Antimetabolites

Question 1

What is an Antimetabolite

Answer 1

its a structural analogue to an endogenous compound–> interferes with its role in cellular metabolism

Question 2

Action of ANtimetabloites

Answer 2

inhibit DNA, RNA and Protein SYnthesis by blocking the folate pathway

Question 3

What are Sulfonamides

Answer 3

are structural analogues of PABA (p-aminobenzoic acid) which is a precursor in bacterial folic acid synthesis

Question 4

Organisms susceptible to Suphonamides require

Answer 4

extracellular PABA to form Dihydrofolic acid

Question 5

Sulfonamides are effective against

Answer 5

Sensitive strains of Gram +ive and -ive bacteria
Bacteriostatic drugs
ARE NEVER 1st LINE DRUGS

Question 6

Spectrum of Sulfonamides

Answer 6

Borad Spectrum
Some Enteric bacteria like E.coli and Salmonella
Rickettsiae

Question 7

What do Sulfonamides not have an effect on

Answer 7

Mammalian cells

Question 8

What is the name of the topical Sulfonamide

Answer 8

Silver Sulfadiazine

Question 9

When is Topical Sulfonamide used

Answer 9

infected leg ulcers
pressure sores
burn wounds

Question 10

What is the name of the Oral Absorbable Sulfonamide

Answer 10

Sulfamethoxazole

Question 11

When is the oral Sulfonamide used

Answer 11

NEVER USED ON ITS OWN
in combination with Trimethoprim (co-trimoxazole)

Question 12

MOA of Sulfonamide

Answer 12

Its a PABA analogue therefore it binds in its place to Dihydropteroate Synthetase

Question 13

Resistance Mechanisms against Sulfonamides

Answer 13

1. Overproduction of PABA
2. Production of Dihydroggen Synthetase with low affininty for Sulfonamides–> bypasses it
3. Loss of permeability to Sulfonamides

Question 14

Absorption and Distribution of Sulfonamides

Answer 14

They are well absorbed from the GIT
Wide distribution to tissues and body fluids (including CNS, CSF), placenta and foetus

Question 15

Which Admin method is not used for Sulfonamides

Answer 15

Topical admin as it causes allergic rxns
*ONLY used in one case

Question 16

Metabolism of Sulfonamides

Answer 16

Extensively metabolized in the liver
They are Acetylated and Glucoronidated before being excreted in the urine

Question 17

SEs of Sulfonamides

Answer 17

1.N,V,H
2.Precipitation of acetylated metabolites in urine–> Crystalluria: lots of water intake required to make urine more alkaline
3. Allergy: rash, SJS, drug fever
4. Cross-sensitivity with other Sulfanilamide derivatives
5. Danger of Kernicterus
6. Agranulocytosis and thrombocytopenia
7. Photosensitivity
8. Hepatotoxicity
9. Reduced efficacy of COC

Question 18

Why are Kernicterus indicated as a SE for Sulfonamides

Answer 18

Bilirubin is pushed from their serum binding sits–> cross BBB and enter Brain nuclei–> cause Toxic Encaphalopathy
*must not be administered during Last 2 wks of pregnancy

Question 19

DIs of Sulfonamides

Answer 19

Oral Anticoagulants (warfarin: decr. m)
Sulfonylureas (glibenclamide: decr M=hypo)
Phenytoin: inhibits its metabolism
Methotexate: decr excretion in urine

Question 20

CIs of Sulfonamides

Answer 20

Babies in first 3wks of life: incr. risk of haemolysis and Kernicerus
Last trimester of pregnancy (last 2 wks)
Porphyria
G6PD deficiency
Allergy

Question 21

What is Trimethoprim

Answer 21

Its a Broad spectrum Bacteriostatci that eventually inhibits DNA Synthesis

Question 22

Uses of Trimethoprim

Answer 22

Acute uncomplicated UTIs
Prophylaxis of UTIs
Respiratory tract infections
Chronic Prostatitis

Question 23

How is Trimethoprim used in SA

Answer 23

Used in combination with Sulfamethoxazole as Co-trimoxazole

Question 24

MOA of Trimethoprim

Answer 24

-Inhibits the bacterial Dihydrofolate Reductase enzyme–> catalyses formation of Tetrahydrofolate form Dihydrofolate
-Inhibits synthesis of Nucleotides
-Inhibits DNA synthesis

Question 25

Resistance Mechanisms against Trimethoprim

Answer 25

1. Reduced cell permeability
2. Overproduction of Dihydrofolate reductase
3. Production of an ALtered Reductase with reduced drug binding

Question 26

Absorption and Distribution of Trimethoprim

Answer 26

Rapidly absorbed
Widely distributed–> therapeutic levels in bile, CSF, Prostatic tissue, vaginal fluid

Question 27

SEs of Trimethoprim

Answer 27

Teratogenic
Glossitis: frequently
Folate Deficiency anemia in people with low folate stores
Skin rashes, pruritus
Nausea, Epigastric Pain
Bone marrow depression: rare
Reduced efficacy of COC

Question 28

Uses of Co-trimoxazole

Answer 28

Recommended for use in HIV patients
Prophylaxis and treatment of Pneumocystis Jirovecii Pneumonia
Prophylaxis of Toxoplasmosis and Isospora belli diarrhea
Treatment of choice for Nocardiosis

Question 29

MOA of Co-trimoxazole

Answer 29

They interrupt the Synthetic pathway of Tetrahydrofolate in 2 ways:
1. inhibit Dihydropteroate Synthetase (sulfamethaoxazole)
2. inhibit Dihydrofolate Reductase (Trimethoprim)

Question 30

Admin of Co-Trimoxazole

Answer 30

1:5 (T:S)–> synergistic
Orally
Large colume of distribution

Question 31

What is the combined effect of Co-trimoxazole

Answer 31

Bactericidal
They are Bacteristatic individually

Question 32

Advantages of Co-trimoxazole

Answer 32

Delays development of resistance against T
Synergistic action
Wider spectrum than T

Question 33

Excretion of Co-trimoxazole

Answer 33

T: mostly unaltered via kidneys
S: Metabolized in Liver and rapidly excreted in the urine

Question 34

SEs of Co-Trimoxazole

Answer 34

NV
Skin rashes+anemia
Long term use=folate shortage–> Megoblastic Anemia
Incr. AEs in elderly on DIRUETICS: Thrombocyropenia
Incr. AEs in AIDS patients=fever+ bone marrow depression

Question 35

DIs of Co-Trimoxazole

Answer 35

1. Digoxin levels may incr.
2. Incr. risk of Thrombocytopenia
3. Oral Contraceptive
4. Incr. risk of hypoglycemia with oral antidiabetic agents
5. May inhibit Phenytoin metabolism
6. Concurrent use with Pyrimethamine: megoblastic anemia
7. Rifampicin use leads to decr levels of Co-trimoxazole
8. Warfarin: incr. bleeding risk
9. Zidovudine: incr. toxicity risk
10. Methotrexate: incr. toxicity risk