Thyroid Hormones And

Anti – Thyroid Drugs

By
Gunjan Kalyani, M.Pharm.
Assistant Professor
Columbia Institute of Pharmacy
Raipur 493111, Chhattisgarh, India
Mobile: +91-8349204583
Mail ID: kalyani.gunjan@yahoo.in
 
Former Research Fellow
National Center for Natural Resources (NCNR)
Pt. Ravishankar Shukla University, Raipur 492010, India
 Thyroid Gland

A. The thyroid gland is the largest endocrine organ,

weighing 10 to 20 g in the adult. It is found on
the ventral surface of the trachea below the
larynx and consists of two lobes joined by an
isthmus.

B. Two pairs of parathyroid glands are located on

the dorsal surface of the thyroid. The thyroid
gland is supplied by nerves from the autonomic
nervous system; the sympathetics increase thyroid
hormone synthesis and secretion, while the
parasympathetics decrease these functions.

C. The thyroid has an excellent blood supply, with

one of the highest rates of blood flow of any
organ in the body.
 THYROID HORMONES AND ANTI – THYROID DRUGS
D. The thyroid is made up of lobules containing a series of follicles.
The lumen of each follicle is surrounded by a single layer of
epithelial cells, called follicular cells, and the lumen filled with a
pink-staining (with hematoxylin and eosin) proteinaceous
material, called colloid.
E. The follicular cells synthesize thyroglobulin, thyroid hormone
precursor, which is extruded into the lumen of the follicle for
storage.
 Thyroid Hormones
A. Thyroid gland produces thyroid hormones. These hormones are
essential for life and have many effects on body metabolism, growth, and
development.
B. Thyroid hormones are derivatives of the amino acid tyrosine bound
covalently to iodine. The two principal thyroid hormones are:
Thyroxine (also known as T4 or L-3,5,3',5'-tetraiodothyronine)
Triiodotyronine (T3 or L-3,5,3'-triiodothyronine)
C. As shown in the figure-1, the thyroid hormones are basically two
tyrosines linked together with the critical addition of iodine at three or
four positions on the aromatic rings. The number and position of the
iodines is important.
D. Several other iodinated molecules are generated that have little or no
biological activity; so called "reverse T3" (3,3’,5’-T3) is such an example.
Thyroid Hormones
 Thyroid Hormones
E. Thyroid hormones are poorly soluble in water, and more than 99% of the
T3 and T4 circulating in blood is bound to carrier proteins. The principle
carrier of thyroid hormones is thyroxine-binding globulin, a glycoprotein
synthesized in the liver.
F. Two other carriers of import are transthyrein and albumin. Carrier
proteins allow maintenance of a stable pool of thyroid hormones from
which the active, free hormones are released for uptake by target cells.
 Metabolism of Thyroid Hormones
A. The thyroid gland secretes about 100 nmol of T4, about 5 nmol of T3 and
less than 5 nmol of rT3.
B. Over 80% of the plasma pool of T3 is derived from the peripheral
metabolism of T4 to T3 by 5'-deiodination. Most of the rT3 is formed from
the 5 deiodination of T4. The 5'deiodinase found mostly in the liver and
kidney is the most abundant deiodinase. The major function of this enzyme
is the splitting off of the 5' I from T4 to provide T3 to the plasma.
C. 5'deiodinase is increased in hyperthyroidism, which accounts for the high
levels of T4 in this condition.
D. During starvation, fasting, or hypothyroidism, levels of 5' deiodinase
decrease. The decline in this enzyme results in less active hormone, T3 being
available and conserves calories and inhibits proteinolysis.
 Metabolism of Thyroid Hormones
E. Another type of deiodinase takes off iodines from 5 and 5' resulting in 3,3-
Diiodothyronine which has very little activity. Thyroid hormones often are
metabolized further by means of progressive deiodination to thyronine
and the breaking of the ether bond to yield tyrosine.
F. When T4 and T3 undergo a selective decarboxylation and deamination,
the products are, respectively 3,5,3',5' tetraiodothyroacetic acid (Tetrac) and
3,5,3' triiodothyroacetic acid (Triac). It has been estimated that these
metabolites have anywhere from 10% to 50% of the biological activity of
their parent compounds.
G. In the liver, intact T3 and T4 can undergo conjugation to yield thyroid
hormones as sulfates or glucuronates. These hormone conjugates enter the
bile and pass into the intestine, where the conjugate is hydrolyzed and the
free T3 or T4 may be reabsorbed into the enterohepatic circulation to be
reused or excreted in the stool.
 Physiological Actions of T3 and T4
Thyroid hormones have various actions on the body; some of them are as
follows:
A. Calorigenic action: T3 increases the oxygen consumption and heat
production in the body, stimulating Na+- K+ ATPase in cells of all
metabolically active tissues. The exceptions are adult brain, lymph nodes,
spleen, uterus, testes, anterior pituitary gland. This action contributes to
the increased metabolic rate and heat sensitivity in hyperthyroid patients.
It controls the basal metabolic rate (BMR) rate.
B. Metabolic action: Thyroid hormones increase the rate at which
carbohydrates are absorbed from the GI tract. In patients with normal
thyroid activity, glucose levels tend to be normal and glycogen synthesis is
stimulated. However, with hyperthyroidism, T3 increases hepatic
glycogenolysis and gluconeogenesis. An increase in T3 exacerbates
symptoms of diabetes mellitus.
 Physiological Actions of T3 and T4
C. Effect on Fetal Development and Maturation: T3 is necessary for fetal
growth and development. Thyroid hormone and growth hormone act
synergistically in the maturation of the fetus and development of the
CNS. When thyroid hormone is absent, children show mental retardation
and dwarfism. Hypothyroid children often exhibit delayed puberty and
bone growth. In some classic experiments, it was shown that tadpoles
treated with T3 and/or T4 metamorphosed early into frogs, whereas
hypothyroid tadpoles never developed into frogs. This is an example of
how important thyroid hormones are for normal growth and maturation.
D. Effect on Cardiovascular system: T3 has a marked positive chronotropic
and ionotropic effect on the heart. This accounts for the increased cardiac
muscle contractility, cardiac output, and heart rate, and for the increased
heart rate in hyperthyroid patients and the slow rate in hypothyroid
patients.
 Physiological Actions of T3 and T4
E. Effect on Sympathetic Nervous System: Thyroid hormones increase the
number of beta-adrenergic receptors in cardiac and skeletal muscle and
adipose tissue. They increase the body's sensitivity to catecholamine action.
This may account for hyperthyroid patients being treated with beta-
adrenergic blocking agents to control their tachycardia and arrhythmias.
F. Other Effects: Thyroid hormones in the euthyroid individual stimulate the
synthesis of skeletal muscle, maintain muscular tone, and increase the
speed of muscle contraction. With hyperthyroidism, protein turns over
rapidly, muscle is lost, and muscle reflexes are accentuated. T3 stimulates
erythropoiesis.
 Diseases Associated with the Abnormal Thyroid
Thyroid hormones have two major physiological effects.
They increase protein synthesis in virtually every body tissue and increase oxygen consumption dependent upon
Na+ -K+ ATPase (Na pump).

