Essential and trace ions

 1- Iron:-
 It is essential to the elementary metabolic processes in
the cell
 In the respiratory chain , iron functions as an electron
carrier
 Iron is responsible for the transport of molecular oxygen in
higher organisms
 both of these functions depend on the ability of iron to
exist in coordination compounds in different states of
oxidation and bonding
occurrence iron bound as mode of linkage function

Blood system Hemoglobin Heme O2 Transport

Plasma Transferrin Fe Transport

Tissue Functional iron Heme Cell respiration

( myoglobin, cell
hemes)

Storage iron Ferritin Iron pool

hemosiderin Detoxication
 Hemglobin consists of four protein chains, each of which
contains a heme unit of a porphyrin ring and ferrous iron.
 Ferritin and hemosiderin are iron storage proteins found in
the liver, spleen, and bone marrow
 Ferritin is a water soluble, crystallizable iron protein built
up from apoferritin and micelles of a colloidal ferric
hydroxide-phosphate complex
 Although the iron in ferritin is stored in the Fe+3 form it is
incorporated and released in the Fe+2 form
 Hemosiderin is water insoluble and is considered by some
to be a dehydrated ferritin.
 The major iron transport protein of blood plasma is a
glycoprotein known as transferrin
 Iron transport into the intestinal mucosa is facilitated by
ascorbic acid, fructose, and other organic molecules
which tend to hold iron in a soluble ferrous state.
 The response of the intestine to iron depletion is more
rapid when erythropoiesis (RBc production)is stimulated
than when storage sites in the liver are reduced
 This has lead to the concept that as transferrin becomes
depleted of iron during RBc formation, transferrin returns
to the intestinal wall to pick up more iron , thereby
signalling the intestine to absorb more iron.
 A person deficient in iron will become anaemic.
 Anaemia is a general term for a condition in which:
1.circulating red blood cells are deficient in number.
2.or deficient in total haemoglobin content per unit of blood
volume.
 The net result is lower oxygen carrying capacity by the
blood.
 Anaemia can be caused by excessive loss of blood or
destruction or they may be due to decreased blood
formation.
 Excessive blood loss can be caused by bleeding ulcer,
haemorrhaging and menstrual flow.
 Blood destruction is caused by haemolytic agents (drug
therapy, infections, toxins )or defective
haemoglobins(sickle cell anaemia, thalassemia).
 Anaemia due to decreased blood formation can be
caused by deficiencies of key materials (cobalamine, folic
acid, pyridoxine and iron ), infections, renal insufficiency,
malignancy, and marrow failure.
 Iron compound used for replacement therapy must meet
two requirements:
1.it must be biologically available, usually water soluble,
ferrous sulphate is the standard to which other iron salts
are compared.
2. must be not irritant .
 Sustained released iron formulation have been utilized to
minimize the irritant property of iron.
 Parenteral iron preparations are indicated only in:
1.defect in iron absorption as in partial gastroctomy,
steatorrhea .
2.iron salt may irritate GIT so not used as in ulcerative
colitis, peptic ulcer.
 Overdosage of oral iron is serious and can cause death,
particularly in young children
 The human lethal dose is considered to be 150 to 200
mg iron / kg body weight.
 Ingestion of 10-15 (300mg ferrous sulfate tablet)may be
lethal to a child, with a mortality rate near 50%
 Iron poisoning progresses in three to four stages
 Stage one begins 30 to 40 minutes after ingestion and
includes gastrointestinal distress due to the astringent action
of ionized iron, developing into cardiovascular collapse, shock
and possible death in six hours.
 In stage two recovery seems apparent and may continue for
10 to 14 hours
 Stage three may then develop with a recurrent cardiovascular
collapse, convulsions, metabolic acidosis, shock, coma, liver
damage, and possible death occurring in one to three days.
 If the patient survives, stage four may occur one to two
months later with gastrointestinal complications ( scarring,
pyloric obstruction) due to the necrotizing effect (cell death) of
the iron.
 Treatment usually includes
1- gastric lavage
2- and administration of salts (sodium bicarbonate and
sodium dihydrogen phosphate) to form insoluble iron
salts.
3-Oral administration of deferoxamine will prevent iron
absorption. Provided kidney damage has not occurred.
 Deferoxamine can be given parenterally to chelate the
iron and allow it to pass out in the urine.
4- Peritoneal dialysis has also been tried with poor results.
 A recent report suggests lavage of the stomach with a
phosphate salt to bind all unabsorbed iron that was not
expelled by emesis.
 Chelation by deferoxamine mesylate (desferal mesylate)
is indicated only when there is unbound iron
demonstrated in the serum.
 Orally administered iron has been shown to interfere with
