Advance brain resuscitation presumed b&c protocol,rkdhaugoda,nepal.

1. Advance Brain Resuscitation
CEREBRO-CARDIO-PULMONARY RESUSCITATION ( CCPR)
MED/CAB PRESUMED B&C PROTOCOL-2017
By- Dr. RAJ KUMAR DHAUGODA
MBBS (1999, TUTH)
MD IN FAMILY MEDICINE (2006,BPKIHS)
Dpt of Emergency , ASSISTANT PROFESS0R, B&C HOSPITAL,Birtamod.

2. Abstract
• The approach to the patient with global Hypoxic Ischemic brain injury is a
difficult task, by using current drugs like –barbiturates, super oxide
dismutase, nimodipine, dizocilpine etc, separately gives the incomplete
results and not fully satisfactory result. It is necessary to ongoing research
& correlation of newer knowledge for newer more effective drugs(
magnesium compound) or techniques e.g. gene therapy, stem cell therapy
etc.It is cleared that we understand most of the patho-physiology of
hypoxic ischemic brain injury in advanced level. But we have not found
such satisfactory drugs to prevent neuronal death or recover ischemic
brain injury so far. Calcium channel blockers & barbiturates have been
used for years but they did not show effective out come. Hence our
medical knowledge, our researches should be correlated and as well as
critical evaluation of literature and their scientific analysis to find out the
newer, effective, cost effective agent, which may act all the steps of
pathogenesis of neuronal damage due to Hypoxic ischemic brain injur

3. ABSTRACT-count.
• . Magnesium has versatile physiological and pharmacological
actions. It protects the cell injury in various steps or by multi
directional physiological action. Theoretically magnesium
attenuates all the biochemical changes during hypoxic- ischemic
brain injuries, e.g. ATP depletion, acidosis, Excitatory amino acid
(glutamate stimulation) or NMDA / non- NMDA receptor
stimulation, increase calcium metabolism, phospholipid
hydrolysis, leukotriens prostaglandin formation, oxygen radical
formation, protein synthesis depletion, alteration of gene
expression and Inflammation. These facts are proved by various
clinical trials done in various medical institutes. And it is tried to
here dialectical analysis of benefits of magnesium compounds in
hypoxic-ischemic brain injury, showing that magnesium is the
master / key / ideal drug for brain resuscitation.

4. BRAIN RESUSCITAION
CEREBRO-CARDIO-PULMONARY
RESUSCITATION ( CCPR)
NEURO-CARDIO-PULMONARY
RESUSCITATION (NCPR)
PR CPR CPCR CCPR
1950 1960 2010 2017
AB ABC CAB MED/CAB

5. PR-1950- AB
Pulmonary resuscitation
Air way clearing and bagging/ ventilation
Poor outcome

6. CPR-1960-ABC
• Cardiopulmonary resuscitation
• ABC
• Airway , breathing and cardiac massage
• POORLY GOOD OUTCOME
• Very poor neuro outcome

7. CPCR -2010 –CAB by AHA
• CARDIOPULMONARY CEREBRAL RESUSCITATION
• ABC IS MODIFIED INTO CAB by AHA in 2010
• CAB= cardiac massage, airway way & breathing
• Relatively good outcome
• Relatively Good neuro outcome too.
• Not an optimum satisfactory neuro outcome
• Searching for relatively optimal method.

8. NCPR -2017 –MED/CAB BY B&C
• Cerebro-cardio-pulmonary resuscitation-CCPR
( Neuro cardio pulmonary resuscitation- NCPR )
• MED SYTMULTANEOPUSLY CAB ( MED/CAB)
• It will give optimal Neuro cardio pulmonary
outcome simultaneouly, including other vital
organs like kidney ,liver and pancreas

9. MED/CAB
MED=MgSO4,EOS,D3 SECOSTEROID -instant
• MAGNESIUM CLORIDE/ MAGNESIUM SULPHATE -
NMDA receptor blocker, Ca++ antagonist
• EXTRACORPOREAL OXYGEN SUPPLY via rectal
supply
• D3 SECOSTEROID INJ TO STIMULATE VDR OF
VITAL ORGANS SUPRESSED BY HYPOXIA
CAB= cardiac massage(manual/automatic), airway
way & breathing

10. Clinical features of H-I
Encephalopathy
• Neonatal seizure - over stimulation of excited neurons and reciprocal membrane
depolarization
• Resp. depression, poor suck - impaired action of neurotransmitters in brain stem.
• Coma - Metabolic disrupt of reticular activating system
• Brain edema - Disturbed - ability to pump water act of hugely- breakdown of blood brain
barriers.
• Patho-physiology of Hypoxic- Ischemia Brain Injury and chemical changes
• Main 3 mechanism –
-Hypoxic- hypoxic (decreased O2 concentration)
-Anemic hypoxia (decreased O2 delivery)
-Ischemia hypoxia (decreased Blood flow)
• Global Ischemia - results from inadequate blood flow.
E.g. during cardiac arrest.
• Or sever hypoxia, severe hypotension, severe birth asphyxia .
• Focal Ischemia - Results from local disruption of Blood supply e.g. ischemia / stroke,
vascular anomalies.

11. Biochemical changes
During Hypoxic- Ischemic Brain injury.
• ATP depletion,
• acidosis
• Excitatory amino acid (glutamate stimulation) or NMDA /
non- NMDA receptor stimulation, increase calcium
metabolism,
• phospholipid hydrolysis
• leukotriens prostaglandin formation,
• oxygen radical formation
• protein synthesis depletion,
• alteration of gene expression (activation of NFkB)
• Increased cytokine production and Inflammation &
apoptosis (neuronal death)

12. current practices of Brain
resuscitation
•
• 1.Barbiturates: -
Decrease seizure
Decrease intracranial pressure
There is some evidence of giving thiopentone 120 mg / kg IV after 30 & 60 minutes of post
ischemia, outcome is ameliorates of brain damage, After global ischemia in monkeys.
• 2.Super oxide dismustase: -
Dimutation reaction of super oxide radical
• 3.Calcium channel Antagonist:
Nimodipine shows increase survival rate up to 12 months after global cerebral ischemia.
• 4.Glutamate Antagonists - E.g. dizocilpine maleate _(NMDA receptor antagonist)
• 5.Nitric oxide syntheses inhibitors:
No satisfactory out came has been reported with N-omega -nitro –L-arginine.
• 6.Hypothermia:
In the global ischemia, the temperature out came is that hyperthermia. (During intra and post
ischemic period)
7. Edaravone- not known MOA, anti oxidant and anti stress agent –used in stroke with lots of S/E
• The approach to the patient with global Hypoxic Ischemic brain injury is a difficult task, by using
above drugs separately gives the incomplete results and not fully satisfactory result

13. Physiological Role of Magnesium
It is required in the activation of more than 300
enzymes.
1. Magnesium is an anti-stress agent.
2. Physiological calcium antagonist.
3. NMDA receptor blocker: (NMDA -receptor is activated in H- I brain
injury).
4. The main biological role of Mg++ in mammalian cell is involved with
anion charge neutralization. Mg++ particularly found in association with
organics polyphosphates such as nucleotide triphosphate and nucleotide
diphosphate (eg. ATP4-.Mg++ and ADP3-.Mg++)
5. The second messenger system - Regulation by Mg++Ion channel.
6. Regulation by Mg++ (Electrolyte Regulation)
7. Magnesium has also vasodilatation action which increases cerebral
blood flow increase perfusion in ischemic brain, Magnesium has also
anti-platelet action, causing decrease in microthrombi formation
8. Magnesium is a potent anti-inflammatory agent-which decreases the
cerebral inflammation and edema drastically
9. Magnesium needs in cellular protein synthesis.

