Induction drugs Flashcards
Test 2
What is the difference between a sedative & a hypnotic?
A hypnotic induces sleep while a sedative induces a state of calm
What drugs do we use for anxiolytics? If we don’t have these, what is an alternative?
Benzos
Small doses/titration of tranquilizers/induction agents
Ex) 1-2cc propofol
Sedative-hypnotics have reversibly depresses what? What is this caused by?
Depresses CNS activity –> decreases sympathetic effects
Synergistic effects
Monitored anesthesia care is the same thing as ___________ (2 things)
Conscious sedation
Procedural sedation
What is the definition of monitored anesthesia care (MAC)?
The administration of both sedatives and analgesics to induce a depressed level of consciousness, allowing patients to tolerate unpleasant procedures and enabling clinicians to perform procedures effectively
When using a CVC/PICC line, where does the blood flow through 1st? PIV?
CVC/PICC: Superior vena cava
PIV: Inferior vena cava
After blood flow through the heart, what is the order of blood flow for anesthesia drugs? What is the percentage? What organs are in each sections?
Vessel rich group (75%) –> muscle group (18%) –> fat (5%) -> vessel poor group (2%)
Vessel rich: brain
heart
liver
kidney
Muscle: skeletal muscle
skin
fat: just fat
vessel poor: bone
tendon
cartilage
What is the exception of anesthesia drugs going to the brain first?
local/regional anesthesia
Which induction agents have analgesia components?
Propofol: high doses
Ketamine
What receptor does ketamine attach to?
NMDA receptor
What are the components of general anesthesia?
HAMSA (means good luck!)
Hypnosis
Analgesia
Muscle relaxation
Sympatholysis
Amnesia
What does sympatholysis mean?
Preventing an increase in HR/BP
What is the most dangerous stage of anesthesia?
Stage 2
What stage do we want to perform surgery in in anesthesia?
Stage 3
What are the 4 airway reflexes?
- Sneezing.
- Coughing.
- Swallowing.
- Gagging.
What is the lightest level of anesthesia?
Stage 1
What is the last sense to be lost during induction?
hearing
When should all of your airway reflexes be present? Absent? Diminished?
Present: stage 1
Absent: stage 3
Diminished: stage 2
What stage do we want to extubate in? Why?
Stage 1
Patient can maintain protective reflexes/airway
What is stage 1 of anesthesia? What is it characterized by?
Analgesia
initiation of an anesthetic –> loss of consciousness
T/F: you are able to open your eyes on command and breathe normally in stage 1 of anesthesia
T
How long does stage 2 of anesthesia last?
5-15 seconds
max 30 secs
What is stage 2 of anesthesia? What is it characterized by?
Delirium
Loss of consciousness –> onset of rhythmicity of vital signs
What are undesirable SE of stage 2 of anesthesia?
-Release of Epi/NE –> undesirable CV instability –> increased HR
dysconjugate ocular movements
Laryngospasms
emesis
When do we go into phase 3 from phase 2?
The time of onset of the drug given
What do we not want to do during phase 2? why?
We don’t want to stimulate the pt at all –> can increase excitement
What is stage 3 of anesthesia? What is it characterized by?
Surgical
Absence of response to surgical incision or laryngoscopy
Depression in all elements of nervous system function (HAMSA)
What stage of anesthesia can you intubate in?
Stage 3
What is stage 4 of anesthesia? What is it characterized by?
Medullary Paralysis
Sensation of spontaneous, respirations, and major cardiac reflexes
BP and HR decrease = no compensatory measures
All reflexes are absent
-Flaccid paralysis
-Marked hypotension with weak irregular pulse
-Main to death
What causes you to go into stage 4 of anesthesia?
Over anesthetizing the patient
During emergence what happens during stage 3 of anesthesia
Reversal agents are given
During emergence what happens during stage 2 of anesthesia
-Assuring pt is able to protect airway & follow commands
-pt has adequate tidal volumes
Inhalation induction takes _________ in pediatrics. What are the time frames for induction? Emergence?
longer
stage 1: 5-10 min
stage2: 2-3 min
Even more prolonged in emergence
What is the most common Barbiturate?
Thiopental (pentothal)
What are barbiturates derived from?
barbituric acid
Which drug is used in the lethal injection cocktail?
Thiopental (pentothal)
What is the gold standard induction drug? Why is this this important?
Barbiturates
Need to understand how this drug works bc we use this as a standard comparison tool for other drugs
T/F: We use barbiturates during induction
F
Other countries do though, just not the US
What are barbiturates MOA? What are the additional receptors barbiturates work on?
