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Submitted to: Sir Dr. Narendar
Sharma
Presenter: Mohammad Waqas
Mairaj
2K16/PHA/56(Morning)
4TH Prof: Pharm-D, University of
Sindh faculty of Pharmacy,
Jamshoro
Date of submission:
1st April, 2019
Topics Slide #
INTRODUCTION 3
GENERAL MECHANISM OF ACTION OF MACROLIDES 4
RESISTANCE 6
SAFETY IN PREGNANCY AND BREAST FEEDING 9
DRUGS INTERACTIONS 10
CLASSIFICATION OF MACROLIDES 12
KETOLIDES 13
FLUOROKETOLIDES 14
NON-ANTIBIOTIC MACROLIDES,
ANTIFUNGAL MACROLIDES,
TOXIC MACROLIDES.
15
ERYTHROMYCIN 16
CLARITHROMYCIN 22
AZITHROMYCIN 25
CASE STUDY 28
REFERENCES 32
 The Macrolides are a class of antibiotics possessing a
large lactone ring to which sugars are attached.
 Macrolides are protein synthesis inhibitors.
 They are bacteriostatic in nature.
 Macrolides terminate protein synthesis by inhibiting
the 50S ribosome via specific binding with the 23S
ribosomal subunit and various proteins.
Inhibition of bacterial protein
biosynthesis, and they are thought to do
this by preventing peptidyl transferase
from adding the growing peptide
attached to tRNA to the next amino acid
Another potential mechanism is
premature dissociation of the peptidyl-
tRNA from the ribosome.
Macrolide antibiotics do so by binding
reversibly to the P site on the 50S
subunit of the bacterial ribosome. This
action is considered to be
bacteriostatic.
CONTD:
IMMUNOMODULATION
E.g: Diffuse pan bronchiolitis
The macrolide antibiotics erythromycin, clarithromycin, and
roxithromycin have proven to be an effective long-term treatment for the
idiopathic, Asian-prevalent lung disease Diffuse pan bronchiolitis (DPB).
controlling symptoms through immunomodulation (adjusting the immune
response), with the added benefit of low-dose requirements.
suppression of not only neutrophil granulocyte proliferation but also
lymphocyte activity and obstructive secretions in airways.
CONTD:
Resistance
1. RIBOSOMAL METHYLATION: THE MLSB RESISTANCE PHENOTYPE
 It is secondary to the acquisition of an erm gene (erythromycin ribosome methylase).
 This gene encodes a ribosomal methylase which dimethylates pneumococcal 23S rRNA at a single site, adenine
at position 2058.
 The modification markedly reduces the affinity of erythromycin for its target, probably by preventing direct
access to the target or by modifying the conformation of the binding site.
 Transposition occurs from chromosome to chromosome of strains of S. pneumonia.
 Regulation of ERM(B) expression and the MLSB resistance phenotype
 The methylase encoded by erm(B) may be constitutively or inducibly synthesized.
 When expression is constitutive, the erm(B) mRNA is active, and its translation by the ribosomes allows
constitutive methylation of the ribosomes,
 When resistance is inducible, erm(B) mRNA is synthesized, but in an inactive conformation, and becomes active
only in the presence of inducing macrolides.
 For a given erm gene, the inducing capacity of the macrolides depends on the antibiotic structure. The global
structure of the drug, rather than the number of atoms in the lactone ring, determines the inducing capacity of a
macrolide.
 Example, erythromycin is an inducer for the production of most Erm methylases, whereas ketolides, which have
a similar lactone ring, are not. For erm(B), the commercially available macrolides (including the 14-, 15-, and 16-
membered macrolides), lincosamides, and streptogramin B antibiotics are inducers of methylase synthesis to
various degrees, leading to cross-resistance to these antimicrobial agents.
The gene responsible for efflux was initially called mefE and was subsequently assigned to the
mef(A) gene class because of its close relatedness to the mefA gene in S. pyogenes. The Mef(A)
pump belongs to the major facilitator superfamily class. It contains 12 transmembrane domains
spanning the cytoplasmic membrane, and efflux is driven by the proton motive force.
Resistance appears to be induced with erythromycin and is expressed at moderate levels, with
erythromycin MICs of between 1 and 64 µg/ml (generally between 8 and 32 µg/ml).
