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222 Cards in this Set
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What is inflammation?
What is the central purpose of inflammation? How long is needed for symptoms to resolve & repair to begin? |
One of the body’s defense mechanisms
Central purpose: contain the injury or destroy the microorganism 8-10 days are normally needed for symptoms to resolve and repair to begin |
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What is the goal of pharmacotherapy for inflammation?
Why is it okay that anti-inflammatories are nonspecific? Give an example of one that is specific. |
Most anti-inflammatories are nonspecific; whether the cause is injury, autoimmune disease or allergy, drugs exhibit the same inhibitory actions
Some are specific (e.g., gout drugs) |
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What is the key mediator of inflammation?
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Histamine is the key mediator of inflammation
Primarily responsible for seasonal allergy symptoms |
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Describe the inflammatory response.
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Mast cells detect foreign agents --> inflammatory response
Histamine dilates blood vessels causing increased capillary permeability Plasma, complement proteins and phagocytes then enter the area to neutralize foreign invaders |
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What is anaphylaxis?
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rapid release of chemical mediators
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What is the role of H1 receptors?
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H1 receptors are present in smooth muscle, the bronchial tree and digestive tract --> itching, pain, vasodilation, edema, bronchoconstriction, etc.
H1 receptors contribute to s/s of inflammation |
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What are the five chemical mediators of inflammation?
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Bradykinin
Compliment Histamine Leukotrienes Prostaglandins |
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What is Bradykinin & where is it located?
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Found inactive in plasma and mast cells
Vasodilator that causes pain with similar effects as histamine |
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What is Compliment?
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Group of at least 20 proteins that combine to destroy an antigen
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What is Histamine & where is it located?
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Stored and released by mast cell
causes smooth muscle contraction, dilation of blood vessels, tissue swelling and itching |
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What are Leukotrienes & where are they located?
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Stored and related by mast cells; similar effects as histamine
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What are Prostaglandines & where are they located?
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Present in most tissues; stored & released by mast cells
Increase capillary permeability & attracts WBCs to site of inflammation; cause pain. |
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NSAIDS
What properties? What is difference among NSAIDs? Why shouldn’t ASA be used for children? Is Acetaminophen an NSAID? |
Analgesic, antipyretic and anti-inflammatory properties
DOC for the treatment of mild/moderate inflammation All have the same efficacy SE differ among NSAID drugs Do not use ASA in children = Reye’s syndrome risk Acetaminophen: has no anti-inflammatory properties; not classified as an NSAID |
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How do NSAIDs work?
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NSAIDS act by inhibiting the synthesis of prostaglandins (lipids found in all tissues)
NSAIDS block inflammation by inhibiting cyclooxygenase (COX), the key enzyme in the biosynthesis of prostaglandins |
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What is COX-1?
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present in all tissues for protective functions such as reducing gastric acid secretion, promoting renal blood flow and regulating smooth muscle tone in blood vessels and the bronchial tree
COX-1 effects include bleeding, GI upset and reduced kidney function |
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What is COX-2?
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present only after tissue injury and serves to promote inflammation
Inhibition of COX-2 produces analgesic, anti-inflammatory and anti-pyretic effects with minimal SE Celecoxib (Celebrex): sole COX-2 inhibitor for moderate/severe inflammatory indications |
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First Generation NSAIDS
Aspirin |
Aspirin binds to both COX-1 and COX-2 enzymes, preventing them from forming inflammatory prostaglandins
Bleeding (GI) is a potential major problem |
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First Generation NSAIDs
Ibuprofen (Motrin, Advil) |
Work by inhibiting prostaglandins & cyclooxygenase (COX).
Developed as aspirin alternatives, Less side effects. Most NSAID selection is due to cost or availability Only 3 NSAIDs are over-the-counter: ASA Ibuprofen (Motrin; Advil) Naproxen (Aleve) |
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Glucocorticoids for Inflammation
Agents? |
Betamethasone (Celestone, Betacort, others)
Cortisone (Cortistan, Cortone) Dexamethasone (Decadron, others) Hydrocortisone (Cortef, others) Methylprednisolone (Depo-Medrol, Medrol, others) Prednisolone (Delta-Cortef, Hydeltrasol, Key-Pred, others) Prednisone (Meticorten, others) Triamcinolone (Aristocort, Atolone, Kenacort, Kenalog) |
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Glucocorticoids for Inflammation
MOA? |
Steroids are released by the adrenal cortex.
Inhibit the biosynthesis of prostaglandins Suppress histamine release and inhibit phagocytosis and lymphocytosis --> reducing inflammation |
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Glucocorticoids for Inflammation
Adverse Effects? |
Suppress adrenal glands (insufficiency), hyperglycemia, mood changes, cataracts, gastritis, electrolyte imbalances, osteoporosis; may mask infections
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Causes of Drug Fever?
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Anti-infectives: Especially those derived from microorganisms such as Amphotericin B or PCN G
SSRIs: Paroxetine (Paxil) may cause serotonin syndrome. Conventional Anti-psychotics: Chlorpromazine (Thorazine) may cause neuroleptic malignant syndrome Anesthetics and depolarizing neuromuscular blockers: Succinylcholine may cause malignant hyperthermia |
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More Causes of Drug Fever?
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Immune modulators: Interferon and monoclonal antibodies (muromonab-CD3) may cause a flu-like syndrome from producing cytokines
Cytotoxic cancer agents Neutropenic agents: NSAIDs, anti-thyroid drugs, anti-psychotics may cause neutropenia and subsequent fever Anaphylaxis to any agent |
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DOC for drug fever?
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IV fluids, antipyretics do not help.
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What is a pathogen?
