Pharmacy Clinic
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Notes on antibiotics
General notes
* Quinolones not used with anions like magnesium or calcium or any other related because they
cause chelation with quinolones and inhibits the absorption of the antibiotics also milk causes the
same.
* Astreonam mimics aminoglycosides action with less renal effect, so can be used as alternatives
for the first one.
Amoxicillin is more absorbable from the GIT so it is with high bioavailability than ampicillin, the later
stay in the gastric leumen more so it is less absorbed and stay more in the GIT and induces gastric
irritations in it and diarrhea.
a. Natural pinicillins like penicillin G, penicillin V, benzathine penicillin, procaine penicillin.
Penicillin v is acid stable and can be used orally
Semisynthetic penicillins subdivided into:
b. Beta lactamase resistant penicillins uses restricted to treatment of staph. infections. Have
to be given every 4 6 hours. Methicillin is given i.v.; others can be given orally. Nafcillin excreted
80% into bile and 20% via kidney; there¬fore, little affected by renal failure.
c. Broad Spectrum penicillins Ampicillin and amoxic¬il¬lin. (Hetacillin, bicampicillin,
pivampicillin and cyclacillin have little or no advan¬tage; all of these are converted to ampicillin
before they are active.) Don't have to remember any but ampicillin and amoxicillin. Amoxicillin has
higher bioavailability than ampicillin due to high absorption rates of it so ampicillin aconcentrationin
the urine increased and induced diarrhea due to osmorality and anti flora actions of it.
d. Antipseudomonal Carbenicillin, ticarcillin, etc. – carboxypenicillins e.g carbencillin and
ticarcillin and ureido penicillins e.g. peipracillin (also cover klebseilla) Are classified as broad spectrum
but, in reality, they have restricted uses. Generally, are used in treatment of pseudomonas
infections (with concurrent aminoglycoside) and in treatment of Proteus (indole +) and anaerobic
infections (the latter in extremely large doses; eg, 20 40 g/day).
e. Anti staph. Aureus penicillins, e.g. cloxacillin and floucloxacillin and mainly active against
gram positive bacteria
All penicillins are excreted through renal pathway, have high t1/2 and low protein binding except
nafcillin and cloxacillin
Pepiracillin is a non linear pharmacokinetic and that because of the limited capacity of both renal and
non renal mechanism of excretion of the drug so as we increase the dose the clearance decreased
leading to accumulation of the drug in the blood and this affects toxicity.
Ampicillin and allopurinol together induces rash due to un known mechanism.
Carbencillin and ticarcillin inhibits the binding of ADP and causing reduction in platelets and so
induces bleeding.
Sodium load penicillins: those that increase sod. In the blood;
• Ampicillin 1g amp. For 3 mmol
• Carbincillin 400 mg for 200 mequiv.
• ticarcillin
• pepiracillin
All these above may induces edema
Potassium load penicillins: those that increase pot. In the blood;
• penicillin G 1.7 mequiv per 1 million unit
Penicillins decrease level of Aminoglycosides when used together but there is a synergistic action
between them
And also there is combined pinicillins like augmentin.
*phynetoin increases body temperature, so some times it induces fever
MRSA: methicillin resistance staphylococcus aureus
MRSE: methicillin resistance staphylococcus epidermedis
IVDU: intravenous drug use (addict)
So cloxacillin is anti staph., but in MRSA not used because it is already the bacteria resistant to it
Vancomicin for MRSA resistant bacteria
Refampin also for MRSA resistant bacteria
Meningitis with salmonella in children is very rare
*****Amikacin not given with netlmicin why??????
Reocephine increase seizure in patient have seizure before, so should be careful in that
****What is the difference between diazepam and clonazepam
Rocephine (3rd generation) excreted by billiary and renal excretion and also Cefoperazone and the
only two that excreted through billiary among Cephalosporins, so diffused directly to the gut and
from the bile and kill the intestinal flora and so it induces diarrhea
Cephalosporins
First and second generation cephalosporines used mainly for gram positive except for first
generation used for neiserria gonorrhea ?????
All first and second cephalosporines cann’t penetrate BBB except cefuroxime
All 3rd and 4th generations penetrate BBB except Cefoperazone
Only ceftriaxone and Cefoperazone are excreted in the bile so it increased in the urinary
tract by diffusing directly from the bile and so kills the intestinal flora and induces osmosis there so
it stimulates diarrhea.
All Cephalosporins are not used for enterococci because of the high MIC.
Never use cephalosporines for enteroccoci, because of the low anti bacterial activity there.
