Chloramphenicol, Tetracycline, Erythromycin Flashcards
TETRACYCLINES
History: _________ was 1st introduced in 1948. 2 years later, _________ became available.
Chlortetracyline
oxytetracycline
Sources
Chlortetracycline is from ________
Oxytetracycline is from ______
Streptomyces
Streptomyces
Tetracycline is created _____________ from _________ and from a species of ________
Semi-synthetically
Chlortetracycline
Streptomyces
Demeclocycline is a product of a mutant strain of ____________
Streptomyces Aureofaciens
Mention 3 semi synthetic cycline derivatives
Metha
Doxy
Mino
Tetracyclines are usually drugs of choice for bacterial infections.
T/F
F
They are not
Tetracyclines
The more lipo____ drugs, ______ and ______ usually are the most active by weight, followed by _______.
Philic
minocycline and doxycycline
tetracycline
Resistance of a bacterial strain to any one member of the class usually results in __________ to other tetracyclines.
cross resistance
Tetracyclines are bacteri_____agents.
Ostatic
Tetracyclines
Rapidly multiplying micro-organisms are least affected.
T/F
F
Most
Tetracyclines
Order of activity : ??
Minocycline
Doxycycline
Tetracycline
Oxytetracycline
In general gram- _____ micro organisms are affected by lower conc. of tetracycline than are grain –______ special agents.
positive
negative
Neisseria gonorrhoea and many strains of N.meningititis are still inhibited by tetracyclines
F
Neisseria gonorrhoea and many strains of N.meningititis were initially inhibited by tetracyclines though sensitivity patterns changed over the
years.
Tetracyclines
Mechanism of Action: Site of action is the ___________, inhibiting ______
bacterial ribosome 30S
protein synthesis.
Absorption, distribution, and Excretion
Most tetracyclines are (adequately or inadequately?) but (completely or incompletely?) absorbed from the GIT.
Most absorption takes place from ________________ and is greater in the ________ state, though more recent studies show that ______ is well absorbed after food and this _______________
adequately
incompletely
stomach and upper small intestine
fasting; doxycycline
even prevents or ameliorates the GIT disturbance initially associated with its administration.
Doxycycline
The drug accumulates with resultant high concentrations in the GIT following repetitive dosing such that many aerobic and anaerobic coliform micro-organisms and gram-positive _______ bacteria are _____.
Consequently, the _______ is altered, the stools become ______,______ and acquire a ____,_____ colour.
Diarrhea can also occur and
ocassionally, pseudomembranous colitis may occur.
Spore-forming
suppressed
intestinal flora
softer, odourless
yellow-green
Tetracycline
Absorption is impaired by ___ products, _______ gels, Nabicarbonate, ____ salts, ____ preparations.
There is irregularity of absorption from GIT hence a wide range of plasma conc in different individuals ff oral administration.
milk
aluminium hydroxide
calcium; iron
They can be divided into 3 groups based on the dosage and frequency of oral administration required to produce effective plasma concentration.
Oxytetracycline and Tetracycline – Adults ___mg 6 hly
methacycline – ___mg 6 hly.
Deoxycycloine and minocycline – ____mg every 12 hours in 1st 24 hours ff by 100mg once a day or twice daily when infection is severe.
250
150
100
Food does not interfare with the absorption of doxycycline and minocycline.
T/F
T
The volume of distribution of many of the tetracycline is relatively larger than that of the body water.
T/F
T
Tetracycline
They are all concentrated in the ____ and
excreted by way of the ____ into the intestine from which they are ___________
liver
bile; partially reabsorbed.
Minocycline reaches a sufficient conc in ______ and _____ to eradicate the meningococcal carrier state.
tears and saline
High conc of tetracycline is found in fetal circulation and breast milk.
T/F
T
Tetracycline
They are stored in _____ cells of the liver, spleen, and bone marrow and in bone and the __________________
main route of excretion is the _____, also in ____.
reticuloendothelial
dentine and enamel of unerupted teeth.
kidney; faeces
Tetracycline
Preps, Routes – usually _____ and some by _______.
Topical administration restricted to use on ______ because of a high risk of _____.
