Drugs to review? Flashcards
Labetalol
CLASS= competitive ß1, ß2 & alpha 1 antagonist
MOA= blocks ß1, ß2 & alpha 1 receptors to block the effects of catecholamines & inhibit G-protein coupled signaling cascade (beta: alpha 7:1) thereby decrease BP, SVR, HR; CO unaffected (no alpha 2, so negative feedback not blocked). Also, decreases stage 4 depolarization in SA & AV node
Pharmacokinetics= 50% PB; onset- 5 min; DOA- 4 hrs; E1/2- 5-8 hrs; conjugation to glucuronic acid & eliminated via liver by CYP2D6 & kidneys. LIpid soluble
SE= hypotension, bradycardia, angina, bronchospasm, mask hypoglycemia, exercise intolerance, exacerbate PVD
CI= hypotension, bradycardia, HB, caution: asthma, COPD, CHF, cardiogenic shock, DM; avoid concurrent use with CCBs; effect decreased by salicylates & NSAIDs (decreases antiHTN effect)
Dose= 5-20 mg IV q 5-10 min (max 300mg)
Atropine
CLASS= tertiary amine anticholinergic- crosses BBB
(Most potent increase in HR)
MOA- Competitively inhibits muscariniac receptors at M1, M2, M3 with most predominant at M2, allowing SNS to dominate, raising the HR.
Pharmacokinetics= 40% PB; onset- 1 min; peak- 1-2 min; DOA- 30-60 min; E1/2- 2 hrs; hydrolyzed in the liver to tropine & tropic acid & excreted 18% unchanged in the urine. VD 1.6 L/kg
SE= increase IOP, sedation, post-op delerium- crosses BBB, increases HR, CO, arrhythmias, IOP, blurry vision; decreases secretions & GI motility, bronchodilation, urinary retention; inhibits diaphoresis; central anti-cholinergic syndrome
CI= glaucoma, renal disease, CAD, caution elderly
Dose= 0.01 mg/kg for reversal; 0.4-1 mg for brady; 1 mg q 3-5 min for asystole, PEA
Ketamine
Class? MOA? Pharmacokinetics? SE? CI? Dose?
CLASS=non-barbiturate induction agent; phencyclidine derivative
MOA= (1) blocks NMDA receptors to inhibit influx of Na+, Ca2+- inhibits the excitatory response of glutamate & produces a “dissociative state anesthesia” via depression of association areas of the brain (depresses cerebral cortex and thalamaus while increasing hippocampus); (1) analgesia effects by interacting with mu, kappa, delta & sigma receptors- (3) works on monoaminergic descending pain pathways & substance P in SC; (4) muscarinic (antagonist?) & (5) Ca++ channel antagonist
Pharmacokinetics= 12% (poor) PB; highly lipid soluble; onset- rapid 30-60sec; DOA= short 5-15min (short d/t redistribution); Vd- 3L/kg; E1/2- 2-3 hrs; acidic soluble & racemic mixture; metabolized by CYP450 to norketamine (active metabolite) then excreted in urine; clearance dependent on HBF
SE= increase CBF, ICP & CMRO2 & IOP; myoclonus, hallucinations & emergence delirium (can prevent with benzos); increase SNS stimulation = increase HR, SVR, BP; direct myocardial depressant (especially in critically ill patients that cannot surmount a SNS response); BRONCHODILATION (SNS); increase PVR; increase saliva production (laryngospasm risk), potentiates NMB’s
CI= psych disorders, head injury (increase ICP), eye injury, CAD, IHD, Systemic or pulmonary HTN
Dose= induction- 0.5-2 mg/kg IV; sedation 0.2-0.5 mg/kg IV; maintenance- 1-2 mg/kg/hr IV; 5-10 mg/kg IM/PR
Succinylcholine
CLASS= Depolarizing NMB; benzylisoquinolone
MOA= PARTIAL AGONIST- Binds to alpha subunits of nicotinic Ach receptors mimicking the action of ACh at the NMJ opening Ca++ channels & depolarizing the motor endplate; fasciculations then flaccid paralysis occurs; Channels stay open & membrane cannot respond to subsequent ACh; effect terminated when SCh diffuses away from the NMJ
Pharmacokinetics= water soluble; small Vd (0.2L/kg) & PB; onset- 30-60 sec; DOA- 8-15 min; E1/2- 2-4 min; rapidly hydrolyzed by plasmaesterases when diffuses away from the NMJ & excreted in the urine
SE= increase ICP, IOP, IGP; histamine release - decrease HR & BP, HYPERK+ (increae 0.5-1 mEq/L) (dysrhythmias); masseter spasm, myalgias, fasciculations, rhabdomyolysis, myoglobinuria, MH
CI= MH, renal patient with high K+, high K, peds unless emergency, caution asthma & COPD; atypical plasma esterase deficiency; muscles weakness like muscular dystrophy; sepsis, burn patients
Dose= laryngospasm-10-20 mg IV; RSI/intubation- 1-1.5 mg/kg; infusion- 2-4mg/min
Atracurium
CLASS= intermediate acting benzyllisoquinoline NDMR (-curium)
pre and post NMJ AcH inhibition
MOA: Competitively inhibit ACh binding at the post-junctional nicotinic receptors thereby preventing Ca++ channels from opening, thus no depolarization of the muscle cell membrane & no contraction
Pharmacokinetics= water soluble; 80% PB; Vd: 0.2L/kg; onset- 2-3 min; DOA- 30-60 min; E1/2- 20 min; metabolized by ester hydrolysis 2/3 & Hofmann elimination 1/3 (temp & pH dependent) & excreted in the urine; has metabolite Laudanosine (can accumulate in RF & cause CNS problems like seizures- is a tertiary amine and can cross BBB)