What are some examples? How can a pathogen infect humans? What are some ways a pathogen can bypass the body defenses? |
An organism capable of causing disease
Viruses, bacteria, fungi, unicellular organisms, etc. To infect humans, pathogens must bypass a number of elaborate body defenses. Entrance may include broken skin, ingestion, inhalation or contact with mucous membranes such as nasal, urinary or vaginal mucosa |
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What is pathogenicity?
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The ability of an organism to cause infection.
Only a few dozen pathogens cause disease in humans |
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What is virulence?
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A highly virulent microbe is one that can produce disease when present in minute numbers
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Pathogens cause disease by what two basic mechanisms?
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1. Sheer numbers – grow quickly
2. Production of toxins |
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What are the three ways to describe/classify bacteria?
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Gram staining
Cellular shape Ability to use oxygen |
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What are Gram positive bacteria? Give three examples.
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Bacteria with a thick cell wall retain a purple color after staining.
Staphylococcus Streptococci Enterococci |
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What are Gram negative bacteria? Give five examples?
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Bacteria with thinner cell walls will lose the violet stain.
Bacteroides Escherichia coli Klebsiella Pseudomonas Salmonella |
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Describe the three classifications of bacteria by cellular shape.
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Bacilli – rod shaped
Cocci – spherical shaped Spirilla – spiral shaped |
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Describe the two classifications of bacteria by ability to use oxygen.
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Aerobic – bacteria that thrive on an oxygen-rich environment
Anaerobic – those that thrive best without oxygen |
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What is the difference between bactericidal & bacteriostatic agents?
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Bactericidal agents: kill bacteria
Bacteriostatic agents: slow the growth of bacteria. When treating infection, don’t be concerned about bactericidal vs bacteriostatic. Be more concerned about the drug specific for that bug. |
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In what three ways are bacterial cells different from human cells?
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Bacteria have cell walls
Use different biochemical pathways Contain certain enzymes that human cells lack |
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How do these differences help with killing off bacteria?
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Antibiotics exert selective toxicity on bacterial cells by targeting these differences
Thus, bacteria can either be killed or their growth severely hampered without major effects on human cells |
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What are mutations?
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Microorganisms have the ability to replicate rapidly
During cell division, bacteria make frequent errors in duplicating their genetic code (mutations) Mutations occur spontaneously and randomly throughout the ribosomal chromosome |
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What affect do these mutations have on drug resistance?
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Although most mutations are harmful to the organism, mutations occasionally result in a bacterial cell that has reproductive advantages over its neighbors.
The mutated bacterium may be able to survive in harsher conditions or perhaps grow faster than other cells Mutations that are of particular importance to medicine are those that confer drug resistance to a microorganism |
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How do antibiotics help promote the development of drug-resistant bacterial strains?
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Killing populations of bacteria that are sensitive to the drug leaves behind those microbes that possess mutations that made them insensitive to the effects of the antibiotic
These drug-resistant bacteria are then free to grow, unrestrained by their neighbors that were killed by the antibiotic, and the patient develops an infection that is resistant to conventional drug therapy = acquired resistance |
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How do bacteria pass the resistance gene to other bacteria?
What created the mutation that caused bacteria to become resistant? |
Bacteria may pass the resistance gene to other bacteria through conjugation, the transfer of small pieces of circular DNA called plasmids.
It is important to understand that the antibiotic did not create the mutation that caused bacteria to become resistant. The bacteria become resistant, not the patient. |
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What can we do to keep antibiotics efficacious? (6)
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Prudent use of antibiotics is critical to future antibiotic efficacy.
Does my patient still need antibiotics? Have I chosen the most narrow agent? – broad, then use specific after C&S What is the duration of therapy? – Autostop dates (except HIV pts) Can we switch to a PO antibiotic? – can D/C pts home, less exposure Get help from the experts (infections disease MD/NP). WASH YOUR HANDS |
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What is the general approach to managing infections?
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Establish Presence of Infection
Establish Severity of Infection Establish Site of Infection Determine Likely Pathogen |
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What are the s/s of infection?
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Signs and symptoms: increased WBC, fever, infiltrates on chest x-ray, erythema, pus, secretions
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What are the considerations for the severity of infection?
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Age of patient, immune status, comorbidities
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What are examples of sites of infection?
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Respiratory, skin, blood, IV line, urine
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What are considerations for the determination of likely pathogen?
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Based on site and/or patient factors
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What is the difference between broad-spectrum & narrow-spectrum antibiotics?
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Broad-spectrum antibiotics: antibacterials effective against many different species of pathogens
Narrow-spectrum antibiotics: antibacterials effective against only one or a restricted group of microorganisms |
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Optimally, laboratory tests should identify the specific pathogen prior to initiating anti-infective therapy.
What samples are used to determine pathogens? |
Urine, stool, blood, spinal fluid, sputum, purulent drainage, etc.
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What is culture and sensitivity?