Physiological pumps conferring erythromycin resistance by efflux have been described for several
gram-positive organisms, such as Cmr from Corynebacterium glutamicum, which belongs to the
major facilitator superfamily class of pumps, but not for S. pneumoniae.
Because the 16-membered macrolides, the lincosamides, and the streptogramin B antibiotics are
not substrates of the pump, these antimicrobial agents remain active, even after induction with
erythromycin.
In vitro selection of E. coli mutants
highly resistant to erythromycin
has been of considerable value for
characterization of the site of
binding of this antibiotic to the
ribosome.
The clinical importance of this
mechanism was recognized several
years ago for microorganisms such
as Helicobacter pylori and
Mycobacterium avium but only
recently for pneumococci
 Erythromycin, roxithromycin and azithromycin are safe to use while breast feeding,
clarithromycin is considered safe to use while breast feeding.
(* Australian Therapeutic Goods Administration Pregnancy Categories)
Category A Erythromycin
Category B1 Roxithromycin
Category B2 Azithromycin
Category B3 Clarithromycin
Drugs
interactions
• Potent hepatic
cytochrome P450
enzyme inhibitors.
• They also have an
inhibitory effect on
transporter
proteins.
• Effects
gastrointestinal
flora and gastric
emptying time.
If possible, it is
recommended
that the
interacting
medicine be
withheld, or
the dose
reduced during
the course
Amiodarone, Methadone, Lithium, Amitriptyline
and Citalopram, Verapamil + Erythromycin.
increased risk of QT interval prolongation.
Warfarin + Clarithromycin and Erythromycin. increased anticoagulant properties,
Dabigatran + Clarithromycin and Erythromycin. signs of bleeding. This effect may be more
pronounced in elderly people, or when renal
function is reduced
Simvastatin and atorvastatin + macrolides
inhibiting CYP3A4 enzymes‫۔‬
statin-induced rhabdomyolysis.
Digoxin + clarithromycin. digoxin toxicity.
 Other medicines that may have significant interactions with macrolides in elderly people or those
with significant co-morbidities include; benzodiazepines, carbamazepine, cimetidine, clozapine,
colchicine and theophylline.
MACROLIDES
Ketolides
Non
antibiotic
macrolides
Antifungal
macrolides
Toxic
macrolides
CLASSIFICATION OF MACROLIDES
Ketolides are a class
of antibiotics that are
structurally related
to the macrolides.
Indications
They are used to
treat respiratory tract
infections caused by
macrolide-resistant
bacteria.
Ketolides are
especially effective,
as they have two
ribosomal binding
sites.
Ketolides include:
Telithromycin - the
first and only
approved ketolide
Cethromycin Solithromycin
TELITHROMYCIN
Fluoroketolides
are a class of
antibiotics that
are structurally
related to the
ketolides.
The
fluoroketolides
have three
ribosomal
interaction sites.
Fluoroketolides
include:
Solithromycin -
the first and
currently the only
fluoroketolide (not
yet approved)
Non-antibiotic
macrolides
• Tacrolimus,
Pimecrolimus, and
Sirolimus,
(immunosuppressants
or
immunomodulators).
• They have similar
activity to ciclosporin.
Antifungal drugs
• Polyene antimycotics,
amphotericin B,
nystatin etc.
• Cruentaren
Toxic macrolides
• produced by bacteria
• the mycolactones.
Antibacterial spectrum
Gram +ve, Gram –ve,
Pneumococci Neisseria sp.
Streptococci Bordetella pertussis
Staphylococci Bartonella henselae
Corynebacterium B quintana
Legionella Rickettsia sp.
Chlamydia Treponema pallidum
C.Pneumonia Campylobacter sp.
Helicobacter Haemophilus influenzae
Listeria Roxithromycin
Antibacterial action of
erythromycin maybe
inhibitory, bactericidal,
particularly at higher
concentrations.
Absorption:
• Activity is enhanced at
alkaline Ph.
• Must be administered
with enteric coating
• Food interferes with
absorption
• Absorbed in body tissues
and fluids except CSF.
Distribution:
• Oral dosage of 2g/day
results in serum
concentration of
2mcg/ml.
• 500mg IV erythromycin
results in peak level of
10mcg/ml after 1 hour of
dosing.