Hyperthyroidism
A. It occurs seven to nine times more likely in women than in men. Hyperthyroidism often occurs between the
ages of twenty and forty, while hypothyroidism often appears after the age of fifty.
B. Certain types of thyroid tumors appear to be more prevalent in certain age groups. In the last few years, case
studies of patients with hyperthyroidism in their youth have shown that, thirty years later, the same
individuals have a greater tendency to develop hypothyroidism.
C. Thyroid problems have a strong genetic component, and may "skip" generations. Family histories may be
useful in suggesting the nature of thyroid problems at early stages.
D. Prematurely gray hair, hair which starts to go gray before the age of thirty, is often a sign of thyroid
dysfunction.
E. Patchy hair loss, usually temporary, is often observed by persons with Graves’ or Hashimoto's disease.
F. A list of conditions related to the thyroid is instructive as to the importance of the thyroid in human disease.
 Diseases Associated with the Abnormal Thyroid
Hypothyroidism in Adults:
It is a state of low serum thyroid hormone resulting from hypothalmic, pituitary, or thyroid insufficiency.
Untreated, can lead to life-threatening myxedema coma (early signs of fatigue, forgetfulness, sensitivity to cold,
unexplained weight gain, constipation progress to decreasing mental stability, dry, flaky inelastic skin; puffy
face, hands, and feet; hoarseness; periorbital edema; upper eyelid droop; dry, sparse hair; and thick, brittle
nails. Underlying decrease in cardiac output and poor peripheral circulation can lead to abrupt coma). Most
common in women, incidence rising significantly in persons aged 40 to 50.

