Students and Politics Analysis

Therapeutic objective of all drugs: to provide maximum benefit with minimum harm Three Most Important Properties of an Ideal Drug: Effectiveness, Safety, Selectivity Nurses are the last line of defense for the patient. It is ethically and legally unacceptable to administer a drug that is harmful to the patient—even though the medication has been prescribed by a licensed prescriber and dispensed by a licensed pharmacist 7 aspects of drug therapy.

Pre-administration assessment: collect baseline date, ID high-risk pts, assess capacity for self-care Dosage and administration – DON’T GIVE ANY DRUG THAT YOU DON’T UNDERSTAND ITS USE Evaluating and promoting therapeutic effects – know rationale for trmt & nature/time course of intended response Minimizing adverse effects – All drugs have the potential to produce undesired effects. Minimizing adverse interactions – drug hx, avoid OTCs that interact Making PRN decisions – pro re nata, meaning “for the thing born” loosely translated to “as needed” Managing toxicity – early identification is key.

Drug Regulation, Development, Names, and Information 617093095885Adverse Drug Reactions (brief key notes): S/sx of liver injury: jaundice (yellow skin & sclera), dark urine, light-colored stools, nausea, vomiting, malaise, abd discomfort, loss of appetite HALF (50%) of all new drugs have serious ADRs that are not revealed during Phase II and Phase III trials. BLACK BOX WARNINGS: Strongest safety warning a drug can carry and still remain on the market – inside the “black box” there is a concise summary of the adverse effects of concern.

00Adverse Drug Reactions (brief key notes): S/sx of liver injury: jaundice (yellow skin & sclera), dark urine, light-colored stools, nausea, vomiting, malaise, abd discomfort, loss of appetite HALF (50%) of all new drugs have serious ADRs that are not revealed during Phase II and Phase III trials. BLACK BOX WARNINGS: Strongest safety warning a drug can carry and still remain on the market – inside the “black box” there is a concise summary of the adverse effects of concern Harris-Kefauver Amendment 1962: drugs had to be proved effective!

Thalidomide (sedative) Controlled Substances Act 1970: regulation of drugs for abuse potential (KNOW THE 5 CATEGORIES) Stages of New Drug Development: Pre-clinical testing (1-5 yrs) Clinical testing (2-10 yrs) Phase I – pre-clinical testing; healthy volunteers or volunteers with disease process Phase II and III – patients (500-5,000) determine therapeutic effect, dosages, safety & effectiveness Phase IV: postmarketing surveillance (released for general use permitting observations of efx in large population) DRUG NAME: Chemical vs Generic vs Trade.

Pharmacokinetics – study of drug movement throughout the body (includes drug metabolism & drug excretion) Absorption (moving the drug into the blood) 66652096626KNOW difference between enteral and parenteral meds. Advantages? Disadvantages? Distribution (drug from the blood into the tissues/cells) – movement of drugs throughout the body.

BBB – Only drugs that are lipid soluble or have a transport system can cross the BBB to a significant degree *Metabolism (“biotransformation” or enzymatic alteration of drug) Metabolism most often takes place in the liver (P450 system) The human body has a group of 12 enzyme families; 3 specifically metabolize drugs: CYP 1, CYP2, CYP3 each metabolizes only certain drugs The most important consequence of drug metabolism is promotion of renal drug excretion (KIDNEYS CAN’T EXCRETE LIPID DRUGS) Special considerations:

Age, Induction of drug metabolism, FIRST-PASS EFFECT, Nutritional status, Competition between drugs (ETOH?), CYP INHIBITORS More important CYP inhibitors are: erythromycin, ketoconazole, and ritonavir because they inhibit several CYP isozymes. Grapefruit juice effect (not occurring with other citrus fruits or juices) raises drug levels mainly by inhibiting metabolism – which increases the drug available for absorption 62750708255Drug Therapy in Pediatric Patients (brief key notes): ^ sensitivity in infants due to immature state of these processes: Absorption – GI emptying irregular.

