UNIT 4 Pharm 1 💊 Flashcards
(171 cards)
1
Q
A
2
Q
Define volume of distribution and recite equation.
A
Theoretical measure of how a drug distributes throughout the body
Assumes the drug distributes instantaneously and is not subjected to biotransformation or elimination before fully distributing.
3
Q
What are the implications when a drug’s Vd exceeds TBW?
A
If Vd > TBW (>0.6L/kg or 42L), the drug is assumed to be lipophilic and distributes into TBW + fat, requiring a higher dose to achieve given plasma concentration
Examples include propofol and fentanyl.
4
Q
What are the implications when a drug’s Vd is less than TBW?
A
If Vd < TBW (>0.6L/kg or 42L), the drug is assumed to be hydrophilic and distributes into some or all of body water, requiring a lower dose to achieve plasma concentration
Examples include neuromuscular blockers and albumin.
5
Q
How do you calculate the loading dose for an IV medication?
A
IV drugs have bioavailability = 1 since all of the drug enters the bloodstream.
6
Q
What is clearance?
A
Volume of plasma that is cleared of a drug per unit of time.
7
Q
What is steady state?
A
When amount entering = amount eliminated, resulting in a stable plasma concentration.
Achieved after 5 half-lives.
8
Q
Compare the alpha and beta distribution phases on the plasma concentration curve.
A
Alpha phase describes drug distribution from plasma to tissues; Beta phase describes drug elimination from the central compartment.
9
Q
What percentage of the initial dose of Esmolol remains after 3 half-lives?
A
12.5%.
10
Q
What is context-sensitive half time?
A
Time required for plasma concentration to decrease by 50% after discontinuing the drug.
11
Q
Which anesthetic has the longest context-sensitive half time?
A
Fentanyl has a longer context-sensitive half time due to extended infusion.
12
Q
What is the difference between a strong and weak acid or base?
A
Strong acids/bases ionize completely; weak acids/bases only partially ionize.
13
Q
What is ionization?
A
The process where a molecule gains a positive or negative charge.
14
Q
What factors determine how much a molecule will ionize?
A
pH of solution and pKa of drug.
15
Q
What happens when you put an acid in a basic solution?
A
Weak bases become non-ionized and lipid soluble; weak acids become ionized and water soluble.
16
Q
Can you tell if a drug is an acid or base by looking at the name?
A
Most drugs are weak acids or weak bases, often prepared as salts.
17
Q
Name 3 key plasma proteins and their binding characteristics.
A
- Albumin - acidic
- A1-acid glycoprotein - basic
- Beta-globulin - basic
18
Q
What conditions decrease serum albumin concentration?
A
- Liver disease
- Renal disease
- Old age
- Malnourishment
- Pregnancy
19
Q
What conditions affect A1-acid glycoprotein concentration?
A
- Increase: surgical stimulation, myocardial infarction, chronic pain, rheumatoid arthritis, advanced age
- Decrease: neonates, pregnancy
20
Q
How do changes in plasma protein binding affect plasma drug concentration?
A
↓ binding increases Cp; ↑ binding decreases Cp.
21
Q
How do you calculate changes in plasma protein binding?
A
[free drug] + [unbound protein binding sites] ↔️ [bound drug].
22
Q
What kinetic model best describes the elimination of a drug cleared from the body at a rate proportional to its plasma concentration?
A
First order kinetics.
23
Q
How does the rate of elimination change for alcohol cleared via zero-order kinetics?
A
A constant amount is eliminated per unit of time, independent of plasma concentration.
24
Q
What is the function of phase 1 reaction in drug metabolism?
A
Small molecular changes that increase polarity to prepare for phase 2 reaction.
25
List 3 examples of phase 1 reactions.
* Oxidation
* Reduction
* Hydrolysis
26
What is the function of phase 2 reactions?
Conjugates an endogenous, highly polar substrate to the molecule, resulting in a water-soluble, biologically inactive molecule ready for excretion.
27
List 5 common substrates for phase 2 reactions.
* Glucuronic acid
* Glycine
* Acetic acid
* Sulfuric acid
* Methyl group
28
Discuss enterohepatic circulation and list 2 drug examples.
Some conjugated compounds are excreted in bile, reactivated in the intestine, and reabsorbed into systemic circulation.
## Footnote
Examples include diazepam and warfarin.
29
What is the extraction ratio?
