Intravenous Anesthetics Flashcards
What is the induction dose of Propofol?
What is the duration of action of Propofol?
Induction: 1-2.5 mg/kg IV
Duration: 3-8 min
What is “balanced anesthesia”?
Using smaller doses of multiple drugs rather than using larger doses with one or two drugs
What is the induction dose of Thiopental?
What is the duration of action for Thiopental?
Induction: 3-5 mg/kg IV
Duration: 5-10 min
What is the induction dose of Methohexital?
What is the duration of action of Methohexital?
Induction: 1-1.5 mg/kg IV
Duration: 4-7 min
What is the induction dose of Midazolam?
What is the duration of action of Midazolam?
Induction: 0.1-0.3 mg/kg IV
Duration: 15-20 min
What is the induction dose of Diazepam?
What is the duration of action of Diazepam?
Induction: 0.3-0.6 mg/kg IV
Duration: 15-30 min
What is the induction dose for Lorazepam?
What is the duration of action of Lorazepam?
Induction: 0.03-0.1 mg/kg IV
Duration: 60-120 min
What is the induction dose for Ketamine?
What is the duration of action of Ketamine?
Induction: 1-3 mg/kg IV, 4-8 mg/kg IM (*can be given IM)
Duration: 5-10 min
What is the induction dose of Etomidate?
What is the duration of action of Etomidate?
Induction: 0.2-0.3 mg/kg IV
Duration: 3-8 min
What is the induction dose for Dexmedetomidine?
What is the duration of action of Dexmedetomidine?
Induction: N/A
Duration: N/A
What are the 4 components of General Anesthesia?
Anxiolysis
Hypnosis
Analgesia
Paralysis
What is the Meyer-Overeton rule?
The potency of an anesthetic is proportional to it’s lipid solubility - this suggests a lipophilic site of action
Most anesthesia agents work by…?
Increasing inhibitory neurotransmitters and decreasing excitatory neurotransmitters
What is Neostigmine?
A drug used to reverse muscle relaxants. One side effect is that it causes bradycardia - so we give glycopyrrolate to reverse those effects.
The central compartment of the body includes:?
- The plasma and the vessel-rich group of tissues (Liver, brain, heart, and kidneys).
- Elimination of the intravenous medications occurs through the central compartment - this is the area of action for the sedatives and narcotics
What is the peripheral compartment?
This is considered to be the vessel-poor group which includes muscle, bone, skin, and fat.
What is the distribution of cardiac output?
VRG - 75%
Muscle - 19%
Fat - 6%
VPG - 0.5%
What factors affect distribution?
- Protein binding decreases available drug
- Protein availability - affects bound and free fraction of the drug
- Lipid solubility
- Ionization
What is the volume of distribution?
Quantifies the distribution of a medication between plasma and the rest of the body after dosing
Equation - total amount of drug int he body divided by drug blood concentration
What is the mechanism of action of Propofol?
- Presumed interaction with GABA
- Delays the dissociation of GABA from receptors (1. increasing GABA activated openig of chloride ion channels, 2. Also acts as a sodium channel blocker)
- Hyper-polarization of cell membranes
How is propofol metabolized?
Via glucoronidation in the liver (Clearance exceeds heaptic blood flow, 30% may occur in the lungs), renal excretion
Propofol Pharmacokinetics
- 95-99% protein binding
- Elimination half life 30-60 minutes
- Tissue uptake & redistribution are important factors in termination of action
What is the therapeutic plasma concentration of propofol?
1.5 - 5
What is context sensitive half times for various IV anesthetics?
- the time for plasma level to decrease 50% after stopping infusion
- Time of infusion affects rate at which drug level decreases
What are the cardiovascular effects of propofol?
- decreases SBP, MAP, SVR
- No change to HR
- Profound arterial and venous vasodilation decreases preload and afterload
- Also blunts the baroreceptor response as well
What are the pulmonary/respiratory effects of propofol?
- RR depressed dose dependent - apnea after bolus
- Reduces airway reflexes
What are the CNS effects of propofol?
- Decreases CBF, ICP, CMRO2, IOP
- Beware of decreasing SBP and CBP because of decreased CPP
What are other considerations of Propofol?
