SEE BASIC SCIENCES: PHARMACOLOGY REVIEW Flashcards
1
Q
Rate of change proportional to amount of drug at any given time is PROPORTIONAL to the concentration present
A
FIRST-ORDER KINETIC
2
Q
Constant amount of drug elimination over a specific amount of time
A
Zero order kinetic
3
Q
A drugs that undergoes first order kinetic: increase drugs concentration will
A
lead to a larger amount of drugs elimination
4
Q
What are determinant of drug tissue uptake include?
A
Blood flow
BBB
Ionization
lipid solubilty
Protein binding
5
Q
4 methods of Drug metabolism are
A
Oxidation
Reduction
Hydrolysis
Conjugation
6
Q
3 methods prepare for the fourth one with drug metabolism
A
Oxidation, reduction and hydrolysis prepare for conjugation
7
Q
Effect on MAC: GENDER
A
No change in MAC
8
Q
Effect on MAC: woman with red hair
A
Increased MAC
9
Q
Effect on MAC: Pregnancy
A
Decrease MAC
10
Q
Effect on MAC: Chronic ETOH abuse
A
Increase MAC
11
Q
Effect on MAC: BP means greater than 40mmHg
A
No change in MAC
12
Q
Effect on MAC: Alpha 2 agonists
A
Decrease MAC
13
Q
Effect on MAC: Hyperthermia
A
Increase MAC
14
Q
Effect on MAC: Drugs that increase CNS catecholamines
A
Increase MAC
15
Q
Effect on MAC: Lidocaine
A
Decrease MAC
16
Q
Effect on MAC: Hypernatremia
A
Increase MAC
17
Q
Effect on MAC: acute alcohol intoxification
A
Decrease MAC
18
Q
When do pharmacokinetics interactions occur
A
When a drug alters the ADME of another drug
19
Q
Drugs with identical mechanism lead to ____Effects
A
Additive (2 effects leads to a greater effect of the 2 drugs combined
20
Q
Inducer of hepatic drug metabolism (RPP CSC)
A
Rifampin
Phenytoin
Phenobarbital
Carbamazepine
Smoking
St John’s Wort
Barbiturates
Tobacco
21
Q
What is the alveolar anesthetic concentration that blunts ADRENERGIC RESPONSE to noxious stimuli in 50% of patients?
A
MAC-BAR
22
Q
MAC BAR is the
A
MAC required to blunt adrenergic response in 50% patients
23
Q
Goals of drug combination
A
Decrease toxicity
Increase and maintenance of efficacy
24
Q
Most important organ for metabolism
A
Liver
25
Hepatic drug clearance depends on
Hepatic blood flow
Extent of binding of the drug to blood
intrinsic ability of the liver to Metabolize the drug
26
Vd: is greater with lipophillic or lipophobic?
lipophillic
27
Dose response curve can determine pharmacodynamics?
no
28
What does the dose response curve tell you?
Response observed to a quantity of a drug.
29
Which of the following requires energy provided by the hydrolysis of ATP ?
Active transport
30
What is the phase II reaction?
Drug molecules who underwent reduction , hydrolysis or oxidation are assimilated- CONJUGATED into compounds more readily removed from the body.
31
Occurence of plasma concentration of a drug exceeding the capacity of metabolizing enzymes
Zero order kinetics.
32
Prolonged exposure of receptors leads to
lower drug effect at the target site
33
Prolonged receptor inactivity results in production of a
Relative maximal or super-maximal effect at the receptor
34
Chronically denervated NMJ will _____the specific receptors in an attempt to produce a signal in the face of lower concentration of agonists
Up regulate
35
Drugs that are incapable of producing a MAXIMAL effect even at very high concentration are called?
Partial agonist (only a limited response)
36
During a constant infusion , plasma steady state drug concentration reaches 90%
3 half lives.
37
When a steady state is achieved when
The quantity of a drug administered is equal to the quantity of drug that is eliminated via metabolism
38
and
50% of steady state
39
After 2 half-lives, you will have reached
75% of steady state,
40
After 3 half-lives you will have reached
87.5% of steady state.
41
The rule of thumb is that steady state will be achieved after
5 half-lives (97% of steady state achieved)
42
What % of IV -administered drug remains after after 5 elimination half-times have passed ?
3%
43
How to calculate 5 half lives
50x50x50x50x50 = 312500000 x 100 = 3.125
100- 3.125= 96.
44
Why is IV loading dose use ?