How much drug is delivered to a clearing organ vs. how much is removed by that organ.
30
What is perfusion-dependent elimination in hepatic clearance?
For drugs with high hepatic extraction ratio (> 0.7), clearance is dependent on liver blood flow.
31
What is capacity-dependent elimination in hepatic clearance?
For drugs with low hepatic extraction ratio (< 0.3), clearance is dependent on the liver's ability to extract it from the blood.
32
Which will have a greater effect on the metabolism of theophylline: prolonged hypotension or CYP inhibition?
CYP inhibition.
33
What’s the difference between hepatic enzyme inducers and inhibitors?
Inducers increase enzyme activity; inhibitors decrease enzyme activity.
34
List 2 drug classes and 7 drugs metabolized by pseudocholinesterase.
* Esters
* NMBDs (SCh and Mivacurium)
* Chloroprocaine
* Tetracaine
* Procaine
* Benzocaine
* Cocaine
35
List 6 drugs metabolized by non-specific plasma esterases.
* Esmolol
* Remifentanil
* Remimazolam
* Clevidipine
* Atracurium
* Etomidate
36
List 1 drug biotransformed by alkaline phosphatase hydrolysis.
Fospropofol.
37
Define pharmacokinetics.
What body does to drug (absorption, distribution, metabolism, and elimination).
38
Define pharmacodynamics.
What drugs do to body (relationship between effect site concentration and clinical effect).
39
What is potency and how is it measured?
Dose required to achieve a given clinical effect, measured by ED50 and ED90.
40
How is potency measured on the dose-response curve?
Drug A is more potent than B, indicated by a left shift on the x-axis.
41
What is efficacy and how is it measured on the dose-response curve?
Measure of intrinsic ability of drug to produce a clinical effect, measured on the y-axis.
42
What does the slope of the dose-response curve tell you?
How many receptors must be occupied to elicit a clinical effect.
43
What are the differences between a full agonist, partial agonist, antagonist, and inverse agonist?
* Full agonist - turns on specific cellular response
* Partial agonist - partially turns on
* Antagonist - blocks agonist from binding
* Inverse agonist - causes opposite effect of full agonist
44
What is competitive antagonism? Give an example.
Reversible antagonism that can be overcome by increasing agonist concentration. Example: Atropine.
45
What is noncompetitive antagonism? Give an example.
Irreversible antagonism that cannot be overcome, requiring new receptors. Example: ASA.
46
Define ED50.
Effective dose 50 – expected clinical response in 50% of population.
47
Define TD50.
Toxic dose in 50% of population.
48
Define therapeutic index.
Safety margin for a desired clinical effect.
49
What is chirality?
Part of stereochemistry dealing with molecules that have a center of three-dimensional asymmetry.
50
What is an enantiomer? What is the clinical relevance?
Chiral molecules that are non-superimposable mirror images; different enantiomers can produce different clinical effects.
51
What is a racemic mixture? List some commonly used ones.
A mixture containing 2 enantiomers in equal amounts. Examples: bupivacaine, ketamine, isoflurane, desflurane.
52
What is the MOA of propofol?
Direct GABA agonist that increases Cl- conductance, leading to neuronal hyperpolarization.
53
What is the dose, onset, duration, and clearance mechanism for propofol?
* Dose: 1.5-2.5 mg/kg IV
* Onset: 30-60s
* Duration: 5-10mins
* Clearance: liver (P450) + extrahepatic metabolism
54
What are the CV and respiratory effects of propofol?
* CV: ↓ BP, SVR, contractility, venous tone
* RESP: shifts CO2 response curve down and right, causing respiratory depression/apnea
55
What are the CNS effects of propofol?
↓ CMRO2, anticonvulsant properties, ↓ cerebral blood flow, ↓ ICP, ↓ intraocular pressure.
56
What is the formulation of propofol, and is there a patient population where this is a problem?
1% solution in an emulsion of egg lecithin, soybean oil, and glycerol; concerns regarding allergies to these components.
57
What is propofol infusion syndrome (PIS)?
A condition associated with high mortality due to impaired oxidative phosphorylation and fatty acid metabolism.
58
What are the risk factors for propofol infusion syndrome?
* > 4mg/kg/hr
* > 48hr infusion duration
* Adults > kids
* Inadequate O2 delivery
* Sepsis
* Significant cerebral injury
59
What is propofol infusion syndrome (PIS)?