- Has hypnotic properties, but NOT analgesia
- Allergic reactions - contraindicated with egg allergy
- Bacteria formation in solution
- Reduces PONV & PDNV
- Burns upon rapid injection in small vein
- Bronchodilator, decreases airway reflexes
What is Propofol infusion syndrome?
- Acute refractory bradycardia (kids)
- RBBB is an early sign
- May lead to asystole if one or more: metabolic acidosis, rhabdomyolysis, hyperlipidemia, Enlarged or fatty liver
- Associated with propofol infusion greater than 4 mg/kg for long duration (>48 hours)
What is the initial dose of Fospropofol?
Initial dose: 6.5 mg/kg
- additional 1.6 mg/kg as needed
- reduce dose 25% for >65 years and ASA 3-4
- perianal paresthesia in 74%
- not currently at UIHC
What is the mechanism of action of Etomidate?
- rapid onset of sleep (30-60 sec)
- assumed to enhance the effects of GABA
- rapid awakening
What are the pharmacokinetics of Etomidate?
- 75% protein bound
- Hydrolyzed to inactive metabolites via ester hydrolysis
- Elimination half life is 75 min
- Excretion is 85% renal, 15% biliary
What are the CV effects of Etomidate?
- typically does not affect SBP, HR, or SVR
What are the pulmonary effects of Etomidate?
- minimal respiratory depression, increased with opioids
What are the CNS effects of Etomidate?
- decreases CBF, ICP, and CMRO2
What are some other considerations for Etomidate?
- burns on injection
- myoclonus
- ADRENAL SUPPRESSION - inhibits 11beta-hydroxylase and to a lesser extent 17alpha hydroxylase; inhibits the production of cortisol and aldosterone to cause hypotension
- no analgesia
- increases PONV vs NaP or Propofol
What is the mechanism of action for Ketamine?
- NMDA, Opioid, Monoaminergic, Muscarinic receptors, and voltage gated Ca channels
What are the pharmacokinetics for Ketamine?
- extremely lipid soluble
- metabolized in the liver to norketamine (1/3 - 1/5 the potency of ketamine)
- Norketamine is hydroxylated and conjugated to H2O soluble and excreted (90% renal)
- elimination half life 2-3 hours
What are the CV effects of Ketamine?
- increases SBP, HR, and SVR
What are the pulmonary effects of Ketamine?
- No respiratory depression, but increased with the use of opioids
- we can give Ketamine out in the holding area because it doesn’t cause respiratory depression
What are the CNS effects of Ketamine?
- Increased CBF, ICP, CMRO2
What dose of Ketamine can provide profound adjunctive analgesia?
0.2-0.5 mg/kg can provide profound analgesia
What do you have to beware of with Ketamine?
- Emergence Delirium
- Visual, auditory, proprioceptive, and confusion
- Premedicating with Midazolam seems to help
What are the Barbiturates?
- Thiopental
- Thiamylal
- Methohexital
- Barbituric Acid
What is the mechanism of action of Barbiturates?
- Interact with GABAa (alpha subunit) receptor
- different from the GABA or the BZD site
- directly activate CL ion channels, increase their opening - increases the efficacy of GABA
- hyperpolarize postsynaptic cell membranes
- Also block the AMPA receptors
What are the pharmacokinetics of Barbiturates?
- NaP 83% protein bound
- Highly lipid soluble = rapidly into CNS
- Achieve CNS uptake in 30 sec
- Prompt awakening after a single dose
- HEpatic metabolism (inactive) and eliminated by the kidneys
What are the CV effects of the Barbiturates?
- Decrease SBP and SVR
- Increase HR
What are the pulmonary effects of Barbiturates?
- Respiratory depression, APNEA, return with slow respers and decreased tidal volumes
What are the CNS effects of Barbiturates?
- Decreased CBF, ICP, CMRO2
What are the renal effects of Barbiturates?
- Modest decrease in blood flow and GFR
What are the pH effects on Barbiturates?
- Metabolic acidosis increases the effect of Barbiturates
- Metabolic alkalosis decreases the effect of Barbiturates
- Respiratory acidosis has much less effect
What do you have to beware of with Barbiturates?
- Extravasation causes tissue sloughing
- NaP + SUX = concrete in IV line
- Intrarterial injection causes severe vasoconstriction
- Induce the P-450 system
- Contraindicated in patients with Acute Intermittent Porphyria
What are the Barbiturates Key Points?