To achieve effective target concentration (therapeutic plasma concentration) immediately
45
For anaphylaxis to occur what must have happened?
Prior exposure is needed for sensitization . UPon subsequent exposure, the IgE antibodies form during the initial exposure
46
Type I hypersensitivity reaction
Mediators release from mast cells and basophils after antigen binding to IgE antibodies on cell membrane
47
Type II hypersensitivity reaction (2 cells)
Antibody dependent, cell mediated cytotoxic hypersensitivity: IgG or IgM mediated
48
Type III hypersensitivity reaction
Circulating soluble antigens and antibodies bind to form iNSOLUBLE complexes that deposit in vasculature
49
Type IV hypersensitivity reaction I
interaction with sensitized cytotoxic ells.
DElayed hypersensitivity reaction I
50
Type IV hypersensitivity reaction I
interaction with sensitized cytotoxic ells.
DElayed hypersensitivity reaction
51
Anaphylaxis is what type of hypersensitivity reactions?
Type I
52
ABO incompatibility is what type of hypersensitivity reactions?
Type II
53
Serum sickness after SNAKE BITE what type of hypersensitivity reactions?
Type III
54
Contact dermatitis is what type of hypersensitivity reactions?
Type IV
55
Vasoactive mediators release during anaphylaxis are
HIstamine
Leukotrienes
Prostaglandins
56
Vasoactive mediator that releases endothelium derived factor Nitric oxide from vascular endothelium?
Histamine
57
Vasoactive mediators that releases endothelium derived factor Nitric oxide from
HIstamine
58
All vasoactive mediators do that
Increased capillary permeability
59
Vasoactive mediator that contracts vascular smooth muscle and airway
Histamine
60
Vasoactive mediator that cause intense bronchoconstriction
Leukotrienes
61
Vasoactive mediator that causes NEGATIVE INOTROPY
Leukotrienes
62
Vasoactive mediator that causes coronary artery vasoconstriction?
Leukotrienes
63
Vasoactive mediator that is synthesized after mast cell activation through Lipoxygenase pathway? (LL)
Leukotrienes
64
Vasoactive mediators that causes Pulmonary HTN and bronchospasm
Prostaglandins
65
Vasoactive mediator that is synthesized after mast cell activation through cyclooxygenase pathway?
Prostaglandins
66
What lab provide immediate proof of anaphylaxis?
Serum Tryptase level (within 60-120 mins)
67
Tryptase and anaphylaxis
Stored in mast cells, an is an integral component, and released into the systemic circulation when anaphylaxis occur but NOT DURING ANAPHYLACTOID
68
Primary treatment of anaphylaxis should include
Airway support
100% O2
stopping all drugs
IV fluids and EPINEPHRINE
69
Responsible for MOST INTRAOPERATIVE anaphylactic reactions?
Muscle relaxants (not ABT)
70
Patient with which allergies have a cross-sensitivity to LATEX (BAK)
Bananas
Avocados
Kiwis
71
Pharmacodynamic interaction when
Drug alters the sensitivity of a target receptor or tissue to the effects of a second drug. (differ from pharmacokinetics which is when one drugs alter ADME)
72
An example of Pharmacodynamic interaction?
Second gas effect
73
What is the second gas effect?
Administration of Nitrous along with VA results in an additive effect by both agents
74
Drug that activates or stimulates a receptor
Agonist
75
Absorption, distribution, metabolism and excretion of inhaled or injected drugs
pharmacokinetics
76
Responsiveness of receptors to drugs, and the mechanims by which drugs causes these effects to occur?
Pharmacodynamics
77
A drug that binds to receptors to prevent exogenous or endogenous substances from activating them
Antagonists
78
An effet produced by 2 drugs acting together that is greater than would occur with each drug alone
Synergistic
79
Calculation by which a dose of a drug is administred by IV and is divided by the plasma concentration to reflect the apparent volume of the drug into various intercellular compoenents
Volume of distribution
80
Transmembrane protein macromolecule that acts as a mechanism for a drug to being to and exert its effect?