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The process of growing the pathogen and identifying the most effective antibiotic to treat
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Natural Penicillins
Agents? |
Penicillin G, Penicillin V (Pen V, Pen-VK)
Used infrequently due to resistance; erythromycin is alternative. |
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Natural Penicillins
MOA |
binds to receptors (penicillin-binding proteins) on the bacteria’s cell wall which results in cell lysis
Should be given 1-2 hours before or after meals. |
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Natural Penicillins
Spectrum? |
against gram positive, less active against gram negative
Streptococcal, meningococcal infections & neurosyphillis. Mainly used for Neiseria & syphilis |
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Natural Penicillins
Adverse Effects? |
hypersensitivity reactions, rash, phlebitis, diarrhea, GI upset, sodium/potassium overload, renal dysfunction, C. difficile, seizures, fever, thrombocytopenia
Anaphylaxis in 0.04% to 2% |
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Antistaphylococcal Penincillins
Agents? |
nafcillin (Nafcil)
dicloxacillin (Dynapen) oxacillin Empirical use has decreased due to resistance |
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Antistaphylococcal Penincillins
MOA? |
binds to receptors (penicillin-binding proteins) on the bacteria’s cell wall which results in cell lysis
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Antistaphylococcal Penincillins
Spectrum? |
beta-lactamase producing Staph (usually limited to treatment of these bacteria); less active than natural penicillins against gram positive bacteria
limited spectrum, DOC for MSSA infections, bacteremia, endocarditis. More effective than broad spectrum |
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Antistaphylococcal Penincillins
Adverse Effects? |
hypersensitivity reactions, rash, phlebitis, diarrhea, GI upset, sodium/potassium overload, renal dysfunction, C. difficile, seizures, fever, thrombocytopenia
Anaphylaxis: 0.04% to 2% |
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Amino-Penicillins
Agents? |
amoxicillin (Amoxil, Trimox)
ampicillin (Principen) |
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Amino-Penicillins
MOA? |
binds to receptors (penicillin-binding proteins) on the bacteria’s cell wall which results in cell lysis (bacteriocidal)
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Amino-Penicillins
Spectrum? |
active against many gram negative rods and have the same activity as natural penicillins against gram positive bacteria
Ampicillin: enterococcus infections, alternative for VRE Amoxicillin: CAP, UTI, sinusitis, otitis, safe in pregnancy |
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Amino-Penicillins
Adverse Effects? |
hypersensitivity reactions, rash, phlebitis, diarrhea, GI upset, sodium/potassium overload, renal dysfunction, C. difficile, seizures, fever, thrombocytopenia
Anaphylaxis: 0.04% to 2% Adjust dose in renal impairment |
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PCN with Beta-lactamase Inhibitor
Agents? |
amoxicillin/clavulanic Acid (Augmentin),
ampicillin/sulbactam (Unasyn) piperacillin/ tazobactam (Zosyn), ticarcillin/clavulanic acid (Timentin) |
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PCN with Beta-lactamase Inhibitor
MOA? |
binds to receptors (penicillin-binding proteins) on the bacteria’s cell wall which results in cell lysis
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PCN with Beta-lactamase Inhibitor
Spectrum? |
extended-spectrum; active against anaerobes in addition to gram negative and gram positive bacteria
Broad: not use 1st line in comm acquired Pip/tazo: diabetic foot infection, HAP Amp/sulb: animal/human bites, pyelonephritis |
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PCN with Beta-lactamase Inhibitor
Adverse Effects? |
hypersensitivity reactions, rash, phlebitis, diarrhea, GI upset, sodium/potassium overload, renal dysfunction, C. difficile, seizures, fever, thrombocytopenia
Anaphylaxis: 0.04% to 2% |
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Anti-Pseudomonal Penicillins
Agents? |
piperacillin (Pipracil)
ticarcillin (Ticar) Piperacillin: on drug shortage list |
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Anti-Pseudomonal Penicillins
MOA? |
binds to receptors (penicillin-binding proteins) on the bacteria’s cell wall which results in cell lysis
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Anti-Pseudomonal Penicillins
Spectrum? |
Active against anaerobes, some gram positive, gram negative as well as Pseudomonas
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Anti-Pseudomonal Penicillins
Adverse Effects? |
hypersensitivity reactions, rash, phlebitis, diarrhea, GI upset, sodium/potassium overload, renal dysfunction, C. difficile, seizures, fever, thrombocytopenia
Anaphylaxis: 0.04% to 2% Adjust dose for renal impairment |
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PCN Patient Teaching
If allergic? Full course? |
Wear medical alert bracelet if allergic to PCN
Complete the full course of treatment |
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PCN Patient Teaching
Which three PCNs to take w/meals? When do you take all other PCNs? Why not take w/acidic fruit juice? |
Take PCN V, amoxicillin and amoxicillin-clavulanate with meals to decrease GI distress
Take all other PCNs with a full glass of water, one hour before or 2 hours after meals to increase absorption Take oral PCN with water because acidic fruit juice can inactivate antibacterial activity |
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First-generation Cephalosporins
Agents? |
cefazolin (Ancef),
cephalexin (Keflex), cefadroxil (Duricef) |
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First-generation Cephalosporins
MOA? |
binds to receptors (penicillin-binding proteins) on the bacteria’s cell wall which results in cell lysis
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First-generation Cephalosporins
Spectrum? |
very active against gram positive cocci, inactive against enterococci and MRSA; limited activity against gram negative (E. coli, Klebsiella, & Proteus)
DOC for antibiotic prophylaxis, cellulitis Used in Community Acquired Infections Not for CNS infections |
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First-generation Cephalosporins
Adverse Effects? |
Phlebitis, diarrhea, allergic reactions, rash, C. difficile, seizures, fever, thrombocytopenia
Cross-reactivity with PCN allergy: 10% Adjust dose for renal impairment |
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Second-generation Cephalosporins
Agents? |
cefuroxime (Zinacef, Ceftin),
cefoxitin (Mefoxin), cefotetan (Cefotan), cefaclor (Ceclor), cefprozil (Cefzil), loracarbef (Lorabid) |
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Second-generation Cephalosporins
MOA? |
binds to receptors (penicillin-binding proteins) on the bacteria’s cell wall which results in cell lysis
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Second-generation Cephalosporins
Spectrum? |
have extended gram negative coverage and some anaerobic coverage; less coverage against gram positive organisms than first generation
DOC for antibiotic prophylaxis (GI procedures), CAP, abdominal and pelvic infections Not for CNS infections |
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Second-generation Cephalosporins
Adverse Effects? |