Protein binding of drugs – they have relatively low albumin Blood-brain barrier – not fully developed & allows drugs through Hepatic metabolism – low; not mature until ~1 Renal drug excretion – low; not mature until ~1 Children ~1-12 metabolize drugs faster than adults For pediatric patients taking a medication with no established dosage, most commonly the dose should be based on body surface area (BSA). 00Drug Therapy in Pediatric Patients (brief key notes):

^ sensitivity in infants due to immature state of these processes: Absorption – GI emptying irregular Protein binding of drugs – they have relatively low albumin Blood-brain barrier – not fully developed & allows drugs through Hepatic metabolism – low; not mature until ~1 Renal drug excretion – low; not mature until ~1 Children ~1-12 metabolize drugs faster than adults For pediatric patients taking a medication with no established dosage, most commonly the dose should be based on body surface area (BSA).

*Excretion (drugs/metabolites out of the body) *these both are “elimination” Minimum effective concentration THERAPEUTIC RANGE Toxic concentration Half-life – time required for the amount of drug in the body to decrease by half/50% (not a specific amount) Time to plateau – w/ same size dose, is (~4-5) 4-6 half-lives depending on drug, absorption and clearance Pharmacodynamics – study of what drugs do to the body and how they do it Dose response relationships – relationship between the size of an administered dose and the intensity of the response produced Drug-Receptor Interactions – Drugs can only mimic or block the body’s own regulatory molecules. Lock and key mechanism Agonist vs Antagonist (competitive vs non-competitive) vs Partial Agonist Receptor sensitivity (up and down-regulation) Interpatient Variability in Drug Responses 5567680127635Drug Therapy in Geriatric Patients (brief key notes): Hepatic metabolism declines with age.

Renal function undergoes progressive decline Drug accumulation d/t to reduced renal excretion is the most important cause of adverse drug reactions in the elderly Use creatinine clearance, not serum creatinine, because lean muscle mass (source of creatinine) declines in parallel with kidney function. Abnormal creatinine clearance = < ~105-110 mL/min/1. 73 m2 00Drug Therapy in Geriatric Patients (brief key notes): Hepatic metabolism declines with age Renal function undergoes progressive decline Drug accumulation d/t to reduced renal excretion is the most important cause of adverse drug reactions in the elderly Use creatinine clearance, not serum creatinine, because lean muscle mass (source of creatinine) declines in parallel with kidney function. Abnormal creatinine clearance = < ~105-110 mL/min/1.

73 m2 ED50 (average effective dose for 50% of the population) = standard dose Over and under treatment possible NURSES ARE RESPONSIBLE FOR RECOGNIZING TOO MUCH/LITTLE HAS BEEN ADMINISTERED Therapeutic Index – ratio of the drug’s LD50 (average lethal dose to 50% of the animals treated) to its ED50 – how safe is this drug? ^ the therapeutic index = safer the drug Drug-Drug interactions: Risk for serious drug interaction is directly proportionate to the number of drugs a patient is taking When the drug says “take with food”, administer with or shortly after a meal When the drug says “take on an empty stomach”, administer either 1 hour before meal or 2 hours after St. John’s wort induces drug-metabolizing enzymes > reduces blood levels of many drugs AUTONOMIC NERVOUS SYSTEM ANS effects…

Skeletal muscle, Cardiac output, Vascular tone, Respiration, GI function, Uterine motility, Glandular secretions, Pain perception, ideation and mood SNS EFFECT PSNS (SLUDGE) ^ CO/HR v Constriction Vascular tone Dilate ^ Respiration v v GI motility ^ Constipation GI Diarrhea Xerostomia Secretions Salivating Mitosis Eye Miosis Ejaculate Sex Erection Relax Uterine SM Contract Contract Prostate Relax Definitions Agonist – directly activate receptor (morphine, epi, insulin) Antagonist – prevent receptor activation (naloxone, antihistamines, beta blockers) Direct acting – Stimulate receptor Indirect acting – Stimulate release of NT Sympathomimetic – adrenergic (SNS) Sympatholytic – antiadrenergic Parasympathomimetic – cholinergic (PSNS) Parasympatholytic – anticholinergic Cholinesterase – breaks down ACh.