14. discussion
• (By above patho-physiology of Hypoxic- ischemic brain injury &
role of magnesium in brain injury)
• Magnesium is the master agent due to its versatile physiological
and pharmacological actions. It protects the cell injury in various
steps or by multi directional physiological action of magnesium.
• Theoretically magnesium attenuates all the biochemical changes
during hypoxic- ischemic brain injuries, e.g. ATP depletion,
acidosis, Excitatory amino acid (glutamate stimulation) or NMDA /
non- NMDA receptor stimulation, increase calcium metabolism,
phospholipid hydrolysis, leukotriens prostaglandin formation,
oxygen radical formation, protein synthesis depletion, alteration
of gene expression and Inflammation.

15. magnesium is the master / key / ideal
drug for brain resuscitation-evidences
• Randomized controlled trial of MgSO4 infusion for severe Birth asphyxia-
paed. Int 2002, Oct 44(5) 505-9)(Ichiba H, Tamai H, Negioh H &
colleages)- magnesium study group Department of paed Osaka, (PMID-
12225549). 250mg/kg/day for 3days is both safe and able to improve out
come in infants with severe birth ASPHYXIA.
• 2. Effects of magnesium sulphate on Brain damage by complete global
brain ischemic (Dept of Anesthesiology & Resuscitology, Okamaya
university med. School).
• By Okawa M. (Masui 1992 mar- 14(3): 341-55 (PMID- 1560573). Result- is
the magnesium therapy is very useful for cerebral resuscitation after
cardiac arrest
• 3. Magnesium as a Neuroprotective agent on cerebral ischemia. By
C.C. Ionita , J.F. kirmani, A.R. Xavier et al. Current medicinal chemistry-
CNS agents, Dec 2004, vol-4 No-4, page 215- 228(8).
• “ Experimental stroke models and pilot clinical studies have provided
encouraging data regarding the neuro protective role of Mg++ in acute
ischemic stroke observations from subarachnoid hemorrhage (SAH)
animal models have suggested Mg++ have neuro protective action.

16. Research-evidences
4. Magnesium sulphate for Brain injury: -
(National Institute of Neurological disorders and stroke) (Clinical trials.
Gov.)
Result: - Magnesium sulphate has Neuro protective role in Brain injury.
5. Magnesium therapy and recovery of function in experimental
model of Brain injury and Neuro degenerative disease. By Hoane MR
(PMID 15577099)- The role of Mg++ in brain injury has been well
established.
Result: - Mg++ therapy is effective in facilitating Recovery function and
exhibits very robust & unique effects.
6. Magnesium is a potent anti-inflammatory agent-which decreases the
cerebral inflammation and edema drastically(Mazur A, Maier JA, Rock E,
Gueux E, Nowacki W, Rayssiguier Y; Arch Biochem Biophys. 2006 Apr 19)

17. EXTRA pulmonary OXYGEN THERAPY
to increase oxygenation to vital organs
• ECMO-via portable device- VA/VV
• Intra-rectal oxygen supply via catheter
• Intra-gastric
• Intra-peritoneal oxygen therapy
(peritoneal microbubble oxygenation-PMO )

18. D3 SECOSTEROID INJ.
TO STIMULATE VDR OF VITAL ORGANS AND TO DECREASE
INFLAMMATION
• ALL VITAL ORGANS AND GLANDS CONTAIN
VDR – ARE COMPROMISED BY STREES
/HYPOXIA/TRAUMA /INFECTIONS
• D3 ANTI-INFLAMMATORY,
IMMUNOMODULATOR, ANTI-MICROBIAL AND
ANTI VIRAL PROPERTIES

19. THE ROLE OF MAGNESIUM IN THE
EVOLUTION OF PROTOPLANETARY DISKS.
•
• Crystalline Silicate (ferromagnesium silicate)
• Mg Compound (Crystalline olivine (Mg2FeSio4) and crystalline pyroxene (MgFeSio3) and
Amorphous Silica (SiO2) are the building blocks of planets, comets and protoplanetary disk.
• (Ref: - Nature, international weekly journal of science, 25, November 2004, page 479 - 481)
• “Our solar system was formed from a cloud of gas and dust. Most of the dust mass is contained in
amorphous silicates, yet crystalline silicates are abundant thruought the solar system, reflecting the
thermal and chemical alteration of solids during planet formation. (Even primitive bodies such as
comets contain crystalline silicates - Hanner, M.S., Lynch, D.K. & Russel, R.W. the 8 - 13 micron
spectra of comets and the compositional analyses 425, 274 - 285 (1994). Here it is reported
spatially resolved detections and compositional analysis of these building blocks in the innermost
two astronomical units of three protoplanetary disks. it found the dust in these regions to be highly
crystallized, more so than any other dust observed in young stars until now. In addition, the outer
region of one star has equal amount of pyroxene and olivine, where as the inner regions are
dominated by olivine. The spectral shape of the inner disk spectra shows surprising similarity with
solar system comets. Redial mixing models naturally explain this resemblance as well as the
gradient in chemical composition our observation imply that silicates crystallize before any
terrestrial planets are formed, consistent with the composition of meteorites in the solar system”.
• Comets formed in the icy region of the solar nebula, farther than 5AU from the sun.
• Cometary crystalline silicates one are Mg. rich: - Croviseir J. et.al.

20. THE ROLE OF MAGNESIUM IN THE
EVOLUTION OF PROTOPLANETARY DISks.
• The spectra of Comet Hale Bopp (c/1995, 01) observed with the infrared space
observatory at 2.9 AU from the sun. Science 275, 1904 - 1907 (1997)
•
• It has been suggested that the degree of crystalline of protoplanetary disks slowly
increases with time after the accretion of matter on the star has stopped. This
evidence is based on the lack of crystalline silicates in infrared spectra of
embedded young stars in the active phase. Which are still accreting gas and dust
from an interstellar cloud.
• “The star with the highest abundance of crystalline silicates in our sample, HD
142527, is also the youngest one, with an age of a approx 1 million years” (R.V.B.
et.al)
• “Therefore our observations indicates that as was the case in the early Solar
System the silicate dust (magnesium rich) in the inner regions of proto planetary
disks is highly crystalline before planet formation occurs. Thus magnesium rich
silicate crystalline is the building blocks of planet and comets and asteroids.”
•