PIS is associated with high mortality, caused by an increase in long chain triglycerides that impairs oxidative phosphorylation and fatty acid metabolism, starving cardiac and skeletal muscle cells of oxygen.
## Footnote
Propofol infusion syndrome is particularly dangerous in certain clinical settings.
60
What are the risk factors for PIS?
* > 4mg/kg/hr (67mcg/kg/min)
* > 48hr gtt duration
* adults > kids
* inadequate O2 delivery
* sepsis
* significant cerebral injury
## Footnote
These factors increase the likelihood of developing PIS.
61
What is the clinical presentation of PIS?
* metabolic acidosis (base deficit >10mmol/L)
* rhabdomyolysis
* enlarged or fatty liver
* renal failure
* hyperlipidemia
* lipemia (cloudy plasma or blood) may be an early sign
## Footnote
Clinical signs may vary in severity.
62
When must a propofol syringe be discarded?
Syringe should be discarded after 6 hours; infusion after 12 hours (including tubing).
## Footnote
This is due to the risk of bacterial and fungal growth.
63
What preservatives are used in brand and generic propofol?
* Brand (Diprivan) contains EDTA.
* Generic formulations may contain metabisulfite or benzyl alcohol.
## Footnote
Metabisulfite can cause bronchospasm in asthmatic patients; benzyl alcohol should be avoided in infants.
64
How can prop injection pain be minimized?
* injecting into a larger vein or more proximal
* using lidocaine
* using opioids
## Footnote
These methods can help alleviate discomfort during propofol administration.
65
What dose of propofol can be used to treat PONV?
10-20 mg IV or 10 mcg/kg/min.
## Footnote
This can help manage postoperative nausea and vomiting.
66
How is Fospropofol converted to its active form?
Fospropofol is a prodrug, which explains its slower onset (5-13 mins) and duration (15-45 mins).
## Footnote
This conversion is important for understanding its pharmacokinetics.
67
What is the primary mechanism of action for anesthesia produced by ketamine?
NMDA antagonist that dissociates thalamus from limbic system and antagonizes glutamate.
## Footnote
It also targets secondary receptors like opioid and muscarinic receptors.
68
What are the potential routes of administration for ketamine and their doses?
* IV: induction 1-2mg/kg, analgesia 0.1-0.5 mg/kg
* IM: 4-8 mg/kg
* PO: 10 mg/kg
## Footnote
Each route has different onset times and applications.
69
What is the onset, duration, and clearance mechanism for ketamine?
* Onset: IV – 30-60s, IM – 2-4 mins, PO – varies
* Duration: 10-20 mins (60-90 for full orientation)
* Clearance: Liver P450s
## Footnote
Active metabolite Norketamine is 1/3 the potency of ketamine.
70
What are the cardiovascular effects of ketamine?
* ↑ SNS tone, CO, HR, SVR, PVR
* sub-hypnotic dose (<0.5 mg/kg) does not activate SNS
* myocardial depressant effects can be unmasked in patients with depleted catecholamines
## Footnote
Caution is advised in patients with RV failure.
71
What are the respiratory effects of ketamine?
* bronchodilation
* intact upper airway tone and reflexes
* maintains respiratory drive
* brief period of apnea may occur post-induction
* ↑ oral and pulmonary secretions
## Footnote
Increased secretions can raise the risk of laryngospasm.
72
What are the CNS effects of ketamine?
* ↑ CMRO2, CBF, ICP, EEG activity
* nystagmus
* emergence delirium
## Footnote
These effects require caution, especially in patients with a history of seizures.
73
Discuss ketamine & delirium: presentation, treatment, and risk factors.
* Presentation: nightmares & hallucinations
* Treatment: benzodiazepines (versed > diazepam)
* Risk factors: >15yo, females, dose > 2mg/kg, hx of personality disorder
## Footnote
Emergence delirium can occur within 24 hours.
74
Discuss the analgesic properties of ketamine.
* Good opioid-sparing effect
* Relieves somatic > visceral pain
* Blocks central sensitization and wind-up in dorsal horn of SC
* Prevents opioid-induced hyperalgesia
## Footnote
Particularly effective for burn patients and those with chronic pain.
75
What is the dose, onset, duration, and clearance for etomidate?
* Dose: 0.2-0.4 mg/kg IV
* Onset: 30-60 secs
* Duration: 5-15 mins
* Clearance: hepatic
## Footnote
Etomidate is known for hemodynamic stability.
