Sunday, April 27, 2008

Glucose problems made EZ

Another common subject on the NCLEX and USMLE examinations is the complications associated with elevated glucose. As most of you reading this blog know, glucose levels in the blood typically fluctuate only minor amounts between 80 and 110. This tight control is met through the balanced work of two pancreatic secretions named Insulin and Glucagon. Insulin picks up glucose from the blood and delivers it to cells in need of energy, or to the liver for storage. Glucagon senses when the level is low and frees stored glucose from its glycogen framework, into the bloodstream. However, for some this control malfunctions, and signs and symptoms begin to be seen. This imbalance is a life threatening emergency, and its recognition is vital to helping save our patients. What follows is a brief synopsis of a few glucose imbalance issues, and what we as practitioners must do about it.


Diabetic KetoAcidosis (DKA): (5-10% mortality)
– Almost exclusively in Type 1 diabetics
– S/S: Polyuria, dehydration, ab pain, fruity breath, AMS, ↓ Na/Mg/Phos, ↑K (↓ total body), + following:
• Hyperglycemia (above 250)
• Metabolic acidosis (pH below 7.3, HCO3 below 15, AG above 20)
• Ketonuria/Ketonemia
– TX:
• IV insulin bolus (0.1 unit/kg) then IV infusion with same amount per hr AFTER making sure pt is not ↓ K
– Continue until acidosis corrects then taper
• NS immediately upon diagnosis
– Switch to D5NS when glucose below 250; Why in the world would I give D5NS when a patient still has high glucose levels? The most important problem is the acidosis that is occurring. To reverse this we give insulin to drive glucose into the cell. Remember that K rushes into the cell along with the glucose, and wherever K can go, H+ can go. Since high levels of H+ in the blood is the cause of the acidosis, we give insulin to drive this H+ intercellularly, thereby reversing acidosis. We can't give insulin if the level of glucose is too low, so we give D5NS to keep levels around 250 so we can give insulin until the acidosis is gone.
• Add KCl to IV fluids once K below 5; replenish other electrolytes as necessary


Hyperosmolar Hyperglycemic nonketotic syndrome (HHNS):
– Severe ↑ Glucose, almost exclusively in Type 2 diabetics
– Similar to DKA but usually have much higher glucose (above 600) and NO acidosis or ketonuria/ketonemia
– Treat with fluids and low dose Insulin infusion
– An important distinction is that DKA usually occurs in Type 1 Diabetics, while HHNS most often occurs in Type 2 Diabetics. Remember this as it is a common question in the NCLEX world.

Hypoglycemia:
– Patho: When glucose drops to 80 = insulin levels ↓ ; 70 = Glucagon ↑; 50 = epinephrine ↑ along with s/s such as sweaty, ↑BP, ↑HR, tremors; Also around 50 CNS s/s (drowsy, h/a, confused) begin
– Note: S/S from epinephrine release are absent if pt is on a BB
– TX: If pt is alcoholic give Thiamine before any other treatment to prevent encephalopathy
• Can eat = ↑ sugar food;
• Can Not eat = ½ - 2 amps D50 IV push; (Glucagon alternative option if no IV access is available, however is of no use in prolonged hypoglycemia because stores of glycogen are depleted)

Points to remember:
– For high sugar (DKA, HHNS) most of the signs and symptoms are from polyuria, so look for dehydration and electrolyte imbalances...remember High and Dry
– For low sugar most of the signs and symptoms are from the release of epinephrine, so look for things that would happen when someone was high on adrenaline, such as hypertension, sweating, tachycardia and tremors.
– Imperative that you can recognize the difference between these two, as you are almost guaranteed to see a question relating to this difference!

Saturday, April 12, 2008

Antibiotics made EZ...Part 2

If you have been studying for your NCLEX or USMLE examination for a while, you may have noticed there is some confusion about antibiotics. OK, hopefully you had a chance to read through the Antibiotics made EZ, Part 1. If you havn't, it may be better for you to jump down and read about the bugs, before we dive into the drugs. One of our worst mistakes in the vietnam war, was going into a country completely ignorant of our enemy. We took the wrong guns, and the wrong equipment, and paid for it. Same thing goes here. If you don't know the bugs, reading about the drugs listed below, will make little sense.

