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NUR FARAH BINTI
MUHAMMAD
012013100104
OUTLINES
• Penicillin G
• Ampicillin
• 3rd generation Cephalosporin
• 4th generation cephalosporin
• References
• have greatest activity against gram-positive
organisms, gram-negative cocci, and non-β-
lactamase producing anaerobes
• Have limited activity against gram-negative
bacilli, and they are susceptible to hydrolysis
by β-lactamases
Bind to penicillin-
binding protein (PBP)
Inhibit transpeptidation
reaction
Inhibit bacterial cell
wall synthesis
• IV administration
• Absorption in the stomach is impaired by food (at
least 1-2 hrs before/after meal)
• Half life: 30 minutes
• Widely distributed throughout the body
• Penetration in CSF is poor but in present of
inflammation(meningitis) adequate amount may
reach these site
• Metabolized in the liver & excreted in the urine
• Narrow spectrum,
bactericidal
• Cocci:
Streptococci(except
group D or enterococci)
• Bacilli: Gram-positive
bacilli(majority of B.
anthracis,
Corynebacterium
diphtheriae).
Antimicrobial of bacterial meningitis 2
USES CONTRAINDICATIONS
• Streptococcal
infections(pharyngitis).
• Pneumococcal infections.
• Meningococcal infections.
• Gonorrhea.
• History of previous
administration and allergic
manifestations.
• History of asthma, allergic
rhinitis, hay fever will
increased risk penicillin
allergy.
• Penicillin + methotrexate
Mechanism: competitive inhibition of renal
tubular secretion of methotrexate
Effect: elevate serum methotrexate
concentrations
• Extended spectrum of penicillin
• Improved activity against Gram-negative
organism
Bind to penicillin-
binding protein (PBP)
Inhibit transpeptidation
reaction
Inhibit bacterial cell
wall synthesis
• Oral, i.m, i.v(commonly) administration
• Half life: 1 hrs
• Penetration in CSF is poor but in present of
inflammation(meningitis) adequate amount
may reach these site
• Metabolised in the liver & excreted in the
urine
• Broad spectrum, bactericidal
• Gram-positive: Streptococcus spp., Enterococcus spp.,
Listeria monocytogenes
• Gram-negative bacilli: H. influenza, E. coli, Proteus,
Salmonella and Shigella
• drug of choice for the gram-positive bacillus Listeria
monocytogenes
• Diarrhea, nausea, rash
• Headache, and dizziness
• Nephritis
• Neurotoxicity
• Hematologic toxicities
USES CONTRAINDICATIONS
• Upper respiratory infections.
• Urinary tract infections.
• Meningitis
•Allergy to penicillins
•Infectious mononucleosis
•Allergy to cephalosporins,
carbapenems
•Adjust dose in renal failure
• Ampicillin + probenecid
Mechanism: decrease renal ampicillin
excretion
Effect: elevate serum ampicillin concentrations
Cefotaxime & Ceftriaxone
MOA:
Bind to PBP Inhibit transpeptidation
reaction Inhibit cell wall synthesis
• Administered intravenously
• Half life: 7-8 hrs
• Achieve levels in the CSF sufficient to inhibit
most susceptible pathogens
• Metabolized in the liver
• Mainly excreted in the feces and others are
excreted in the urine
• Broad spectrum
• active against citrobacter,
Serratia marcescens and
beta-lactamase-
producing strains
of Haemophilus and
Neisseria
• generally not active
against Enterobacter
species
Hypersensitivity:
-anaphylaxis, fever, skin rashes, nephritis,
granulocytopenia, and hemolytic anemia
Toxicity
-pain (IM injection), thrombophlebitis (IV
injection), renal toxicity
USES CONTRAINDICATION
• Meningitis caused by
meningococci and H.
influenzae
• Pyelonephritis.
• Septicemia.
• Community-acquired
pneumonia
• patients with history of
penicillin allergy
• patients with history of GI
disease, especially colitis
• Breastfeeding women
Cefepime
MOA:
Bind to PBP Inhibit transpeptidation
reaction Inhibit cell wall synthesis
• must be administered parenterally
• Penetrates well into CSF
• Half life: 2 hrs
• Excreted in the urine
• Broad spectrum, bectericidal
• Good activity against P. aeruginosa,
Enterobacteriaceae, S. aureus and
S.pneumoniae
• Highly active against Hemophilus and
Neisseria sp.
