Principles of Drug Action Antibiotics

Question 1

What are B-lactam antibiotics?

Answer 1

Four-membered ring

Highly reactive

Nitrogen atom attached to B-carbon atom relative to the carbonyl

Question 2

What does a B-lactam attack to work?

Answer 2

Irreversibly inhibits the transpeptidase domain

Question 3

What does a Penicillin B-lactam need to work?

Answer 3

Bicyclic ring system

Ionized carboxylic acid

Amide group

High ring strain, high activity, but high instability

Question 4

What are some of the early Penicillin B-lactams and how did they work?

Answer 4

Penicillin G, N, and T

All are acid labile (can be altered by stomach acid) and can’t be given orally

Not broad spectrum (Either good gram + or - activity)

Susceptible to acid hydrolysis/ ring opening due to no resonance in the ring and highly reactive carbonyl group

Question 5

What are the Aminopenicillins?

Answer 5

Less electronegative version of the penicillins, higher stability

Can be given orally and be effective

More effective against gram - bacteria

Question 6

What are the Carboxypenicillins?

Answer 6

Poor acid lability

Low bioavailability

Good against gram + and - bacteria

Question 7

What are the Ureidopenicillins?

Answer 7

Good against gram + and - aerobic bacteria

Question 8

What are the Cephalosporin B-lactams?

Answer 8

Strained bicyclic ring with B-lactam ring and dihydrothiazine ring (six membered ring with sulfur and nitrogen)

Less ring strain overall

Question 9

What are the advantages/disadvantages of 1st Gen Cephalosporins?

Answer 9

Advantages: Greater acid stability, Broader initial spectrum

Disadvantages: Poor oral bioavailability, lower potency

Examples: Cephalexin, Cefazolin

Question 10

What are the 2nd Gen Cephalosporins?

Answer 10

Increased resistance to deacetylation

Broader spectrum

Examples: Cefuroxime

Question 11

What are the 3rd Gen Cephalosporins?

Answer 11

Replace thiophene ring with aminothiazole ring

Greater penetration and greater potency against gram - bacteria

Examples: Cefotaxime, Ceftriaxone, Ceftazidime, Cefdinir, and Cefoperazone

Question 12

What are the 4th Gen Cephalosporins?

Answer 12

Greater penetration and potency against gram - bacteria

Zwitterionic (both positive and negative charge on molecule) and aminothiazole ring give activity against Pseudomonas

Question 13

What are the Carbapenem B-lactams?

Answer 13

Opposite stereochemistry

Carbon in ring instead of sulfur

Double bond, increased strain, but higher reactivity

Greatest potency, broadest spectrum of activity

Question 14

What is the B-lactam mechanism of selectivity?

Answer 14

Our cells do not have cell wall, but the invaders do, so it expresses the penicillin binding protein

Question 15

What are the adverse effects of B-lactams?

Answer 15

No predictable effects
Carbapenems: Seizures

Question 16

What is the Glycopeptide mechanism of selectivity?

Answer 16

Goes to cell wall and picks specific protein to inhibit, does not target host cells because of stereochemistry (D vs L alanine)

Question 17

What are the adverse effects of Glycopeptides?

Answer 17

Ototoxicity
Nephrotoxicity

Question 18

What is the mechanism of selectivity of the Isonicotinates?

Answer 18

Does only target formation of mycolic acid, which is only in bacteria

Question 19

What are the adverse effects of Isonicotinates?

Answer 19

Peripheral neuropathy
Hepatotoxicity
Hematological (Anemia, Thrombocytopenia)

Question 20

What is the mechanism of selectivity for Diamines?

Answer 20

We do not have cell wall, so only targets arabinosyl transferase in bacteria

Question 21

What are the adverse effects of Diamines?

Answer 21

Optic neuritis
Hepatotoxicity