- Awakening due to redistribution
- NaP causes dose dependent decrease in SBP, SVR, CO d/t myocardial depression and increased venous capacitance
- Potent respiratory depressants
- Poor analgesics - may cause hyperalgesia
- Contraindicated in Acute Intermittent Porphyria
- Can cause histamine release
- Avoid SUBQ and Intra-arterial injection d/t tissue sloughing
What are benzodiazepines used for?
- Sedation, anxiolysis, anticonvulsant effects, spinal-cord mediated muscle relaxation, and anterograde amnesia and at high doses unconsciousness and respiratory depression
What are some considerations for Benzodiazepines?
- No analgesic properties
- High therapeutic indexes
- Benzodiazepine + Narcotic = T.I. less than 10
What is the primary inhibitory neurotransmitter?
GABA
What is the mechanism of action for Benzodiazepines?
- They facilitate action of GABA at the alpha subunit
- Enhanced opening of the Cl channels
- Hyperpolarization of postsynaptic membrane
- Postsynaptic neurons resistant to excitation
What are the pharmacokinetics of Diazepam?
- Very lipid soluble - rapid uptake by brain, rapid redistribution, large VD: 1-1.5 L/kg, 0.2-0.5 ml/kg/min clearance rate
- Long Elimination half-life - 21-37 hrs in healthy volunteers, much longer in the elderly, duration of action is determined by metabolism and elimination
How is Diazepam metabolized?
- Primarily metabolized in the liver via oxidative N-demethylation
- 3 active metabolites:
- Desmethyldiazepam - slightly less active than diazepam, metabolized more slowly than diazepam
- oxazepam
- Temazepam
- Hepatic clearance does not change as we age - bodily proportion of fatty tissue increases, which increases VD for lipid soluble drugs and takes longer to metabolize
- Cimetidine delays hepatic clearance
What are the anesthetic effects of Diazepam?
- Reduces the dose of induction agent
- Reduces the MAC of inhalation agent
- 0.2 mg/kg IV diazepam reduces MAC of halothane from to 0.48% - increasing the dose dies not further reduce the MAC
What are the pharmacokinetics of Midazolam?
- 2-4 times as potent as diazepam
- Imidazole ring (water soluble at pH <4, closes upon injection and becomes highly lipid soluble)
- 96-98% protein bound
- Very lipid soluble
- Large volume of distribution - 1-1.5 L/Kg
- High rate of clearance - 6-8 ml/kg/min
- Short elimination half-life - 1-4 hrs in healthy volunteers
What are other considerations of Midazolam?
- oxidative hydroxylation in the liver
- glucoronide conjugation in the kidneys
- metabolism not affected by H2 receptor antagonists
- Depressed ventilation with 0.15 mg/kg dose
- dose related decrease in CBF and CMRO2
- crosses the U-P (utero-placental) membrane - don’t give to pregnant women
What drug is more potent than diazepam or midazolam?
Lorazepam
What is the elimination T1/2 of Lorazepam?
10-20 hours
How is Lorazepam metabolized?
- metabolized to inactive metabolites via glucuronide conjugation in the liver
- metabolism is not altered by age, liver dysfunction, or H2 receptor antagonists
Why do the clinical effects of Lorazepam outlast that of diazepam?
Lorazepam dissociates from the GABAa slower
What are some other considerations of Lorazepam?
- Reliable GI and IM absorption - dissolved in propylene or polyethelyne glycol
- Less lipid soluble than diazepam
- Elderly pts are sensitive to BZDs
- Slow onset limits usefulness as IV pre-med or intra-op sedative
Lorazepam is an excellent PO pre-medication. What are the doses?
- 0.5-2.0 mg @ HS and 0.5-2.0 mg PO @ 06-0700
- 50 mcg/kg (max. 4 mg) gives maximal anterograde amnesia for up to 6 hours
- Larger doses produce greater sedation without increased amnesia
What drug is given to reverse BZDs?
Flumazenil - is a specific and exclusive BZD competitive antagonist with a high affinity for the BZD receptor
- It reverses all BZD effects in a dose dependent manner
- There is not an abrupt reversal of sedative/amnestic effects as with narcotic reversal with nalaxone
- onset of action is 30 sec-2min
What is the dosing for Flumazenil?
