Pharmacology - Microbiology

Tigecycline Mechanism: Tetracycline derivative. Binds to 30S, inhibiting protein synthesis. Generally bacteriostatic. Clinical use: Broad-spectrum anaerobic, gram ⊝, and gram ⊕ coverage. Multidrug-resistant organisms (MRSE, VRE) or infections requiring deep tissue penetration. Adverse effects: GI symptoms: nausea, vomiting

CD4 <200 cells/mm3: TMP-SMX- Infection: Pneumocystis pneumonia CD4 <100 cells/mm3: TMP-SMX- Infection: Pneumocystis pneumonia and toxoplasmosis CD4 <50 cells/mm3: Azithromycin or clarithromycin- Infection: Mycobacterium avium complex

MRSA: vancomycin, daptomycin, linezolid, tigecycline, ceftaroline, doxycycline VRE: linezolid and streptogramins (quinupristin, dalfopristin) Multidrug-resistant P aeruginosa/Actinetobacter baumanii: polymyxins B and E (colistin)

Anidulafungin, caspofungin, micafungin Mechanism: Inhibit cell wall synthesis by inhibiting synthesis of β-glucan. Clinical use: Invasive aspergillosis, Candida. Adverse effects: GI upset, flushing (by histamine release).

Mechanism: Interferes with microtubule function; disrupts mitosis. Deposits in keratin-containing tissues (eg, nails). Clincal use: Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm). Adverse effects: Disulfiram-like reaction, ↑ cytochrome-450 activity and warfarin metabolism, teratogenic, carcinogenic, confusion, headaches.

Permethrin – inhibits Na+ channel deactivation → neuronal membrane depolarization Malathion – acetylcholinesterase inhibitorLindane – blocks GABA channels → neurotoxicity Use: Scabies (Sarcoptes scabiei) and lice (Pediculus and Pthirus).

Mechanism: Preferentially inhibits viral DNA polymerase. Does not require phosphorylation by viral kinase. Clinical use: CMV retinitis in immunocompromised patients; acyclovir-resistant HSV. Long half-life.- Similar indication as foscarnet. Adverse effects: Nephrotoxicity (co-administer with probenecid and IV saline to ↓ toxicity).

Regimen consists of 3 drugs to prevent resistance: 2 NRTIs + integrase inhibitor

Glycoproteins normally synthesized by virus-infected cells, exhibiting a wide range of antiviral and antitumoral properties. IFN-α: Chronic hepatitis B and C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, renal cell carcinoma, malignant melanoma.IFN-β: Multiple sclerosis.IFN-γ: Chronic granulomatous disease. Adverse effects: Flu-like symptoms, depression, neutropenia, myopathy.

Goals include the reduction of pathogenic organism counts to safe levels (disinfection) and the inactivation of all microbes including spores (sterilization). Autoclave: Pressurized steam at >120°C. Sporicidal. May not reliably inactivate prions. Alcohols: Denature proteins and disrupt cell membranes. Coagulation of cytoplasm. Not sporicidal. Chlorhexidine: Denature proteins and disrupt cell membranes. Not sporicidal. Chlorine: Oxidizes and denatures proteins. Sporicidal. Hydrogen peroxide: Free radical oxidation. Sporicidal. Iodine and iodophores: Halogenation of DNA, RNA, and proteins. May be sporicidal. Quaternary amines: Impair permeability of cell membranes. Not sporicidal.

Colistin (polymyxin E), polymyxin B Mechanism: Cation polypeptides that bind to phospholipids on cell membrane of gram ⊝ bacteria. Disrupt cell membrane integrity → leakage of cellular components → cell death. Use: Salvage therapy for multidrug-resistant gram ⊝ bacteria (eg, P aeruginosa, E coli, K pneumoniae). Polymyxin B is a component of a triple antibiotic ointment used for superficial skin infections. Adverse effects: Nephrotoxicity, neurotoxicity (eg, slurred speech, weakness, paresthesias), respiratory failure.

Macrocylic antibiotic (related to macrolides) - Inhibits the sigma subunit of RNA polymerase, leading to protein synthesis impairment and cell death - Bactericidal activity against C difficile - Administered orally and has minimal systemic absorption

Inhibits docking. Binds CCR-5 on surface of T cells/monocytes, inhibiting interaction with gp120.

Hepatitis C therapy. Used as combination therapy. Viral phosphoprotein (NS5A) inhibitor.NS5A plays important role in replication.

Hepatitis C therapy.- Also used to treat RSV in adults. Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase. Adverse effects: Hemolytic anemia, severe teratogen.

Hepatitis C thearpy. Used in combination therapy. HCV protease (NS3A/4A); prevents viral replication. Adverse effects: Photosensitivity reactions, rash.

Hepatitis C therapy. Used in combination therapy. Inhibits HCV RNA-dependent RNA polymerase (NS5B) acting as chain terminator. Adverse effects: Fatigue, headache, nausea.

1st generation cephalosporin

1st generation cephalosporin

2nd generation cephalosporin

2nd generation cephalosporin

2nd generation cephalosporin

2nd generation cephalosporin

3rd generation cephalosporin

3rd generation cephalosporin

3rd generation cephalosporin

3rd generation cephalosporin - Pseudomonas

4th generation cephalosporin

5th generation cephalosporin

First-line: Tenofovir (NtRTI) - Entecavir (NRTI) - Interferon-α

NNRTI - Vivid dreams- CNS symptoms

NNRTI

NNRTI

NRTI - Contraindicated if patient has HLA-B*5701 mutation due to ↑ risk of hypersensitivity

NRTI Side effect: Pancreatitis

NRTI

NRTI

NRTI

Pathophysiology:- Nonspecific binding to ribosomal proteins → impaired metabolism, impaired protein, RNA, and DNA synthesis- Bactericidal Route of elimination: Mostly renal Clinical use: Uncomplicated UTIs Adverse effects:- Acute nitrofurantoin-induced pulmonary injury→ Short-term: Acute hypersensitivity pneumonitis→ Long-term: Interstitial lung disease- GI side effects- Triggers hemolytic anemia in G6PD-deficient patients Contraindications:- Renal injury- Breastfeeding women