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B&B Week 6 Flashcards > Lecture 15: Pharmacology and Intravenous Anesthetics > Flashcards

Lecture 15: Pharmacology and Intravenous Anesthetics Flashcards

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1
Q

What are the 5 A’s of amnesia?

A
  1. amnesia
  2. anesthesia
  3. analgesia
  4. akinesia
  5. areflexia
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2
Q

When do you give sedatives or hypnotics?

A
  • ICU sedation
    • procedural sedation
    • seizure treatment
    • generalized anxiety disorder, panic disorder
    • ethanol withdrawal
    • insomnia
    • muscle spasms
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3
Q

What neurotransmitters are involved in sedation/hypnotics?

A 
GABA
Histamine
Serotonin
Norepinephrine
Acetylcholine
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4
Q

What is Hypnosis?

A

Leads to a state of unconsciousness (cause sleep)

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5
Q

What is sedation?

A

Leads to a decrease activity; calming, relaxing effect; does not necessarily induce sleep though it does at high doses

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6
Q

What are the Pharmacokinetic characteristics?

A

i. Route of administration
ii. Elimination
iii. Metabolism
iv. Distribution

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7
Q

What is the difference between drug elimination and redistribution?

A

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)

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8
Q

When you give drug to patient, where does it go first?

A

Central compartment

Most well perfused (brain, kidney, liver)

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9
Q

Where does the drug go after the central compartment?

A

Fat (slowly equilibrating compartment)

Muscle (rapid equilibrating compartment)

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10
Q

How does drug stop working?

A

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

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11
Q

What is the context-sensitive half time?

A

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

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12
Q

What drugs have the longest context-sensitive half-time? Significance?

A

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

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13
Q

What are the characteristics of pharmacodynamics?

A
  1. Receptor agonist, antagonist, partial agonist
  2. Genetic variability in receptor density and sensitivity
  3. Dosre response
  4. efficacy, potency, toxicity
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14
Q

What are examples of drugs with long context-sensitive half-times? Significance?

A
  1. Diazepam (longest)
  2. Thiopental
    You don’t want to give them because it is harder to control
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15
Q

What is the problem with fat soluble drugs?

A

We never get a steady state, because the drug distributes from plasma, to perfused tissues, muscle groups, then fat groups

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16
Q

What are key features of propofol?

A 
Milk of amnesia
Contraindicated in Egg allergy
Killed Michael Jackson
Used for the induction/maintenance of general anesthesia
Acts through GABA
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17
Q

Why is propofol a drug of abuse?

A
  1. Increases dopamine concentrations in nucleus accumbens
  2. Euphoria, feeling of well-being, like cocaine
  3. Sexual dreams
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18
Q

What are the adverse effects of propofol?

A
  1. VERY PAINFUL on injection
  2. propofol related infusion syndrome (PRI)
  3. Hypertriglyceridemia (because a calorie source) and pancreatitis
  4. decreased poly chemotaxis
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19
Q

What are the ABSOLUTE contraindications? Relative contraindications?

A
  1. egg protein and allergy to propofol
  2. hemodynamic instability (hypotension)
  3. awareness under anesthesia (for TIVA)
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20
Q

What is the redistribution half-life of propofol? Significance?

A

2-8 minutes

That means patient wakes up in 2-8 minutes

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21
Q

How is propofol metabolized?

A

Hepatic, renal

Glucuronidated or sulfated prior to excretion

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22
Q

For a kid how much propofol do you need vs. an elderly person?

A

Kid needs MORE propofol because more head in proportion of body…elderly person needs less

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23
Q

What is the MOA of propofol?

A
  • it potentiates the effects of GABA

- does NOT affect pain…only affects consciousness

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24
Q

What are the physiological effects?

