33)Sulphonamides. Drugs used to trrat tuberculosis

Question 1

Sulphonamides

Answer 1

A group of antimicrobials that contain a sulphonamide group

• Allergies to these drugs are common
• Competitive inhibitors to dihydropteroate synthase enzyme ⇢ involved in folate synthesis
• Bacteriostatic
• Broad spec ⇢ G⁺ + G^-ve bacteria, toxoplasma + protozoal agents

Question 2

Classification

Answer 2

Oral:

• Short acting ⇢ Sulfadiazine + Sulfadimidine
• Medium acting ⇢ Sulfamethoxazole + Sulfamoxole
• Long acting ⇢ Sulfadozine + Sulfamethoxypyrazine

Absorbable oral

Non-absorbable TOPICAL

• Sulfacetamide + Silver Sulfadiazine

Question 3

Pharmacodynamics

Answer 3

• Inhibits synthesis of folic acid by being structural analogs of PABA
• This allows them to inhibit folic acid pathway ⇢ Inhibits growth of MO
• They inhibit dihydropteroate synthase by competing w/PABA
• Trimethoprim + Sulfamethoxozole = inhibits 2 steps of DNA synthesis = Bactericidal action

Question 4

Pharmacokinetics

Answer 4

Absorbed from stomach and SI

Widely distributed through tissues ⇢ crosses BBB + placenta

Metabolised in liver

Excreted in kidney via GF

High range in plasma binding 10-90%

Excreted via urine, faeces, bile + milk

Question 5

Clinical uses in dentistry

Answer 5

Broad spec against G⁺ + G^-ve

Chloroquine-resistant Plasmodium Falciparum

Toxoplasma infection

Chlamydia infection

UTIs

Burn infections ⇢ Silver Sulfadiazine

GI infections

Oral, non-absorbable drugs used to treat ⇢ ulcerative colitis, enteritis + IBDs

Bacterial conjunctivitis

Meningitis ⇢ Sulfadiazine

Topical used for ⇢ burn sepsis, wounds, conjunctivitis + colitis

Question 6

Adverse effects

Answer 6

Hypersensitivity ⇢ Rashes + Steven-Johnson syndrome

GI ⇢ Nausea, vomiting + diarrhoea

Heamatotoxicity ⇢ Thrombocytopenia + Aplastic anomia

Acute haemolysis ⇢ in persons w/ G6P dehydrogenase deficiency

Nephrotoxicity ⇢ Sulphonamides precipitate in urine at acidic PH ⇢ Crystaluria + Hematuria

Question 7

Drugs used to treat tuberculosis

Answer 7

Isoniazid

Rifampicin/Rifampin

Ethambutol

Streptomycin

Pyrazinamide

Question 8

Isoniazid

Answer 8

Activated by mycobacterial catalse - peroxide

Pharmacodynamics ⇢ inhibits mycelia acid synthesis

Question 9

Pharmacokinetics of isoniazid

Answer 9

Well absorbed orally but can be given IM

Excreted in kidney

Bacteriostatic

Narrow spec ⇢ only against mycobacteria

Resistance ⇢ change in target enzyme

Question 10

Adverse effects of isoniazid

Answer 10

Skin rashes

Peripheral neuritis

Hepatotoxicity

Insomnia + Restlessness

Question 11

Drug interactions of Isoniazid

Answer 11

Inhibit hepatic metabolism of carbamazepine, phenytoin + warfarin

Pyridoxine + Vitamin B6 ⇢ prevent peripheral neuropathy + CNA toxicity

Question 12

Rifampicin/Rifampin

Answer 12

Pharmacodynamics ⇢ inhibits synthesis of nucleic acids

Pharmacokinetics:

• Oral admin
• Excreted in faeces, sweat, tears + urine

Broad spec - Bactericidal against M.Tuberculosis + G^-ve MOs

Resistance ⇢ occurs via change in drug sensitivity of polymerase

Question 13

Adverse effects of rifampin

Answer 13

Flu-like syndrome

proteinuria

Metabolites of rifampin ⇢ red/orange saliva, sputum, tears + sweat

Skin rashes

Liver dysfunction

Thrombocytopenia

Question 14

Ethambutol

Answer 14

Mechanism ⇢ inhibits synthesis of arabinogalactan

Narrow spec ⇢ only against M.Tuberculosis

Bacteriostatic

Adverse effects:

• Dose dependant visual disturbances ⇢ ⇣ visual acuity, Red/Green colour blindness, Optic neuritis + possible retinal damage
• Headache, Hyperuricemia, Confusion + Peripheral Nueritis

Question 15

Adverse effects recap

Answer 15

Isoniazid

• Hepatitis, Convulsions, Optic neuritis + Hypersensitivity

Rifampin

• Nausea, vomiting, rash, hepatitis + flu-like syndrome

Ethambutol

• Reversible optic neuritis, exacerbation of gut

Pyrazinamide

• Hepatotoxicity, Hyperuricemia, rash, avoid during pregnancy

Streptomycin

• Vestibular toxicity, parenthesia of face, rash, angioedema + avoid pregnancy