SE= Histamine release; decrease BP (minimal) & increase HR; skin flushing (all related to histamine release); muscle weakness; NMB can be potentiated with IA’s, ketamine, some abx, lithium, LA’s, antiarrhythmics, Mg++
CI= conscious patient, hypersensitivity; caution with asthma, COPD, CAD, seizure hx, muscle weakness, myasthenia gravis (increase sensitivity); metabolite can accumulate with renal problems; prolonged action in acidosis & hypothermia
Dose= initial- 0.5 mg/kg IV; maintenance- 0.08 - 0.1 mg/kg q 20-45 min
Cisatracurium
CLASS= intermediate acting benzyllisoquinoline NDMR; (-curium) stereoisomer of Atracurium (A/C)
MOA: Competitively inhibit ACh binding at the post-junctional nicotinic receptors thereby preventing Ca++ channels from opening, thus no depolarization of the muscle cell membrane & no contraction
Pharmacokinetics= water soluble; Vd: 0.2L/kg; onset- 3-5 min; DOA- 30-60 min; E1/2- 30 min; metabolized 80% by Hofmann elimination (temp & pH dependent) & excreted in the urine; has metabolite Laudanosine 1/5 that of Atracurium (can accumulate in RF & cause CNS problems like seizures)
SE= NO histamine & CV stable; good choice if CV instability or severe renal dysfunction, asthma or COPD or peds (immature liver); muscle weakness; potentiated NMB with IA’s, ketamine, some abx (such as aminoglycosides), lithium, LA’s, antiarrhythmics, Mg++
CI= conscious patient, hypersensitivity; muscle weakness, myasthenia gravis (give 1/10th of dose), seizure hx; metabolite can accumulate with renal problems; prolonged action in acidosis & hypothermia
Dose= initial- 0.1-0.2 mg/kg IV; maintenance- 0.02 mg/kg IV q 40-60 min
Rocuronium
CLASS= short-intermediate acting steroid derivative NDMR
MOA: Competitively inhibit ACh binding at the post-junctional nicotinic receptors thereby preventing Ca++ channels from opening, thus no depolarization of the muscle cell membrane & no contraction
Pharmacokinetics= water soluble; Vd: 0.2L.kg; onset-30-60sec ; DOA- 30-90 min; E1/2- 2 hrs; hepatic metabolism with renal (30% unchanged) & biliary (50%) elimination (Prolonged effects in hepatic, renal, & biliary disease)
SE= NO histamine & CV stable; bronchospasm; muscle weakness; effects potentiated IA’s, ketamine, some abx, lithium, LA’s, antiarrhythmics, Mg++
CI= conscious patient, hypersensitivity, myasthenia gravis, caution muscle weakness; caution hepatic, renal, & biliary disease; hypothermia prolongs action
Dose= initial- 0.6-1.2 mg/kg (low = intubation; high = RSI); defasiculating- 0.06-0.1mg/kg (5-10 mg per lecture); maintenance- 0.1-0.2 mg/kg
Vecuronium
CLASS= intermediate acting steroid derivative NDMR
MOA: Competitively inhibit ACh binding at the post-junctional nicotinic receptors thereby preventing Ca++ channels from opening, thus no depolarization of the muscle cell membrane & no contraction
Pharmacokinetics= 80% PB; Vd: 0.2L/kg; onset-3-5 min; DOA- 30-60 min; E1/2- 1hr; hepatic metabolism with renal (30% unchanged) & biliary (50%) excretion (prolonged effects in hepatic, renal, & biliary disease); active metabolite= 3-desacetyl vecuronium (was called 3-OH in lecture) (50% as potent as parent)
SE= NO histamine & CV stable; bronchospasm; muscle weakness, can cause SA node exit block; NMB potentiated with IA’s, ketamine, some abx, lithium, LA’s, antiarrhythmics, Mg++
CI= conscious patient; hypersensitivity; myasthenia gravis, caution muscle weakness; caution hepatic, renal, & biliary disease; hypothermia prolongs action
Dose= initial- 0.1 mg/kg; defasiculating 0.01mg/kg IV; maintenance- 0.01-0.02mg/kg q 25-45 min
Pancuronium
CLASS= long acting steroid derivative NDMR
MOA: Competitively inhibit ACh binding at the post-junctional nicotinic receptors thereby preventing Ca++ channels from opening, thus no depolarization of the muscle cell membrane & no contraction
Pharmacokinetics= small PB; Vd: 0.2L/kg; onset- 3-5 min; DOA- 2-3 hours; E1/2- 2 hrs; 10-20% hepatic metabolism with renal excretion (80% unchanged); 3 active metabolites- most is the 3-desacetyl pancurounium (50% as potent as parent)- (aka 3-OH in lecture) prolonged excretion in renal, hepatic disease, elderly & obese
SE= SNS stimulation = increase HR, BP; bronchospasm; no histamine; muscle weakness, NMB potentiated with IA’s, ketamine, some abx, lithium, LA’s, antiarrhythmics, Mg++
CI= conscious patient, hypersensitivity, renal dysfunction; CAD, HF or HD, myasthenia gravis, caution muscle weakness
Dose= initial- 0.1 mg/kg; maintenance- 0.01-0.02 mg/kg q 40-60 min
Morphine
CLASS= Natural opioid agonist
