induction drugs Flashcards
The vessel rich group is ____% of CO
75%
The vessel rich group is made up of
brain, heart, liver, kidney
The muscle group is _____% of CO
18%
The muscle group is made up of
skeletal muscle, skin
The fat group is _____% of CO
5%
The vessel poor group is ____% of CO
2%
The vessel poor group is made up of
bone, tendon, cartilage, hair, nails
What are the 5 components of anesthesia
- Hypnosis
- Analgesia
- Muscle relaxation
- Sympatholysis
- Amnesia
Which anesthetics provide sedation but no analgesia?
barbituates and etomidate
Which stage of anesthesia do we want to extubate in, why?
Stage 1 because patient can protect their own airway
What are the 4 airway reflexes
sneeze, cough, swallow, gag
What stage do airway reflexes diminish
stage 2
What vital sign changes in stage 2 of anesthesia
HR increases, then decreases once stage 3
what is the MOA of barbiturates
potentiate GABA-a channel activity; directly mimics GABA
also acts on glutamate, adenosine, and neuronal nicotinic ACh receptors
Which anesthetic are CBF and CMRO2 not coupled
inhaled volatiles
Onset timing of barbiturates
rapid, 30seconds
Metabolism of barbiturates takes place in
Hepatocytes
Excretion of barbiturates
renal
Protein binding of barbiturates
70-85% bound to albumin
What is the effect on redistribution if the drug has a high protein binding capacity?
longer duration of action
barbiturates are considered weak acid or base?
acid
What are the 2 classifications of barbiturates
Oxybarbiturates and thiobarbituates
Which drugs are oxybarbiturates?
Methohexital, phenobarbital, pentobarbital
Which drugs are thiobarbiturates?
Thiopental, Thiamylal
Dose of thiopental
4-5mg/kg IV
Why should thiopental be dosed in IBW
Has a fat/blood coefficient of 11. rapid redistribution into fat
How does Methohexital’s duration of action compare to thiopental?
shorter DOA; has lower lipid solubility
At normal pH, thiopental is _____% non-ionized
61%
At normal pH, methohexital is ____% non-ionized
76%
Why is it that: the greater the ratio of fat to body weight = the less the blood volume (mL/kg)
adipose tissue has decreased blood supply
Methohexital is associated with what excitatory phenomena?
myoclonus and hiccoughs
Methohexital dose (IV and rectal)
1.5mg/kg IV
20-30mg/kg rectal
What is Methohexital’s effects on seizure threshold
Lowers seizure threshold, decreased seizure duration
What are barbiturates effects on CV system
Transient 10-20mmHg decrease in SBP, compensatory transient 15-20 increase HR bpm
Histamine release
Barbiturate use should be used in caution in which patient population
Caution with lack of baroreceptor response: hypovolemia, CHF, B-blockade
Barbiturate effects on ventilation
Dose dependent depression of ventilatory centers: pons and medulla less sensitive to CO2. Slowed RR and Vt when returning to spontaneous ventilation
Barbiturate effects on intra-arterial injection
Immediate arterial vasoconstriction, excrutiating pain, blanching and cyanosis. Can result in permanent nerve damage.
Tx = Lidocaine or papaverine to vasodilate and increase blood flow
Barbiturate use is the desired drug if ________ monitoring is required
SSEP
What are barbiturates effects on hepatic enzymes?
Induction of hepatic enzymes with chronic infusion: accelerated metabolism of anticoagulants, phenytoin, TCAs, digoxin, corticosteroids, bile salts, and vit K. May persist for 30days
What are barbiturates effects on the kidneys
Modest, transient decreases in renal blood flow and GFR
Tx= crystalloid 10-30ml/kg
Propofol MOA
selective modulator of y-aminobutyric acid (GABA) type A receptors
increases Cl- conductance and hyperpolarizes post synaptic neuron
Also potentiates activity at glycine receptors, partially contributes to hypnosis effect
Propofol doses (induction, conscious sedation, maintenance, antiemetic)
Induction: 1.5-2.5 mgkg IV
Conscious sedation; 25-100 mcg/kg/min
Maintenance: 100-300 mcg/kg/min
Sub-hypnotic/antiemetic: 10-15mg IV followed by 10mcg/kg/min
Propofol concentration and composition
1% solution = 10mg/mL
10% soybean oil- medium for stabilization and dispersment
2.25% glycerol-emulsifier to avoid oil droplets, isotonic with blood
1.2% purified egg phosphatide (lecithin) (egg allergy cross reaction)
Propofol is good to be used for how long after punctured?
