Antimicrobials Flashcards
1
Q
Facts about SSI?
A
- SSI most common healthcare associated infection
- SSI develop 2-4% of 30 million surgical patient
- represent 14-16% of all hospital acquired infections annually in use and cost 9.8 bllio dollars/year
- 3% surgical mortality and lead to
- increased readmission
- increased length of stay (7-10 days)
- increased hospital costs (additional $3000-29k per diagnosis)
2
Q
What defines a SSI?
A
- Infection r/t operative procedure that occurs at or near the sx inc within 30 days of procedure
- purulent exudate draining
- positive culture obtained from sx site that was closed initially
- surgeon’s dx of infection
- sx site that requires reopening d/t at least one of following signs
- tenderness
- swelling
- redness
- heat
3
Q
Are SSIs preventable?
A
most are preventable
more difficult in immunosuppressed/ or when vascular supply is decreased
4
Q
How can anesthesia providers impact SSI prevention?
A
- Timely and appropriate use abx
- maintenance of normothermia
- underestimate; up to 50% prevention
- colder patient increase ROI
- underestimate; up to 50% prevention
- Proper syringe/med administration practices
- perioperative glucose control
- particularly CT cases and also GI (29–> 14% risk of infection)
5
Q
What are some surgical risks for devleoping SSI?
A
- Procedure type (ie GI vs cataract)
- skill of surgeon (big impact)
- use of foreign material or implantable device
- ortho, pacemaker, heart valve, don’t have blood supply
- risk of infection increase bc can’t treat with abx
- ortho, pacemaker, heart valve, don’t have blood supply
- degree of tissue trauma
6
Q
What are patient risks for devleoping SSI?
A
- DM
- Smoking use
- obesity
- malnutrition
- systemic steroid use (long term)
- immunosuppressive therapy (chronic)
- intraoperative hypothermia
- trauma
- prosthetic heart valves
- extremes of age
- hair removal
- preop hospitalizations
major underlying theme is good vascular supply
7
Q
When should antibiotics be timed in OR?
A
- Antibiotic prophylaxis 1 hour before incision had the lowest rate of SSI
- 30-60 min before incision is the ideal window for drug admin
8
Q
What adverse outcomes is hypothermia associated with?
A
- Increased blood loss
- increased transfusion requirements
- prolonged PACU stay
- post op pain
- impaired immune function
compromised neutrophil function–> vasoconstriction–> tissue hypoxia and increased incidence of SSI
9
Q
What are some SCIP measures?
A
- SCIP -Inf 1- prophylactic abx received within 1 hour sx incision
- SCIP INf2- prophylactic abx selection for surgical patient
- making sure it’s appropriate
- SCIP 3- Prophylactic abx d/c’ed within 24 h after surgery end time
- SCIP 4- Cardiac sx patient with controlled 6am postop glucose <200
- SCIP 5- Postop wound infection dx during index hospitalization
- SCIP 6- Sx patient with appropriate hair removal
- SCIP 7- Coloretal sx patient with immediate postop normothermia
10
Q
What is the new delhi metallo- beta lactamas 1 gene?
A
- Beta lactamase has resistanc eto pretty much every abx except 2
- Mechanism
- increase active transport out of bacterial cell and or decrease the active transport into the cell
- structural changes in drug target (PCN binding protein)
- changes how PCN binds to bacteria
- production of drug antibiotic antagonist- beta lactamase
- enzymatic drug destruction
- the more abx are used, the more resistance develops (in target bacteria nd normal flora)
- can share resistance with other bacteria
- abx are used extensively in hospitals
- 1.7 mil pt acquire nosocromial infeciton, almsot 10,0000 die
11
Q
What are some CDC priorities to prevent microbial resistance?
A
- Flu vaccine
- protection against sequellae
- limit invasive catheter and use vigilant infection contorl with placement
- involve infectious disease experts
- id and target speicfic microbe
- quality control mech for abx use
- use local info about pathogen and sensitivity “antibiogram”
- treat infection, not contamination or colonization
- limit vanc use
- avoid using when infection is cured or not likely present
- isolation/infectious control procedures
- hand washing
12
Q
Antimicrobial therapy and anesthesia implications?