That being said, lets take a look at some of the most common medications used to treat Bacterial infections. NOTE that this is empiric therapy only...meaning these are the best options for treatment, BEFORE, our culture and sensitivity comes back. Once those results are ready, they should guide what we use. Also, the spectrum of resistance may be different wherever you live, so these are general recommendations on the most popular drugs. Ok that being said, lets take a look at the first and largest group...the Beta Lactams

Beta Lactams: the Penicillins

Penicillins (PCNs)
MOA: All Beta Lactams are Bactericidal, inhibiting cell wall synthesis; Preg Cat B

Natural Penicillins
Spectrum: G(+): Strep, Bacillus, Clostridium; G(-): Neisseria
Facts: Relatively few side effects; Allergic reactions relatively common; 98% of Staph are resistant to PCN due to enzyme able to destroy medication (PCNase)
PCN G: IV, IM (often only 1 injection need, i.e. Syphillis)
PCN V: PO, poorly absorbed so only for minor infections

Penicillinase (PCNase) Resistant PCNs
Spectrum: G(+): Staph (only indication though spectrum similar to PCN)
Facts: Original Drug was Methicillin but caused too much Interstitial Nephritis and was withdrawn; Despite this, Staph resistant to this class was termed Methicillin resistant (MRSA or MRSE)Oxacillin (PO, IV); Cloxacillin & Dicloxacillin (PO); Nafcillin (IV)

Aminopenicillins
Spectrum: G(+): Same as PCN plus Enterococcus plus G(-): Moraxella, E.Coli, Salmonella, H.influenzae, H.Pylori;Facts: NH3 group makes enhanced activity against G(-); 2nd most common cause of C.Dif Colitis Amoxicillin: PO; ENT infections, Cellulitis, Gonorrhea, C.A.Pneumonia (Strep)
Ampicillin: IV; Listeria, Enterococcus

Extended Spectrum PCNs
Spectrum: Same as AminoPCNs plus G(-): Pseudomonas, Proteus, Bacteroides
Facts: Broad Spectrum, usually reserved for serious infections with susceptible bacteria; No PCNase resistance when given alone; Often combo w/Aminoglycoside for Pseudomonas
Ticarcillin (IV); Piperacillin alone withdrawn (Combination drug Zosyn still available)

PCN/Beta Lactamase Inhibitor Combinations

Facts: PCNase inhibitor added to a Beta Lactam to extend coverage, mainly against S.aureus
Unasyn: Ampicillin + PCNase inhibitor
Augmentin: Amoxicillin + PCNase inhibitor
Zosyn: Piperacillin + PCNase inhibitor (Very Broad Spectrum)

Beta Lactams: the Cephalosporins
Class Facts:
Similar to PCN in most ways, but only 5-10% of PCN allergic will be allergic to Cephs
Generally avoided only if history of Anaphylaxis with PCN
Generally do not cover Anaerobes, Pseudomonas or cross BBB unless indicated
Do not cover MRSA (except Ceftaroline) or Enterococcus
Preg Cat B; Do not take with Alcohol; Consume at least 3 L water daily; Take w/food (avoid GI probs)
All Cephs can cause ↑PT/INR (give Vit K) and C.Dif Colitis

1st GenerationSpectrum: Broad G (+) i/c PCNases; limited G (-): E.Coli, Proteus, Klebsiella
Cephalexin (Keflex): PO; Cellulitis, Cystitis
Cefazolin (Ancef, Kefzol): IV; Surgical prophylaxis (protect against skin bugs)

2nd GenerationSpectrum: G (+): Same as 1st Gen plus G (-): H.Influenzae, Neisseria
Cefuroxime (Zinacef): PO, IV; Limited anaerobes; Cross BBB
Cefoxitin (Mefoxin): IV; Abdominal surgery prophylaxis; Excellent against Anaerobes (i.e. DM foot infections, Peritonitis, etc)

3rd GenerationSpectrum: Excellent G (-) coverage; limited G (+)
Ceftriaxone (Rocephin): IV; qd dosing; Crosses BBB; Meningitis, Encephalitis, Gonorrhea
Ceftazidime (Fortaz): IV; Pseudomonas, Neutropenic Sepsis, Serious infx only; Cross BBB

4th GenerationSpectrum: Excellent G (+), Excellent G (-) coverage i/c Pseudomonas; Cross BBBSE: Psuedomembranous Colitis (C.Dif) most frequent in class
Cefipime: IV; Cross BBB; Complicated UTI, Severe Sepsis
Cefdinir: PO

5th Generation
Spectrum: Excellent G (+), Excellent G (-) coverage i/c MRSA
Ceftaroline: IV/IM; Pneumonia and Skin infections including MRSA
Ceftobiprole (proposed): Not yet available, but on FDA Fast-track; Claims more extensive coverage with less susceptibility though FDA states studies not conclusive