21. NO MAGNESIUM= NO LIFE
Magnesiumferrosilicate dust forms protoplanatary disk, which
Forms our planetary system ultimately including Earth
Energy from sun chlorophyll of plants in Earth( contains Mg++)-
captures photon of sun.
By MG++ OF chlorophyll of plant ready food(containing Mg++) for
animal.
Magnesium is also called “Biological glue”. That means all the process /
chemical reaction / food production and relation of universe, plant
kingdom and animal kingdom connected by means magnesium element
CRP
Vasculitis (inflammation) = ---------
Mg++

22. THE ROLE OF MAGNESIUM
IN PHOTOSYNTHESIS
• Magnesium is also called “Biological glue”. That means all the process / chemical
reaction / food production and relation of converse, plant kingdom and animal
kingdom connected by means magnesium element.
• The key role of magnesium in the photosynthesis reaction is the most important
biological phenomena by which the regulation of ecosystem is occurred.
• Photosynthesis is the process by which plants, some bacteria, and some protistans
use the energy from sunlight to produce sugar, which cellular respiration converts
into ATP, the “fuel” used by all living things. The conversion of unusable sunlight
energy into usable chemical energy is associated with the actions of the green
pigment chlorophyll. Most of the time, the photosynthetic process uses water and
releases the oxygen that we absolutely must have to stay alive. Oh yes, we need
the food as well.
• The chemical reaction of this process as:
•
• In presence of sun light (photon)
• 6H2O + 6CO2 ---------------------------- C6H12O6+ 6O
• oxidation of Mg++ ion in chlorophyll pigment
• (Six molecules of water plus six molecules of carbon dioxide produce one molecule
of sugar plus six molecules of oxygen)

23. Chlorophyll molecules contain an atom
of magnesium
• Chlorophyll molecules contain an atom of magnesium,
which loses electrons and becomes oxidized by sunlight
(photons). An adjacent electron transport chain
accepts the electrons. After chlorophyll has lost
electrons, enzymes * splits the water (photolysis)
releasing electrons to reduce chlorophyll (Reduction of
magnesium ion), the two H+ ions made available by
photolysis are pumped into the thylakoid lumen by PQ
a mobile carrier in the electron transport chain
embedded in the thylakoid membrane. Electrons do
not stop until they pass throughout photo system - I
and finally reduce NADP+ to NADPH2.
•

24. Mg++ in chlorophyll molecule
The structure of Chlorophylls .

25. Role of magnesium in crops and soil
•
• (Magnesium as fertilizer and drugs for bad
crops and soil)
• Crops and Soils Susceptible to Magnesium
Deficiency• Magnesium deficiency affects many crops: sugar beet, cereals, cotton, potato, hops, citrus, kiwi, plum, sunflower, rose, brassica, pepper, lettuce, tomato, nutand vine. Fruit crops are
highly susceptible to magnesium deficiency during heavy fruit production. Magnesium is a secondary nutrient mostly commonly abounded in soil. Very poor (acid) sandy soils are
known for magnesium deficiency. Magnesium is not strongly adsorbed to clay minerals and organic matter and can be easily replaced by other cations at the complex.
• Magnesium deficiency is induced by high contents of calcium, ammonium or potassium in the soil. Magnesium deficiency is also common on acidic soils by the antagonistic behavior of
sodium.
•
• Effects and Symptoms of Magnesium Deficiency in plants
• In green leaves a major function of magnesium is its role as the central atom in the chlorophyll molecule and is part of the cell wall structure.
• Thereby magnesium performs a key role in the regulation of cellular pH and the cation-anion balance.
• Magnesium activates several important enzymatic reactions in protein synthesis and energetic household. In almost all phosphorylation reactions magnesium is the cofactor and it
accomplishes a bridging function in the photosynthesis.
• Deficiency symptoms of magnesium are quite distinctive. Leaves from monocotyledons (cereals) get stripes along the leaves, so called ‘tigering’. Leaves from dicotyledons keep their
green veins, but the mesophyll will color light
green to yellow; bronzing in citrus.
• In a further stage necrotic stains appear, that resembles potassium deficiency.
• Effects of low magnesium on fruit appear to be caused by the reduction in leaf surface and photosynthetic capacity.

26. Magnesium , CRP and inflammation
• CRP is taken as Biological functional marker (BFM) of
Hypomagnesaemia. In this condition there is
increased C-RP level in the blood circulation and
when Mg++ supplementation is done, there is
decreased level of CRP accordingly.
• Inflammation (vasculitis) is connected in terms of
TNF- alpha and C-RP and stress factors.
• C-RP is used, here, as generalized parameter, to
measure its value. Because it is easy, relatively cost
effective, available most of the parts of even 3rd world
countries.

27. Magnesium formula =CRP in mg/dl × 35 × total body wt.(by rkd)
• The normal range of CRP (high sensitivity ) 0.02 - 0.8 mg / L, Routine CRP range = 0.08 – 3.1 mg/L ( Ref.Harrison
16th ed. Part-2 ,appendices: laboratories values of clinical importance, page no. A-4 )
• The normal serum level of Mg++ 1 mmol /L (average ranges of level 0.8 -1.2 mmol/L or 1.8 – 3 mg/dl
,Ref.Harrison 16th ed. Part-2 ,appendices: laboratories values of clinical importance, page no. A-5 )
•
• 1 gram MgSO4 contains 4.1 mmol. Mg++
• Or
• 1 mmol Mg++ = approx 250 mg MgSO4
• Hence the ratio of CRP: MgSO4 0.8 mg/ L (CRP)
• = --------------------
• 250 mg (MgSO4)
•
• 8 mg / L (CRP)
• = ----------------------
• 2500 mg (MgSO4)
•
• 1 mg / L (CRP )
• = -------------------
• 2500 / 8 mg (MgSO4)
•
• 1 mg / L (CRP)
• = ---------------------
• 350 mg (MgSO4)
•

28. The formula for total MgSO4 needed in mg
= CRP (in mg/dl) × 35 × total B.W.
• Hence, total needed amount of MgSO4 for given CRP level in mg / L and total body weight per kg.
• Total needed MgSO4 in mg =CRP (mg/L) × 350 mg × total body wt.
•
•
• When CRP is given in mg/dl then =CRP mg / dl × 1/10 × 350 × total body wt.
• =CRP in mg/dl × 35 × total body wt.
• Hence,
• The formula for total MgSO4 needed in mg = CRP (in mg/dl) × 35 × total B.W.
• For example: - A 15 years old, 30 kg female with sepsis with CRP 50mg/dl, then we can calculate
the total amount of MgSO4 in mg for given body weight and CRP level.
• Here,total amount of needed
•
• MgSO4 = CRP (in mg/dl) × 35 × total body weight.
• = 50 × 35 × 30 mg
• = 1750 × 30 mg
• = 52500 mg
• = 52.5 gram
• CRP
Vasculitis (inflammation) = ---------
• Mg++