A
- Prophylaxis before sx
- anesthesia plays important role in timely admin of ABX
- reimbursement for quality care
- Potential for adverse reactions
- hypersensitivity reaction (dose independent)
- one drop of medicine will cause anaphylaxis
- if PCN anaphylaxis, avoid any beta lactams
- direct organ toxicity (dose related)
- potential for super infections
- id patients at risk for complications
- hypersensitivity reaction (dose independent)
- cross reaction with other meds we give
13
Q
WHat’s bacteriostatic?
A
Keep bacteria from replicating so we can allow the immune system to work
- antiobiotic can only do so much without the immune system
- when used, the duration of therapy must be long enough to allow cellular and humoral defense mechanisms to eradicate the bacteria
14
Q
What’s bacteriocidal?
A
Drugs that actually kill bacgteria directly
15
Q
What are some bactericidal drugs?
A
- PCN and cephalosporins
- Isoniazid
- metronidazole
- polymyxins
- rifampin
- vanc
- aminoglycosides
- bacitracin
- quinolones
16
Q
WHat are some bacteriostatic abx?
A
- Chloramphenicol
- Clindamycin
- Macrolides
- sulfonamides
- tetracyclines
- trimethoprim
17
Q
Goals and general rules for antimicrobials and anesthesiology?
A
- Inhibit microorganisms at concentration that are tolerated by the host
- MIC= Minimum inhibitory concentration
- seriously ill/immunocompromised select bactericidal
- narrow specturm before broad spectrum or combo therapy to preserve normal flora
- can cause 2nd super infection like c diff
18
Q
Basic for how antimicrobials work?
A
- Selective toxicity
- exploid cellular biological diff between microbes and mammals
- METHODs:
- bacterial cell wall- we don’t have cell wall
- bacterial enzyme inhibition- ex, folic acid formation- those enzymes aren’t present in us. bacteria, however, makes folic acid from PABA
- bacterial ribosome
- just different enough that we can target it
- bacterial cell wall- we don’t have cell wall
19
Q
What are some beta lactam examples?
A
PCN
Cephalosporin
Carbapenems
20
Q
MOA of beta lactam abx?
A
- Weaken bacterial cell wall
- bind to pcn binding proteins (only expressed during bacterial proliferation)
- Active autolysins ( decrease inhibition of murein hydrolasw- enzymatic destruction of cell wall)
- actually inhibit murein hydrolase, this allows autolysins to work
- Inhibit transpeptidases enzyme- needed for cell wall synthesis and integrity
- can’t form cross bridges with peptidoglycan strands
- weakens cell wall
21
Q
Diff between gram - and +?
A
- Gram- has extra outer membrane
- harder for some drugs to penetrate outer membrane
22
Q
What is basic structure of PCN?
Bactericidal or bacteriostatic?
Allergies?
A
- Basic structure is dicyclic nucleus that consists of thiazolidine ring connected to B-lactam ring
- several subtypes based on structure, B lactamase activity and spectum
- Bactericidal
- Allerigc reactions are principles concern (1-10%)
- anaphylaxis only 0.004-0.04% patient exposed iwth a 10% mortality
- laryngeal edema, bronchoconstriction, severe hypotension
- may occur on 1st exposure
- Organisms (don’t need for test…)
- pneumococcal
- meningococcal
- streptococcal
- actinomycosis
23
Q
Excretion PCN?
A
- Renal excretion rapid (PCN G)
- plasma concentrationd ecreases 50% in 1st hour
- 10% glomerular filtration
- 90% tubular secretion
- Anuria increases elimination half-time by 10 fold
- adjust dose in renal failure
- administration of probenecid will reduce renal excreiton and prolong action
- (used this to advantage in WWII d/t limited supply of PCN)
24
Q
What are second generation penicillins? Examples?
