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Glossary of Spring POP final UCSD SSPPS SOM

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All of the following may occur in migraine headaches EXCEPT:
A. Vasoconstriction.
B. Cerebral ischemia.
C. Increased extracellular [K+], resulting in hyperpolarization and depressed cortical function.
D. Release of substance P and CGR
C
A, E. Cerebral blood flow typically undergoes a biphasic change during a migraine headache: an initial vasoconstriction → ↓cerebral blood flow (the hyporemia or oligoremia phase), followed by a secondary vasodilation (the hyperemia phase).
B. Ischemia (≡ obstruction of blood supply) is essentially synonymous with hyporemia/oligoremia.
C. Increased extracellular [K+] causes depolarization, not hyperpolarization. Note that this increase in extracellular [K+] is caused by the O2 deprivation that occurs during the initial hyporemia/oligoremia phase.
D. Sensory C fibers of the trigeminal nerve become sensitized during the hyporemia/oligoremia phase and release substance P and CGRP.
F. Substance P/CGRP cause additional vasodilation and plasma extravasation.
All of the following are true regarding the treatment of migraine headaches EXCEPT:
A. NSAIDs often can terminate mild headaches.
B. Ergotamine is the agent of choice for mild headaches because it has the fewest side effects.
C. Sumatripta
B
B. Ergotamine can be effective in the treatment of migraine, but it is not the agent of choice because it can cause limb ischemia and other side effects. Since the introduction of the triptans, it is used primarily in resistant cases.
C. Sumatriptan can terminate migraine headaches in over 70% of patients!
D, E. Both β adrenergic antagonists (e.g., propranolol) and Ca2+ channel blockers (e.g., verapamil) can be used as prophylactic therapy in patients with frequent migraines. Other drugs that can be used prophylactically for frequent migraines include TCAs (e.g., amitriptyline), and antiepileptic drugs (e.g., valproic acid and topiramate).
A. 5-HT1 receptors
B. 5-HT2 receptors
C. 5-HT3 receptors
D. 5-HT4 receptors
E. All of the above
F. None of the above

Ligand-gated ion channels?
C 5-HT3 receptors are ligand-gated ion channels; the remaining 5-HT receptors are GPCRs.
A. 5-HT1 receptors
B. 5-HT2 receptors
C. 5-HT3 receptors
D. 5-HT4 receptors
E. All of the above
F. None of the above

Stimulation by sumatriptan accounts for its antimigraine effects?
A Sumatriptan is a 5-HT1B/D agonist; this agonist effect is believed to (1) block the release of substance P and CGRP from sensory C fibers of the trigeminal nerve (presynaptic effect); and/or (2) cause cerebral vasoconstriction, thereby counteracting the cerebral vasodilation that occurs in the hyperemia phase and that also is produced by substance P and CGRP.
A. 5-HT1 receptors
B. 5-HT2 receptors
C. 5-HT3 receptors
D. 5-HT4 receptors
E. All of the above
F. None of the above

Stimulation by ondansetron accounts for its antiemetic effects?
F The antiemetic effects of ondansetron result from blockade, not stimulation, of 5-HT3 receptors
A. Apomorphine
B. Cisplatin
C. Metoclopramide
D. Promethazine
E. Scopolamine

Causes emesis by stimulating 5-HT release from enterochromaffin-like cells in the intestinal mucosa?
B Cisplatin, a drug used in cancer chemotherapy, can increase 5-HT release from ECL cells in the intestinal mucosa. The 5-HT then stimulates 5-HT3 receptors on vagal afferents, thereby eliciting the vomiting reflex.
A. Apomorphine
B. Cisplatin
C. Metoclopramide
D. Promethazine
E. Scopolamine

Causes emesis by stimulating D2 receptors in the chemoreceptor trigger zone?
A Apomorphine stimulates D2 receptors in the chemoreceptor trigger zone (CTZ), which in turn stimulates the vomiting center.
A. Apomorphine
B. Cisplatin
C. Metoclopramide
D. Promethazine
E. Scopolamine

Inhibits emesis by blocking D2 receptors in the chemoreceptor trigger zone and by increasing the rate of gastric emptying?
C Both metoclopramide and promethazine block D2 receptors, but only metoclopramide also increases the rate of gastric emptying.
A. Apomorphine
B. Cisplatin
C. Metoclopramide
D. Promethazine
E. Scopolamine

Widely employed for the prevention of motion sickness?
E Remember the Transderm Scop® patch discussed in Winter POP! The antimotion sickness effect of scopolamine probably is due to its ability to block the mAChRs that are involved in mediating vestibular input to the CTZ.
All of the following are correct regarding the sensitivity to local anesthetics EXCEPT:
Less Sensitive , More Sensitive
A. Large fiber diameters, Small fiber diameters
B. Myelinated fibers, Unmyelinated fibers
C. A fibers, C fibers
F D. Recall that autonomic preganglionic fibers always are myelinated, whereas autonomic postganglionic fibers always are unmyelinated.
F. Since local anesthetics (LAs) block Na+ channels by entering the open channel from the cytoplasmic side, a greater frequency of depolarization results in more frequent channel opening and therefore an increased likelihood of block.
Local anesthetics:
A. Typically have pKas below 6.0.
B. Are injected in acidic solutions to increase their solubility.
C. Only protonated molecules cross cell membranes.
D. Only unprotonated molecules block Na+ channels.
E. Block
B A. LAs are weak bases with pKas typically ≈ 8 to 9.
B. In an acidic solution, a weak base LA is more likely to be in the protonated (ionized) form and therefore is more soluble. Following injection into the ECF, the higher pH (7.4) favors the formation of the unprotonated, nonionized form, which is then able to cross cell membranes. The somewhat lower ICF pH (≈ 6.8) favors the formation of the protonated, ionized form, which then enters the Na+ channel from the cytoplasmic side and blocks it.
C. Only unprotonated, nonionized LAs cross cell membranes.
D. Only protonated, ionized LAs block Na+ channels.
E. Peptide Na+ channel blockers such as TTX and saxitoxin block Na+ channels from the outside.
Regarding local anesthetics:
A. Cardiovascular toxicity (e.g., decreased contractility, decreased conduction velocity) typically is seen at lower plasma concentrations than CNS toxicity (e.g., convulsions, coma).
B. A patient who develops a ras
E A. Cardiovascular toxicity is seen at higher plasma concentrations than CNS toxicity.
B. Benzocaine is an ester, so a patient is most likely to develop future hypersensitivity reactions to other ester LAs, such as procaine or tetracaine.
C. Vasoconstrictors can be used to prolong the duration of action of LAs administered by infiltration (intradermal injection in the immediate area of surgery), but are not used in appendages because of the danger of ischemia and tissue necrosis.
D. Procaine has a short duration of action (t1/2 ≈ 30 min, which is the shortest t1/2 of the ester LAs used clinically). Bupivacaine has a long duration of action (t1/2 ≈ 4 to 6 hr, which is the longest t1/2 of the amide LAs used clinically).
E. Neurological complications (e.g., CSF leakage, resulting in headaches) are more likely with intrathecal (subdural) administration (aka spinal anesthesia), since the dura mater is penetrated.
A. ACh L. Ca2+
B. Dopamine M. K+
C. GABA N. Na+
D. Glutamate O. Cl-
E. Serotonin P. μ
F. Substance P Q. κ
G. Brainstem R. δ
H. Dors. root gang. S. Depolarizing
I. Nodose ganglion T. Hyperpolarizing
J. Dor
7. H
8. J
9. F
10. P
11. L
12. P
13. J
14. D
15. M
16. T
Which of the following volatile anesthetics has the most “ideal” properties?