Receptor
81
Reflect the concentration of an inhaled anesthetic measureed at 1 atm in the body to prevent skeletal muscel movement in response to a srugical incision
MAC
82
Difference in slope, efficacy and individual responses, , depics relationship between the dose of a drug administered or plasma concentration, and the resulting pharmacological effect
Dose-response curve
83
Enantiomers are
Chemical substance of exact bu opposite shape, mirror images of each other
84
When 2 enantiomers are present in 50:50 portion, subtances are known as
Racemic mixtures
85
Define competitive antagonism
Competitive antagonism is based on the principle that an agonist or antagonist can bind to the same recognition site(s) on the receptor, and when both agonist and antagonist are present concomitantly, they can compete for such sites. Increasing concentration of an antagonist drugs (such as NDNMB, progressively inhibit the responses to an unchanging concentration of an agonists
86
Simple competitive antagonism definition?
increase in the available concentration of an agonist cannot overcome the effect produced by the antagonist.
87
A drug that activate a receptor by binding to it
Agonist
88
Define Non-competitive antagonism?
After administration of an antagonist, even high concentrations of an agonists cannot completely overcome the antagonism
89
A drug that bins to the receptor without activating the receptor and at the same time prevents an agonist from stimulating the receptor
Antagonist
90
What does HOFFMAIN ELIMINATION rely on to degrade CISATRACURIUM?
Normal body temperature
pH
91
What is therapeutic Index?
relates the dose of a drug required to produce a desired effect to the dose that produces an undesired effect.
92
Formula for TI
LD 50/ ED 50
93
Where are the hepatic microsomal enzymes that participates in metabolism of many drugs found? (GHAK)
GI tract
Hepatic smooth ER
Adrenal cortex
Kidneys
94
How many half lives to eliminate 97 % of the drugs?
5
95
CYP 450 3 A4 composes what % of CYP 450 activity?
40-45
96
Responsible for the largest portion of drug metabolism in the body?
CYP 450
97
Name ending "tron" associated with
Serotonin blockers
98
Serotonin blocking drugs act on the
5HT3 receptor
99
Name 3 serotonin blockers
ondansetron
dolesetron
granisetron
100
Name ending "pril" associated with
ACEI
101
Name ending "dipine" associated with
CCB exception verapamil, cardizem
102
Name ending "tidine" associated with
H2 receptors blockers (antagonists)
103
Phase I reactions are (everything except conjugation)
Methylation
Oxidation
Reduction
Dealkylation
Deamination
104
What is the significance of phase II reactions?
Compound can be readily eliminated from the body
105
Phase II reaction involves conjugation of the drug with
Glucuronide
Sulfate
Taurine
Glycine
106
Is phase II always required to complete drug metabolism ?
NO
107
Does phase II always follow phase I
NO
108
Physiological stimuli responsible for stimulating the release ADH include?
Stress and anxiety
Hyperthermia
Presence of histamine-releasing stimulus
109
Pharmacological stimuli that stimulates the release of ADH
PPV of the lungs
Beta adrenergic stimulation
110
ADH secreted by
Posterior pituitary
111
Increased serum osmolarity indicates
Insufficient water content
112
What is the target site for ADH ?
Collecting tubules of the kidney
113
Primary goal of ADH is to e prevent
water loss thereby decrease serum osmolarity and increasing circulating volume.
114
To minimize risk of Compound A production during SEVOFLURANE administration which of the following actions may be taken?
Run lower levels of sevoflurane
Use hydrated soda lime absorbent
Maintain gas flows equal to or greater than 2L/min
115
What are the factors that increase the risk of compound A formation ?
Low gas flow states
Increased levels of sevoflurane
Dry or warm CO2 absorbents
116
Which inhaled anesthetic is associated with the greatest production of heat in dessicated Co2 absorbent? how?
Sevoflurane; loss of moisture into the CO2 absorbent, facilitates an exothermic reaction between sevo and the absorbent. CAN lead to fire in the circuit
117
Which of the inhaled anesthetic is associated with the highest production of CO in dessicated CO2 absorbent?
Desflurane; Results in the production of the greatest amount of CO
118
Does higher doses of opioid decrease the MAC requirements of VA?
NO. MAC of VA is influenced to only a small degree so even higher amount of opiods analgesics won't affect MAC
119
VP of desflurane is (high/low)
High
120
Halogenated anesthetics least metabolized?
Desflurane
121
The speed of an inhaled anesthetic action is determined by its solubility and expressed as which of the following?
Blood:gas solubility coefficient
122
The speed with which a volatile anesthetic vapor enters the pulmonary circulation is represented by the
Blood: gas solubility coefficient
123
Which of the following are the 2 main organs involved with volatile agent metabolism?
Lunger
Liver
124
The main elimination of volatile anesthetics via the
lung on exhalation
125
Responsible for a small amount of VA metabolism
Cytochrome isoenzymes
126
Vapor pressure refers to
Pressure of the vapor resulting from vaporization . Pressure at which molecules of a volatile liquid escape the liquid phase.