76
What are the cardiovascular and respiratory effects of etomidate?
* CV: hemodynamic stability, minimal changes to HR, SV, CO
* Resp: mild respiratory depression
## Footnote
Etomidate does not block SNS response to direct laryngoscopy.
77
What are the CNS effects of etomidate?
* ↓ CMRO2, CBF, ICP
* CPP stays the same
* no analgesia
## Footnote
Important for understanding its use in anesthesia.
78
What is the relationship between etomidate and myoclonus?
Myoclonus may occur due to an imbalance between excitatory and inhibitory pathways in the thalamocortical tract; it is not a seizure.
## Footnote
This can be a concern during administration.
79
What is the relationship between etomidate and seizures?
* No increased risk of seizures if no prior history.
* Can increase epileptiform activity in patients with a history of seizures.
## Footnote
This can be useful for seizure mapping.
80
What is the relationship between adrenocortical suppression and etomidate?
Etomidate inhibits 11-beta-hydroxylase, suppressing cortisol and aldosterone synthesis for 5-8 hours.
## Footnote
Avoid in septic or acute adrenal failure patients due to increased mortality risk.
81
What induction agent is most likely to cause PONV?
Etomidate (30-40% incidence).
## Footnote
This is an important consideration for postoperative care.
82
What are the two sub-classes of barbiturates? List examples.
* Thiobarbs: thiopental, thiamylal
* Oxybarbs: methohexital, pentobarbital
## Footnote
The subclass affects the pharmacokinetics and pharmacodynamics.
83
What is the mechanism of action for thiopental?
GABA-A agonist that decreases activity in the reticular activating system in the brainstem.
## Footnote
At low doses, it increases GABA affinity; at high doses, it stimulates GABA-A receptors directly.
84
What is the dose, onset, duration, and clearance mechanism for thiopental?
* Adult: 2.5 - 5 mg/kg
* Child: 5-6 mg/kg
* Onset: 30-60 secs
* Duration: 5-10 mins
* Clearance: liver P450s
## Footnote
Redistribution, not metabolism, determines awakening.
85
What are the cardiovascular and respiratory effects of thiopental?
* CV: hypotension from venodilation and ↓ preload, preserved baroreceptor reflex
* Resp: depression, bronchoconstriction
## Footnote
Less hypotension compared to propofol.
86
What are the CNS effects of thiopental?
* ↓ CMRO2, CBF, ICP, EEG activity
* no analgesia
## Footnote
Important for its use in neuroanesthesia.
87
In what circumstances can thiopental be used for neuroprotection?
It can be used for focal ischemia but not for global ischemia (e.g., cardiac arrest).
## Footnote
This is crucial for surgical planning.
88
Discuss the pathophysiology of acute intermittent porphyria.
It is caused by a defect in heme synthesis, leading to the accumulation of heme precursors such as ALA.
## Footnote
Acute intermittent porphyria is the most common and dangerous form.
89
What drugs should be avoided in patients with acute intermittent porphyria? Why?
* Barbs
* etomidate
* ketamine
* ketorolac
* amiodarone
* CCBs
## Footnote
These drugs can induce ALA synthase, accelerating the production of heme precursors.
90
What is the treatment for acute intermittent porphyria?
* liberal hydration
* glucose supplements
* heme arginate
* prevent hypothermia
## Footnote
These treatments aim to reduce ALA synthase activity.
91
What is the risk of intra-arterial injection of thiopental? What is the treatment?
Risk of intense vasoconstriction and tissue necrosis; treatment involves injecting vasodilators like phentolamine.
## Footnote
This is critical to prevent severe complications.
92
What induction agent is the gold standard for ECT? Why?
Methohexital is the gold standard due to its ability to decrease seizure threshold and produce better quality seizures.
## Footnote
Dose: 1-1.5 mg/kg.
93
What is the mechanism of action for dexmedetomidine?
Alpha-2 agonist that decreases cAMP and inhibits the locus coeruleus in the pons, providing sedation.
## Footnote
It also provides analgesia through alpha-2 stimulation in the dorsal horn of the spinal cord.
94
What is the dose, onset, duration, and clearance for precedex?
* Dose: 1mcg/kg over 10 mins, 0.4-0.7 mcg/kg/hr gtt
* Onset: 10-20 mins
* Duration: 10-30 mins after infusion stopped
* Clearance: liver P450s
## Footnote
Important for procedural sedation.
