeine:
“Anger - a better alternative to caffeine.”
― Ilona Andrews, Magic Rises

82. INTRODUCTION
Caffeine (1,3,7-trimethylxanthine) is a purine alkaloid that occurs naturally in
coffee beans .
Caffeine is an alkaloid from methylxanthines called 3,7-dihydro-1,3,7-
trimethyl-1H-purine-2,6,-dione or 1,3,7-trimethylxanthine.
Some physiological effects associated with caffeine administration include
central nervous system stimulation, acute elevation of blood pressure,
increased metabolic rate, and diuresis.
Caffeine is rapidly and almost completely absorbed in the stomach and
small intestine and distributed to all tissues, including the brain.
It is found in varying quantities in the seeds, leaves
fruits of some plants, where it act as a natural
pesticide.
Beverage containing coffee such as coffee, tea
soft drinks, & energy drinks.

83. HISTORY
 1st use of caffeine as early as 600,000 BCE .
 1820 - Caffeine was first isolated from coffee by German chemist Friedlieb
Ferdinand Runge,.
 1821 - . Pelletier coined the term "caffeine" from the French word for coffee
(café), and this term became the English word "caffeine".
 1821 - Pure caffeine extracted from coffee.
 1880 - Caffeinated soft drinks appear.
 1903 - Researchers remove caffeine from beans ‘without destroying the flavor’.
 1923 - Decaffeinated coffee is introduced to the United States.
 1940 - The US imports 70 percent of the world coffee crop.
 1962 - American per-capita coffee consumption peaks at more than three cups
a day.
 1995 - Coffee becomes the worlds most popular beverage (overtaking tea ) .

84. Which Foods and Beverages Contain Caffeine
Table 1. Caffeine source and amount of caffeine content

86.  Coffee contain caffeine and theophylline
 Theophylline is a dimethylxanthines that have two rather than three
methyl groups 3,7-dihydro-1,3-dimethyl-1H-purine-2,6-dione; 1,3-
dimethylxanthine,
 Is considerably weaker than caffeine and having about one tenth the
stimulating effect of either. It has a stronger effect on the heart and
breathing than caffeine. For this reason it is often the drug of choice in
home remedies for treating asthma bronchitis and emphysema. The
theophylline found in medicine is made from extracts from coffee or tea.

87. Why do people become addicted to
caffeine?

A person who drinks 1 cup of coffee a day over seven
days will build a tolerance to this amount of caffeine.
This person will have to consume 2 cups of coffee to feel
the same effects as before but again will build a
tolerance to that amount of caffeine. Over time this
cycle will lead to an addiction to caffeine and will have
negative side effects on the body.

88. Caffeine as a Drug
The behavioral effects of caffeine can be
characterized principally as a reduction in fatigue
and boredom, as well as a delay in the onset of
sleep.
Recent evidence suggests that caffeine might
lower the risk of developing Parkinson’s disease in
men.
A comparable protective role in women is
currently uncertain. © Copyright
2011, Pearson
Education, Inc.
All rights
reserved.

89. Caffeine as a Drug
Health risks from moderate consumption of
caffeine are not clinically significant, except for
the adverse effects on fetal development during
pregnancy, the development of bone loss
among the elderly, a possible adverse effect on
the cardiac condition of patients already
suffering from cardiovascular disease, and the
aggravation of panic attacks among patients
with this disorder. © Copyright
2011, Pearson
Education, Inc.
All rights
reserved.

90. Mechanism of Action
 Caffeine's primary mechanism of
action is as an
antagonist of adenosine receptors
in the brain.
Adenosine in the
Brain
 In the brain neurons are transmitting
electrical energy.
 When activity is too high adenosine
molecules stop the neuron cells
from firing.
Caffeine blocks adenosine
receptors with its own
molecule preventing the
adenosine molecule from
binding.
Brain activity remains at its
excited state and can even
increase in activity because
adenosine is unable to slow
it down.

91. Similar chemical struct = mimicking behavior

92. The binding of Adenosine
to an adenosine receptor
causes the receptor to
undergo a shape change
which triggers a
biochemical cascade. The
end result is the opening of
ion channels and the
slowing of activity.
The binding of caffeine to
a adenosine receptor
causes a shape change
that does not initiate a
biochemical cascade.
Instead, neuronal activity
remains the same or
increase.
Adenosine Caffeine
Adenosine
Receptor
Adenosine
Receptor

93. Caffeine Extraction Processes
Super critical Fluid Extraction
Microwave-assisted extraction
ultrasonic extraction
heat reflux extraction

94. Health Benefits of Caffeine
Caffeine helps ward off Alzheimer’s.
In Japan researchers have shown that caffeine
increases memory.
Caffeine detoxes the liver and cleanses the colon
when taken as a caffeine enema.
Caffeine can stimulate hair growth on balding men
and women.
Caffeine relieves post work-out muscle pain by up
to 48%.
Caffeine can ease depression by increasing
dopamine in the brain.

