Pharm2 - Induction Agents
Terms in this set (94)
Potency of thiobarbiturates vs oxybarbiturates
Thiobarbiturates are more potent than oxybarbiturates as they are more lipid soluble
(the exception is methohexital which is an oxybarbiturate & is actually more potent than thiobarbiturates d/t ionization & physiologic pH)
Mechanism of action of barbiturates (as well as benzos, propofol, etomidate)
Decrease the dissociation of GABA from its receptor which keeps the chloride channel open resulting in hyperpolarization of the postsynaptic neuron.
A reason to not give barbiturates (x2)
-Don't give if hypovolemic (Barbiturates depress sympathetic NS transmission resulting in hypotension)
-Thiopental is contraindicated in patients with intermittent porphyria (porphyria = genetic condition where porphyrin cannot be converted into heme & it accumulates in blood & urine)
Potency of thiopental vs thiamylal vs methohexital
Methohexital: 2.5 (lower ionization & physiologic pH)
Thiopental induction dose
(unconsciousness in 30 sec)
Methohexital induction dose
Induction agent that can be given rectally for uncooperative patients
Methohexital 20-30 mg/kg
Induction agent most associated with causing seizures
Methohexital at high doses cause seizures in 1/3 of patients
(can be used when seizure activity desired- ECT, resection of seizure-producing tissue)
What induction agent is related to emergence delirium?
What agents may make this worse?
What agents may help reduce this?
-Made worse by atropine (best to give glycopyrrolate) and droperidol
-Benzodiazepenes (Versed esp.) helps to reduce emergence delirium
Describe the metabolism of methohexital vs other barbiturates (x4)
-Remains in plasma longer (less lipid soluble)
-Redistribution still occurs (allows early awakening)
-3-4x greater hepatic clearance (more rapid recovery of psychomotor function)
-High hepatic extraction ratio (more dependant on CO & hepatic blood flow) where thiopental has low H.E.R.
What are the indications of barbiturates? (x4)
-Induction of anesthesia
-Treatment of ICP
-Treatment of hyperbilirubinemia and kernicterus with phenobarbital.
-Induce seizure activity for procedures this is desired (methohexital)
Which agent is the only barbiturate with actions sufficiently different from the thiobarbiturates to offer an alternative to other IV induction agents?
Which barbiturate is associated with a more rapid recovery of consciousness?
What agents are classified as thiobarbiturates? (x2)
What agents are classified as oxybarbiturates? (x3)
What are the chemical differences between oxybarbiturates and thiobarbiturates?
Oxybarbiturates have an oxygen atom at carbon atom 2. Replacement of the oxygen with a sulfur atom results in thiobarbiturates.
Which type of barbiturate has a greater lipid solubility and what does it result in?
=greater hypnotic potency, faster onset and shorter duration of action.
Explain the mechanism of prompt awakening that occurs with barbiturates
Prompt awakening after a single dose of thiopental, thiamylal, and methohexital is the result of redistribution from the brain to inactive tissues.
Are thiobarbiturates or oxybarbiturates more protein bound?
Thiobarbiturates are more protein bound than oxybarbiturates.
(more lipid soluble & drugs that compete for protein binding cause thiobarbiturates to have an increased effect)
Site of metabolism for oxybarbiturates vs thiobarbiturates
Oxybarbiturates: hepatocytes only
Thiobarbiturates: extra-hepatic sites such as the kidneys.
Thiopental's metabolism is dependent on what?
Hepatic enzyme activity & protein binding
(Thiopental has a low hepatic extraction ratio so metabolism is dependent on hepatic enzyme activity not hepatic blood flow)
What agent is the only barbiturate that has significant renal excretion in the unchanged form?
Where is methohexital metabolized?
(less than 1% excreted unchanged in urine)
Methohexital's metabolism is dependent on what?
Cardiac output and hepatic blood flow.
(high hepatic extraction ratio)
How much of thiopental and methohexital is excreted unchanged in the urine?
Less than 1%.
What are the drawbacks of barbiturates? (x8)
-More drug interactions
-Lower therapeutic index than benzos
-Tolerance more easily than benzos
-A higher risk for abuse
-Paradoxical excitation especially in the elderly
-Decrease in pain threshold with small doses
-Lack specificity of effect in the CNS
What is an advantage of methohexital?
Associated with a more rapid recovery of consciousness.
What is the principal disadvantage of methohexital?
-Increased excitatory phenomena (myoclonus [involuntary skeletal muscle movements] & hiccough)
What are the major side effects of barbiturates? (x6)
-Cardiovascular system depression
-Mild and transient decrease in BP
-Dose dependent depression of the medullary and pontine ventilatory centers
-Modest fall in renal blood flow and glomerular filtration rate
-Tolerance and physical dependence
Which agent is useful to induce seizure acidity in procedures in which seizure activity is desirable?
Which agent is useful for induction of anesthesia in patients with increased ICP?
What are the hazards of high doses of barbiturates? (x3)
-Hypotension which can decrease cerebral perfusion pressure.