A
- Expand spectrum but increased risk of secondary infection from normal flora
- Gram (-) bacilli–> h influenza
- e. coli
- Amoxicillin
-
Ampicillin
- 50% excreted unchanged by kidney 6 hours after admin
-
Organisms
- pneumococcal
- meningococcal
- streptococcal
-
actinomycosis
*
25
Q
Third generation PCN? Advese effects?
A
- Organism
- same as second + pseudomonas aeruginosa and proteus
- Example- carbenicillin
- elimination half time 1 hour (2 hours renal dx)
- 85% excreted unchanged by kidney
- high sodium load
- hypokalemia
- metabolic alkalosis- concerned especially in anesthsia
- prolonged bleeding time despite normal PLT count
Not used often. Need risk/benefit analysis. lots of adverse effects
26
Q
What are beta lactamase resistant PCN?
Agent? How does it work?
A
- Agents:
- dicloxacillin
- Nafcillin
- penetrates CSF 80% secreted in bil (good renal dys.)
- Oxacillin
- Spectrum of activity?
- Narrow spectrum agents
- binds irreversibly to b lactamas enzymes
- large side gorup sterically hinders b lactamase form cleaving b-lactam ring
-
Gram positive activity- streptococci and staphylococci
- no gram -
27
Q
What are some b-lactam/b-lactamase inhibitor combo drugs? When do we use them?
A
- Combo of beta lactam ring with beta lactamase inhibitor
- Ampicillin/Sulbactam (Unasyn)
- Amoxicillin/Clavulanic Acid (augmentin)
- Ticarcillin/Clavulanic acid (Timentin)
- Pipercillin/Tazobactam (Zosyn)
- Braod spectrum agnets
- gram positive
- gram negative
- anaerobe
Don’t give zosyn before every case because you knock out native flora (= lots diarrhea/yeast infection)
also want to preserve this combo drugs for when we need it
28
Q
What are cephalosporins?
static or cidal?
MOA?
A
- Beta lactam antibiotics
- favorable therapetuic index
- Bactericidal
- MOA- bind to PBP
- Activate autolysins
- inhibit transpeptidases enzyme needed for cell wall syntheis and integrity
- once you disturb cell wall, water rushes in and bacteria bursts
- MOA- bind to PBP
- Differenct b/w drugs depends on side chains
- can be expensive and can access diff areas (ie BBB)
29
Q
What is the activity of 1st and 2nd generation cephalosporins?
A
- More gram positive activity
- beta-lactamase susceptible
30
Q
What is activity of 3rd and 4th generation cephalosporins?
A
- Increase gram negative actiivty
- increase activity against anaerobes
- ability to penetrate the BBB into CSF
ID docs like to keep aside for serious infections that aren’t reacting
Can be very expensive
31
Q
Examples of each generation of cephalosporin?
A
- First generation
- cephalexin, cefazolin
- Second generation
- cefuroxime, cefoxitin, cefotetan
- Third generation
- ceftazidime, ceftriaxone, cefotaxime
- Fourth generation (broadest)
- cefepime (Neurosurgery use)
- Fifth gen
- Ceftaroline (MRSA coverage)
32
Q
Elimination of cephalosporin?
A
- Primarily renal (dose reduciton in renal disease)
- Ceftriaxone is the exception
- 33-67% excreted unchanged and sig hepatic metabolism
- longest E1/2 T of 3rd generation
- 33-67% excreted unchanged and sig hepatic metabolism
- Routes of admin
- 1st and 2nd both have IV and oral
- Broadest spectrum cephalosporin are generally administered IV
33
Q
Use for Cefazolin?
Anaphylaxis? Allergic reaction? Cross reactivity?
Excretion?
A
- Very common for SSI prophylaxis (CV, ortho, biliary, pelvic, intraabdominal)
- Allergy incidence is 1-10%
- life threatening anaphylaxis -.02%
- laryngeal edema, bronchoconstriciton, severe hypotension<– main, first sign
- get out of beta lactams if anaphylaxis!