Beta Lactams: The Carbapenems

Carbapenems
Spectrum: Broadest Spectrum of any Antibiotic; Indicated for severe bone, skin, tissue infections, as well as Endocarditis, Abdominal infx, Pneumonia, UTIs, Sepsis, Acinetobacter
Used as last resort in hospitalized patientOnly obvious omission is lack of coverage against C.Difficile, Atypicals, and MRSA
Restricted use by ICU IV infusion for significant infections, to keep resistance low
SE: Nephrotoxicity and Seizures (usually with preexisting Renal or CNS disease) Preg Cat C
Imipenem (Primaxin): IV; Combined with Cilastatin to block enzyme that breaks down drug
SE: Sz in 1.5% of pts on typical dose, 10% if above 500 mg q6h (So not for Meningitis)
Meropenem: IV; May kill G (+) a bit slower than Imipenem, but less Sz, no need for Cilastatin

Beta Lactams: The Monobactams

Monobactams
Spectrum: Limited to aerobic G (-) i/c Pseudomonas; Severe systemic infections and UTIsThis powerful GNR drug is usually combo with Vanco or Clinda for Powerful Broad spectrum
Preg Cat B
Safe to administer to pt w/PCN allergy
Crosses BBB
SE: Severe nephrotoxicity if given with aminoglycosides; Monitor renal function even if given alone; Eosinophilia rarely
Aztreonam: IV, Advantage of preserving all normal G (+) and anaerobic flora

Macrolides
Class Facts:
Broad Spectrum: Similar coverage to PCN plus Atypicals (Chlamydia and Mycloplasma), plus Spirochetes (Syphillis and Lyme) plus additional G (-) i/c H.influenzae
As a rule, Clarithromycin has most and Azithromycin the least G (+) coverage
Bacteriostatic, inhibiting protein synthesis
Do NOT cross BBB, so not for meningitis
Except Azithromycin, CP450 inhibited, increasing drug levels of Theophylline, Digoxin, Coumadin, etcFood decreases absorption of Macrolides
Often used as alternative when pt is PCN allergic
Can cause QT prolongation and Rhabdomyolysis (especially with Statins)
Exhibits Enterohepatic recycling (excreted in bile, then reaborbed; cx for buildup to toxic levels)
Since excreted in bile, not kidneys, no need for adjustment in renal failure
Azithromycin: IV, PO; qd dosing; No effect on CP450 so fewer drug interactions, and no enterohepatic recycling; Atypical Pneumonia, Chlamydia
Clarithromycin: PO; H.Pylori, Pneumonia, M.Avium Complex
Erythromycin: PO, IV, Topical, Opthalmic; Acne, Skin Infx, Eye infx, Diabetic Gastroparesis
SE: Cholestatic jaundice, GI distress (overall a very safe drug)

Fluoroquinolones
Class Facts:
Spectrum: Broad coverage of G (-), variable G (+), broad coverage of Atypicals
As a rule, increasing Generations have better G (+) and anaerobic coverage, but less Pseudomonas
Bactericidal, inhibiting bacterial DNA production
Precautions
Cx w/arrhythmias, CI if pt on antiarrhythmic meds
As a rule, any abx that targets bacterial flora (G -), effects coagulation by inhibiting Vitamin K
Preg Cat C
Binds Ca, Al, Zn, Mg so do not administer with Milk, Vitamins, or Antacids
Electrolyte interference may cause arrhythmias (QT prolongation), Seizures, Neuropathy, and this is increased when taking with NSAIDs
May cause weakness in M.Gravis
May cause Pseudomembranous colitis, Rhabdomyolysis
Spontaneous tendon rupture can occur when taken with Corticosteroids
Do not administer with Milk, Vitamins, or AntacidsHigh % of unmetabolized drug is excreted in urine, making it excellent for UTI
1st Gen: Did not contain Fl, and were just Quinolones; Much less effective, not used today
2nd Gen: Best antipseudomonal and G (-) in class; weakest G (+) and anaerobe
Ciprofloxacin: PO, IV, Opthalmic; Nosocomial Pneumonia, UTI, Infx Diarrhea (not C.Dif); Not for children below 18
3rd Gen: Levofloxacin (Levaquin): IV, PO; qd dosing; UTI, Community (CAP) or Legionella Pneumonia
4th Gen: Best G (+) and anaerobe in class; weakest G (-) and antipseudomonal in class Moxifloxacin: Pneumonia (CAP); Only Quinolone not renally excreted