Between barbiturates and isoflurane which agent is preferable if profound EEG is desired?
What is the side effect with overdose or large doses of barbiturates required to lower ICP?
Direct myocardial depression.
(also causes vasodilation, hypotension & ↓CPP)
What side effect occurs with thiopental and thiamylal (1:30,000) & how to treat
Anaphylaxis (immune-mediated histamine release)
-Treat with epinephrine & aggressive IVF resuscitation
Which induction agent is contraindicated in hypovolemic patients?
What does the depression of the medullary and pontine ventilatory centers by barbiturates lead to?
↓ response to hypercapnea (↓ respiratory rate, ↓ tidal volumes)
What is the mechanism of barbiturates that causes a modest fall in renal blood flow and glomerular filtration rate?
Decrease in BP and CO.
Which induction agent produces a modest decrease in hepatic blood flow?
(Thiopental happens to have a low hepatic extraction ratio & is dependant on hepatic enzyme activity rather than hepatic blood flow)
Which agent is the most potent enzyme inducer of the barbiturates?
(metabolism of oral anticoagulants, phenytoin, TCA, corticosteroids, vitamin K, BCP may be increased)
What agent is contraindicated in patients with intermittent poryphyria?
What does intra-arterial injection of barbiturates result in?
Immediate, intense vasoconstriction and excruciating pain that radiates along the distribution of the artery. Gangrene and permanent nerve damage may result.
What is the treatment of intra-arterial injection? (x5)
-Dilute the drug
-Prevent arterial spasm
-Maintain blood flow
-Vasodilate (Lidocaine, papaverine, phenoxybenzamine) -Reduce pain (Sympathectomy of the upper extremity produced by a brachial plexus block.)
Anaphylaxis vs anaphylactoid
Anaphylaxis: immune mediated & requires prior exposure
Anaphylactoid: require no previous exposure or sensitization but results in hystamine release, vasodilation, wheals, and welts
What agent can impair neutrophil function?
What are the clinical uses of propofol? (x4)
-IV conscious sedation
-As a part of TIVA
What are the non-hypnotic applications of propofol? (x4)
-Antiemetic (decreases post-op N&V, effective tx for chemo induced N&V)
-Antipruritic (effective in the tx of pruritis associated with neauraxial opioids)
-Antioxidant properties similar to vitamin E
What is the mechanism of action of propofol? (x2)
-Interaction with GABA (enhance effect?)
-↓ dissociation of GABA from GABA receptor
(Exert sedative-hypnotic effects via interaction with GABA. It may also decrease the rate of GABA dissociation from the GABA receptor.)
What is the precautions/contraindications of propofol?
-Risk for bacterial contamination
-Peds = risk for
Use cautiously in peds d/t reports of metabolic acidosis, lipemic plasma, bradycardia, and progressive myocardial failure. Elderly require lower induction doses. Potential for bacterial contamination, .
What are the potential side effects of propofol administration besides it's effect on BP (especially concerning for pediatric pts)? (x4)
-Progressive myocardial failure
How can bacterial contamination with propofol be prevented? (x4)
-Change infusion lines Q12h,
-Discard unused portion in 6 hours.
In what patients can exaggerated BP effects occur with propofol? (x3)
-Patients with compromised LV function d/t CAD.
What are the CV effects of propofol? (x5)
-↓cerebral perfusion pressure.
-Risk for profound bradycardia and asystole.
How does propofol effect the respiratory system? (x3)
-Causes dose dependent depression of ventilation with apnea occurring in 25 to 35% of patients (effect is enhanced with pre-op administration of opioids)
-↓s tidal volume and respiratory rate.
-Causes bronchodilation and ↓s the incidence of intra-operative wheezing in patients with asthma.
When would etomidate be used for induction?
-If unstable CV system
(Alternative to propofol or barbiturates for induction of anesthesia especially in the presence of an unstable CV system.)
What are the cerebrovascular effects of etomidate? (x3)
-↓s cerebral blood flow
-↓s cerebral metabolic rate
What are the contraindications/precautions of etomidate? (x3)
-Can cause hypotension if given to hypovolemic patients.
-Use with caution or avoid in patients that may require an intact cortisol response (sepsis or hemorrhage patients).
-Use cautiously in patients with focal seizures.
What is the CV profile of etomidate & when might BP decrease? (x2)
Cardiovascular stability is characteristic of etomidate (minimal changes in HR, SV, CO)
-Mean BP may decrease 15% d/t fall in SVR.
-May cause ↓BP if given to hypovolemic pt
How does etomidate effect ventilation & for how long?
(less ventilatory suppression than other induction agents)
-Apnea may occasionally occur after rapid IV injection
-Causes a decrease in tidal volume
-↑ respiratory rate (compensation for ↓TV)
-Effects on breathing are transient (3-5 min).