Hypothyroidism in Children (Cretinism)

This is a Deficiency of thyroid hormone secretion during fetal development or early infancy results in infantile
cretinism (congenital hypothyridism). Respiratory difficulties, persistent jaundice, and hoarse crying in infants;
stunted growth (dwarfism), bone and muscle dystrophy, and mental deficiency in older children. 3 times more
common in girls than in boys. Infants not treated within first 3 months or children within two years suffer
irreversible mental retardation.

Thyroiditis
Thyroiditis is the inflammation of thyroid gland can be divided into catagories of autoimmune (long-term
inflammatory disease; Grave's Disease, Hashimoto's Disease), subacute granulomatous (self-limiting
inflamation), Riedel's (rare, invasive fibrotic process), and miscellaneous (acute suppurative, chronic infective,
chronic non-infective). More common in women than in men (5 to 7 times more common).
 Diseases Associated with the Abnormal Thyroid
Hyperthyroidism (Grave's Disease, Basedow's disease, Parry's disease, thyrotoxicosis)
Hyperthyroidism is a metabolic imbalance that results from thyroid hormone overproduction. Most common is
Grave's disease. Only 5% of hyperthyroid patients are under age 15.

Grave's Disease
Toxic goiter is a cause of 80% of hyperthyroidism. A diffusely enlarged thyroid gland associated with
hyperthyroidism is known as Grave's disease. Autoimmune disease. Highest incidence between ages of 30 and
40. Disorder of unknown etiology characterized by exophthalmos, enlarged pulsating thyroid gland, marked
acceleration of heart rate, tendency to profuse sweats, nervous symptoms (fine muscular tremors, restlessness,
irritability), psychic disturbances, emaciation, and increased metabolic rate.

Hashimoto's Disease
Struma (goitre) lymphomatosa (multiple lymphomas in various parts). A progressive disease of the thyroid
gland, with extensive acidophilic (readily acid dye stained cell) degeneration of its epithelial elements and
replacement by lymphoid and fibrous tissue. Hashimoto's disease results in hypothyroidism. Initially, the thyroid
is enlarged and there may be transient hyperthyroidism, followed by a euthyroid state and then hypothyroidism
with eventual atrophy years later. Hashimoto's thyroiditis results from abnormal T cell activation and
subsequent B cell stimulation to secrete a variety of auto-antibodies.
 Diseases Associated with the Abnormal Thyroid
Simple Goitre (nontoxic goitre)
Thyroid gland enlargement not caused by inflamation or a neoplasm. Normally results from inadequate dietary
intake of iodine. Affects no particular segment of the population. Affects more females than males, especially
during adolescence, pregnancy, and menopause when demand for thyroid hormone increases.

Plummer's Syndrome
It is a toxic multinodular goitre (common in women over 60). Nodule's within thyroid independently make T4.
The abnormally high amount suppresses secretion of TSH (thyroid stimulatory hormone) by anterior pituitary,
causing main gland to shut down. [different from Plummer-Vinson's Syndrom: dysphagia (difficulty in
swallowing) with glossitis (tongue inflammation), hypochromic anemia, splenomegaly, and atrophy in the
mouth, pharynx, and upper esophagus.
 Structure Activity Relationship of Iodothyronines

A. Figure shows the three-dimensional shape of the hormonally active thyroxine

molecule. The following observations can be made from the three-dimensional shape.
B. Because of the steric effect of the large iodine atoms in position 3 and 5, the planes of
two aromatic rings are perpendicular to each other and are separated by oxygen atom
which holds the rings at an angle of about 120o.
C. The amino acid side chain has the carboxyl group at the maximum distance from the
aromatic ring bearing the side chain. The phenolic hydroxyl group is coplanar with its
aromatic ring.
Based on many
Structure molecular
Activity modifications
Relationship of the thyroid hormones, a few observations
of Iodothyronines
regarding the structure-activity relationship have been made.