GABA activitiy on the GABAA channel
Addtl receptors: Glutamate
-adenosine
-neuronal nicotinic Achl
Barbiturates are a cerebral ____________. What does this mean? What does this decrease your risk of?
Vasoconstrictor
Decrease CBF & CMRO2 –> decreased metabolism and need for O2 in the brain
Decreases risk of CVA/stroke
How much does barbiturates decrease CMRO2 by?
55%
T/F: barbiturates has an analgesia component
F
Some sort of pain medication has to be given in conjunction with this
T/F: Volatile agents are couple. What does this mean?
F
Increase CBF = decrease CMRO2
(& vice versa)
What are barbiturates pharmacokinetics?
Onset.
Redistribution.
Onset: 30 secs
-rapid onset & awakening dt rapid uptake
Redistribution/reversal:
-5 mins: 1/2 dose
-30 mins: 10%
Describe what happens with barbiturates during a prolonged infusion
lengthy context-sensitive half-time dt groups/organs acting as a reservoir –> prolong effects after dc of infusion.
Describe barbiturates distribution in the skeletal muscles
-Initial site of redistribution from VRG
-Equilibrium at 15 mins to plasma (within 15 minutes, the drug concentration in the plasma/VRG declined, and is now distributing into lower-perfusion tissues)
-Decreased perfusion: shock dt decreased CO
-Elderly dt decreased muscle mass
Describe barbiturates distribution in the fat. What consideration should we have for this?
-acts as a reservoir dt barbs being highly lipid soluble
Considerations:
Dose based on LEAN body weight/ideal body weight (IBW) to avoid cumulative effects with large doses
We use _______ to dose barbiturates
IBW
Lean body weight
Barbiturates are metabolized ____% in the liver, and excreted in the ______
99%
kidney
Barbiturates half time is ______ in pediatric pts
shorter
Barbiturates protein binds to ________. What is the percentage? Why is this important?
Albumin
70-85%
-Being this highly protein bound makes the plasma act as a second reservoir –> when it unbinds –> sedative effects
What is the effect on redistribution if the drug has a high protein binding capacity?
Longer duration of action
What is the difference between the ionized and the non-ionized form of barbiturates?
Non-ionized:
-More lipid soluble
-Favors acidosis
-Hangover effect
Ionized:
Less lipid soluble
-favors alkalosis
-lingers intravascularly –> attaches to albimun
What are previous uses of barbiturates?
Grand mal seizures
-pre-medication
-uncooperative/young patient (rectal)
-increased ICP
-cerebral protection
-induction
Which isomer is more potent in barbiturates?
S(-) I am more is much more potent than R(+)
T/F: barbiturates only exist in racemic mixtures
T
What are the barbiturates names?
Oxybarbiturates:
Methohexital
Phenobarbital
Pentobarbital
Thiobarbiturates:
Thiopental
Thiamylal
Which barbiturate is used for electroconvulsive therapy (ECT)?
Methohexital
What is the dose for Thiopental (Pentothal)?
4 - 5 mg/kg IV
What are the pharmacokinetics for Thiopental (Pentothal)? Redistribution/reversal; halftime; fat/blood partition coefficient
Redistribution/reversal: 30 min –> 10% brain
-rapid redistribution
halftime: longer than methohexital dt being more lipid soluble –> lingers in fat compartment longer
fat/blood partition coefficient: 11 (# high –> longer DOA) –> calculate dose on IBW
What is partition coefficient?
Describes the distribution of a given agent at equilibrium between two substances at the same temperature pressure and volume
Describes the distribution of an anesthetic between blood and gas at the same partial pressure
-a higher blood-gas coefficient correlates with higher solubility of anesthetic in blood, and thus slowing the rate of induction
At normal pH, _____% of Methohexital (Brevital) is non-ionized and _____% of Thiopental (Pentothal) is non-ionized
76%
61%
Oxybarbiturates have oxygen at the _________ position.
2nd
How does Thiobarbiturates compare to oxybarbiturates?
Oxygen in the 2nd position replaced with a sulfur –> makes more lipid soluble –> greater hypnotic potency
Increasing body fat = _____ blood volume. Why?
decreased
adipose tissue has decreased blood supply
How does Methohexital (Brevital) affect seizure activity? What are the AE?
Decreases seizure threshold –> induces seizure activity in pts undergoing temporal lobe resection
AE: Excitatory phenonmena –> Myoclonus & hiccoughs
How can you prevent the excitatory phenomena associated with Methohexital (Brevital)?