Never inject _______ and rarely given ________.
oral capsules
I.V injection
the eye; sensitization
intrathecally
intramuscularly
Tetracycline
UNTOWARD EFFECTS
____ irritation, ______ burning and stress, ______ discomfort, nausea, and vomiting.
The larger the dose the greater the likelyhood of an irritative reaction.
__________, ______ toxicity, ______ toxicity.
GIT
Epigastric
abdominal
Photocoxicity; hepatic; Renal
Tetracycline
UNTOWARD EFFECTS
_______ then _______ discolouration of teeth if administered up to ___ years, however, generally most authorities agree that it should not be administered to children up to ____ years of age.
The deciduous teeth are at the greatest danger affected if given from ___________ to _______ of the postnatal period, while the greatest danger to the permanent teeth coloration occurs if given between the ages of ______ and _______ . Super infection.
Yellowish then Brownish; 8
12
mid- pregnancy to 4/6 months
2 months and 5 years
CHLORAMPHENICOL
History: produced by _________
streptomyces venezuelae
Mechanism of action: Chloramphenicol inhibits ______ in bacteria by binding (reversibly or irreversibly?) to the ___S ribosomal subunit near the site of
action of the _______ antibiotics and _______, which it inhibits (competitively or non competitively?) .
It also inhibits _______ protein synthesis in _______ cells
protein synthesis
reversibly
50
macrolide; clindamycin
Competitively ; mitochondrial; mammalian
Chloramphenicol
Resistance has been growing, in the case of gram negative bacteria it is due to the presence of a specific _____ acquired, a specific _______ inactivates the drug.
plasmid
acetyl transferase
Absorption, Distribution, Fate and Excretion
Two forms are available for oral administration (1) the _________ and (2) the ___________
Hydrolysis of (2) occurs rapidly and
almost completely by __________ in the ___________.
active drug
prodrug chloramphenicol palmitate
pancreatic lipases
duodenum
Chloramphenicol
Bioavailability is greater for the proactive drug than active drug
F
Active is more than proactive
Chloramphenicol
Absorption of I.M. is usually not ________, however, I.V. of the parenteral form succinate is as suitable as
P.O. or I.M.,
Clearance is by the _____ hence ____ insufficiency, poor ______ function in neonates lead to conc. In plasma.
This is well distributed in body fluids and readily reaches therapettic conc in CSF (____% of plasma) in the presence or absence of meningitis.
predicable
kidney; renal; renal
60
Chloramphenicol
Doesn’t readily traverse the placental barrier and is not secreted in milk.
T/F
F
The major route of elimination of chloramphenicol is _____ metabolism to the inactive _______.
This metabolite as well as cholamphenicol is excreted in ______.
hepatic; glucoromide
Urine
THERAPUTIC USES of chloramphenicol
____________ when the strains causing the organism are susceptible though the use of other newer drugs which usually do not possess serious untoward effects and can be administered for shorter periods has overtaken chloramphenicol in this regard.
Typhoid fever
Chloramphenicol therapeutic uses
It was very valuable against ______ infection especially ______ and ________, but it is now rarely indicated because of the ___________
bacterial anaerobic
intra-abdominal and brain abscesses
availability of numerous equally effective and less toxic alternative.
Chloramphenicol
Used in _______ diseases when tetracycline cannot be used.
Rickettsial
Chloramphenicol
Hematological Toxicity: Type A ADVERSE DRUG REACTION presenting as _________
Type B ADVERSE DRUG REACTION presenting as _______
Type C ADVERSE DRUG REACTION presenting as ________
Type D ADVERSE DRUG REACTION presenting as _______. This occurs sometime after the patient has taken the drug.
dose related anaemia.
aplastic anemia
anemia after chronic administration
aplastic anaemia
Chloramphenicol
In Type B ADVERSE DRUG REACTION
These patients present in ______ fashion. Who develops anemia cannot
be predetermined, the duration of drug use may not be commensurate with _________ or _______
an unpredictable
develop of anemia or depth of anemia
Gray baby syndrome can occur in adults
T/F
T
Chronic administration of ____ or acute administration of ______ shortens the t1/2 of chloramphnicol leading to sub-theraputic concentrations of the drug
phenobarbital
rifampin
Erythromycin is produced by a strain of ______________(formerly _________ ) and belongs to the ________ group of antibiotics.