127
What are the 2 most soluble volatile anesthetics
Isoflurane
Halothane
128
Rate of uptake is dependent on
1) alveolar ventilation rate 2) partial pressure of gas (concentration effect) 3) breathing system
129
For poorly soluble anesthetic agents (ex. N2O, desflurane), an increase in FA/Fi depends
very little on alveolar ventilation
130
Enflurane has a blood/gas partition coefficient of 1.7. What does that mean?
if the gas is in equilibrium the concentration in blood will be 1.7 times higher than the concentration in the alveoli. Thus, it makes sense that a gas with a higher blood gas coefficient will require higher uptake of gas into the blood and induction will be slower.
131
Higher partition coefficient = ______ipophilicity = _____potency = ______ solubility
higher; higher; higher
132
MAC and Blood gas coefficient
MAC decreases as blood gas partition coefficient increases, generally speaking
133
High solubility = more anesthetic needs to be dissolved =
slower onset
134
Solubility represented by a higher blood:gas coefficient represents
The speed with which the agent is taken up into the pulmonary circulation
135
The oil:gas partition coefficient is related to a volatile's agent
Potency
136
Potency and MAC relationship
Potency is inversely related to MAC
137
The slowest induction is possible with which of the following
Halothane and INCREASED CO state
138
The speed of an inhalation induction is inversely related to the
Blood: gas coefficient in the presence of increased CO.
139
MAC decrease ______per decade of age
6%
140
Inhalational anesthetics on CBF and ICP
All inhalational anesthetics increase CBF and ICP
141
Nitrous compared to volatile agents
Nitrous increase CMRO2, volatile agents do not
142
NO has a blood:gas partition ratio of 0.47 and is thus
30 times more soluble in blood than nitrogen,
143
Nitrous and volatile agents of seizure threshold
Increase the seizure threshold but only nitrous increase CMRO2
144
Nitrous is a myocardial depressant or stimulant?
Nitrous is a sympathetic stimulant produce increase blood pressure, CO and HR
145
Volatiles agents: myocardial depressant or stimulant?
VA are myocardial depressants
146
What hemodynamics may be afffected with the use of Nitrous oxide?
Elevated RV EDP
147
PVR and N2O
PVR is increased in the presence of N2O due to vasoconstriction of the pulmonary vasculature. Increase PVR results in increase RVEDP
148
What is the B:G coefficient of Nitrous
0.47
149
What is the B:G coefficient of sevo
0.65
150
What is the B:G coefficient of Isoflurane
1.4
151
What is the B:G coefficient of Desflurane
0.42
152
Which inhalational agent is a halogenated alkane?
Halothane
153
Which inhalational agent is halogenated with FLUORINE
Desflurane
Sevoflurane
154
Which agent results in an increased heart rate during
inhalational anesthesia?
Sevoflurane > 1.5 MAC
155
Which inhalational agent is the least desirable
or a patient with chronic bronchitis and a 50-pack/
year history o smoking?
Desflurane
156
Which agent increases the cerebral metabolic rate or
oxygen (CMRO2)?
N2O
157
Which o the following halogenated agents potentiates
the effects of epinephrine the most?
Halothane
158
What is the recommended minimum liter flow to
avoid renal injury when using sevoflurane?
2L/min
159
T e patient is scheduled or a total knee arthroscopy
under general anesthesia. T e patient’s history includes
retina surgery using sulfur hexafluoride 2 months ago.
What will you avoid?
(A) Nitrous oxide Nitrous oxide expands the gas bubble and may cause intraocular hypertension
160
Which o the following would be appropriate
anesthesia induction techniques or a severely hypertensive patient with coronary artery disease and moderate ventricular dysfunction?
(A) Inhalational induction with sevoflurane
161
Which inhaled agent is most associated with emergence
delirium in children?
(A) Sevoflurane
162
An inhalational induction with will likely cause catecholamine release, urther increasing blood pressure and heart rate?
desflurane
163
What type of vaporizer contains desflurane?
Electronic
164
When using evoked potentials, which o the ollowing
will you avoid?
Isoflurane
165
The patient is scheduled or laser removal of vocal
cord papilloma. What will you avoid?
Nitrous
166
What is the Vapor pressure of isoflurane?
239
167
What is the Vapor pressure of Desflurane?