29. C-RP is non-specific biological marker
of inflammation and body stress,
• C-RP is non-specific biological marker of inflammation and body stress,
raised its value in various types of Inflammations and exposure to stress factor by
the body systems.
• For example: - C-RP rises in following condition (just some examples)
• Infections, cancers
• Hypoxic bain injury
• Hypertension
• Diabetes mellitus
• chronic alcohol use
• Smoking
• Low level of physical exercise
• Chronic fatigue / chronic diseases
• Excessive physical exercise
• Excessive coffee / tea in take
• High fatty diet
• Depression, psychosis
• Taking high dose estrogen
• Hypomagnesaemia

30. For Research evidence: -
CRP  1 / Mg++
• a) A recent study suggests a link between increased CRP levels and
development of age related macular degeneration (Seddon JM, et al, JAMA, 2004,
29 (6) - 704 - 710)
•
• b) Another recent study also suggests a link between increase CRP levels and
increased risk of Colon cancers. (Erlinger TP, et al. JAMA, 2004, 291(9), 585 - 590)
•
• c) ‘Magnesium intake reduces colorectal cancer risk’ - Journal of the American
Medical Association, 293: 86 - 89, 2005, January Issue.
•
• Here, analyzing of above three studies, there is clearly seen the association
between CRP, Mg++ level and degeneration (vasculitis) of macula.
• The relations are seen as
• CRP  vasculitis (macular degeneration)
• CRP  colon cancer
• Level of Mg++  1 / colorectal cancer
• CRP  1 / Mg++

31. CHEMISTRY OF MAGNESIUM:-
•
• Valency of magnesium =2,
• atomic No.=12,
• Atomic mass = 24.3050
• color is grayish white,
• Alkaline Earth metal,
• Discovered in: 1755
• Discovered by: Joseph Black of Scotland
• Named from:- Magnesia ; an ancient city of Greece
• Magnesium metal is obtained industrially from seawater (By electrolysis of
MgCl2), Mg ++ is not found freely, but found in its various salts / compound e.g.
MgCl2, MgSO4.
• Through the evolution, magnesium has role in numerous biological processes,
including its role as component of Chlorophyll in plants.
• Its major role in mammalian biology is to complex highly charged anions,
including organic poly phosphate (e.g. ATP, ADP, GTP, cAMP) and nucleic acids
(RNA & DNA) by which it can facilitate enzyme substrate interactions or stabilize
confirmations of polymers.
• Bank of Mg++ in the earth is seawater and sea is the 1st place to evolution of
organism in the earth.

32. Biological Benefits of magnesium
• Magnesium is critical to all species, especially plants and animals.
• Chlorophyll, the pigment that is responsible for photosynthesis, has a
single magnesium atom at its center.
• Without magnesium, chlorophyll would lose its ability to utilize sunlight.
• In humans, magnesium is used for a variety of purposes, such as in the
structure of bones and teeth, in cellular energy production, and in the
functioning of the nervous system, immune system.
• It is required in the activation of more than 300 enzymes.
• Humans suffering a magnesium deficiency experience a condition very
similar to the delirium tremens, mostly seen in alcoholics.
• Magnesium is an element that is required by our bodies for numerous
different functions.
• We need it for the proper growth, formation and function of our bones
and muscles. In fact, magnesium and calcium even control muscles
contraction.

33. Biological Benefits of magnesium
• Magnesium prevents some heart disorders and high blood pressure. Higher intake
of magnesium is also associated with improved lung function. Our bodies use it to
help convert our food into energy and it helps our bodies absorb calcium and
potassium.
• This important element also helps our brains function normally. Magnesium even
helps to prevent depression.
• Magnesium is essential in allowing our body to control insulin levels in blood. This
means that it is very important in the amount of energy that our body has to
operate. It is suspected that taking extra magnesium might be beneficial for those
suffering from fatigue.
• Taking extra magnesium is helpful for treating some medical conditions.
Magnesium is used in emergency situations such as an acute heart attack or acute
asthma attack,eclampsia etc. In non-emergency situations, magnesium is
sometimes given to asthma sufferers in a pill form. It relaxes the muscles along the
airway to the lungs, which allows asthma patients to breathe easier.
• Magnesium is effective in treating numerous heart / lung diseases and has been
used for over 50 years.
• Foods high in magnesium include fish, , lean meat, whole grains, seeds,
vegetables nuts , fruits and water containing high magnesium salts.

34. Metabolism of magnesium
• Mg++ is absorbed from the small intestine, and basically, excreted from kidney. During Mg++
deprivation, there is decreased urinary excretion of magnesium.
•
• Normal total body magnesium content about 25 gm (1000 mmol), 54% found in bone, 45 in soft
tissue, and 1% in extra cellular. Thus even only change small value (deficiency) in extra cellular
Mg++ level, there is invariably also changed in bone and soft tissue magnesium component.
•
• The normal serum Mg++ is (mean value) 1 mmol/L. Most of plasma Mg++ i.e. 60% ionized,
remaining 40% is complexed to anions such as phosphate, citrate and sulphate and bound to
protein.
•
• The magnesium content of soft tissue varies between 2.5 - 9 mmol/kg wet tissues. The higher the
metabolic activity of the cell the higher the magnesium content, for example, the magnesium
content of liver cell is about four times that of red cells.
•
• Within the cell the significant amount of Mg++ are in the nucleus, mitochondria, and endoplasmic
reticulum and in the cytosol. Within the cell, most of the magnesium is bound to protein and other
negatively charged molecules such as nucleotides (eg. ATP, ADP, DNA and RNA), in the cytoplasm,
about 80% of the Mg++ is complexed with ATP (frausto da Silva and Williums, 1919). 1-5% of total
cellular magnesium is free Mg++ ion (Ramani, et al 1993)
•
• Magnesium is the most important element of earth and second most common intracellular mineral
(cation_ of human cells).

35. Physiological Role of Magnesium:-
• 1. The main biological role of Mg++ in mammalian cell is involved
with anion charge neutralization. Mg++ particularly found in
association with organics polyphosphates such as nucleotide
triphosphate and nucleotide diphosphate (eg. ATP4-.Mg++ and
ADP3-.Mg++)
• 2. Mg++ also found associated with other highly anionic species,
including multisubstituated phosphates of sugars, such as iconostas
triphosphate, nucleic acids (RNA and DNA) and some carbohydrates
(eg. Isocitrate. Mg++ as substrate for Isocitrate lyase, Carboxylase
groups in proteins (Frausto da Silva and Williams, 1991, COWAN,
1995)
• 3. Magnesium ion is normally bound between the B and Y -
phosphates of nucleotide triphosphate such as ATP, and between
the  and B - phosphates of nucleotide diphosphate such as ADP.

