Exam 2 Review Complete Exam Notes PDF

EXAM 2 WEEKS 2 AND 3 PHARMACOLOGY WEEK 2 AGENDA Antimicrobial Therapy Basics Cell wall synthesis inhibitors: 1. Penicillins 2. Vancomycin 3. Cephalosporins 4. Carbapenems Ribosomal protein synthesis inhibito...

EXAM 2 WEEKS 2 AND 3 PHARMACOLOGY WEEK 2 AGENDA Antimicrobial Therapy Basics Cell wall synthesis inhibitors: 1. Penicillins 2. Vancomycin 3. Cephalosporins 4. Carbapenems Ribosomal protein synthesis inhibitors: 1. Macrolides 2. Aminoglycosides 3. Lincosamides 4. Tetracyclines 3 AGENDA Folic acid synthesis inhibitors: 1. Sulfonamides 2. Trimethoprim Nucleic acid synthesis inhibitors: 1. Fluoroquinolones 2. Metronidazole (Flagyl) Antivirals Antifungals 4 ANTIMICROBIAL THERAPY BASICS Folic acid synthesis 6 BACTERICIDAL VS BACTERIOSTATIC Bactericidal (kill bacteria) Bacteriostatic (inhibit bacteria growth) Cell wall synthesis inhibitors: Ribosomal protein synthesis inhibitors: 1. Penicillins 1. Macrolides 2. Vancomycin 2. Aminoglycosides* 3. Cephalosporins 3. Lincosamides 4. Carbapenems 4. Tetracyclines Nucleic acid synthesis inhibitors: Folic acid synthesis inhibitors: 1. Fluoroquinolones 1. Sulfonamides 2. Metronidazole (Flagyl) 2. Trimethoprim *can be both depending on concentration 7 BACTERIA OF CONCERN “URGENT”: “Serious”: 1. Candida aureus 1. VRE 2. Clostridium difficile (C-diff) – contact 2. MRSA – contact precautions precautions 3. Carbapenem-resistant Enterobacteriaceae (CRE) 8 BETA LACTAM RING – A FEATURE OF MANY ANTIBIOTICS THAT DISRUPTS MICROBE CELL WALLS Beta Lactamase (penicillinase) Beta Lactamase Inhibitors Enzyme in the microbe that breaks down the Drugs that prevent beta lactamase from beta lactam ring inactivating antibiotics Examples include: 1. Sulbactam 2. Avibactam 3. Tazobactam 4. Clavulanic acid “I sat in clavulanic acid!” 9 CELL WALL SYNTHESIS INHIBITORS 1. Penicillins 2. Vancomycin 3. Cephalosporins 4. Carbapenems BACTERICIDAL PENICILLINS – B-LACTAM RING INHIBITS TRANSPEPTIDASE Narrow-spectrum Broad-spectrum Adverse Effects penicillinase sensitive: aminopenicillins: Allergic reaction Penicillin G Ampicillin Oral contraceptives fail Penicillin V Amoxicillin Narrow-spectrum Broad-spectrum penicillinase resistant: antipseudomonal* penicillins: Nafcillin Ticarcillin Oxacillin Piperacillin Dicloxacillin *effective against pseudomonas aeruginosa 11 VANCOMYCIN – B-LACTAM RING INHIBITS TRANSGLYCOSYLATION Narrow-spectrum with some CSF Adverse Effects: activity Hypersensitivity (red Used for: man syndrome) 1. C-diff (oral) Ototoxicity 2. MRSA (IV) Nephrotoxicity Thrombophlebitis 12 CEPHALOSPORINS 5 generations with increasing CSF activity (12) Adverse Effects CSF 1st Gen (2) – susceptible to B-lactamases Allergic reaction 2nd Gen (3) Bleeding Calcium deposits 3rd Gen (5) – resistant to B-lactamases (lung/kidney precipitates) 4th Gen (1) Alcohol intolerance 5th Gen (1) 13  CEPHALOSPORINS 1st Gen Cefazolin Surgical prophylaxis Cephalosporin Soft-tissue/UTI 2nd Gen Cefuroxime URI Cefoxitin Abd surgery prophylaxis Cefotetan – bleeding, alcohol Abd surgery prophylaxis intolerance 3rd Gen (all used for Cefixime meningitis) Cefdinir Ceftriaxone – bleeding, Gonorrhea alcohol intolerance, calcium precipitates Cefotaxime Gonorrhea