written Flashcards
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Adverse Effects of Penicillins:
1- Allergic Reactions: Urticaria, angioedema & Anaphylactic shock:
a- Avoid by: - Ask for previous history.
- Dermal sensitivity test.
b- Treatment of Anaphylactic shock: Adrenaline + Cortisol + Antihistaminic.
c- Never reuse penicillin again.
d- Cross allergy with Cephalosporins (10%).
2- Diarrhea due to superinfection, especially after oral Ampicillin:
a- Candida albicans — monilial thrush & diarrhea. Treat by Nystatin.
b- Antibiotic associated (Pseudomembranous) colitis. Caused by enterotoxins
produced by Staph. or Clostridium difficil. Treated by Oral Vancomyein or
Metronidazole.
3- CNS irritation (seizures) may occur with large doses in patients with renal failure or
intra-thecal injection of penicillin.
4-Ampicillin induces skin rash in 10% of patients & in ALL patients with infective
mononucleosis, leukemia & taking allopurinol.
5- Benzathine penicillin— Pain.-at site of injection.
6- Nafcillin case neutropenia
7- Oxacillin can cause hepatitis
APCD page 150
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Toxicity of Cephalosporins:
1- Allergy & partial Cross-allergy with penicillins (10%).
2- GIT upsets and Superinfections.
3- Irritant: - .M. — Painful, so add lidocaine.
- .V. - Thrombophlebitis.
4- Nephrotoxicity specially Cephaloridine
It is augmented by concurrent use of Frusemide and Gentamicin.
5- Ceftriaxone + Calcium — Insoluble salts in Bile — Biliary Sludge.
6- Cefamandole, Cefoxitin & Cefoperazone:
a- Hypoprothrombinemia (can be prevented by Vit K 10 mg twice weekly)
b- Disulfiram like action — Alcohol intolerance.
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vancomycin moa
Inhibits early steps of Cell wall synthesis — Peptidoglycan polymerization >Bactericidal.
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vancomycin uses
a- IV in MRSA & Enterococcal infections.
b- IV prophylactic before dental operations in patients with prosthetic valve or joint.
c- Orally in pseudomembranous colitis.
Monitoring of the plasma trough level may be necessary to confirm adequate
concentration
adverse effects of vancomycin
a- Ototoxic.
b- Nephrotoxic.
c- Rapid IV infusion — Histamine release —>Red man syndrome & Shock
the van is NOT RED
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Mechanism of Action of aminoglycosides
They bind to 30 S ribosomal subunit leading to inhibition of
bacterial protien synthesis
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uses of aminoglycosides
A) Systemic use: gentamicin, amikacin, tobramycin, and netilmicin
1. Used in serious gram-negative infections (Klebsiella, Proteus,
Pseudomonas, Enterobacter & Serratia), and Staphylococcal & Enterococcal
infections.
2. When Pseudomonal infections it may be necessary to add a beta lactam with
antipseudomonal action such as piperacillin/tazobactam [Tazocin]
3. Bacterial endocarditis. Add Benzyl penicillin.
B) Topical uses:
1. Topical neomycin or gentamicin (Cream, ointment or Solution) in burns, wounds &
skin lesions.
2. Oral neomycin for gut de-contamination: It is not absorbed but acts locally in the
GIT
C) used in TB streptomycin
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Toxicity of Aminoglycosides:
ototoxicity
nephrotoxicity
Teratogenic
neuromuscular blockade
allergic manifestation
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Anti-Bacterial Activity of Tetracyclines:
Concentrated in bacteria by specific transport proteins unique to bacterial cytoplasmic membrane. Attach to 30 8 ribosomal subunits leading to inhibition of
protein synthesis.
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antibaxterial activity of marcolides
- They bind irreversibly to 50 S ribosomal subunits leading
to inhibition of Translocation leading to decreased Protein synthesis. - Bacteriostatic and cidal
- Selectivity: Humans have different ribosomal subunits
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theerpeutic uses of marcolides
- Drug of CHOICE in Bordetella pertussis.
- Drug of CHOICE in corynebactrial infections e.g. Diphtheria.
- Drug of CHOICE in Atypical Pneumonia caused by Mycoplasma &
Legionella. - Drug of CHOICE in Chlamydial infection: Respiratory, Genital & ocular.