MAC (%), PCfat/blood, PCblood/gas
A. 0.5 1.5 0.8
B. 3.0 4.0 6.5
C. 7.0 5.0 12.5
D. 50.0 20.0 10.5
E. 102.0 3.0 2.2
A The “ideal” volatile anesthetic would have a low MAC (high potency; therefore, not much gas is needed – and many of the volatile anesthetics are expensive to purify!), a low PCfat/blood (not much partitioning into fat), and a low PCblood/gas (i.e., a low solubility → rapid onset and recovery). Other qualities of an “ideal” anesthetic include analgesia, amnesia, muscle relaxation, non-toxic, non-explosive, inexpensive, rapid changes in depth of anesthesia, no excessive depression of cardiovascular and respiratory function, etc. It should be noted, however, that it is unlikely that a volatile anesthetic as “ideal” as the one described in choice A could be identified: a highly potent agent (MAC 0.5%) is likely (according to the Overton-Meyer hypothesis) to be quite lipid soluble and therefore would be expected to have a relatively high PCfat/blood (much greater than 1.5).
A volatile anesthetic is administered at 1.0 MAC to a patient weighing 70 kg, of which 60% is water and 15% is fat. The patient has a cardiac output of 6 liters/min and a ventilation of 7 liters/min. The anesthetic has the following properties:
MAC
D PCblood/gas = cblood/calveolar, so cblood = PCblood/gas • calveolar = 0.6 • 2.0% = 1.2%. Regarding the % unit, you are familiar with this unit from the Respiratory Physiology section of OP; FIO2 = 0.21 or 21% is an example. In anesthesiology, the % unit is used not only for anesthetic concentrations in a gas phase (i.e., for calveolar), but also (somewhat inappropriately!) for cblood (as in this question), cfat (see question 39), etc.
A volatile anesthetic is administered at 1.0 MAC to a patient weighing 70 kg, of which 60% is water and 15% is fat. The patient has a cardiac output of 5 liters/min and a ventilation of 6 liters/min. The anesthetic has the following properties:
MAC
B PCblood/gas = cblood/calveolar, so cblood = PCblood/gas • calveolar = 1.4 • 1.4% ≈ 2%.
MAC*(%), PCblood/gas, PCfat/blood
A. Ether 7, 12, 5
B. Isoflurane 1.4, 1.4, 45
C. Sevoflurane 2, 0.65, 48
D. Desflurane 6, 0.45, 27
E. Nitrous oxide 105, 0.47, 2.3

Least potent?
E Recall that potency is reciprocally related to the MAC.
MAC*(%), PCblood/gas, PCfat/blood
A. Ether 7, 12, 5
B. Isoflurane 1.4, 1.4, 45
C. Sevoflurane 2, 0.65, 48
D. Desflurane 6, 0.45, 27
E. Nitrous oxide 105, 0.47, 2.3

Most Potent?
B
MAC*(%), PCblood/gas, PCfat/blood
A. Ether 7, 12, 5
B. Isoflurane 1.4, 1.4, 45
C. Sevoflurane 2, 0.65, 48
D. Desflurane 6, 0.45, 27
E. Nitrous oxide 105, 0.47, 2.3

Can only achieve stage I or stage II of anesthesia?
E
MAC*(%), PCblood/gas, PCfat/blood
A. Ether 7, 12, 5
B. Isoflurane 1.4, 1.4, 45
C. Sevoflurane 2, 0.65, 48
D. Desflurane 6, 0.45, 27
E. Nitrous oxide 105, 0.47, 2.3

Most rapid onset and recovery of agents that can be us
D All agents listed except N2O can be used to achieve stage III (the surgical stage), but desflurane has the most rapid onset and recovery because of its low solubility (PCblood/gas = 0.45).
MAC*(%), PCblood/gas, PCfat/blood
A. Ether 7, 12, 5
B. Isoflurane 1.4, 1.4, 45
C. Sevoflurane 2, 0.65, 48
D. Desflurane 6, 0.45, 27
E. Nitrous oxide 105, 0.47, 2.3

Irritating agent that can form explosive peroxides?
A
MAC*(%), PCblood/gas, PCfat/blood
A. Ether 7, 12, 5
B. Isoflurane 1.4, 1.4, 45
C. Sevoflurane 2, 0.65, 48
D. Desflurane 6, 0.45, 27
E. Nitrous oxide 105, 0.47, 2.3

Approximately 0.02% of inhaled dose is metabolized by
D Desflurane undergoes the least cytochrome P450 metabolism (0.02%) of all halogenated hydrocarbon volatile anesthetics. This is important because the centrilobular necrosis that occasionally is seen with halothane, the first halogenated hydrocarbon volatile anesthetic, probably is caused by a free radical intermediate generated during P450 metabolism (approximately 20% of an inhaled dose of halothane is metabolized by cytochrome P450) and probably is the cause of halothane hepatitis (primarily for this reason, the use of halothane has declined markedly in recent years).
A. Fentanyl
B. Ketamine
C. Midazolam
D. Propofol
E. Thiopental

Short-acting agent (due to
redistribution from brain to other tissues; metabolism actually is slow [metabolic t1/2 ≈ 24 hr]) that often is used for indu
E Propofol also is a short-acting agent, primarily as a result of redistribution from brain to other tissues. But propofol has a metabolic t1/2 ≈ 30 – 60 min, so metabolism also contributes to its short duration of action. Because its metabolic t1/2 is so much shorter than that of thiopental (metabolic t1/2 ≈ 24 hr), propofol does not accumulate in adipose tissue as thiopental does.
A. Fentanyl
B. Ketamine
C. Midazolam
D. Propofol
E. Thiopental

Related to phencyclidine; affects NMDA receptor?
B
A. Fentanyl
B. Ketamine
C. Midazolam
D. Propofol
E. Thiopental

Should be avoided in patients with certain forms of porphyria?
E Barbiturates are contraindicated in patients with certain porphyries (variegate and intermittent) because they can induce ALA synthase.
A. Fentanyl
B. Ketamine
C. Midazolam
D. Propofol
E. Thiopental

Can cause respiratory depression and rigidity of jaw, neck, and upper torso?
A Rigidity of the jaw, neck, and upper torso can be seen with other opioid analgesics as well and probably is due to a central effect of these agents
A. Fentanyl
B. Ketamine
C. Midazolam
D. Propofol
E. Thiopental