Cholinesterase inhibitor – prevents breakdown of ACh and ACh inhibitor CATECHOLAMINES NON-CATECHOLAMINES Short DOA Can’t give PO Can’t cross BBB Longer DOA Can give PO Crosses BBB Epinephrine, Norepinephrine, Dopamine, Dobutamine, Isoproterenol Phenylephrine, ephedrine, terbutaline Neurotransmitters of the PNS Acetylcholine – released from preganglionic and postganglionic (PSNS) neurons Norepinephrine – released from post-ganglionic (SNS) neurons Epinephrine – released from adrenal medulla (anaphylactic shock) Dopamine – used for shock and hypotension Class Drug MOA Therapeutic Uses Adverse Effects Additional Info/Contraindications Cholinergic Parasympathomimetic.

Muscarinic agonist Bethanechol ^ cholinergic rec. in the smooth muscle of the urinary bladder & GI tract: ^ peristalsis, GI secretions, bladder muscle contraction Urinary retention Treat loss of tone in GI tract GERD Abx cramps, diarrhea, N/V, salivation Urinary urgency Lacrimation, miosis, sweating Bronchial constriction/asthma attacks, v BP, ^ HR, flushed OD: give Atropine CI: obstruction of GU/GI, peritonitis, Parkinson’s disease, v HR, asthma Pregnancy category C drug DI: cholinesterase inhibitors Anti-cholinergic Parasympatholytic Muscarinic antagonist Atropine Blocks ACh at PSNS receptor: ^ CO, v secretions, antagonizes histamine/serotonin Pre-op use Treat vHR.

Eye exams Dry mouth, blurry vision, urinary hesitancy, constipation, palpitation, anhidrosis, ^ temp, hallcuinations OD: give Physostigmine CI: narrow-angle glaucoma, CAD, obstruct GU/GI, paralytic ileus, hernia, asthma NI: ice chips, fluids, assess lung sounds Acetylcholinesterase inhibitor Neostigmine Prevents the breakdown of ACh into choline and acetic acid (indirect-acting cholinergic agonist).

Myasthenia Gravis OD: give Atropine ANTIBIOTICS Bactericidal – Bringing death to bacteria; directly lethal to bacteria at clinically achievable concentrations Bacteriostatic – Restrain the development or production of bacteria; slow bacterial growth but do not cause cell death—that is For immunocompromised patients: give them a bactericidal drug B/C bacteriostatic drug doesn’t kill the bacteria and their immunocompromised system won’t be strong enough to kill it!!

Kernicterus – bilirubin-induced brain dysfunction from accumulation of bilirubin in CNS tissues (jaundice) Gram (+) = 2 layers; cytoplasmic membrane has PBPs, Gram (-) = 3 layers; thin cell wall; outer layer difficult to penetrate Principle of ABX therapy: SELECTIVE TOXICITY – Toxic to microbes—Harmless (or less toxic) to host 7 Major Specific Mechanism of Actions (MOAs) for anti-infectives Inhibit.

CW synthesis or activate enzymes that disrupt the CW Penicillins, Cephalosporins, Amphotericin B, Itraconazole Increase cell wall permeability Amphotericin B Lethal inhibition of protein synthesis (bactericidal) Aminoglycosides Nonlethal inhibition of protein synthesis Tetracyclines, Erythromycins Inhibit DNA or RNA synthesis or disrupt DNA function Rifampin, Fluoroquinolones, Metronidazole Antimetabolites Sulfonamides & Trimethoprim Suppress viral replication Antivirals Acquired Resistance to Antimicrobial Drugs – Over time, organisms develop resistance.

May have been highly responsive and then became less susceptible to one or more drugs **Antibiotics must not be discontinued prematurely When conditions demand that nurses start therapy before lab data, samples of exudates and body fluids have to be obtained for culture BEFORE treatments ANTIBACTERIAL DRUGS Narrow Spectrum Broad Spectrum Gram (+) Cocci and Gram (+) Bacilli Gram (-) Aerobes Mycobacterium tuberculosis Gram (+) Cocci and Gram (-) Bacilli Penicillin G and V PCN-ase resistant penicillins (NODM) Vancomycin, Erythromycin, Clindamycin Aminoglycosides Cephalosporins (1st/2nd gen) Isoniazid Rifampin Ethambutol Pyrazinamide Broad-spectrum penicillins (AA).