absorption of tetracycline presumably by forming a 1:1
chelate.
 Oral ferrous salts may aggravate gastrointestinal diseases
such as peptic ulcer , regional enteritis, and ulcerative
colitis.
 Official iron product:
 There are three officially approved iron salts available for
the oral administration of iron.
 1.Ferrous sulphate FeSo4.7H2O
 Ferrous sulfate U.S.P occurs as pale, bluish green
crystals or granules which are odorless.
 it is oxidizes readily in moist air to form brownish yellow
basic ferric sulphate [Fe4(OH)2(SO4)5 ]
 Ferrous sulphate is the most widely used oral iron
preparation and is considered as the drug of choice for
treating uncomplicated iron deficiency anaemia.
 It can be irritating to GIT mucosa due to the astringent
action of soluble iron but iron salt equivalent doses are
used.
 Usual dose : 300mg, the equivalent of 60mg of elemental
iron, two or three times a day.
 Dosage forms: dried ferrous sulfate tablets, and syrup.
 2.Ferrous fumarate.
 Ferrous fumarate U.S.P occurs as a reddish orange to
red-brown, odorless powder.
 It is resistant to oxidation on exposure to air so it may be
superior to both ferrous sulphate and gluconate.
 Usual dose : 200mg, the equivalent of 60mg of elemental
iron, two or three times a day.
 Dosage forms: ferrous fumarate tablets
 3.Ferrous gluconate.
 Ferrous gluconate N.F. occurs as a yellowish gray or pale
greenish yellow, fine powder or as granules having a
slight odor.
 It has a good bioavailability .
 Usual dose : 300mg, the equivalent of 35mg of elemental
iron, three times a day.
 Dosage forms: ferrous gluconate tablets
 It is doubtful if it is any less irritating than ferrous fumarate
or sulfate when equivalent doses of iron are administered
why?? (H.W.)
 Parenteral administration of iron:
 1-Iron dextran injection, U.S.P. (Imferon)
 is a sterile , colloidal solution of ferric hydroxide
[Fe(OH)3] complexed with partially hydrolyzed dextran
(glucose polymer) of low M.wt., in Water for Injection.
 The PH will between 5.2 and 6.5. prior to mixing, it is a
dark brown, slightly viscous liquid.
 It is for I.M. injection only.
 It is used only in confirmed cases of severe iron
deficiency anemia where oral therapy is contraindicated
or ineffective, or if the patient cannot be relied upon to
take oral medication.
 Usual dose: intramuscular, the equivalent of 100mg of
iron once a day.
 2- Iron sorbitex injection. U.S.P. (Jectofer)
 Is a sterile solution of a complex of iron , sorbitol, and
citric acid that is stabilized with the aid of dextrin and an
excess of sorbitol.
 The PH is between 7.2 and 7.9. by itself, iron sorbitex is a
dark brown, clear liquid.
 Is to be administered by the I.M. route only.
 Usual dose: intramuscular, the equivalent of 100mg of
iron once a day.
 the concurrent administration of oral iron is
contraindicated
 The patient “s urine can become dark on standing due to
the formation of iron sulfide.
2.Copper:
 It is required for many enzymes, for synthesis of
haemoglobin and for normal bone formation.
 Unlike iron it is believed that most of the population obtain
the sufficient amount of copper from food, water, and
cooking utensils.
 Copper supplements are probably not necessary.
 The adult human is estimated to contain about 2mg/kg of
copper, distributed mostly in enzymes and other proteins.
 The average daily intake is estimated at 2-5 mg per day.
 Copper is solubilized in stomach acid and absorbed from
the stomach and upper small intestine,
 From intestine copper moves into the blood where it
exists first as copper albumin complex, then goes to the
liver where the copper become part of copper protein,
ceruloplasmin .
 Ceruloplasmin copper is not released until the protein is
catabolized
 Copper is found in the brain in form of cerebrocuprein, in
blood cells as erythrocuprein.
 Several roles in metabolism have been attributed to
copper :
1. haemoglobin formation.
 copper is required to prevent anaemic conditions through:
a. facilitate iron absorption.
b. Stimulates enzymes involve haeme and globin
biosynthesis.
c. Could involve in metabolism of stored iron .
2. It is important in oxidative phosphorylation (ATP
production by cellular respiration )
Copper is a constituent of cytochrome oxidase.
3. It is associated with the formation of aortic elastin.
It may be that copper is necessary for amine oxidase
activity and may play a role in the formation of cross
linkages of elastin .
4. It is a component of tyrosinase , an enzyme responsible
for conversion of tyrosine to the black pigment, melanin.
A copper deficiency in animals may cause loss of hair color
which can be attributed to reduced tyrosinase activity.
Albinisim is associated with either an absence of or an
inactive form of tyrosinase.
 Wilson disease a condition of excess copper storage.
 Is of genetic origin, being transmitted by an autosomal
recessive gene
 There is a decrease in ceruloplasmin conc. which lead to
a decrease in total blood copper ,and characterized by
