Title: Top Ten Drugs or Classes in the Intensive Care Unit
1Top Ten Drugs (or Classes) in the Intensive Care
Unit
- Rob MacLaren, PharmD, FCCM, FCCP
- Associate Professor
- University of Colorado School of Pharmacy
2Objectives
At this lectures conclusion
- Explain the mechanisms of action of agents
commonly used in the intensive care unit. - Describe the clinical application of agents
commonly used in the intensive care unit. - Develop a dosing regimen and monitoring plan for
agents commonly used in the intensive care unit. - Proton pump inhibitors and histamine-2 receptor
antagonists analgesics, sedatives and
neuromuscular blocking agents fluids,
vasopressors, and inotropes ACLS,
antiarrhythmics, loop diuretics, and
antihypertensives anticoagulants and
procoagulants antibiotics and antifungals.
3Case
- 47 yo male admitted to the MICU with CAP / COPD
exacerbation (PMH of COPD, CAD, and NIDDM). - Intubated for hypoxia and eventually placed on
Assist Control, 15/15-18 bpm, 8 mL/kg, 70, and 7
cm H2O PEEP to maintain PaO2 90 mmHg and O2sat
80. - Patient is agitated and restless (not
autoPEEP). - Within hours, Bp 60s/20s and HR 120s.
Received 4L NS with minimal response. - What ICU drugs does this patient require and why?
4Proton Pump Inhibitors / Histamine-2 Receptor
Antagonists
5Clinical Applications of Proton Pump Inhibitors /
Histamine-2 Receptor Antagonists
- PPIs
- Treatment of nonvariceal upper gastrointestinal
hemorrhage - Esomeprazole, pantoprazole, omeprazole _at_ 80 mg iv
bolus then 8 mg/hour x 72hrs then 40 mg po/iv
q12hrs. - Lansoprazole _at_ 60 mg iv bolus then 6 mg/hour x
72hrs then 30 mg po/iv q12hrs. - Prevention of stress-related mucosal hemorrhage
- Esomeprazole, pantoprazole, omeprazole _at_ 40 mg
po/iv q24hrs. - Lansoprazole _at_ 30 mg po/iv q24hrs.
- H2RAs
- Prevention of stress-related mucosal hemorrhage
- Famotidine 20 mg iv q12hrs, ranitidine 50 mg iv
q8hrs, cimetidine 300 mg iv q6hrs.
6Pharmacologic Targets of Proton Pump Inhibitors /
Histamine-2 Receptor Antagonists
GASTROENTEROLOGY.2000118(2)s9-s31
7Monitoring of PPIs and H2RAs
- PPIs
- Advantages Oral/IV formulations, ease of dosing,
supporting clinical data for NVUGB SRMD, low
drug interactions, more pH control. - Disadvantages Possible associations with
clostridium difficile infection and pneumonia
some drug interactions (omeprazole) slightly
higher cost. - H2RAs
- Advantages Oral/IV formulations, ease of dosing,
supporting clinical data for SRMD, inexpensive. - Disadvantages Possible association with
pneumonia and thrombocytopenia some drug
interactions (cimetidine) confusion infusion
rate dependent bradycardia.
8Analgesia, Sedation, Neuromuscular Blockade
9Clinical Applications of Analgesia, Sedation,
Neuromuscular Blockade
- Analgesia
- To prevent / reduce pain and sedation.
- Opioids used most commonly.
- Sedation
- To reduce anxiety and improve comfort (e.g.
ventilator support). - Common agents benzodiazepines (GABA receptor
agonists), propofol (??? MOA). - Neuromuscular Blockade
- To facilitate mechanical ventilation (extreme
nonphysiologic modes). - Common agents succinylcholine (depolarizing) and
competitive acetylcholine antagonists
(nondepolarizing).
10Analgesic Agents
11Monitoring of Analgesia
- Pain control
- Subjective facial expressions, guarding,
restlessness, anxiety, irritable, sleep
disturbance. - Objective diaphoresis, verbal response,
tachycardia, hypertension, muscle tension,
dilated pupils, tachypnea, spasm. Pain scores. - Opiate abstinence/withdrawal syndrome
- Subjective agitation, restlessness,
irritability, anxiety, insomnia, tremor,
dysphoria. - Objective tremor, seizure, tachycardia,
hypertension, fever, diaphoresis, dilated pupils,
vomiting. Validated tools in NICU and PICU. - Prevent by dose weaning, transdermal fentanyl,
enteral methadone.