664
168
What is the Vapor pressure of Sevoflurane?
157
169
What is the Vapor pressure of Nitrous oxide?
39000
170
Blood-gas Partition coefficient of Isoflurane
1.4
171
Blood-gas Partition coefficient of Desflurane
0.42
172
Blood-gas coefficient Partition of Sevoflurane
0.69
173
Blood-gas coefficient Partition of Nitrous oxide
0.47
174
Brain-Blood coefficient Partition of Isoflurane
1.6
175
Brain-Blood coefficient Partition of Desflurane
1.3
176
Brain-Blood coefficient Partition of Sevoflurane
1.7
177
Brain-Blood coefficient Partition Nitrous Oxide
1.1
178
MAC of Isoflurane
1.1
179
MAC of Desflurane
6.0
180
MAC of Sevoflurane
2.0
181
MAC of Nitrous oxide
104
182
What is the relationship between the partition coefficient with the rate of induction?
INVERSELY proportional
183
What are the determinant of the speed of onset and offset ? BIAC2CG
B/G partition coefficient
Inspired anesthetic concentration
Alveolar ventilation
Concentration effect
2nd gas effect
Cardiac output
Gradient between alveolar and venous blood
184
The mechanism of action of nitrous oxide is thought to be attributed to ?
The antagonisms of NDMA receptors in the CNS
185
The mechanism of action of Volatile anesthetics is thought to be attributed to what actions on what receptors?
GABAa, Glycine and glutamate receptors play a role
186
What determines the speed of induction of general anesthesia?
The rate of the rise of the ration of FA/FI
187
What are the 2 opposing processes that determine FA/FI at a given time?
Anesthetic delivery to and uptake from alveoli
188
How does the blood gas partition coefficient affect the rate of rise of the FA/FI?
Lower solubility in blood will lead to lower uptake of anesthetic into the bloodstream, thereby increasing the rate of rise of teh FA/FI at a given time.
189
2 patient condition that increases solubility of halogenated volatile anesthetics in blood
Hypothermia
Hyperlipidemia
190
How does Alveolar Ventilation affect the rate of rise of the FA/FI?
Increasing MV increasing FA/FI
191
What is the concentration effect?
As FI increases, the rate of FA/FI also increases. For a gas with a FI like nitrous , a large amount is taken up into blood and there is a large loss of the total gas volume. The remaining nitrous is concentrated and the addition of more anesthetic with the next breath will increase the concentration further.
192
With the concentration effect the uptake of a large gas volume (such as nitrous) creates what?
draws more fresh what into the alveoli, thereby increasing FA and augmenting the inspired TV.
193
What explains why the rate of FA/FI is faster for nitrousoxide than desflurane? (even though the blood-gas partition coefficient for desflurane is smaller)
The concentration effect.
194
What is the 2nd gas effect?
It is a direct outcome of the concentration effect. When nitrous and a potent inhalation anesthetic are administered together, the uptake of nitrous oxide concentrates the second gas (such as isoflurane) and increases the input of additional second gas in the alveoli via the augmentation of inspired volume.
195
How does CO affects the rate of rise of FA/FI?
An increase in cardiac output, and therefore pulmonary blood flow, will increase the anesthetic uptake and decrease the rate of rise in FA/FI?
196
Mnemonic for FA/FI chart (FA on the left, time bottom)
NDSIEH
197
Explain how the gradient between alveolar and venous blood affect FA/FI?
The uptake of anesthetic into the bloodstream will decrease as the anesthetic partial pressure gradient between the alveolar gas and the venous blood decreases. This gradient is particularly large early in the course of anesthetic administration.
198
Distribution of volatile anesthetics in the tissues: Rate of equilibration of anesthetic partial pressure between blood and a particular organ system depends on what factors?
Tissue Blood flow
Tissue solubility
Gradient between arterial blood and tissue
199
Tissue blood flow affect rate of equillibration of anesthetics partial pressure, explain.
Equillibration occurs first in the tissue with increase perfusion. VESSEL RICH GROUP of highly perfused organs system, which receives about 75% of the CO . Remainder of the CO goes to muscle and fat
200
Anesthetic agents with high-tissue solubility are ______(slower/faster) to equillibrate?
Slower
201
Gradient between arterial blood and tissue: Until equillibration is reached between the anesthetic partial pressure in the blood and a particular tissue, a _______exist that leads to the uptake of anesthetic by the tissue. The rate of uptake will (decrease/Increase) _____as the gradient decreases
gradient ; decrease
202
What is the predominant route of elimination of VA?
