Pharmacology of Antibiotics and Sulfonamides

Exam 2 - Weeks 2 & 3 Pharmacology

• Exam covers weeks 2 and 3 of the pharmacology course.

Week 2 Agenda

• Antimicrobial Therapy Basics
  • Cell wall synthesis inhibitors:
    • Penicillins
    • Vancomycin
    • Cephalosporins
    • Carbapenems
  • Ribosomal protein synthesis inhibitors:
    • Macrolides
    • Aminoglycosides
    • Lincosamides
    • Tetracyclines
  • Folic acid synthesis inhibitors:
    • Sulfonamides
    • Trimethoprim
  • Nucleic acid synthesis inhibitors:
    • Fluoroquinolones
    • Metronidazole (Flagyl)
• Antivirals - DNA, RNA, and Antiretrovirals (discussed in week 3)
• Antifungals - Polyenes, Azoles, and Topical/superficial

Week 3 Agenda

• Antihistamines and Bronchodilators,
• Antihyperlipidemics,
• Anticoagulants and Fibrinolytics,
• Tuberculosis drugs

Antimicrobial Therapy Basics

• Antibiotic Mechanisms of Action:
  • Antibiotics can inhibit or kill target cells by affecting cell walls, enzyme action, protein synthesis, and nucleic acid synthesis.
• Antibiotic Spectrum:
  • Narrow spectrum antibiotics affect fewer microbes, and broad spectrum antibiotics affect many microbes.
• Resistance:
  • Resistance supports bacterial growth, making it difficult to treat infections.
  • Acquired, innate, and environmental resistances complicate treatment.
• Superinfections:
  • Antibiotics can affect the "good" microbes, allowing for secondary infections to take over.
• Bacteria of Concern: - "Urgent": - Candida aureus - Clostridium difficile (C-diff) - Carbapenem-resistant Enterobacteriaceae (CRE) - "Serious": - Vancomycin-resistant Enterococci (VRE) - Methicillin-resistant Staphylococcus aureus (MRSA)

Beta Lactam Ring

• Beta-lactamases: Enzymes that break down the beta-lactam ring in antibiotics.
• Beta-lactamase inhibitors: Drugs that prevent beta-lactamases from inactivating antibiotics.

Cell Wall Synthesis Inhibitors

• Bactericidal
• Detail of Penicillins, Vancomycin, Cephalosporins, Carbapenems

Penicillins

• Narrow-spectrum (penicillinase-sensitive): Penicillin G, Penicillin V
• Narrow-spectrum (penicillinase-resistant): Nafcillin, Oxacillin, Dicloxacillin
• Broad-spectrum: Ampicillin, Amoxicillin
• Broad-spectrum antipseudomonal: Ticarcillin, Piperacillin
• Adverse effects: Allergic reactions; oral contraceptives may be affected.

Vancomycin

• Narrow-spectrum
• Used for: C-diff (oral), MRSA (IV)
• Adverse Effects: Hypersensitivity reactions (red man syndrome), ototoxicity, nephrotoxicity, thrombophlebitis.

Cephalosporins

• 5 generations with increasing CSF activity. -First generation (susceptible to B-lactamases), -Second generation, -Third generation (resistant to B-lactamases), -Fourth generation, -Fifth generation
• Adverse effects: Allergic reactions, bleeding, calcium deposits (lung/kidney), and alcohol intolerance.

Carbapenems

• Broad-spectrum with large CSF activity.
• Used for: Pseudomonas aeruginosa (severe hospital infections).
• Adverse effects: Hypersensitivity, GI issues, suprainfections, and seizures.

Ribosomal Protein Synthesis Inhibitors

• Bacteriostatic
• Include Macrolides, Aminoglycosides, Lincosamides, and Tetracyclines

Macrolides

• Broad-spectrum with no CSF activity
• Used for: Legionnaire's disease, whooping cough, diphtheria, and prophylactic dental or heart conditions.
• Adverse effects: QT prolongation, jaundice, auditory impairment

Aminoglycosides

• Broad-spectrum
• Used for: Pseudomonas aeruginosa
• Adverse effects: Ototoxicity, nephrotoxicity

Lincosamides

• Broad-spectrum with anaerobic penetration
• Used for: Bone, lung, oral, pelvic infections
• Adverse effects: Affects gut bacteria for 2+ weeks (C-diff), glossitis, stomatitis, esophagitis

Tetracyclines

• Broad-spectrum
• Used for: Malaria prophylaxis, Rocky Mountain Spotted Fever, Lyme disease, and acne.
• Adverse effects: Dental staining, skeletal growth depression in children, photosensitivity, and organ toxicity

Folic Acid Synthesis Inhibitors

• Bacteriostatic
• Include Sulfonamides and Trimethoprim
• Adverse effects: Crystalluria, Stevens-Johnson syndrome, hemolytic anemia, and photosensitivity.

Sulfonamides

• Broad-spectrum
• Used for: Ear infections, eye infections, UTIs, Traveler's diarrhea, burns
• Adverse effects: Crystalluria, Stevens-Johnson syndrome, hemolytic anemia, photosensitivity

Trimethoprim

• Broad-spectrum
• Used for: UTIs, ear infections, bronchitis, HIV/AIDS
• Adverse effects: Megaloblastic anemia, leukopenia, granlocytopenia

Nucleic Acid Synthesis Inhibitors

• Bactericidal
• Include Fluoroquinolones and Metronidazole.

Fluoroquinolones

• Broad-spectrum
• Used for: Typhoid, TB, GU infections, UTIs
• Adverse effects: Tendonitis, long QT, photophobia, taste disorders.