12Pain Assessment Behavioral Scale (PABS)
Score 0 no evidence of pain. 1-3 Mild pain.
4-6 moderate pain. 7-10 Severe Pain.
13Sedative Agents
14Monitoring of Sedation
- Level of sedation all agents equally efficacious
with appropriate monitoring but 62 of ICUs use
sedation scoring. - Unique side effects
- Prolonged awakening (benzos).
- Propylene glycol toxicity (anion gap met
acidosis) and ppt with lorazepam. - Hypertriglyceridemia, pancreatitis, hypercaloric
intake, hypotension, preservatives, and possible
immunomodulation with prop. - Sedation abstinence/withdrawal syndrome
- Agitation, restlessness, anxiety, insomnia,
tremor, tachycardia, hypertension, fever.
15Monitoring of Sedation
Riker Sedation-Agitation Scale
16Neuromuscular Blocking Agents
- Depolarizing (succinylcholine)
- Used for procedures (e.g. intubation).
- Dose 1-2 mg/kg iv.
- Contraindicated if hyperkalemia, increased ICP,
crush/burn injury, bronchoconstriction,
denervation syndrome. - Nondepolarizing (competitive antagonists)
- Used for intermittently for procedures,
intracranial pressure, or shivering and
continuously to facilitate mechanical ventilation
(extreme nonphysiologic modes).
17Nondepolarizing NMBs
18Neuromuscular Blockade Monitoring
- Train of Four (TOF)
- Using peripheral nerve stimulation, monitor
number of twitches of ulnar nerve or facial nerve
in response to preset amount of current (40
mAmp). - Response of 4/4 is lt 75 paralyzed, 3/4 is 75-80
paralyzed, 2/4 is 80-90 paralyzed, 1/4 is
90-100 paralyzed, and 0/4 is 90-100 paralyzed. - Use of TOF reduces drug cost and occurrence of
neuropathies. - Ventilator synchrony and / or ? ICP.
- Adverse effects neuropathy (reduced with TOF),
histamine release (atra gt miva gt rest), vagolytic
(pan gt vec gt roc gt rest), reduced corneal reflec
(lacrilube, eye drops), drug interactions to ??
NMB.
19Fluids, Vasopressors, Inotropes
20Fluid Replacement
21Vasopressors and Inotropes
In Pharmacotherapy A Pathophysiologic Approach
(7th ed). DiPiro JT ed. Chicago, Il
McGraw-Hill. 2008.
22? NO and K-ATP
23Vasopressin
- Acts at vasopressin (V) receptors
- Vascular V1 receptors enhance calcium release
from sarcoplasmic reticulum to vasoconstrict.
Greatest vasoconstriction in skin, skeletal
muscle, fat, pancreas, and thyroid gland. - Renal V2 receptors enhance fluid retention in
collecting tubules but vasoconstriction of
efferent gt afferent increases GFR net effect is
increase urine output. - V3 receptors increase ACTH (cortisol) release.
- Dose for sepsis 0.01 0.04 units/min (not to be
titrated to response as this is replacement
dosage). - Reduces the dose of the traditional catecholamine
vasopressor possibly increases urine production.
24Potential Side Effects
In Pharmacotherapy A Pathophysiologic Approach
(7th ed). DiPiro JT ed. Chicago, Il
McGraw-Hill. 2008.