Can cause emergence psychosis?
B Emergence psychosis can be avoided or minimized by prior administration of a benzodiazepine and allowing the patient to recover in a dark room.
A. Fentanyl
B. Ketamine
C. Midazolam
D. Propofol
E. Thiopental

Can cause an increase in blood pressure?
B Ketamine is contraindicated in patients with hypertension
A. Fentanyl
B. Ketamine
C. Midazolam
D. Propofol
E. Thiopental

Can have hyperalgesic effects?
E
A. Fentanyl
B. Ketamine
C. Midazolam
D. Propofol
E. Thiopental

Used as a preanesthetic agent to reduce anxiety and produce amnesia?
C
A. Fentanyl
B. Ketamine
C. Midazolam
D. Propofol
E. Thiopental

Administered in a fat emulsion that is easily contaminated?
D
A. Fentanyl
B. Ketamine
C. Midazolam
D. Propofol
E. Thiopental

Effects can be reversed by flumazenil?
C Flumazenil is a competitive antagonist at the BDZ binding site on the GABAA receptor
Important principles in anesthesia include:
A. A constant depth of anesthesia should be maintained throughout a surgical procedure.
B. Barbiturates such as secobarbital can be used as preanesthetic medications to decrease anxiety.
C. Atrop
G A. The depth of anesthesia is appropriately varied throughout a surgical procedure. For example, greater depth may be required during intubation or while making an incision.
B. Barbiturates are useful only for their sedative effects; they do not significantly decrease anxiety in a surgical setting (for example, they are much less anxiolytic than a visit from an anesthesiologist!). Even as sedatives they are not the agents of choice because barbiturates cause cardiovascular and respiratory depression and can have hyperalgesic effects.
C. When highly irritating general anesthetics such as ether were commonly used, atropine was routinely given as a preanesthetic medication to decrease upper respiratory secretions. With newer, less irritating anesthetics, atropine only is given as needed during a procedure to counteract major decreases in heart rate (e.g., due to opioids or vagovagal reflexes elicited by the surgical manipulation of abdominal viscera).
D. β Antagonists such as propranolol should not be discontinued immediately prior to surgery, because abrupt withdrawal can cause arrhythmias (probably because up-regulation of β receptors occurs when a patient takes β antagonists chronically). However, the dose of the β antagonist should be reduced prior to surgery if possible.
E. In patients taking anticoagulants, spinal anesthesia is much more dangerous than general anesthesia.
A. Depolarizing agents
B. Competitive agents
C. Both
D. Neither

Can cause two phases of block?
A
A. Depolarizing agents
B. Competitive agents
C. Both
D. Neither

Action can be terminated by the administration of an anti-ChE?
B An anti-ChE will potentiate the neuromuscular blockade produced by depolarizing agents.
A. Depolarizing agents
B. Competitive agents
C. Both
D. Neither

Class includes drugs that can be inactivated by BuChE?
C The depolarizing agent succinylcholine and at least one competitive agent (mivacurium) can be hydrolyzed by BuChE (aka plasma cholinesterase). The competitive agent atracurium is hydrolyzed by plasma esterases (not cholinesterases) and also can undergo spontaneous hydrolysis in plasma.
A. Aspirin
F. Mivacurium
B. Atracurium
G. Morphine
C. Dantrolene
H. Rocuronium
D. Meperidine
I. Succinylcholine
E. Midazolam
J. Thiopental

Analgesic with a toxic metabolite that may cause seizu
D The metabolite normeperidine may be responsible for the seizures caused by high doses of meperidine.
A. Aspirin
F. Mivacurium
B. Atracurium
G. Morphine
C. Dantrolene
H. Rocuronium
D. Meperidine
I. Succinylcholine
E. Midazolam
J. Thiopental

Neuromuscular blocking agent with most rapid onset of
I Rocuronium also has a rapid onset of action, but not as rapid as succinylcholine.
A. Aspirin
F. Mivacurium
B. Atracurium
G. Morphine
C. Dantrolene
H. Rocuronium
D. Meperidine
I. Succinylcholine
E. Midazolam
J. Thiopental

Neuromuscular blocking agent with shortest duration of
I Mivacurium also has a short duration of action, but not as short as succinylcholine
A. Aspirin
F. Mivacurium
B. Atracurium
G. Morphine
C. Dantrolene
H. Rocuronium
D. Meperidine
I. Succinylcholine
E. Midazolam
J. Thiopental

Neuromuscular blocking agent that is hydrolyzed sponta
B
A. Aspirin
F. Mivacurium
B. Atracurium
G. Morphine
C. Dantrolene
H. Rocuronium
D. Meperidine
I. Succinylcholine
E. Midazolam
J. Thiopental

Neuromuscular blocking agent that is contraindicated i
I Succinylcholine can cause life-threatening hyperkalemia (by causing prolonged opening of the ion channel of the NM receptor), particularly in patients at risk for developing hyperkalemia. It is therefore contraindicated in patients with soft tissue injuries or burns, since these conditions also can cause a loss of K+ from cells
A. Aspirin
F. Mivacurium
B. Atracurium
G. Morphine
C. Dantrolene
H. Rocuronium
D. Meperidine
I. Succinylcholine
E. Midazolam
J. Thiopental

Must be available in all operating rooms?
C Dantrolene blocks Ca2+ release from the sarcoplasmic reticulum in skeletal muscle and is used to treat malignant hyperthermia, a life-threatening condition induced by halogenated hydrocarbon volatile anesthetics and by succinylcholine in a small number of patients (who apparently have a mutation in their skeletal muscle RyR1 receptors or L-type Ca2+ channels). Dantrolene also can be used to treat the neuroleptic malignant syndrome.
Concerning seizures and their therapy, all of the following are true EXCEPT:
A. Absence seizures occur primarily in children.
B. Only generalized seizures result in a loss of consciousness.
C. Seizures can be treated by drugs that block Na
B B. Complex partial seizures also result in a loss of consciousness.
Concerning seizures and their therapy, all of the following are true EXCEPT:
A. A drug eliminated by first-order kinetics should be given approximately every t1/2 to avoid large fluctuations in plasma concentration.
B. When starting therapy wit
C A, B. These general pharmacokinetic principles were discussed in the POP Mini-Course.
C. Therapeutic ranges of AEDs are useful as guidelines only; there is much individual variability.
D. Teratogenicity is an important problem with first-generation AEDs; not enough data are yet available on the effects of fetal exposure to second-generation AEDs.
E. Nystagmus actually is a useful side effect, because it represents a good sign that the patient is in the therapeutic range.
F. Since most AEDs are eliminated by first-order kinetics, doubling the plasma concentration will double the rate of elimination: -dc/dt = kecp. Note that first-order kinetics of elimination often is referred to as linear kinetics, since a plot of average cp vs dose is linear (as predicted from the equation for the calculation of the maintenance dose: MD = Clearance • cpss/Bioavailability). Non-linear kinetics include zero-order kinetics (phenytoin) and kinetics in which the clearance increases as cp increases (carbamazepine).
A. Carbamazepine
B. Ethosuximide
C. Gabapentin
D. Lamotrigine
E. Phenobarbital
F. Phenytoin
G. Valproic acid