95
What are the cardiovascular effects of precedex?
* bradycardia
* hypotension
* rapid administration can cause temporary hypertension
## Footnote
These effects need to be monitored closely.
96
Why is precedex attractive for procedural sedation?
It does not cause respiratory depression and maintains oxygenation, blood pH, or CO2 response curve.
## Footnote
This makes it safer for patients with difficult airways.
97
What are the CNS effects of precedex?
* sedation that mimics natural sleep
* patients arouse easily
* no reliable amnesia
* decreases CBF with no changes in CMRO2 and ICP
## Footnote
Understanding these effects is important for sedation protocols.
98
How does precedex provide analgesia?
By decreasing glutamate and substance P release from the dorsal horn of the spinal cord.
## Footnote
This mechanism is crucial for its pain management properties.
99
Aside from IV, what other routes can precedex be administered? What is the dose?
Nasal and buccal routes offer high bioavailability (3-4 mcg/kg 1hr pre-op).
## Footnote
These routes can be useful in certain clinical scenarios.
100
How does the imidazole ring in midazolam affect its solubility?
It can be open or closed depending on pH; acidic = open (↑ water solubility), physiological pH = closed (↑ lipid solubility).
## Footnote
This property allows midazolam to be water soluble in the vial without additional solvents.
101
What is the mechanism of action for versed?
GABA-A agonist that increases the frequency of channel opening, leading to neuronal hyperpolarization.
## Footnote
This is different from other GABA-A agonists that primarily increase channel open-time.
102
What are the IV and PO doses for versed? Why are they different?
* IV sedation: 0.01 – 0.1 mg/kg
* IV induction: 0.1 – 0.4 mg/kg
* PO sedation in kids: 0.5 -1mg/kg
## Footnote
Differences are due to significant first-pass metabolism affecting bioavailability.
103
Which induction agents produce an active metabolite?
* midazolam = 1-hydroxymidazolam (0.5x potency)
* ketamine = Norketamine (0.33-0.5x potency)
* Fospropofol = propofol
## Footnote
Important to consider in patients with liver or kidney issues.
104
What are the cardiovascular and respiratory effects of midazolam?
* CV: minimal effects at sedation dose, ↓ BP and SVR at induction
* RESP: minimal sedation effects, respiratory depression at induction
## Footnote
Opioids can potentiate respiratory depressant effects.
105
What are the CNS effects of midazolam?
* minimal effects at sedation dose
* induction: ↓ CMRO2, CBF, anterograde amnesia, anticonvulsant effects
## Footnote
Midazolam does not produce isoelectric EEG.
106
What are the unique features of remimazolam?
Ultra-short acting benzodiazepine, must be protected from light, single-use vial discarded after 8hrs, metabolized by plasma esterases.
## Footnote
Contraindicated in patients with a history of severe hypersensitivity to dextran 40.
107
What is the reversal agent for benzodiazepines? How does it work?
Flumazenil, a competitive antagonist for the GABA-A receptor, has a high affinity but short duration (30-60 mins).
## Footnote
Initial dose is 0.2 mg IV, titrated in 0.1mg increments.
108
What are the side effects of flumazenil?
In benzodiazepine-dependent patients, it can precipitate withdrawal symptoms, including seizures.
## Footnote
Caution is required when using flumazenil.
109
How can you differentiate between chemical structures of halogenated agents?
Count the halogens: halothane (3 fluorines + 1 bromine), isoflurane (5 fluorines + 1 chlorine), desflurane (6 fluorines), sevoflurane (7 fluorines).
## Footnote
This is important for understanding their pharmacological properties.
110
How does fluorination affect the physiochemical characteristics of halogenated agents?
Adding fluoride ions tends to decrease potency, increase vapor pressure, and increase resistance to biotransformation.
## Footnote
Sevoflurane is heavily fluorinated but still more potent than desflurane.
111
What is vapor pressure and how is it affected by ambient temperature?
Vapor pressure is the pressure exerted by a vapor in equilibrium with its liquid or solid phase; it is directly proportional to temperature.
## Footnote
Higher temperatures lead to increased vapor pressure.
112
How is anesthetic delivery affected by altitude?
Depth of anesthesia is determined by partial pressure (PP) of the anesthetic agent, which decreases with altitude due to lower atm pressure.