• anaphylaxis, fever, skin rashes
• nephritis, granulocytopenia, and hemolytic
anemia
• Renal toxicity
USES IS SAME AS 3rd
GENERATION
CEPHALOSPORIN
• Basic & Clinical Pharmacology, 12th Edition
Katzung
• Lippincott Illustrated Reviews: Pharmacology
Sixth Edition
• Essentials of Pharmacology, 6th Edition, KD
Tripathi.
• http://www.drugbank.ca/drugs/DB00415
• http://www.drugs.com/mtm/ampicillin.html
DRUGS FOR NON-BACTERIAL
MENINGITIS
NUR FARAH BINTI MUHAMMAD
012013100104
Regime of treatment:
Tuberculous meningitis
Parasitic meningitis
Lyme meningitis
Syphilitic meningitis
Drug therapy:
Isoniazid
Rifampin
Pyrazinamide
Dexamethasone
Amphotericin B
Miconazole
Doxycycline
References
Initial Therapy:
Isoniazid – 300mg/d
Rifampicin – 600mg/d
Pyrazinamide – 30mg/kg/d
Ethambutol – 15-25 mg/kg/d
Pyridoxine – 50mg/d
Good Response
: Discontinue
Pyrazinamide
after 2 months
continue H & R
for 6 – 12
months
Inadequate
Resolution :
Continue for 9
– 12 months
Corticosteroid
(dexamethasone)
IV, 60-80 mg/d for 6
weeks
TUBERCULOUS
MENINGITIS
PARASITIC MENINGITIS
Amphotericin B
Miconazole
Rifampin
High -dose IV and intrathecal
LYME MENINGITIS
Ceftriaxone (2 g/day for 14-28 days)
Penicillin G (20 million U/day for 14-28 days)
Doxycycline (100 mg orally or IV every 12 hours for
14-28 days)
SYPHILITIC MENINGITIS
Aqueous crystalline penicillin G (2-4 million U/day IV every 4
hours for 10-14 days)
IM penicillin G benzathine (2.4 million U).
Most active drug for treatment of TB
Bactericidal for actively growing tubercle bacilli
Penetrates into macrophages and is active against
both extracellular and intracellular organisms.
Isoniazid (prodrug)
Converted to active form by
mycobacterial catalase-
peroxidase (KatG)
Block synthesis of mycolic
acids
Disruption of bacterial cell
wall
readily absorbed after oral administration
Absorption is impaired if taken with food (high-fat
meals)
The drug diffuses into all body fluids, cells, and
caseous material. Drug concentrations in the (CSF)
are similar to those in the serum.
Metabolized in the liver (N -acetyltransferase)
Isoniazid metabolites and a small amount of
unchanged drug are excreted, mainly in the urine
Immunologic reactions
Fever, skin rashes
Direct toxicity
Isoniazid-induced hepatitis (can be fatal)
Clinical hepatitis with loss of appetite, nausea,
vomiting, jaundice, and right upper quadrant pain
hepatocellular, damage.
Peripheral neuropathy
CNS
convulsions, seizures
USES CONTRAINDICATIONS
Treating or preventing
tuberculosis (TB)
•Liver problem may occur in
alcoholic
•Hepatitis
•Patient receiving certain
medicines to treat HIV infection
Isoniazid + Phenytoin/ Carbamazepine/ Ethosuximide
Mechanism: Isoniazid inhibits metabolism of above
drugs
Effect: Increased effects of above drugs (nystagmus and
ataxia)
has broader antimicrobial activity than isoniazid,
bactericidal
active against gram-positive and gram negative cocci,
some enteric bacteria, mycobacteria, and chlamydiae
Rifampicin binds to β subunit of
bacterial DNA-dependent RNA
polymerase
Inhibit bacterial DNA-dependent
RNA polymerase
Inhibits RNA synthesis
Administered orally
Distribution of rifampin occurs to all body fluids and
organs. Concentrations attained in the CSF are
variable, often 10% to 20% of blood concentrations.