What are the side effects of etomidate? (x3)
-Adrenocortical suppression (bad for septic, hemorrhagic, or otherwise very sick patients)
-Pain occuring during IV injection is frequent (80%) (35% propylene glycol)
-Myoclonus in 50% of patients
What is the mechanism of action of ketamine? (x5)
Ketamine Interacts with:
-*N-methyl-D-aspartate (NMDA) receptors (antagonizes the excitatory NMDA)
-*Opoid receptors (blocks Mu, agonist at Kappa)
-*Muscarinic receptors (anticholinergic effects)
What is the opioid receptor activity of ketamine?
Mu (antagonist) = euphoria [elation]
Kappa (Agonist) = dysphoria [depression]
(May be an antagonist at mu receptors and an agonist at kappa receptors.)
What suggests that ketamine is an antagonist at the muscarinic receptor?
It produces anticholinergic symptoms (emergence delirium, bronchodilation, sympathomimetic action).
What is the clinical use of ketamine & 3 beneficial properties?
-useful in hypovolemic patients d/t drugs CV-stimulating effects.
-Has bronchodilator activity (successful treatment of status asthmaticus)
In what patients should ketamine be avoided? (x4)
-Pts with impaired cardiac function
-Hypertensive pts (systemic or pulmonary hypertension)
-nystagmus may make eye surgery difficult.
Which agent can be mixed with propofol for production of TIVA and has more stable hemodynamics than propofol and fentanyl without incidence of emergence reactions?
What are the S.E. of ketamine? (x3)
-Stimulates the CV system
-May increase ICP placing patients with intracranial pathology at risk.
What are the CV effects of ketamine? (x3)
-↑SBP (20-40 mmHg)
-↑cardiac work & mycoardial O₂ consumption
(Increases systemic and pulmonary arterial pressure, cardiac work, and myocardial oxygen requirements. Increase in SBP 20-40 mmHg.)
How does ketamine affect ventilation and the airway? (x4)
-Salivary secretions are increased necessitating protection of airway (giving glycopyrrolate may help)
-Doesn't produce significant depression of ventilation
-Apnea can occur if the drug is given rapidly IV or if an opioid is included.
-Has bronchodilatory activiey (status asthmaticus has successfully been treated with ketamine)
What are the risk factors of emergence delirium associated with ketamine? (x4)
(Incidence between 5-30%)
-doses >2 mg/kg
-history of personality disorders or frequent dreaming.
What is the emergence from ketamine anesthesia associated with & what is the incidence of this occurring?
(Visual, auditory, proprioception, confusional illusions, which may progress to delirium.)
How is emergence delirium prevented when giving ketamine? (x2)
-Give Versed at least 5 minutes prior to induction
-Inhalation agents & thiopental also help reduce delirium
(Benzodiazepines (Versed) have proven to be the most effective. Give a benzo 5 minutes prior to induction.)
Which benzodiazepine is most effective in preventing emergence delirium when giving ketamine?
(Midazolam is more effective than diazepam.)
What agents may increase the incidence of emergence delirium when giving ketamine? (x2)
Atropine or droperidol.
Propofol + pediatric strabismus surgery =
Increase incidence of oculocardiac reflex (bradycardia) in pediatric strabismus surgery.
Induction agent characterized by cardiovascular stability & how this stability may be compromised
-Doses greater than 0.45 mg/kg [recommended is 0.3 mg/kg] may lead to ↓BP/CO
What is unique about Ketamine (x5)
-CV stimulating effects
-Emergence delirium (reduce by giving versed as premed)
-↑s salivary secretion (must give antisialagogue [↓ production of saliva] like glycopyrrolate)
-Doesn't normally suppress ventilation
What is unique about Propofol
What is unique about etomidate (x3)
-CV stability (Ok if no CV reserve)
-Less ventilatory depression (↓TV but ↑RR to compensate & only lasts 3-5 min)
Which induction agent would be beneficial to a hypovolemic patient
Ketamine (CV-stimulating effects)
What will determine whether-or-not you can use barbiturates?
Concentration of propofol (mg/mL)
1% solution (10 mg / mL)
Propofol induction dose & how to adjust for elderly
1.5-2.5 mg / kg (↓25-50% in the elderly)
Etomidate induction dose
0.2-0.4 mg / kg
Ketamine IV & IM induction doses
1-2 mg/kg IV
2-4 mg/kg IM
Mechanism of action of Dexmedetomidine (Precedex®)
α₂ agonist (like clonidine)
Dexmedetomidine (Precedex®) uses
Adjunct for anesthesia & ICU sedation
Dexmedetomidine (Precedex®) bolus & maintenance doses
Bolus: 1 mcg/kg IV over 10 minutes
Maint: 0.2-0.7 mcg/kg/hr (max 24 hrs)
Which induction agent tends to cause nystagmus?
Which induction agent causes intense analgesia
Which induction agent is associated with increased salivary production (may require giving an antisialigogue such as glycopyrrolate)
Propofol dose for conscious sedation
What is the maintenance dose for propofol anesthesia?
What is the analgesic dose for ketamine?
(1/4th the induction dose)