phlebitis, diarrhea, allergic reactions, rash, C. difficile, seizures, fever, thrombocytopenia, disulfiram reaction (cefotetan)
Cross-reactivity with PCN allergy: 10% |
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Third-generation Cephalosporins
Agents? |
cefotaxime (Claforan),
ceftriaxone (Rocephin), ceftazidime (Fortaz), cefpodoxime (Vantin), cefixime (Suprax), cefdinir (Omnicef) |
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Third-generation Cephalosporins
MOA? |
binds to receptors (penicillin-binding proteins) on the bacteria’s cell wall which results in cell lysis
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Third-generation Cephalosporins
Spectrum? |
most of these agents are active against gram positive but less than the first generation cephalosporins; major advantage is their expanded gram negative coverage
DOC for CAP, UTI, meningitis, endocarditis (excellent CNS penetration) |
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Third-generation Cephalosporins
Adverse Effects? |
phlebitis, diarrhea, allergic reactions, rash, C. difficile, seizures, fever, thrombocytopenia
Cross-reactivity with PCN allergy: 10% Ceftazidime effective vs. Pseudomonal infections |
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Fourth-generation Cephalosporins
Agents? |
cefepime (Maxipime)
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Fourth-generation Cephalosporins
MOA? |
binds to receptors (penicillin-binding proteins) on the bacteria’s cell wall which results in cell lysis
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Fourth-generation Cephalosporins
Spectrum? |
broad spectrum; active against gram positive and gram negative including pseudomonas, but weak against anaerobes
DOC for HAP, neutropenic fever, hospital acquired UTI |
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Fourth-generation Cephalosporins
Adverse Effects? |
phlebitis, diarrhea, allergic reactions, rash, C. difficile, seizures, fever, thrombocytopenia
Cross-reactivity with PCN allergy: 10% Adjust dose for renal impairment |
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Fifth-generation Cephalosporins
Agents? |
ceftaroline (Teflaro)
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Fifth-generation Cephalosporins
MOA? |
binds to receptors (penicillin-binding proteins) on the bacteria’s cell wall which results in cell lysis
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Fifth-generation Cephalosporins
Spectrum? |
broad spectrum; active against gram positive and gram negative bacteria
DOC for HAP, neutropenic fever Can be used for CAP, skin/soft tissue infections Role in therapy still to be defined |
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Fifth-generation Cephalosporins
Adverse Effects? |
phlebitis, diarrhea, allergic reactions, rash, C. difficile, seizures, fever, thrombocytopenia
Cross-reactivity with PCN allergy: 10% Adjust dose for renal impairment |
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Monobactams
Agents? |
aztreonam (Azactam)
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Monobactams
MOA? |
binds to receptors (penicillin-binding proteins) on the bacteria’s cell wall which results in cell lysis
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Monobactams
Spectrum? |
narrow spectrum; resistant to beta-lactamase producing organisms and are only active against gram negative organisms
No activity against gram positive or anaerobic organisms – not for pseudomonal coverage. Primarily used as an alternative for PCN allergic patients |
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Monobactams
Adverse Effects? |
phlebitis, rash, diarrhea, nausea, abnormal LFT’s
NO cross-reactivity with PCN allergy Adjust dose for renal impairment |
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Carbapenems
Agents? |
imipenem (Primaxin),
meropenem (Merrem), doripenem (Doribax), ertapenem (Invanz) |
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Carbapenems
MOA? |
binds to receptors (penicillin-binding proteins) on the bacteria’s cell wall which results in cell lysis
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Carbapenems
Spectrum? |
extended spectrum antibiotic: gram negative, gram positive and anaerobic coverage
Not active vs. MRSA, VRE, atypical pathogens or Stenotrophomonas Ertapenem does NOT cover Pseudomonas or C. diff, but does still cover ESBL Should NOT be used routinely |
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Carbapenems
Adverse Effects? |
hypersensitivity reactions, rash, phlebitis, renal dysfunction, C. difficile, seizures, fever, thrombocytopenia
Cross-reactivity with PCN allergy: thought to be fairly high (up to 40%) – Don’t use first line! |
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Macrolides
Agents? |
erythromycin,
azithromycin (Zithromax), clarithromycin (Biaxin) |
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Macrolides
MOA? |
inhibit protein synthesis by reversibly binding to the 50S ribosomal subunit of the bacteria resulting in cell death
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Macrolides
Spectrum? |
limited gram positive activity, little gram negative activity, active against Chlamydia and Mycoplasma
DOC for atypical PNA coverage Azithromycin: MAC prophylaxis & treatment, chlamydial infections, PNA (5 day Tx w/ Z-pack) |
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Macrolides
Adverse Effects? |
GI intolerance: diarrhea, nausea, metallic taste (possibly less with azithromycin & clarithromycin), cholestatic hepatitis, rash
Many drug-drug interactions (erythromycin) |
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Telithromycin (Ketek)
MOA? |
similar to that of macrolides, and is related to 50S ribosomal subunit binding with inhibition of bacterial protein synthesis
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Telithromycin (Ketek)
Spectrum? |
similar to macrolides, with additional activity against multi-resistant S. pneumoniae (including erythromycin-resistant and penicillin-resistant strains), methicillin-resistant Staphylococcus aureus, H. influenzae, and enterococci
FDA removed all labeled indications except CAP due to adverse effect profile |
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Telithromycin (Ketek)
Adverse Effects? |
diarrhea, nausea, vomiting, dizziness, headache, abnormal vision, blurred vision, prolonged Q-Tc interval, Torsade's de pointes, hepatotoxicity
Many drug-drug interactions Adjust dose for renal impairment |
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Tetracyclines
Agents? |
tetracycline,
doxycycline (Vibramycin), minocycline (Minocin) |
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Tetracyclines
MOA? |
inhibits protein synthesis of bacteria (does not produce cell death, but halts cell reproduction)
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Tetracyclines
Spectrum? |
active against gram positive and gram negative as well as anaerobes, mycoplasma, rickettsia, chlamydia
DOC for atypical PNA coverage, acne Due to the emergence of resistance these agents have lost some of their usefulness NOT for CNS infections |
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Tetracyclines
Adverse Effects? |
GI intolerance, stains and deforms teeth in children, vertigo, affects bone growth, phlebitis, photosensitivity, hepatotoxicity
Many drug-drug & drug-food (Ca, Fe) interactions Not for pregnant women or children |
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Why are tetracyclines contraindicated in children < or = 8 years of age?