Ceftazidime Pseudomonas aeruginosa 4th Gen Cefepime Meningitis, febrile neutropenia, pneumonia 5th Gen Ceftaroline MRSA 14  CEPHALOSPORINS 2nd Gen: 3rd Gen: “a Furry Fox in the Tetons” “Taz and Tax Tried to Fix me Dinner” Cefuroxime Ceftazidime Cefoxitin Cefotaxime Cefotetan Ceftriaxone Reversed order Cefixime Cefdinir 15 CARBAPENEMS Broad-spectrum with large CSF activity Adverse Effects: Penetrates all tissues and CSF Hypersensitivity Used for: GI issues Pseudomonas aeruginosa (severe hospital infections) Suprainfections Seizures 1. Imipenem – give with cilastatin* 2. Meropenem 3. Ertapenem 4. Doripenem *prevents degradation by kidneys 16 RIBOSOMAL PROTEIN SYNTHESIS INHIBITORS 1. Macrolides 2. Aminoglycosides* 3. Lincosamides 4. Tetracyclines BACTERIOSTATIC MACROLIDES – INHIBIT PEPTIDYLTRANSFERASE Broad-spectrum with no CSF activity Adverse Effects: Used for: QT prolongation Legionnaire’s disease Jaundice Whooping cough Auditory impairment Diphtheria Prophylactic dental work (endocarditis) 1. Erythromycin – motilin receptor 2. Azithromycin 3. Clarithromycin 4. Dirithromycin 18 AMINOGLYCOSIDES – INHIBIT RNA SYNTHESIS Broad-spectrum Adverse Effects: Used for: Ototoxicity Pseudomonas aeruginosa (severe Nephrotoxicity infections) 1. Amikacin Ototoxic 2. Gentamicin 3. Neomycin Nephrotoxic 4. Tobramycin 5. Streptomycin 19 LINCOSAMIDES – INHIBIT RIBOSOMAL PROTEIN SYNTHESIS Broad-spectrum with anaerobic Adverse Effects: penetration Affects gut bacteria for Used for: 2+ weeks (C-diff ) BLOP infections Glossitis Bone, Lungs, Oral, Pelvis Stomatits Esophagitis 1. Clindamycin 2. Lincomycin 20 TETRACYCLINES – INHIBIT RIBOSOMAL PROTEIN SYNTHESIS Broad-spectrum Adverse Effects: Used for: Dental staining Malaria prophylaxis Skeletal growth depression Rocky Mountain Spotted Fever Don’t use in pediatrics Lyme Disease Photosensitivity Acne Organ toxicity Periodontal disease 1. Tetracycline 2. Demeclocycline Short-acting to long-acting 3. Doxycycline 4. Minocycline 21 FOLIC ACID SYNTHESIS INHIBITORS 1. Sulfonamides 2. Trimethoprim BACTERIOSTATIC SULFONAMIDES – INHIBIT FOLIC ACID SYNTHESIS Broad-spectrum Adverse Effects: Used for: Crystalluria Ear infections Stevens-Johnson Eye infections Syndrome UTIs Hemolytic anemia Traveler's diarrhea Burns Photosensitivity 1. Sulfisoxazole 2. Sulfamethoxazole short-acting 3. Sulfamethizole 4. Sulfadiazine 5. Sulfadoxine – long-acting 23 SULFONAMIDES LED TO THE FOOD, DRUG, AND COSMETIC ACT AFTER THE ELIXIR POISONING THAT KILLED MANY. 24 TRIMETHOPRIM* – INHIBIT FOLIC ACID SYNTHESIS Broad-spectrum Adverse Effects: Used for: Megaloblastic anemia UTIs Leukopenia Ear infection Granlocytopenia Bronchitis HIV/AIDS 25 NUCLEIC ACID SYNTHESIS INHIBITORS 1. Fluoroquinolones 2. Metronidazole (Flagyl) BACTERICIDAL FLUOROQUINOLONES – INHIBIT GYRASE AND TOPOISOMERASE Broad-spectrum Adverse Effects: Used for: Tendonitis Typhoid Long QT TB Photophobia GU infections Taste UTIs 27 FLUOROQUINOLONES – INHIBIT GYRASE AND TOPOISOMERASE 28 METRONIDAZOLE (FLAGYL) – DESTROYS DNA HELICAL STRUCTURE Broad-spectrum Adverse Effects: Used for: Reddish-brown urine Parasitic diseases Metallic taste Trichomoniasis Disulfirim reaction C-diff Oral candidiasis 29 ANTIVIRALS 1. DNA Antivirals 2. RNA Antivirals 