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Review Questions
Pharmacology-Y2S1B1
| Review Question | Answer |
|---|---|
| 4 drug classes in b-lactam family | penicillins, monobactams, carbapenems, cephalosporins |
| 2 bonds formed to ensure stability of bacterial cell wall | glycosidic (transglycosilase; PBP) and peptide (transpeptidase) |
| how does MOA of vancomycin differ from MOA of b-lactams | Vancomycin interrupts the formation of both glycosidic AND peptide bonds; much less resistance |
| 2 options to treat cellulitis with an IV anti-staph penicillin | Nafcillin (renal dose adjust) and oxacillin |
| drug of choice for switching from IV nafcillin/oxacillin to PO for discharge? | dicloxacillin |
| piperacillin-tazobactam (Zosyn) is a member of which penicillin family? | extended spectrum; antipseudomonal (Timentin is 2nd in this family); they cover G+s, G-s and anaerobes; reserved for serious infx |
| most common adverse side effect from penicillin | anaphylaxis; but Aztreonam (monobactam) can be used in b-lactam allergic pts |
| 2 cephalosporins with pseudomonas coverage | Ceftazidime (3rd gen) and Cefepime (4th gen); they must be reserved for serious infections; (not all cephalosporins are active against enterococcus) |
| First generation cephalosporins | most active against G+s |
| 3rd generation cephalosporins | more active against G-s; Cefotaxime and Ceftriaxone don't have pseudomonas coverage, so they can be used widely as "workhorses" |
| Pure Food and Drug Act of 1906 | prohibited mislabeling and adulteration of drugs (after gov't bought adulterated quinine) |
| Opium Exclusion Act of 1909 | prohibited importation of opium |
| Harrison Narcotic Act of 1914 | Established regulation for use of opiates and cocaine (marijuana added in 1937) |
| Federal Food, Drug, and Cosmetic Act of 1938 | demonastration of safety prior to marketing; NOT efficacy; after elixir of sulfanilamide scandal/deaths |
| Durham Humphrey Amentdment of 1951 | delineated differences btw prescription and OTC |
| Kefauver-Harris Amendment of 1962 | demonstrate EFFICACY and SAFETY prior to marketing; Drug Efficacy Study Implementation (DESI) established w/NAS with guidelines for reporting adverse (teratogenic or carcinogenic) reactions; following Thalidomide incident |
| Orphan Drug Act of 1983 | provide incentives for manufacturers to develop drugs with smaller target population |
| Drug Price Competition and Patent Restoration Act of 1984 | NDAs for generic drugs (required bioequivalence data); patent life extended for delay in drug review by FDA |
| Expedited Drug Approval Act of 1992 | accelerated FDA approval for drugs of priority status; detailed post marketing pt surveillance (ex: HIV) |
| Generic Drug Enforcement Act of 1992 | (blank) |
| Dietary Supplement Health and Education Act of 1994 | (blank) |
| FDA Modernization Act of 1997 | (blank) |
| Bioterrorism Act of 2002 | (blank) |
| Drug Discovery | 1. ID/elucidate new targets; 2. Rational drug design (chem/transport mech); 3. Modify an existing molecule; 4. Screen for biologic activity; 5. Biotech/cloning using genes to produce larger ptns ("high through-put" screen); 6. Pharmacogenomics/proteomics |
| Basic and clinical evaluation of new drugs | 1. discovery/screening - in vitro; 2. Preclinical safety/toxicity testing - in vivo (potency/efficacy; tolerance) and toxicity (acute/chronic LD50, teratogen, carcinogen); 3. Evaluation of drug in humans |
| Preclinical Research -Drug synthesis | chemical (solid phase); identification of lead compound |
| Preclinical Research - drug development | drug screening assay, in vitro animal model (pharmacology), bioavailability testing in animals, physiologically based PK models, Allometric dose scaling for humans |
| Phase I Clinical Trials | healthy adult volunteers (safety, PK, side effects) |
| Phase II Clinical Trials | Patients (efficacy, safety, PK, side effects; Proof of concept; Pt's response to drug; Single-blind placebo controllled |
| Phase III Clinical Trials | Specific Patient subpopulation; efficacy for specific indications (n>1000); Randomized, double-blind placebo controlled |
| Phase IV Post FDA Approval | determine efficacy for specific indication; determine drug utilization patterns and additional efficacy; monitor rare, severe side effects/toxicity |