• Serum half life is 1.5
hours normally, 5 hours
in anuria patients.
Metabolism:
• Metabolized in Phase
II of glucourinadation
pathway.
Excretion:
• Excreted in the
bile, and lost in
feces with 5% in
urine.
Pharmacokinetics
• Corynebacterial infections (diphtheria, sepsis, erythrasma)
• Chlamydial infections (genital, neonatal, respiratory, ocular)
• Community acquired pneumonia.
1st line treatment
• Endocarditis during dental procedures in individuals with valvular heart disease.
Prophylaxis
Erythromycin is also useful as a substitute in penicillin-
allergic individuals with infections caused by
staphylococci, streptococci or pneumococci.
Gastro-
intestinal
effects
anorexia, vomiting,
nausea, diarrhea
due to direct
stimulation of gut
motility.
Liver
toxicity
Estolate
erythromycins
can cause acute
cholestasis
hepatitis, fever,
eosinophilia,
rashes.
Drug
interactio
ns
Erythromycins
inhibits CYP450,
inhibiting the
metabolism of
theophylline, oral
anticoagulants,
cyclosporine and
methyl
prednisolone.
Adverse reactions:
Erythromycin
Topical:
Topical ointments
2%
Topical pads 2%
Topical solution
2%
Topical gel 2%
Erythromycin
stearate Tablet: 250mg PO Q6H 500mg PO Q12H Amebiasis:
500mg PO 16H for
10-14 days
Legionnaires
disease:
1-4g/day PO in
divided doses for
21 days
Urethritis
caused by C
trachomatis or
U urealyticum:
500mg PO Q6H
for 7 days;
alternatively
333mg PO Q8H
for 7 days
Syphilis:
30-40mg PO in
divided doses for
10-15 days
Renal
imapairment:
Dose adjustment
is not necessary.
Brands Manufacturing company
ACUMEN Rakaposhi pharmaceutical (pvt) ltd
DELTACIN Delta pharma (pvt) ltd
ERYTHROCIN Indus pharma (pvt) ltd
TILORYTH Glitz pharma
• Similar as erythromycin except that it is more active
against
• Mycobacterium avium complex.
• Also has activity against Toxoplasma gondii, M leprae.
Antibacterial
spectrum:
• A 500mg dose produces serum concentrations of 2-3 mcg/ml.
• Has half life of 6 hours, so given Q12H.
• Recommended dosage is 250-500mg Q12H or 1000mg of
extended release formulation once daily.
• Improved oral absorption as compared to erythromycin.
• Metabolized in liver, eliminated in urine.
• Dose reduction unto 250mg once or twice daily is
recommended in patients with creatinine clearance <30ml/min.
Pharmacokinetics:
• Similar as erythromycins.Drug interactions:
Oral
suspension:
125mg/5ml 250mg/5ml Tablet: 250mg
500mg
Tablet,
extended
release
500mg
Mycobacterial
infection
500mg PO Q12H
for 7-14 days; use
in combination
with ethambutol
Peptic ulcer
disease
500mg PO Q8-
12H for 10-14
days
Pharyngitis,
Tonsillitis
250mg PO Q12H
for 10 days
Community
acquired
Pneumonia
250mg PO Q12H
for 7-14 days
Skin/Skin
structure
infection
500mg PO twice
daily for 7 days
Brands Manufacturing company
KLARCAY Caylexpharmaceuticals (pvt) ltd.
KLARI Meditech pharmaceuticals
KLARIBACT Merck private ltd.
KLARICID
Abbott laboratories (Pakistan)
limited.
Antibacterial spectrum
• Its spectrum and
clinical uses are
identical to those of
erythromycin.
• It is active against M
avium complex and T
gondii.
• It is slightly less
active against
staphylococci,
streptococci
• More active against H
influenza and
chlamydia.
Pharmacokinetics
• Well absorbed orally.
• Should be administered 1 hour before
or 2 hour after meal.
• A 500mg dose of azithromycin
produces serum concentrations of
approx. 0.4mcg/ml.
• It can penetrate into most tissues
except CSF.
• Its tissue concentration exceeds its
serum concentration by 10-100 folds
(high bioavailability).
• Its elimination half life is 2-4 days.