MOA: Activates Mu, Kappa & delta G protein coupled opioid receptors in the brain, spinal cord, & peripheral afferent neurons causing Ca2+ channel inactivation presynaptically to inhibit the release of excitatory NT’s such as Epi, NE & Substance P or post synapatically increase K+ conductance to hyperpolarize the cell & directly decrease neurotransmission; this increasing the pain threshold, alters pain perception & inhibits ascending pain pathways
Pharmacokinetics= 30% PB; 23% non-ionized (pKa= 7.9); low lipid solubility; Vd: 3L/kg
- IV peak- 15-30 min; DOA- 3 hrs; E1/2- 3-4 hrs
- Hepatic & renal metabolism to morphine-3 glucoronide (less active) & morphine-6-glucoronide (active metabolite which is 650x more potent) & excreted in the urine (1-12% unchanged) & feces
SE= analgesia, euphoria, sedation, N/V/C, pruritus, dry mouth, urinary retention; SOO spasm; dose-dependent respiratory depression (decrease RR & increase TV), dose dependent decrease HR, BP, SVR more profound w/ HISTAMINE release; inhibits SA/AV node; delayed respiratory depression in epidural & spinals b/c not as lipid soluble
CI= allergy, respiratory depression, asthma, COPD; renal disease (metabolites can accumulate); synergistic hypnosis & respiratory depression w/ Benzo’s & other CNS depressants; decrease dose in peds & elderly
Dose= 0.01-0.2mg/kg – usually 2.5-15mg IV (in divided 1-4 mg doses q 5 min) Q 3-4 hours; infusion 0.8-10mg/hr
Meperidine
CLASS= phenyl-piperidine synthetic opioid agonist
MOA: Activates Mu, Kappa & delta G protein coupled opioid receptors in the brain, spinal cord, & peripheral afferent neurons causing Ca2+ channel inactivation presynaptically to inhibit the release of excitatory NT’s such as Epi, NE & Substance P or post synapatically increase K+ conductance to hyperpolarize the cell & directly decrease neurotransmission; this increasing the pain threshold, alters pain perception & inhibits ascending pain pathways
MOA cont.: anti-cholinergic effects (atropine-like structure), Alpha-2 agonist, blocks Na channels
Pharmacokinetics= 1/10th as potent as morphine. 60% PB; nonionized- 10% (pKa: 8.5); low lipid solubility; Vd: 4L/kg;
- Onset fast; peak 5-10min; DOA- 3 hrs; E1/2: 3-4hrs
- Liver metabolism to normeperdine (½ as potent as parent & can cause seizures & myoclonus) & excreted in the urine
- 65% pulmonary 1st pass effect
SE= analgesia, euphoria, sedation; N/V/C, pruritus, dry mouth, urinary retention; SOO spasm; dose dependent respiratory depression (increase RR & decrease__TV); dose dependent decrease BP & SVR more profound w/ HISTAMINE release, decrease shivering; sympathomimetic - increase HR & direct cardiac depressant
CI= allergy, respiratory depression, asthma, COPD; caution seizure hx, CAD; fatal interaction with MAOIs; decrease dose in renal disease (metabolites can accumulate); decrease dose in peds & elderly
Dose= 50-100 mg IV; 12.5mg for shivering (total dose should not exceed 1 gram/24 hrs)
Hydromorphone
CLASS= semi-synthetic opioid agonist that is derivative of morphine & 5x more potent than morphine
MOA: Activates Mu G protein coupled opioid receptors in the brain, spinal cord, & peripheral afferent neurons causing Ca2+ channel inactivation presynaptically to inhibit the release of excitatory NT’s such as Epi, NE & Substance P or post synapatically increase K+ conductance to hyperpolarize the cell & directly decrease neurotransmission; this increasing the pain threshold, alters pain perception & inhibits ascending pain pathways
Pharmacokinetics= 8-19% PB; onset <30 minutes ; peak- 5-10 min; DOA-2-4 hrs (longer); E1/2- 1-3 hrs; significant 1st pass metabolism in liver with 95% metabolized to Hydromorphone-3- glucuronide (inactive) & excreted in the urine
SE= analgesia, more sedation & less euphoria than Morphine; N/V/C, pruritus, dry mouth, urinary retention, SOO spasm; dose dependent respiratory depression (decrease RR & increase__TV); Dose dependent decrease HR, BP, SVR
CI= allergy, respiratory depression; synergistic hypnosis & respiratory depression w/ Benzo’s & other CNS depressants; decrease dose in peds & elderly; increased ICP without controlled ventilation
Dose= 1-4 mg IV q 4-6 hrs
Fentanyl
CLASS= Phenyl piperidine synthetic opioid agonist
MOA: Activates Mu G protein coupled opioid receptors in the brain, spinal cord, & peripheral afferent neurons causing Ca2+ channel inactivation presynaptically to inhibit the release of excitatory NT’s such as Epi, NE & Substance P or post synapatically increase K+ conductance to hyperpolarize the cell & directly decrease neurotransmission; this increasing the pain threshold, alters pain perception & inhibits ascending pain pathways
Pharmacokinetics= 100x more potent than MSO4 (morphine)
- 80% PB; non-ionized- <10% (pKa= 8.4); high lipid solubility; Vd-4L/kg