taken up by the liver and undergoes enterohepatic
recycling
Elimination of rifampin and its metabolites is
primarily through the bile and into the feces; a small
percentage is cleared in the urine
Generally well tolerated
harmless orange color to urine, sweat, and tears(soft
contact lenses may be permanently stained)
hepatitis
Nausea, vomiting, rashes,and nephritis
Flulike-syndrome (fever, chills, myalgias, anemia, and
thrombocytopenia)
USES CONTRAINDICATIONS
•Mycobacterial infections
•Bacterial infections
(meningococcal carriage)
•used as prophylaxis in contacts
of children with Haemophilus
influenzae type b disease
•treatment of serious
staphylococcal infections such
as osteomyelitis and prosthetic
valve endocarditis
•allergic to any ingredient in
rifampin or to any rifamycin
(eg, rifabutin)
•Pregnant women
•Breastfeeding women
Rifampin + OCP
• Mechanism: Rifampicin is an enzyme inducer. It
induces metabolism of OCP
• Effect: Contraceptive failure
stable and slightly soluble in water
inactive at neutral pH, but at pH 5.5 it inhibits
tubercle bacilli (bactericidal)
drug is taken up by macrophages and exerts its
activity against mycobacteria residing within the
acidic environment of lysosomes
Pyrazinamide(Pro-
drug)
Converted to active
form (pyrazinoic
acid)by mycobacterial
pyrazinamidase
Pyrazinoic acid disrupts
mycobacterial cell
membrane metabolism and
transport functions
*EXACT MECHANISM IS
UNKNOWN
Administered orally
well absorbed from the gastrointestinal tract and
widely distributed in body tissues, including inflamed
meninges
Metabolized by the liver, but metabolites are renally
cleared
Hepatitis
Hyperuricemia
Gastrointestinal disturbances
USES CONTRAINDICATION
Treating active tuberculosis in
combination with other
medicines
•Allergic to any ingredient in
pyrazinamide
•Have gout or severe liver
problems
•Pregnant & breastfeeding
women
Shown to improve overall outcome for patient with
certain types of bacterial meningitis, such as
H.influenza, tuberculous and pneumococcal
meningitis
First dose should be given prior to starting antibiotics
To decrease cytokine related damage , especially to
8th nerve
Corticosteroids diffuse across the cell
membrane and binds to a cytoplasmic
receptor. The receptor forms a dimer.
After dimerizing, the receptor– hormone
complex recruits coactivator proteins and
translocates into the nucleus, where it attaches
to gene promoter elements.
There it acts as a transcription factor to turn
genes off (when complexed with corepressors)
Inhibits protein synthesis for immunological
response (mediators and leukocytes)
Can be administered orally, intravenously and
intramuscularly.
>90% of absorbed glucocorticoids are bound to
plasma proteins, mostly corticosteroid-binding
globulin or albumin.
Corticosteroids are metabolized by the liver
microsomal oxidizing
enzymes. The metabolites are conjugated to
glucuronic acid or sulfate, and the products are
excreted by the kidney.
Antimicrobial of bacterial meningitis 2
USES CONTRAINDICATIONS
•Relief of inflammatory
symptoms
•Replacement therapy for
primary adrenocortical
insufficiency (Addison disease)
•Diagnosis of Cushing
syndrome (supression test)
•Replacement therapy for
congenital adrenal hyperplasia
(CAH)
•Treatment of allergies
•Acceleration of lung
maturation
•Hypersensitivity
•Cerebral malaria
•Lactating mother
•Systemic fungal infection
Prototype of polyene antimicrobials used
systemically.
antifungal antibiotics produced by Streptomyces
nodosus.
nearly insoluble in water
Amphotericin B binds to ergosterol in
the plasma membranes of sensitive
fungal cells
Forms pores (channels) that require
hydrophobic interactions between the
lipophilic segment of the polyene
antifungal and the sterol
Pores disrupt membrane function,
allowing electrolytes (particularly
potassium) and small molecules to
leak from the cell
Resulting in cell death
Administered intravenously with colloidal
suspension of amphotericin B and sodium
desoxycholate
Widely distributed in the body, but poor penetration
in CSF
Binds to sterols in tissues and lipoproteins in plasma
and stays in the body for long period.
About 60% of AMB is metabolized in liver.
The serum half life is 15 days.
Excretion occurs slowly both in urine and bile, but
urinary concentration of active drug is low.
ADVERSE EFFECT
Low therapeutic index
Fever, chills, malaise, weight loss
N & V, diarrhea, epigastric pain
Thrombophlebitis
Muscle and joint pain
Headache
Decreased renal function : azotemia,
hypokalemia, hyposthenuria, renal
tubular acidosis, and nephrocalcinosis.