- Cross reactivity with other cephalosporins
- PCN and cephalosporin cross reactivity only 1% (but when it happens, it’s life threatening!)
- Renal excretion
34
Q
Adverse effects cephalosporin?
A
- Hypersensitivity: cross reactivity in pt with PCN allergy
- Bleeding
- cefoperazone, cefotetan, cetraixone
- inhibits conversion of Vit K to active form
- typically see this on chronic use
- cefoperazone, cefotetan, cetraixone
- Thrombophlebitis (IV site)
- Hemolytic anemia (rare)
- Superinfection (c diff)
35
Q
Drug interactions for cephalosporins?
A
- Probenecid (prolong DOA by delaying elimination)
- Alcohol- disulfiram like reaction
- inhibit aldehyde dehydrogenase- acetyl aldehyde build up in blood makes people feel awful
- Anticoagulants/ anti PLT drugs with cefoperazone, cefetetan, ceftriaxone
- Calcium and ceftraixone= FATAL precipitates
focus on cephalosporins!
36
Q
MOA of monobactams?
A
- Cell wall agent
- inhibits cell wall synthesis= cell lysis and death occur
- has high affinity to specific PBP3 in gram negative bacteria only
- highly resistant to beta-lactimases
37
Q
Spectrum of activity monobactam?
Excretion? Adverse effects?
Example?
A
Example- azteronam (azactam)
- Narrow spectrum
- excellent gram negative
- no activity against gram positive
- penetrates CSF
- Excretion- unchanged by kidney
- Expensive
- Few adverse effects
- most sig. risk is super infection (c diff) interesting because narrow spectrum…
- Good subsititue for pt with PCN allergy- cros s reactiivty unlikely
- lacks thiazolidine ring and dihydrothiazine ring
38
Q
What are macrolides?
Example?
MOA?
A
- not beta lactam.
- Broad spectrum agent usually bacteriostatic (bacteriocidal in high concentrations)
- Examples
- erythromycin
- clarithromycin
- azithromycin
- Compound characterized by macrolytic lactone ring containing 14-16 atoms with deoxy sugar attached
- big bulky molecule
- MOA
- Bind to 50 s subunit of the ribosome to block protein syntehsis
- Spectrum of activity- relatively broad- similar to PCN/useful with PCN allergy
- activity against gram positive and negative pathogens
- limited activity against anaerobs
- very good against atypical pathogens
- CAP, legionnaire’s, pertussis, acute diphtheria, chlamydial infection
39
Q
Macolide uses?
A
Bowman said not tested….
- URI
- Pharyngitis
- tonsilitis
- sore throat
- Otitis media
- Lower resp tract
- pneumonia
- MAC
- legionnaire’s anthrax
- Ulcers (H pylori)
- SRDS
40
Q
Adverse effects erythromycin (macrolide)?
A
- inhibit p450
-
increase qtc
-
prolongs cardiac repolarization
- reports of torsades
-
CYP3A inhibitor (verapamil, diltiazem, protease inhibitors, azole antifungals) can increase plasma concentration and increase risk of fatal vent. dysrhythmia
- 5x increase in SCD when erythromycin and cyp3a4 inhibitors are presecribed together
-
prolongs cardiac repolarization
- IV formulationa ssocaited with tinnitus hearing loss
- thrombophelbitis
- N/V/D
- ABD pain
- liver toxicity
- slow gastric emptying
- cholestasic hepatitis
41
Q
How are macrolides metabolized?
A
cyp 450
- increase serum concentration of theophylline, warfarin, cyclosporin, methylprednisolone, and digoxin
- excreted mostly in bile
- no need to alter in renal dose
42
Q
What do you need at baseline when patient taking erythromycin?
A
baseline EKG
(QT prolongation!)
43
Q
What class is clindamycin? MOA? DOSING? use?