- Fast onset; peak- 6.4 min; short DOA- 1 hr; E1/2- 3-6 hrs;
- Liver metabolism (n-dealkylation & hydroxylation) that is dependent on HBF & excreted in the urine
- Weak active metabolite norfentanil
- 75% pulmonary 1st pass effect & Secondary peak
- Longer context sensitive ½ time with infusions
SE= analgesia, euphoria, sedation, N/V/C, pruritus, dry mouth, urinary retention; SOO spasm; dose-dependent respiratory depression (decrease RR & increase__TV), dose dependent decrease HR, BP, SVR; seizure like activity, muscle rigidity & wooden chest syndrome; blunts SNS response to DVL
CI= allergy, respiratory depression, caution in hepatic/renal disease, head trauma (increase ICP), gallbladder disease, bradyarrhythmias; synergistic hypnosis & respiratory depression w/ Benzo’s & other CNS depressants; decrease dose in peds & elderly
Dose= bolus- 1-2 mcg/kg (analgesia); 25-100mcg (pre-med); infusion- 0.01-0.05 mcg/kg/min
Sufentanil
Sufentanil- Phenyl-piperidine synthetic opioid agonist; most potent opioid
MOA: Activates Mu G protein coupled opioid receptors in the brain, spinal cord, & peripheral afferent neurons causing Ca2+ channel inactivation presynaptically to inhibit the release of excitatory NT’s such as Epi, NE & Substance P or post synapatically increase K+ conductance to hyperpolarize the cell & directly decrease neurotransmission; this increasing the pain threshold, alters pain perception & inhibits ascending pain pathways
Pharmacokinetics= 1000x more potent than morphine
- 90% PB; 20% non-ionized (pKa= 8.0) ; highest lipid solubility; Vd-3L/kg
- Fast onset; peak – 6.2 min; short DOA- 30 min; E1/2- 2.5 hr
- Liver & SI metabolism & excreted in urine
- Active metabolite desmethylsufentanil
- 75% pulmonary 1st pass effect & Secondary peak
SE= analgesia, euphoria, sedation, N/V/C, pruritus, dry mouth, urinary retention; SOO spasm; dose-dependent respiratory depression (decrease R__R & increase__TV), dose dependent decrease HR, BP, SVR; bronchospasm; seizure like activity, muscle rigidity & wooden chest syndrome; blunts SNS response to DVL
cyp 3a inhibitors may increase levels of sufentanil
CI= allergy, asthma, airway obstruction; caution in hepatic & renal dysfunction; synergistic hypnosis & respiratory depression w/ Benzos & other CNS depressants; decrease dose in peds & elderly
Dose= analgesia -0.1-1 mcg/kg; infusion- 0.0015-0.01mcg/kg/min
Remifentanil
CLASS= phenyl-piperidine synthetic opioid agonist with ester link
MOA: Activates Mu G protein coupled opioid receptors in the brain, spinal cord, & peripheral afferent neurons causing Ca2+ channel inactivation presynaptically to inhibit the release of excitatory NT’s such as Epi, NE & Substance P or post synapatically increase K+ conductance to hyperpolarize the cell & directly decrease neurotransmission; this increasing the pain threshold, alters pain perception & inhibits ascending pain pathways
Pharmacokinetics= 80% PB; 65% non-ionized (pKa= 7.3); high lipid solubility; Vd- 0.4L/kg
- Onset 1-3 min; peak- 2 min; DOA- shortest 10 min; rapidly metabolized by tissue & plasma esterases
SE= analgesia, euphoria, sedation, N/V/C, pruritus, dry mouth, urinary retention; SOO spasm; dose-dependent respiratory depression (decrease RR & increase TV), dose dependent decrease HR, BP, SVR; skeletal muscle rigidity, blunts SNS to DVL
CI= allergy, respiratory depression; do not use in epidural/spinals (d/t glycine prep); need plan for post-op pain; synergistic hypnosis & respiratory depression w/ Benzo’s & other CNS depressants; decrease dose in peds & elderly
Dose= initial- 1-2 mcg/kg; infusion- 0.05-0.25 mcg/kg/min
Lidocaine
CLASS=amide LA (& Class IB antiarrhythmic – its active metabolite monoethyglycinexylidide blocks Na+ channels in cardiomyocytes,decrease AP duration & refractory period)
- LA MOA- bind to H-gate of Na channel and physically obstruct the channel
- keeps Na channel in closed/inactivated state and prevents further transmission AP (unionized portion diffuses across membrane, ionized portion blocks channel)
Pharmacokinetics=
- pKa- 7.9; non-ionized- 24%, PB- 70% (PB 50% for antiarrhythmic); low potency & low lipid solubility
- Fast onset & moderate DOA (1-2hr); E1/2- 1.5hr (antiarrhythmic- 1-8 hrs)
- Intrinsic vasodilator activity; uptake into the lungs
- CYP450 liver metabolism that depends on HBF & excreted in urine
- 2 active metabolites- xylidide & monoethylglycinexylidide
SE= TNS, high incidence of cauda equina syndrome (specfiically high concentraiton lidocaine); BLUNT SNS TO DVL
LA toxicity
5-10 mcg/ml: circumoral numbness, lightheadedness, tinnitus, skeletal muscle twitching, visual disturbances, systemic hypotension, myocardial depression, & tachycardia, decreased SVR & cardiac output.
