Download Tetracyclines:

Tetracyclines:
Supervised by:
Dr. Qadria AL-Deab
Dr. Areej Altaweel
Tetracyclines:
-a broad-spectrum antibiotics.
-It is commonly used to treat acne,
infection, and other infections caused by
bacteria.
-The first of these compounds was
chlortetracycline followed by
oxytetracycline and tetracycline.
Tetracycline divided into:
a) Naturally occurring:
1-tetracycline
2-chlortetracycline
3-oxytetracycline
4-demeclocycline
Semisynthetic occurring:
1-doxycycline
2-minocycline
3-meclocycline
4-lymecycline
5-methacycline
6-rolitetracycline
Total Synthesis of the
Tetracyclines:
Structure and chemical characteristics
•
Structure activity relationship
•
R5
Chlortetracycline
H
Oxytetracycline
H
Tetracycline
H
Demethylchlortetracycline
H
Rolitetracycline
+
Metacycline
H
Doxycycline
H
Minocycline
H
R4
R3
R2
R1.
H
OH
CH3
Cl
OH OH
CH3
H
H
OH CH3
H
H
OR
H
CI
H
OH
CH3 H
OH
CH2
H
OH
H
CH3 H
H
H
N(CH3)2
• Retention of the configuration of the
asymmetric centres C-4, C-4a and C-12a is
essential, whereas the configurations at C-5,
C-5a and C-6 may be altered:
• 1- The amide hydrogen may be replaced
with a methyl group, but larger groups have
a deleterious effect except for those which
are eliIminated spontaneously in water .
• 2-The dimethyl amino group may be
replaced by a primary amino group
without loss of in vitro activity but all
other changes so far lead to decreased
bacteriostatic action .
• The hydrophobic part of the molecule
from C-5 to C-9 may be altered in
various ways:
• modifications at C-6 and C-7 in
particular afford products having
greater chemical stability.
• increased antibiotic activity and more
favourable pharmacokinetics
• Dehydrogenation to form a double
bond between C-5a and C-11a
markedly decreases activity
• Polar substituents at C-5 and C-6
contribute decreased lipid versus water
solubility to the tetracycline
• . The drugs are amphoteric, meaning
they will form salts with both strong
acids and bases. Thus, they may exist
as salts of sodium or chloride.
Spectrum:
-The tetracyclines are broad-spectrum
antibiotics.
-They are active against the following
microorganisms:
1_ gram-positive and gram-negative bacteria
2_ spirochetes
3_ mycoplasmas,
4_ rickettsiae,
6_ Candida albicans
7_Mycoplasma pneumoniae
8_Chlamydia trachomatis
9_Borrelia recurrentis.
10_Yersinia pestis
11_Vibrio cholerae
12_ Campylabacter fetus
13_Brucella specie
14_Streptococcus pneumoniee.
15_Neisserie gonorrhoeae
Mechanism of action:
Mechanism of resistance :
There are three types of tetracycline
resistance:
1)tetracycline efflux.
2)ribosomal protection.
3)tetracycline modification.
Types of tetracyclines:
1-Demeclocycline:
Uses:
-treat cancer patients with SIADH.
-treat hyponatremia.
-combined with hydrocortisone in a paste used
by dentists .
-treat trachoma.
Side effect:
Dermatological:-Skin reactions, photosensitivity
GIT:-nausea, vomiting, and diarrhea.
CNS:-Dizziness,visualdisturbances .
Immune System:-allergic reactions.
Other:-yellowish-grayish-brown discoloration of the
teeth.
Pharmacodynamics/Kinetics:
-Absorption: ~50% to 80%.
-Protein binding: 41% to 50%
-Metabolism: Hepatic.
-Half-life elimination: 10-17 hours
-Time to peak, serum: 3-6 hours
-Excretion: Urine
2-Chlortetracycline:
Uses:
-used as antibacterial and antiprotozoal agent.
-In veterinary medicine, it is commonly used
to treat conjunctivitis in cats.
3-Oxytetracycline:
Uses:
-treat Spirochaetal infection.
-treating Non-Specific-Urethritis.
-treating Clostridial wound infection and Anthrax.
Side effects:
-Local irritation after intramuscular injection.
-Gastrointestinal:-anorexia, nausea, vomiting.
-Renal toxicity.
-Hypersensitivity reactions: Urticaria.
-Blood: Hemolytic anemia, thrombocytopenia,
neutropenia
1-tetracycline:
Uses:
-Tetracycline's primary use is for the
treatment of acne vulgaris and rosacea.
-It is also used to treat a very wide range
of infections.
Side effects:
-Gastrointestinal: anorexia, nausea,
vomiting, diarrhea,
-Skin: rashes, dermatitis.
-Renal Toxicity
-Hepatic Cholestasis:
-Hypersensitivity
Reactions:Anaphylaxis,
Miscellaneous: Dizziness and headache
4- Minocycline:
Uses:
-typhus fever and Q fever.
-Psittacosis Trachoma
-Nongonococcal urethritis.
-Brucellosis.
Side effects:
-Hypersensitivity reactions:Urticaria,anaphylaxis.
-GI :Anorexia, nausea, vomiting, diarrhea.
-Hepatic toxicity: Hyperbilirubinemia.
-Respiratory:Cough, dyspnea.
-Blood:Agranulocytosis, hemolytic anemia.
-CNS: Convulsions, dizziness,sedation.
-Oral cavity discoloration.
Pharmacokinetics:
-rapidly absorbed from the GIT.
-The peak plasma concentrations slightly
decreased.
-serum half-life ranged from 11 to 16 hours in
hepatic dysfunction, and from 18 to 69 hours
with renal dysfunction.
5-doxycyclines
Uses:
used in the treatment of chronic adult
periodontitis.
Side Effects:
-Nausea, Vomiting,Diarrhea.
-photosensitivity, rash.
-dyspepsia
-dysphagia.
-Watery diarrhea
-Bloody stools
Drug interaction of tetracyclines::
antacids containing aluminum,
calcium, or magnesium, and
iron-containing preparations
Impaire the Absorption of
tetracyclines
anticoagulant therapy
Because tetracyclines have
been shown to depress plasma
prothrombin activity, patients
who are on anticoagulant
therapy may require downward
adjustment of their
anticoagulant dosage.
bacteriostatic drugs
interfere with the bactericidal
action of penicillin, it is
advisable to avoid giving
tetracycline-class drugs in
conjunction with penicillin.
oral contraceptives
Concurrent use of tetracyclines
with oral contraceptives may
render oral contraceptives less
effective.
ergot alkaloids or their
derivatives are given with
tetracyclines.
Increased risk of ergotism
Bile acid sequestrants
May decrease tetracycline
absorption
Iron preparations
May decrease absorption of
tetracyclines
Methoxyflurane:
Methoxyflurane
anesthes
Methotrexate:
when concurrent with
tetracycline) may
cause fatal
nephrotoxicity;
concurrent use is
contraindicated.
Clearance of
methotrexate (highdose therapy) may be
decreased by
tetracyclines.
TETRACYCLINES AVAILABLE IN THE UNITED STATES
Generic name
Trade names
Preparations
Demeclocycline
Declomycin
Oral
Doxycycline
Vibramycin,
Doryx, Doxycin,
Monodox, and
others
Oral and
parenteral
Minocycline
Minocin
Oral and
parenteral
Oxytetracycline
Terramycin
Oral and
parenteral
Tetracycline
Achromycin V,
Panmycin,
Robitet,
Sumycin,
Tetracyn, and
others
Oral and
parenteral