A
- Class-Linomycins
-
MOA- Blocks protein synthesis by binding to 50S ribosomal subunit
- usually bacteriostatic agent
- Similar to erythromycin in antimicrobial activity
- more active with anerobs
- Psudomembranous colitis–> severe diarrhea should indicate discontinuation of therapy
-
Dosing
- 10% of administered dose excrete unchanged
- decrease dose -severe liver disease
-
Use
- female GU surgery
44
Q
Side effects clindamycin?
A
- Diarrhea
- skin rash/hpersensitivity
- Blood dyscrasias (eosinophilia, leukopenia, thrmbocytopenia)
- ask if easily bruising/bleeding
- prolonged pre and post junction effects at NMJ in the absence of NDMR
- Concurrent admin with NDMR can produce long lasting, profoudn NMB, NOT antagonized by AChE or Ca
- get very profound block
- no data with suggamadex use
- Concurrent admin with NDMR can produce long lasting, profoudn NMB, NOT antagonized by AChE or Ca
45
Q
What class is Vancomycin? MOA? Spectrum of activity?
A
- Class- glycopeptide
- MOA
- inhibits bacterial cell wall synthesis= cell lysis and death
- binds and inactivates cell wall precursors
- bactericidal “slowly” cidal
- Spectrum
- gram positive ONLY
-
SYNERGISTIC effect with aminoglycosides!
- once vancomycin destorys cell wall, aminoglycosides get in easier and impair ribosome function
-
SYNERGISTIC effect with aminoglycosides!
- Narrow but
- activity against MRSA <– why we don’t want to use it all the time
- Severe c-diff infection
- good choice in severe PCN allergy
- severe staph infection
- streptococccal, enterococcal endocarditis
- cardiac/orthopedic procedures using prosthetic devices
- csf and shunt related infections
- gram positive ONLY
46
Q
Administration of vancomycin? Dose adjustment? Interaction?
A
- Dose 10-15 mg/kg over 60 minutes
- non negotiable!
- 12 hours of therapeutic plasma concentation
- can start up to 2 hours preop
- 1 gram in 250 mL
- Can get rapid profound hypotension/cardiac arrest with rapid infusion
- Only PO for intestinal infection
- SLOW CSF penetration unless there is meningeal inflammation
-
Dose adjusted for renal insufficiency
- Renal excretion 90% unchanged
- elimination 1/2 time is 6 hours
- up to 9 days in renal pt
- Interaction
- other nephrotoxic drug
- return of NMB?
- Narrow therapeutic index
47
Q
Vancomycin side effects?
A
- Thrombophlebitis/phlebosclerotic (irritating to tissue)
-
Nephrotoxicity (renal failure)
- RARE unless concomitant treatment with other nephrotoxic drugs
-
Ototoxicity when concentration are >30 mcg/mL
- also if administered with aminoglycosides
- Hypersensitivity (maculopapular skin rash)
- Severe hypotension and red man syndrome (flushing d/t histamine relase) if given IV in less than 30 min
- Admin of diphenhydramine 1mg/kg and cimetidine 4mg/kg 1 hour before induction limits histamine related effects
- rare: immune mediated thrombocytopenia and bleeding
48
Q
Aminoglycosides MOA?
A
- Bactericidal
- MOA
- bind to 30s ribosome subunt and block the intiiation of protein synthesis in bacterial cells
- effective for aerobic gram negative and positive bacteria
- mycobacterium tuberculosis
49
Q
Aminoglycosides elimination?
S
A
- Extensive renal excretion through glomerular filtration (almost 100%)
- highly water soluble (polar)
- Vd= extracellular volume
- 2-3 hour elimination half time that is increased 20-40 fold with renal failure
50
Q
Aminoglycosides side effects?
A
- Limited by their toxicity
- cross the placenta could cause harm
- ototoxicity
- esp with diuretics such as furosemid, mannitol
- Nephrotoxicity
- esp with amphotericin B, cyclosporin, etacynic acid, vanc, nsaids
-
Skeletal muscle weakness- inhibit the pre-juncitonal release of ACh and decrease post synpatic sensitivity to neurotransmitter (impact on pt with NM pathology ie myasthenia gravis)
- can even see it if surgeon irrigated with aminoglycosides
- AChE and Ca can be helpful to prevent weakeness
51
Q
Gentamicin? Class? Use?