## Footnote
This can risk underdosing with volatile anesthetics.
113
What is vapor pressure (VP)?
Pressure exerted by a vapor in equilibrium with its liquid or solid phase inside closed containers.
114
How does temperature affect vapor pressure?
VP is directly proportional to temperature (↑ temp = ↑ VP).
115
What determines the depth of anesthesia?
The partial pressure (PP) of the anesthetic agent in the brain.
116
How does altitude affect anesthetic delivery?
At higher elevations, atmospheric pressure decreases, which lowers the partial pressure of gases, risking underdosing of volatile anesthetics.
117
What happens to SEVO or ISO at elevation?
Underdosing is not an issue because the conventional variable bypass vaporizer auto compensates for elevation changes.
118
What is the problem with DES at elevation?
Underdosing can occur unless the vaporizer is calibrated to the lower atmospheric pressure.
119
Calculate the delivered partial pressure of 6% DES at sea level.
45.6 mmHg (0.06 x 760 mmHg).
120
Calculate the delivered partial pressure of 6% DES 1 mile above sea level.
37.2 mmHg (0.06 x 620 mmHg).
121
What are the vapor pressures of SEVO, ISO, DES, and N2O?
* SEVO = 157 mmHg
* ISO = 238 mmHg
* DES = 669 mmHg
* N2O = 38,770 mmHg
122
Which inhalation anesthetic is stable in soda lime?
N2O is stable; SEVO, ISO, and DES are not stable.
123
What byproduct does SEVO produce in soda lime?
Compound A.
124
What byproduct does ISO produce in soda lime?
Carbon monoxide (CO) only if desiccated.
125
What byproduct does DES produce in soda lime?
Carbon monoxide (CO) only if desiccated.
126
What is solubility?
The tendency of a solute to dissolve into a solvent.
127
What does the blood:gas partition coefficient describe?
The relative solubility of a volatile anesthetic in blood versus alveolar gas when the partial pressures between the two compartments are equal.
128
What is the blood:gas solubility for SEVO, ISO, DES, and N2O?
* SEVO = 0.65
* ISO = 1.45
* DES = 0.42
* N2O = 0.46
129
What are the steps to establish an anesthetic concentration inside the alveolus?
* Turn the vaporizer on
* Ventilation washes the agent into alveoli
* Buildup of anesthetic partial pressure opposed by continuous uptake in blood
* Cardiac output distributes agent throughout the body
130
What does the FA/FI curve indicate?
It allows prediction of the speed of induction of anesthesia.
131
How does low solubility affect the FA/FI curve?
Low solubility leads to decreased uptake into blood, resulting in a faster rate of rise and quicker onset.
132
What factors can increase FA/FI?
Greater wash in and/or decreased uptake.
133
What factors can decrease FA/FI?
Reduced wash in and/or increased uptake.
134
Which patient will have the fastest onset of SEVO?
Patient B, because lower cardiac output leads to faster induction.
135
What are the four tissue groups and their CO distribution?
* Vessel rich
* Muscle
* Fat
* Vessel poor
136
How are inhalation anesthetics removed from the body?
* Via alveoli (most important)
* Hepatic biotransformation
* Percutaneous loss (minimal)
137
What is the minimum fresh gas flow requirement for SEVO according to FDA recommendations?
Minimum FGF of 1 L/min for up to 2 MAC hours, then 2 L/min after 2 MAC hours.
138
What is a MAC hour?
1 MAC hour = 1% SEVO x 2 hrs, 2% SEVO x 1 hr, 4% SEVO x 30 mins.
139
Which volatile anesthetic is associated with trifluoroacetic acid metabolism?
Halothane.
140
What is a potential consequence of trifluoroacetic acid metabolism?
Halothane hepatitis due to high liver concentration.
141
What are theoretical consequences of sevoflurane metabolism?
Liberation of inorganic fluoride ions leading to possible fluoride-induced high output renal failure.
142
What is the concentration effect?
Increased rate of alveolar uptake as the concentration of a gas is increased.
143
How does the concentration effect relate to N2O?
N2O causes a higher inflow of anesthetic agent, increasing alveolar ventilation.
144
What is the second gas effect?
N2O hastens the onset of the second gas.
145
What is diffusion hypoxia?
N2O moves from body to lungs, diluting alveolar O2 and CO2, leading to decreased respiratory drive and hypoxia.