presence of large amounts of copper in the brain along
with an excessive urinary output ,increased copper levels
in liver, brain, kidney, and cornea.
 Pencillamine is the drug of choice which is a
chelating agent , in addition to diet restriction.
 Uses of Copper
1. Topically as fungicide and astringents.
2. Antidote for phosphorous poisoning.
3. Essential component of Fehling and benedict solutions
which are used for determination of glucose.
 a positive test is the production of cuprous oxide.
3.zinc :
 Zinc essential for:
1.Several enzymes as alcohol dehydrogenase, alkaline
phosphatase, carbonic anhydrase, glutamic
dehydrogenase and others.
2.Zinc bound to RNA stabilizing secondary and tertiary
structures.
3.For normal growth and reproduction.
4.It has a beneficial effect on tissue repair and wound
healing.
5.Zinc complexes with insulin present in B cells of
pancreas.
6. Necessary for vitamin A mobilization from liver and vit. A
metabolism affected by zinc deficiency.
Low plasma zinc level is found in:
1.Alcoholic cirrhosis (progressive liver disease).
2.Uremia.
3. Myocardial infarction.
4.Cystic fibrosis with growth retardation.
 Food sources of zinc includes : seafood, nuts, meat,
eggs, and milk.
 A person on vegetable diet may not receive a sufficient
amount of zinc (10-15 mg daily) because phytic acid
which found in vegetable proteins such as soya bean
combine with zinc and decrease its absorption.
 Zinc sulfate is official as a topical astringent.
 4- Selenium :
 The main function of selenium is to mediate the activity of
the enzyme glutathione peroxidase, which acts as an
antioxidant.
 The oral administration of large doses of selenium salts
produce intestinal irritation and interference with the
functioning of small blood vessels and blood-forming
organs.
 It may be of therapeutic value in the treatment of
kwashiorkor, a protein deficiency affecting large numbers
of children and infants in south america, africa and asia
 Selenium has been implicated in cellular respiration and
as an antioxidant in conjunction with vitamin E.
 Selenium is official as Selenium sulfide N.F., a suspension
for the treatment of seborrheic dermatitis of the scalp
(dandruff).
 5- Sulfur:
 Sulfur is widely distributed throughout the body in:
 1. Proteinase a. Sulfhydryl groups of cysteine.
b. Disulfide linkages in protein from cystine
 2. Mucopolysaccharides and sulfolipids as sulphate salts
and esters.
 Dietary sulfur comes from these same groupings found in
plant and animal foodstuffs.
 Sulphur has been used therapeutically as :
 1.Cathartic action.
 2.Parasiticide in scabies.
 3.Stimulant in alopecia
 6- Iodine(Iodide):
 Iodide is an essential ion necessary for the synthesis of
two hormones produced by thyroid gland, triiodothyronine
T3 and thyroxineT4.
 Internally iodine or iodide can be administered, since
iodine is reduced to iodide in the intestinal tract but more
common iodide salts are administer because of solubility
reasons.
 Iodine have :
1. biochemical role in thyroid hormone formation.
2. pharmacological action as:
 a. Fibrinolytic agent.
 b. Expectorant .
 c. Bactericidal agent.
 The usual daily iodine requirement for an average male is
140 micrograms and female about 100 micrograms.
 Lack of sufficient iodine in diet result in an enlargement of
thyroid gland.
 When iodine is administered its uptake is governed by
three principle factors:
1.The character of local thyroid tissue because abnormal
thyroid tissue (tumorous) has a slower uptake of iodide
and a lower content of iodine than normal tissue.
2. Blood level of inorganic iodide ,because a high level
keeps the iodine at high level in the colloids thus using up
only a small part of the administered iodide.
3. The level of TSH in blood which is hormone secreted by
anterior pituitary gland because the thyrotropin content
has a direct bearing on the complete utilization of iodine in
the formation of of the iodinated hormones, and
thyrotropin also controls the release of thyroid hormone
from the thyroid gland .
 Excess of iodide inhibit release of TSH and decrease
production of thyroid hormones.
 The effect of such antithyroid drugs as propylthiouracil is
not to inhibit iodine uptake but rather to block the enzyme
system that iodinates the amino acid precursor .
 Thyroid gland regulates:
1.metabolism of the body.
2. affect growth and development of the body.
 Iodide therapeutically used as :
 Improving agent in hyperthyroidism.
 Radioactive iodide used which administered in the form of
sodium iodide .the body converts the inorganic radioactive
iodide into thyroglobin in the thyroid gland ,thus subjecting
the gland to radiation that will cut down its activity.
 Official iodine product
 Strong iodine solution U.S.P. (Lugol ‘s solution)
 Contains 5g of iodine and 10g of potassium iodide per
100ml total volume
 It is a transparent liquid having a deep brown color and
odor of iodine.
 Usual dose: 0.1 to 0.3 ml three times a day