A
- Aminoglycosides
- broader spectrum (pleural, ascitic, synovial infection)
- toxic level- >9mcg/mL should be monitored
52
Q
Amikacin class? Highlights?
A
- Aminoglycosides
- Derivative of kanamycin with very little antibiotic resistanc
- useful in gentamicin or tobramycin resistant gram negative bacilli
- similar side effects as gentamicin
- do not use with PCN (may antagonize PCN effects)
53
Q
Neomycin? Class? highlights?
A
- Aminoglycosides
- ropical treatment for skin, eye and mucous membrane infections
- adjunct therapy to hpeatic coma (decreases ammonia concnetration)
- administer to decrease bacteria in intestine before GI surgery
- may have course of abx before sx
- Most nephrotoxic
- think twice before admin toradol
54
Q
MOA Linezolid (Zyvox)?
Spectrum?
A
- Bacteriostatic
- inhibits baterial protein syntehsis by preventing formation of a functional ribosomal subunit (23s) initiation complex that is essential for the bacterial translation process
- Spectrum:
- gram positive
- not active against gram negative
-
MRSA and VRE
- preserve for when necessary to avoid resistance
55
Q
Adverse effects linezolid?
A
- Thombocytopenia, anemia, leukopenia, pancytopenia (esp >2 weeks of tx)
- cbc check!
- GI effects
- RARE: optic and peripheral neuropathy
- formulated with phyenlalanine
- avoid in PKU
- Weak MAOI
- watch for additive NE and serotonergic effects used with other serotonergic agents and/or indirect sympathomimetics
- risk of serotonin syndrom and HTN crisis
- ephedrine and SSRI contraindicated
- watch for additive NE and serotonergic effects used with other serotonergic agents and/or indirect sympathomimetics
56
Q
Fluroquinolones use, MOA?
A
- Bactericidal broad spectrum
- enteric gram - baccilli and mycobacterium
- Useful in treatment of complicated GI and GU infection. TB, URI and anthrax!
- Ciprofloxacin
- Levofloaxacin
- Moxifloxacin
- MOA
- Inhibit DNA gyrase nd topoisomerase which are critical bacterial enzymes used in DNA replication and cell division
- gyrase- supercoild dna
- topoisomerase- separates strands during replication
- Inhibit DNA gyrase nd topoisomerase which are critical bacterial enzymes used in DNA replication and cell division
57
Q
Adverse effects fluoroquinolones? Interactions?
A
- Class warning for QT prolongation
- Nause CNS disturbances, opportunistic candida, rashes, phototoxicity
- C. diff super infection
- muscle weakeness in myasthenia gravis patients
- Tendinitis and achilles tendon rupture d/t extracellular cartilage matrix weakening
- highest risk >65 yo, corticosteroid, transplant
- avoid IV form <18 yo
- devastating se
-
Interactions:
- CYP 450 interaction (incrase theophylline, warfarin, tinidazole)
58
Q
Use fluoroquinolones? Excreiton?
A
- Useful in treatment of variety of systemic infections including anthrax
- GI absorption rapid and penetration to body fluid and tissues is excellent
- Renal excretion, through glomerular filtration and renal tubular secretion
- decrase dose in renal dysfunction
- E 1/2 time 3-8 hours
59
Q
Sulfonamides MOA? Drug Example?
A
Ex- sulfamethoxazole and trimethoprim
- Bacteriostatic
- MOA- ntimicrobial actiivty due to ability of these drugs to prevent normal use of PABA by bacteria to synthesize folic acid
- inhibit microbial synthesis of folate production
60
Q
Excretion sulfonamides?
A
- Portion of drug is acetylated in the liver and other is renall excreted
- renal dx- dose reduced
61
Q
Sulfonamides clinical uses? S/E?
