Intravenous Anesthetic Agents Flashcards
1
Q
Drug distribution in the body: central
A
- plasma and vessel-rich group of tissues
- liver, brain, heart, and kidneys
- elimination of intravenous medications occur through the central compartment. This is the area of action for the sedative and narcotics
2
Q
Drug distribution in the body: peripheral
A
-this is considered to be the vessel-poor group which includes muscle, bone, skin, and fat
3
Q
Distribution of Cardiac Output: VRG? Muscle? Fat? VPG?
A
VRG= 10% body mass but 75% CO Muscle= 50% body mass but 19% CO Fat= 30% body mass but 6% CO VPG= bones and skeletal structures, 20% body mass but 0.5% CO
4
Q
Factors affecting distribution: Drug binding
A
- Protein binding decreases available drug:
- albumin binds acidic drugs (barbs)
- A1AG bind basic drugs (local anesthetics) - Protein availability:
- —decreased albumin d/t liver, kidney, CHF, increased d/t
- —-increased A1AG d/t trauma, infection, MI, chronic pain
5
Q
What two factors affect distribution of drugs?
A
- Lipid solubility: good for anesthetic agents
2. Ionization: affects crossing cell membranes
6
Q
Volume of Distribution:
A
- Vd quantifies the distribution of a medication between plasma and the rest of the body after dosing
- Theoretical volume in which the amount of drug would need to be uniformly distributed to produce the observed blood concentration
- The initial VD describes the distribution of a drug throughout the body after dosing and prior to reaching a steady state equilibrium
7
Q
VD equation
A
total amount of drug in the body/ drug blood concentration
8
Q
High Vd
A
- highly lipid soluble drugs and therefore non-polar
- low rate of ionization
- low plasma binding
9
Q
Vd blood, extracellular, and total body water
A
<0.2= blood (confined to blood) 0.2-0.7= extracellular .7= total body water (meaning it goes everywhere)
10
Q
Propofol MOA
A
- presumed interaction with GABA
- delays the dissociation of GABA from receptors
- increasing GABA activated opening of chloride ion channels
- also acts as a sodium channel blocker
- hyper polarization of cell membranes (why patients go to sleep)
11
Q
Propofol Pharmacokinetics
A
95-99% protein binding
- elimination half life 4-7 hours
- tissue uptake and redistribution are important factors in termination of action
- metabolized via glucoronidation in the liver
- clearance exceeds hepatic blood flow
- renal excretion
12
Q
Propofol therapeutic range
A
- rapid upstroke of blood levels on induction
- rapid decline over 5 minutes
- below therapeutic window by 7 minutes
- if no additional agent given, patient will wake up due to redistribution
13
Q
Propofol CV, pulmonary and CNS effects
A
- CV: Decreased SBP, Decreased MAP, Decreasd SVP, HR same
- Pulmonary: RR depressed dose dependent
- CNS: CBF decreased, ICP decreased, CMRO2 decreased
14
Q
Propofol induction dose and continuous infusion dose
A
- Supplied 10 mg/ml
- Induction: 1.5-2.5 mg/kg intravenous
produces unconsciousness in 30-60 seconds
decreased PONV - Continuous infusion: sedation to general anesthesia. 25 to 100 mcg/kg/min= sedation, 100-300 mcg/kg/min= anesthesia TIVA
- Beware: allergic reactions, bacteria formulation in solution
15
Q
Propofol infusion syndrome
A
- Acute refractory bradycardia (kids)
- RBBB is an early sign
- May lead to systole if one or more:
- metabolic acidosis
- rhabdomyolisis
- hyperlipidemia
- enlarged or fatty liver
- Associated with propofol infusions > 4mg/kg for long duration ( > 48 hours)
16
Q
Propofol key points:
A
- Awaken due to redistribution
- CV depression slightly > than NaP
- Resp effects similar to NaP but good bronchodilator
- Does NOT cause PONV and PDNV
- Good hypnotic
- Burns upon rapid injection in small vein
- Contraindicated with egg allergy
17
Q
Fospropofol
A
- prodrug multicompartment model needed
- supplied 35 mg/ml
- initial dose 6.5 mg/kg (between 60-90 kg)
- additional 1.6 mg/kg as needed
- <60 kg or >90 use 60 or 90 kg
- reduce dose 25% for >65 years and ASA 3-4
- perianal paresthesia in 74%
- not currently in use at UIHC
18
Q
Barbituartes MOA
A
- interact with GABAA receptor (beta subunit)
- directly activate Cl- ion channels, increase their duration of opening (increases the efficacy of GABA)
- hyerpolarize post synaptic cell membranes
- also block AMPA receptors
19
Q
Barbs Pharmacokinetics
A
- NaP 83% protein bound (albumin)
- highly lipid soluble- rapidly into CNS
- achieve CNS uptake in 30 seconds
- prompt awakening after a single dose
- hepatic metabolism (inactive) and eliminated by kidneys)