25ACLS, Antiarrhythmics, Diuretcis, and
Antihypertensives
26ACLS Drugs of Interest
- Vasoapressors
- Epinephrine
- Vasopressin
- Rate Control
- Adenosine
- Atropine
- Anti-arrhythmics
- Amiodarone
- ß blockers
- Diltiazem
- Lidocaine
- Magnesium
27Other Code Cart Medications
- Other
- Albuterol nebs
- Calcium chloride
- Dextrose
- Magnesium
- Nitroglycerin
- Sodium bicarbonate
- Dopamine drip
- Lidocaine drip
- Flumazenil
- Naloxone
- Pulmonary Embolism
- tPA- alteplase
- Anaphylaxis
- Epinephrine
- Antihistamines
- Corticosteroids
- Inhaled ß- agonists
28Vasopressors
- Epinephrine
- 1st line vasopressor in ACLS algorithm
- Indications
- V Fib / V Tach (after shocking)
- PEA
- Asystole
- Dose
- IV / IO Push 1 mg repeated every 3-5 minutes
- Continuous infusion 0.01 to 0.5 mcg / kg / min
- ET route 2 to 2.5 mg diluted in 10 mL NS
- Intracardiac 0.3 to 0.5 mg
- Other
- Incompatible with sodium bicarbonate
- Vasopressin
- Indications
- V Fib / V Tach (after shocking)
- PEA
- Asystole
- Dose
29Atropine in Pulseless Arrest
- Atropine
- Acetylcholine receptor antagonist- reverses
cholinergic mediated decreases in heart rate
(vagolytic effect) - In slow PEA or Asystole only
- Give 1mg q 3-5 minutes (along w/ epinephrine or
vasopressin) - Up to maximum dose of 3mg
30Anti-arrhythmics
- Amiodarone
- MOA blocks K, Na, and Ca channels ß- blocker
- Indications
- Recurrent pulseless V Fib / V Tach
- Dose 300mg IV push (dilute in 20-30 mL D5W)
- May follow with 150 mg IV push in 3-5 min
- Available as abboject syringe (150mg/3mL)
- Wide QRS complex arrhythmia w/ pulse
- Dose 150mg IV over 10 minutes, may repeat prn
- Continuous infusion 1mg/min x 6 hours, then
0.5mg/min x 18 hours - Considerations
- Long half-life hypo- or hyperthyroid, hepatic or
pulmonary fibrosis, smurf-like skin must
dilute in nonPVC bag
31Anti-arrhythmics with PULSE
- Diltiazem
- MOA Ca channel blocker
- Inhibits automaticity in SA node
- Inhibits conduction through the AV node
- Arterial vasodilation
- Indications
- Control VENTRICULAR rate in A Fib / Flutter
- May terminate reentrant arrhythmias reentrant
arrhythmias - Avoid in A Fib/flutter associated w/
Wolff-Parkinson-White syndrome - Do NOT use in wide-complex rhythm
- Dose
- 15 to 20 mg IV / IO push over 2 minutes
- May repeat dose in 15 minutes at 20 to 25 mg over
2 minutes - Continuous infusion 5 to 15 mg/hr, titrated to
appropriate heart rate
32Re-entry Tachyarrhythmia
- Adenosine
- MOA
- Decreases conduction velocity
- Prolongs the refractory period
- Inhibits AV node conduction
- Indications
- Reentry arrhythmia involving AV or sinus node
- Conversion of paroxysmal supraventricular
tachycardia - Will NOT convert A fib, A flutter, or V tach
- May help diagnosis of arrhythmia
- Dose
- 6mg given rapidly IV push over 1 to 3 seconds
followed by 20 mL NS bolus elevate extremity - 2nd dose may be given in 1 to 2 minutes if
needed- 12 mg
Results in conversion to sinus rhythm
33Naloxone
- Opioid mu-receptor antagonist
- Dose
- Suspected emergent narcotic OD 0.4-2mg
- If no response then not likely narcotic OD
- May repeat after 2-3 min if needed
- If not emergent (alive) 0.1-0.2mg given in small
increments to avoid severe pain - May induce w/d and may be outlasted by opioid
34Flumazenil
- Benzodiazepine binding site antagonist
- Displaces benzodiazepines binding thereby
reversing clinical effects - Dose 0.2mg/dose at 60 second intervals
- May repeat with escalating doses (0.5mg)
- If respond then re-sedate, repeat effective dose,
maximum recommended 3mg in one hour time - Rarely see additional response at 5mg
- May induce w/d and may be outlasted by benzo
35Blood Pressure Management
Crit Care 200812237. J Neurol 2006253985-99.