Extended-spectrum penicillins Cephalosporins (3rd/4th gen), Tetracyclines, Carbapenems, Trimethoprim, Sulfonamides, Fluoroquinolones Drug Class Inhibitors of CW synthesis Drugs that disrupt the cell membrane Bactericidal inhibitors of protein synthesis Bacteriostatic inhibitors of protein synthesis Drugs that interfere with synthesis or integrity of bacteria DNA or RNA Antimetabolites (disrupt specific biochem rxns) Representative Antibiotic Penicillins Cephalosporins Carbapenem Vancomycin Telavancin Aztreonam Teicoplanin Fosfomycin Amphotericin B Daptomycin Azole drugs Aminoglycosides Tetracyclines Clindamycin Macrolides Chloramphenicol Linezolid Telithromycin.

Dalfopristin/Quinupristin Tigecycline Mupirocin Fluoroquinolones Metronidazole Rifampin Sulfonamides Trimethoprim Drug Class ANTI-INFLAMMATORIES BRONCHODILATORS ANTI-INFLAMMATORY / BRONCHODILATOR COMBINATION Glucocorticoids – Inhaled Glucocorticoids – Oral Leukotriene modifiers Cromolyn IgE Antagonist SABA, Inhaled LABA, Inhaled LABA, oral Methylxanthines Anticholinergic Representative Antibiotic Beclomethasone dipropionate Budesonide Fluticasone Mometasone furoate Prednisolone Prednisone Montelukast, oral Zafirlukast, oral Zileuton, oral Cromolyn, inhaled Omalizumah, subQ Albuterol Levalbuterol Pirbuterol Arformoterol Formoterol Indacaterol Salmeterol Albuterol.

Terbutaline Theophylline, oral Ipratropium, inhaled Tiotropium, inhaled Budesonide/formeterol, Fluticasone/Salmeterol, Mometasone/formeterol ANTIBIOTIC CLASS: PENICILLIN (PCN) > “-cillin” suffux Penicillin: Low toxicity Molecular structures has ? -lactam ring (cephalosporins, aztreonam, imipenem, meropenem & ertapenem have ? -lactam ring = same MOA) Method of Action (MOA): Weaken cell wall which causes cell wall to take up water & burst (osmotic lysis) = bactericidal (through activation of autolysins and inhibition of transpeptidases) Only effective against cells that are undergoing growth and division (vegetative) Most effective against gram(+) bacteria.

Works on g (-) in higher doses; Ampicillin able to cross outer membrane of g (-) bacteria. Adverse Effects: Diarrhea Renal failure or use of Probenecid = delays renal excretion = prolonging antibiotic effects 1-10% of people have allergic reaction (rash > anaphylaxis). Tell pt to report SIGNS. 5-10% will have a cross-sensitivity to cephalosporins and carbapenems Alternatives to PCN: Erythromycin, Clindamycin, or Vancomycin Resistance to PCN Occurs 2 Ways: Inability of PCN to reach their targets Inactivation of PCN by bacterial enzymes Production of penicillin-binding proteins (PBPs) that have a low affinity for penicillins Beta-Lactamases (enzymes).

Cleave beta-lactam rings; specific to PCN called “Penicillinase” G (-) produce PCNase in small amounts, but secrete them into the periplasmic space (more concentrated) G (+) produce PCNase in large amounts; goes into surrounding medium (^ scattered = v effective) Pharmacokinetics Renally excreted Sub-classes Individual Drugs Effective Against Route/Dosage Adverse Effects Additional Information Narrow-Spectrum PCN – PCNase sensitive Penicillin G Potassium, Procaine (IM), Benzathine (IM) Penicillin V Gram (+) bacteria Streptococcus species, anaerobes Potassium Pen G – IV Procaine/Benzathine Pen G – IM only PCN V – PO Distribution to most tissues/body fluids usually Distribution ^ during inflammation (blood flow ^) to CSF, joints, and eyes. Narrow-Spectrum PCN – PCNase resistant – Anti-staphylococcal Nafcillin Dicloxacillin Oxacillin Methicillin.