Ceftriaxone 2g single dose better that 1g twice daily…why???
The degree of protein binding of ceftriaxone is concentration dependent and decreases nonlinearly
with increasing concentrations of the drug. It has been suggested that ceftriaxone may have more
than one concentration-dependent protein binding site.The drug is 93—96% bound to plasma
proteins at a concentration less than 70 µg/mL, 84—87% bound at a concentration of 300 µg/mL,
and 58% or less bound at a concentration of 600 µg/mL. Ceftriaxone binds mainly to albumin.
Protein binding of ceftriaxone is lower in neonates and children than in adults
So as we increase the single dose the free drug in the plasma increased leading to increase volume
of distribution and so increase the effectiveness
Vancomycin:
• Vancomycin used only for gram positive bacteria
• Vancomycin induces red neck syndrome due to the stimulation of histamine release,
metronidazole also do that if given with alcohol and this called disulfiram like reaction
• Fucidic acid and ciprofloxacin also act against MRSA
• Vancomycin for MRSA resistant bacteria
• Vancomycin induces hypotension so if given in rapid IV infusion it drops BP very rapidly and
for that it is given for .5 – 1-hour infusion.
• If we give the patient fucidic acid with rifambin with vancomycin to gather then we must
check three things:
1) Efficacy
2) Toxicity
3) Drug interactions
Aminoglycosides
• Aminoglycosides used only for gram negative infections and they are very potent but they
affect renal function because they are excreted 100% by renal so used some times for UTI.
• We always start with Gentamicin and if resistance developed then we shift to Amikacin
because if the organism resistant to genta, it is sensitive to Amikacin but the opposite is not write,
when the organism develop resistance to Amikacin then 80 % of the organism become resistance
to Gentamicin, and if the organism develop resistance against genta, then it becomes resistance to
netlmicin.
• Genta is 100% excreted in the urine and so remain long time there and for that reason no
need to give high dose for UTI and enough to give 4mg/l as a therapeutic level
Chloramphenicol
Why oral preparation of Chloramphenicol is better that IV ???
2
Cholramphenicol good for UTI in case of complicated infection happened and bacteria
reaches systemic circulation, but if uncomplicated then Chloramphenicol become not so good for
that, because it under goes liver metabolism and excretion and little by renal one.
* Quinolones not used with anions like magnesium or calcium or any other related because they
cause chelation with quinolones and inhibits the absorption of the antibiotics also milk causes the
same.
* Astreonam mimics aminoglycosides action with less renal effect, so can be used as alternatives
for the first one.
Amoxicillin is more absorbable from the GIT so it is with high bioavailability than ampicillin, the later
stay in the gastric leumen more so it is less absorbed and stay more in the GIT and induces gastric
irritations in it and diarrhea.
a. Natural pinicillins like penicillin G, penicillin V, benzathine penicillin, procaine penicillin.
Penicillin v is acid stable and can be used orally
Semisynthetic penicillins subdivided into:
b. Beta lactamase resistant penicillins uses restricted to treatment of staph. infections. Have
to be given every 4 6 hours. Methicillin is given i.v.; others can be given orally. Nafcillin excreted
80% into bile and 20% via kidney; there¬fore, little affected by renal failure.
c. Broad Spectrum penicillins Ampicillin and amoxic¬il¬lin. (Hetacillin, bicampicillin,
pivampicillin and cyclacillin have little or no advan¬tage; all of these are converted to ampicillin
before they are active.) Don't have to remember any but ampicillin and amoxicillin. Amoxicillin has
higher bioavailability than ampicillin due to high absorption rates of it so ampicillin aconcentrationin
the urine increased and induced diarrhea due to osmorality and anti flora actions of it.
d. Antipseudomonal Carbenicillin, ticarcillin, etc. – carboxypenicillins e.g carbencillin and
ticarcillin and ureido penicillins e.g. peipracillin (also cover klebseilla) Are classified as broad spectrum
but, in reality, they have restricted uses. Generally, are used in treatment of pseudomonas
infections (with concurrent aminoglycoside) and in treatment of Proteus (indole +) and anaerobic
infections (the latter in extremely large doses; eg, 20 40 g/day).
e. Anti staph. Aureus penicillins, e.g. cloxacillin and floucloxacillin and mainly active against
gram positive bacteria
All penicillins are excreted through renal pathway, have high t1/2 and low protein binding except
nafcillin and cloxacillin
Pepiracillin is a non linear pharmacokinetic and that because of the limited capacity of both renal and
non renal mechanism of excretion of the drug so as we increase the dose the clearance decreased
leading to accumulation of the drug in the blood and this affects toxicity.