36Vasodilators Nitroglycerin
Mechanism primarily a venous dilator, mild
arterial dilator Administration continuous
infusion via infusion pump 5-200
mcg/min Benefits Decrease in PCWP and slight
decrease in MAP and SVR Adverse effects
hypotension, tachycardia, tolerance
37Loop Diuretics
Mechanism decreased Na/water resorption in the
kidney Administration continuous infusion via
infusion pump or intermittent dosing Furosemide
20-80 mg q1-2 hours PRN 10-40
mg/hr Bumetanide 0.25-4 mg/hr Benefits
decrease in PCWP, pulmonary congestion,
preload, and intravascular volume Adverse
effects volume depletion, electrolyte
imbalance, azotemia, contraction alkalosis,
ototoxicity
38Anticoagulants and Procoagulants
39Mechanisms of Anticoagulants
INTRINSIC SYSTEM
EXTRINSIC SYSTEM
(Collagen)
(Tissue Factor)
XII
XIIa
Heparin
Factor III Ca
XI
XIa
Ca
IX
VII
VIIa
IXa PF 3 Ca VIII
Fondaparinux
LMWH
Xa Ca PF 3 V
X
X
APC
XIII
Thrombin
Prothrombin (II)
XIIIa
Fibrin (monomer/ polymer)
Stable Fibrin Polymer
Fibrinolytics
Fibrinogen (I)
DTI
Adapted from Circulation 2007116552.
40Clinical Profiles
Ann Pharamcother 2006401558-71.
41Dosing of Anticoagulants
- DVT pharmacoprophylaxis
- MICU/SICU UFH 5000 U sc q8hrs.
- Trauma LMWH gt 3400 IU sc q24hrs.
- Ortho LMWH gt 3400 IU sc q24hrs or fondaparinox
2.5 mg sc q24hrs. - Burn or Neurosurg UFH 5000 U sc q8hrs or LMWH gt
3400 IU sc q24hrs IPC/GCS. - Anticoagulation
- Therapeutic heparin infusion (aPTT).
- High dose LMWH.
- HIT
- DTIs (argatroban, bivalirudin, lepirudin).
- Doses needed usually much lower than recommended.
42Blood Products
Pharmacotherapy 20072757S. Pharmacotherapy2007
2769S.
43Pharmacologic Agents
NEJM 20073562301. Pharmacotherapy 20072793S.
Pharmacotherapy20072769S.
44Antibiotics and Antifungals
45Common ICU Antibiotics
- ß-lactams
- Penicillins
- Cephalosporins
- Carbapenems
- Monobactams
- Fluoroquinolones
- Levofloxacin, ciprofloxacin, moxifloxacin,
gemifloxacin, gatifloxacin - Aminoglycosides
- Gentamicin, tobramycin, amikacin
- Macrolides
- Erythromycin, azithromycin, clarithromycin
- Others
- Vancomycin, linezolid, daptomycin
46Antibiotics Mechanisms of Action
- ß-Lactam antibiotics
- Inhibit cell wall (peptidoglycan) synthesis
- Fluoroquinolones
- Induce negative supercoils in bacterial DNA by
inhibiting DNA gyrase. - Aminoglycosides
- Disrupt protein synthesis through selectively and
specifically binding to 30S ribosomal subunit. - Macrolides
- Reversibly bind to the 50S ribosomal subunit to
inhibits protein translation. - Others
- Vancomycin inhibits cell wall (peptidoglycan)
synthesis by high-affinity binding to cell wall
precursor called D-alanyl-D-alanine. - Linezolid inhibits an early step in bacterial
protein synthesis by preventing the formation of
the tRNAfMet-mRNA-30S (or 50S) subunit ternary
complex. - Daptomycin binds to Gram-positive bacterial cell
membrane by inserting calcium-dependent lipid
tail and rapidly depolarizes the cell membrane.