• Community acquired pneumonia can
be treated with 500mg dose loading
dose, followed by 250mg single daily
dose for next 4 days.
Drug
interactions
• Doesn’t
inactivates
CYP450
enzyme, so it is
free from drug
interactions.
Suspension 500mg 2.5g
Suspension
reconstituted
100mg/5ml
200mg/5ml Packet 1g Tablet 250mg, 500mg,
600mg
Acute otitis
media
500mg PO
once, then
250mg once
daily for 4 days
Acute
bacterial
sinusitis
500mg/day PO
for 3 days or 2g
PO once
Genital ulcer
disease
1g PO once
Pharyngitis/
Tonsillitis
500mg PO
once, then
250mg once
daily for 4 days
Uncomplicated
Gonococcal
infections
Ceftriaxone
250mg IM once
+ Azithromycin
1g PO once.
Brands Manufacturing company
ZOLIB Stalwart pharmaceuticals (pvt) ltd
AZOM Lotus pharmaceuticals (pvt) ltd
AZOMAX Novartis pharma (pak) ltd
AZOMAX Novartis pharma (pak) ltd
PATIENT
PERSONAL
INFORMATION:
Age: 26 years
Gender: Male
Weight: 62kgs
PAST DIAGNOSIS:
No chronic pathology.
CLINICAL DIAGNOSIS:
Acute bronchitis, Acute sinusitis,
Hypersensitivity symptoms,
LABORATORY REPORTS:
Typhidot;
• -veIgG
• -veIgM
CBC;
• 15.5 g/dlHemoglobin=
• 45.3%Hematocrit=
• 5.58RBC=
• 5.58Neutrophils
• 22%Lymphocytes=
• 4%Monocytes=
• 1%Eosinophils=
• 0Basophils=
• 6mm/1HrESR
DRUG ALLERGIES:
Allergic to Sulfa groups
Penicillin allergic
PAST MEDICATIONS:
NA
PRESENT MEDICATIONS:
Fexofenadine 60mg OD.
Paracetamol 1g BID.
AZITHROMYCIN dehydrate
250mg q12h.
Seven seas OD.
Montelukast sodium 10mg
OD.
THERAPEUTIC
INTERVENTIONS:
Azithromycin
should be
prescribed as
500mg once as
loading dose
and then
continued as
250mg q24h.
Azithromycin is
used as a
prophylaxis
therapy of
typhoid, so it
must be stopped
after Typhidot
report to avoid
GI disturbance.
For the
symptomatic
treatment of
non-productive
of cough,
Dextromethorp
han syrup must
be prescribed.Patient
compliance
maybe an issue
in this regimen,
dosage forms
must be
changed.
Proper
counselling
must be done,
wearing a mask
to avoid
pollution and
dust can
improve the
conditions.
INTRODUCTION, GENERAL
MECHANISM OF ACTION
OF MACROLIDES,
CLASSIFICATION OF
MACROLIDES,
(KETOLIDES,
FLUOROKETOLIDES, NON-
ANTIBIOTIC MACROLIDES,
ANTIFUNGAL
MACROLIDES, TOXIC
MACROLIDES).