Why are tetracylcines classified as pregnancy category D? |
Contraindicated in children < 8 years of age --> yellow-brown discoloration of the teeth
Pregnancy category D --> effect linear skeletal growth of the fetus and child |
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Tetracyclines & oral contraceptives?
Expiration dates? Risk of Candida? |
Decrease the effectiveness of oral contraceptives
Toxic effects may occur if taken past the expiration date (do not save medication) May increase the risk of oral/perineal Candida |
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Issues with Tetracycline & milk, antacids, & lipid lowering drugs?
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Do not take with milk products, Fe supplements, Mg containing laxatives or antacids
Wait 1-3 hours before taking antacids; Wait at least 2 hours before taking lipid-lowering drugs such as colestipol (Colestid) and cholestyramine (Questran) |
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Aminoglycosides
Agents? |
gentamicin (Garamycin),
tobramycin (Nebcin), amikacin (Amikin), colistimethate (Colistin) – older agent revived d/t resistance streptomycin |
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Aminoglycosides
MOA? |
inhibits protein synthesis (irreversibly binds to 30S ribosomes) resulting in cell death
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Aminoglycosides
Spectrum? |
active against gram negative organisms; given in combination with beta-lactam for gram positive synergy (never use alone for the treatment of gram positive infections)
Not used regularly, but can be effective if dosed properly |
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Aminoglycosides
Adverse Effects? |
nephrotoxicity, ototoxicity, neuromuscular blockade, muscle weakness
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Aminoglycosides
Dosing issues? |
Dose adjusted to achieve therapeutic peak and trough. Draw as close as possible before & after dose
Primarily administered IV or IM Nebulized therapy: tobramycin, amikacin, Colistin 1st dose massive (7mg/kg), then Q24, then Q36. Tradition dose Q8 round the clock |
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Sulfonamides
Agents? |
trimethoprim (Trimpex),
trimethoprim/sulfamethoxazole (Bactrim, Septra) Most common: Bactrim, used when pt goes home |
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Sulfonamides
MOA? |
inhibits the conversion of dihydrofolic acid in the bacteria halting reproduction
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Sulfonamides
Spectrum? |
inhibits gram positive and gram negative organisms; active against toxoplasma and PCP
Primary use: UTI, MRSA skin infections, DOC for PCP treatment and prophylaxis |
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Sulfonamides
Adverse Effects? |
pruritus, photosensitivity, GI intolerance, renal failure, hyperkalemia, bone marrow suppression, Steven Johnsons Syndrome
Combination of trimethoprim and sulfamethoxazole results in bacteria cell death Adjust dose for renal impairment |
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Fluoroquinolones
Agents? |
ciprofloxacin (Cipro),
levofloxacin (Levaquin), norfloxacin (Noroxin) – spontaneous bacterial peritonitis prophylaxis ofloxacin (Floxin) Newer Agents: moxifloxacin (Avelox), gemifloxacin (Factive) |
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Fluoroquinolones
MOA? |
inhibits bacterial DNA resulting in cell death in susceptible organisms
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Fluoroquinolones
Spectrum? |
active against gram negative but less active against gram positive; newer agents have enhanced activity against gram positive and anaerobic organisms
NOT recommended for patients < 18 years of age Resistance rates are rising!! (>65%) |
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Fluoroquinolones
Adverse Effects? |
GI intolerance, headache, dizziness, diarrhea, photosensitivity, insomnia, Q-Tc prolongation, damage growing cartilage, tendonitis
Adjust dose for renal impairment Avoid in pregnancy Do not use w/anti-arrhythmic! |
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Clindamycin (Cleocin)
MOA? |
inhibits protein synthesis (50S ribosomal subunit) halting bacterial reproduction
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Clindamycin (Cleocin)
Spectrum? |
active against gram positive and anaerobic organisms only
Alternative for PCN allergic patients Can be used for PNA & MRSA (confirm with susceptibility) Surgical prophylaxis for PCN allergic patients |
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Clindamycin (Cleocin)
Adverse Effects? |
diarrhea (C. difficile) w/prolonged use, rash, phlebitis, blood dyscrasias, nausea, vomiting, diarrhea, dyspepsia
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Metronidazole (Flagyl)
MOA? |
causes the formation of toxic metabolites within the bacterial cell resulting in cell death
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Metronidazole (Flagyl)
Spectrum? |
active against gram negative anaerobic organisms only
Primary uses: anaerobic infections (abscess), aspiration PNA, intra-abdominal infections, vaginitis (trichomonas infection, bacterial vaginosis), infectious diarrhea DOC for C. difficile |
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Metronidazole (Flagyl)
Adverse Effects? |
GI intolerance, metallic taste, headache, peripheral neuropathy, phlebitis, taste disturbances, disulfiram-like reaction w/ EtOH (even 24-48 hrs after d/c)
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Vancomycin (Vancocin)
MOA? |
inhibits bacterial cell wall synthesis resulting in cell death
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Vancomycin (Vancocin)
Spectrum? |
active against gram positive organisms. No activity against gram negative or anaerobes
DOC for MRSA, VAP Alternative for surgical prophylaxis in PCN allergic patients Oral vancomycin for refractory C. difficile colitis |
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Vancomycin (Vancocin)
Adverse Effects? |
phlebitis at injection site, “red-man syndrome”, fever, nephrotoxicity, rash
Dose adjusted to achieve therapeutic trough Adjust dose for renal impairment |
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Quinupristin/Dalfopristin (Synercid)
MOA? |
