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Question 1

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Adverse Effects of Penicillins:

Answer 1

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

Question 2

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Toxicity of Cephalosporins:

Answer 2

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.

Question 3

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vancomycin moa

Answer 3

Inhibits early steps of Cell wall synthesis — Peptidoglycan polymerization >Bactericidal.

Question 4

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vancomycin uses

Answer 4

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

Question 5

adverse effects of vancomycin

Answer 5

a- Ototoxic.
b- Nephrotoxic.
c- Rapid IV infusion — Histamine release —>Red man syndrome & Shock

the van is NOT RED

Question 6

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Mechanism of Action of aminoglycosides

Answer 6

They bind to 30 S ribosomal subunit leading to inhibition of
bacterial protien synthesis

Question 7

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uses of aminoglycosides

Answer 7

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

Question 8

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Toxicity of Aminoglycosides:

Answer 8

ototoxicity
nephrotoxicity
Teratogenic
neuromuscular blockade
allergic manifestation

Question 9

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Anti-Bacterial Activity of Tetracyclines:

Answer 9

Concentrated in bacteria by specific transport proteins unique to bacterial cytoplasmic membrane. Attach to 30 8 ribosomal subunits leading to inhibition of
protein synthesis.

Question 10

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antibaxterial activity of marcolides

Answer 10

1. They bind irreversibly to 50 S ribosomal subunits leading
   to inhibition of Translocation leading to decreased Protein synthesis.
2. Bacteriostatic and cidal
3. Selectivity: Humans have different ribosomal subunits

Question 11

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theerpeutic uses of marcolides

Answer 11

1. Drug of CHOICE in Bordetella pertussis.
2. Drug of CHOICE in corynebactrial infections e.g. Diphtheria.
3. Drug of CHOICE in Atypical Pneumonia caused by Mycoplasma &
   Legionella.
4. Drug of CHOICE in Chlamydial infection: Respiratory, Genital & ocular.
   Specially in Neonates & Pregnancy.
5. Sexually transmitted diseases (STD): Gonorrhea, Syphilis & Chlamidia.
6. Penicillin substitute in Staph., Strept.& Pneumococcal in patients allergic to
   penicillin.
7. In rheumatic patients taking penicillin as prophylaxis priorto dental
   procedures to avoid bacterial endocarditis.
   Topically in Acne vulgaris.

BAPA SCCR

Question 12

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Adverse Effects of Macrolides:

Answer 12

1. Most common is Epigastric pain. Erythromycin > Others.
2. Cholestatic jaundice.
3. Large doses of erythromycin — Reversible Ototoxicity.

Question 13

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Anti-Bacterial Activity of Fluoroquinolones

Answer 13

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.

Question 14

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Therapeutic uses of fluorquinolones

Answer 14

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

Question 15

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adverse effects of fluorquinolones

Answer 15

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

Question 16

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Adverse Effects of Sulfonamides

Answer 16

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

Question 17

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Anti-Bacterial Activity of cotrimoxazole

Answer 17

1. They produce Sequential Block in the synthesis of Folinic acid & DNA — Synergism.
2. More potent, wider spectrum & less bacterial resistance than each drug alone.

Question 18

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Therapeutic Uses of co trimoxazole

Answer 18

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.

Question 19

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adverse effects of co-trimoxazole

Answer 19

ABC DDDD + megaloblastic anemia

Question 20

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Anti-Bacterial Activity of Rifampicin:

Answer 20

• 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.

Question 21

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Therapeutic Uses of Rifampicin:

Answer 21

1. First line drug in T.B. + Isoniazid.
2. Leprosy.
3. Drug of choice in prophylaxis of Meningococcal meningitis
   days.
4. Resistant bacterial infections e.g. Staph.

Question 22

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Adverse Effects & Drug Interactions of Rifampicin:

Answer 22

1. Orange-red discoloration of secretions e.g. Tears, saliva, sweat, sputum & urine.
2. Allergy — Flu-like syndrome.
3. G.L.T. upset.
4. CNS — Headache, Confusion & Ataxia.
5. Hepatic Microsomal Enzyme Inducer

Question 23

Anti-Bacterial Activity of .IN.H. (isoniazid

Answer 23

1- Tuberculo- Static & Cidal.
2- inhibit Mycolic acid synthesis — inhibit Synthesis of Cell Wall.

Question 24

adverse effect of isoniazid

Answer 24

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

Question 25

# w Mechanism of antifungal action of amotercin B

Answer 25

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.

Question 26

# w uses of amphotercin B

Answer 26

Fungal meningitis, fungal pneumonia, **aspergillosis**, histoplasmosis and candidiasis.

Question 27

# w Adverse Effects of amphotercin B

Answer 27

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

Question 28

# w The antifungal activity of azole drugs

Answer 28

reduction of ergosterol synthesis by inhibition of fungal cytochrome P450 enzymes.

Question 29

# w KETOCONAZOLE

Answer 29

inhibit mammalian cytochrome P450 enzymes Used only topically as shampoo useful in the treatment of seborrheic dermatitis and pityriasis versicolor.

Question 30

# w ITRACONAZOLE

Answer 30

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**.

Question 31

FLUCONAZOLE

Answer 31

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**.

Question 32

# w VORICONAZOLE

Answer 32

treatment of choice for invasive aspergillosis, and has excellent activity against candida. effect: Visual disturbances Photosensitivity dermatitis

Question 33

# w POSACONAZOLE

Answer 33

**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**.