Lecture Notes on Pharmacology

Aminoglycosides

Worrisome Side Effects: Nephrotoxicity, neuromuscular blockade, autotoxicity, teratogenicity.
Mechanism of Action: Irreversible inhibition of the initiation complex through binding to the 30S ribosomal subunit.
Contraindications: Autoimmune condition like Myasthenia gravis.
Resistance Mechanisms: Inactivation by bacterial transferase enzymes through acetylation, phosphorylation, or adenylation.

Penicillinase-Sensitive Penicillins: Amoxicillin, ampicillin, aminopenicillin.
- Target Organisms: H. influenza, H. pylori, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, Enterococci.
Penicillinase-Resistant Penicillins: Dicloxacillin, nafcillin, oxacillin.
- Main Target: Staph aureus.
Mechanism of Resistance: Altered penicillin-binding protein target site (MRSA).

Clindamycin: Pseudomembranous colitis.
Linazolid:
- Clinical Uses: Gram-positive species, MRSA, VRE.
- Concerning Side Effects: Bone marrow suppression, peripheral neuropathy, serotonin syndrome.
Chloramphenicol: Dose-independent aplastic anemia.
Cephalosporins:
- Generations and Uses:
  - 1st generation: Gram-positive cocci, Proteus mirabilis, E. coli, Klebsiella pneumonia.
  - 2nd generation: Gram-positive cocci, H. influenzae, Enterobacter aerogenes, Neisseria species, Serratia marcescens, Proteus mirabilis, E. coli, Klebsiella pneumonia.
  - 3rd generation: Serious gram-negative infections, pseudomonas (Ceftazidime).
  - 4th generation: Cefepime.
  - 5th generation: Effective against MRSA.
- Side Effect: Leads to Vitamin K deficiency.
Tetracyclines:
- Side Effects: GI distress, teeth discoloration, bone growth inhibition in children, photosensitivity.
- Effective Against: Rickettsia, Chlamydia (due to intracellular accumulation).
- Doxycycline: Best for renal failure patients, effective against community-acquired MRSA.
Macrolides:
- Side Effects: Arrhythmias (prolong QT interval).
- Use: Atypical pneumonia (Legionella, Mycoplasma, Chlamydia).
Fluoroquinolones:
- Side Effects: Tendinitis, tendon rupture (especially in patients >60).
- Mechanism of Resistance: E-flux pumps, chromosome mutations, plasmid-mediated resistance.

Amphotericin B:
- Mechanism: Binds ergosterol, forms membrane pores.
- Minimize Nephrotoxicity: Increase hydration.
Azoles: Inhibit testosterone synthesis.
Rifamicins:
- Mechanism: Inhibition of DNA-dependent RNA polymerase.
- Rifabutin: Better for HIV patients due to less p450 stimulation.
Ethambutol: Side effect of optic neuropathy.
Isoniazid: Resistance through mutations leading to underexpression of CATG.

Guanosine Analogs: Resistance via mutated viral thymidine kinase.
Ribavirin: Inhibits synthesis of guanine nucleotides by inhibiting IMP dehydrogenase.

Beta Blockers:
- Effects: Decrease heart rate, contractility, and blood pressure.
- Overdose Treatment: Saline, atropine, glucagon.
Calcium Channel Blockers:
- Dihydropyridine Side Effects: Peripheral edema, flushing, dizziness.
- Non-Dihydropyridine Side Effects: Cardiac depression, AV block, constipation.
Nitrates:
- Effects: Decrease end-diastolic volume, ejection time, MVO2; increase heart rate (reflexive response).
Digoxin:
- Side Effects: Blurry yellow vision.
- Mechanism: Inhibits sodium-potassium ATPase.

Acetaminophen: N-acetylcysteine (replenishes glutathione).
Benzodiazepines: Flumazenil.
Opioids: Naloxone.
Iron Toxicity: Deferoxamine, deferaserox, deferaprone.
Cyanide Poisoning: Hydroxocobalamin, nitrates, sodium thiosulfate.
Heparin Overdose: Protamine sulfate.
Warfarin Toxicity:
- Immediate Reversal: FFP or PCC.
- Delayed Reversal: Vitamin K.

SIADH Inducing Drugs: Carbamazepine, cyclophosphamide, SSRIs.
Peripheral Neuropathy: Associated with Isoniazid and Phenytoin.
Pill-Induced Esophagitis Prevention: Upright posture and adequate water ingestion.