10-15 mcg/ml: seizures, unconsciousness
15-25 mcg/ml: apnea, coma
>25 mcg/ml: cardiovascular depression/collapse
CI= methemoglobinemia
LA hypersensitivity to amide LA, coagulopathies, infection, hypovolemia, refusal, inability to cooperate inexperience of provider
Antiarrhythmic hypersensitivity; WPW syndrome, HB, hepatic disease; CYP450 inhibitors such as Cimetidine & Propranolol decrease metabolism
Dose=
MAX: 4mg/kg & with epi 7mg/kg;
Spinal MAX- 30-100mg (1-2mL) (1.5-5%)
Epidural: 15-30 ml of 1-2%
PNB- volume depends on location- 1-2%
Intubation to blunt DVL & antiarrhythmic- 1-2 mg/kg (max antiarrhythmic: 3mg/kg)
Bupivicaine
CLASS= amide LA
Pharmacokinetics=
- pKa- 8.1; non-ionized- 17%, PB- 95%; very potent & highly lipid soluble
- Moderate onset & long DOA (4-8hr); E1/2- 3.5hr
- CYP450 liver metabolism that depends on HBF
SE= differential blockade; TNS, “very low risk for neuro complications with spinal” (CB) ; highly CV toxic hypotension, myocardial depression, AV block, arrhythmias; local anesthestic toxicity (cirucmoral numbness, tinnitus, vision changes, dizziness, restlessness, muscle twitching in face/extremities–> seizures)–> CNS depression, apnea, hypotension).
CI= refusal, inability to cooperate, coagulopathies, hypovolemia, infection @ site; inexperience of clinician; extreme caution in poor CV function & HB
Dose=
- MAX- 2.5mg/kg
- Spinal MAX - spinal-15-20mg (0.5, 0.75%, 3-4 mL)
- Epidural- 15-30 ml of 0.125-0.5%
- PNB- amount depends on location- 0.25-0.5%
Ketorolac? Toradol?
CLASS= non-steroidal anti-inflammatory drug
MOA= blocks cyclooxygenase 1 & 2; inhibits prostaglandin synthesis causing anti-inflammatory effects & analgesia effects; also blocks synthesis of thromboxane A2 causing REVERSIBLE inhibition of platelet aggregation
Pharmacokinetics=99% PB; onset- 10 min; peak- 2-3 hrs; DOA 6-8 hours; E1/2- 5 hrs (prolonged to 6-8 hrs in elderly); liver conjugation &60% excreted unchanged in urine
SE=no respiratory or CV depression; impaired bone healing,increasebleeding time,GIB/ulcerations; bronchospasm (increaseleukotrienes), renal toxicity/ARF; black box- do not use peri-op in CABG, can causeincrease CV effects like MI & stroke; can inhibit platelet function
DDI’s= reduces effect of diuretics, beta blockers, & ACEI’s; increased risk of bleeding when combined with other anticoagulants; increases levels of other protein bound drugs such as Warfarin; AVOID with Probenecid =increases levels/prolongs action of Ketorolac
CI=asthma–> bronchospasm, ASA allergy, RF, liver failure, GIB, coagulation problems, 3rd trimester; NO post-CABG
Dose= 30 mg IV x 1 or q 6 hrs (max daily is 120mg)- do not give longer than 5 days; decrease dose in elderly to 15mg
Metoclopramide
CLASS= central dopamine receptor antagonist & serotonin-4 receptor agonist
MOA= blocks the DA2 receptors centrally in the CRTZ of the medulla preventing N/V; stimulates serotonin-4 receptors causing increase gastric motility & peristalsis; this is also accomplished by increase ACh @ the muscarinic post-synaptic receptors; increase LES tone & relaxation of pylorus & duodenum
Pharmacokinetics= 30-40% PB;; Vd 2-4L/kg; onset- 1-3 min; DOA- 1-2 hrs; E1/2- 2-4 hrs; metabolized in the liver & 40% excreted unchanged in the urine
SE= increase gastric motility, LES tone; decrease N/V; extrapyramidal SE, abdominal cramping (w/ rapid administration), sedation, prolactin secretion, dry mouth
DDI’s= potentiates sedation of CNS depressants; inhibits plasma cholinesterases thus may prolong Succinylcholine & Mivacurium , MAOIS, TCA, pt with EPS
CI= Parkinson’s, bowel obstruction, GI hemorrhage, seizure disorders, arrhythmias with Zofran; do not give with phenothiazines, MAOI, TCA, pt c EPS; pheochromocytoma
Dose= 10-20 mg IV over 3-5 min 15 min before induction
Ondansetron
CLASS= serotonin-3 receptor antagonist
MOA= blocks serotonin receptors peripherally on vagal nerve terminals in GI tract & centrally in the CRTZ
Pharmacokinetics= 70% PB; Vd 2-2.5 L/kg; onset- 30 min; DOA- 4-8 hrs; E1/2- 3-4 hrs; metabolized in the liver with renal excretion (5% unchanged)
SE= HA with rapid administration, fatigue, arrhythmias (w/ Reglan), constipation, diarrhea
CI= hypersensitivity, liver disease (decrease dose), SSRIs, Generally not recommended for treatment of existing chemotherapy-induced emesis or
for prophylaxis of nausea from agents with little potential to cause nausea
Dose= 4-8mg IV over 2-5 min
Famotidine
CLASS= selective competitive H2 receptor antagonist (MOST potent)
MOA: Competitively bind to H2 receptors, inhibiting the binding of histamine to gastric parietal cells, decrease cAMP & secretion of H+ ions, decrease gastric acid secretion from the parietal cells; can prevent Mendelsson syndrome or to treat GERD or ulcers; crosses BBB
Pharmacokinetics= 20% PB; onset- 30 min; DOA- 8 hrs; E1/2- 3 hrs; liver metabolism with 75% excreted unchanged in the kidneys; must be given IV d/t extensive first pass effect
SE= dMultisystem disease and advanced age increase severity of side effects. Diarrhea, HA, fatigue, skeletal muscle pain, confusion (crosses BBB), arrhythmias; rapid IV administration may cause bradycardia & hypotension (Give over 2 minutes for famotidine)
CI= caution liver/renal disease, hypersensitivity; may alter absorption of some drugs by increasing gastric pH
Dose= 20 mg IV over 2 min
FUrosemide?