synergistic combination that irreversibly binds to separate sites on the bacteria to inhibit protein synthesis
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Quinupristin/Dalfopristin (Synercid)
Spectrum? |
active against gram positive organisms, NOT active against E. faecalis
Drug of last resort! Primary use: VRE, VRSA, alternative to vancomycin for MRSA |
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Quinupristin/Dalfopristin (Synercid)
Adverse Effects? |
phlebitis, arthralgias/myalgias, hyperbilirubinemia, nausea, diarrhea, rash
Resistance can occur during treatment Several drug-drug interactions Reduce dose in hepatic impairment Incompatible with saline solutions |
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Linezolid (Zyvox)
MOA? |
inhibition of bacterial protein synthesis. Inhibition of protein synthesis occurs at a very early stage resulting in a lack of cross-resistance with existing antimicrobials
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Linezolid (Zyvox)
Spectrum? |
active against gram positive organisms
Should not be used routinely! Primary use: VRE, VRSA, alternative to vancomycin for MRSA |
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Linezolid (Zyvox)
Adverse Effects? |
N/V/D, headache, dizziness, insomnia, rash, thrombocytopenia, myelosuppression (anemia, leukopenia, pancytopenia, and thrombocytopenia)
Many drug-drug interactions No dosage adjustment for hepatic or renal impairment |
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Daptomycin (Cubicin)
MOA? |
binds to bacterial cell membranes and causes cell death by inducing depolarization of the membrane potential, leading to disruption of DNA, RNA and protein synthesis
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Daptomycin (Cubicin)
Spectrum? |
active against gram positive organisms; no gram negative activity
Should not be used routinely! Should NOT be used for pulmonary infections Primarily used for vancomycin resistant infections (VRE, VRSA) |
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Daptomycin (Cubicin)
Adverse Effects? |
diarrhea, vomiting, pain in throat, rhabdomyolysis, renal failure, myopathy, asthmatic pulmonary eosinophilia
Adjust dose for renal impairment |
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Tigecycline (Tygacil)
MOA? |
binds to the 30s subunit on the ribosome and interferes with bacterial synthesis (bacteriostatic) glycylcycline, is a derivative of minocycline (tetracyclines)
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Tigecycline (Tygacil)
Spectrum? |
broad spectrum: active against gram positive, gram negative, anaerobes and atypical organisms
Should not be used routinely! NO activity against Pseudomonas or Proteus Primarily used for multi-drug-resistant infections (MDR) infections |
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Tigecycline (Tygacil)
Adverse Effects? |
abdominal pain, diarrhea, nausea, vomiting, headache, pancreatitis, elevated LFT’s, anaphylaxis
Adjust dose for hepatic impairment |
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Urinary Antiseptics: nitrofurantoin (Macrodantin, MacroBid)
MOA? |
Inactivates/alters bacterial ribosomal proteins and other macromolecules inhibiting the syntheses of bacterial DNA, RNA, cell wall and protein
Exert antimicrobial activity in the urine but have little or no systemic antibacterial effect |
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Urinary Antiseptics: nitrofurantoin (Macrodantin, MacroBid)
Spectrum? |
active against the common gram positive urinary pathogens and has moderate activity against gram negative pathogens
Limited to therapy and prevention of uncomplicated UTI’s |
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Urinary Antiseptics: nitrofurantoin (Macrodantin, MacroBid)
Adverse Effects? |
GI intolerance, rash, peripheral neuropathy
Contraindicated in renal impairment Overused in elderly leading to CNS effects |
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What is the organism that causes TB?
What organs are effected by TB? How does the immune system respond? |
Mycobacterium tuberculosis
Typically invades the lungs, but may travel to any body system, particularly bone, via the blood or the lymphatic system The body activates the immune system and attempts to isolate the pathogens by creating a wall around them |
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What are tubercules?
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Slow-growing mycobacteria usually become dormant, existing inside cavities called tubercles
May remain dormant (even during an entire lifetime) or reactivate |
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What are two other types of human mycobacteria?
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Mycobacterium leprae – responsible for leprosy
Mycobacterium avium complex (MAC) – infection in the lungs, commonly observed in AIDS patients; Azithromycin and Clarithromycin used to treat |
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What is 1 of 3 differences in treating TB vs other infections?
Hint: resistance |
Mycobacteria have a cell wall that is resistant to penetration by antiinfective
drugs For medication to reach the organisms in tubercles, therapy must be for 6 to 12 months |
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What is 2 of 3 differences in treating TB vs other infections?
Hint: pharmacotherapy |
Pharmacotherapy requires at least two and sometimes four or more antibiotics administered concurrently
Mycobacterium grow slowly and resistance is common Using multiple drugs in different combinations for long periods of time lowers the potential for resistance and increases the success of therapy |
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What is 3 of 3 differences in treating TB vs other infections?
Hint: other uses for TB drugs |
TB drugs are used extensively for chemoprophylaxis
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What are the two broad categories of antitubercular drugs?
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First-line agents: safer and generally, the most effective
Second-line agents: more toxic, less safe and reserved for when resistance develops |
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What are the three “workhorse” drugs used in treating TB?