https://en.wikipedia.org/w
iki/Macrolide
RESISTANCE TO
MACROLIDES:
https://aac.asm.org/conte
nt/46/9/2727
SAFETY IN PREGNANCY
AND BREAST FEEDING,
DRUGS INTERACTIONS:
https://bpac.org.nz/bpj/20
12/may/macrolides.aspx
REFERENCES:
ERYTHROMYCIN
Katzung
http://www.druginfosys.com/av
ailablebrands.aspx?query=500%
20mg&form=Tabs&drugCode=28
3&drugName=Erythromycin&Ing
Medscape
AZITHROMYCIN
Katzung
http://www.druginfosys.com/av
ailablebrands.aspx?query=200%
20mg/5ml&form=Susp&drugCod
e=808&drugName=Azithromycin
&Ing==1
Medscape
CLARITHROMYCIN
Katzung
http://www.druginfosys.com/av
ailablebrands.aspx?query=125%
20mg/5ml&form=Susp&drugCod
e=858&drugName=Clarithromyci
n&Ing==1
Medscape

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Macrolides

  • 1. Submitted to: Sir Dr. Narendar Sharma Presenter: Mohammad Waqas Mairaj 2K16/PHA/56(Morning) 4TH Prof: Pharm-D, University of Sindh faculty of Pharmacy, Jamshoro Date of submission: 1st April, 2019
  • 2. Topics Slide # INTRODUCTION 3 GENERAL MECHANISM OF ACTION OF MACROLIDES 4 RESISTANCE 6 SAFETY IN PREGNANCY AND BREAST FEEDING 9 DRUGS INTERACTIONS 10 CLASSIFICATION OF MACROLIDES 12 KETOLIDES 13 FLUOROKETOLIDES 14 NON-ANTIBIOTIC MACROLIDES, ANTIFUNGAL MACROLIDES, TOXIC MACROLIDES. 15 ERYTHROMYCIN 16 CLARITHROMYCIN 22 AZITHROMYCIN 25 CASE STUDY 28 REFERENCES 32
  • 3.  The Macrolides are a class of antibiotics possessing a large lactone ring to which sugars are attached.  Macrolides are protein synthesis inhibitors.  They are bacteriostatic in nature.  Macrolides terminate protein synthesis by inhibiting the 50S ribosome via specific binding with the 23S ribosomal subunit and various proteins.
  • 4. Inhibition of bacterial protein biosynthesis, and they are thought to do this by preventing peptidyl transferase from adding the growing peptide attached to tRNA to the next amino acid Another potential mechanism is premature dissociation of the peptidyl- tRNA from the ribosome. Macrolide antibiotics do so by binding reversibly to the P site on the 50S subunit of the bacterial ribosome. This action is considered to be bacteriostatic. CONTD:
  • 5. IMMUNOMODULATION E.g: Diffuse pan bronchiolitis The macrolide antibiotics erythromycin, clarithromycin, and roxithromycin have proven to be an effective long-term treatment for the idiopathic, Asian-prevalent lung disease Diffuse pan bronchiolitis (DPB). controlling symptoms through immunomodulation (adjusting the immune response), with the added benefit of low-dose requirements. suppression of not only neutrophil granulocyte proliferation but also lymphocyte activity and obstructive secretions in airways. CONTD:
  • 6. Resistance 1. RIBOSOMAL METHYLATION: THE MLSB RESISTANCE PHENOTYPE  It is secondary to the acquisition of an erm gene (erythromycin ribosome methylase).  This gene encodes a ribosomal methylase which dimethylates pneumococcal 23S rRNA at a single site, adenine at position 2058.  The modification markedly reduces the affinity of erythromycin for its target, probably by preventing direct access to the target or by modifying the conformation of the binding site.  Transposition occurs from chromosome to chromosome of strains of S. pneumonia.  Regulation of ERM(B) expression and the MLSB resistance phenotype  The methylase encoded by erm(B) may be constitutively or inducibly synthesized.  When expression is constitutive, the erm(B) mRNA is active, and its translation by the ribosomes allows constitutive methylation of the ribosomes,  When resistance is inducible, erm(B) mRNA is synthesized, but in an inactive conformation, and becomes active only in the presence of inducing macrolides.  For a given erm gene, the inducing capacity of the macrolides depends on the antibiotic structure. The global structure of the drug, rather than the number of atoms in the lactone ring, determines the inducing capacity of a macrolide.  Example, erythromycin is an inducer for the production of most Erm methylases, whereas ketolides, which have a similar lactone ring, are not. For erm(B), the commercially available macrolides (including the 14-, 15-, and 16- membered macrolides), lincosamides, and streptogramin B antibiotics are inducers of methylase synthesis to various degrees, leading to cross-resistance to these antimicrobial agents.
  • 7. The gene responsible for efflux was initially called mefE and was subsequently assigned to the mef(A) gene class because of its close relatedness to the mefA gene in S. pyogenes. The Mef(A) pump belongs to the major facilitator superfamily class. It contains 12 transmembrane domains spanning the cytoplasmic membrane, and efflux is driven by the proton motive force. Resistance appears to be induced with erythromycin and is expressed at moderate levels, with erythromycin MICs of between 1 and 64 µg/ml (generally between 8 and 32 µg/ml). Physiological pumps conferring erythromycin resistance by efflux have been described for several gram-positive organisms, such as Cmr from Corynebacterium glutamicum, which belongs to the major facilitator superfamily class of pumps, but not for S. pneumoniae. Because the 16-membered macrolides, the lincosamides, and the streptogramin B antibiotics are not substrates of the pump, these antimicrobial agents remain active, even after induction with erythromycin.