95. Caffeine increases stamina during exercise.
Caffeine protects against eyelid spasm.
Caffeine may protect against Cataracts.
Caffeine may prevent skin cancer. A new study
out of Rutgers University found that caffeine
prevented skin cancer in hairless mice.
People who consume caffeine have a lower risk
of suicide.
Caffeine may reduce fatty liver in those with
non-alcohol related fatty liver disease. This study
comes out of Duke University.

96. Negative Side Effects of Caffeine
Effects on Heart Rate and Blood
Pressure
Osteoporosis
Diabetes
Loss of sleep
Fertility and miscarriage
Hormonal Effects

97. Fig. 5. Main symptom of caffeine overdose

98. Caffeine products
Scitec Caffeine capsuleAlpecin Caffeine Shampoo
Plantur 39 Caffeine Tonic
Alert energy caffeine gum
Nestle Nescafe gold coffee
Cocacola Beverage
Awake caffeinated
chocolate

99. Decaffeinated products
Nescafe decaf coffee
Tassimo nabob decaf coffee
Zevia caffeine free cola
Twinings pure green tea

100. Conclusion
The good and bad of caffeine
Caffeine is part of modern life. Regular coffee drinkers
include the majority of adults and a growing number of
children. The recommendation for most people is to enjoy
one or two cups of coffee a day, which will allow you to
capitalize on its health benefits without incurring health
drawbacks. Extensive recent research has put forth that
coffee is far more healthful than it is harmful. Very little bad
and a lot of good come from drinking it.

101. References
 Carrillo, J.A., and Benitez, J. 2000. Clinically significant pharmacokinetic interactions
between dietary caffeine and medications. Clin. Pharmacokinet, 39:127–153.
 de Vreede-Swagemakers, J.J., Gorgels, A.P., Weijenberg, M.P. et al. 1999. Risk indicators
for out-of-hospital cardiac arrest in patients with coronary artery disease. J. Clin
Epidemiol., 52:601–607.
 Gary W. Arendasha,b,∗ and Chuanhai Caob,c. 2010. “Caffeine and Coffee as
Therapeutics Against Alzheimer’s Disease” Journal of Alzheimer’s Disease 20 S117–S126
 Greenland, S. 1993. A meta-analysis of coffee, myocardial infarction, and coronary death.
Epidemiology., 4:366–374.
 Hammar, N., Andersson, T., Alfredsson, L. et al. 2003. Association of boiled and filtered
coffee with incidence of first nonfatal myocardial infarction: the SHEEP and the VHEEP
study. J. Intern. Med., 253:653–659.
 Haskó G, Linden J, Cronstein B, Pacher P (September 2008). "Adenosine receptors:
therapeutic aspects for inflammatory and immune diseases". Nat Rev Drug Discov 7 (9):
759–70. doi:10.1038/nrd2638. PMC 2568887. PMID 18758473.

102.  Higdon, Jane V., And Frei, Balz., 2006. ” Coffee and Health: A Reviewof Recent
Human Research”. Critical Reviews in Food Science and Nutrition, 46:101–123
 http://www.energyfiend.com/top-10-caffeine-health-benefits
 James, J.E. 2004. Critical review of dietary caffeine and blood pressure:A relationship
that should be taken more seriously. Psychosom. Med.,66:63–71.
 Kawachi, I., Colditz, G. A., and Stone, C. B. 1994. Does coffee drinking increase the
risk of coronary heart disease? Results from a meta-analysis. Br. Heart J., 72:269–275.
 Kuffler SW, Edwards C (November 1958). "Mechanism of gamma aminobutyric acid
(GABA) action and its relation to synaptic inhibition". J. Neurophysiol. 21 (6): 589–610.
PMID 13599049.
 Mukamal, K.J., Maclure, M., and Muller, J.E., 2004. Caffeinated coffee consumption
and mortality after acute myocardial infarction. Am. Heart J., 147:999–1004.
 Spiller, M.A. 1998. The Chemical Components of Coffee. In: Caffeine.pp. 97–161.
Spiller, G. A., Ed., CRC Press, Boca Raton.
 Tavani, A., Bertuzzi, M., Negri, E. et al. 2001. Alcohol, smoking, coffee and risk of non-
fatal acute myocardial infarction in Italy. Eur. J. Epidemiol., 17:1131–1137