A. The ether oxygen can be replaced isosterically by sulphur or methylene which

also provide an angle of 120o. This change does not qualitatively impair the
activity.
B. A phenolic hydroxyl group at 4’ position is important for hydrogen bonding to
transport proteins. It can, however, be replaced by isosteric groups like NH2 or by
a group that can generate a hydroxyl group after metabolism (OCH3 or
OCOCH3). But such a change results in reduced hormonal activity.
C. The 3’-position ortho to the hydroxyl and away from the other aromatic ring
must be substituted by a lipophilic group. This can be a halogen (preferably
Iodine) or any alkyl group approximately of the same size as Iodine such as an
isopropyl group.
D. The 3’-monosubstituted compounds are more active than the 3’,5’-disubstituted
molecules.
E. Triiodothyronine is four times more potent than thyroxine, while 3’-isopropyl-
3,5-diiodothyronine has seven times the activity.
F. The iodine atoms at 3 and 5 positions can be replaced by non-polar groups
(such as methyl), as long as they keep the aromatic rings perpendicular to each
other.
G. The amino acid side chain can be varied, but should be para to the aromatic
 Thyroid Preparations (Hormones)
Powdered thyroid gland (officially termed as Thyroid) obtained from domesticated animals and the pure
hormones L-Thyroxine and L-Triiodothyronine (Liothyronine), both as sodium salts are the thyroid agents used
as replacement therapy in hypothyroidism to correct thyroid deficiency.

Official drugs
A. Thyroid, I.P.
B. Liothyronine Sodium, B.P.

Use: Liothyronine sodium is a synthetic version of one of the two hormones made by the thyroid gland,
triiodothyronine. It is used for the treatment of hypothyroidism in adults and children. Prolonged
hypothyroidism can result in a condition called myxedema in which patients develop swollen lips, thickened
nose, and unusual deposits of material in the skin that are dry and waxy. These deposits also may appear in
body tissues other than the skin. Liothyronine also is used in a test of the thyroid gland to determine if the
thyroid is functioning normally.
Dose: The usual starting dose of liothyronine is 5 to 25 µg per day.
 Thyroxine Sodium, I.P., B.P.

Levothyroxine occurs as light yellow to buff-coloured powder or fine, slightly coloured crystalline powder. It is
stored in tightly-closed, light-resistant containers.

It is readily absorbed from the gastrointestinal tract. It is eliminated slowly from the body and has a half-life of
6 to 7 days.
Use: It is primarily indicated for the treatment of hypothyroidism.
Treatment is usually long term as it is replacing thyroid hormone the body is not producing.
The dosage is usually adjusted according to response and blood test results.
 Anti-Thyroid Drugs
A. Anti-thyroid drugs (ATDs) are compounds that interfere with the body’s production of thyroid hormone,
thereby reducing symptoms of hyperthyroidism.
B. ATDs were discovered accidentally in the mid-1940’s when thiocyanate compounds used for heart disease
were found to cause hypothyroidism.
C. This led to the development of a number of compounds specifically tailored to reduce thyroid hormone
production.
Classification of Anti-thyroid Drugs
A. These drugs inhibit the synthesis of thyroid hormone.
B. They exert immediate effect since they act at the first stage of iodine incorporation by the gland. They are categorized as
under:
Thioamides; Thiourea and thiouracil derivatives
Thiouracils: Methylthiouracil, Propylthiouracil, etc.
Imidazoles: Methimazole, Carbimazole, Centimizone, etc.
Aniline derivatives
Sulphonamies: Sulphanilamide, Sulphaguanidine, Carbutamide, Para aminosalicylic acid
Polyhydric phenols: Resorcinol
Ionic inhibitors: Potassium perchlorate, Thiocyanate
Miscellaneous agents
Lithium carbonate
Adrenergic blockers: Propranolol
 Structures of Anti-thyroid Drugs