Metronidazole

• Broad-spectrum.
• Used for: Parasitic diseases, Trichomoniasis, C-diff
• Adverse effects: Reddish-brown urine, metallic taste, Disulfirim reaction, and oral candidiasis

Antivirals

• DNA Antivirals

• RNA Antivirals

• Antiretrovirals

• Detail each category.

Antifungals

• Polyenes

• Azoles

• Topical/superficial

• Detail each category.

Fungal Infections

• Systemic vs superficial
• Opportunistic vs non-opportunistic
• Opportunistic infections occur in immunocompromised individuals; Healthy individuals can get non-opportunistic infections.

Polyenes

• Used for: Fungal infections
• Adverse effects: Transfusion reaction, nephrotoxic, hypokalemia, and bone marrow repression.
• Example: Amphotericin B

Azoles

• Inhibit creation of ergosterol
• Adverse effects:
• Example: Itraconazole, Fluconazole, Ketoconazole

Topical/Superficial Antifungals

• Used for: Ringworm, yeast infections, thrush
• Examples: Tolnaftate, Nystatin, Clotrimazole, Miconazole

Antihistamines and Bronchodilators

• Antihistamines: First generation, second generation

• Bronchodilators: Short-acting beta agonists (SABAs), long-acting beta agonists (LABAs), inhaled steroids, monoclonal antibodies, LTRAS, and other miscellaneous topics

Histamine Release

• The body's response to histamine release, detailed.

Antihyperlipidemics

• HMG-CoA reductase inhibitors (statins),
• *Fibrates, Bile acid binding resins,
• Niacin,
• Cholesterol absorption inhibitors,
• PCSK9 inhibitors,
• Detailed information for every topic.

Statins

• First line to treat elevated LDL
• Adverse effects: Myopathy, rhabdomyolysis, hyperglycemia, joint pain.
• Indications: Elevated LDL, to stabilize plaque to prevent MI
• Contraindications: Fibrates, Macrolides

Fibrates

• Upregulate LPL (lipoprotein lipase)
• Adverse effects: NVD
• Indications: Hyperlipidemia
• Contraindications: Statins, Gallstones, Pregnancy

Bile Acid Binding Resins

• Binds to bile acids in intestines, forming complex

• Adverse effects: NVD, Decrease absorption of fatsoluble vitamins

• Indications: Hyperlipidemia

• Contraindications: Other drugs (don't take 1-2 hours prior)

Niacin (Nicotinic Acid/Vitamin B3)

• Inhibits lipase, and reduces VLDL and LDL
• Adverse effects: Flushing, Pruritus, NV, Hyperuricemia
• Indications: Hyperlipidemia

Cholesterol Absorption Inhibitors

• Blocks cholesterol absorption.
• Adverse effects: Myopathy.
• Indications: Hyperlipidemia (lowers by 20% alone).
• Contraindications: Liver dysfunction, Pregnancy

PCSK9 Inhibitors

• PCSK9 inactivates LDL receptors.
• Inactivating PCSK9 allows more LDL receptors to remove LDL.
• Adverse effects: Nasopharyngitis, pruritus, allergic reactions
• Indications: Hyperlipidemia (lowers by up to 60%)

Anticoagulants and Fibrinolytics

• Indirect thrombin inhibitors (e.g., heparin),,
• Vitamin K antagonists (e.g., warfarin),,
• Direct factor Xa inhibitors,
• Direct thrombin inhibitors,
• Antiplatelet drugs (e.g., aspirin),,
• Fibrinolytics (e.g., tissue plasminogen activator (tPA))

Heparin

• Mechanism of Action: Inactivates factor Xa and inhibits thrombin.
• Monitoring: Monitor PTT (2-3x normal)
• Adverse Effects: Heparin-induced thrombocytopenia (HIT), osteoporosis
• Reversal Agent: Protamine sulfate

LMWH (Low Molecular Weight Heparin)

• Examples: Enoxaparin, Dalteparin, Tinzaparin

Vitamin K Antagonists (Warfarin)

• Mechanism of Action: Vitamin K antagonist
• Monitoring: Monitor INR (2-4.5)
• Slow acting (3 days).
• Adverse effects: Increased bleeding, possible drug interactions (avoid grapefruit juice).
• Pregnancy Class X.
• Reversal Agent: Prothrombin-complex concentrates (immediate), Vitamin K (6-12 hours).

Direct Factor Xa Inhibitors

• Examples: Rivaroxaban, Apixaban, Edoxaban
• Monitoring: Not needed. Do not use with artificial heart valves

Direct Thrombin Inhibitors

• Examples: Bivalirudin, Argatroban, Dabigatran
• Do not use with artificial heart valves

Antiplatelet Drugs

• Mechanism of Action: Thromboxane A2 inhibitors (e.g., aspirin), ADP receptor inhibitors (e.g., clopidogrel), Glycoprotein IIb/IIIa inhibitors. Note-super aspirins used in stent replacements.
• Examples: Aspirin, Ticlopidine, Clopidogrel, Prasugrel, Abciximab, Tirofiban

Fibrinolytics/Thrombolytics

• Mechanism of Action : Directly convert plasminogen to plasmin, degrading fibrin clots.
• Examples: Urokinase, Streptokinase, Tenecteplase, Alteplase (tPA), Reteplase
• Reversal Agent: Aminocaproic acid

Anti-Tuberculosis Drugs

• MDR-TB : Resistance to at least rifampin and isoniazid.

• XDR-TB: Resistance to at least rifampin, isoniazid, and fluoroquinolones and an injectable second-line drug (aminoglycosides)

• Detailed information for each.

  • Use of DOT (directly observed therapy).
  • Intermittent dosing.

Latent TB

-Two treatment options
  - Isoniazid every day for 9 months (270 doses)
  -Isoniazid + rifampin every week for 3 months (12 doses)

Additional Drug information for Anti-tuberculosis medications