Chemo Pharmacology | Hasnat Hussain (Reus-11)

Chemotherapy
Q.1) Write a note on mechanism of bacterial resistance against
penicillins.
ANS:
Mechanism of bacterial resistance against penicillins:
Natural resistance
In organisms that lack a peptidoglycan cell wall e.g. mycoplasma.
In organisms that have an impermeable cell wall.
Acquired resistance
This is obtained from resistance encoding plasmids. One or more of the
following properties can be acquired by the bacteria through plasmids.
(i)

(ii)

(iii)

Beta-lactamase
This enzyme breaks the beta-lactam ring present in the
penicillin thus leading to loss of bactericidal activities of the
penicillin.
Decreased Permeability
Decreased penetration prevents the drug to reach target PBPs.
An efflux pump can pump the drug out of the bacteria thus
reducing intracellular amount of drug.
Altered PBPs
Bacteria modify their PBPs and make them having a lower
affinity for penicillin. (e.g. MRSA)

Q.2) Write a note on antifungal spectrum and drug interactions of

ketoconazole.
ANS:

Chemo Pharmacology | Hasnat Hussain (Reus-11)

Antifungal Spectrum of Ketoconazole:

Oral Ketoconazole

Histoplasma
Blastomyces
Candida
Coccidioides

Topical Ketoconazole
Used to treat:
Tinea corporis, tinea cruris and tinea pedis caused by trichophyton
rubrum, trichophyton mentagrophytes and epidermophyton floccosum.
Tinea versicolor caused by malassezia fufur
Cutaneous candiasis caused by candida species
Seborrheic dermatitis
Dandruff
Drug Interactions of Ketoconazole:
Ketoconazole is an enzyme inhibitor. It can potentiate the toxicities of
cyclosporine, phenytoin, triazolam and warfarin.
Rifampin (enzyme inducer) + Ketoconazole decreased action of
ketoconazole.
H2 blockers, antacids, PPIs and sucralfate (all these drugs reduce gastric
acidity) can decrease absorption of ketoconazole.
Ketoconazole + Amphotericin B decreased fungicidal action of
amphotericin B due to decreased ergosterol in fungal membrane.

Q.3) Enumerate drugs used in enteric fever.

ANS:
Drugs used in Enteric Fever (Typhoid):
Ampicillin

Chemo Pharmacology | Hasnat Hussain (Reus-11)

Amoxicillin
Chloramphenicol
Ciprofloxacin and Levofloxacin (fluoroquinolones)
Trimethoprim-sulfamethoxazole (co-trimoxazole)
Ceftriaxone, cefotaxime and cefixime (Third gen. cephalosporins)

Q.4) Explain the mechanism of action of fluoroquinolones and their

adverse effects.
ANS:
Mechanism of action of Fluoroquinolones:
Enter the bacterium by diffusion through water-filled porins.
Inhibit transcription of DNA in the bacteria by inhibiting topoisomerase
II (DNA gyrase). This will prevent recoiling of supercoiled DNA, thus
normal transcription and replication wont occur.
Also inhibit topoisomerase IV, which will prevent separation of
replicated DNA into two daughter cells during division. Thus, division
wont occur.
Adverse Effects of Fluoroquinolones:
GIT
Nausea, vomiting , diarrhea
CNS
Headache
Dizziness
Phototoxicity
Sunlight should be avoided.
CT problems
Joints cartilage erosion

Chemo Pharmacology | Hasnat Hussain (Reus-11)

Tendinitis
Tendon rupture (Achilles tendon especially)
Nephrotoxicity

Q.5) Write down the mechanism of action and anti-bacterial

spectrum of macrolides.
ANS:
Mechanism of action of Macrolides:
Bind irreversibly to 50s subunit of bacterial ribosome inhibit
translocation steps of protein synthesis.
Also interfere at other steps such as transpeptidation.

Anti-bacterial Spectrum of Macrolides:

Gram positive cocci
Staphylococcus aureus
Streptococcus pyogenes
Streptococcus pneumoniae
Gram positive bacilli
Corynebacterium diphtheriae
Gram negative cocci
Neisseria gonorrhoeae
Gram negative rods

Bordatella pertussis
Campylobacter jejuni
Haemophilus influenzae
Legionella pneumophila

Chemo Pharmacology | Hasnat Hussain (Reus-11)

Spirochetes
Treponema pallidum
Mycoplasma
Mycoplasma pnemoniae
Chlamydia
Chlamydia pneumoniae
Chlamydia psittaci
Chlamydia trachomatis

Q.6) Classify anti-TB drugs and write down the treatment regimens
of TB.
ANS:
Anti-TB drugs
First Line Drugs

Isoniazid
Rifampicin
Ethambutol
Pyrazinamide

Second Line Drugs

Streptomycin
Capreomycin
Cycloserine
Ethionamide
Fluoroquinolones (ciprofloxacin, levofloxacin)
Macrolides (azithromycin, clarithromycin)

Chemo Pharmacology | Hasnat Hussain (Reus-11)

Treatment regimens of TB
The best regimen is the combined treatment with isoniazid, rifampicin,
ethambutol and pyrazinamide for the first two months (induction phase) and
after that continuing with only isoniazid and rifampicin for another 4 months
(continuation phase).
There is another regimen in which only isoniazid and rifampicin are used daily
for a period of nine months. If this combination doesnt work or toxic effects
are observed, then other combinations can be used, but they will require a
longer period of treatment.
E.g.
Isoniazid + Ethambutol for 18-24 months.
Rifampicin + Ethambutol for 12 months.