3. Antiretrovirals DNA ANTIVIRALS – NUCLEIC ACID INHIBITORS (DNA) Acyclovir – inhibits DNA strand growth 1. Herpes 2. Pregnancy safe 2. Valacyclovir: used to reduce transmission between monogamous partners Ganciclovir – blocks DNA strand growth 1. CMV 2. Teratogenic; bone marrow suppression Docosanol – blocks viral entry 1. HSV1 blisters 2. Fat derived 3. Minimal side effects 31 RNA ANTIVIRALS – BLOCK VIRAL REPLICATION Adamantanes – blocks viral uncoating 1. Amantadine 2. Rimantadine Neuraminidase N Inhibitors – prevents budding 1. Oseltamivir 2. Zanamivir Used for influenza A & B Must take within 30 – 36 hours after symptom onset Ribavirin and Palivizumab for RSV in children 32 ANTIRETROVIRALS Used for HIV Five categories: 1. NRTI – Nucleoside reverse transcriptase inhibitors 2. NNRTI – Non-nucleoside reverse transcriptase inhibitors 3. PI – Protease inhibitors 4. INSTI – Integrase inhibitors 5. FI – Fusion inhibitors 33 ANTIRETROVIRALS Used for HIV Five categories: 1. NRTI Antiretroviral Therapy: 2. NNRTI 2 NRTI + 1 NNRTI 3. PI 2 NRTI + 2 PI 4. INSTI 2 NRTI + INSTI/FI 5. FI 34  ANTIRETROVIRALS NRTI – adverse effects of lactic acidosis INSTI and hepatic steatosis Abacavir Zidovudine Lamivudine Emtricitabine Dolutegravir Tenofovir FI Enfuvirtide NNRTI - CYP450 PI Ritonavir Darunavir 35 HEPATITIS C Ribavirin + interferon: same drug as used for RSV in children Telaprevir: Protease inhibitor (PI) Sofosbuvir 36 ANTIFUNGALS 1. Polyenes 2. Azoles 3. Topical/superficial FUNGAL INFECTIONS Systemic vs superficial Opportunistic vs non-opportunistic Opportunistic occur in immunocompromised individuals Non-opportunistic can occur in healthy individuals 38 POLYENES – DISRUPT FUNGAL CELL MEMBRANE (BINDS TO ERGOSTOL) Amphotericin B: Adverse Effects: Used for: Transfusion reaction Fungal infections Nephrotoxic IV only Hypokalemia Bone marrow suppression 39 AZOLES – INHIBITS CREATION OF ERGOSTEROL Inhibits CYP450 (no grapefruit juice). All can be taken PO Itraconazole Fluconazole – penetrates CSF GI upset Cardio suppression Seizures Hepatotoxic Birth defects Hypokalemia Ketoconazole Avoid antacids & H2 Hypertension antihistamines Inhibits testosterone Gynecomastia Menstrual irregularities 40 TOPICAL/SUPERFICIAL Used for: Ring worm, yeast infections, thrush Tolnaftate Superficial mycosis Nystatin Yeast infections (thrush) Clotrimazole Miconazole Vaginal yeast infections 41 WEEK 3  AGENDA Antihistamines and Bronchodilators Antihyperlipidemics Anticoagulants and Fibrinolytics Tuberculosis drugs  ANTIHISTAMINES AND BRONCHODILATORS 1. Antihistamines (1st gen, 2nd gen) 2. SABAs and LABAs 3. Inhaled steroids 4. Monoclonal antibodies 5. LTRAs 6. Miscellaneous  ANTIHISTAMINES Uses: 1. First-Generation 2. 3. 1. Sedative 4. 2. Anticholinergic effects 5. Uses: Second-Generation 1. Cetirizine: allergies 2. Fexofenadine: allergies 3. Loratadine: allergies  ANTIHISTAMINE ADVERSE EFFECTS Anticholinergic effects Dry mouth Blurred vision (mydriasis) Urinary retention Constipation Tachycardia  BRONCHODILATORS Short-acting Beta agonists 1. Albuterol (SABAs) (acute asthma) Long-acting Beta agonists 1. Salmeterol (LABAs) 2. Formoterol (prophylaxis)  SABA AND LABA ADVERSE EFFECTS Beta-receptor stimulation Tachycardia Palpitations Angina Hypertension Anxiety Insomnia Tremors  OTHER AIRWAY DRUG CLASSES 1. 