Aminoglycosides
•Class Facts:
–Spectrum: Primarily aerobic G (-) coverage i/c Pseudomonas, some G (+) staph
–Often used in combination with G (+) drugs for Broad Spectrum coverage; Rarely used alone
–Quinolones are often used initially instead, due to high resistance to this class, unless high suspicion of Pseudomonas
–Bactericidal, blocking protein synthesis
–Allergies are very uncommon with this class
–Precautions:•Nephrotoxicity (renal failure) and Ototoxicity (hearing loss) fairly common, so not for long term –Nephrotoxicity risk increased when taking with Vanco, Cyclosporine, or IV contrast–Ototoxicity risk increased when taking with Loop Diuretics
•Measure Trough concentrations to assure efficacy, at least every 5d (30m before next dose)
•Most Preg Cat D (exception is Streptomycin which is a B)
•Decrease intestinal Vitamin K synthesis (anticoagulant quality)
•Can bind Ca, causing neuromuscular weakness and neuropathy
–Not absorbed well, so no PO
•Streptomycin: Eye infx, Tuberculosis; Limited use due to high resistance
•Tobramycin: Best antipseudomonal in class; MRSA (w/Ampicillin)
•Gentamicin: Excellent antipseudomonal; Endocarditis (w/PCN)
•Neomycin: Hepatic Encephalopathy (kills Ammonia producing GI flora); Only drug in class given PO as it is used to clean GI tract and is not absorbed; Very toxic if given IV
•Amikacin: Synthetic derivative of Neomycin; Often still effective when bugs are resistant to all other Aminoglycosides

Tetracyclines
•Class Facts:
–Spectrum: Very broad coverage of G (-), G (+), Atypicals, Protozoa; i/c Chlamydia, Mycoplasma, and Acinetobacter–Broad spectrum limited only by significant resistance, and indications now i/c: Acne, Rosacea, Anthrax, Bubonic Plague, Elephantitis, Malaria, Cholera, Syphillis, Rickettsia (Q fever)–Also inhibits ADH, and is used for SIADH–Bacteriostatic, inhibiting protein synthesis
–Precautions
•With odd strength comes odd SE; These i/c: Candida superinfections, Pseudomembranous Colitis (C.Dif), Thrombocytopenia, Coagulation irregularities, Hemolytic anemia, Lupus exacerbations, Nephrotoxicity•Bind Ca, Mg, Al, so do not give with milk, antacids, or iron salts; Also cause tooth discoloration in growing teeth (young pts); Cause weakness in M.Gravis
•Preg Cat D–Cause fibrosis in pleura, so used for direct administration to resolve pleural effusions
•Doxycycline (Vibramycin): PO, IV; You name it this will treat it, but use less harmful drugs, if effective, first
•Demeclocycline (Declomycin): PO; Reserved for the treatment of SIADH

Miscellaneous

Bactrim
•PO, IV; Sulfonamide, primarily used for UTI and Pneumocystis Carinii Pneumonia (in HIV pt)
•SE: Renal stones, Stevens Johnson syndrome, Allergic reaction common; Many drug interactions; Blood Dyscrasias (report any s/s of new infx)

Vancomycin•PO, IV; Spectrum i/c all G (+); Used for MRSA and MRSE; PO is useful for C.Dificile Colitis
•SE: Nephro/Ototoxic (Measure Peak/Trough levels); Red Man Syndrome (from rapid infusion; 60m min)

Metronidazole
•PO, IV; Excellent GPR/GNR Anaerobic coverage, used for intrabdominal; C.Dificile Colitis
•SE: Serious reaction if taken within days of Alcohol

Clindamycin
•PO, IV; Excellent Anaerobic coverage (rule is Clinda above diaphragm, Metro for below) as well as G (+)
•Often used for serious G (+) sepsis w/possible anaerobic component (i.e. postop abdomen surgery)
•Does not cross BBB; Esophagitis common if not administered with water
•SE: Pseudomembranous Colitis (C.Dif) common post treatment (10%)

Linezolid (Zyvox)
•PO, IV; Spectrum similar to Vanco plus most anaerobes; Used for VRSA, VRE
•SE: May decrease platelet count (3%); MAOI w/high risk of Serotonin Syndrome with SSRIs

Synercid
•IV; Alternative to Zyvox for VRSA, VRE
•SE: Serious arthralgia, myalgias; Central line only as thrombophlebitis in up to 75% of pts via Peripheral

Colistin
•IV; Mainly used for treatment of Acinetobacter and severe Pseudomonal infx; Spectrum i/c GNR
•Was actually first G (-) drug on market, gradually replaced by Aminoglycosides, then brought back into use by developing resistance to those drugs
•Developed so long ago, no actual recommended dosages have been studied (nightmare to prescribe)
•SE: Nephrotoxicity, Neurotoxicity (less common than with Aminoglycosides)