R = CH2CH2CH3
Propylthiouracil Methimazole

Carbimazole Sulphanilamide

Sulphanilamide Para - amionosalicylic acid

Sulphaguanidine Resorcinol
 Mechanism of Action
Thioamides:
Mechanism of Action
A. It prevents thyroid hormone synthesis by inhibiting the thyroid peroxidase-catalyzed reactions &
blocking iodine organification (the major mechanism of action).
B. It blocks coupling of iodotyrosines.
C. It inhibits the peripheral deiodination (deiodinase D1) of T4 to T3.
Potassium Iodide
Mechanism of Action:
D. Iodine has several effects on thyroid function:
E. A major action of iodide is to inhibit hormone release from the thyroid gland.
F. This is the most acute effect of iodine on thyroid status, and occurs within hours after starting therapy
(Ross, 2017). This effect may result from inhibition of thyroglobulin proteolysis (which is necessary for
production/excocytosis of thyroid hormones) (Dong & Greenspan, 2015).
G. Interferes with the synthesis of thyroid hormones by inhibiting thyroidal peroxidase inside the thyroid
gland. This decreases thyroid hormone biosynthesis.
H. The maximal effect of iodine on thyroid hormone concentration occurs after ~10 days of treatment
(Ross, 2017).
I. Iodine therapy is typically given only for a few weeks because the thyroid gland will commonly “escape”
from iodide block in 2-8 weeks.
 Mechanism of Action
Radioactive Iodine
Mechanism of Action:
A. I-131 is rapidly absorbed & is concentrated in the thyroid where it is incorporated into storage follicles.
B. It's therapeutic effect depends on emission of beta rays with an effective half-life of ~56 days.
C. Beta particles act on parenchymal cells with little damage to surrounding tissue.

Propylthiouracil
Mechanism of Action
D. It prevents thyroid hormone synthesis by inhibiting the thyroid peroxidase-catalyzed reactions & blocking
iodine organification (the major mechanism of action).
E. It blocks coupling of iodotyrosines.
F. It inhibits the peripheral deiodination (deiodinase D1) of T4 to T3.
 Introduction

Aminoglycosides are potent, broad-spectrum antibiotics that act through inhibition

of protein synthesis.

The class has been a cornerstone of antibacterial chemotherapy since streptomycin

(Fig. 1) was first isolated from Streptomyces griseus and introduced into clinical
use in 1944.

Several other members of the class (Fig. 1) were introduced over the intervening
years including neomycin (1949, S. fradiae), kanamycin (1957, S. kanamyceticus),
gentamicin (1963, Micromonospora purpurea), netilmicin (1967, derived from
sisomicin), tobramycin (1967, S. tenebrarius), and amikacin (1972, derived from
kanamycin).

A shift away from systemic use of the class began in the 1980s with the
availability of the third-generation cephalosporins, carbapenems, and
fluoroquinolones, which were perceived to be less toxic and/or provide broader
coverage than the aminoglycosides.
 Introduction

However, increasing resistance to these classes of drugs, combined with more

extensive knowledge of the basis of aminoglycoside resistance, has led to renewed
interest in the legacy aminoglycosides and the development of novel aminoglycosides
such as arbekacin and plazomicin.

These latter agents were designed to overcome common aminoglycoside resistance

mechanisms thereby maintaining potency against multidrug-resistant (MDR)
pathogens.

Additionally, improved dosing schemes have been developed that attempt to reduce
aminoglycoside toxicity while maintaining efficacy. 
 Chemistry of Aminoglycosides

Aminoglycosides are group of

natural and semi-synthetic
antibiotics.

They have polybasic amino groups

linked glycosidically to two or more
aminosugar like: sterptidine, 2-
deoxy streptamine, glucosamine.

Aminoglycosides which are derived

from: Streptomyces genus are
named with the suffix –mycin.

While those which are derived

from Micromonospora are named
with the suffix –micin.
 Examples of Aminoglycosides

S. No Antibiotic Source
1 Streptomycin Streptomyces griseus
2 Neomycin S. fradiae
3 Kanamycin S. kanamyeleticus
4 Gentamycin Micromonospora purpura
5 Netilmicin Micromonospora species
6 Tobramycin S. tenebrarius
7 Framycetin S. decaris
8 Paromomycin S. rimosus and S. paramomycinus
 Examples of Aminoglycosides

Neomycin

Streptomycin
Examples of Aminoglycosides

Kanamycin Tobramycin
 Classification of Aminoglycosides
Streptomycin (Streptomyces griseus)
Systemic Gentamicin (Micromonospora purpurea)
Aminogycosides Kanamycin (S. kanamyceticus)
Tobramycin (S. tenebrarius)
Amikacin (Semisynthetic derivative of Kanamycin)
Sisomicin (Micromonospora inyoensis)
Netilmicin (Semisynthetic derivative of Sisomicin)

Aminoglycosides

Topical Neomycin (S. fradiae)

Aminoglycosides Framycetin (S. lavendulae)
 Mechanism of action 

The aminoglycosides exhibit bactericidal effects as a result of several phenomena.