USES CONTRAINIDICATIONS
•Antifungal agent with the
broadest spectrum of action
•Use in treatment for:
aspergillosis, cryptococcosis
(torulosis), North American
blastomycosis, systemic
candidiasis, coccidiomycosis,
histoplasmosis, zygomycosis
including mucormycosis and
infections due to related
susceptible species of
Conidiobolus and Basidiobolus,
and Sporotrichosis
Contraindicated in those
patients who have shown
hypersensitivity to
Amphotericin B or any other
component in the formulation
Antineoplastic agents: enhance the potential for
renal toxicity, bronchospasm and hypotension.
Antineoplastic agents (e.g., nitrogen mustard, etc.)
should be given concomitantly only with caution.
Corticosteroids and Corticotropin (ACTH): may
potentiate Amphotericin B-induced hypokalemia
predisposisng the patient to cardiac dysfunction.
Digitalis glycosides: Amphotericin B-induced
hypokalemia may potentiate digitalis toxicity. Serum
potassium levels and cardiac function should be
closely monitored.
• Imidazole antifungal agent
• commonly applied topically to the skin or to mucous
membrane to cure fungal infections
• Prevents fungal organisms from producing vital
substances required for growth and function.
Miconazole interacts
with 14-α demethylase,
a cytochrome P-450
enzyme that is necessary
to convert lanosterol to
ergosterol
As ergosterol is an
essential component of
the fungal cell
membrane, inhibition of
its synthesis results in
increased cellular
permeability causing
leakage of cellular
contents.
Miconazole may also
inhibit endogenous
respiration, interact with
membrane
phospholipids, inhibit
the transformation of
yeasts to mycelial forms,
inhibit purine uptake,
and impair triglyceride
and/or phospholipid
biosynthesis.
• Administered by topically and vaginally.
• Minimal systemic absorption following topical
application to skin.
• Only small amounts absorbed systemically following
intravaginal administration
• Drugs metabolized by hepatic microsomal enzymes.
• Systemically absorbed drug excreted in urine and
feces
• Burning, stinging, swelling, irritation, redness,
pimple-like bumps, tenderness, or flaking of the
treated skin
USES CONTRAINDICATIONS
•Dermatophytoses
•Pityriasis (Tinea)
Versicolor
•Cutaneous Candidiasis
•Vulvovaginal Candidiasis
•Known hypersensitivity to
miconazole or any
ingredient in the
formulation
DRUG INTERACTION
• Warfarin + miconazole
-may increase the plasma concentrations and
hypoprothrombinemic effect of warfarin
-cause to bleed more easily
Antimicrobial of bacterial meningitis 2

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Antimicrobial of bacterial meningitis 2

  • 2. OUTLINES • Penicillin G • Ampicillin • 3rd generation Cephalosporin • 4th generation cephalosporin • References
  • 3. • have greatest activity against gram-positive organisms, gram-negative cocci, and non-β- lactamase producing anaerobes • Have limited activity against gram-negative bacilli, and they are susceptible to hydrolysis by β-lactamases
  • 4. Bind to penicillin- binding protein (PBP) Inhibit transpeptidation reaction Inhibit bacterial cell wall synthesis
  • 5. • IV administration • Absorption in the stomach is impaired by food (at least 1-2 hrs before/after meal) • Half life: 30 minutes • Widely distributed throughout the body • Penetration in CSF is poor but in present of inflammation(meningitis) adequate amount may reach these site • Metabolized in the liver & excreted in the urine
  • 6. • Narrow spectrum, bactericidal • Cocci: Streptococci(except group D or enterococci) • Bacilli: Gram-positive bacilli(majority of B. anthracis, Corynebacterium diphtheriae).
  • 8. USES CONTRAINDICATIONS • Streptococcal infections(pharyngitis). • Pneumococcal infections. • Meningococcal infections. • Gonorrhea. • History of previous administration and allergic manifestations. • History of asthma, allergic rhinitis, hay fever will increased risk penicillin allergy.