146
How does N2O affect closed air spaces?
N2O accumulates faster than nitrogen, potentially causing expansion and complications.
147
What are the MAC values for inhalation agents?
* ISO = 1.2
* SEVO = 1.88 or 2
* DES = 6.6
* N2O = 104
148
What is MAC-bar?
Alveolar concentration required to block autonomic response following supramaximal painful stimulus (~1.5 MAC).
149
What factors increase MAC?
* Chronic alcohol consumption
* Acute amphetamine intoxication
* Acute cocaine intoxication
* MAOIs
* Ephedrine
* Levodopa
* Hypernatremia
* Age 1-6 months
* Hyperthermia
* Red hair
150
What factors decrease MAC?
* Acute alcohol intoxication
* IV anesthetics
* N2O
* Opioids
* Alpha-2 agonists
* Lithium
* Lidocaine
* Hydroxyzine
* Hyponatremia
* Older age
* Prematurity
* Hypothermia
* Hypotension
* Hypoxia
* Anemia
* CPB
* Metabolic acidosis
* Hypo-osmolarity
* Pregnancy
* PaCO2 > 95 mmHg
151
What factors do not affect MAC?
Gender, hypertension, thyroid conditions, potassium levels, magnesium levels, and PaCO2 between 15-95 mmHg.
152
What is the Meyer-Overton rule?
States that lipid solubility is directly proportional to the potency of an inhaled anesthetic.
153
What is the unitary hypothesis?
All anesthetics share a similar mechanism of action, although each may work at different sites.
154
What is the most important site of halogenated anesthetic action in the brain?
GABA-A receptor.
155
How do halogenated anesthetics produce immobility?
By acting on the ventral horn of the spinal cord.
156
Which cerebral receptors are stimulated by nitrous oxide?
NMDA antagonism and K+ 2P-channel stimulation.
157
How do halogenated anesthetics affect blood pressure?
Decrease mean arterial pressure in a dose-dependent fashion.
158
How do halogenated anesthetics affect heart rate?
They decrease SA node automaticity and conduction velocity in a dose-dependent manner.
159
Why do DES and ISO sometimes increase heart rate?
Due to sympathetic nervous system activation from respiratory irritation.
160
What is the relationship between ISO and coronary steal?
ISO is a coronary artery dilator, which may contribute to coronary steal syndrome.
161
How does N2O affect hemodynamics?
Activates the SNS, increasing mean arterial pressure.
162
How do halogenated anesthetics contribute to hypercarbia?
By dose-dependent depression of central chemoreceptors and respiratory muscles.
163
How do halogenated anesthetics affect cerebral metabolic rate?
CMRO2 decreases only to the extent that they reduce electrical activity.
164
How do halogenated agents affect evoked potentials?
Produce a dose-dependent effect on evoked potentials.
165
What happens to CMRO2 at 1.5 – 2 MAC?
CMRO2 cannot be reduced any further
## Footnote
This indicates a limit to metabolic reduction under certain anesthetic conditions.
166
How do volatile anesthetics (VA) affect cerebral blood flow (CBF) and intracranial pressure (ICP)?
VA uncouples the relationship between metabolic requirement and blood flow: CMRO2 decreases and CBF increases, leading to increased ICP
## Footnote
This effect can be detrimental, especially in patients with compromised intracranial dynamics.
167
What is the effect of nitrous oxide (N2O) on CMRO2 and CBF?
N2O increases both CMRO2 and CBF appropriately
## Footnote
This contrasts with the effects of volatile anesthetics.
168
How do halogenated agents affect evoked potentials (EPs)?
DES, ISO, and SEVO produce a dose-dependent effect: decrease amplitude and increase latency
## Footnote
This means signals are weaker and take longer to conduct.
169
What happens to evoked potential amplitude when N2O is added?
It leads to more profound amplitude reduction
## Footnote
Therefore, the use of N2O is discouraged in certain contexts.
170
Which type of evoked potential is most sensitive to the effects of volatile anesthetics?
Visual evoked potentials are the most sensitive
## Footnote
They are affected more than SSEPs and MEPs, with brainstem evoked potentials being the most resistant.
171
What is the relationship between N2O and bone marrow depression?
N2O inhibits methionine synthase and folate metabolism, which can cause megaloblastic anemia
## Footnote
This highlights a significant side effect of N2O use.
