Lecture 15: Pharmacology and Intravenous Anesthetics Flashcards
What are the 5 A’s of amnesia?
- amnesia
- anesthesia
- analgesia
- akinesia
- areflexia
When do you give sedatives or hypnotics?
- ICU sedation
- procedural sedation
- seizure treatment
- generalized anxiety disorder, panic disorder
- ethanol withdrawal
- insomnia
- muscle spasms
What neurotransmitters are involved in sedation/hypnotics?
GABA Histamine Serotonin Norepinephrine Acetylcholine
What is Hypnosis?
Leads to a state of unconsciousness (cause sleep)
What is sedation?
Leads to a decrease activity; calming, relaxing effect; does not necessarily induce sleep though it does at high doses
What are the Pharmacokinetic characteristics?
i. Route of administration
ii. Elimination
iii. Metabolism
iv. Distribution
What is the difference between drug elimination and redistribution?
Redistribution = measurement used to gauge the length of effect of drug in body
-as soon as drug redistributes, the drug effect is gone
Elimination doesn’t say anything about how long effects last)
When you give drug to patient, where does it go first?
Central compartment
Most well perfused (brain, kidney, liver)
Where does the drug go after the central compartment?
Fat (slowly equilibrating compartment)
Muscle (rapid equilibrating compartment)
How does drug stop working?
Because it has decreased concentration in central compartment…so you can have drug in body while it doesn’t do shit
That’s why redistribution is more important than elimination half-life
What is the context-sensitive half time?
The half-time of the drug depends on how long you give it
The longer you infuse a drug, the longer it takes to eliminate
What drugs have the longest context-sensitive half-time? Significance?
The ones that are most stored in fat (because the fat will release drugs into plasma once it has decreased in concentration in central compartment)
This means that the higher the context-sensitive half-time, the less likely you’re going to want to give this guy intravenously UNLESS you want to knock people out for a long ass time
What are the characteristics of pharmacodynamics?
- Receptor agonist, antagonist, partial agonist
- Genetic variability in receptor density and sensitivity
- Dosre response
- efficacy, potency, toxicity
What are examples of drugs with long context-sensitive half-times? Significance?
- Diazepam (longest)
- Thiopental
You don’t want to give them because it is harder to control
What is the problem with fat soluble drugs?
We never get a steady state, because the drug distributes from plasma, to perfused tissues, muscle groups, then fat groups
What are key features of propofol?
Milk of amnesia Contraindicated in Egg allergy Killed Michael Jackson Used for the induction/maintenance of general anesthesia Acts through GABA
Why is propofol a drug of abuse?
- Increases dopamine concentrations in nucleus accumbens
- Euphoria, feeling of well-being, like cocaine
- Sexual dreams
What are the adverse effects of propofol?
- VERY PAINFUL on injection
- propofol related infusion syndrome (PRI)
- Hypertriglyceridemia (because a calorie source) and pancreatitis
- decreased poly chemotaxis
What are the ABSOLUTE contraindications? Relative contraindications?
- egg protein and allergy to propofol
- hemodynamic instability (hypotension)
- awareness under anesthesia (for TIVA)
What is the redistribution half-life of propofol? Significance?
2-8 minutes
That means patient wakes up in 2-8 minutes
How is propofol metabolized?
Hepatic, renal
Glucuronidated or sulfated prior to excretion
For a kid how much propofol do you need vs. an elderly person?
Kid needs MORE propofol because more head in proportion of body…elderly person needs less
What is the MOA of propofol?
- it potentiates the effects of GABA
- does NOT affect pain…only affects consciousness
What are the physiological effects?
Loss of consciousness HYPOtension -vasodilation/sympathetic tone Apnea -bronchodilation, decreased response to hypercarbia and hypoxia DECREASED respiration -DECREASED cerebral metabolic rate -DECREASED cerebral blood flow Kind of like desflurane except desflurane has increased cerebral blood flow
What do you need to know about etomidate?
Used for INDUCTION of general anesthesia
Used for known or anticipated hemodynamic instability
Used for illness, cardiac anesthesia
What is the MOA of etomidate?
Potentiates the effects of GABA
No effects on pain
Causes adrenocortical suppression
What are the pharmacokinetic features of etomidate?