  • 8. In vitro selection of E. coli mutants highly resistant to erythromycin has been of considerable value for characterization of the site of binding of this antibiotic to the ribosome. The clinical importance of this mechanism was recognized several years ago for microorganisms such as Helicobacter pylori and Mycobacterium avium but only recently for pneumococci
  • 9.  Erythromycin, roxithromycin and azithromycin are safe to use while breast feeding, clarithromycin is considered safe to use while breast feeding. (* Australian Therapeutic Goods Administration Pregnancy Categories) Category A Erythromycin Category B1 Roxithromycin Category B2 Azithromycin Category B3 Clarithromycin
  • 10. Drugs interactions • Potent hepatic cytochrome P450 enzyme inhibitors. • They also have an inhibitory effect on transporter proteins. • Effects gastrointestinal flora and gastric emptying time. If possible, it is recommended that the interacting medicine be withheld, or the dose reduced during the course
  • 11. Amiodarone, Methadone, Lithium, Amitriptyline and Citalopram, Verapamil + Erythromycin. increased risk of QT interval prolongation. Warfarin + Clarithromycin and Erythromycin. increased anticoagulant properties, Dabigatran + Clarithromycin and Erythromycin. signs of bleeding. This effect may be more pronounced in elderly people, or when renal function is reduced Simvastatin and atorvastatin + macrolides inhibiting CYP3A4 enzymes‫۔‬ statin-induced rhabdomyolysis. Digoxin + clarithromycin. digoxin toxicity.  Other medicines that may have significant interactions with macrolides in elderly people or those with significant co-morbidities include; benzodiazepines, carbamazepine, cimetidine, clozapine, colchicine and theophylline.
  • 13. Ketolides are a class of antibiotics that are structurally related to the macrolides. Indications They are used to treat respiratory tract infections caused by macrolide-resistant bacteria. Ketolides are especially effective, as they have two ribosomal binding sites. Ketolides include: Telithromycin - the first and only approved ketolide Cethromycin Solithromycin TELITHROMYCIN
  • 14. Fluoroketolides are a class of antibiotics that are structurally related to the ketolides. The fluoroketolides have three ribosomal interaction sites. Fluoroketolides include: Solithromycin - the first and currently the only fluoroketolide (not yet approved)
  • 15. Non-antibiotic macrolides • Tacrolimus, Pimecrolimus, and Sirolimus, (immunosuppressants or immunomodulators). • They have similar activity to ciclosporin. Antifungal drugs • Polyene antimycotics, amphotericin B, nystatin etc. • Cruentaren Toxic macrolides • produced by bacteria • the mycolactones.
  • 16. Antibacterial spectrum Gram +ve, Gram –ve, Pneumococci Neisseria sp. Streptococci Bordetella pertussis Staphylococci Bartonella henselae Corynebacterium B quintana Legionella Rickettsia sp. Chlamydia Treponema pallidum C.Pneumonia Campylobacter sp. Helicobacter Haemophilus influenzae Listeria Roxithromycin
  • 17. Antibacterial action of erythromycin maybe inhibitory, bactericidal, particularly at higher concentrations. Absorption: • Activity is enhanced at alkaline Ph. • Must be administered with enteric coating • Food interferes with absorption • Absorbed in body tissues and fluids except CSF. Distribution: • Oral dosage of 2g/day results in serum concentration of 2mcg/ml. • 500mg IV erythromycin results in peak level of 10mcg/ml after 1 hour of dosing. • Serum half life is 1.5 hours normally, 5 hours in anuria patients. Metabolism: • Metabolized in Phase II of glucourinadation pathway. Excretion: • Excreted in the bile, and lost in feces with 5% in urine. Pharmacokinetics
  • 18. • Corynebacterial infections (diphtheria, sepsis, erythrasma) • Chlamydial infections (genital, neonatal, respiratory, ocular) • Community acquired pneumonia. 1st line treatment • Endocarditis during dental procedures in individuals with valvular heart disease. Prophylaxis Erythromycin is also useful as a substitute in penicillin- allergic individuals with infections caused by staphylococci, streptococci or pneumococci.