Exhalation ; After the VA is turned off, the anesthetics tissue and alveolar partial pressure decrease
203
What is the predominant route of metabolism of VA?
VA undergoes degrees of hepatic biotransformation
204
What is the predominant route of Anesthetic loss?
Skin or/and visceral membranes
205
CV effect and nitrous oxide
HR, BP, SNS
Mild sympathetic NS stimulant
HR and BP unchanged usually
206
Resp effect and nirous oxide
May increase PVR
Mild resp depressant
207
VA and CNS effects: low doses
Alpha, delta and slow oscillation are present at lower does of iso, des, and sevo.
208
VA and CNS effects: high doses
theta oscillation appears follwed by burst suppression
209
VA on SSEPs (remember dail)
DAIL
Decrease amplitude of SSEPS
Increase latency of SSEPS
210
VA on CBF and CMRO2
Increase CBF and decrease CMRO2: uncouple autoregulation of CBF
211
VA on Cardiovascular system?
Dose dependent Myocardial depression and systemic Vasodilation
HR unchanged
212
Action of desflurane on CV
Increase SNS stimulation
Tachycardia
Hypertension
Usually on induction, or when the concentration is abruptly increased.
213
What can VA do to the myocardium?
May sensitize the myocardium to the arrhythmogenic effects of catecholamines, which is a concern during infiltration of epi-containing solutions, or administration of sympathomimetic agents.
214
What are the RESP effects of VA?
Dose dependent respiratory depression with decrease TV, increase RR and increase arterial CO2 pressure
215
VA, light anesthesia and resp
May precipitate coughing, laryngospasm, or bronchospasm particularly in patients with asthma or COPD
216
What makes sevo more suitable for use as an inhalation agent?
Lower pungency
217
VA on bronchioles
Bronchodilatory effects EXCEPT desflurane which has mild bronchoconstricting activity
218
What are the effects of VA on HPV?
Inhibit HPV which may contribute to pulmonary shunting.
219
Neuromuscular system and VA
Dose dependent decrease in skeletal muscle tone'
May lead to MH
220
VA and hepatic system
Halothane can lead to hepatitis
221
VA and renal system
Decrease RBF through decrease in MAP or increase in renal vascular resistance
222
3 adverse effects of NITROUS OXIDE
Expansion of closed gas spaces
Diffusion hypoxia
Inhibition of tetrahydrofolate synthesis
223
Nitrous and explansion of closed gas spaces, explain?
Because nitrous oxide is 35 times more soluble in blood than nitrogen , closed air space will expand as the amount of nitrous oxide diffusing into these spaces is greater than the amount of nitrogen diffusing out.
224
What is the predominant constituent in closed gas-contraining spaces in the body ?
Nitrogen
225
Spaces that nitrous oxide can diffuse to?
Pneumothorax
occluded middle ear
Bowel lumen
Pneumocephalus
226
ETT cuff and the use of N2O
Nitrous oxide will diffuse into the cuff of an ETT and may increase the pressure within the cuff. The cuff pressure should be assessed intermittently and if necessary , adjusted.
227
Diffusion hypoxia with which gas? explain
Nitrous oxide; After you d/c nitrous oxide , its rapid elimination from the blood into the lung may lead to a low partial pressure of O2 in the alveoli, resulting in hypoxia and hypoxemia with supplemental oxygen is not administered.
228
Caution of nitrous oxide administration in patient with this deficiency ? why?
B12 ; because nitrous inhibits methionine synthase, a vitamin B12 dependent enzyme necessary for the synthesis of DNA. It should be use with caution with pregnant patients and those deficient in vitamin B12
229
Desflurane can be degraded to
CO in CO2 absorbents (especially baralyme). More likely when absorbent is new or dry.
230
Sevoflurane can be degraded to
Fluoromethyl 2-2 difluoro-1-vinyl ether (compound A) which shows that it can lead to renal toxicity in animal models
231
Compound A concentration increase at
low fresh gas rates.
232
Mechanism of action of barbiturates? on RAS, neurotransmitters
Depresses the Reticular activating system
Depression of NDMA in a concentration dependent manner
Depression of Excitatory neutrotransmitters (glutamate and nicotinic)
Enhance Inhibitory neutrotransmitters
233
The sodium salts of barbiturate in solution are (acidic/basic; stable/unstable)
Alkaline (pH>10)
Relatively unstable
234
Are sodium salts of barbiturates water soluble?
yes
235
Prompt awakening from a a single dose of thiopental or methohexital reflects ?