(no longer available) Staphylococcus aureus Staphylococcus epidermis Nafcillin – IV Dicloxacillin – PO Oxacillin- IV, PO Methicillin causes interstitial nephritis HIGHLY resistant to ? -lactamase MRSA resistant to PCN b/c ? -lactam ring is major reason for development/evolution of MRSA (Methicillin-Resistant Staphylococcus Aureus). Broad-spectrum PCN – Aminopenicillins -PCNase sensitive Ampicillin Amoxicillin Gram (-) bacteria: E. coli, H. influenzae, H. pylori, Salmonella, Shigella Ampicillin – PO, IV Amoxicillin – PO Rash & Diarrhea (most w/ Ampicillin) Suprainfection Active against some gram (-) bacteria Refrigerate oral suspensions Extended Spectrum PCN – Penicillinase sensitive – Anti-pseudomonals Ticarcillin Piperacillin E. coli Pseudomonas eruginosa Ticarcillin – IV.

Piperacillin – IV Disrupts PLT formation bleeding Ticarcillin: causes Na2+ overload. MONITOR pts w/ CHF At risk to ? -lactamases = ineffective to S. aureus Can be paired w/ Aminoglycoside to ^ toxicity against pseudomonas, but DO NOT mix w/ PCN in the same IV solution b/c it can inactivate AG PCN w/ ? -lactamase inhibitor Broad: Ampicillin/sulbactam (Unasyn) Amoxicillin/clavulanic acid (Augmentin) Extended: Ticarcillin/clavulanic acid (Timentin) Piperacillin/tazobactam (Zosyn) Combo w/ PCN Clavulanic acid ^risk for diarrhea, especially in children Nursing implications Interview patient for history of PCN allergy. NOTE: Skin test can lead to anaphylaxis.

MONITOR INTAKE AND OUTPUT FOR SIGNS OF KIDNEY DYSFUNCTION. Avoid toxic build-up of PCN. IV PCN used? Monitor patient for at least 30 minutes IM PCN? Aspirate to avoid injection into artery or peripheral nerves. Also, monitor for at least 30 minutes PO PCN? Take with full glass of water 1 hour before meals or 2 hours after meals (PCN V and Amoxicillin can be taken with meals) ALWAYS INFORM THEM TO FINISH COMPLETE COURSE OR ANTIBIOTICS ANTIBIOTIC CLASS: CEPHALOSPORIN > “ceph-” or “cef-” prefix Cephalosporin: Very similar to PCN b/c molecular structures are very similar Molecular structures also has ? -lactam ring = same MOA as PCN Method of Action (MOA):

Binds to PBPs; disrupts CW synthesis; causes CW lysis = bactericidal Only effective against cells that are undergoing growth and division (vegetative) Gram (-) activity ? -lactamase resistance CSF distribution 1st gen Low Low Poor 2nd gen Higher Higher Poor 3rd gen Higher Higher Good 4th gen highest Highest Good Pharmacokinetics Poor GI absorption; therefore many must be given parenterally Renally excreted except Ceftriaxone (liver) Adverse Effects: Well-tolerated; low toxicity Thrombophlebitis Hemolytic anemia Hypersensitivity reactions Drug Interactions: 5-10% will have a cross-sensitivity to penicillins (b/c similar molecular structure).

Probenecid – delays renal excretion = prolonging antibacterial effects Bleeding caused by: cefmetazole, cefoperazone, cefotetan, ceftriazone Alcohol reacts w/: cephazolin, cefmetazole, cefoperazone, cefotetan Ca2+ + Ceftriaxone for neonates= precipitant in lungs and kidneys Resistance to Cephalosporin: Cleave beta-lactam rings; specific to Cephalosporins called “Cephalosporinases” Gram (-) produce Cephalosporinases in small amounts, but secrete them into the periplasmic space (more concentrated) Gram (+) produce Cephalosporinases in large amounts and export it into the surrounding medium (more scattered so less effective) Sub-classes Individual Drugs Effective Against Route Additional Information First Generation – Cep-nase Sensitive (VERY) Cephalexin Cefazolin Staphylococci Streptococci PO, IM, IV.