- 0.2 mg IV over 15 seconds
- Wait 45 sec
- Re-dose 0.2 mg increments over 15 sec
- DO NOT EXCEED 3.0 mg/hour
- If no response after 1 mg Flumazenil consider other causes -
1. Incomplete reversal of muscle relaxation
2. residual anesthetic agents
3. hypoxemia
4. hypercarbia
5. Surgical complication
What are Physostigmine and Aminophylline?
- Other agents used to reverse BZDs
- They are not recommended b/c they are nonspecific, unpredictable, and inconsistent
What is Dexmedetomidine?
Alpha 2 - adrenergic agonist - sedation, anxiolysis, hypnosis, analgesia, sympatholysis
What is the mechanism of action of dexmedetomidine?
- Nonselective alpha 2 agonist
- Alpha 2 adrenoreceptors are membrane spanning G proteins
- -inhibition of adenylate cyclase
- -modulation of ion channels
- -alpha 2B & alpha 2C receptors in the brain and spinal cord and stimulation leads to sympatholysis, sedation, and antinociception
- Sedation - receptors in the locus cereleus
- Analgesia - receptors in LC and spinal cord
What are the CV effects of Dexmedetomidine?
- decreased HR and SVR
- indirectly decreases CO, SBP & contractility
What are the pulmonary effects of Dexmedetomidine?
- decreases minute ventilation but maintains CO2 response
- Similar to natural sleep
What are the CNS effects of Dexmedetomidine?
- not well defined
- some neuroprotection?
What is the premedication dose of Dexmedetomidine?
- 0.33-0.67 mcg/kg 15 min before surgery
- decreases induction agent dose
- decreases MAC
What is the MAC dose of Dexmedetomidine?
- 1 mcg/kg over 10 minutes
- slower onset and offset than propofol
- similar cardiorespiratory effects
- 0.7 mcg/kg/min keeps BIS 70-80
How is Dexmedetomidine used as maintenance of general anesthesia?
- reduces MAC of inhaled agent
- reduces postoperative opioid requirements
- not useful as a solo general anesthetic
What is the mechanism of action of Droperidol?
- Acts centrally at sites where dopamine, norepinephrine, and serotonin act
- Alters normal CNS signal transmission
- Exerts antiemetic effect at red astrocytes in the Chemo-receptor trigger zone
- Has moderate alpha-adrenergic blocking ability
- May occupy GABA receptors on the postsynaptic membrane casuing a buildup of dopamine in the inter-synaptic cleft
- Neuroleptic anesthesia - catatonic like state
What are the CV effects of Droperidol?
- decreases SVR, MAP
- does not affect CO or contractility
- Prolonged QT interval (delayed repolarization, torsades de pointes)
What are the respiratory effects of Droperidol?
Minimal
What are the CNS effects of Droperidol?
NO human data
- may worsen extrapyramidal side effects
- contraindicated in Parkinson Dz.
What are the uses of Droperidol?
Antiemetic: 0.625-1.25 mg IM/IV in adults
Premedication: similar
What is the onset of action of Droperidol?
What is the duration of action of Droperidol?
Onset: 5-8 min
Duration: 3-6 hours
What are the pharmacokinetics of Droperidol?
- elimination half-life 1.7-2.2 hours
- Hepatic transformation - two metabolites
- elimination liver and kidneys
What is the most common IV anesthetic agent?
Propofol - provides rapid onset and offset, potentiates GABA induced Cl channels
What IV induction agent is contraindicated in the porphyria patient?
NaP - rapid onset and offset with single dose
What are BDZ primarily used for?
- Anxiolysis, amnesia, and sedation
- Act through the GABA receptor
What IV agent is a phencyclidine derivative?
Ketamine - produces dissociative anesthesia and also analgesia, works on the NMDA receptor
What IV agent is an imidazole derivative that preserves cardiac function?
Etomidate - can suppress adrenocortical function and increases PONV
What IV agent is an alpha 2 adrenergic agonist that produces sedation, hypnosis, and analgesia?
Dexmedetomidine - acts on alpha 2’s in the LC
What IV agent is a butryphenone (Haloperidol derivative), major tranquilizer, rarely used for GA - BUT is a potent antiemetic?
Droperidol - may cause R on T and Torsades de Pointes