Redistribution
236
What is the determining or limiting factor for the duration of action of a barbiturate?
redistribution the barbiturate undergoes
237
CV effects following barbiturate administration?
Increase HR
Decrease Venous return
Decrease BP
238
Barbiturates on CBF , CMRO2 and iCP
Decrease CBF, CMRO2 and ICP
239
Barbiturates are neuro____
protective
240
Names 2 barbiturates
Thiopental
Methohexital
241
Onset of action of barbiturates
30-45 seconds, f/b rapid termination of effects due to redistribution
242
How are barbiturates metabolized?
Hepatic metabolism
243
With hepatic metabolism, thiopental vs methohexital which one has higher clearance?
Methohexital
244
Prolonged infusion of barbiturates effects
Prolonged sedation and unconsciousness due to reduced rate of consciousness , return of the drug to the central compartment and hepatic metabolism
245
The context senstive half time of thiopental is
long even after short infusion
246
Barbiturates on cerebral vascular bed
Dose-dependent cerebral vasoconstriction decrease CBF and CMRO2, and ICP
247
Do barbiturates affect cerebral autoregulation?
NO, Cerebral autoregulation remains unaffected.
248
Thiopental and EEG
At high does will produce isoelectric EEG
249
Methohexital and seizures
Methohexital can elicit seizure activity
250
Barbiturates on SSEPs, MEPs,
Minimal effects
251
Barbiturates on BAEPs
Dose dependent depressio
252
Barbiturates on CV
Venodilation and depress myocardial contractility , leading to dose-dependent decreases in BP and CO especially for patient who are preload dependent.
253
Barbiturates on baroreceptors
Remain intact; so hypotension will still lead to tachycardia.
254
Barbiturates on RESP
Dose dependent decrease in RR and TV
255
Barbiturates on ventilatory response
Ventilatory responses to hypoxia and hypercabia are depressed.
256
Barbiturates: after induction what occurs
Apnea result for 30-90 seconds.
257
Barbiturates compared with propofol
Laryngeal reflexes remain intact with barbiturates, so the incidence of cough and laryngospasm is higher,
258
Reduce dose of barbiturates in those kind of patients?
Hypovolemic
elderly
Hemodynamically compromised patients
259
Barbiturates admnistration caution
Do not mix with drugs with lower pH solution such as succinylcholine and cause precipitation of other drugs such as VEC. Therefore, use free running IV and avoid simulataneously injection with other drugs.
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Thiopental have histamine release
yes
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Absolute contraindications of barbiturates
Acute intermittent Porphyria
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Why no barb in porphyria?
Barb induce porphyrin synthetic enzymes such gamma-aminolevulinic acid synthetase
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Barbiturates and IV
May cause pain at the site of administration due to venous irritation.
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Thiopental injection what can it cause? How do you treat?
Can cause severe pain and tissue necrosis if injected extravascularly or intra-arterialy . Treat with PHENTOLAMINE (alpha blocker) heparin, vasodilators, and regional sympathetic blockade.
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Often seen during induction with methohexital
Myoclonus
Hiccups
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Barbiturates protect agains focal ischemia or global?
focal
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Barbiturates and EEG
High does can cause electrical silence on the EEG.
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Anticonvulsant activity of a barbiturate is structurally related to
PHENYL GROUP (the methyl group does not have anticonvulsant property)
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What can lead to higher concentration of thiopental in the brain?
When the central component is reduced(hypovolemia)'
When albumin is decreased (Liver disease)
When there is increased non-ionized fraction of the drug (acidosis)
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Thiopental and elimination
Prolonged in the elderly because with increasing age the time for the drug to go from the central compartment via redistribution increases.
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When using methohexital , full recovery of psychomotor function after the single dose is more rapid compared to thiopental why?
ENHANCED METABOLISM; hepatic extraction of methohexital occurs at a rate 3-4 times greather than that for either thiopental or thiamylal.
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How is methohexital excreted?
Feces
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The only opioid receptor that produces respiratory stimulation ?
sigma receptor
274
The sigma opioid receptor produces
Respiratory stimulation
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What are the endogenous peptide that bind to opioid receptors?
Endorphin
Enkephalin
Dynorphin
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What is the principal effect of opioid receptor activation ?
Decrease in release and response to excitatory neurotransmitters.
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What happens when opiate receptors are activated?