Pretreat w/ opioids
How do you calculate IBW?
Men:
52 + (1.9Kg x inches over 5ft)
Women:
49 + (1.7Kg x inches over 5ft)
What is the dose for Methohexital (Brevital)?
Induction: 1.5 mg/kg IV
Per rectum (PR): 20-30 mg/kg
Methohexital (Brevital) ___________ seizure duration by _______% in ECT patients compared to Etomidate.
Decreases
35-45%
Continuous infusion of Methohexital (Brevital) puts pt at risk of what?
1/3 pts experience post op seizures
What are the CVS SE of barbiturates?
Lack of baroceptors: hypovolemia
CHF
Beta blockade
Induces histamine release:
usually asymptomatic
What happens if the Thiopental (Pentothal) histamine release induces in anaphylactoid response?
This is a risk with previous exposure
Epi/Vaso –> 1mg in 10cc –> give 1 cc at a time.
What are normal CV effects of Thiopental (Pentothal)?
Transient 10-20mmHg decrease in SBP
Transient 15-20 increase in HR
What are the SE of Barbiturates on ventilation?
Dose dependent:
depresses ventilatory centors (medullary/pontine = medulla/pons) –> making them less sensitive to CO2
Return to spontaneous ventilation:
characterized by slow frequency (decreased RR) & decreased tidal volumes (shallow breaths)
What happens if you accidentally give a barbiturate through an A-line? How do you treat this?
Intense vasoconstriction
-excruciating pain radiating along that artery
-obscure distal radial pulses
-blanching of the extremity
-cyanosis
-gangrene
-permanent nerve damage
Tx: Vasodilators –> Lidocaine or Papaverine
-sustain blood flow –> fluids
Volatile agents ______ sensory output
depress
When ___________ monitoring is required, barbiturates are the desired drug.
SSEP (somatosensory evoked potential) monitoring
How long is enzyme induction with continuous infusion of barbiturates?
2 - 7 days
not w/ 1 time induction agents, but w/ continuous infusions
What drugs do barbiturates accelerate metabolism of? How long does this last? What considerations should I have??
Anticoagulants
-phenytoin
-TCAs
-digoxin
-corticosteroids
-bile salts
-vitamin k
This can last for up to 30 days
-May need low molecular wt heparin q12h dt decreased effectiveness of anticoagulants
-increase risk of seizure dt increase metabolism of anticonvulsants
How does barbiturates affect the kidneys? What consideration should I have?
Moderate/ transient decrease in RBF & GRF dt transient hypotension
considerations: make sure pt is normotensive
-Crystalloids: 10 - 30 mg/kg
What is the MOA of Propofol?
mediates GABA on GABA-A receptor
What is the dose for propofol?
Induction: 1.5 - 2.5 mg/kg IV
Conscious sedation (MAC): 25 - 100 ug/kg/min
Maintenance: 100 - 300 ug/kg/min
Propofol has a _____ injection time of _____ & produceses unconsciousness within _________
rapid
<15 seconds
30 seconds
Propofol has ______ CNS effects
minimal
What is the concentration of 1% propofol? 2%?
1%: 10mg/1ml
2%: 20mg/1ml
What is the propofol composed of? What is the relevance of these ingredients?
10% soybean oil: lipid component; aids in emulsification/mixing of drug evenly
2.25% glycerol: emulsication agent; makes closer to isotonic; decreases pain upon injection
1.2% purified egg phosphatide: emulsifier/stabilization agent
what specific allergy is contra with propofol?
Egg yolk
If egg or egg white allergy –> not anaphylaxis reaction –> will give trial dose
What component of propofol causes the pain upon injection?
Soybean oil
What are the differences in the commercial brands of propofol?
Diprivan: most common
Ampofol: low emulsion
No preservative
Higher pain on injection
Aquavan: Prodrug
Less pain on injection but pain in genital area (dysesthia)
slower onset
larger Vd
higher potency
Cyclodextrins: still in clinical trials
claims no pain upon injection but does
Whch version of propofol has the highest potency?
Aquavan
Along with GABA-A receptor, proprofol potentiates activity at _______ receptors which contributes to what effect?
glycine-R
hypnosis effect
T/F: propofol induced immobility is caused by spinal cord depression
F
mainly works in brain
Propofol is cleared in the ______ 1st and then in the ______ 2nd
Lung
Liver
What are the active metabolites of propofol? Which is the main one?