A
- Clinical use
- UTI
- IBS
- Burns
- S/E
- skin rash to anaphylaxis
- photosensitivity (sunburn)
- allergic nephritis
- drug fever
- hepatotoxicity
- acute hemolytic anemia
- thrombocytopenia
- increase effect of PO anticoag.
62
Q
MOA Metonidazole? Use?
A
- Bactericidal
- anaerobic gram neg bacilli and clostridium
- Useful wide variety of infection
- CNS
- Abdominal and pelvic sepsis
- pseudomembranous colities
- endocarditis
- Well absorbed orally and widely distributed in tissue, including CNS
- Preop for colorectal sx
63
Q
S/E Metronidazole
A
dry mouth
metallic taste
nausea
avoid alcohol
rare: neuropathy and pancreatitis
64
Q
What are 1st line agents against TB?
A
Antimycobacterial agents
-
Isoniazid- bacteriostatic-cidal if bacteria are dividing
- hepato-renal toxicity
-
Rifampin- bacteriocidal
- hepatic enzyme induction
- hepato renal toxicity, thormbocytopenia, anemia
-
Ethambutol- bacteriostatic
- optic neuritis
-
Pyrazinamide- bacteriostatic
- liver toxicity
Used in combo therapy (3 or 4 agents) for 2 mo followed by min 4 months of therapy with 2 agents
65
Q
General lenght of time for TB treatment?
A
Used in combo therapy (3 or 4 agents) for 2 mo followed by min 4 months of therapy with 2 agents
66
Q
Example of antifungal? MOA?
A
- Amphotericin B
- MOA: Binds to ergosterol in fungal membrane to form pores
- altered membrane permeability causes leakage of cellular contents
- ergosterol is like cholesterol but slightly diff, lots of S/E
- Given for yeasts and fungi
- poor po absorption
67
Q
Amphotericin B excretion? side effects?
A
- Slow renal excretion
- renal funciton is impaired in 80% of patient treated with this drug
- most recover after drug is stopped but some resulting permanent decrease in GFR may remain
- monitor plasma levels
- S/E
- fever, chills, dypsnea, hypotension can occur (give benadryl, tylenol prior)
- impaired hepatic function
- hypokalemia
- allergic reaction
- sz
- anemia
- thrombocytopenia
68
Q
Highlights acyclovir?
A
- used to treat herpes
- may cause renal damage if infused rapdily
- thrombophlebitis
- patient may complain of HA during infusion
69
Q
Interferons highlights?
A
- Term used to designate glycoproteins produced in response to viral infection
- bind to receptors on host cell membrane and induce the production of enzymes that inhibit viral replication- degradation of viral mRNA
- enhance tumoricidal activities of macrophages
- treatment for chronic hep B and C
- nasal sprays
70
Q
Interferon s/e?
A
- Usually feel pretty terrible
- need plan B for discomfort
- flu like symptoms
- hematologic toxicity
- decreased mental concnetration
- development of autoimmune conditions
- depression irritability
- rashes
- aloplcia
- changes in CV, thyroid, hepatic function
71
Q
Steps in HIV replication cycle?
A
- Fusion of HIV cell to the host cell surface
- CCR5/CXCR4 proteins
- HIV RNA, reverse transcriptase, integrase, and other viral proteins enter the host cell
- Viral DNA is formed by reverse transcription
- Viral DNA is transported across the nucleus and integrates into host DNA
- New viral RNA and proteins move to cell surface and a new, immature, HIV virus forms
- The virus matures by protease releasing individal HIV proteins
72
Q
What is CCR5/CXCR4?
A
- Expressed on some HIV to help dock onto cell
- can block these proteins and decrease HIV effectiveness
73
Q
What do reverse transcriptase inhibitors do?
A
block RT of RNA–> DNA
74
Q
What are integrase inhibitors?
A
prevent integration of viral DNA into host DNA
75
Q
What are protease inhibitors?
A
inhibit chopping proteins into functional unit
76
Q
What should CRNA note when patient on antiretroviral?
A
- existence of adverse effects
- interactions with other meds
77
Q
Side effects/ interactions of Nucleoside reverse transcriptase inhibitors? Drug example?