What are the two options for the 4th drug? What kind of monitoring is required? |
Isoniazid
Rifampin Pyrazinamide Ethambutol OR Streptomycin Baseline & monthly LFTs |
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Antituberculosis Drugs: Isoniazid
Adverse Effects? |
Peripheral neuropathy, hepatitis, skin rashes, fever, arthralgia, hypersensitivity reactions
Monitor LFTs Some drug interactions Supplement pyridoxine (B6) |
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Antituberculosis Drugs: Rifampin
Adverse Effects? |
hepatitis, thrombocytopenia, renal failure, “flu-like” syndrome, cutaneous reactions
Monitor LFTs Many drug interactions, esp HIV pts Red/orange discoloration of body secretions |
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Antituberculosis Drugs: Pyrazinamide
Adverse Effects? |
hepatitis, fever, skin rashes, arthralgia, GI upset, hyperuricemia (gout) encourage hydration
Monitor LFTs No drug interactions Adjust dose for Renal impairment |
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Antituberculosis Drugs: Ethambutol
Adverse Effects? |
optic neuritis, skin rashes, drug fever, hyperuricemia
Monitor red-green color discrimination & visual acuity Adjust dose for renal impairment No drug interactions |
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Antituberculosis Drugs: Streptomycin
Adverse Effects? |
vestibular and/or auditory or 8th nerve dysfunction, renal dysfunction, skin
rashes, neuromuscular blockade IM injection Audiometric and neurologic examination; renal function Use with caution / adjust dose for renal dysfunction Some drug interactions |
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Antituberculosis Drugs
Second-Line Agents |
Amikacin (Amikin)
Capreomycin (Capastat Sulfate) Ciprofloxacin (Cipro)* Cycloserine (Seromycin) Ethionamide (Trecator-SC) Levofloxacin (Levaquin)* Rifabutin (Mycobutin) Rifapentine (Priftin) – used in HIV pts instead of Rifampin *Fluoroquinolones used only when there is resistance to primary treatment |
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Antituberculosis Drugs
Duration in Months? Isoniazid, rifampin, pyrazinamide |
6 mos
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Antituberculosis Drugs
Duration in Months? Isoniazid, rifampin |
9 mos
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Antituberculosis Drugs
Duration in Months? Rifampin, ethambutol, pyrazinamide |
6 mos
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Antituberculosis Drugs
Duration in Months? Rifampin, ethambutol |
12 mos
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Antituberculosis Drugs
Duration in Months? Isoniazid, ethambutol |
18 mos
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Antituberculosis Drugs
Duration in Months? All others? |
≥ 24 mos
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Testing for PPD?
|
PPD – universal standard, cheapest, but need to return in 3 days
If BCG vaccine, PPD will always be positive, requires yearly Chest X-ray IGRA – Interferon Gamma Release Assay |
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Populations who should receive Chemoprophylaxis
Skin reaction of 5mm |
HIV infected persons, contacts of known cases or chest film typical for TB
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Populations who should receive Chemoprophylaxis
Skin reaction of 10mm |
Immigrants from high prevalence areas or those in high risk groups; healthcare workers
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Populations who should receive Chemoprophylaxis
Skin reaction of 15mm |
For all other person not in high risk groups
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Anti-fungals: Amphotericin B
Agents? |
amphotericin B (Fungizone),
amphotericin B Lipid Complex (Abelcet, Ambisome) Drug of choice for most fungal infections Premedicate for infusion related reactions |
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Anti-fungals: Amphotericin B
MOA? |
binds to sterols in the cell membrane of susceptible fungi causing changes in the permeability of the membrane
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Anti-fungals: Amphotericin B
Adverse Effects? |
thrombophlebitis, injection site pain, diarrhea, indigestion, loss of appetite, nausea, vomiting, anemia, myalgia, HA, fever, shivering, malaise, dysrhythmia, hypokalemia, seizures, agranulocytosis, SJS, nephrotoxicity
Confusion between the different formulations has led to fatal overdose or subtherapeutic doses Test dose ? |
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Antifungals: Echinocandins
Agents? |
anidulafungin (Eraxis),
caspofungin (Cancidas), micafungin (Mycamine) DOC for Aspergillus Not considered first-line agents |
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Antifungals: Echinocandins
MOA? |
inhibits the synthesis of β (1,3)-D-glucan, an essential component of the cell wall of filamentous fungi
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Antifungals: Echinocandins
Adverse Effects? |
diarrhea, hypokalemia, headache, fever, VTE, abnormal liver function, hepatic necrosis, seizures, respiratory distress, hypotension
Adjust dose of caspofungin for hepatic impairment Several drug-drug interactions (caspofungin) |
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Antifungals: Azole Antifungal Agents
Agents? |
fluconazole (Diflucan),
intraconazole (Sporanox), ketoconazole (Nizoral), posaconazole (Noxafil), voriconazole (Vfend) Most frequently prescribed systemic antifungal |
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Antifungals: Azole Antifungal Agents
MOA? |
inhibition of fungal cytochrome P450-dependent ergosterol synthesis (mediated via 14-alpha-sterol demethylase) resulting in a loss of ergosterol in the fungal cell wall
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Antifungals: Azole Antifungal Agents
Adverse Effects? |
diarrhea, nausea, vomiting, peripheral edema, headache, visual disturbance, fever, prolonged QT interval, Torsade's de Pointes, increased LFT’s, hepatitis, liver failure, optic neuritis, agranulocytosis, hypokalemia, pancreatitis, SJS
Adjust dose for renal and hepatic impairment Many drug-drug interactions |
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Flucytosine (Ancobon)
MOA? |
penetrates into fungal cells and converted to fluorouracil, an antimetabolite which interferes with DNA synthesis; interrupts nucleic acid and protein synthesis
Considered a drug of choice (alone or in combination with amphotericin B) in the treatment of chromomycosis |
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Flucytosine (Ancobon)
Adverse Effects? |
abdominal pain, diarrhea, nausea, vomiting, confusion, headache, hallucinations, leukopenia, myelosuppression, thrombocytopenia, renal failure, cardiac toxicity
Adjust dose for renal impairment Several drug-drug interactions Should NOT be used alone in other fungal infections due to rapid development of resistance |