| Safety Tests - acute toxicity | LD50; MTD; 2 routes, 1 dose |
| Safety Tests - Subacute Toxicity | 3 doses; autopsy, hematology, histology, target organ toxicity |
| Safety Tests - Chronic Toxicity | 6mo-yrs; long term |
| Safety Tests - Reproductive toxicity | reproduction, progeny, postnatal development, teratogenicity, lactation |
| Safety Tests - Carcinogenictity | 2yrs autopsy, hematology, histology, target organ toxicity |
| Safety Tests - Mutagenicity | genetic stability; forced mutations in culture cells |
| Safety Tests - Toxicity | mechanisms of toxicity; biochemical pathways involved; toxicological assays |
| Treating a pt w/severe G- sepsis with a carbapenem; which 2 agents would be best choice d/t greater spectrum of coverage? | Imipenem and meropenem "gorillas" are broad spectrum agents reserved for life-threatening infxn where other agents can't be used |
| Side effect of imipenem | seizures |
| Ertapenem lacks activity against? | pseudomonas, therefore can be used as a first line agent in outpt/home health care via IM or IV |
| 2 Drugs commonly used for their ANAEROBIC activity: | Clindamycin (plus G+; sometimes used in case of b-lactam allergy) and Metronidazole (plus parasites) |
| Clindamycin's biggest risk factor is: | causing C. difficil |
| Anti-anaerobe drug used to treat C. difficil colitis | 1. metronidazole or 2. ORAL vancomycin |
| What 2 organisms does Metronidazole cover? | 1. C. difficil (certain anaerobes), 2. certain protozoa ==> they all reduce the nitro group to a toxic product |
| Atypical Bacteria | Seen in resiratory tract infx: Mycoplasma pneumonia, Chlamydia pneumonia, and Legionella |
| 3 Drug Classes Effective against Atypical Bacteria | Fluoroquinolones, Tetracyclines (both used extensively as 1st line drug against pneumonia), and Macrolides (second line in case of allergy) |
| 4 Agents Classically Active Against MRSA: | Vancomycin, Linezolid (the two most common); and Daptomycin (new/unique MOA; cellulitis/osteomyelitis...NOT MRSA-pneumonia) and Synercid (rarely used d/t arthralgias) |
| Which drugs treat MRSA pneumonia? | Vancomycin or Zyvox |
| What agent covers Flukes and Tapeworms? | Praziquantel - taken orally; active against most |
| Aminoglycosides and Vancomycin are "Narrow Therapeutic Agents," what does that mean? | relatively small difference btw efficacy and toxicity, so levels need to be monitored; Aminoglycosides - PEAKS and TROUGHS; Vancomycin - TROUGHS |
| Aminoglycosides | peaks and troughs; concentration-dependent killing (ie - the higher the peak, the better the kill_ |
| Vancomycin | troughs; Time-dependent killing (ie - the peak doesn't matter, but the trough does as it needs to remain above the MIC for the time period to be effective) |
| 3 Clinically Relevant Aminoglycosides | Gentamicin, Tobramycin, Amikacin; they are synergistic with b-lactams for Enterococcus killing |
| Aminoglycosides - Amikacin | has different peak/trough ranges; can be active against bacteria resistant to gentamicin and tobramycin |
| Linezolid (zyvox) differs from other protein synthesis inhibitors in which way? | it works in the initiation phase of ptn synthesis, which is earlier than the other agents working in binding to the ribosome; The advantage is reduced cross-resistance; It prevents 70s ribosome formation; taken ORALLY; MRSA/VRE w/o peaks and troughs |
| Which anti-TB agent is implicated in the most number of drug interactions? | RIFAMPIN - major inducor of CYP450 enzyme system; alters metabolism of other drugs; (Rifampin is also used w/other agents to treat Staph infxn in prostethic osteomyelitis) |
| How do therapies differ btw Tx of latent and active TB? | 1. Active TB - initial phase of 2mo w/4drugs followed by a "continuation phase" 4-7mo on 2 drugs; 2. Latent TB - Take either isoniazid for 6-9mo or Rifampin for 4mo |
| What are the different options for latent TB? (1st, 2nd, 3rd line) | Isoniazid (INH), Rifampin, Pyra |
| What are second line agents for use in active TB? | Cycloserine and Ethionamide |
| Why are SMX-TMP compined in one pill? What are its main uses? Drawbacks? | (blank) |
| Pt started on isoniazid therapy and after 1mo LFT AST is very high. What should you do? | (blank) |
Created by:
bscaryp