Redistribution = 2-8 minutes
Elimination = 3-5 hours (but this doesn’t say anything about how long effects last)
Metabolized by liver and excreted in urine/bile
What are the physiologic effects of etomidate?
It does NOT fuck with cardiovascular system so no hypotension
It does NOT fuck with respiratory system so no respiratory depression
Can cause seizures
Same neurologic effects as propofol (decreased metabolism and blood flow in brain)
What are the adverse effects of etomidate?
- adrenal suppression
- INCREASED postop NAUSEA/vomiting relative to propofol
What are the absolute contraindications of etomidate?
Allergy to etomidate Relative: adrenal insufficiency -critical illness -history of postop nausea/vomiting Therefore it is NOT abusable lmao
What is thiopental?
A BARBITURATE Used in the second world war and in lethal injections Related to phenobarbital, pento barbital Acidic motherfuckerr Cousins used for seizure therapy lol Potentiates effect on GABA
What do you need to know about thiopental?
Used for INDUCTION general anesthesia
-related to drugs that help induce seizures
What are the pharmacokinetic features of thiopental?
5-10 half life redistribution
Metabolism: in the liver and excreted into kidneys
It is an EXCEPTION to rule of hepatic metabolism because it is largely unchanged when excreted in kidney
-zero order kinetics at high doses
Which IV anesthetic is not metabolized in the liver?
Thiopental
What are the contraindications of thiopental?
Acute Intermittent Porphyria
What is the MOA of thiopental?
Barbiturates bind to post-synaptic GABA receptor
- increase the duration of chloride channel opening when GABA binds
- activates chloride flow in absence of GABA
What are the physiologic effects of thiopental?
Same as propofol
Exception: Methohexital DECREASES seizure threshold relative to other induction agents
What are the adverse effects of thiopental?
Garlic/onion taste
- tissue irritation/necrosis
- stimulation of porphyrin formation
- ANTI-analgesic effect
What are absolute contraindications in thiopental? Relative contraindications?
ACUTE INTERMITTENT PORPHYRIA
Allergy to thiopental
And
Hemodynamic instability/questionable IV access
What drug is ketamine most like?
PCP (phencyclidine)
What is porphyrin?
A group of organic compounds
Example: heme
What does Ketamine do to you?
Causes dissociative hypnosis
A lot like PCP or Phencyclidine…PCP allows you to have dissociative hypnosis
Used as recreational drug
S-enantiomer has all the nice effects
R-enantiomer has all the negative effects
What is the key delineating factor of ketamine?
You don’t have to give it IV (can give it PO, IM, intranasal, etc.)
It is DIFFERENT from the other three IV anesthetics (etomidate, propofol, thiopental)
Has analgesic effect
What are pharmokinetics of ketmamine?
11-16 mins of redistribution half-life
Elimination = 203 hours
Metabolism = hepatic degradation
What are the desirable properties of ketamine?
IV, PO, IM intranasal Analgesic (only IV anesthetic that is analgesic) Hypnotic/amnestic Maintains sympathetic tone…HYPERtension POTENT bronchodilator/analgesic Preserves respiration
What is the MOA of ketamine?
Primary NMDA receptor ANTAGONIST
What are the undesirable properties of ketamine?
Increase salivation/lacrimation
Causes dysphoria (a state of unhappiness)
Increase intracranial pressure
Increased myocardial work
What are the adverse effects?
Salivation
Dysphoria/dissociation
Sympathetic stimulation (tachycardia and hypertension)
Absolute contraindications of ketamine? Relative contraindications?
Allergy to ketamine And Psychosis Compromised myocardial function Intracranial hypertension
What are examples of other sedative/hypnotics
- benzodiazepines (important)
- opioids (important)
- alpha-2 adrenoreceptor antagonists
- dopamine antagonists
- antihistamines
- Z-drugs
- Melatonin agonists
- general anesthetics like halothane, flurane
What is the sedative ingredient in Tylenol PM?
Diphenhydramine
-a sedative
What is diphenhydramine?
The sedative ingredient in Tylenol
What are the delineating factors of Propofol?
- rapid onset/offset
- used for anesthetic induction, TIVA (total intravenous anesthetic), ICU sedation
- partially metabolized by EXTRAhepatic tissues
- causes hemodynamic instability
What are the delineating factors of Etomidate?