36. Physiological Role of Magnesium:-
• 4. Mg++ serves to neutralize the negative charge density on the ATP or
other nucleotide tri or diphosphate and to facilitate binding of the
nucleotide phosphate to the enzymes that use them as substrates. In most
reactions in which Mg++ is involved, it is present as a complex with a
nucleotide triphosphate or diphosphate, which serves as substrate. The
Mg++ in these complexes does not interact directly with the enzyme in
most cases but is linked by the substrate in an enzyme substrate - metal
types of substrate bridge complex; Mg++ plays a dominant which are wide
spread in metabolism. These reactions are including those catalyzed by
Kinesis, G-proteins Adenylcyclase, ATP Synthetase, and ATPase a reaction
coupled to ATP hydrolysis.
• 5. Mg++ also is required for binding to some enzymes or other proteins
to stabilize then in the active confirmation or to induce the formation of
binding site or active site. Some enzymes known to require enzyme bound
Mg++ in these enzymes coordinates the binding of substrate to active site.
• 6. Mg++ also is bound to the myosin regulatory light chain in the actin -
myosin complex and is present glutamate synthesized.

37. Physiological Role of Magnesium:
• Mg++ also required for the conformational
regulation of the binding of elongating factors.
• 8. Additionally, Mg++ is found in association
with DNA and RNA, which are negatively charged
polymers due to the phosphate groups in the
nucleotide chains. Mg++ stabilizes bending of
RNA & DNA into particular curve or folded
structure.
• 9. On overall, Mg++ is required for regulation of
more than 300 enzymes and many
neurotransmitters of human body.

38. Role of Mg++ in Cellular Energy Metabolism
• 1. Mg++ ion is involved in many steps in central pathway of carbohydrates, lipid and protein
metabolism and in mitochondrial ATP synthesis eg. Many steps of glycolytic pathway require Mg++,
either in the form of a complex with the ATP or ADP substrate or as a part of the metallo - enzyme
itself.
• 2. The steps catalyzed by hexokinase and phospho-fructokinase requires Mg. ATP (i.e. ATP4-
.Mg++) as substrate, where as the steps catalyzed by phosphoglycerate kinase and pyravate kinase
require Mg.ATP (i.e. ADP3-.Mg++) as substrate. Thus there are numerous role of Mg++ complexed
ATP, acts as substrate for enzymatic activities.
• 3. Mg++ is required for phosphorylation and dephosphorylation reaction. ADP
phosphorylation by mitochondrial ATP Synthetase (F1F0-ATPase) involved in oxidative
phosphorylation utilizes Mg. ADP as substrate.
• 4. In cardiac and skeletal muscle as well as other soft tissues. The creatinine -
phosphocreatinine cycles acts as a serves for high-energy phosphate.
•
• Creatinine kinase
• MgATP+Creatinine-----------------------Mg++ - ADP + Phosphocreatinine
•
• Here, phosphocreatinine can be used to convert ADP to ATP when the muscle is subjected to a
heavy workload.
• Hence, it is true for all kinase enzymes that are Mg++ is an activating ion functioning with ADP &
ATP.

39. Role of Mg++ in Nucleic Acid and Protein Synthesis
• 1. The transcription, translation and replication of nucleic acids (RNA & DNA)
require enzymes that catalyze the hydrolysis and formation of phosphodiester
bonds. Almost all these enzymes require Mg++ for optimal activity. For instance,
DNA polymerase - I is thought to require Mg++ for stabilization of the confirmation
required for catalysis, RNA polymerize which catalyzer transcription. (The
sysnthesis of RNA using a DNA template) also require Mg++, the Mg++ cation again
is thought to effect a conformational change in the enzyme to produce a
catalytically competent state.
• 2. Replicating cells must is able to synthesize new protein and all cells must
continually replace protein that is degraded. Protein synthesis has been reported
to be highly sensitive to magnesium depletion. Mg++ required virtually in every
step of protein biosynthesis; the formation of the aminoacyl transfer RNA species,
which requires (Mg.ATP) and the maintenance of its confirmation (which is
required for recognition by messenger RNA) as well as the maintenance of the
ribosome, require Mg++.
• 3. Mg++ also is required for structure and activity of elongation factor -
Guanosine triphosphate (GTP) complexes that allow protein synthesis to begin and
for the GTPase activities that occur during elongation and termination of protein.

40. The second messenger system - Regulation by Mg++
• 1. Many hormones, neurotransmitters and other cellular
effectors regulate cellular activity via the Adenylate cyclase system.
The hormone receptor unit interfaces with Adenylate cyclase via
guanine nucleotide - binding protein (G- protein). Activation or
inhibition of Adenylate cyclase involves the dissociation of a G-
protein in to X and B-Y subunits, this process requires the presence
of GTP and Mg++ As it is the case for other ATP utilizing enzymes
the actual substrate for Adenylate cyclase is Mg ATP. There is also
evidence for an Mg++ bonding site on Adenylate cyclase through
which Mg++ directly increases enzyme activity. G-proteins, along
with GTP and Mg++, are also required for many other signaling
events in cells for example, in many endocrine disorder, there are
found hypomagnesaemia e.g. a. Diabetes b. Hyperaldosterionism c.
Thyrotoxicosis d. Hyperparathyroidism.hypothyroidism etc.

41. The second messenger system - Regulation by Mg++
2. Another group of hormones and neurotransmitters exerts their effects by raising
the ionized calcium concentration in the cytosol of their target cells through the
activation pf the phosphoinositol cycle. One of the principal mechanisms by which
this is thought to occur by receptor mediated activation of phospholipase-c. This
phospholipase-c hydrolyses a specific phospholipid present in the plasma
membrane, phosphotidylinositol 4,5 biphosphate (PIP2) to yield two biologically
active products, Diacylglycerol and ionositol triphosphate (IP3). Diacylglycerol
activates protein kinase-c, and IP3 triggers calcium release from endoplasmic
reticulum, The IP3 is rapidly inactivated by dephosphorylation,It appears that
Mg++ is essential for the normal functioning of this phosphoinositol cycle because
the kinase that forms the PIP2 , as well as the enzymes that inactivate IP3 requires
Mg++ at concentration that are physiological. (Connolly et al, 1985, valve et al,
1990)
• Higher Mg++ concentration decrease intracellular Ca++ by two mechanism
• Non-competitive inhibition of IP3 binding to the receptor
• Inhibition of the release of Ca++ via IP3 gated channel.
• -(Volpe ET. Al, 1990)
• Thus mechanism is the physiological calcium antagonist and vise versa. Mg++
regulates all the hormones and neuro transmitters at the physiological
concentration in the cell.

42. Ion channel Regulation by Mg++ (Electrolyte Regulation)
• 1. Ion channel constitute a class of protein that is responsible for
generating electrical signals across cell membrane. These proteins allow
passage of ions into or out of cells when the channels are open. Ion
channels are classified according to the type of ion they allow to pass,
such Na+, K+ or Ca++ (Acker man and clap ham, 1997). Mg++ plays an
important role in a function of a number of ion channels. Magnesium
deficiency results in cellular potassium depletion. Several mechanisms
may contribute to the potassium loss. Mg++ is necessary for the active
transport of K+ out of cells by the Na+/ K+ ATPase pump. Magnesium
depleted animals & humans have been found to have reduction in the
concentration of Na+/ K+ ATPase pumps in skeletal muscle, causing
decrease in cellular K+ (Dorup, 1994). The ATPase activity also is
dependent on Mg++ ion, there fore Na+ & K+ may be impaired during
magnesium deficiency.
• 2. Another mechanism for the K+ loss is an increased efflux of K+ from
cell via other Mg++ sensitive K+ channel, Mg++ is also involved in
regulating a number of K+ channel in heart muscle. Deficiency of Mg++ is
caused by reduced amount of Intracellular K+ causing - Arrhythmia in the
cardiac muscle.