Ribosomal binding on 30s and 50s subunits as well as the interface produces
misreading; this disturbs the normal protein synthesis. Cell membrane damage also
plays an integral part in ensuring bacterial cell death.
 Mechanism of action 
A
Aminoglycoside (represented by red
circles) binds to the 30S ribosomal
subunit and interferes with
initiation of protein synthesis by
fixing the 30S–50S ribosomal
complex at the start codon (AUG)
of mRNA.

As 30S–50S complexes downstream

complete translation of mRNA and
detach, the abnormal initiation
complexes, so-called streptomycin
monosomes, accumulate, blocking
further translation of the
message. Aminoglycoside binding to
the 30S subunit also causes
misreading of mRNA.
 Mechanism of action
B & C 
Misleading of mRNA leads to
premature termination of
translation with detachment of the
ribosomal complex and incompletely
synthesized protein.

Incorporation of incorrect amino

acids (indicated by the red X),
resulting in the production of
abnormal or non-functional
proteins.
 Structure-Activity Relationship

A. The aminoglycosides consist of two or more amino sugars joined in glycoside

linkage to a highly substituted 1,3- diaminocyclo hexane (aminocyclitol), which is
a centrally placed ring.

B. The ring is a 2-deoxy streptamine in all aminoglycosides except streptomycin and

dihydrostreptomycin, where it is streptidine.

C. Thus, In kanamycin and gentamycin families, two amino sugars are attached to
2-deoxy streptamine.

D. In streptomycin, two amino sugars are attached to strepidine.

E. In neomycin family, there are amino sugars attached to 2-deoxy streptamine.

F. The aminoglycoside antibiotics contain two important structural features. They

are amino sugar portion and centrally placed hexose ring, which is either 2-
deoxystreptamine or streptidine.
 Structure-Activity Relationship

A. Amino sugar portion

B. Centrally placed hexose ring (aminocyclitol ring)

A. Amino sugar portion

The bacterial inactivating enzymes

targets C-6 and C-2 position and
the substitution with methyl group
at C-6 increases the enzyme
resistance.

Cleavage of 3-hydroxyl or the 4-

hydroxyl or both groups does not
affect the activity.
 Structure-Activity Relationship

Centrally placed hexose ring

(aminocyclitol ring)
Various modifications at C-1 amino
group have been tested. The acylation
(e.g. amikacyn) and ethylation (e.g. 1-
N-ethylsisomycin) though does not
increase the activity helps to retain
the antibacterial potency.

In sisomicin series, 2-hydroxylation

and 5-deoxygenation result in the
increased inhibition of bacterial
inactivating enzyme systems. Thus,
very few modifications of the central
ring are possible, which do not violate
the activity spectrum of
aminoglycosides.
 Clinical Uses of Aminoglycosides

Serious, life-threatening gram-negative infection

Complicated skin, bone or soft tissue infection
Complicated urinary tract infection
Septicemia
Peritonitis and other severe intra-abdominal infections
Severe pelvic inflammatory disease
Endocarditis
Mycobacterium infection
Neonatal sepsis
Ocular infections (topical)
Otitis externa (topical)
 Drug Resistance

Most resistance to aminoglycosides is caused by bacterial inactivation by intracellular

enzymes. Because of structural differences, amikacin is not inactivated by the
common enzymes that inactivate gentamicin and tobramycin. Therefore, a large
proportion of the gram-negative aerobes that are resistant to gentamicin and
tobramycin are sensitive to amikacin. In addition, with increased use of amikacin, a
lower incidence of resistance has been observed compared with increased use of
gentamicin and tobramycin.

P. aeruginosa may show adaptive resistance to aminoglycosides. This occurs when

formerly susceptible populations become less susceptible to the antibiotic as a result
of decreased intra-cellular concentrations of the antibiotic. This decrease may
result in colonization, slow clinical response or failure of the antibiotic despite
sensitivity on in vitro testing. 6

Aminoglycosides are often combined with a beta-lactam drug in the treatment

of Staphylococcus aureus infection. This combination enhances bactericidal activity,
whereas aminoglycoside monotherapy may allow resistant staphylococci to persist
during therapy and cause a clinical relapse once the antibiotic is discontinued.
 Drug Resistance
Infective endocarditis that is due to enterococci with high levels of resistance to
aminoglycosides is becoming increasingly common. All enterococci have low-level
resistance to aminoglycosides because of their anaerobic metabolism. In the
treatment of bacterial endocarditis, a beta-lactam drug is also used synergistically
to facilitate aminoglycoside penetration into the cell.