Glucuronic acid
Sulfate
What are the characteristics of propofol? halftime; Vd; clearance; BP; trend; HR trend; context sensitive
halftime: 0.5 - 1.5 h
Vd: 3.5-4.5 L/kg
Clearance: 30 - 60 ml/kg/mins
BP: decrease
HR: decrease
context sensitive: 40 mins (based on 8 hr infusion)
What are the characteristics of Etomidate? halftime; Vd; clearance; BP; trend; HR trend
halftime: 2 - 5 h
Vd: 2.2-4.5 L/kg
Clearance: 10 - 20 ml/kg/mins
BP: No change
HR: No change
What are the characteristics of Ketamine? halftime; Vd; clearance; BP; trend; HR trend
halftime: 2 - 3 h
Vd: 2.5 - 3.5 L/kg
Clearance: 16 - 18 ml/kg/mins
BP: Increase
HR: Increase
Propofol is metabolized by _________ after leaving VPG
plasma esterases
T/F: Propofol has no influence on people with renal dysfuntion and cirrhosis
T
What are the doses for propofol? induction; MAC; sub hypnotic; anticonvulsant; antipruritic
Induction: 1.5 - 2.5 mg/kg IV
MAC: 25 - 100 ug/kg/min
Subhypnotic: 10 - 15 mg IV –> 10 ug/kg/min
Anticonvulsant: 1mg/kg
Antipruritic: 10 mg IV
Peds: require higher doses dt larger central volume and clearance rate from high HR/metabolism)
Elderly: decrease dose (25-50%)
What should the plasma levels of propofol be?
Unconscious to induction: 2-6 ug/ml
Awake: 1-1.5 ug/ml
What is the DOC for brief endoscopy procedures?
Propofol
Propofol has minimal __________ and ______ effects? What do we need to add on?
analgesic & amnestic
Versed = amnestic
pain med
Propofol is more effective than ______ as an antiemetic. What is its MOA?
Zofran
depresses subcortical pathways
direct depressant effect on vomiting center
The other benefits of propofol is that it is a potentent ____________, has ________ effects at low doses, and acts as a ________dilator
potent antioxidant
analgesia
bronchodilator
What are the major CNS effects of propofol?
Decreases: CMRO2, CBR, ICP, CPP
-Autoregulation rt CBF/PaCO2 are maintained
-EEG changed similar to thiopental
-No SSEP suppression (unless volatiles or nitrous added)
-Myoclonus during induction/emergence
Why is propofol a great drug for neuro?
No SSEP suppression (unless volatiles or nitrous added)
What are the waves of the EEG? What does each one mean? Which EEG wave do we want for Sx anesthesia?
Alpha: awake
Beta: concentrating
Delta: Deep sleep
Gamma: testing
Theta: light sleep
We want Delta waves
What are the major CV SE of propofol?
Decreased SBP more than thiopental
-inhibit SNS –> decreased SVR
-decrease intracellular Ca dt laryngoscopy stimulus (goes back up)
-low BP exagerated in: hypovolemia, elderly, LV compromise
Bradycardia
-inhibit SNS
-depressed baroreceptors –> No compensatory increase in HR for drop in BP
-Can lead to asystole in healthy adults
What should we give with propofol to help balance the bradycardia? Why?
Atropine
Glycopyrrolate
Counteracts the decreased vagal tone response, which is profound in pediatrics.
What are the pulmonary SE of propofol?
Dose dependent depression of ventilation
-synergestic effects w opioids
-intact hypoxic pulm vasconstriction response
What are the hepatic & renal SE of propofol?
Liver transaminase enzymes or creatinine concentrations are normal
Prolonged infusions:
–Hepatocellula injury
–Propofol infusion syndrome
–Green urine
–Cloudy urine
What is the green urine in propofol from? How does this alter renal function?
Phenols
There is no alteration in renal function
What is the cloudy urine in propofol from? How does this alter renal function? How do you Tx it?
uric acid crystallization
no alteration in renal function
increase amount of fluids/crystalloids given
Propofol _______ IOP. What considerations should I have?
Decreases
Good for Sx in trendelenberg
Propofol __________ platelet aggregation
inhibits
What is propofol infusion syndrome?
Lactic acid induced by high doses of propofol
infusion > 75 ug/kg/min longer than 24h
S/S: severe/refractory/fatal bradycardia in peds
-rhabdo
Late: cardiogenic shock
Dx: ABG
serum lactate
Tx: ECMO