43. Ion channel Regulation by Mg++ (Electrolyte Regulation)
• 3. Magnesium has been called “ Nature’s physiological calcium channel
blocker” (Iseri and French, 1984). During Mg++ deficiency, Intracellular
calcium rises.
•
• As calcium ion plays an important role in skeletal and smooth muscle
contraction, a state of magnesium depletion results muscle cramp,
hypertension, and coronary and cerebral vasospasm (Alturas and Altura,
1995)
• It is found that in lab studies: -
•
• In severe hypomagnesaemia there is occurred (intracellular serum)-
Hypokalemia, Hyponatremia, Hypophosphate and Hypocalcaemia. Some
studies linked decreased parathyroid hormone to hypomagnesaemia as
well as end organ resistance to Para thyroid hormone from
hypomagnesaemia).
•
• Thus, it is cleared that Mg++ regulates al the remaining electrolytes viz:
Na+, K+, Ca++ and phosphates, and other trace elements e.g. zinc etc.

44. Requirement of Magnesium:
• The recommended daily allowance (RDA) of magnesium 320-420 mg/kg
• The mean intake of magnesium by women and men in the USA has been
estimated to be 228 and 323 mg respectively for women and men. Which
are closed to average requirement 265 and 350 mg/day, but are less than
the RDA’s recommended meeting the nutrient needs of essentially all
individuals with in a population (Cleave land et al, 1996). This suggests
magnesium intake is marginal or low for a propertion of the population.
• Epidemiological studies have suggested an inverse relationship between
dietary magnesium intake and blood pressure (Altura and altura, 1995).
• There is inverse relationship between magnesium intake and vascular
diseases and sudden death( Altura and Altura, 1995).
• There is also an inverse association between low magnesium intake and
osteoporosis. (Freudenheim et al, 1986, Yano et al, 1985).
• Body obtains Mg++ by nutrition, 50% from grains (whole grains), wheat /
Barley / Nuts, 25% from fruits, 25% from vegetable, meats, seafoods &
fish.
•

45. Some important facts on Magnesium
•
• The serum level of magnesium does not necessarily with total body stores and
patients with magnesium deficiency are frequently asymptomatic, therefore,
magnesium deficiency might be difficult to diagnose of magnesium deficiency (9)
• .It should exist, regardless of measured serum level, in those conditions which are
accompanied by magnesium deficiency , such as use of drugs which cause renal
wasting of magnesium (e.g. digoxin, gentamycin, loop. diuretics), alcoholism,
hypokalemia and hypocalcemia or patients with diabetes mellitus.
• It is necessary to discriminate between magnesium deficiency due to an
insufficient magnesium intake which requires oral physiological supplementation
and magnesium depletion related to a dysregulation of the mechanisms of
magnesium status which requires or less specific regulation of its causal
dysregulation. (10).
• The average intake of magnesium in the western diet is often barely adequate to
meet daily requirements and therefore, magnesium deficiency is very in these
countries.
• Hypomagnesemia is a common disorder found in 65% of an intensive care unit
population (11) and 11% of a in-patient population (12).

46. Some important facts on Magnesium
• Other investigators have shown that the prevalence of hypomagnesemia in acute
care patients in two divisions of a consolidated medical center was 26.1% to 41.4%
compared to a frequency of 3.5% and 12.5% in the chronic care population (13).
• Magnesium deficiency might be asymptomatic even in severe cases. If present, the
clinical manifestations of magnesium deficiency generally fall within one of five
categories : cardiovascular effects, respiratory function, neurologic and
neuromascular effects, psychiatric disturbances or metabolic abnormalities (14).
• Magnesium deficiency affects different targets in the cardiovascular system
:Magnesium dietary intake modulates blood lipid levels, atherogenesis and
atherosclerosis (15).
• Magnesium deficiency enhances the uptake and metabolism of LDL by cultured
human endothelial cells (16).
• Magnesium modulates serum lipid uptake in macrophages, smooth muscle cells
and arterial wall (17).
• Magnesium supplementation markedly attenuates the artheroselerotic process,
while dietary deficiency of magnesium augments atherogenesis. Both magnesium
aspartate and magnesium sulfate were equipotent in preventing the development
of atherosclerosis and the rise in serum triglycerides caused by cholesterol loading,
although only magnesium aspartate lowered the serum cholesterol levels (18).

47. Some important facts on Magnesium
• Magnesium deficiency might be a contributing factor to ischemic heart disease
and to variant angina (19-21).
• Magnesium has antiarrythmic effect. It prolongs the PR interval, prolongs the
sinuatrial conduction time, increases the AV nodal refractory period, reduces
automaticity and has no effect on atrial or ventricular refractoriness or conduction
. Patients with congestive heart failure are usually treated by digitalis and loop
diuretics which are well known causes of magnesium deficiency .Magnesium is a
crucial cofactor in the Na-K-ATPase enzyme. Thus, magnesium deficiency reduces
the ability of the cell to accumulate potassium against a concentration gradient.
The lowered intracellular potassium concentration leads to a less negative resting
membrane potential, which may make the cell more easily depolarized and
increases cellular excitability (22).
• Magnesium therapy prevented ventricular premature beats in patients with
congestive heart failure (23), terminated supraventricular tachyeardia (24, 25),
multifocal atrial tachycardia (26), atrial fibrillation (27), intractable ventricular
arrythmia (28) and torsades de pointes (29).
• Magnesium deficiency is associated with myocardial injury (cell degeneration,
fibrosis, necrosis and calcifications). Magnesium deficiency decreases the body's
antioxidant capacity and the resistance of the tissues to free radicals. This might be
the mechanism which associates magnesium deficiency with cardiomyopathy (30).
•

48. References
• Mortha H. Stipunik, Biochemistry and physiological aspect of Human nutrition, chapter 29, page 671 - 684, WB
Sauder Company, 2000)
• Frausto da Silva and Williams, 1991, COWAN, 1995
• Altura and altura, 1995
• Cleave land et al, 1996
• Connolly et al, 1985, valve et al, 1990
• Iseri and French, 1984
• Acker man and clap ham, 1997
• Volpe ET. Al, 199
• WAKER WEC, PARISI AF: Magnesium metabolisms. N Engl J Med 1968; 278: 658-63, 712-7, 772-6.
• DURLACH J, DURLACH V, BAC P et al. : Magnesium and therapeutics. Magnes Res 1994; 7: 313-28.
• 11. RYZEN E, WAGERS PW, SINGER FR et al. : Magnesium deficiency in a medical ICU population. Crit Care Med
1985; 13: 19-21.
• 12. WONG ET, RUDE RK, SINGER FR et al. : A high prevalence of hypomagnesemia in hospitalized patients, Am J
Clin Pathol 1983; 79: 348-52.
• 13. LUM G: Hypomagnesemia in acute and chronic patient care population. Am J Clin Pathol 1992; 97: 827-30.
• 14. FLINK EB : Magnesium deficiency. Etiology and clinical spectrum. Acta Med Scand 1981 ; 647 (Suppl) : 125-37
• 15. OUCHI Y, TABATA RE, STERGIOPOULOS K et al. : Effect of dietary magnesium on development of atherosclerosis
in cholesterol fed rabbits. Arteriosclerosis 1990; 10: 732-7