- NEVER RUN INFUSION OF THIOPENTAL
20
Q
Barbs: CV, Pulmonary, CNS, Renal, PH effects
A
- CV: decreased SBP, increased HR, decreased SVR
- Pulmonary: resp depression, apnea, return with slow reapers and low tidal volumes
- CNS: decreased CBF, decreased ICP, decreased CMRO2
- Renal: modest decrease in blood flow and GFR
- pH: metabolic acidosis increases the effect of barbs; metabolic alkalosis decrease the effect of barbs
21
Q
Barbs- thiopental and methohexital solutions
A
- Thiopental supplied in 2.5% solution (25 mg/ml)
2. Methohexital 1% solution (10 mg/ml)
22
Q
Barbs induction of anesthesia
A
-induction dose: 3-5 mg/kg NaP
1-1.5 mg/kg methohexital
-rectal methohexital 20-30 mg/kg sedative (circulation directly into rectal vein- lose to 1st pass effect)
23
Q
Beware of Barbs
A
- extravasation causes tissue sloughing
- NaP + SUX= concrete in IV
- Intra arterial injection= severe vasoconstriction
- induce the p-450 system
- contraindicated in patients with Acute Intermittent Porphyria*
24
Q
Barbs Key Points
A
- awakening due to redistribution
- NaP causes dose dependent decrease in SBP, SVR, CO due to 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
25
Q
Etomidate MOA and pharmacokinetics
A
- MOA: rapid onset of sleep= 30-60 seconds
- assumed to enhance effects of GABAA (Gaba A receptors with B3 subunits)
- rapid awakening
Pharmacokinetics:
- 75% protein bound
- hydrolyzed to inactive metabolites via ester hydrolysis
- elimination half life is 3-5 hours
- clearance is 5-6X pentothal; equivalent to propofol
- excretion 85% renal, 15% biliary
26
Q
Etomidate CV, pulmonary, and CNS effects
A
- CV effects: SBP equal or decreased, HR equal or decreased, SVR equal or decreased
- Pulmonary: minimal respiratory depression, increased with opioids
- CNS: decreased CBF, decreased ICP, CMRO2 decreased
27
Q
Etomidate: induction dose
A
- supplied 2 mg/ml vials
- induction of anesthesia: 0.2-0.4 mg/kg, burns on injection
- Beware: myoclonus, adrenal suppression (inhibits 11 Beta- hydroxylase and to a lesser extent 17 alpha hydroxylase), increases PONV than propofol
- no analgesia
28
Q
Ketamine MOA
A
MOA: NMDA; opioid; monoamingeric; muscarinic receptors; and voltage gated Ca+ channels
29
Q
Ketamine Pharmacokinetics
A
- extremely lipid soluble (5-10X NaP)
- metabolized in liver to norketamine (1/3 to 1/5 potency of Ketamine)
- norketamine is hydroxylated and conjugated to H2O soluble and excreted
- elimination half life 2-4 hours; approx dexmed
- excretion >90% renal
30
Q
Ketamine CV, Pulmonary, CNS effects
A
- CV: SBP, HR and SVR all increased
- Pulmonary: no respiratory depression, increased with opioids
- CNS: CBF increased, ICP increased, CMRO2 increased
31
Q
Ketamine induction dose
A
- Supplied 10 mg/ml; 50 mg/ml; 100 mg/ml vials
- Induction of anesthesia: 1-3 mg/kg IV or 4-8 mg/kg IM
- adjunctive analgesic: 0.2-0.5 mg/kg can provide analgesia
32
Q
Ketamine Beware
A
- Emergence delirium: visual, proprioceptive, and confusion
- premedicating with midaz seems to help
33
Q
Benzodiazepines
A
- used for sedation, anxiolysis, anticonvulsants, spinal-cord mediated muscle relaxation, and anterograde amnesia, and at high doses unconsciousness and respiratory depression
- NO analgesic properties
- High Therapeutic Indexes high 100s
- Benzo + narcotic= TI <10
34
Q
BZD site on GabaA Receptor
A
- GABA is primary inhibitory NTM
- BZD facilitates action of GABA at the alpha subunit (2 alpha and 2 beta sites)
- enhanced opening of Cl- channels
- hyper polarization of post synaptic membrane
- post synaptic neurons resistant to excitation
35
Q
Diazepam
A
- Very lipid soluble: rapid uptake by then brain, rapid redistribution
- large VD: 1-1.5 L/kg
- 0.2-0.5 ml/kg/min clearance rate
- Long elimination half life: 20-50 hours in healthy volunteers
- much longer in the elderly (closer to 80 hours)
- duration of action is determined by metabolism and elimination
36
Q
Diazepam Metabolism
A
- primarily metabolized in the liver via oxidative N-demethylation
- 3 active metabolites: desmethyldiazepam, oxazepam, temazepam
- Hepatic Clearance does not change as we age: body proportion of fatty tissues increases, increase VD for lipid soluble drugs and takes longer to metabolize
- Cimetidine delays hepatic clearance: affects diazepam and desmethyldiazepam clearance
37
Q
Anesthetic effects of Diazepam
A
- reduces the dose of induction agent
- reduces MAC of inhalation agent
- .2 mg/kg IV diazepam reduces MAC of Halothane from .75% to .48%