- drug of choice in hemodynamically compromised patients (little physiological effects)
- causes adrenocortical suppression
- causes NAUSEA and VOMITING
What are the delineating factors Thiopental
- very similar to propofol in pharmacokinetic properties
- contraindicated in porphyria
What are the delineating factors of Ketamine?
- causes sympathetic stimulation
- potent analgesic
- causes dissociative anesthesia and dysphoria
- contraindicated in psychosis
- does NOT REQUIRE IV access (can be given PO)
Why do IV induction agents cause hypotension?
Decrease vasomotor tone
Decrease cardiac output
Myocardial depression
What anesthetic do you give A 25 yo man with developmental delay, claustrophobia, fear of needles and no IV access presenting for inguinal hernia repair?
Ketamine
How does drug stop working?
Because it has decreased concentration in central compartment…so you can have drug in body while it doesn’t do shit
That’s why redistribution is more important than elimination half-life
What is the context-sensitive half time?
The half-time of the drug depends on how long you give it
The longer you infuse a drug, the longer it takes to eliminate
What drugs have the longest context-sensitive half-time? Significance?
The ones that are most stored in fat (because the fat will release drugs into plasma once it has decreased in concentration in central compartment)
This means that the higher the context-sensitive half-time, the less likely you’re going to want to give this guy intravenously UNLESS you want to knock people out for a long ass time
What are the characteristics of pharmacodynamics?
- Receptor agonist, antagonist, partial agonist
- Genetic variability in receptor density and sensitivity
- Dosre response
- efficacy, potency, toxicity
What are examples of drugs with long context-sensitive half-times? Significance?
- Diazepam (longest)
- Thiopental
You don’t want to give them because it is harder to control
What is the problem with fat soluble drugs?
We never get a steady state, because the drug distributes from plasma, to perfused tissues, muscle groups, then fat groups
What are key features of propofol?
Milk of amnesia Contraindicated in Egg allergy Killed Michael Jackson Used for the induction/maintenance of general anesthesia Acts through GABA
Why is propofol a drug of abuse?
- Increases dopamine concentrations in nucleus accumbens
- Euphoria, feeling of well-being, like cocaine
- Sexual dreams
What are the adverse effects of propofol?
- VERY PAINFUL on injection
- propofol related infusion syndrome (PRI)
- Hypertriglyceridemia (because a calorie source) and pancreatitis
- decreased poly chemotaxis
What are the ABSOLUTE contraindications? Relative contraindications?
- egg protein and allergy to propofol
- hemodynamic instability (hypotension)
- awareness under anesthesia (for TIVA)
What is the redistribution half-life of propofol? Significance?
2-8 minutes
That means patient wakes up in 2-8 minutes
How is propofol metabolized?
Hepatic, renal
Glucuronidated or sulfated prior to excretion
For a kid how much propofol do you need vs. an elderly person?
Kid needs MORE propofol because more head in proportion of body…elderly person needs less
What is the MOA of propofol?
- it potentiates the effects of GABA
- does NOT affect pain…only affects consciousness
What are the physiological effects?
Loss of consciousness HYPOtension -vasodilation/sympathetic tone Apnea -bronchodilation, decreased response to hypercarbia and hypoxia DECREASED respiration -DECREASED cerebral metabolic rate -DECREASED cerebral blood flow Kind of like desflurane except desflurane has increased cerebral blood flow
What do you need to know about etomidate?
Used for INDUCTION of general anesthesia
Used for known or anticipated hemodynamic instability
Used for illness, cardiac anesthesia
What is the MOA of etomidate?
Potentiates the effects of GABA
No effects on pain
Causes adrenocortical suppression
What are the pharmacokinetic features of etomidate?
Redistribution = 2-8 minutes
Elimination = 3-5 hours (but this doesn’t say anything about how long effects last)
Metabolized by liver and excreted in urine/bile
What are the physiologic effects of etomidate?
It does NOT fuck with cardiovascular system so no hypotension
It does NOT fuck with respiratory system so no respiratory depression
Can cause seizures
Same neurologic effects as propofol (decreased metabolism and blood flow in brain)
What are the adverse effects of etomidate?
- adrenal suppression
- INCREASED postop NAUSEA/vomiting relative to propofol
What are the absolute contraindications of etomidate?
Allergy to etomidate Relative: adrenal insufficiency -critical illness -history of postop nausea/vomiting Therefore it is NOT abusable lmao
What is thiopental?