49. References
• 16. YOKOYAMA S, GU J, KASHIMA K et al. : Combined effects of magnesium deficiency and an atherogenic level of
low cultured human endothelial cells. II electron microscopic data. Magnes Res 1994; 7: 97-105.
• 17. ALTURA EM, ALTURA BT : Cardiovascular risk factors and magnesium: relationship to atherosclerosis, ischemic
heart disease and hypertension. Magnes Trace Elem 1992; 10 :182-92. 18. ALTURA BT, BURST M, BLOOM S et al. :
Magnesium dietary intake modulates blood lipid levels and atherogenesis. Proc Natl Acad Sci USA 1990; 87: 1840-
4.
• 19. EISENBERG MJ : Magnesium deficiency and sudden death. Am Heart J 1992; 124 : 544-9.
• 20. RASMUSSEN HS, Mc NAIR P, GORANSSON L et al. : Magnesium deficiency in patients with ischemic heart
disease with and without acute myocardial infarction uncovered by an intravenous loading test. Arch Intern Med
1988; 148: 329-32.
• 21. GOTO K, YASUE H, OKUMURA K et al. : Magnesium deficiency detected by intravenous loading test in variant
angina pectoris. Am J Cardiol 1990; 65: 709-12.
• 22. Mc LEAN RM : Magnesium and its therapeutics uses : a review. Am J Med 1994; 96: 63-76.
• 23. GOTTLIEB S, FISHER ML, PRESSEL MD et al. : Effects of intravenous magnesium sulfate on arrhythmias in
patients with congestive heart failure. Am Heart J 1993; 125: 1645-50.
• 24. WESLEY RC, HEINES DE, LERMAN BB et al. : Effect of intravenous magnesium sulfate on supraventricular
tachycardia. Am J Cardiol 1989; 63: 1128-31.
• 25. SAGER PT, WIDERHORN J, PETERSON R et al. : Prospective evaluation of parenteral magnesium sulfate in the
treatment of patients with reentrant AV supraventricular tachycardia. Am Heart J 1990; 119 : 308-16.
• 26. ISERI LT, FAIRSHTER RD, HARDEMANN JL et al. : Magnesium and potassium therapy in multifocal atrial
tachycardia. Am Heart J 1985; 110 : 879-85.
• 27. DE CARLI C, SPROUSE G, LA ROSA JC: Serum magnesium levels in symptomatic atrial fibrillation and their
relation to rhythm control by intravenous digoxin. Am J Cardiol 1986; 57: 956-9.
• 28. ISERI LT, CHUNG P, TOBIS J : Magnesium therapy for intrac- table ventricular tachyarrythmias in
normomagnesemic pa- tients. West J Med 1983; 138: 823-8.
• 29. TOPOL EJ, LERMAN BB : Hypomagnesemic torsades de pointes. Am J Cardiol 1983; 52 : 1367-8.
• 30. FREEDMAN AM, ATRACKHI AH, CASSIDY NM et at. : Magnesium deficiency-induced cardiomyopathy :
protection by vitamin E. Biochem Biophys Res Commun 1990; 170 : 1102-6.

50. Causes 0f Hypomagnesaemia:
• Although magnesium deficiency is a common
clinical problem,serum magnesium level are
often overlooked or not measured in patient with
at risk for the disorder approximately 10% 0f
patients admitted to city hospitals are
hypomagnesemic,and upto 65% of patients in
intensive care units may be magnesium
deficient.(ref-Harrison’s principles of internal
medicine, part -2,15th ed. Page 2197.)

51. Causes of magnesium depletion:
• 1. Most common cause of magnesium depletion:-Is the chronic dietary insufficiency intake of magnesium
(Low magnesium containing diet, (magnesium intake is marginal or low for a proportion of popular even in
developed countries) - cleave land ET, al 1996).
• 2. Another common cause is stress (physical, mental, emotional, diseased conditions, or infective/ parasite
invasion, viral infections, physiological stress e.g. pregnancy,lactation, growing age/ advance age, trauma, any
surgery). In these stress full conditions, there is increased metabolic rate of the body, increased sympathetic
overdrive and increased renal excretions of Mg++ causing relative hypomagnesaemia. It is well known that the
relationship of any stress full condition in the body and serum level of magnesium in the body is inversely
proportional to stress.
• 3. GI disorders: -
• Total potential nutrition for long time
• Prolong nasogastric suction or vomiting
• Acute and chronic diarrheas
• Extensive bowel resection (sort bowel syndrome)
• Intestinal and bowel fistula, biliary fistula
• acute pancreatitis
• Malabsorption syndrome/ ch. Pancreatic
• celiac disease
• Cystic fibrosis
• Intestinal lymphangiatasia
• Protein - calorie malnutrition
• Primary intestinal hypomagnesaemia with secondary hypocalcaemia
• Cholestatic lever disease
•

52. Causes of magnesium depletion:
• 4. Renal losses: - (Renal disorders)
• chronic paranteral fluid with out Mg++ therapy
• Osmotic diruresis (manitol, hyperglycemia, DKA/DM)
• Hypercalcemia
• Drugs: - Diuretics (except K+ sparing diuretics)
• a. Frusemide, thiazides, ethacrrnic and, acetazolamide)
• b. Amino glycosides:- Getamicin, Amikacin
• c. Amphotericin-B
• d. Alcohol (ethanol)
• e. Pentamidine
• f. Cisplastin, tricolimus
• g. Cyclosporin
• h. Carbenicillin, ticascillin
• i. High dose fluoride (fluoride poisoning)
• j. Digoxin

53. Causes of magnesium depletion
• Diabetes mellitus/ DKA - Hyperglycemia - Excretion of Mg++
• Primary aldosteronism
• renal diseases: -
• chronic pyelonephritis
• interstitial nephritis
• Glomerulonephritis
• Diuretic phase of acute tubular neurosis
• Post obstructive nephropathy
• renal tubular acidosis
• Post renal transplantation
• Nephrotic syndrome (excessive loss of protein and Mg++ also excretes with proteinuria)
• Genetic diseases
• a. Gitel man syndrome
• b. Barter syndrome
• c. Autosomal recessive renal magnesium wasting
• d. Infantile primary hypomagnesaemia
• e. Hypomagnesaemia with hypercalciurea
• f. Mitochondrial disorders
• g. Autosomal dominant hypoparathyroidism
•

54. Causes of magnesium depletio
5. Rapid administration of citrated blood, may drop Mg++ temporarily becomes citrate chelates
circulating magnesium ions.
6. Metabolic Acidosis / Respiratory Alkalosis
• a) Starvation
• b) Sepsis
• c) Infants of diabetic mother
• d) DKA untreated
• e) Ch. Alcoholism
•
7. Endocrine disorders
• a. Hyperaldosterionism
• b. Hyperparathyroidism
• c. Thyrotoxicosis
• d. Hypothyroidism
• e. Diabetes mellitus /DKA
• f. Vitamin -D deficiency
• g. Osteoporosis
• h. Hungry bone syndrome (post parathyroidectomy)
• i. SAIDH.