Used most often b/c inexpensive, often just as effective as newer drugs, & narrow antimicrobial spectrum Second Generation – Cep-nase Sensitive Cefaclor Cefoxitin Cefuroxime Pneumonia: H. influenza Klebsiella & Pneumococci, Staph. PO, IM, IV Cefuroxime – the only one that can be given both IM & PO Cefotetan causes bleeding tendencies and alcohol intolerance (check PTT) Third Generation – Cep-nase Resistant (HIGHLY) Cefotaxime Ceftriaxone *liver excretion* Cefoperzone Cefditoren Meningitis & Pseudomanas aeruginosa PO, IM, IV Ceftriaxone + Ca2+: Only give through different IV lines & w/ 48 hours between the two Cefditoren – excreted w/ carnitine.

Don’t give to pts w/ carnitine deficiency Fourth Generation – Cep-nase Resistant (HIGHEST) Cefepime Meningitis & Pseudomanas aeruginosa PO, IM, IV Most activity against gram (-) Most resistance against ? -lactamases Deepest penetration into CSF Nursing Implications Monitor allergic reactions Cefditoren tablets contain milk-protein ? don’t give to patients w/ milk-protein allergy Check PTT before giving cefmetazole, cefoperazone, cefotetan, ceftriazone Alcohol interacts w/ cefazolin, cefmetazole, cefoperazone, and cefotetan. Warn patients not to take with alcohol Monitor for thrombophlebitis—rotate injection site, inject cephalosporins slowly & dilute solutions Monitor for C.diff infection – notify HCP if diarrhea occurs! If CDI is diagnosed, cephalosporin will be discontinued Advise patients to take with food, refrigerate oral suspensions.

ALWAYS INFORM THEM TO FINISH COMPLETE COURCE OR ANTIBIOTICS ANTIBIOTIC CLASS: CARBAPENEMS (used with Cephalosporins) > “-penem” suffix Carbapenems: Molecular structures has ? -lactam ring, but resistant to almost all ? -lactamases Extremely broad antimicrobial spectrum (more than almost any other drug), but low toxicity Has ability to penetrate gram(-) bacteria Method of Action (MOA): Binds to PBP1 & PBP2 weakening of wall, lysis & death = bactericidal Elimination: Primarily renal Adverse Effects:

Well tolerated; low toxicity Can have a cross-sensitivity to other ? -lactam antibiotics (b/c similar molecular structure) Interacts with Valproate – reduces blood level of valproate (necessary to control seizures) Individual Drugs Effective Against (+/-) Route Additional Information Imipenem (broadest) Gram(+) = High for cocci Gram(-) = High for most cocci & bacilli Anaerobes, Staphylococcus aureus, Pseudomanas aeruginosa IM, IV Dipeptidase inactivates Imipenem ? combine w/ an inhibitor (cilastine) Must be combined with other antibiotic (like Cephalosporins) when treating Pseudomanas aeruginosa Meropenem Gram(+) = High Gram(-) = High for aerobes & anaerobes.

Bacterial Meningitis (children must be >3 mos) IV Also used in complicated intra-abdominal infections in children & adults Skin infections Nosocomial infections where other antibiotics will not work Ertapenem Gram(+) = Less than others Most anaerobes IM, IV Is used for acute pelvic inflammation, UTI’s, skin & community-acquired pneumonia Doripenem Pseudomanas aeruginosa IV Complicated intra-abdominal infections and complicated UTIs Reserve for seriously ill people ANTIOBIOTIC CLASS: MONOBACTAM Method of Action ?-lactam antibiotic, but safe for pts w/ ? -lactam allergy Binds to PBP3 Sub-classes Individual Drugs Effective Against (+/-).

Route Adverse effects Narrow-Spectrum Aztreonam (Azactam) P.aeruginosa, Neisseria Gram(-) aerobic bacteria IV, IM, inhaled Similar to other ? -lactam antibiotics Individual Drug MoA Effective Against (+/-) Route Adverse effects Fosfomycin (single-dose therapy) Disrupts synthesis of peptidoglycan strands that composes cell wall UTI caused by E. coli and Enterococcus faecalis PO – water-soluble powder in packets Diarrhea, headache, vaginitis, nausea ANTIBIOTIC: VANCOMYCIN > “vanco-” prefix Vancomycin: No ? -lactam ring (can be used on patients allergic to PCN) Use for pts allergic to PCN and Cephalosporin (last resort b/c toxic! ) DOC for MRSA Use for severe infections only Method of Action (MOA): Binds to molecules that are precursors to cell wall synthesis.