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Terbinafine (Lamisil)
MOA? |
inhibits the biosynthesis of ergosterol which is an integral component of fungal cell membrane
Primarily used for less severe dermal mycosis/onychomycosis Available as oral and topical |
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Terbinafine (Lamisil)
Adverse Effects? |
diarrhea, disorder of taste, indigestion, nausea, headache, agranulocytosis, liver failure, SLE, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis
Not recommended in hepatic or renal impairment Several drug-drug interactions |
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Topical Antifungals & Indications
Butenafine (Mentax, Lotrimin Ultra) |
Pityriasis versicolor, Tineacorporis, Tinea cruris, Tinea pedis
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Topical Antifungals & Indications
butoconazole (Gynazole-1) |
Candidal vulvovaginitis
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Topical Antifungals & Indications
ciclopirox (Loprox) |
Onychomycosis, Seborrheic dermatitis, Tinea
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Topical Antifungals & Indications
clotrimazole (Lotrimin) |
Candidal vulvovaginitis, Candidiasis, Pityriasis versicolor, Tinea corporis, Tinea cruris, Tinea pedis
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Topical Antifungals & Indications
enconazole (Spectazole) |
Candidiasis of skin, Pityriasis versicolor, Tinea corporis, Tinea cruris, Tinea pedis
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Topical Antifungals & Indications
ketoconazole (Nizoral) |
numerous
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Topical Antifungals & Indications
miconazole (Oravig) |
Oropharyngeal candidiasis
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Topical Antifungals & Indications
naftifine (Naftin) |
Tinea, Cruris, pedis or corporis
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Topical Antifungals & Indications
nystatin (Mycostatin) |
Candidal vulvovaginitis, Candidiasis of skin/cutaneous/ mucocutaneous
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Topical Antifungals & Indications
oxiconazole (Oxistat) |
Pityriasis versicolor, Tinea (superficial), Tinea corporis, Tinea cruris, Tinea pedis
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Topical Antifungals & Indications
terbinafine (Lamisil) |
Dermal mycosis, Onychomycosis due to dermatophyte, Tinea capitis
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Topical Antifungals & Indications
tolnaftate (Tinactin) |
Tinea (superficial)
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Drugs for Nonmalarial Protozoal Infections
Agents |
Iodoquinol (Yodoxin)
Metronidazole (Flagyl) Paromomycin (Humatin) Pentamidine (Pentam) Sodium Stibogluconate (Pentostam) Tinidazole (Tindamax) |
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Nonmalarial Protozoal Infections
Comments |
Protozoa may cause harm to travelers to Africa, South America and Asia
Parasites often thrive in poor sanitary and personal hygiene conditions; high density populations Immunocompromised are at increased risk |
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Nonmalarial Protozoal Infections
Examples |
Plasmodium – most significant disease world wide
Amebiasis Toxoplasmosis Giardiasis Cryptosporidiosis Trichomoniasis Trypanosomiasis Leishmaniasis |
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Malaria
Comments |
Caused by 4 species of the protozoan Plasmodium
Malaria is the 2nd most common fatal infectious disease in the world |
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Malaria
Course of disease |
Begins with a bite from an infected female Anopheles mosquito – carrier of the parasite
14-25 days later, Plasmodium multiplies in the liver and transforms into progeny called merozoites Merozoites infect RBCs --> high fever, chills, N, V, D |
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Drugs for Malaria
Chloroquine (Aralen) |
Treatment and chemoprophylaxis of infection with sensitive parasites
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Drugs for Malaria
Quinine |
Oral treatment of P falciparum infections
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|
Drugs for Malaria
Quinidine |
Intravenous therapy of severe infections with P falciparum
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Drugs for Malaria
Mefloquine (Lariam) |
Chemoprophylaxis and treatment of infections with P falciparum
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|
Drugs for Malaria
Primaquine |
Radical cure and terminal prophylaxis of infections with P vivax and P ovale; alternative chemoprophylaxis for all species
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Drugs for Malaria
Sulfadoxinepyrimethamine (Fansidar) |
Treatment of infections with some chloroquine-resistant P falciparum, including combination with artesunate; intermittent preventive therapy in endemic areas
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Drugs for Malaria
Atovaquoneproguanil (Malarone) |
Treatment and chemoprophylaxis of P falciparum infection
|
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|
Drugs for Malaria
Doxycycline |
Treatment (with quinine) of infections with P falciparum; chemoprophylaxis
|
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|
Drugs for Malaria
Artemether/Lumefantrine (Coartem) |
Treatment of P falciparum malaria
|
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|
Prevention of Malaria
Chloroquine |
Areas without resistant P falciparum
500 mg weekly |
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Prevention of Malaria
Malarone |
Areas with chloroquineresistant P falciparum
1 tablet (250 mg atovaquone/100 mg proguanil) daily |
|
|
Prevention of Malaria
Mefloquine |
Areas with chloroquineresistant P falciparum
250 mg weekly |
|
|
Prevention of Malaria
Doxycycline |
Areas with multidrugresistant P falciparum
100 mg daily |
|
|
Prevention of Malaria
Primaquine |
Terminal prophylaxis of P vivax and P ovale infections; alternative for primary prevention
52.6 mg (30 mg base) daily for 14 days after travel; for primary prevention 52.6 mg (30 mg base) daily |
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|
Drugs for Helminthic Infections
Agents? |
Albendazole (Albenza)
Ivermectin (Stromectol) Mebendazole (Vermox) Praziquantel (Biltricide) Pyrantel (Ascarel) |
|
|
Helminths?
|
Various species of parasitic worms
Classified as roundworms (nematodes), flukes (trematodes) or tapeworms (cestodes) |
|
|
Helminthic Infections
Ascariasis |
most common helminth disease world wide, caused by the roundworm, Ascaris lumbricoides
Common in the South East among children 3-8 years (contaminated soil and poor hand washing) |
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Helminthic Infections
Enteriobiasis |
most common helminth infection in the United States caused by the pinworm, Enterobius vermicularis
|