47ß-Lactams Adverse Effects
- Relatively low toxicity, generally well tolerated
especially in low-moderate doses - Gastrointestinal nausea, vomiting, abdominal
pain, diarrhea (20-30 incidence with ampicillin) - Skin rash ? most commonly reported with
ampicillin and amoxicillin (5-10 vs. 1-2 with
other penicillins) - Rash during ampicillin administration does NOT
necessarily signify a serious hypersensitivity
reaction - Hematologic neutropenia, prolonged bleeding
times, thrombocytopenia - CNS mental status changes, seizures in high-risk
patients - Electrolytes hypokalemia, hypernatremia
- Hepatic transaminase elevations, biliary
sludging - Renal interstitial nephritis, acute tubular
necrosis - Hypersensitivity (1-10 anaphylactic reactions
in 0.015 cross-sensitivity 5-10)
48Fluoroquinolones Adverse Effects
- Among the safest and best tolerated of all
antibiotic classes - GI nausea, vomiting, diarrhea (1-6)
- CNS headache, dizziness, insomnia (1-6)
- Rash lt1 for most agents, 3-4 for gemifloxacin
- Incidence of rash with gemifloxacin substantially
higher in women lt40 years of age (10 by 7 days
of therapy, 15 by 10 days) - Increased liver transaminases (lt2)
- Glucose abnormalities uncommon, but probably
increased with gatifloxacin - Risk factors include renal dysfunction, elderly,
Type I or II diabetics - QTc prolongation, risk of cardiac arrhythmias
low risk overall but possibly higher with
moxifloxacin - Risk factors include previous cardiac disease,
concomitant antiarrhythmic drugs, renal
dysfunction, electrolyte abnormalities - Tendonitis or tendon rupture (rare)
- Very low risk of photosensitivity
49Aminoglycosides Adverse Effects
- Nephrotoxicity (usually reversible)
- 8-26 of all patients receiving aminoglycosides
develop nephrotoxicity - Aminoglycosides eliminated via glomerular
filtration - At high doses and over prolonged periods of time,
drug accumulates within the proximal tubule cells
and results in cellular necrosis - Major risk factors dose and serum levels,
duration of administration,
underlying renal disease/injury - Ototoxicity
- Hearing loss
- High frequency tones usually most effected
- Can result in complete and permanent hearing loss
- Vestibular impairment
- Disequilibrium, vertigo, nausea
- Incidence and severity of ototoxicity is time-
and agent-dependent - Not always reversible
- Neuromuscular weakness
- Aminoglycosides enhance acetylcholinesterase.
- Skin rashes and drug fever are other adverse
effects, but considered minor
50Macrolides Adverse Effects
- GI irritability due to the motility-stimulating
effects - Thrombophlebitis with IV products
- avoided with adequate dilution (250 ml) and slow
infusion (45-60 min) - Allergic reactions skin rash, fever,
eosinophilia - Cholestatic hepatitis estolate preparation
chiefly in adults, pregnant women - Ototoxicity with high doses, reversible
- Torsade de pointes - rare
- Superinfections - Candida spp.
- Pseudomembranous colitis - rare
51Vancomycin Adverse Effects
- Infusion-related reactions
- Red man or Red neck syndrome (pruritus,
flushing, rash of upper body) occurs 0-35,
usually 10-20 minutes after start of infusion - Nephrotoxicity
- Incidence lt5 when administered alone but
increased by concomitant use of aminoglycosides
or other nephrotoxic drugs - Recent data also suggest daily doses ?4 grams may
increase risk - Ototoxicity
- Very unusual
- Tinnitis, vertigo, hearing loss
- Neutropenia, thrombocytopenia (rare)
- Phlebitis and pain at IV administration site
(common)
52Linezolid Adverse Effects
- Considered to be a safe, well tolerated drug in
most patients - GI nausea, vomiting, diarrhea (3-6)
- Headache (2-4)
- Elevation of hepatic transaminases (3-7)
- Reversible bone marrow suppression (1-5)
- Thrombocytopenia, leukopenia, anemia
- Usually occurs late in therapy (gt10-14 days)
- Most common in severely ill patients
- Taste alterations, tongue discoloration (2-3)
- Injection site reactions
53Daptomycin Adverse Effects
- Considered to be a safe, well tolerated drug
- GI constipation, nausea, vomiting, diarrhea
(3-6) - CNS Headache, insomnia, dizziness (2-5)
- Rash (4)
- Elevations in creatine phosphokinase (CPK)
- Occurs in lt3 of patients, usually asymptomatic
- Muscle weakness, myalgias observed in early
studies - Elevation of hepatic transaminases (3)
- Injection site reactions
- Pneumonia failure
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56UCH Anaerobes
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58Antifungals Mechanisms of Action
Cell wall Echinocandins (caspofungin,
anidulofungin, micafungin) Inhibit ß-(1-3)
glucan synthase
Plasma membrane
DNA synthesis Flucytosine
Polyenes (amphoterecin) Bind to ergosterol
Azoles (fluconazole, voriconazole, posaconazole)
Inhibit ergosterol synthesis
59Antifungals Clinical Applications
60Other Common Agents
- Corticosteroids (methylprednisolone, prednisone,
hydrocortisone, dexamethasone) - Bronchodilators (albuterol, ipratropium)
- Octreotide
- Prokinetic agents (erythromycin, metoclopramide),
laxatives - Nutrition
- Electrolytes
61Lifes a Beach but
Ill Take Questions