CLASS= loop diuretic
MOA= inhibits Na/2Cl/K pump in the thick ascending limb of loop of Henle causing excretion of H2O, Na+, Cl-, K+, Mg2+ & Ca2+; evokes renal production of prostaglandin; used for treatment of edema, hypercalcemia & differential diagnosis of oliguira
Pharmacokinetics= 90% PB; onset of diuresis- 5 min; DOA- 2 hours; E1/2- 1 hr; hepatic metabolism with 50% excreted by kidneys (glomerular filtration & renal tubular secretion) & 30% excreted unchanged in the bile
SE= hypotension, hyperglycemia, electrolyte imbalances = especially hypokalemia & hypochloremia, nephrotoxicity, ototoxicity, potentiates NMB, decrease clearance of lithium; possible cross reaction if have sulfa allergy
CI/Caution= fluid & electrolyte abnormalities (hyperK), can increase risk of nephrotoxicity or ototoxicity if administered with aminoglycosides & cephalosporins
Dose= 0.1-1 mg/kg IV; titrate & start with 5-40 mg IV
Mannitol
CLASS= osmotic diuretic (6 carbon hexose sugar)
MOA= increase osmolarity of the plasma drawing fluid into the intravascular space = causing increase UOP & diuresis; used to decrease ICP & IOP & differential diagnosis of oliguria
Pharmacokinetics= onset- 15 min; DOA- 3-6 hrs; E1/2- 1 hr; cleared by the kidney 100% unchanged- none is reabsorbed
SE= HA, convulsions, rash, blurry vision, pulmonary edema, hypovolemia, electrolyte imbalances; hypokalemic hypochloremic alkalosis; decrease ICP & IOP
CI= hypovolemia, severe kidney disease, CV dysfunction, intracranial bleeding
Dose= 0.25-1 g/kg over 30-60 min
Dexamethason
CLASS= corticosteroid with ONLY glucocorticoid properties
MOA= enters the cell & binds to glucocorticoid & receptors in the cytoplasm forming a steroid-receptor complex that enters the nucleus & affects DNA transcription; Metabolically causes an increase nutrient availability by increase BG, amino acids, & Triglycerides; inhibits the inflammatory process by inhibiting phospholipase A2 = decrease arachnidonic acid = decrease inflammatory mediators such as leukotrienes, cytokines, & prostaglandins
ALSO- inhibits COX & Lipoxygenase pathways- may lead to analgesia effects; antiemetic property MOA unknown (poss. decrease prostaglandin, increase endorphins & appetite)
Good: Antiemetic, analgesia, periop airway edema, cerebral edema
Pharmacokinetics=DOA= 72hrs; E1/2- 3 hrs; liver metabolism with 30% excreted unchanged in the urine; antiemetic effect may last 24 hrs
SE= perineal burning, increase BG, HTN, HYPOK+; immunosuppression, HPA axis suppression, delayed wound healing, fat redistribution, muscle & bone wasting
CI= caution in DM, untreated infection, hypersensitivity
Dose= 4-10 mg IV
Nitroglycerin
CLASS= organic nitrate
MOA= produces NO, which activates guanylate cyclase, increase cGMP inhibiting Ca2+ entry into cell & increase uptake of Ca2+ into the smooth ER causing peripheral & SM vasodilation; Dilates Venous> arterial to decrease preload with NO change in SVR & HR; increaseCA blood flow to ischemic areas; relaxes SM in GI tract and SOO
Pharmacokinetics= 60% PB; large Vd; onset- immediate; DOA- 5min; E1/2- 5 min; metabolized rapidly with nitrate metabolite that is capable of producing methemoglobin by oxidation of ferrous to ferric ion in Hgb with <1% excreted unchanged in the urine
SE= increase ICP; dizziness, HA, syncope, N/V, MI, decrease venous return, CA vasodilation, decrease hypoxic vasoconstriction; increase bleeding time,; relaxes SM & SOO spasm,; can cause tachyphylaxis (need nitrate free periods);
CI= do not use with PDIs; hypotension, hypertrophic cardiomyopathy, aortic stenosis, increase ICP, anemia, cardiac tamponade, caution in liver failure increase risk of methemoglobinemia,
Dose= initially 5-10 mcg/min & titrate to 5-200 mcg/min; 200 mg at a time for SOO spasm
Nitroprusside
CLASS= direct nonselective peripheral vasodilator
MOA= prodrug that interacts with oxyhemoglobin dissociates to methemoglobin, NO, & cyanide; NO activates guanylate cyclase, increase cGMP inhibiting Ca2+ entry into cell & increase uptake of Ca2+ into the smooth ER causing peripheral & SM vasodilation; equally dilates venous to ê preload & arteries to decrease afterload; reflex increase HR & contractility
Pharmacokinetics= onset- immediate; E1/2- 5 min; metabolism- transfer of an electron from iron to SNP yields methemoglobin & SNP radical- 5 cyanide ions released; 1 reacts with methemoglobin to form cyano-methemoglobin (nontoxic) & the rest are metabolized in the liver & kidney & converted to thiocyanate which is cleared by the kidney (slowly cleared- takes 2-7 days)
keep bag covered- light can conver SNP–> aquapentacyanoferrate and release hydrogen cyanide in the presence of light
SE= methemoglobinemia (higher risk with gtt >2mcg/kg/min), cyanide toxicity (s/s development is tachyphylaxis of drug), thiocyanate toxicity (causing seizures, & mental status changes), hypotension, tachycardia, increase bleeding time (plt inhib), increase ICP, Tachyphylaxis, hypoxia, lactic acidosis, decrease hypoxic vasoconstriction, CORONARY STEAL
CI= renal failure, hypotension, hypertrophic cardiomyopathy, aortic stenosis, increase ICP, caution CAD, don’t use with PDIs
Dose= 0.3-10 mcg/kg/min (maintain <2mcg/kg/min to reduce r/f toxicity) or 1-2 mcg/kg for HTN crisis bolus
Transexamic Acid (TXA )
Class: Antifibrionlytic: lysine analog
MOA: Competitively inhibits plasminogen activation (binds to kringle domain in palce of lysine on plasminogen)
reduces plasmin concentrationa nd fibrinolytic activity; TXA directly inhibits plasmin at high doses
- Still examining exact MOA- Alternative hypothesis is that TXA improves survival via reduciton of proinflammatory plasmin activity
Pharmacokinetcis: 3% PB vd 9-12 L; 95% excreted unchanged (reduce dose in renal pts) Onset 5-15 min; DOA 3 HOURS. E1/2T: 2-11 Hours
S/E: Seizures (gaba blockade), vision changes, ureteral obstructionand bleeding, renal toxicity
C/I: (not given in lecture…) from pfizer website:
- In patients with subarachnoid hemorrhage. Anecdotal experience indicates that cerebral edema and cerebral infarction may be caused by CYKLOKAPRON in such patients.