Excitatory neurotransmitter release is inhibited presynaptically, while a decrease response to the transmitters occurs postsynaptically.
278
Endorphins are agonists of which opioid receptor?
Epsilon
279
The primary mechanism of action of opiates is via
µ-receptor agonism.
280
Opioids location in the brain?
the dorsal horn (layers 4 and 5 of the substantia gelatinosa) of the spinal cord, which inhibits the transmission of nociceptive information;
281
EnKEphalins are agonist of which opioid receptor?
DELTA (KEd)
282
Dynorphins are agonists of which opioid receptor?
Kappa
283
What increases the amount of pulmonary uptake of lipid soluble opioids?
History of tobacco use.
284
Advantage of the use of neuraxial opioids over IV opioids or regional anesthesia over local anesthetics
NO loss of proprioception
No SNS denervation
No skeletal muscle weakness
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What is the most common side effect of neuraxial opioids?
Pruritus (highest incidence of occurrence)
286
What is the triad of opioid overdose? MHC
Miosis
Hypoventilation
Coma
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The primary sign of opioid overdose is
Respiratory depression that can progress to apnea
288
Morphine cause supraspinal analgesia by acting on which opioid receptor?
Mu 1
289
Morphine cause spinal analgesia by acting on which opioid receptor?
Mu 2
290
How is morphine metabolized?
Hepaticallly and renally
291
Morphine metabolims occurs by
glucoronic acid conjugation primarily in hepatic and renal (extra hepatic sites)
292
What is the least protein-bound opioid agonist?
Morphine (35% only )
293
Protein bound % of Meperine, sufentanyl and fentanyl
>60%
294
Both analgesic and possess weak local anesthetic properties?
Meperidine (alteration of nerve conduction)
295
What is the least-lipid soluble opioid agonist?
Morphine
296
In order of LEAST to most lipid soluble opiods : MR. MASF
Morphine < remifentanil< meperidine< alfentanil< sufentanily< fentanyl
297
Morphine-6- Glucuronide is a ______Potent and_______-lasting opioid agonist than morphine
MORE ; LONGER
298
What is the metabolite of morphine?
Morphine-6-glucuronide
299
Which of the following patients would have a prolonged elimination half time of fentanyl?
Elderly (aging changes in the liver main cause)
Continuous infusion lasting longer than 2 hours
300
What is the pharmacologically active metabolite of fentanyl?
No significant active metabolite.
301
The context sensitive half time of fentanyl
Initially it is shorter than that of sufentanil, but after 2 hours of infusion its longer.
302
When a continuous infusion of fentanyl last beyond 2 hours, the half life becomes become _____Than sufentanil
Greater than sufentanil
303
How long does it take for plasma fentanyl concentration to plateau with the use of the transdermal patch?
12-18 hours
304
What is the major obstacle to transdermal administration of a medication?
Stratum corneum
305
How much of an initial IV fentanyl dose undergoes first pass pulmonary uptake? why?
75%; because it is highly lipid solubility
306
Compared to fentanyl and sufentanil, alfentanil has a more ________onset of action? why?
rapid; high degree of nonionization
307
At physiological pH, what % of alfentanil is in the non-ionized form?
90%
308
Compared to fentanyl, alfentanil is ______potent and has a ______ onset of action
less : more rapid
309
Alfentanyl potency
10-20% of that of fentanyl strength, 1/3 of fentanyl duration
310
What can alter the elimination half time of alfentanil? and why?
Cirrhosis of the liver; Because almost all of a dose of alfentanil is metabolized by the liver within an hour of administration. Therefore, disease of the liver alters the half life of alfentanyl
311
What is the most potent analgesis?
Sufentanil
312
The standard to which opioid are compared to ?
Morphine
313
Fentanyl potency
75-125 times more potent than morphine
314
Sufentanil potency
5-10 times more potent than fentanyl
315
Sufentanil is _____Protein bound than fentanyl, and it has a _______volume of distribution
more; smaller (sufentanil 92.5% PB, 79-87% proteinb for fentanyl)
316
For a continuous infusion lasting more than 2 hours (fentanyl) and less than 8 hours (alfentanil) rank the following opioid agonists from shortest to longest context-sensitive half-time? SAF
Sufentanil< alfentanil< fentanyl
317
Symptom of normeperidine toxicity ?
Seizures and myoclonic activity
318
Most effective opioid for decreasing shivering?
Meperidine (NDMA receptor activity , NE inhibitor in central neurons)