  • 19. Gastro- intestinal effects anorexia, vomiting, nausea, diarrhea due to direct stimulation of gut motility. Liver toxicity Estolate erythromycins can cause acute cholestasis hepatitis, fever, eosinophilia, rashes. Drug interactio ns Erythromycins inhibits CYP450, inhibiting the metabolism of theophylline, oral anticoagulants, cyclosporine and methyl prednisolone. Adverse reactions:
  • 20. Erythromycin Topical: Topical ointments 2% Topical pads 2% Topical solution 2% Topical gel 2% Erythromycin stearate Tablet: 250mg PO Q6H 500mg PO Q12H Amebiasis: 500mg PO 16H for 10-14 days Legionnaires disease: 1-4g/day PO in divided doses for 21 days Urethritis caused by C trachomatis or U urealyticum: 500mg PO Q6H for 7 days; alternatively 333mg PO Q8H for 7 days Syphilis: 30-40mg PO in divided doses for 10-15 days Renal imapairment: Dose adjustment is not necessary.
  • 21. Brands Manufacturing company ACUMEN Rakaposhi pharmaceutical (pvt) ltd DELTACIN Delta pharma (pvt) ltd ERYTHROCIN Indus pharma (pvt) ltd TILORYTH Glitz pharma
  • 22. • Similar as erythromycin except that it is more active against • Mycobacterium avium complex. • Also has activity against Toxoplasma gondii, M leprae. Antibacterial spectrum: • A 500mg dose produces serum concentrations of 2-3 mcg/ml. • Has half life of 6 hours, so given Q12H. • Recommended dosage is 250-500mg Q12H or 1000mg of extended release formulation once daily. • Improved oral absorption as compared to erythromycin. • Metabolized in liver, eliminated in urine. • Dose reduction unto 250mg once or twice daily is recommended in patients with creatinine clearance <30ml/min. Pharmacokinetics: • Similar as erythromycins.Drug interactions:
  • 23. Oral suspension: 125mg/5ml 250mg/5ml Tablet: 250mg 500mg Tablet, extended release 500mg Mycobacterial infection 500mg PO Q12H for 7-14 days; use in combination with ethambutol Peptic ulcer disease 500mg PO Q8- 12H for 10-14 days Pharyngitis, Tonsillitis 250mg PO Q12H for 10 days Community acquired Pneumonia 250mg PO Q12H for 7-14 days Skin/Skin structure infection 500mg PO twice daily for 7 days
  • 24. Brands Manufacturing company KLARCAY Caylexpharmaceuticals (pvt) ltd. KLARI Meditech pharmaceuticals KLARIBACT Merck private ltd. KLARICID Abbott laboratories (Pakistan) limited.
  • 25. Antibacterial spectrum • Its spectrum and clinical uses are identical to those of erythromycin. • It is active against M avium complex and T gondii. • It is slightly less active against staphylococci, streptococci • More active against H influenza and chlamydia. Pharmacokinetics • Well absorbed orally. • Should be administered 1 hour before or 2 hour after meal. • A 500mg dose of azithromycin produces serum concentrations of approx. 0.4mcg/ml. • It can penetrate into most tissues except CSF. • Its tissue concentration exceeds its serum concentration by 10-100 folds (high bioavailability). • Its elimination half life is 2-4 days. • Community acquired pneumonia can be treated with 500mg dose loading dose, followed by 250mg single daily dose for next 4 days. Drug interactions • Doesn’t inactivates CYP450 enzyme, so it is free from drug interactions.
  • 26. Suspension 500mg 2.5g Suspension reconstituted 100mg/5ml 200mg/5ml Packet 1g Tablet 250mg, 500mg, 600mg Acute otitis media 500mg PO once, then 250mg once daily for 4 days Acute bacterial sinusitis 500mg/day PO for 3 days or 2g PO once Genital ulcer disease 1g PO once Pharyngitis/ Tonsillitis 500mg PO once, then 250mg once daily for 4 days Uncomplicated Gonococcal infections Ceftriaxone 250mg IM once + Azithromycin 1g PO once.