  • 9. • Penicillin + methotrexate Mechanism: competitive inhibition of renal tubular secretion of methotrexate Effect: elevate serum methotrexate concentrations
  • 10. • Extended spectrum of penicillin • Improved activity against Gram-negative organism
  • 11. Bind to penicillin- binding protein (PBP) Inhibit transpeptidation reaction Inhibit bacterial cell wall synthesis
  • 12. • Oral, i.m, i.v(commonly) administration • Half life: 1 hrs • Penetration in CSF is poor but in present of inflammation(meningitis) adequate amount may reach these site • Metabolised in the liver & excreted in the urine
  • 13. • Broad spectrum, bactericidal • Gram-positive: Streptococcus spp., Enterococcus spp., Listeria monocytogenes • Gram-negative bacilli: H. influenza, E. coli, Proteus, Salmonella and Shigella • drug of choice for the gram-positive bacillus Listeria monocytogenes
  • 14. • Diarrhea, nausea, rash • Headache, and dizziness • Nephritis • Neurotoxicity • Hematologic toxicities
  • 15. USES CONTRAINDICATIONS • Upper respiratory infections. • Urinary tract infections. • Meningitis •Allergy to penicillins •Infectious mononucleosis •Allergy to cephalosporins, carbapenems •Adjust dose in renal failure
  • 16. • Ampicillin + probenecid Mechanism: decrease renal ampicillin excretion Effect: elevate serum ampicillin concentrations
  • 17. Cefotaxime & Ceftriaxone MOA: Bind to PBP Inhibit transpeptidation reaction Inhibit cell wall synthesis
  • 18. • Administered intravenously • Half life: 7-8 hrs • Achieve levels in the CSF sufficient to inhibit most susceptible pathogens • Metabolized in the liver • Mainly excreted in the feces and others are excreted in the urine
  • 19. • Broad spectrum • active against citrobacter, Serratia marcescens and beta-lactamase- producing strains of Haemophilus and Neisseria • generally not active against Enterobacter species
  • 20. Hypersensitivity: -anaphylaxis, fever, skin rashes, nephritis, granulocytopenia, and hemolytic anemia Toxicity -pain (IM injection), thrombophlebitis (IV injection), renal toxicity
  • 21. USES CONTRAINDICATION • Meningitis caused by meningococci and H. influenzae • Pyelonephritis. • Septicemia. • Community-acquired pneumonia • patients with history of penicillin allergy • patients with history of GI disease, especially colitis • Breastfeeding women
  • 22. Cefepime MOA: Bind to PBP Inhibit transpeptidation reaction Inhibit cell wall synthesis
  • 23. • must be administered parenterally • Penetrates well into CSF • Half life: 2 hrs • Excreted in the urine
  • 24. • Broad spectrum, bectericidal • Good activity against P. aeruginosa, Enterobacteriaceae, S. aureus and S.pneumoniae • Highly active against Hemophilus and Neisseria sp.
  • 25. • anaphylaxis, fever, skin rashes • nephritis, granulocytopenia, and hemolytic anemia • Renal toxicity USES IS SAME AS 3rd GENERATION CEPHALOSPORIN
  • 26. • Basic & Clinical Pharmacology, 12th Edition Katzung • Lippincott Illustrated Reviews: Pharmacology Sixth Edition • Essentials of Pharmacology, 6th Edition, KD Tripathi. • http://www.drugbank.ca/drugs/DB00415 • http://www.drugs.com/mtm/ampicillin.html
  • 27. DRUGS FOR NON-BACTERIAL MENINGITIS NUR FARAH BINTI MUHAMMAD 012013100104
  • 28. Regime of treatment: Tuberculous meningitis Parasitic meningitis Lyme meningitis Syphilitic meningitis Drug therapy: Isoniazid Rifampin Pyrazinamide Dexamethasone Amphotericin B Miconazole Doxycycline References
  • 29. Initial Therapy: Isoniazid – 300mg/d Rifampicin – 600mg/d Pyrazinamide – 30mg/kg/d Ethambutol – 15-25 mg/kg/d Pyridoxine – 50mg/d Good Response : Discontinue Pyrazinamide after 2 months continue H & R for 6 – 12 months Inadequate Resolution : Continue for 9 – 12 months Corticosteroid (dexamethasone) IV, 60-80 mg/d for 6 weeks TUBERCULOUS MENINGITIS
  • 30. PARASITIC MENINGITIS Amphotericin B Miconazole Rifampin High -dose IV and intrathecal LYME MENINGITIS Ceftriaxone (2 g/day for 14-28 days) Penicillin G (20 million U/day for 14-28 days) Doxycycline (100 mg orally or IV every 12 hours for 14-28 days)
  • 31. SYPHILITIC MENINGITIS Aqueous crystalline penicillin G (2-4 million U/day IV every 4 hours for 10-14 days) IM penicillin G benzathine (2.4 million U).