- increasing the dose of diazepam does not further reduce the MAC
38
Q
Midazolam
A
-2-4 times as potent as diazepam
-imidazole ring (water soluble at pH <4), ring closes upon injection and becomes highly lipid soluble
-96-98% protein bound
-very lipid soluble (rapid intake by brain, redistribution and re-uptake)
-Large Volume of Distribution: 1-1.5 L/kg
-High rate of clearance: 6-8 ml/kg/min
Short elim half life: 1.7-2.6 hours in healthy adults
39
Q
Midaz Pharmacokinetics:
A
- Oxidative hydroxylation in liver
- Glucoronide conjugation in the kidneys
- Excretion in the urine
- Metabolites are minimally active
- Metabolism not affected by H2 receptor antagonists
- Cardiac responses minimal and similiar to NaP
- Depressed ventilation with 0.15 mg/kg dose
- Renal failure has minimal effects on T 1/2, Vd, and clearance
- Dose related decrease in CBF and CMRO2
- Crosses the U-P membrane
40
Q
Lorazepam (Ativan)
A
- more potent than diazepam or midday
- elimination t 1/2 is 10-20 hours
- less lipid soluble than diazepam
- reliable GI and IM absorption- dissolved in propylene or polyethylene glycol
- clinical effects may outlast diazepam dissociates from the GabaA slower
- metabolized to inactive metabolites via glucuronide conjugation in the liver
- metabolism is not altered by age, liver dysfunction, or H2 receptor antagonists
41
Q
Lorazepam as PO pre-med
A
- Excellent PO pre-med: 0.5-2.0 mg at night and 0.5-2.0 mg PO at 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
- Elderly patients are sensitive to benzo
- Slow onset limits usefulness as IV pre med or intra op sedation
42
Q
Reversal of BZDs
A
- Flumazenil: specific and exclusive BZD competitive antagonist with a high affinity for BZD receptor
- Reverses all BZD effects
- Not an abrupt reversal of sedative/amnesic effects as nalaxone w/ opioid reversal
- Onset is 30 seconds to 2 minutes
- Redistribution T1/2 is 7-15 minutes (may need to redose)
43
Q
Flumazenil Dosing
A
- 0.2 mg IV over 15 sec(wait 45 seconds, redone 0.2 mg increments over 15 seconds)
- Do NOT exceed 3.0 mg per hour
- If no response after 1 mg flumazenil consider other causes:
- incomplete reversal of muscle relaxation
- residual anesthetics agents
- narcotic overdose
- hypoxemia
- hypercarbia
- surgical complication
44
Q
Reversal of BZDs (other agents)
A
- Non specific, unpredictable, and inconsistent
- Recommended since Flumezenil
- Physostigmine: tertiary amine, cholinesterase inhibitor that causes build up of Ach in brain tissue
- Aminophylline: 1 mg/kg may antagonize the sedative effects of adenosine in the CNS
45
Q
Midaz: active drug vs pro drug
A
- Active Drug: lipophilic
2. Prodrug: hydrophilic
46
Q
Dexmedetomidine
A
- Alpha 2 adrenergic agonist:
- sedation
- anxiolysis
- hypnosis
- analgesia
- sympatholysis
47
Q
Dexmedetomidine MOA
A
- Nonselective alpha 2 agonist
- alpha 2 adrenoreceptors are membrane spanning G proteins (inhibition of adenylate cyclase, modulation of ion channels)
- sedation- receptors in locus ceruleus
- analgesia- receptors in LC and spinal cord
48
Q
Dex CV, pulmonary, CNS effects
A
- CV: decreased HR, decreased SVR, indirectly decreased CO, SBP, and contractility
- Pulmonary: decrease minute ventilation but maintains CO2 response, similar to natural sleep
- CNS: not well defined, some neuroprotection?
49
Q
Dex Premedication
A
- premedication: .33 to .67 mcg/kg 15 minutes before surgery
- decrease induction agent dose
- decrease MAC
- MAC: 1 mcg/kg over 10 minutes (slower onset and offset than propofol)
- .7 mcg/kg/min keeps BIS 70-80
- Maintenance of GA: reduce MAC of inhaled agent, reduces post operative opioid requirements, note useful as solo general anesthetic
50
Q
Droperiodol MOA
A
- MOA: acts centrally at sites where dopamine, norepi, and serotonin
- 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 post synaptic membrane causing build up of dopamine in inter synaptic cleft
- neuroleptic anesthesia
51
Q
Droperidol CV, Resp, CNS effects
A
- CV: decreased SVR, Map, Equal CO, equal contractility (prolonged QT= delayed repolarization, torsades de pointes)
- Respiratory: minimal
- CNS: decreased CBF in dogs- no human data, may worsen extrapyramidal side effects
Contraindicated in Parkinson’s Disease ****
52
Q
Droperiodol uses and pharmacokinetics
A
Uses:
1. antiemetic: 0.625-1.25 mg IM/IV in adults
Pharmacokinetics:
- onset 5-8 minutes
- Vd 2.0L/kg
- Duration of action: 3-6 hours
- Elimination half life: 1.7-2.2 hours
- Hepatic transformation: 2 metabolites
- Elimination liver and kidneys