Specifically blocks T-type Ca2+ channels in thalamic neurons?
B
A. Carbamazepine
B. Ethosuximide
C. Gabapentin
D. Lamotrigine
E. Phenobarbital
F. Phenytoin
G. Valproic acid

Metabolized by zero-order (dose-dependent) kinetics?
F Note that zero-order kinetics of elimination often is referred to as dose-dependent kinetics: at low doses (before the elimination mechanism is saturated), elimination often is first-order¬; as the dose increases (and the elimination mechanism becomes saturated), elimination becomes zero-order.
A. Carbamazepine
B. Ethosuximide
C. Gabapentin
D. Lamotrigine
E. Phenobarbital
F. Phenytoin
G. Valproic acid

Eliminated entirely by renal excretion?
C
A. Carbamazepine
B. Ethosuximide
C. Gabapentin
D. Lamotrigine
E. Phenobarbital
F. Phenytoin
G. Valproic acid

Used only for absence seizures?
B
A. Carbamazepine
B. Ethosuximide
C. Gabapentin
D. Lamotrigine
E. Phenobarbital
F. Phenytoin
G. Valproic acid

First choice broad spectrum agent?
G
A. Carbamazepine
B. Ethosuximide
C. Gabapentin
D. Lamotrigine
E. Phenobarbital
F. Phenytoin
G. Valproic acid

Can cause gingivitis (gum hypertrophy) and hirsutism (heavy growth of hair) with long-term use?
F
A. Carbamazepine
B. Ethosuximide
C. Gabapentin
D. Lamotrigine
E. Phenobarbital
F. Phenytoin
G. Valproic acid

Can cause alopecia (hair loss) and weight gain with long-term use?
G
A. Carbamazepine
B. Ethosuximide
C. Gabapentin
D. Lamotrigine
E. Phenobarbital
F. Phenytoin
G. Valproic acid

Can cause blurred vision and diplopia at high doses?
A
In the CNS, dopamine is:
A) Less abundant than NE
B) localized primarily in neurons with a diffuse pattern of innervation
C) metabolized to 5-HIAA
D) primarily an agonist at ionotropic receptors
E) released from nerve terminals b
E
In a neuron that receives glutamatergic and GABAergic input, NMDA receptor activation is most likely to occur when:
A) glutamate release is decreased, GABA release is decreased, glycine is absent
B) glutamate is decreased, GABA release is decre
E
A. ACh
B. Baclofen
C. Bicucculine
D. Dopamine
E. GABA
F. Glutamate
G. glycine
H. MPTP
I. NMDA
J. Norepinephrine
K. picrotoxin
L. serotonin
M. strychnine

which one is an indoleamine?
L
A. ACh
B. Baclofen
C. Bicucculine
D. Dopamine
E. GABA
F. Glutamate
G. glycine
H. MPTP
I. NMDA
J. Norepinephrine
K. picrotoxin
L. serotonin
M. strychnine

most abundant transmitter in C
F
A. ACh
B. Baclofen
C. Bicucculine
D. Dopamine
E. GABA
F. Glutamate
G. glycine
H. MPTP
I. NMDA
J. Norepinephrine
K. picrotoxin
L. serotonin
M. strychnine

Most abundant catecholamine is
D
A. ACh
B. Baclofen
C. Bicucculine
D. Dopamine
E. GABA
F. Glutamate
G. glycine
H. MPTP
I. NMDA
J. Norepinephrine
K. picrotoxin
L. serotonin
M. strychnine

NT whose effects are terminate
A
A. ACh
B. Baclofen
C. Bicucculine
D. Dopamine
E. GABA
F. Glutamate
G. glycine
H. MPTP
I. NMDA
J. Norepinephrine
K. picrotoxin
L. serotonin
M. strychnine

Blocks ion channel?
K
A. ACh
B. Baclofen
C. Bicucculine
D. Dopamine
E. GABA
F. Glutamate
G. glycine
H. MPTP
I. NMDA
J. Norepinephrine
K. picrotoxin
L. serotonin
M. strychnine

Blocks GABA binding site?
C
A. ACh
B. Baclofen
C. Bicucculine
D. Dopamine
E. GABA
F. Glutamate
G. glycine
H. MPTP
I. NMDA
J. Norepinephrine
K. picrotoxin
L. serotonin
M. strychnine

blocks glycine binding site?
M
A. ACh
B. Baclofen
C. Bicucculine
D. Dopamine
E. GABA
F. Glutamate
G. glycine
H. MPTP
I. NMDA
J. Norepinephrine
K. picrotoxin
L. serotonin
M. strychnine

precursor is a major excitator
E
A. ACh
B. Baclofen
C. Bicucculine
D. Dopamine
E. GABA
F. Glutamate
G. glycine
H. MPTP
I. NMDA
J. Norepinephrine
K. picrotoxin
L. serotonin
M. strychnine

Metabolized to a neurotoxin?
H
A. ACh
B. Baclofen
C. Bicucculine
D. Dopamine
E. GABA
F. Glutamate
G. glycine
H. MPTP
I. NMDA
J. Norepinephrine
K. picrotoxin
L. serotonin
M. strychnine