- In patients with active intravascular clotting.
- In patients with hypersensitivity to tranexamic acid or any of the ingredients
DOSE: 1 gm in 100 cc NS over 10 min then 1 gm in 100 cc NS over 8 hours. Do not admin in same line as blood, VIIa, or PCN. Stored 15-30C
Hydrochlorothiazide
CLASS= thiazide diuretic
MOA= inhibits the reabsorption of Na+ & Cl- in the ascending loop of Henle & DCT, thereby enhancing Na+ & H2O excretion; used for treatment of HTN usually in combo with ßB
Pharmacokinetics= 70% PB; onset- 2 hrs; DOA- 6-14 hrs; E1/2- 6-14 hrs; 100% excreted unchanged in the urine
SE= hypotension, rash, hyperglycemia, decrease K+ & Mg2+, electrolyte imbalances, potentiates NMB, nephropathy, increase digoxin toxicity, low ceiling effect
CI= renal failure, pregnancy, Antiarrhythmic agents that prolonged QTI causing torsades, decrease dose in elderly
Dose= 25-100 mg/day PO in 1-2 doses; max 200 mg
Propranolol
CLASS= nonselective beta antagonist; ß1=ß2
MOA= antagonizes the ß1 & ß2 receptors equally to block the effects of catecholamines & inhibit G-protein coupled signaling cascade; ß1- decrease contractility, HR, CO & O2 demands; ß2 blockade= increase PVR & increase CA vascular resistance (offset by decrease demand on the heart with the ß1)
Pharmacokinetics= 90% PB; high lipid solubility; large first pass effect; onset- 5 min; DOA- 4 hrs; E1/2- 2-3 hrs; extensive pulmonary uptake; liver metabolism by CYP450 which relies on HBF & excreted in the urine (can decrease clearance of other drugs metabolized by CYP 450- LA, benzos, warfarin, etc.)
SE= hypotension, bradycardia, bronchospasm, Na+ retention d/t renal response from decrease CO, mask hypoglycemia, exacerbate PVD
CI= HB, bradycardia, hypotension, asthma/bronchospasm, CHF, DM, decrease clearance of LA; decrease pulmonary 1st pass effect of fentanyl
Dose= 0.05 mg/kg IV or 1-10 mg (slowly 1mg q 5 min)
Octreotide
CLASS= synthetic analog of endogenous polypeptide hormone somatostatin (produced by the delta cells of the pancreas)
MOA= binds to somaostatin receptors on carcinoid tumors to decrease amount of serotonin released from tumor & decrease vasoactive amines; also inhibits release of GH, VIP, glucagon & insulin; selective vasoconstriction of splanchnic vasculature to redistribute blood flow (tx. esophageal varices)
Pharmacokinetics= 65% PB; onset- rapid; peak- 2 hrs; E1/2- 2 hrs; liver metabolism & excreted 30% unchanged in the urine
SE=decrease glucose tolerance, hyperglycemia, ecreased GI motility, N/V, bradycardia & heart block possible w/ IV boluses
CI= hypersensitivity; caution in DM (exacerbation)
Dose= carcinoid crisis- 50-100 mcg/hr; 25-200 mcg bolus PRN; 25-50 mcg/hr for bleeding varices
Sugamamadex?
CLASS: novel modified cyclodextrin molecule- arranged in a ring shape
MOA: Cycodextrin with 8 sugars arrange in a ring, with a hydrophobic cavity which encapsulates and forms complexes with nondepolarizing NMB rocuronicum and vecurionium,. Has a very high association rate and low dissasociation rate. Can be used to reverse even a deep bockade (1-2 Post tetanic contraction (PTC)
PK: Vd 30L/kg; E1/2 T= 2 hours; metabolism of sugammadex is very limited; excreted predominately unchanged by the kidneys.