If the above first line drugs regimens dont work, then second line drugs are
used, but with a long term course.

Q.7) Explain the basis of the following combinations;

(i) Ampicilin and Gentamicin
(ii) Sulphamethoxazole and Trimethoprim
ANS:
Ampicillin and Gentamicin
Ampicillin is a beta-lactam drug while gentamicin is an aminoglycoside.
Combination of these two drugs will cause synergism.
Ampicillin will inhibit the cell wall synthesis no cell wall increased
permeability of bacteria to drugs gentamicin will enter the bacteria
easily enhanced antimicrobial effects (synergism).

Chemo Pharmacology | Hasnat Hussain (Reus-11)

Sulphamethoxazole and Trimethoprim

Combination of trimethoprim with sulfamethoxazole (cotrimoxazole)
shows greater antimicrobial activity than same quantities of either drug
used alone.
The synergism of cotrimoxazole results from its inhibition of two steps in
the synthesis of tetrahydrofolic acid.
Sulfamethoxazole inhibits the addition of PABA to dihydrofolic acid
precursors, and trimethoprim prevents the conversion of dihydrofolic
acid into tetrahydrofolic acid.
Both of these drugs together will completely cut off the folate supply to
the bacteria thus inhibiting the bacterial growth and division which is
impossible without folate.

Q.8) Write briefly on

(i) Superinfection
(ii) Chemoprophylaxis
ANS:
Superinfection
Infections caused by the opportunistic organisms due to inhibition of the
normal flora during antimicrobial therapy.
Drug therapy with broad spectrum antimicrobials or combination of
various drugs can inhibit the normal flora of various organs which will
lead to the growth and colonization of opportunistic organisms e.g. fungi
or resistant bacteria. These infections are usually difficult to treat.
E.g. food poisoning due to clostridium difficile after taking broad
spectrum antibiotics.
Chemoprophylaxis
Chemoprophylaxis means the administration of drugs for the purpose of
preventing rather than the treatment of infections.

Chemo Pharmacology | Hasnat Hussain (Reus-11)

E.g. administration of antibiotics by immunodeficient patients to prevent

opportunistic infections.
The use of chemoprophylaxis is limited primarily by three factors:
All medications have the potential to cause side effects.
The cost may be high.
Can cause bacterial resistance.
In general, chemoprophylaxis should be done only when the benefits are more
than the risks.

Q.9) Classify beta-lactam antibiotics. Describe the drug interactions

b/w ciprofloxacin and theophylline. Whats the rationale for using
pyridoxine with isoniazid?
ANS:
Beta-lactam antibiotics
Penicillin
(i)

(ii)

Narrow Spectrum
Penicillinase sensitive (penicillin G and penicillin V)
Penicillinase resistant (methicillin and nafcillin)
Broad Spectrum
Ampicillin
Amoxicillin
Piperacillin

Cephalosporins

First generation cefazolin

Second generation cefprozil
Third generation cefixime
Fourth generation cefipime

Carbapenems

Chemo Pharmacology | Hasnat Hussain (Reus-11)

Imipenem
Meropenem
Doripenem
Monobactams
Aztreonam

Drug interactions b/w ciprofloxacin and theophylline

Ciprofloxacin inhibits the metabolism of theophylline and thus increases
its serum level by inhibiting the enzyme cytochrome P-450.
Rationale for the use of pyridoxine (vit.B6) with isoniazid
Peripheral neuritis is the most common adverse effect of isoniazid. It
occurs due to pyridoxine deficiency.
So, pyridoxine is administered along with isoniazid to prevent pyridoxine
deficiency and subsequent peripheral neuritis.

Q.10) Explain the mechanism of action of sulphonamides.

ANS:
Mechanism of action of sulphonamides
Dihydrofolic acid is synthesized from p-amino benzoic acid (PABA),
pteridine and glutamate.
Sulphonamides are synthetic analogs of PABA.
Because of their similarity with PABA, the sulphonamides compete with
PABA for the bacterial enzyme, dihydropteroate synthetase. Thus,
inhibiting the synthesis of bacterial dihydrofolic acid.

Chemo Pharmacology | Hasnat Hussain (Reus-11)

Q.11) Enumerate aminoglycosides. Write down the mechanism of

action and adverse effects.
ANS:
Aminoglycosides

Amikacin
Gentamicin
Neomycin
Streptomycin
Tobramycin

Mechanism of action
Enter into the bacterium through porins bind 30S ribosomal unit
distort its structure protein synthesis inhibited, misreading of mRNA
bacteria killed.
Adverse effects
Described previously in ANS unit.

Prepared By: Hasnat Hussain (REUS11) J

(Gullaly-motu)