Saccharopolyspora erythraea
Streptomyces erythraeus
macrolide
Erythromycin is (acidic or basic?) and readily forms salts with acids.
Basic
Erythromycin is a white to off-white powder, _______ in water, and _______ in alcohol, chloroform, and ether
slightly soluble
soluble
The passage of the erythromycin across the blood-brain barrier _____eases in meningitis.
Incr
Erythromycin crosses the placental barrier
fetal plasma levels of erythromycin are high.
Erythromycin is excreted in human milk.
Erythromycin is removed by peritoneal dialysis or hemodialysis.
T/F
T
F(low)
T
F(it’s not)
In the presence of normal hepatic function, erythromycin is concentrated in the _____ and is excreted in the _____
liver; bile
the effect of hepatic dysfunction on biliary excretion of erythromycin is known.
Mention it
It’s not known
After oral administration, less than ___% of the administered dose can be recovered in the active form in the urine.
5
Optimal blood levels are obtained when Erythromycin Base Filmtab tablets are given in the _____ state (at least ____________________).
fasting
1⁄2 hour and preferably 2 hours before meals
Erythromycin acts by inhibition of protein synthesis by binding ___ S ribosomal subunits of susceptible organisms.
50
Erythromycin does not affect nucleic acid synthesis.
T/F
T
Many strains of ___________ are resistant to erythromycin alone but are susceptible to erythromycin and _____ used concomitantly.
Haemophilus influenzae
sulfonamides
Tetracycline is effective against ____,______,______,______
Ricketssiae
Chlamydia
Mycoplasma
Atypical Mycobacteria
Chloramphenicol can be exerted through the breast milk
Tetracycline can be excreted through the breast milk
Erythromycin can be excreted through the Breast milk
T/F
T
T
T
Chloramphenicol is mainly used to treat ________
But can also be used to treat _____ when ———- isn’t available
Typhoid fever
Ricketssiae; tetracycline
Tetracycline- acidic or basic?
Erythromycin- acidic or basic?
Acidic
Basic
Mention 2 other drug classified with erythromycin?
Clarithromycin
Azithromycin
Chloramphenicol is effective against anerobic organisms
T/F
T
Chloramphenicol can inhibit clindamycin competitively because both have similar mechanism of action
T/F
F
Chloramphenicol may cause hepatotoxicity
T/F
F
Aminoglycosides = only against gram ____,_____ ; ____- spectrum
Chloramphenicol: ____ spectrum; preferred for ______
neg aerobes; narrow
broad; anaerobes
Tetracyclines = _____ spectrum; preferred for _______
broad
intracellular microbes
Chloramphenicol: by ____,___,______
(Poorly or well ?) absorbed; relatively fairly distributed . Loves the ____,____,_____ ; metabolized in the liver; excreted in kidney and breast milk
oral, IV, topical
Well
placenta, cns, breast.
Tetracycline: by mainly ____ but also ____; good absorption ; poorly distributed, loves the _____, and _______ ; kidney and liver excretes them
oral; IV
bones and teeth
Macrolide administration: ____ and ——— ; (complete or incomplete?) absorption ; well distribution; well found in placenta; excreted through the kidney
oral and IV
Incomplete
Aminoglycosides = inhibit ____ stage
Chloramphenicol = inhibits _____
Tetracycline = inhibits _____
Macrolide= inhibits _____
initiation
transpeptidation
elongation
translocation
Chemistry
Aminoglycosides = ______________
Chemistry of chloramphenicol =_________
Chemistry of tetracycline = ——————
Chemistry of macrolide=_______ + ________
2amino sugar + 2 deoxystreptamin
nitrobenzene ring
4 naphthalene carboxamide
lactose ring+ sugar
Bacterio____ - Aminoglycosides
Bacterio_____-tetracycline
Bacterio______- chloramphenicol
cidal
static
Static
