Dhps Inhibitors And Dhfr Inhibitors

Front 1

Short acting well absorbed sulfonamides

6-9hr half-life

1-4hr absorption

Back 1

Sulfacytine

Sulfisoxazole

Sulfamethizole

Front 2

Intermediate acting + Slow absorption sulfonamides

10-12-17hr half life

4-8hr absorption

Back 2

Sulfadiazine

Sulfamethoxazole

Sulfapyridine

Front 3

Long acting + Moderate absorption sulfonamides

7-9 days half life

Back 3

Sulfadoxine

Sulfalene

Front 4

Non-absorbable sulfonamide

Back 4

Sulfasalazine

Front 5

Topicalsulfonamides

Back 5

Sulfacetamide

Mafenide Acetate

Silver sulfadiazine

Front 6

Inhibitors of DHPS

Back 6

Sulfonamides

Front 7

Inhibitors of DHFR

Back 7

Trimethoprim

Pyrimethamine

Front 8

DHFR

Back 8

Dihydrofolate Reductase

Front 9

DHPS

Back 9

Dihydropteroate synthetase

Front 10

Cotrimoxazole is a combination of

Back 10

Trimethoprim and sulfamethoxazole

Front 11

Sulfonamide used for Urinary Tract Infection

Back 11

Sulfisoxazole

Sulfamethoxazole

More soluble at urinary pH therefore less liable to cause crystalluria

Front 12

General adverse effects of sulfonamides

n.b. not recommended in third trimester of pregnancy

Back 12

Nephrotoxicity: Crystalluria, hematuria

(hydration and alkalisation prevents it)

Hypersensitivity: rashes, angioedema

Hematotoxicity: hemolytic anemia

(acute hemolysis in patients with G6PDH deficiency), granulocytopenia, thrombocytopenia

GI disturbance: nausea, vomiting, diarrhoea

Kernicterus in newborns

Front 13

Sulfonamide with highest risk of crystalluria

Back 13

Sulfadiazine

Front 14

Urinary pH predisposing crystalluria

Back 14

Acidic

Front 15

How to avoid crystalluria?

Back 15

Hydration and alkalisation

Front 16

Sulfonamide for GI disease

e.g. Chronic inflammatory bowel disease, ulcerative colitis, Crohn's disease, enteritis

Back 16

Sulfasalazine

Front 17

4 clinical features of Cotrimoxazole

Back 17

1. Broad antibacterial spectrum

2. Bactericidal action

3. Compound drug with trimethoprim and sulfamethoxazole

4. Good absorption from GI tract

Front 18

Why can sulfonamides cause kernicterus?

n.b. kernicterus= bilirubin induced brain dysfunction

Back 18

SA displaces bilirubin by binding to serum albumin; bilirubin can cross the BBB and cause brain dysfunction.

Front 19

Cotrimoxazole effect in HIV patient with Pneumocystis Jiroveci pneuomonia

Back 19

Fever, rashes, diarrhea pancytopenia

Front 20

Sulfonamide for bacterial conjunctivitis and trachoma

Back 20

Sulfacetamide

Front 21

Sulfonamide used to prevent infection of burn wounds

Back 21

Silver sulfadiazine

Front 22

First choice drug for toxoplasmosis

Second choice drug for malaria

Back 22

Sulfadiazine with pyrimethamine

Front 23

Sulfonamide antimicrobial activity and resistance

Back 23

Bacteriostatic

Broad antimicrobial spectrum:

1. Gram +ve and -ve

2. Some protozoa

3. Enteric bacteria

Resistance due to plasmid transfers or mutations resulting in:

1. PABA overproduction

2. Altered dihydrosynthetase

3. Decreased cellular permeability to sulfonamides

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Sulfonamide mechanism of action

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1. Selective and competitive inhibition of dihydropteroate synthetase

2. Synthetic analogue to PABA; critical in the synthesis of nucleotides for DNA and RNA synthesis

3. Certain microbes require PABA for dihydrofolate necessary for purines.

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Sulfonamide pharmokinetics:

metabolism

Back 25

Acetylated in liver

Inactive metabolites precipitate at neutral or acidic pH--> crystalluria

Front 26

Sulfonamide pharmokinetics:

distribution

Back 26

Binds to serum albumin

Crosses BBB enters CSF

Crosses placental barrier

Well to modest tissue penentration

Front 27

Trimethoprim mechanism of action

Back 27

Selective inhibitor of bacterial dihydrofolate reductase

Blocks conversion of dihydrofolate into tetrahydrofolate necessary for purines and amino acids

Front 28

Uses of trimethoprim

Back 28

Broad antibacterial spectrum

UTI, bacterial prostatis, vaginitis

Pneumocystis

With pyrimethamine to treat leishmaniasis and toxoplasmosis and sometimes malaria

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Trimethoprim pharmokinetics

Back 29

Half life 10-12hrs

Penetrates CSF

Excreted unchanged through kidneys

Front 30

Mechanism of action of Cotrimoxazole

Back 30

Sulfamethoxazole inhibits PABA incorporation to dihydropteroate synthetase,

Trimethoprim prevents reduction of dihydrofolate to tetrahydrofolate

Front 31

Antimicrobial activity of Cotrimoxazole

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Bactericidal action

Broader spectrum:

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PABA

Back 32

P-aminobenzoic acid

Front 33

Cotrimoxazole uses

Back 33

Pneumocystis Jiroveci Pneumonia

Listeriosis

Prostate and Urinary tract infection

GI infection

Respiratory infection

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Drug interactions

Back 34

Increased prothrombin index with warfarin

Increased plasma half life of anti-epileptic drug phenytoin

Increased concentration of methotrexate due to displacement from albumin-binding sites