A 
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
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25
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
26
What is the MOA of etomidate?
Potentiates the effects of GABA No effects on pain Causes adrenocortical suppression
27
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
28
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)
29
What are the adverse effects of etomidate?
- adrenal suppression | - INCREASED postop NAUSEA/vomiting relative to propofol
30
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 ```
31
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 ```
32
What do you need to know about thiopental?
Used for INDUCTION general anesthesia | -related to drugs that help induce seizures
33
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
34
Which IV anesthetic is not metabolized in the liver?
Thiopental
35
What are the contraindications of thiopental?
Acute Intermittent Porphyria
36
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
37
What are the physiologic effects of thiopental?
Same as propofol | Exception: Methohexital DECREASES seizure threshold relative to other induction agents
38
What are the adverse effects of thiopental?
Garlic/onion taste - tissue irritation/necrosis - stimulation of porphyrin formation - ANTI-analgesic effect
39
What are absolute contraindications in thiopental? Relative contraindications?
ACUTE INTERMITTENT PORPHYRIA Allergy to thiopental And Hemodynamic instability/questionable IV access
40
What drug is ketamine most like?
PCP (phencyclidine)
41
What is porphyrin?
A group of organic compounds | Example: heme
42
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
43
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
44
What are pharmokinetics of ketmamine?
11-16 mins of redistribution half-life Elimination = 203 hours Metabolism = hepatic degradation
45
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 ```
46
What is the MOA of ketamine?
Primary NMDA receptor ANTAGONIST
47
What are the undesirable properties of ketamine?
Increase salivation/lacrimation Causes dysphoria (a state of unhappiness) Increase intracranial pressure Increased myocardial work
48
What are the adverse effects?
Salivation Dysphoria/dissociation Sympathetic stimulation (tachycardia and hypertension)
49
Absolute contraindications of ketamine? Relative contraindications?
``` Allergy to ketamine And Psychosis Compromised myocardial function Intracranial hypertension ```
50
What are examples of other sedative/hypnotics
1. benzodiazepines (important) 2. opioids (important) 3. alpha-2 adrenoreceptor antagonists 4. dopamine antagonists 5. antihistamines 6. Z-drugs 7. Melatonin agonists 8. general anesthetics like halothane, flurane
51
What is the sedative ingredient in Tylenol PM?
Diphenhydramine | -a sedative
52
What is diphenhydramine?
The sedative ingredient in Tylenol
53
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
54
What are the delineating factors of Etomidate?
- drug of choice in hemodynamically compromised patients (little physiological effects) - causes adrenocortical suppression - causes NAUSEA and VOMITING
55
What are the delineating factors Thiopental
- very similar to propofol in pharmacokinetic properties | - contraindicated in porphyria
56
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)
57
Why do IV induction agents cause hypotension?
Decrease vasomotor tone Decrease cardiac output Myocardial depression
58
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
59
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
60
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
61
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
62
What are the characteristics of pharmacodynamics?
1. Receptor agonist, antagonist, partial agonist 2. Genetic variability in receptor density and sensitivity 3. Dosre response 4. efficacy, potency, toxicity
63
What are examples of drugs with long context-sensitive half-times? Significance?
1. Diazepam (longest) 2. Thiopental You don’t want to give them because it is harder to control
64
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
65
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 ```
66
Why is propofol a drug of abuse?
1. Increases dopamine concentrations in nucleus accumbens 2. Euphoria, feeling of well-being, like cocaine 3. Sexual dreams
67
What are the adverse effects of propofol?
1. VERY PAINFUL on injection 2. propofol related infusion syndrome (PRI) 3. Hypertriglyceridemia (because a calorie source) and pancreatitis 4. decreased poly chemotaxis
68
What are the ABSOLUTE contraindications? Relative contraindications?
1. egg protein and allergy to propofol 2. hemodynamic instability (hypotension) 3. awareness under anesthesia (for TIVA)
69
What is the redistribution half-life of propofol? Significance?
2-8 minutes | That means patient wakes up in 2-8 minutes
70
How is propofol metabolized?
Hepatic, renal | Glucuronidated or sulfated prior to excretion
71
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
72
What is the MOA of propofol?
- it potentiates the effects of GABA | - does NOT affect pain…only affects consciousness
73
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 ```
74
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
75
What is the MOA of etomidate?
Potentiates the effects of GABA No effects on pain Causes adrenocortical suppression
76
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
77
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)
78
What are the adverse effects of etomidate?
- adrenal suppression | - INCREASED postop NAUSEA/vomiting relative to propofol
79
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 ```
80
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 ```
81
What do you need to know about thiopental?
Used for INDUCTION general anesthesia | -related to drugs that help induce seizures
82
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
83
Which IV anesthetic is not metabolized in the liver?
Thiopental
84
What are the contraindications of thiopental?
Acute Intermittent Porphyria
85
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
86
What are the physiologic effects of thiopental?
Same as propofol | Exception: Methohexital DECREASES seizure threshold relative to other induction agents
87
What are the adverse effects of thiopental?
Garlic/onion taste - tissue irritation/necrosis - stimulation of porphyrin formation - ANTI-analgesic effect
88
What are absolute contraindications in thiopental? Relative contraindications?
ACUTE INTERMITTENT PORPHYRIA Allergy to thiopental And Hemodynamic instability/questionable IV access
89
What drug is ketamine most like?
PCP (phencyclidine)
90
What is porphyrin?
A group of organic compounds | Example: heme
91
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
92
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
93
What are pharmokinetics of ketmamine?
11-16 mins of redistribution half-life Elimination = 203 hours Metabolism = hepatic degradation
94
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 ```
95
What is the MOA of ketamine?
Primary NMDA receptor ANTAGONIST
96
What are the undesirable properties of ketamine?
Increase salivation/lacrimation Causes dysphoria (a state of unhappiness) Increase intracranial pressure Increased myocardial work
97
What are the adverse effects?
Salivation Dysphoria/dissociation Sympathetic stimulation (tachycardia and hypertension)
98
Absolute contraindications of ketamine? Relative contraindications?
``` Allergy to ketamine And Psychosis Compromised myocardial function Intracranial hypertension ```
99
What are examples of other sedative/hypnotics
1. benzodiazepines (important) 2. opioids (important) 3. alpha-2 adrenoreceptor antagonists 4. dopamine antagonists 5. antihistamines 6. Z-drugs 7. Melatonin agonists 8. general anesthetics like halothane, flurane
100
What is the sedative ingredient in Tylenol PM?
Diphenhydramine | -a sedative
101
What is diphenhydramine?
The sedative ingredient in Tylenol
102
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
103
What are the delineating factors of Etomidate?
- drug of choice in hemodynamically compromised patients (little physiological effects) - causes adrenocortical suppression - causes NAUSEA and VOMITING
104
What are the delineating factors Thiopental
- very similar to propofol in pharmacokinetic properties | - contraindicated in porphyria
105
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)
106
Why do IV induction agents cause hypotension?
Decrease vasomotor tone Decrease cardiac output Myocardial depression
107
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

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