  • 27. Brands Manufacturing company ZOLIB Stalwart pharmaceuticals (pvt) ltd AZOM Lotus pharmaceuticals (pvt) ltd AZOMAX Novartis pharma (pak) ltd AZOMAX Novartis pharma (pak) ltd
  • 28. PATIENT PERSONAL INFORMATION: Age: 26 years Gender: Male Weight: 62kgs PAST DIAGNOSIS: No chronic pathology. CLINICAL DIAGNOSIS: Acute bronchitis, Acute sinusitis, Hypersensitivity symptoms,
  • 29. LABORATORY REPORTS: Typhidot; • -veIgG • -veIgM CBC; • 15.5 g/dlHemoglobin= • 45.3%Hematocrit= • 5.58RBC= • 5.58Neutrophils • 22%Lymphocytes= • 4%Monocytes= • 1%Eosinophils= • 0Basophils= • 6mm/1HrESR
  • 30. DRUG ALLERGIES: Allergic to Sulfa groups Penicillin allergic PAST MEDICATIONS: NA PRESENT MEDICATIONS: Fexofenadine 60mg OD. Paracetamol 1g BID. AZITHROMYCIN dehydrate 250mg q12h. Seven seas OD. Montelukast sodium 10mg OD.
  • 31. THERAPEUTIC INTERVENTIONS: Azithromycin should be prescribed as 500mg once as loading dose and then continued as 250mg q24h. Azithromycin is used as a prophylaxis therapy of typhoid, so it must be stopped after Typhidot report to avoid GI disturbance. For the symptomatic treatment of non-productive of cough, Dextromethorp han syrup must be prescribed.Patient compliance maybe an issue in this regimen, dosage forms must be changed. Proper counselling must be done, wearing a mask to avoid pollution and dust can improve the conditions.
  • 32. INTRODUCTION, GENERAL MECHANISM OF ACTION OF MACROLIDES, CLASSIFICATION OF MACROLIDES, (KETOLIDES, FLUOROKETOLIDES, NON- ANTIBIOTIC MACROLIDES, ANTIFUNGAL MACROLIDES, TOXIC MACROLIDES). https://en.wikipedia.org/w iki/Macrolide RESISTANCE TO MACROLIDES: https://aac.asm.org/conte nt/46/9/2727 SAFETY IN PREGNANCY AND BREAST FEEDING, DRUGS INTERACTIONS: https://bpac.org.nz/bpj/20 12/may/macrolides.aspx REFERENCES:

Editor's Notes

  1. 1.(similarly to chloramphenicol as well as inhibiting ribosomal translation. 2. Summarize protein synthesis. 3. Macrolides are actively concentrated within leukocytes, and thus are transported into the site of infection.
  2. Wordly meaning of immunomodultion.? Tell about which organism cause this.? This is evident, as the treatment dosage is much too low to fight infection, and in DPB cases with the occurrence of the macrolide-resistant bacterium Pseudomonas aeruginosa, macrolide therapy still produces substantial anti-inflammatory results.
  3. Cat:A:-- safe to use, but consider an alternative in the first trimester (unconfirmed reports of an association with congenital cardiac malformations). Cat:B1 B2:-- considered safe. Cat:B3:-- uncertain safety in pregnancy, consider an alternative.
  4. Erythromycin and clarithromycin are more commonly associated with medicine interactions than other macrolides. Elderly people and those with renal or liver impairment are more likely to be affected by medicines interacting with macrolides.
  5. 1. short-term risk of hypotension or shock amongst elderly people. 2. Warfarin may need to be temporarily stopped or the dose reduced if there is no alternative. The INR should be monitored if warfarin and macrolides are taken at the same time. 3. macrolides inhibiting CYP3A4 enzymes. This can result in an increased risk of statin-induced rhabdomyolysis. Azithromycin interacts less with CYP3A4 enzymes, however, there have also been occasional reports of rhabdomyolysis in patients taking azithromycin, Pravastatin is not significantly metabolised by CYP3A4, therefore is less likely to be affected by concurrent macrolide use. 4. digoxin dose should be reduced by half and the patient monitored for symptoms of toxicity.
  6. Solithromycin, the first and currently the only fluoroketolide (not yet approved).