Specially in Neonates & Pregnancy. - Sexually transmitted diseases (STD): Gonorrhea, Syphilis & Chlamidia.
- Penicillin substitute in Staph., Strept.& Pneumococcal in patients allergic to
penicillin. - In rheumatic patients taking penicillin as prophylaxis priorto dental
procedures to avoid bacterial endocarditis.
Topically in Acne vulgaris.
BAPA SCCR
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Adverse Effects of Macrolides:
- Most common is Epigastric pain. Erythromycin > Others.
- Cholestatic jaundice.
- Large doses of erythromycin — Reversible Ototoxicity.
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Anti-Bacterial Activity of Fluoroquinolones
They enter the bacteria by passive diffusion through the porins —_inhibit Bacterial Topoisomerase Il (DNA gyrase) & Topoisomerase IV enzymes — Inhibition of DNA gyrase prevents the relaxation of supercoiled DNA required for normal transcription and replication. Inhibition of topoisomerase IV interferes with separation of replicated chromosomal DNA into daughter cells during cell division — decrease DNA Replication > BACTERICIDAL.
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Therapeutic uses of fluorquinolones
Infections of the urogenital & GIT tract caused by gram negative organisms.
Respiratory, skin & soft tissue infection.
Gonorrhea
Resistant T.B
Typical & atypical pneumonia
Tract infection and tb and typtical and atypical pneumonia
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adverse effects of fluorquinolones
GIT upsets: (most common).
. Allergy: skin rash
Photosensitivity, use sun-screens & sun-blocks.
. CNS: Headache, dizziness & confusion, insomnia.
Seizures specially if used with NSAID — Avoid in Epileptics.
Chondrolytic— Reversible arthropathy — Avoid in pregnancy, lactation and in
children up to age of 18 years.
Rupture of tendons (Achilles tendon) specially in elderly taking glucocorticoids.
Nephrotoxic & Crystaluria.
The 3 generation may cause prolongation of Q-T intervalGIT upsets: (most common).
. Allergy: skin rash
Photosensitivity, use sun-screens & sun-blocks.
. CNS: Headache, dizziness & confusion, insomnia.
Seizures specially if used with NSAID — Avoid in Epileptics.
Chondrolytic— Reversible arthropathy — Avoid in pregnancy, lactation and in
children up to age of 18 years.
Rupture of tendons (Achilles tendon) specially in elderly taking glucocorticoids.
Nephrotoxic & Crystaluria.
The 3 generation may cause prolongation of Q-T interval
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Adverse Effects of Sulfonamides
Allergy (Hypersensitivity):
a. Manifestations: Fever, Photosensitivity & Stevens-Johnson syndrome.
b. Cross-Allergy with other Sulfonamides e.g. Diuretics (Thiazides, Frusemide,
Bumetanide & Carbonic anhydrase inhibitors), Diazoxide & Sulfonylureas.
Blood dyscrasias:
a. Hemolysis in patients with GBPD deficiency.
b. Bone marrow inhibition.
Crystaluria: Avoided by, plenty fluid intake and alkalinization of urine.
Diarrhea— GIT disturbances & Superinfection.
Damage > Nephrotoxicity & Hepatotoxicity
Displace bilirubin — Kermnictrus. Avoid during pregnancy & lactation.
Drug Interactions:
a. Displace Warfarin & Tolbutamide — Initial increase in their activity.
b. Methenamine — Releases Formaldehyde — Inactivates Sulfa.
ABC DDDD page 170
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Anti-Bacterial Activity of cotrimoxazole
- They produce Sequential Block in the synthesis of Folinic acid & DNA — Synergism.
- More potent, wider spectrum & less bacterial resistance than each drug alone.
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Therapeutic Uses of co trimoxazole
Respiratory tract infection.
Urinary tract infection (UTI).
Protatitis.
Gonococcal infection (Urethral & Oropharyngeal).
Shigella & Salmonella enteritis.
Systemic salmonella (Typhoid fever & Carrier).
Prevention & treatment of Toxoplasmosis.
Prevention & treatment of Nocardiosis. Drug of CHOICE.