Ampicillin and allopurinol together induces rash due to un known mechanism.
Carbencillin and ticarcillin inhibits the binding of ADP and causing reduction in platelets and so
induces bleeding.
Sodium load penicillins: those that increase sod. In the blood;
• Ampicillin 1g amp. For 3 mmol
• Carbincillin 400 mg for 200 mequiv.
• ticarcillin
• pepiracillin
All these above may induces edema
Potassium load penicillins: those that increase pot. In the blood;
• penicillin G 1.7 mequiv per 1 million unit
Penicillins decrease level of Aminoglycosides when used together but there is a synergistic action
between them
And also there is combined pinicillins like augmentin.
*phynetoin increases body temperature, so some times it induces fever
MRSA: methicillin resistance staphylococcus aureus
MRSE: methicillin resistance staphylococcus epidermedis
IVDU: intravenous drug use (addict)
So cloxacillin is anti staph., but in MRSA not used because it is already the bacteria resistant to it
Vancomicin for MRSA resistant bacteria
Refampin also for MRSA resistant bacteria
Meningitis with salmonella in children is very rare
*****Amikacin not given with netlmicin why??????
Reocephine increase seizure in patient have seizure before, so should be careful in that
****What is the difference between diazepam and clonazepam
Rocephine (3rd generation) excreted by billiary and renal excretion and also Cefoperazone and the
only two that excreted through billiary among Cephalosporins, so diffused directly to the gut and
from the bile and kill the intestinal flora and so it induces diarrhea
Cephalosporins
First and second generation cephalosporines used mainly for gram positive except for first
generation used for neiserria gonorrhea ?????
All first and second cephalosporines cann’t penetrate BBB except cefuroxime
All 3rd and 4th generations penetrate BBB except Cefoperazone
Only ceftriaxone and Cefoperazone are excreted in the bile so it increased in the urinary
tract by diffusing directly from the bile and so kills the intestinal flora and induces osmosis there so
it stimulates diarrhea.
All Cephalosporins are not used for enterococci because of the high MIC.
Never use cephalosporines for enteroccoci, because of the low anti bacterial activity there.
Ceftriaxone 2g single dose better that 1g twice daily…why???
The degree of protein binding of ceftriaxone is concentration dependent and decreases nonlinearly
with increasing concentrations of the drug. It has been suggested that ceftriaxone may have more
than one concentration-dependent protein binding site.The drug is 93—96% bound to plasma
proteins at a concentration less than 70 µg/mL, 84—87% bound at a concentration of 300 µg/mL,
and 58% or less bound at a concentration of 600 µg/mL. Ceftriaxone binds mainly to albumin.
Protein binding of ceftriaxone is lower in neonates and children than in adults
So as we increase the single dose the free drug in the plasma increased leading to increase volume
of distribution and so increase the effectiveness
Vancomycin:
• Vancomycin used only for gram positive bacteria
• Vancomycin induces red neck syndrome due to the stimulation of histamine release,
metronidazole also do that if given with alcohol and this called disulfiram like reaction
• Fucidic acid and ciprofloxacin also act against MRSA
• Vancomycin for MRSA resistant bacteria
• Vancomycin induces hypotension so if given in rapid IV infusion it drops BP very rapidly and
for that it is given for .5 – 1-hour infusion.
• If we give the patient fucidic acid with rifambin with vancomycin to gather then we must
check three things:
1) Efficacy
2) Toxicity
3) Drug interactions
Aminoglycosides
• Aminoglycosides used only for gram negative infections and they are very potent but they
affect renal function because they are excreted 100% by renal so used some times for UTI.
• We always start with Gentamicin and if resistance developed then we shift to Amikacin
because if the organism resistant to genta, it is sensitive to Amikacin but the opposite is not write,
when the organism develop resistance to Amikacin then 80 % of the organism become resistance
to Gentamicin, and if the organism develop resistance against genta, then it becomes resistance to
netlmicin.
• Genta is 100% excreted in the urine and so remain long time there and for that reason no
need to give high dose for UTI and enough to give 4mg/l as a therapeutic level
Chloramphenicol
Why oral preparation of Chloramphenicol is better that IV ???
2
Cholramphenicol good for UTI in case of complicated infection happened and bacteria
reaches systemic circulation, but if uncomplicated then Chloramphenicol become not so good for
that, because it under goes liver metabolism and excretion and little by renal one.