This weakens cell wall which causes cell wall to take up water & burst (osmotic lysis) = bactericidal Only effective against gram(+) bacteria Elimination Renal elimination Adverse Effects – dose related: Red Man Syndrome (if IV too rapid) E. g. flushing, rash, pruritus, urticaria, tachycardia, hypotension Nephrotoxicity Ototoxicity (may be permanent if exceed 30mcg/mL) Thrombophlebitis (change infusion site & dilute) Individual Drugs Effective Against Route Pharmacokinetics Nursing Implications Additional Information Vancocin Vancoled Pseudomembranous colitis C. difficile S. aureus, & S. epidermidis MRSA PO, IV Slow IV over 60 min + Give PO only if infection in GI Intrathecal administration IV if meningeal infection Monitor serum drug levels (peak/trough).

Check blood drug levels 1. 5-2. 5 hours after infusion is complete (peak levels at 30-40 mcg/mL, trough 15-20 mcg/mL) Monitor serum Creatinine level (50% increase) Try Flagyl for C. difficile first. Only use Vanc if Flagyl fails. Telavancin Synthetic Vanc Gram(+) bacteria IV Adverse effects of Televancin: Taste disturbance, nausea, vomiting, foamy urine Prolong QT interval Red man syndrome (give slow IV) Kidney damage (measure function at baseline, every 72 hours during treatment, and at end of treatment) Teicoplanin (Targocid)

Similar structure & actions to Vanc MRSA C. difficile IV Additional Information of Teicoplanin: No Red Man Syndrome No ototoxicity ANTIBIOTIC CLASS: TETRACYCLINE > “-cycline” sufffix Tetracyclines: These are mostly 2nd line agents when infections resistant to 1st line agents (due to overuse and resistance factors) All are broad-spectrum; main differences are pharmacokinetics Method of Action (MOA): Inhibit bacterial growth & replication by inhibiting protein synthesis, but are only bacteriostatic Gram(+) and gram(-) Distribution: Poor distribution to CSF, so not effective against meningitis Crosses placenta & can enter fetal circulation, so try to avoid in pregnant women Adverse Effects: Renal toxicity.

Hepatotoxicity Phototoxicity GI: GI irritation: burning, cramps, N/V, diarrhea & cramps Bones/Teeth – bind to Ca+2 in developing teeth causing brown/yellow discoloration. Avoid in children under 8 y/o when tooth enamel is being formed. Suprainfection: Causes C. difficile severe diarrhea Also fungi in mouth pharynx, vagina & bowel (Candida albicans) stop tetracycline Sub-classes Individual Drugs Effective Against Route Elimination Short-acting – Low-lipid solubility Tetracycline Oxytetracycline H. pylori, Rickettsia, Spirochetes, Brucella, Chlamydia, Mycoplasm, Borrelia burgodorfer, Bacillus antracis, Vibrio cholerae, Lyme disease Acne vulgaris.

Peptic Ulcer Disease (PUD) (use in combo with metronidazole/flagyl) PO preferred, IV, IM Absorption reduced by food Renally eliminated. Do not give to pts. with renal failure (Renal toxicity in pts. with renal disease) Intermediate-acting – Moderate lipid solubility Demeclocycline PO Long-acting – High lipid solubility Doxycycline Minocycline PO, IV Absp NOT reduced by food Hepatically eliminated Therefore, can give to pts. with renal failure Nursing Implication: Should be taken on an empty stomach: give 2 hours before or 2 hours after chelating agents. Chelation canceling absorption of drug Council pts to avoid calcium (milk, antacids), iron, magnesium (laxatives), aluminum & zinc for 2 hours before/after taking Tetracyclines.