6 hours
Prolonged propofol IV infusions can cause
increased triglycerides
Ampofol is
low-lipid emulsion version of propofol, higher incidence of pain on injection
Aquavan (fospropofol) is
water soluble pro-drug of propofol that reduces pain on injection
causes burning in genital area (dysesthia)
slower onset, larger Vd, and higher potency
Main target of anesthetics
brain
Primary clearance of propofol occurs in
lungs > hepatic
With IV medications, 1st pass occurs first where?
lungs
Metabolism of propofol occurs in
liver: CYP450
water-soluble and glucuronic acid metabolites
Which type of drugs are more prone to pulmonary 1st pass effect?
IV lipid soluble drugs
Propofol 1.5-2.5mg/kg IV is equivalent to what dose of Thiopental or Methohexital?
Thiopental 4-5mg/kg IV
Methohexital 1.5mg/kg IV
What is one of the most important advantages of propofol compared with alternative drugs administered for the same purpose?
More rapid return of consciousness with minimal residual CNS effects
How does generic propofol differ from Diprivan
differ in respects to preservatives and pH. Diprivan uses disodium edetate with sodium hydroxide to adjust the pH to 7-8.5.
Generic incorporates sodium metabisulfite as the preservative and has a lower pH (4.5-6.4).
Propofol is not a _______ compound
chiral; should not be mixed with other drugs.
ex. mixing propofol with lidocaine can cause oil droplets which may cause pulmonary embolism
Propofol E1/2 time (hrs)
0.5-1.5hrs
Propofol Vd (L/kg)
3.5-4.5 L/kg
Propofol clearance (ml/kg/min)
30-60 ml/kg/min
Propofol effects on BP and HR
both decreased
Etomidate E1/2 time (hrs)
2-5hrs
Etomidate Vd (L/kg)
2.2-4.5 L/kg
Etomidate Clearance (ml/kg/min)
10-20 ml/kg/min
Etomidate effects on HR and BP
No change to either
Ketamine E1/2time (hrs)
2-3hrs
Ketamine Vd (L/kg)
2.5-3.5 L/kg
Ketamine Clearance (ml/kg/min)
16-18 ml/kg/min
Ketamine effects on HR and BP
both increased
In contrast to volatile anesthetics, immobility during propofol anesthesia is
not caused by drug-induced spinal cord depression
What are propofol concerns in pregnancy and neonate?
Crosses the placenta but is rapidly cleared in the neonatal circulation.
Ion trapping can occur (occurs when a drug accumulates in the fetus due to a difference in pH between the mother and the fetus (fetus normally lower than mother).
Green urine from propofol occurs because of
phenols, no alteration in renal function
cloudy urine from propofol occurs because of
uric acid crystallization, no alteration in renal function
Children require _____ doses of propofol compared to adults
higher; larger central distribution volume and clearance rate
Elderly propofol dose
25-50% lower induction dose
In addition to sedation, other effects of propofol are
anti-emetic: low incidence of PONV, chemotherapy-induced N/V
anticonvulsant and amnestic properties
anti-pruritic effects: d/t neuraxial opiods or cholestasis
analgesia at low doses
bronchodilator: decreased airway resistance, good for asthmatics
potent antioxidant
NOT a MH trigger
Propofol is _____ effective than Zofran
more
How does propofol exhibit anti-emetic effects
depresses subcortical pathways and has a direct depressant effect on the vomiting center (hindbrain).