When high-level resistance occurs, it is typically due to the production of

inactivating enzymes by the bacteria. Because of the increasing frequency of this
resistance, all enterococci should be tested for antibiotic susceptibility.

As with all antibiotics, resistance to aminoglycosides is becoming increasingly

prevalent. Repeated use of aminoglycosides, especially when only one type is
employed, leads to an increased incidence of resistance. 8 Nevertheless, resistance
to aminoglycosides requires long periods of exposure or very large inocula of
organisms and occurs less frequently than with other agents, such as third-
generation cephalosporins, which are also effective against gram-negative
organisms.
 Risk Factors to Aminoglycoside

The aminoglycoside can produces Potentially alterable factors

severe adverse effects, which
Use of diuretics
include nephrotoxity, ototoxicity,
and neuro effects. Radiographic contrast exposure

These properties have limited the Effective circulating volume depletion

use of aminoglycoside Use of ACE inhibitors
chemotherapy to serious systemic
indications. Use of NSAIDs
Use of other nephrotoxic medications
Concomitant use of amphotericin (Fungizone IV)
Use of cisplatin (Platinol)
Unalterable factors
Age
Pre-existing renal disease
 Conclusion

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-

negative antibacterial therapeutic agents that inhibit protein synthesis and contain
as a portion of the molecule an amino-modified glycoside (sugar).

The term can also refer more generally to any organic molecule that contains
amino-sugar substructures.

The aminoglycoside antibiotics contain one or more amino sugars linked to an

aminocytitol ring by glycosidic bonds.

Aminoglycoside antibiotics display bactericidal activity against Gram-negative

aerobes and some anaerobic bacilli where resistance against Gram-positive and
anaerobic Gram-negative bacteria.

Streptomycin, the first antibiotic of this group.

 Conclusion
Aminoglycosides are potent bactericidal
antibiotics that act by creating fissures in
the outer membrane of the bacterial cell.
They are particularly active against
aerobic, gram-negative bacteria and act
synergistically against certain gram-
positive organisms.
Gentamicin is the most commonly used
aminoglycoside, but amikacin may be
particularly effective against resistant
organisms.
Aminoglycosides are used in the treatment
of severe infections of the abdomen and
urinary tract, as well as bacteremia and
endocarditis.
They are also used for prophylaxis, especially
against endocarditis. Resistance is rare but
increasing in frequency.
Avoiding prolonged use, volume depletion and
concomitant administration of other potentially
nephrotoxic agents decreases the risk of toxicity.
Single daily dosing of aminoglycosides is possible
because of their rapid concentration-dependent
killing and post-antibiotic effect and has the
potential for decreased toxicity.
Single daily dosing of aminoglycosides appears to
be safe, efficacious and cost effective. In certain
clinical situations, such as patients with
endocarditis or pediatric patients, traditional
multiple dosing is still usually recommended.
 Acknowledgements

A. D.A.V. Public School, ACC Colony, Jamul – 490024, Durg, Chhattigarh, India (1990 – 2004)
B. University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India
(2005 – 2009)
C. Shri Rawatpura Sarkar Institute of Pharmacy, Kumhari, Durg, Chhattisgarh, India (2010 – 2012)
D. Royal College of Pharmacy, Raipur, Chhattisgarh, India (March – October 2013)
E. National Center for Natural Resources (NCNR), Pt. Ravishankar Shukla University, Raipur,
Chhattisgarh, India (2013 – 2017)
F. Columbia Institute of Pharmacy, Raipur 493111, Chhattisgarh, India ( 2017 – till date)
G. Gratitude to Resp. Prof. Shiv Shankar Shukla Sir, Columbia Institute of Pharmacy, Raipur 493111,
Chhattisgarh, India (Mentor)
H. Gratitude to Resp. Prof. Atanu Kumar Pati, Vice Chancellor, Gangadhar Meher University,
Sambalpur, Odisha
I. Gratitude to Resp. Prof. Mitashree Mitra, Dept. of Anthropology, PRSU, Raipur, Chhattisgarh.
J. Gratitude to Resp. Vishal S. Deshmukh Sir (M.Pharm. Supervisor)
Thanks for studying !!!!