  • 32. Most active drug for treatment of TB Bactericidal for actively growing tubercle bacilli Penetrates into macrophages and is active against both extracellular and intracellular organisms.
  • 33. Isoniazid (prodrug) Converted to active form by mycobacterial catalase- peroxidase (KatG) Block synthesis of mycolic acids Disruption of bacterial cell wall
  • 34. readily absorbed after oral administration Absorption is impaired if taken with food (high-fat meals) The drug diffuses into all body fluids, cells, and caseous material. Drug concentrations in the (CSF) are similar to those in the serum. Metabolized in the liver (N -acetyltransferase) Isoniazid metabolites and a small amount of unchanged drug are excreted, mainly in the urine
  • 35. Immunologic reactions Fever, skin rashes Direct toxicity Isoniazid-induced hepatitis (can be fatal) Clinical hepatitis with loss of appetite, nausea, vomiting, jaundice, and right upper quadrant pain hepatocellular, damage. Peripheral neuropathy CNS convulsions, seizures
  • 36. USES CONTRAINDICATIONS Treating or preventing tuberculosis (TB) •Liver problem may occur in alcoholic •Hepatitis •Patient receiving certain medicines to treat HIV infection
  • 37. Isoniazid + Phenytoin/ Carbamazepine/ Ethosuximide Mechanism: Isoniazid inhibits metabolism of above drugs Effect: Increased effects of above drugs (nystagmus and ataxia)
  • 38. has broader antimicrobial activity than isoniazid, bactericidal active against gram-positive and gram negative cocci, some enteric bacteria, mycobacteria, and chlamydiae
  • 39. Rifampicin binds to β subunit of bacterial DNA-dependent RNA polymerase Inhibit bacterial DNA-dependent RNA polymerase Inhibits RNA synthesis
  • 40. Administered orally Distribution of rifampin occurs to all body fluids and organs. Concentrations attained in the CSF are variable, often 10% to 20% of blood concentrations. taken up by the liver and undergoes enterohepatic recycling Elimination of rifampin and its metabolites is primarily through the bile and into the feces; a small percentage is cleared in the urine
  • 41. Generally well tolerated harmless orange color to urine, sweat, and tears(soft contact lenses may be permanently stained) hepatitis Nausea, vomiting, rashes,and nephritis Flulike-syndrome (fever, chills, myalgias, anemia, and thrombocytopenia)
  • 42. USES CONTRAINDICATIONS •Mycobacterial infections •Bacterial infections (meningococcal carriage) •used as prophylaxis in contacts of children with Haemophilus influenzae type b disease •treatment of serious staphylococcal infections such as osteomyelitis and prosthetic valve endocarditis •allergic to any ingredient in rifampin or to any rifamycin (eg, rifabutin) •Pregnant women •Breastfeeding women
  • 43. Rifampin + OCP • Mechanism: Rifampicin is an enzyme inducer. It induces metabolism of OCP • Effect: Contraceptive failure
  • 44. stable and slightly soluble in water inactive at neutral pH, but at pH 5.5 it inhibits tubercle bacilli (bactericidal) drug is taken up by macrophages and exerts its activity against mycobacteria residing within the acidic environment of lysosomes
  • 45. Pyrazinamide(Pro- drug) Converted to active form (pyrazinoic acid)by mycobacterial pyrazinamidase Pyrazinoic acid disrupts mycobacterial cell membrane metabolism and transport functions *EXACT MECHANISM IS UNKNOWN
  • 46. Administered orally well absorbed from the gastrointestinal tract and widely distributed in body tissues, including inflamed meninges Metabolized by the liver, but metabolites are renally cleared
  • 48. USES CONTRAINDICATION Treating active tuberculosis in combination with other medicines •Allergic to any ingredient in pyrazinamide •Have gout or severe liver problems •Pregnant & breastfeeding women
  • 49. Shown to improve overall outcome for patient with certain types of bacterial meningitis, such as H.influenza, tuberculous and pneumococcal meningitis First dose should be given prior to starting antibiotics To decrease cytokine related damage , especially to 8th nerve
  • 50. Corticosteroids diffuse across the cell membrane and binds to a cytoplasmic receptor. The receptor forms a dimer. After dimerizing, the receptor– hormone complex recruits coactivator proteins and translocates into the nucleus, where it attaches to gene promoter elements. There it acts as a transcription factor to turn genes off (when complexed with corepressors) Inhibits protein synthesis for immunological response (mediators and leukocytes)
  • 51. Can be administered orally, intravenously and intramuscularly. >90% of absorbed glucocorticoids are bound to plasma proteins, mostly corticosteroid-binding globulin or albumin. Corticosteroids are metabolized by the liver microsomal oxidizing enzymes. The metabolites are conjugated to glucuronic acid or sulfate, and the products are excreted by the kidney.