1. 2. 3. 2. OTHER AIRWAY DRUG CLASSES  MISCELLANEOUS BRONCHODILATORS 1. Caffeine 2. Theophylline 3. Tiotropium - Long-acting muscarinic antagonist (LAMA) - Used prophylactically for asthma and COPD - Anticholinergic adverse effects  ANTIHYPERLIPIDEMICS 1. HMG-CoA reductase inhibitors (statins) 2. Fibrates 3. Bile acid binding resins 4. Niacin 5. Cholesterol absorption inhibitors 6. PCSK9 inhibitors  1. Simvastatin STATINS 2. Rosuvastatin 3. Atorvastatin Adverse effects: Indications:     Contraindications     FIBRATES 1. Fenofibrate Adverse effects: Indications:   Contraindications:     BILE ACID 1. Cholestyramine BINDING RESINS Adverse effects Indications:    Contraindications:   NIACIN (NICOTINIC 1. Niacin ACID/VITAMIN B3) Adverse effects: Indications:      CHOLESTEROL ABSORPTION 1. Ezetimibe INHIBITORS Adverse effects: Indications:   Contraindications:    1. Evolocumab PCSK9 INHIBITORS 2. Alirocumab Adverse effects: Indications:     ANTICOAGULANTS AND FIBRINOLYTICS 1. Indirect thrombin inhibitors 2. Vitamin K antagonists 3. Direct factor Xa inhibitors 4. Direct thrombin inhibitors 5. Antiplatelet drugs 1. Thromboxane A2 inhibitors 2. ADP receptor inhibitors 3. Glycoprotein llb/lllb receptor 6. Fibrinolytics  ANTICOAGULANTS AND FIBRINOLYTICS Adverse effects: Increased bleeding Contraindications: Hemorrhage, recent surgery, brain injuries, ulcers (this is true for all anticoagulants and fibrinolytics!)  INDIRECT THROMBIN INHIBITORS 1. Heparin 1. Unfractioned heparin (HMW) 2. Low molecular weight heparin (LMWH) 2. Fondaparinux 1. Binds to Xa, not thrombin 2. No heparin induced thrombocytopenia 3. Not reversed by protamine sulfate  HEPARIN MOA: inactivates factor Xa and inhibits thrombin. Monitor PTT (2-3x normal) Rapid acting Safe in pregnancy Adverse effects: Heparin induced thrombocytopenia, osteoporosis Reversal agent: Protamine sulfate  LMWH 1. Enoxaparin 2. Dalteparin 3. Tinzaparin  VITAMIN K ANTAGONISTS WARFARIN MOA: Vitamin K antagonist. Monitor INR (2 – 4.5) Slow acting (3 days) Pregnancy class X Avoid grapefruit juice Reversal agent: Prothrombin-complex concentrates (immediate), Vitamin K (6-12 hours) VITAMIN K Vitamin K helps produce various clotting factors. It can be given PO or IV if too much bleeding is happening (Warfarin overdose). Vitamin K is given to newborns to ensure proper blood clotting ability (next term!).  DIRECT FACTOR X INHIBITORS A 1. Rivaroxaban 2. Apixaban 3. Edoxaban  DIRECT THROMBIN INHIBITORS 1. Bivalirudin 2. Argatroban 3. Dabigatran  ANTIPLATELET DRUGS Thromboxane A2 inhibitors (prevents platelet aggregation) 1. Aspirin ADP receptor inhibitors (super aspirins – used in stent replacement) 1. Ticlopidine 2. Clopidogrel 3. Prasugrel Glycoprotein llb/lllb receptor (used in coronary angioplasty) 1. Abciximab 2. Tirofiban  FIBRINOLYTICS/THROMBOLYTICS “U are a STAR” 1. 2. 3. 4. 5. ANTI-TUBERCULOSIS  TB THERAPY PHASES 1. 1. Induction: 2 months of 4 drugs 2. 1. Isoniazid, rifampin, pyrazinamide, ethambutol 2. Continuation: 4 months of 2 drugs 1. Isoniazid, rifampin 1. 2. LATENT TB TB + HIV  ANTI-TUBERCULOSIS DRUGS 1. 2. 3. 4. 5. 6. 7. THANK YOU Joshua Hogan [email protected]