55. Causes of magnesium depletion
• 8. Miscellaneous causes -
• Advance age group (old age)
• Physiological stress (pregnancy, anb lactation ( ↑demand)
• rapidly growing child,
• premature baby
• intrauterine growth retardation
• Low birth weight baby
• Birth asphyxia (Stress)
• infantile seizures
• Lactating mother,
• Baby of diabetic mother
• Players (excessive physical activities)
• Mental stress: -Anxiety, depression, mood disorder schizophrenia,
• Congenital cardiovascular diseases - with CCF, increased metabolic rate.

56. Causes of magnesium depletion
• Hyper reactive Airway disease(increased muscle work)
• Burn severe pain,panceatitis
• Many surgical intervention
• Past strokes, post MI, post injuries.
• Many enzymatic disorder - (enzymes def diseased)
• Many oncogenic diseases, cancer
• HIV infection, chronic fatigue syndrome
• Many autoimmune and degenerative diseases
• Many connective tissue disorders R.A./ SLE/ psoriasis/dermatomyositis
• Many systemic vasculitic diseases
• Excessive intake of Caffeine, Carbolic acid (coke,pepsi), tea, glucose, fats
•
• Theoretically: - In any condition, viz increased metabolic disorders (increased metabolic rate),
Relative decreased intake of Mg++ increased renal loss of Mg++ (By drugs, diseases) and many
stressful condition physical, mental, surgical, biological, infections) ,Over all leads relative
Hypomagnesaemia Causing more disease symptoms and increased pathogenesis of diseases
progressively.
• Hypomagnesaemia yet is frequently overlooked in our medical practice

57. Drugs that cause loss of body magnesium:
• Drugs that cause loss of body magnesium:
• Alcohol 1,2,3,4,5,6,7
Alcohol-withdrawal-stress 8
Cocaine 9
Beta-adrenergic agonists 10 (for asthma)
Corticosteroids (CS) 11 (for asthma)
Theophylline 12 (for asthma)
Diuretics 13,14
Thiazide 15
Caffeine. 16,17,18
Phosphates (found in cola drinks) 19
• OTHER CAUSES OF LOSS OF Mg:
Physical or mental stress 20,21
Dietary fat 22
Dietary Calcium 23,,24,25,26,,27
•

58. references
•
• 1. Kalbfleish, J. M., et al. Effects of Ethanol Administration on Urinary Excretion of magnesium and other
electrolytes in alcoholic and normal subjects. Journal of Clinical Investigations. Vol. 42. 1963.
• 2. Role of magnesium and calcium in alcohol-induced hypertension and strokes as probed by in vivo television
microscopy, digital image microscopy, optical spectroscopy, 31P-NMR, spectroscopy and a unique magnesium ion-
selective electrode ALCOHOL. CLIN. EXP. RES. (USA), 1994, 18/5 (1057-1068) abstract.shtml
• 3. Kalbfleisch JM, Lindeman RD, Ginn HE, Smith WO: Effects of ethanol administration on urinary excretion of
magnesium
and other electrolytes in alcoholic and normal subjects. J Clin Invest 42:1471-1475, 1963.
• 4. Mendelson JH, Ogata M, Mello N: Effects of alcohol ingestion and withdrawal on magnesium states of
alcoholics: clinical
and experimental findings. Ann N Y Acad Sci 162:918-933, 1969.
• 5. Lindeman RD.: Nutritional influences on magnesium homeostasis with emphasis on renal factors. In Magnesium
in Health
and Disease,eds M Cantin, MS Seelig, Spectrum, NY,NY, 1980, pp 381-399 (2nd Intl Mg Sympos, Quebec, Canada,
1976)
• 6. Flink EB, Stutzman FL, Anderson AR, Konig T, Fraser R: Magnesium deficiency after prolonged parenteral fluid
administration and after chronic alcoholism complicated by delirium tremens. J Lab Clin Med 43:169-183, 1954.
• 7. Flink EB: Magnesium deficiency in alcoholism. Alcoh: Clin Exp Res 10:590- 594, 1986.
• 8. Flink EB, Shane SR, Scobbo RR, Blehschmidt NG, McDowell P: Relationship of free fatty acids and magnesium in
ethanol withdrawal in dogs. Metabolism 28:858-865, 1979.
• 9. Cocaine Induces Rapid Loss of Intracellular Free Mg2+ In Cerebral Vascular Smooth Muscle Cells. Altura BM,
Zhang A, Cheng TPO, Altura BT. European J. of Pharmacology --- Molecular Pharm. Section, 246 (1993) 299-301
• 10. Consequences of Magnesium Deficiency on the Enhancement of Stress Reactions; Preventive and Therapeutic
Implications (A Review) Seelig, M.S. Journal of the American College of Nutrition, Vol. 13, No. 5, 429-446 (1994)
conseq.shtml
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conseq.shtml
• 13. Ryan MP, Ryan MF, Counihan TB: The effect of diuretics on lymphocyte magnesium and potassium. Acta med
Scandinav Suppl 647:153-161, 1981.
• 14. Widman L, Dyckner T, Wester PO: Effect of moduretic and aldactone on electrolytes in skeletal muscle in
patients on long-term diuretic therapy. Acta med Scandinav Suppl 661:33-35, 1982.
• 15. The Effect of Varying Molar Ratios of Potassium-Magnesium Citrate on Thiazide-induced Hypokalemia and
Magnesium Loss. Journal of Clinical Pharmacology (Vol. 38, Issue 11) Nov. 1998
• 16. Influence of injected caffeine on the metabolism of calcium and the retention and excretion of sodium,
potassium, phosphorus, magnesium, zinc and copper in rats. J Nutr. 116(2):273-80, 1986 Feb.
• 17. Calcium and magnesium contents and volume of the terminal cisternae in caffeine-treated skeletal muscle. J
Cell Biol. 99(2):558-68, 1984 Aug.
• 18. Effect of caffeine and theophylline on Mg ++ -dependent ATPase. Arch Int Physiol Biochim. 80(4):815-8, 1972
Oct.
• 19. Prepublication copy, 1997, of the Dietary Reference Intakes for Magnesium, from the Institute of Medicine of
the National Academy of Science. Page 6-5 . exhibitk.shtml
• 20. Durlach, J. (1989): Recommended dietary amounts of magnesium: Mg RDA. Magnesium Res. 2, 195-203.
• 21. Consequences of Magnesium Deficiency on the Enhancement of Stress Reactions; Preventive and Therapeutic
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