  • 53. USES CONTRAINDICATIONS •Relief of inflammatory symptoms •Replacement therapy for primary adrenocortical insufficiency (Addison disease) •Diagnosis of Cushing syndrome (supression test) •Replacement therapy for congenital adrenal hyperplasia (CAH) •Treatment of allergies •Acceleration of lung maturation •Hypersensitivity •Cerebral malaria •Lactating mother •Systemic fungal infection
  • 54. Prototype of polyene antimicrobials used systemically. antifungal antibiotics produced by Streptomyces nodosus. nearly insoluble in water
  • 55. Amphotericin B binds to ergosterol in the plasma membranes of sensitive fungal cells Forms pores (channels) that require hydrophobic interactions between the lipophilic segment of the polyene antifungal and the sterol Pores disrupt membrane function, allowing electrolytes (particularly potassium) and small molecules to leak from the cell Resulting in cell death
  • 56. Administered intravenously with colloidal suspension of amphotericin B and sodium desoxycholate Widely distributed in the body, but poor penetration in CSF Binds to sterols in tissues and lipoproteins in plasma and stays in the body for long period. About 60% of AMB is metabolized in liver. The serum half life is 15 days. Excretion occurs slowly both in urine and bile, but urinary concentration of active drug is low.
  • 57. ADVERSE EFFECT Low therapeutic index Fever, chills, malaise, weight loss N & V, diarrhea, epigastric pain Thrombophlebitis Muscle and joint pain Headache Decreased renal function : azotemia, hypokalemia, hyposthenuria, renal tubular acidosis, and nephrocalcinosis.
  • 58. USES CONTRAINIDICATIONS •Antifungal agent with the broadest spectrum of action •Use in treatment for: aspergillosis, cryptococcosis (torulosis), North American blastomycosis, systemic candidiasis, coccidiomycosis, histoplasmosis, zygomycosis including mucormycosis and infections due to related susceptible species of Conidiobolus and Basidiobolus, and Sporotrichosis Contraindicated in those patients who have shown hypersensitivity to Amphotericin B or any other component in the formulation
  • 59. Antineoplastic agents: enhance the potential for renal toxicity, bronchospasm and hypotension. Antineoplastic agents (e.g., nitrogen mustard, etc.) should be given concomitantly only with caution. Corticosteroids and Corticotropin (ACTH): may potentiate Amphotericin B-induced hypokalemia predisposisng the patient to cardiac dysfunction. Digitalis glycosides: Amphotericin B-induced hypokalemia may potentiate digitalis toxicity. Serum potassium levels and cardiac function should be closely monitored.
  • 60. • Imidazole antifungal agent • commonly applied topically to the skin or to mucous membrane to cure fungal infections • Prevents fungal organisms from producing vital substances required for growth and function.
  • 61. Miconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme that is necessary to convert lanosterol to ergosterol As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Miconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis.
  • 62. • Administered by topically and vaginally. • Minimal systemic absorption following topical application to skin. • Only small amounts absorbed systemically following intravaginal administration • Drugs metabolized by hepatic microsomal enzymes. • Systemically absorbed drug excreted in urine and feces
  • 63. • Burning, stinging, swelling, irritation, redness, pimple-like bumps, tenderness, or flaking of the treated skin
  • 64. USES CONTRAINDICATIONS •Dermatophytoses •Pityriasis (Tinea) Versicolor •Cutaneous Candidiasis •Vulvovaginal Candidiasis •Known hypersensitivity to miconazole or any ingredient in the formulation
  • 65. DRUG INTERACTION • Warfarin + miconazole -may increase the plasma concentrations and hypoprothrombinemic effect of warfarin -cause to bleed more easily