week 6

Question 1

sulfonamides are structural analogs to what?

Answer 1

PABA

Question 2

mechanism of action of sulfonamides

Answer 2

Bacteriostatic.
Structural analogues of PABA.
This competitively inhibits the enzyme dihydropteroate synthase, that converts PABA to dihydropteoic acid, a precursor in the synthesis of folic acid.
Disrupts nuleic acid and protein synthesis in the bacteria.

Question 3

spectrum of activity of sulfonamides

Answer 3

Gram +ve organisms (strep, Staph a, MRSA)
Gram -ve (E.coli, Klebsiella pneumoniae, salmonella, shigella)
Chlamydia

Question 4

Resistance mechanisms against sulfonamides

Answer 4

Overproduction of PABA.
Altered target enzyme, mutations in dihydropteoate synthase.
Decreased drug uptake.
Increased efflux , enhances expulsion of sulfonamides

Question 5

main classes of antifungals

Answer 5

Azoles, Polyenes, Echinocandins, Allylamines

Question 6

examples and mechanism of action of Azoles

Answer 6

Fluconazole, Itranaconazole.
Inhibit ergosterol synthesis by blocking lanesterol demethylase, disrupting cell membrane integrity

Question 7

examples and mechanism of action of Polyenes

Answer 7

Amphotericin B.
bind to ergesterol, forming pores in the fungal cell membrane, leading to cell death

Question 8

examples and mechanism of action of Echinocandins

Answer 8

Caspofungin.
Inhibit B-glucan synthase, disrupting cell wall organelles

Question 9

example and mechanism of action of Allylamines

Answer 9

Terbinifine.
Inhibit squalene epoxidase, leading to ergesterol deficiency and accumulation of toxic sterol intermediates

Question 10

side effects of amphotericin B

Answer 10

Nephrotoxicity - dose modification in extreme renal dysfunction.
Infusion related reaction - fever, chills, headache, confusion, rigors, nausea, hypotension , occurs in 50% patients

Question 11

mechanism of action of AZT

Answer 11

a nucleoside reverse transcriptase inhibitor.
it is activated and then incorporated in viral DNA leading to its termination and halting viral DNA synthesis

Question 12

clinical uses of AZT

Answer 12

Treatment of HIV.
Prevention of mother to child transition.
PEP.

Question 13

pharmacokinetics of AZT

Answer 13

Oral or IV.
Bioavailability 60-70% with a wide volume distribution.
Short half life ~ 1 hour.
metabolised in the liver.
excreted in the urine.

Question 14

mechanism of action of cephalosporins

Answer 14

Bacteriacidal agents.
Inhibit cell wall synthesis.
Bind to penicillin binding proteins.
Disrupt final stages of peptidoglycan cross linking in bacterial cell wall.
Leads to cell lysis.

Question 15

Examples of 1st generation cephalosporins

Answer 15

Cefazolin, cephalexin, cephalothin

Question 16

Coverage of 1st generation cephalosporins

Answer 16

Gram +ve cocci - Staph a., strep pneumoniae.
some Gram -ve rods - E.coli

Question 17

examples of 2nd generation cephalosporins

Answer 17

cefuroxime, cefoxitin, cefaclor

Question 18

spectrum of 2nd generation cephalosporins

Answer 18

Broader gram -ve covergae including H. influenzae

Question 19

examples of 3rd generation cephalosporins

Answer 19

Ceftriaxone, Cefotaxime

Question 20

spectrum of 3rd generation cephalosporins

Answer 20

enhanced activity against gram -ve.
Enterobacteria and N. gonorrhoea.
Penetrate CSF - used in meningitis

Question 21

4th generation cephalosporins example

Answer 21

Cefepime

Question 22

coverage of 4th generation cephalosporins

Answer 22

Broad spectrum includes pseudomonas aerginosa

Question 23

5th generation cephalosporins

Answer 23

Ceftaroline

Question 24

spectrum of 5th generation cephalosporins

Answer 24

effective against MRSA

Question 25

mechanism of action of metronidazole

Answer 25

It is a prodrug. Requires reduction yo its active form by anaerobes or protozoa. Results in nitroso radicals that disrupt DNA synthesis.

Question 26

Pharmacokinetics of metronidazole

Answer 26

Absorption; well absorbed, high bioavailability Distribution; low protein binding, wide distribution, can penetrate the CSF Metabolism - hepatic metabolism, half life 8 hours, excreted renally

Question 27

Metronidazole and warfarin interaction.

Answer 27

Inhibits metabolism of warfarin due to inhibiting CYP2C9. Leads to increased plasma levels of warfarin. Increased INR and increase bleeding risk.

Question 28

mechanism of action of macrolides

Answer 28

Inhibit bacterial synthesis by binding 50s ribosomes. Bacteriostatic but in high doses are bactericidal.

Question 29

spectrum of macrolides

Answer 29

Gram +ve cocci - Strep pneumoniae, strep pyogenes. Atypical - mycoplasma, chalmydia, legionella. Some gram +ve - H. influenza. Other - neisseria, bordetella.

Question 30

examples of macrolides

Answer 30

erthromycin clarithromycin azithromycin

Question 31

side effects of macrolides

Answer 31

GI upset taste disturbance QT interval prolongation Hepatotoxicity

Question 32

mechanism of action of aciclovir

Answer 32

A guanine nucleoside analog. Activated by by viral thymidine kinase, then further phosphorylated by host kinases to active triphosphte form. Competitively inhibits viral DNA polymerase and into viral DNA causing termination.

Question 33

spectrum of aciclovir

Answer 33

HSV 1 + 2 VZV less effective against EBV and CMV

Question 34

pharmacokinetics of aciclovir

Answer 34

Poor oral availability ~15-20% renally excreted, has to be dose adjusted in renal failure. half life 2-3 hours. Valaciclovir is an oral prodrug with better bioavailability.