A BARBITURATE Used in the second world war and in lethal injections Related to phenobarbital, pento barbital Acidic motherfuckerr Cousins used for seizure therapy lol Potentiates effect on GABA
What do you need to know about thiopental?
Used for INDUCTION general anesthesia
-related to drugs that help induce seizures
What are the pharmacokinetic features of thiopental?
5-10 half life redistribution
Metabolism: in the liver and excreted into kidneys
It is an EXCEPTION to rule of hepatic metabolism because it is largely unchanged when excreted in kidney
-zero order kinetics at high doses
Which IV anesthetic is not metabolized in the liver?
Thiopental
What are the contraindications of thiopental?
Acute Intermittent Porphyria
What is the MOA of thiopental?
Barbiturates bind to post-synaptic GABA receptor
- increase the duration of chloride channel opening when GABA binds
- activates chloride flow in absence of GABA
What are the physiologic effects of thiopental?
Same as propofol
Exception: Methohexital DECREASES seizure threshold relative to other induction agents
What are the adverse effects of thiopental?
Garlic/onion taste
- tissue irritation/necrosis
- stimulation of porphyrin formation
- ANTI-analgesic effect
What are absolute contraindications in thiopental? Relative contraindications?
ACUTE INTERMITTENT PORPHYRIA
Allergy to thiopental
And
Hemodynamic instability/questionable IV access
What drug is ketamine most like?
PCP (phencyclidine)
What is porphyrin?
A group of organic compounds
Example: heme
What does Ketamine do to you?
Causes dissociative hypnosis
A lot like PCP or Phencyclidine…PCP allows you to have dissociative hypnosis
Used as recreational drug
S-enantiomer has all the nice effects
R-enantiomer has all the negative effects
What is the key delineating factor of ketamine?
You don’t have to give it IV (can give it PO, IM, intranasal, etc.)
It is DIFFERENT from the other three IV anesthetics (etomidate, propofol, thiopental)
Has analgesic effect
What are pharmokinetics of ketmamine?
11-16 mins of redistribution half-life
Elimination = 203 hours
Metabolism = hepatic degradation
What are the desirable properties of ketamine?
IV, PO, IM intranasal Analgesic (only IV anesthetic that is analgesic) Hypnotic/amnestic Maintains sympathetic tone…HYPERtension POTENT bronchodilator/analgesic Preserves respiration
What is the MOA of ketamine?
Primary NMDA receptor ANTAGONIST
What are the undesirable properties of ketamine?
Increase salivation/lacrimation
Causes dysphoria (a state of unhappiness)
Increase intracranial pressure
Increased myocardial work
What are the adverse effects?
Salivation
Dysphoria/dissociation
Sympathetic stimulation (tachycardia and hypertension)
Absolute contraindications of ketamine? Relative contraindications?
Allergy to ketamine And Psychosis Compromised myocardial function Intracranial hypertension
What are examples of other sedative/hypnotics
- benzodiazepines (important)
- opioids (important)
- alpha-2 adrenoreceptor antagonists
- dopamine antagonists
- antihistamines
- Z-drugs
- Melatonin agonists
- general anesthetics like halothane, flurane
What is the sedative ingredient in Tylenol PM?
Diphenhydramine
-a sedative
What is diphenhydramine?
The sedative ingredient in Tylenol
What are the delineating factors of Propofol?
- rapid onset/offset
- used for anesthetic induction, TIVA (total intravenous anesthetic), ICU sedation
- partially metabolized by EXTRAhepatic tissues
- causes hemodynamic instability
What are the delineating factors of Etomidate?
- drug of choice in hemodynamically compromised patients (little physiological effects)
- causes adrenocortical suppression
- causes NAUSEA and VOMITING
What are the delineating factors Thiopental
- very similar to propofol in pharmacokinetic properties
- contraindicated in porphyria
What are the delineating factors of Ketamine?
- causes sympathetic stimulation
- potent analgesic
- causes dissociative anesthesia and dysphoria
- contraindicated in psychosis
- does NOT REQUIRE IV access (can be given PO)
Why do IV induction agents cause hypotension?
Decrease vasomotor tone
Decrease cardiac output
Myocardial depression
What anesthetic do you give A 25 yo man with developmental delay, claustrophobia, fear of needles and no IV access presenting for inguinal hernia repair?
Ketamine