Metabolized to HVA in the CNS?
D
Conventional antipsychotic drugs as a class:
A) show clinical potency that correlated with affinity for D1 dopamine receptors
B) cause postural hypotension due to blockade of mAChRs
C) increase the seizure threshold
D) inhibit prolact
E
Advantages of the atypical antipsychotic drug risperidone over conventional antipsychotics include:
A) alleviation of negative symptoms
B) lower addiction potential
C) lower cost
D) more rapid onset of action
E) no risk of EPS
A
The SSRI antidepressants as a class:
A) block presynaptic 5-HT2 receptors
B) cause insomnia
C) inhibit DA uptake
D) lack major CV side effects
E) take effect more rapidly than the TCAs
D
SSRIs inhibit a larger percentage of NE or 5-HT at a given dose?
Inhibit much more NE reuptake than 5-HT at a given dose.
Calculate the amount of ethanol consumption (i.e. the dose in grams) by a 60kg male patient whose blood ethanol level is 70mg%. Assume ethanol has a Vd of 0.65L/kg and a bioavailability of 1.0
27.3 gm.
Cp = Dose/VD; the dose must be multiplied by the bioavailability (F) if the drug is not administered IV (in this problem, as in many calculations with ethanol, bioavailability is assumed to be 1.0). Therefore Dose = Cp • VD = 700 mg/liter • 0.65 liters/kg = 455 mg/kg = 0.455 g/kg. So for this 60 kg patient, the dose is 0.455 g/kg • 60 kg = 27.3 gm.
True or False?
in acute alcohol toxicity, owing to high levels of ingested ethanol, P450 induction can lead to increased blood levels of acetylaldehyde?
False Cytochrome P450 is induced in chronic alcoholism, not acute alcohol toxicity.
True or False?
disulfiram must be metabolized by glutathione-S-transferase and S-methyltransferase before it can inhibit ALDH
false
Disulfuram must be metabolized by glutathione reductase and S-methyl transferase to form the active inhibitor of ALDH, diethylthiomethylcarbamate.
True or False?
Ethanol enhances hepatic triglyceride synthesis partly via induction of alpha methyl phosphate acyl transferase
false
Ethanol enhances hepatic triglyceride synthesis partly via induction of α-glycerol-phosphate acyl transferase.
True or False?
mild daily ethanol consumption (about 40ml) is associated with reduced plasma ratios of HDL:LDL and protection against coronary artery insufficiency
false
Mild daily ethanol consumption is associated with increased plasma ratios of [HDL]:[LDL].
True or False?
Reductive storage, a biochemical condition associated with ethanol consumption, can lead to lactic acidemia
true
True or False?
folate administration will increase intracellular levels of formic acid in patients suffering from methanol poisoning
false
Folate reduces intracellular levels of formic acid by accelerating its non-enzymatic conversion to CO2 and H2O.
True or False?
In the CNS, during acute elevations in blood ethanol, neuronal kainate and GABAa receptor activity are attenuated
false
During acute elevations in blood ethanol, neuronal kainite receptor activity is attenuated, but neuronal GABAA activity is enhanced.
True or False?
In the CNS, during acute elevations in blood ethanol, neuronal membrane fluidity and adenosine uptake are elevated
false
Membrane fluidity is increased, but adenosine uptake is inhibited.
True or False?
In the CNS, during acute elevations in blood ethanol, neuronal NMDA and Ca receptor activity are augmented
false
Neuronal NMDA and Ca2+ receptor activity are inhibited.
True or False?
In the CNS, during acute elevations in blood ethanol, vasomotor depression leads to cutaneous vasodilation
true
the pharmacokinetic properties that differ amongst the BDZs include all the following except:
A) biologic half-life
B) conversion to biologically active metabolites
C) glucuronidation as a required step in metabolism
D) extent to whic
C
In choosing a sedative hypnotic for sleep therapy, it is important to recognize theat:
A) the available drugs are not effective inless used for a few weeks
B) daytime sedation is not a concern if the parent drug is rapidly metabolized
C) e
C
list representative drugs that are classified as mu, delta, and kappa agonists.
μ agonists: morphine, meperidine, methadone, fentanyl, codeine (partial agonist) buprenorphine (partial agonist), β-endorphin (endogenous peptide)

δ agonists: leu- and met-enkephalin (endogenous peptides), β-endorphin (endogenous peptide)