A
Drug example- Zidovudine (AZT)
- nausea/diarrhea
- myalgia
- increased LFTs
- pancreatitis
- peripheral neuropathy
- renal toxicity
- bone marrow suppression , anemia,
- lactic acidosis,
Interaction
- methadone (co exist)
-
inhibition cyp 450
- zidovudine+ coritcosteroids can = severe mhyopathy including respiratory muscle dysfunction
78
Q
Protease inhibitor interaction? Drug example?
A
Drug example: (Ritonavir)
- HLD
- Glucose intolerance
- abnormal fat distribution
- altered LFT
- inhibition CYP 450 (Decreased fentanyl clearance)
-
AGES CV system: 30 yo with system like 60/70 yo
- increased HLD, cushing syndrome, abnormal fat
79
Q
Nonnucleoside analog reverse transcriptase inhibitor side effects influencing anesthetic? Drug examples?
A
- Delavirdine inhibits cytochrome P450. may increase concnetration sedatives, antiarrhythmics, warfarin, Ca channel blockers
- Nevirapine induces cyp 450 by 98%!!
just look up the drugs!!
80
Q
Integrase strand transfer inhbitors side effects that impact anesthesia?
A
newer agent- appear well tolerated
S/E may be unknown
81
Q
Chemokine receptor 5 antagonist and entry inhibitors side effects that impact anesthetic?
A
- Appear well tolerated- newer, may have unknown SE
- Appears to interact with midazolam altering clearance and drug effect
82
Q
3 anesthetic meds that interact with protease inhibitors (Ritonavir)?
A
- Midazolam
- increased effects
- small and carefully titrate
- Fentanyl
- increase effects
- start low dose and titrate to pain
-
AVOID (pronounced effects- life threatening)
- meperidine
- amiodarone
- diazepam
83
Q
ABX that are safe for pregnancy?
A
- PCN
- Cephalosporin
- Erythromycin
84
Q
Which abx are cautiously used in pregnancy?
A
- Aminoglycosides (ototoxicity in mom and baby)
- Clindamycin (colitis in mom)
85
Q
ABX contraindicated in pregnancy?
A
- Metronidazole (animal studies)
- Tetracyclines (tooth discoloration)
- fluroquinolones
- trimethoprim
- folic acid pathway
86
Q
Specail consideraitons for parturient patient?
A
- Most abx cross placenta and enter maternal milk
- look at pregnancy category group
- plasma concentration could be 10-50% lower than prediced
- increased maternal blood volume, GFR, metabolism
- Teratogenicity
- concern with any drug
- immature hepatic and renal clearnace
87
Q
Special consideration for elderly?
A
- Renal impairment
- Decrease plasma protein
- Reduced gastric motility and acidity
- altered distribution
- increased total body fat
- decreased plasma albuin
- decreased HBF
- Decreased GFR
88
Q
What abx are safe for elderly if normal Cr? What abx are we cautious with in elderly?
A
PCN and cephalosporin
Caution- aminoglycosides and vanc may require adjustment in dosing
89
Q
Treatment HIV guidelines in labor and delivery?
A
Big takeaway:
- mother should receive IV AZT and the baby should take AZT every 6 hours for 6 weeks after birth
Whole slide:
- During the first trimester, women without symptoms HIV disease may consider delaying treatment until after 10-12 weeks into pregnencies
- after 1st trimester, pregnant women with HIV should receive at least AZT (Zidovudine). The physician can recommend additional meds depending on CD4 count, viral load and drug resistance
- if pt already on anti HIV meds, the MD may recommend changes to the meds (evavirenz is contraindicated), however, generally recommended Zidovudine (AZT) be a part of regimen
- Most mother to child HIV transmission occurs around time of labor and delivery, therefore during this time it is very important for protecting baby from HIV infection
- HAART is recommended even for HIV infected pregnany women who do not need treatment for their own health
- mother should receive IV AZT and the baby should take AZT every 6 hours for 6 weeks after birth
