Non-Beta Lactam Antibiotics

Question 1

Antifolate drugs MOA

Answer 1

inhibits folic acid (THF acid synthesis)

Question 2

Cortimoxazole = _ + _

Answer 2

Sulfonamides

Trimethoprim

Question 3

sulfonamides MOA

Answer 3

inhibits pteridine synthetase (since it is structurally similar to PABA) (PABA + PS)

Question 4

trimethoprim MOA

Answer 4

inhibits DHF reductase (DHF -> THF)

Question 5

Cortimoxazole indications

Answer 5

typhoid fever (1st line)
Pneumocystis jirovecii pneumonia
toxoplasmosis
nocardiosis

Question 6

PK notes Cortimoxazole

Answer 6

wide distribution - crosses PLACENTA

Question 7

Drugs which inhibit protein synthesis via 30S ribosome

Answer 7

Aminoglycosides

Tetracyclines

Question 8

Drugs which inhibit protein synthesis via 50S ribosome

Answer 8

Macrolides
Chloramphenicol
Clindamycin

Question 9

Aminoglycoside MOA (3)

Answer 9

1) inhibits initiation complex formation
2) misread RNA -> wrong protein
3) breaks up polysomes

Question 10

clinical use of Aminoglycosides ALONE

Answer 10

UTI
//
combine with beta-lactam for other

Question 11

adverse effects of Aminoglycoside

Answer 11

ototoxicity (irrev)
nephrotoxicity and neuro block (rev)
allergic rxn

Question 12

given to reverse neuromuscular blockade due to Aminoglycoside

Answer 12

Ca gluconaate, Neostigmine

Question 13

Tetracycline MOA

Answer 13

binds to 30S, blocks tRNA binding to Acceptor site on the mRNA ribosome complex - no peptide elongation

Question 14

bacterial resistance mechanisms against tetracycline

Answer 14

1) impaired influx or impaired efflux by active transport protein pump Tet(AE) - G-
2) protects ribosome by producing proteins which interfere with tetracycline binding Tet(M) - G+

Question 15

How are tetracyclines classified? What are the classifications

Answer 15

By half-life

1) Short-acting (6-8h)
2) Intermediate-Acting (12h)
3) Long-acting (16-18h)

Question 16

Short-acting tetracycline drugs

Answer 16

Chlortetracycline

Oxytetracycline

Question 17

Intermediate-acting tetracycline drugs

Answer 17

Democlocycline

Methacycline

Question 18

Long-acting tetracycline drugs

Answer 18

Doxycycline
Minocycline
Tigecycline

Question 19

Longest acting tetracycline and half-life

Answer 19

Tigecycline, 36 hours

Question 20

Difference of route of excretion of long acting tetracyclines

Answer 20

Long-acting by biliary excretion unlike others which are renal

Question 21

Tetracycline clinical use

Answer 21

Chlamydia
Mycoplasma pneumonia
cholera (short term ok for <8yo)
leptospirosis

Question 22

tetracycline contraindicated for

Answer 22

pregnant & <8yo

Question 23

Aminoglycoside and TEtracycline difference in chemical properties

Answer 23

A - not acid stable, irreversibly binds

T - acid stable, reversible

Question 24

Macrolides MOA

Answer 24

inhibit translocation of tRNA from A to P site

Question 25

Macrolides examples

Answer 25

Erythromycins Clarithomycin Azithromycin Roxithromycin

Question 26

Macrolides Pharmacokinetics

Answer 26

wide distribution but poor CSF penetration

Question 27

Drug interaction with Macrolides

Answer 27

(1) They decrease CYP1A2 and CYP3A3/4 levels -> elevated effects of other drugs (2) +Terfenadine or Astemizole -> cardiac arrhythmias

Question 28

advantages of newer macrolides

Answer 28

less GI side effects

Question 29

macrolide indications

Answer 29

``` atypical pneumonia whooping cough (Borderella pertussis) Gastroeneteritis Diphtheria Penicillin Hypersensitivity alternative drug ```

Question 30

chloramphenicol MOA

Answer 30

binds to 50S ribosomal subunit and inhibits transpeptidation (blocks P-A transfer)

Question 31

chloramphenicol chemistry

Answer 31

oral - palmitate IV - succinate palmitate inactive must be hydrolyzed in s.i. pure chloramphenicol does not dissolve in water

Question 32

T/F Oral route is preferred than IV route for chloramphenicol

Answer 32

T | succinate is an inactive produg, must be hydrolysed first but process is incomplete losing 30%

Question 33

Chloramphenicol indications

Answer 33

reserved for serious infections H. influ - meningitis 1st line for typhoid feer brain abscess

Question 34

Adverse effects of Chloramphenicol

Answer 34

Idiosyncratic aplastic anemia Gray Baby syndrome Optic Neuritis