κ agonists: butorphanol, dynorphins (endogenous peptides)
discuss the intracellular coupling of the mu opioid receptor
The μ opioid receptor is a GPCR that couples to Gi/Go, resulting in the inhibition of adenylyl cyclase, activation of K+ channels → membrane hyperpolarization, and inhibition of voltage-gated Ca2+ channels → ↓neurotransmitter release.
discuss the primary sites of action at which opioids act to produce analgesia
The primary sites at which opioids act to produce analgesia are the amygdala, substantia nigra, periaqueductal gray area (PAG), rostroventral medulla, and spinal cord. Of these sites, the mechanisms for analgesia in the PAG and spinal cord are best understood (see Figures 9 and 10 in the syllabus). In the PAG, opioid binding to presynaptic μ receptors on the nerve terminals of interneurons in the PAG → inhibition of voltage-gated Ca2+ channels →↓GABA release → reduced inhibition of PAG projections to the medulla → increased activation of bulbospinal projections (from medulla to spinal cord) → ↑5-HT and/or NE release in spinal cord → inhibition of spinal pain input. In the spinal cord (dorsal horn), opioid binding to presynaptic μ receptors on the terminals of C fibers activated by painful stimuli → inhibition of voltage-gated Ca2+ channels →↓release of peptide transmitters (e.g., substance P) from C fibers; also, opioid binding to μ receptors on second order neurons in dorsal horn → activation of K+ channels → membrane hyperpolarization → ↓excitability of second order neurons.
indicate the cardiac effects of morphine
The cardiovascular effects of morphine include (a) increased excitation of parasympathetic nerves that innervate the heart (vagus) → ↓heart rate (atropine-sensitive); and (b) release of histamine from mast cells → peripheral vasodilation and hypotension. Note that because opioids are typically well tolerated from a cardiovascular perspective, they are widely used as induction agents in cardiac surgery (especially fentanyl).
what is the WHO ladder?
The World Health Organization (WHO) ladder (Figure 24 in the syllabus) provides a model for graded analgesic therapy. It emphasizes starting with weak opioids and then progressing to stronger opioids for more severe pain states, using combination analgesic therapy (e.g., NSAIDS + opioids), and using adjuvants to manage side effects (e.g., laxatives, antiemetics, and stimulants).
Define tolerance, dependence, and addiction
Tolerance: a decrease in effectiveness of a drug over time with repeated administration; thus, an increased dose is required to yield an equivalent response after successive doses. With opioids, tolerance can be extreme, e.g., 10 mg PO is a high dose in a naïve individual, while 3 gm IV might produce only minor sedation in an extremely tolerant individual.
Dependence: state of adaptation to a specific drug such that abrupt cessation (e.g., by drug abstinence) and/or administration of a specific antagonist → withdrawal syndrome.
Addiction: drug-seeking behavior motivated by a strong desire to acquire a drug for non-therapeutic self-administration; an extreme form of dependence.
what is the origin of the pain associated with migraine?
While the origin of migraine pain is not completely understood, one proposed mechanism is as follows: A primary vasoconstriction (triggered by stress, anxiety, exercise, hunger, and/or various unidentified factors) causes a mild ischemia and results in sensitization of sensory afferents (C fibers) in the trigeminal nerve (CN V). This sensitization may lead to the local release of substance P (SP) and/or calcitonin gene-related peptide (CGRP); these peptides → local cranial vessel dilation, extravasation of plasma from the vessel, and the activation of mast cells. The vasodilation and products from the mast cells → stimulation of the sensitized trigeminal C fibers → pain.
what is the mechanism by which the triptan-like drugs are thought to relieve migraines?
The triptans are 5-HT1B/D agonists. They act at (a) presynaptic 5-HT1B/D receptors on the sensory afferents in the trigeminal nerve → ↓release of SP and/or CGRP; and (b) postsynaptic 5-HT1B/D receptors on the intracranial vessels → vasoconstriction.
what is the receptor at which the ondansetron-like drugs act?
Ondansetron and related drugs (the setrons) are 5-HT3 antagonists.
list two drugs that would be useful in treating the nausea arising from motion sickness
Nausea arising from motion sickness can be treated with anticholinergics (muscarinic antagonists) such as scopolamine [Transderm Scop®] and antihistamines (H1 antagonists) such as dimenhydrinate [Dramamine®] (dimenhydrinate is a salt of diphenhydramine). Note that the effectiveness of antihistamines in treating the nausea arising from motion sickness probably is due primarily to their anticholinergic activity.
what is the mechanism by which metoclopramide controls nausea?
Metoclopramide [Reglan®] controls nausea by blocking D2 receptors in the CTZ of the medulla (area postrema). Metoclopramide also has prokinetic effects in the GI tract (e.g., it increases gastric emptying) by acting as an agonist at 5-HT4 receptors on neurons in the enteric nervous system (ENS) → ↑ACh release.
Why would administration of methoxyflurane to an obese person for a long surgical procedure not only be expensive, but risky?
To understand why the administration of methoxyflurane (PCblood/gas = 12, PCfat/blood = 61; see Table 1 in the syllabus) to an obese person for a long surgical procedure would be both expensive and risky, one needs to calculate the amount of methoxyflurane that would accumulate in the body. During a long procedure, the anesthetic would equilibrate not only throughout body water, but also throughout the body fat. Assume that the patient weighs 80 kg, 50% of which is water and 30% of which is fat; thus, the patient has 40 kg = 40 liters of body water and 24 kg ≈ 24 liters of fat. The volume of gas needed to fill the body water = PCblood/gas • volume of body water = 12 • 40 = 480 liters of gas. The volume of gas needed to fill the body fat = PCfat/blood • PCblood/gas • volume of fat = 61 • 12 • 24 = 17,568 liters of gas (!) Thus, the total volume of gas needed to fill body water plus fat is over 18,000 liters (!!). This would be expensive!! If it is assumed that the anesthetic is eliminated exclusively by ventilation, then the time required to eliminate the anesthetic is ≈ volume of gas (liters) ÷ ventilation (liters/min). [Note that this calculation is very approximate, as it assumes a zero-order elimination process (constant rate); in actuality, the elimination process will be first-order.] If ventilation = 6 liters/min, then the time required to eliminate ≈ 18,000 liters of gas is ≈ 18,000 ÷ 6 = 3,000 min = 50 hours (!!). This would be very risky for the patient!! Thus, a volatile anesthetic with a high PCblood/gas and high PCfat/blood should not be used for a long surgical procedure, particularly in an obese person! [Note that because of its high PCblood/gas and high PCfat/blood, methoxyflurane no longer is used in anesthesiology.]
why does the duration of thiopental anesthesia increase with each successive dose?
With thiopental, as long as the fat, and to some extent the muscle, compartments are not filled with thiopental, the duration of action depends on the redistribution of thiopental from high blood flow areas (e.g., brain) to low blood flow areas (especially fat and to a lesser extent resting muscle), not on the metabolism of thiopental (which actually is relatively slow: t1/2 ≈ 12 hr!!). Following a single bolus, a patient typically will emerge from anesthesia in 10 min as a result of such redistribution. With successive thiopental doses, the fat and muscle compartments become filled, and as they do, redistribution no longer represents a potential mechanism for lowering the concentration of thiopental in blood. Therefore, the body must rely on metabolism to lower the plasma concentration of thiopental, and when the surgery is over, metabolism must eliminate not only the thiopental in plasma, but the relatively large amount of thiopental that accumulated in fat. Because thiopental metabolism is so slow, a patient may require more than a day to emerge from anesthesia after a long thiopental infusion.
whay is nitrous oxide less efficacious in Denver than in San Diego?
The partial pressure is the driving force for equilibration of anesthetics, and the partial pressure of anesthetic PA = PTotal • XA , where PTotal is the total barometric pressure and XA is the mole fraction of the anesthetic gas (i.e., the fraction of the total gas molecules that are molecules of anesthetic). Since N2O is not a potent anesthetic, concentrations up to 80% (XA = 0.80) must be used during induction to obtain the desired PA. At high altitudes, where PTotal is lower, it is not possible to use a higher XA to obtain the desired PA since oxygen demands would be compromised (i.e., if XA > 0.80, then XO2 would have to be less than 0.20, resulting in a very low PO2 ).
What is the desired mode ot elimination of volatile anesthetics?