Prevention & treatment of Pneumocystis carnii in AIDS. Used by IV Infusion.
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adverse effects of co-trimoxazole
ABC DDDD + megaloblastic anemia
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Anti-Bacterial Activity of Rifampicin:
- Bactericidal.
inhibit DNA-dependent RNA polymerase enzyme — inhibit Synthesis of RNA.
2- Spectrum: Mycobacterium T.B. & Leprosy, Some Gram +ve & -ve Bacteria, Chlamydia & pox viruses.
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Therapeutic Uses of Rifampicin:
- First line drug in T.B. + Isoniazid.
- Leprosy.
- Drug of choice in prophylaxis of Meningococcal meningitis
days. - Resistant bacterial infections e.g. Staph.
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Adverse Effects & Drug Interactions of Rifampicin:
- Orange-red discoloration of secretions e.g. Tears, saliva, sweat, sputum & urine.
- Allergy — Flu-like syndrome.
- G.L.T. upset.
- CNS — Headache, Confusion & Ataxia.
- Hepatic Microsomal Enzyme Inducer
Anti-Bacterial Activity of .IN.H. (isoniazid
1- Tuberculo- Static & Cidal.
2- inhibit Mycolic acid synthesis — inhibit Synthesis of Cell Wall.
adverse effect of isoniazid
Slow Acetylators —T I.N.H. # Pyridoxine (Vit B-6) — Peripheral neuritis.
Prevented by Pyridoxine (Vit B-6) 10 — 50 mg day PO.
b- Rapid Acetylators -7 Acetyl-Isoniazid —» Hepatotoxicity.
¢- Hemolysis in patients with Favism
2- Drug Interactions:
a- Isoniazid —» Enzyme Inhibitor — decrease Metabolism of Phenytoin — increase Its plasma level.
b- Rifampicin — Enzyme Inducer — increase Acetylation of I.N.H. > increase Hepatotoxicity.
p.174
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Mechanism of antifungal action of amotercin B
Ergosterol, a cell membrane sterol, is found in the cell membrane of fungi, whereas the
predominant sterol of bacteria and human cells is cholesterol. Amphotericin B binds to
ergosterol and alters the permeability of the cell by forming amphotericin B-associated
pores in the cell membrane through which cell contents leak outside the cells leading to
death of the fungal cells-> fungicidal.
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uses of amphotercin B
Fungal meningitis, fungal pneumonia, aspergillosis,
histoplasmosis and candidiasis.
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Adverse Effects of amphotercin B
Immediate reactions (related to infusion):
Fever, Chills, Vomiting, Hypotension, Headache, Muscle spasm
They can be ameliorated by:
-Slowing the infusion rate or decreasing the daily dose.
-Start with a test dose of 1 mg intravenously.
-Premedication with antipyretics, antihistamines, meperidine or corticosteroids can be
helpful.
Cumulative toxicity:
- Nephrotoxicity: Can be attenuated by administering normal saline infusions with the daily
doses of amphotericin B.
- Hepatotoxicity
- Anemia
- Seizure: following intrathecal injection
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The antifungal activity of azole drugs
reduction of ergosterol synthesis
by inhibition of fungal cytochrome P450 enzymes.
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KETOCONAZOLE
inhibit mammalian cytochrome P450 enzymes
Used only topically as shampoo useful in the treatment of seborrheic dermatitis and pityriasis versicolor.
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ITRACONAZOLE
does not affect mammalian steroid synthesis ]Drug absorption from capsules is increased by food and by
low gastric pH.
penetrates poorly into the cerebrospinal fluid.
- It is used exclusively in the treatment of dermatophytes and
anychomycosis.
FLUCONAZOLE
The azole of choice in the treatment and secondary
prophylaxis of cryptococcal meningitis.
- Intravenous fluconazole has been shown to be equivalent to ampbhotericin B in treatment of candidemia.
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VORICONAZOLE
treatment of choice for invasive aspergillosis, and
has excellent activity against candida.
effect: Visual disturbances
Photosensitivity dermatitis
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POSACONAZOLE
**the broadest-spectrum member ***
It has activity against most species of candida and
aspergillus. It is the only azole with significant activity against
agents of mucormycosis.