S/E: Hypersentiviity, inadeqaute dose can lead to delayed manifesatation of residual block; bradycardia, N/V, hypotension, pain, HA
CI: Renal impairment (avoid in pt with CrCl <30 mL/.min); known hypersensitivity, safety and FDA approval not established for children under 17 (recently ok’ed 2-17 yo). Hormonal contraceptives can be less effective; contraceptive back up needed for 7 days
DOSE: Dependent on level of blockade
- 2mg /kg recommended if 2/4 twitches present on TOF
- 4mg/kg recommneded if 1-2 PTC twitches and no twitch responses to TOF stimulation (deep blockade)
- 16 mg/kg with profound blockade induced by RSI dose of Rocuronium (1.2 mg/kg)
Phenergan
CLASS= phenothiazine; H1 & Dopamine 2 antagonist
MOA= blocks DA receptors in CRTZ preventing N/V & antagonizes H1 @ receptors= decrease histamine mediated response in respiratory tract, GI & blood vessels
Pharmacokinetics= 90% PB; onset- 3-5 min; DOA- 2-4 hrs; E1/2- 9-16 hrs; metabolized in the liver including CYP450 & excreted in the urine
SE= extrapyramidal effects, anticholinergic effects, sedation, arrhythmias (prolonged QT), neuroleptic malignant syndrome
CI= hypersensitivity, peds < 2 yrs old, Parkinson’s; caution in renal, hepatic, cardiac, pulmonary disease; caution will potentiate sedative effects of anesthetics
Dose= 6.25-25 mg IV
Droperidol
CLASS= butyrophenone; DA antagonist
MOA= blocks DA at its receptor on the CRTZ of the medulla preventing N/V
Pharmacokinetics= Highly PB; onset- 30 min; DOA- 12 hrs; E1/2- 2 hrs; metabolized in the liver with 5% renal excretion
SE= extrapyramidal effects; black box- torsades, prolonged QTI; decrease BP, sedation, akathesia,
CI= hypersensitivity, Parkinson’s, history of prolonged QT interval, do NOT give with reglan; caution will potentiate sedative effects of anesthetics
Dose= 0.625-2.5 mg IV
Sodium Citrate/ Bicitra
CLASS= nonparticulate antacid; pH = 8.4
MOA= pH of 8.4 & directly neutralizes gastric acid to NaHCO3; increase gastric acid pH to prevent Mendelsson syndrome
Pharmacokinetics= onset- 15-30 minutes effectiveness; metabolized as NaHCO3 in the kidneys & <5% excreted unchanged in the kidneys
SE= unpleasant taste, increase gastric volume, N/V
CI= low Na+ diet, severe renal impairment, patients taking aluminum antacids
Dose= 15-30 ml 15-30 min preop
Glucagon
CLASS= synthetic analog of endogenous polypeptide hormone glucagon (produced by the alpha cells of the pancreas)
MOA= activates adenylate cyclase = increase cAMP = (1) increases glycogenolysis & gluconeogenesis= increase BG, increase insulin release; (2) induces catecholamine release, increase contractility & increase HR; (3) relaxes smooth muscle; used for hypoglycemia, SOO spasm & ßB OD
Pharmacokinetics= onset- rapid; DOA- 1hr; E1/2- 5 min; metabolized in the liver, kidney & tissues to inactive metabolites
SE= Hyperglycemia, hypoglycemia (paradoxical), hypokalemia, decrease gastric motility, N/V, incrase RBF; relax sphincter of Oddi; tachycardia with Afib
CI= hypersensitivity, pheochromocytoma, insulin-secreting tumor; caution DM
Dose= 1-5 mg IV over 5 min or 20 mg/hr; 0.3 mg IV for SOO spasm
Arginine Vasopressin
CLASS= exogenous antidiuretic peptide & vasopressor
MOA= V1- arterial smooth muscle contraction causing profound vasoconstriction (large doses) V2= collecting duct in nephron, increased H2O permeabiliyt/reabsoprtion back into circulation. V3= increases ACTH release; PromotEs hemostasis by increasing VWF and factor VIII; causes peristalsis by stimulating GI smooth muscle
Pharmacokinetics= onset- rapid E1/2- 10-20 min; metabolized by tissue peptidases (33%) & urinary excretion
SE= increase BP, angina, arrhythmias, CA spasm, increase peristalsis, N/V, abdominal pain, bronchoconstriction; decrease platelet count
CI= CAD (caution), renal disease, asthma, GI obstruction; NSAIDS increase effect
Dose= 40 U IVP for CV arrest ACLS; 20 Units IV for varices; 0.04U/min gtt for sepsis
Oxytocin
CLASS= endogenous posterior pituitary hormone
MOA= binds to oxytocin receptors on the uterus= SM contraction; used to induce or augment labor & contract the uterus post-delivery & decrease chance of hemorrhage
Pharmacokinetics= onset- 1 min; DOA- 1 hr; E1/2- 5 min; metabolized by the liver & kidney; broken down by plasma oxytocinase & metabolism in mammary gland
SE= mom- anaphylaxis, N/V, PP hemorrhage, uterine rupture, arrhythmias & PVCs; baby- Bradycardia, problematic fetal positioning, fetal distress; high doses = decrease SVR & weak vasopressin activity & H2O retention
CI= fetal distress, hypertonic contractions, hypersensitivity
Dose= 0.5-2 mU/min (increase gtt q 15 min by 0.5-2 mU/min until contractions are 2-3 min apart); post partum uterine atony = up to 40mU/min
PP hemorrhage dose 3 unit x 3–. drip 3 unit/hr
If 3 3 unit boluses are not effective–> move to methergine, hemabate