The newer volatile anesthetics are halogenated hydrocarbons, the metabolism of which (by cytochrome P450) can result in the formation of free radical intermediates that can cause liver necrosis or high output renal failure. Thus, a volatile anesthetic that is eliminated by respiration and not by metabolism is preferred. Note that of the halogenated hydrocarbons, halothane undergoes the most P450 metabolism (≈ 20%), while desflurane undergoes the least (≈ 0.02%); enflurane (≈ 2%), isoflurane (≈ 0.2%), and sevoflurane (≈ 3%) are in between.
What is the mechanism of anesthetic action of volatile anesthetics?
Although the Meyer-Overton relationship (Figure 6 in the syllabus) suggests a general interaction of volatile anesthetics with lipid membranes, additional data (e.g., the fact that stereoisomers show different potencies; see Figure 7) suggest a more specific membrane action, probably involving interactions with the GABAA receptor. Volatile anesthetics have been shown to increase GABAA–mediated Cl- influx in a stereospecific manner, and anesthetic action is diminished when expression of the functional form of this receptor is reduced (e.g., in KO mice).
what is MAC and what is MAC-sparing?
MAC represents the minimum alveolar concentration of a volatile anesthetic that blocks the response to a noxious stimulus (e.g., incision) in 50% of patients. A “MAC sparing” agent is a drug that can be given in combination with a volatile anesthetic to reduce the anesthetic requirement (e.g., opioids, neuromuscular blocking agents).
what is the component of the action potential that is blocked by the local anesthetics?
The local anesthetics block the voltage-gated Na+ channels; thus, they block the spike of the action potential.
whay are the clinically useful anesthetics referred to as use-dependent blockers?
The clinically useful local anesthetics are referred to as use-dependent blockers because they enter the open Na+ channel (from the cytoplasmic side). More frequent depolarization → more frequent channel opening → ↑opportunity for the local anesthetic to block the channel.
describe the two structural components and the linkages of the common local anesthetics
The commonly used local anesthetics consist of a hydrophilic domain (tertiary or secondary amine) linked to a hydrophobic domain (aromatic residue); an ester or amide alkyl chain links the two domains.
discuss the sensitization that can occur with local anesthetics
Some individuals can develop hypersensitivity reactions to local anesthetics. The reaction most commonly consists of an allergic dermatitis, but asthmatic or anaphylactic reactions can occur. Hypersensitivity reactions most commonly are seen with local anesthetics of the ester type; if an individual develops a hypersensitivity reaction to one ester local anesthetic, he/she usually will have a hypersensitivity reaction to other ester local anesthetics. Sometimes, such allergic reactions are provoked by preservatives or other solutes (e.g., methylparaben, sulfite) in the local anesthetic solution rather than by the local anesthetic itself.
what is the principal morbidity associated with local anesthetic action and what is its mechanism?
The systemic toxic reactions associated with local anesthetics are a function of the blood level. As the blood level increases, CNS effects are seen first (in the following order: numbness of lips/tongue, lightheadedness, restlessness, tremors, unconsciousness, convulsions, coma, respiratory arrest) followed by cardiovascular depression (in the heart: ↓myocardial excitability, ↓conduction velocity, ↓firing rate, ↓force of contraction; in the blood vessels: arteriolar dilation). Although cardiovascular toxicity typically is seen at higher blood concentrations than CNS toxicity, occasionally low doses of local anesthetics → cardiovascular collapse and death, probably due to the sudden depression of cardiac pacemakers or ventricular fibrillation.
What are steps 1,2,3, and 4 of anesthesia?
(I) analgesia, amnesia, stupor, no loss of consciousness, desynchronized EEG. (II) excitement or delirium (III) surgical anesthesia, inconsciouness, regular respiration, HVSW-EEG = high voltage slow wave electro- encephalogram (IV) medullary depression, respiratory/CV depression, flat EEG
Classes of anesthetics?
Injectable (barbiturates, propofol, etomidate, BDZs, ketamine, opiods), and volatile (chloroform, ether, nitrous oxide, halogenated hydrocarbons)
How to deliver inhalation anesthetics?
Anesthetic plus inhaled gas (air/O2). Dosing is based on % anesthetic in inhaled gas plus total gas flow (ventilatory rate/volume)
Concentration or partial pressure more important for effects of inhaled anesthetics on brain?
Depth of anesthesia is directly related to partial pressure at equilibrium, PPbrain = PPalveolar = PPinhaled gas. Volatile anesthetic dose is aveolar concentration (expressed as % alveolar gas) associated with PP that produces a given degree of anesthesia. Also, movement of volatile anesthetics from one body compartment to another is a function of PP, not concentration. Furthermore, the concentration of the drug in a particular tissue is directly related to its solubility in that tissue, so if want to increase concentration in a 3x less soluble tissue, need to increase PP of the drug 3x to get equal concentration. Values are based on partition coefficient (PC). Drugs will diffuse between tissue until equilibrium is reached (equal PP).
What indexes of potency are used to describe inhalation anesthetics?
MAC = minimum alveolar concentration of anesthetic required to block purposeful somatic movement otherwise evoked by a noxious stimulus in 50% of patients. MACBAR is min alveolar conc that blocks autonomic response evoked by stong stimulus in 50% of patients.
What affects MAC and MACBAR?
Age and anesthetic agent. MAC is maximal at 6mo of age, and decreases 6% each decade (so half in 80yo). Also, agents differ in potency. Methoxyflurane MAC is 0.16%, all the way up to nitrous oxide which is 105%
Movement of inhaled anesthetic into alveoli?
Anesthetic mixes with the gas, is removed by diffusion into alveolar blood, and will continue to do so until PP of avleolar gas is same as PP pulmonary blood
How does inhaled anesthetic move from alveoli into blood?
Rapid process, but thr rate depends on anesthetic solubility in the blood (different than solubility in air or tissues). Agents with PCblood/gas >1.2 have high solubility in blood, e.g. isoflurane versus desflurane, and are more rapidly cleared from alveolus. So desflurane will equilibrate faster because blood can’t hold as much (less soluble).
High versus low solubility is ventilation- or blood flow-limited?
High solubility is ventilation-limited because need a lot of gas to “fill up” the blood with the gas. Low solubulity is blood flow-limited because blood fills up fast, and gas just waits for more blood to come along to fill up
What dictates how fast/well anesthetics get delivered from blood to tissues?
PPblood in blood, volume blood (flow) received by tissue, mass of the tissue, anesthetic solubility in that tissue. Isoflurane has 1.4, 48, 26 tissue/blood partition, while desflurane has 0.45, 2.3, 1.3 (blood, muscle, brain)
How fast does brain equilibrate?
It has low solubility and high blood flow, so rapid (similar to kidney and liver). These are opposite of fat, which is high solubility and low blood flow, so it’s slow equilibration.
Ideal anesthetic?
Low fat PC(blood/gas), low PC(fat/blood), and low MAC. (high PC leads to accumulation and long recovery times),
What is the prodrome of migraines?
Vague changes in mood or appetite
What is the aura of migraines?
Visual disturbances (positive and negative symptoms), motor or sensory disturbances, N/V
Description of the headache of migraines?
Throbbing over one eye, or can be occipital pain. Pain accompanied by malaise, N/V, gastric stasis, light/sound sensitivity, pallor, diuresis
What is the resolution phase of migraines?
HA resolves after 3-4 hrs, but can last 24 hrs or more
What is the class of migraine called classic migraine?
Migraine with aura, has all four aspects (prodrome, aura, HA (with associated pains), and resolution
What is the class of migraine called common migraine?
Migraine without aura
Clinical manifestation of basilar migraine?
Aura, no motor disturbance, originate at brainstem and/or from both hemispheres. Most common in young women and children.
Clinical description of familial hemiplegic migraine?
Rare, aura-associate migraine with unilateral motor weakness and sensory loss. Autosomal dominant inheritance
Who most commonly has basilar artery migraine?
Young women and children
What is the inheritance pattern of familial hemiplegic migraine?
Autosomal dominant
Clinical description of ophthalmologic migraine?
Localized around one eye, followed by unilateral CN III, IV, VI nerve palsy
What is a cluster headache?
Not generally classified as a migraine. It is brief (1-2hrs), rapid, intense, episodic pain around one eye. It can be associated with lacrimation, nasal congestion