ANTIBIOTIC CLASS: MACROLIDES > “-mycin” suffix Macrolides: These are mostly 2nd line agents when infections resistant to 1st line agents (due to overuse and resistance factors) All are broad-spectrum; main differences are pharmacokinetics Use if allergic to PCN (same action, but not same molecular structure) Method of Action (MOA): Inhibition of protein synthesis, but are only bacteriostatic Works on most gram (+) and some gram (-) bacteria Distribution: Wildly distributed; poor CSF distribution Crosses placenta & can enter fetal circulation = avoid in pregnant women Elimination: Hepatically metabolized P450 Renally excreted Drug interactions:

Inhibits P450: ^ Theophylline (asthma), Warfarin (anti-coagulant), Carbamazepine (seizures/bipolar) Prevents binding of Chloramphenicol & Clindamycin to bacterial ribosomes Inhibit Erythromycin Metabolism by: Verapamil, Diltiazem, HIV protease inhibitors & “Azole” antifungals Adverse Effects: Generally very safe QT prolongation; small risk of sudden cardiac death Gastrointestinal suprainfection: pseudomembranous colitis Thrombophlebitis Transient hearing loss w/ high-doses Hypertrophic pyloric stenosis in infants < 2 wks Suprainfection: Causes C. difficile (severe diarrhea) a. k. a. antibiotic-associated pseudomembranous colitis (give Metronidazole/Flagyl or Vancomycin) Individual Drugs Effective Against Route Additional Info.

Erythromycin Respiratory tract infections, acute otitis media, GI infections Bordetella pertussis (Whooping cough), acute diphtheria, Legionella pneumophila, chlamydial infections, M. pneuonia, Streptococcus pneumoniae & Streptococcus pyogenes Mycobacterium avium complex (MAC) infections in pts. with advance HIV infection PO, IV NOTE: Take with food Azithromycin (Doesn’t inhibit metabolism of other drugs) PO, IV Clarithomycin Additionally: H. pylori PO NOTE: ER tabs – take with food Additional adverse reaction: Metallic taste ANTIBIOTIC CLASS: LINCOSAMIDE > “-mycin” suffix (NOT a Macrolide) Lincosamide: Use if allergic to PCN (same action, but not same molecular structure) Only indicated for certain anaerobic infections located outside the CNS Method of Action (MOA):

Inhibiting protein synthesis = bacteriostatic (can be bactericidal against susceptible organisms or in high concentration) Drug interactions: Overlap binding sites with Erythromycin & Chloramphenicol Adverse Effects: Hypersensitive reactions frequent rashes Rapid IV can cause electrocardiographic changes Suprainfection: Causes C. difficile severe diarrhea; can develop during 1st week of treatment but may develop 4-6 weeks after treatment ends. Can be fatal! Individual Drug Effective Against Route Elimination Additional Information Clindamycin (Cleocin) Anaerobic gram(+/-) & most gram(+) aerobes Streptococcal infections Gas gangrene Clostridium perfringens).

Abdominal & pelvic infx Bacteroides fragilis IV, IM, PO, Vaginal suppositories NOTE: Good GI absorption, can take with food Hepatically metabolized Renally eliminated) ? life = 3 hours Reduce in dose in pts w/ liver and kidney problems NEW CLASSES OF ANTIBIOTICS – also inhibit bacterial protein synthesis Individual Drugs Method of Action Effective Against Adverse effects Drug interactions Additional Uses Linezolid (Zyvox) Class: Oxazolidinones Binds to 23S part of 50S ribosome subunit (only ABX that does this) Cross-resistance with other agents unlikely Multi-drug resistant gram(+) pathogens Reserved for infections caused by VRE and MRSA Diarrhea, N/V, HA May cause myelosuppression (anemia, leukopenia, thrombocytopenia pancytopenia) NI:

Monitor CBCs weekly Interacts with MAOIs – causes severe HTN if combined with ephedrine, pseudoephedrine, cocaine, or foods with tyramine Interacts with SSRIs – risk of serotonin syndrome Nosocomial pneumonia caused by S. Aureus CAP – S. pneumoniae Complicated skin and skin structure infection by S. aureus Telithromycin (Ketek) Class: Ketolide Close relative to macrolides Streptococcus