Propofol effects on CBF and CMRO2
decreased both, also decreased ICP
autoregulation r/t CBF and PaCO2 maintained
Propofol effects on EEG
similar to Thiopental
no SSEP suppression (unless volatiles or nitrous added)
good for neuro cases
Can exert excitatory movements on induction/emergence; does NOT produce seizure, myoclonus
EEG waveforms from most active to least active
Gamma (testing) > Beta (concentrating > Alpha (awake) > Theta (light sleep) > Delta (deep sleep)
Propofol effects on BP compared to thiopental
Propofol has greater decrease in SBP than thiopental
inhibition of SNS, vascular smooth muscle relaxation = decreased SVR
decreased intracellular calcium
exaggerated in hypovolemia, elderly, LV compromise
Propofol CV side effects
- Bradycardia and hypotension
- Decreased SNS response
- May depress baroreceptor reflex
- Profound bradycardia and asystole with healthy adult patients
Propofol respiratory side effects
- Dose dependent depression of ventilation, synergistic with opioids
- INTACT hypoxic pulmonary vasoconstriction response
-painful surgical stimulation counteracts the ventilatory depressant effects
Propofol s/e on other organ systems
- Pain on injection (vein size, give lido prior)
- Decreased IOP
- Inhibits platelet aggregation (not significant)
- Allergic reactions
- prolong myoclonus
- abuse and misuse
What is propofol infusion syndrome
- Lactic acidosis from high dose infusions of >75mcg/kg/min longer than 24hrs.
- Severe refractory and fatal bradycardia in children
- s/sx = lactic acidosis, brady-dysrhythmias, rhabdo
- dx= ABG and serum lactate concentrations
- Reversible in the early stage
- Cardiogenic shock, ECMO
Ketamine is a derivative of
Phencyclidine (PCP)
Ketamine resembles a cataleptic state in which
eyes remain open with a slow nystagmic gaze
pt noncommunicative but wakefulness is present; hypertonus and purposeful skeletal movements
Advantages for ketamine over propofol and etomidate
- no pain at injection site
- profound analgesia at subanesthetic doses
What preservative is in ketamine and what does it add to
Benzethonium Chloride, adds to cumulative analgesic effect
What are disadvantages to ketamine
- emergence delirium
- increased aspiration risk s/t increased salivary secretions
- prolongs duration of paralytics
- abuse potential
Differentiate S(+) Ketamine from R(-)Ketamine
S(+)= left isomer, more intense analgesia (2x more than racemic, 4x more than R), more rapid metabolism and recovery, less salivation, lower emergence reactions
Ketamine MOA
Binds noncompetitively to N-methyl-D-aspartate (NMDA) receptors.
- Inhibits activation of NMDA receptors by glutamate and decreases the presynaptic release of glutamate.
- Glycine is an obligatory co-agonist
Other receptor sites: opioid, monoaminergic, muscarinic, and voltage-sensitive sodium and L-type calcium channels & neuronal nicotinic ACh receptors -> Analgesic effects
Weak actions at GABA-A receptors
Ketamine protein binding
NOT protein binding
What metabolite(s) are formed from ketamine
norketamine - active metabolite 1/5-1/3 potency; can prolong analgesia
Ketamine Induction dosage
0.5-1.5mg/kg IV
4-8mg/kg IM
10mg/kg PO
Ketamine maintenance/analgesia dose
0.2-0.5mg/kg IV - analgesia
4-8mg/kg IM
Ketamine neuraxial analgesia dose
Epidural=30mgs
Intrathecal/spinal/SA= 5-50mg in 3mL saline
If using ketamine for induction, what medication should be given preop?
Antisialagogue - glycopyrrolate
according to lecture, Ketamine is a good choice for which patients
Acutely hypovolemic patients, asthmatic, MH risk
- also used for burn patients, psychiatric disorders, reversal of opioid tolerance
according to lecture, ketamine should be avoided for which patients
- Pulmonary HTN
- neuro/increased ICP (is a cerebral vasodilator)
CNS effects of ketamine
Potent cerebral vasodilator
increases CBF 60%
- excitatory activity in EEG, does NOT alter seizure threshold
- increases amplitude with SSEP
CV side effects of ketamine
- resembles SNS stimulation= inc HR, BP, CO, MRO2
- increases plasma epi & norepi levels, can cause unexpected drops in BP and CO s/t depleted catecholamine stores (treat with epi infusion)
ketamine effects on airway and ventilation
- Ventilatory response to CO2 is maintained
- no significant depression of ventilation
- Upper airway skeletal muscle tone and reflexes intact
- Increased salivary and tracheobronchial mucous secretions
- Bronchodilator activity, no histamine release
Preventing emergence delirium from ketamine can be done by giving
IV benzos 5min prior to ketamine