Clinical description of tension headache?
Bilateral, diffuse, felt as a band of pressure or constriction. Has no aura or systemic of neurological disturbances.
Common headache triggers?
Emotional stress, tyramine (cheese, chocolate, red wine), bright lights, loud noise, exercise, hunger
Smoking and contraceptive use and risk of migraines?
Smoking and contraceptive use by migraine sufferers raises risk of stroke by 34X.
What is the referred pain theory of migraines?
The brain parenchyma is insensate, but mechanical and chemical stimulation of meninges and cranial vessels (sensory is CN V), produces focal referred pain
What is the “vasomotor instability” or “modified vascular theory” of migraines?
Vasoconstriction or abnormal A/V shunting leads to mild ischemia→increased extracellular K→cortical spreading depression (and correlated to aura). The initial vasoconstriction sensitizes the trigeminal sensory afferents innervating meningeal blood vessels, which leads to release of SP and CGRP and therefore vasodilation and plasma extravasation, which leads to increased activity in trigeminal sensory afferents, and so referred pain in cranial area innervated by that afferent.
How do ergot alkaloids treat migraines?
Bind 5-HT receptors, leading to potent intracranial veno- and arterio-constriction and inhibition of excitability of C-fiber terminals, possibly by binding to 5-HT1B/D (so pain sensation is decreased).
What are side effects of ergot alkaloids as treatment for migraines?
Limb ischemia, gangrene. Potency of the agents can lead to rebound headaches.
What are four contraindications for ergot alkaloids for treatment of migraines?
Peripheral vascular disease, CAD, THN, renal disease
What is ergotamine? Other drug(s) in this class?
An ergot alkaloid for migraines. Due to alpha1 agonism, it can cause intense peripheral vasoconstriction, limb ischemia, gangrene Another ergot alkaloid is dihydroergotamine. It is also an oxytocin receptor agonist, so can help with uterine contractions to treat bleeding immediately after birth.
What is dihydroergotamine? Other drug(s) in this class?
An ergot alkaloid for migraines. Another ergot alkaloid is ergotamine
What is route of administration of ergot alkaloids?
Sublingual, oral, nasal.
Difference in affinities for 5-HT receptors between ergot alkaloids and triptans?
Ergot alkaloids have high affinity for 5-HT receptors, but less selectivity for 5-HT1B/D than triptans
How do triptans work to treat migraines?
Selectively agonizes 5-HT1B/D receptor, which is Gi coupled to inhibit AC. That leads to inhibition of excitability of peripheral trigeminal nerve terminals supplying intracranial vascular and meningial structures, decreasing SP and/or CGRP and decreasing vasodilation
Route of administration of sumatriptan?
SQ, PO, nasal
Efficacy of sumatriptan in migraines?
70-77% patients improve in 1 hr following SQ injection, but more effective earlier in attack.
What type of migraines can sumatriptan not treat?
Basilar or hemiplegic headache
How is sumatriptan metabolized?
Liver, but metabolites cleared renally
Contraindications for sumatriptan use?
Ischemic heart disease, uncontrolled HTN, Prinzmetal’s angina (focal spasm or angiographically normal coronary arteries)
How are COX inhibitors analgesics?
Inhibit PG synthesis, so less pain
How does ASA/APAP/caffeine treat migraines?
Caffeine causes vasoconstriction. This plus analgesics might work to treat migraines
What categories of drugs to treat mild migraine attacks?
NSAIDS, antiemetics
What categories of drugs are used to treat mild to severe migraines?
Triptans, antiemetics
What categories of drugs are used to treat severe migraines?
SQ triptans, or SQ, IM, IV, or nasal dihydroergotamine in resistant cases, or opioid analgesics as a last resort for pain-free sleep.
What can be used to prevent migraines?
Beta antagonists, antiepileptic drugs, Ca channel blockers, TCAs, Botox (although not FDA approved)
Muscles used in vomiting?
Simultaneous contraction of inspiratory and expiratory muscles, co-contraction of the diaphragm and abdominal muscles increases pressure on the stomach. Glottis is closed to prevent aspiration
Medical problems that can be causes by vomiting?
Weight loss, electrolyte imbalance, inability to complete therapeutic regimen, impair healing (open sutures, etc), risk of aspiration, prevent absorption of drugs
How is vomiting controlled/triggered?
By the emetic center of the 4th cerebral ventricle, which is the final receiving pathway from many stimuli. The chemoreceptor trigger zone (CTZ) is on the floor of the 4th ventricle outside the BBB. Other contributors include the cerebral cortex, the GI tract via CN X to the NTS, and the vestibular apapratus.
How does ipecac cause vomiting?
Activates the CTZ and peripheral vagal afferents
What does apomorphone do, and how does it work?
Induces vomiting by acting on D2 receptors in CTZ
How does motion sickness occur?
Conflicting inputs between visual and vestibular systems ot between 2 vestibular systems.
How are 5-HT3 receptors involved in emesis? Two main locations of these receptors?
Systemic toxins such as cisplatin and radiation increase 5-HT release from enterochromaffin cells in intestinal mucosa, which binds to and opens 5-HT3 ligand-gated cation channels on vagal afferents, leading to depolarization and vomiting reflex. There are also 5-HT3 receptors in the CTZ and medullary emetic center.
Why do 5-HT3 antagonists suppress emesis?
They bind to 5-HT3 receptors on both vagal nerves and the CTZ and medullary emetic centers, to prevent action of 5-HT released from the stimulus of toxins like cisplatin or radiation to induce emesis
In what conditions will 5-HT3 antagonists not prevent emesis?
In the presence of apomorphine, morphine, or motion sickness. They are not universal antiemetics
How are DA receptors involved in emesis?
Visual and vestibular input increase DA released to CTZ, so stimulates the medually emetic center. This is why D2 antagonists can have antiemetic effects and why apomorphine (a D2 agonist) can cause emesis
How are mAChRs involved in emesis?
ACh is released by vestibular input to CTZ, which activates mACh receptors in CTZ, causing emesis. That is why scopolamine can prevent motion-induced nausea
What is scopolamine and how does it work to treat motion sickness?
mAChR antagonist and H1 blocker, so it blocks input to the central emesis center by the vestibular area (good for motion sickness)
At what point in the process of nausea are antiemetics most effective? When should antiemetics be given?
Best when given before onset. Should be given on a scheduled basis, around the clock, throughout the period of anticipated emetic response.
How to improve efficacy of antiemetic therapy?
Combo therapy helps to target multiple transmitter systems. The more neurotransmitters that are blocked from producing emesis, the more effective.
What would happen at equilibrium if the blood was exposed to 1atmosphere of isoflurane, nitrous oxide, and ether?
The PP of a gas in a tissue (or blood) is a function of the solubility of the gas in that tissue. So, based on their solubilities in blood, 1.14L isofluorane, 0.47L nitrous oxide, 12 L ether
The amount of anesthetic delivered to a tissue depends on what 4 properties?
PP(blood) in that tissue, the volume of blood received by the tissue (% cardiac output), mass of the tissue, and anesthetic solubility in that tissue
How does blood flow affect clearance of anesthetic?
High blood flow tissues clear anesthetic faster, but they also come to equilibrium faster when anesthetic is administered.
What are the neuronal effects of gas anesthetics?
Block excitation and spontaneous activity. Block excitatory brainstem and spinal reflexes, and depress cortical EEG (all these due to membrane hyperpolarization)
What is the Meyer-Overton relationship?
Potency (MAC) is inversely proportional to Oil/gas partition coefficient, even across species and 5 log units.
What is the limit to the Meyer-Overton rule of anesthetics interacting with lipid membranes?
Agents with carbon chains greater than 8-10 show no anesthetic activity, giving evidence for a specific pocket in the lipid bilayer for anesthetics to act. Also, stereoisomers show different potencies
What is the role of GABA A receptors for volatile anesthetics?
GABA-activated Cl- channel leads to hyperpolarization. The Cl- current is enhanced by volatile anesthetics, and is a stereospecific effect. The anesthetic action is diminished in KO mice in which the functional GABA is knocked out.
Solubility and potency of nitrous oxide as an inhaled anesthetic?
Low blood solubility (S=0.47), and low potency. Even at 70% (max because O2 has to be given too), can only achieve 2nd stage of anesthesia. Note, stage 1 and 2 are: (I) analgesia, amnesia, stupor, no loss of consciousness, desynchronized EEG. (II) excitement or delirium.
A good use for nitrous oxide?
Good for analgesia, and also in combo with isoflurane, especially to reduce concentration of other anesthetics needed compared to their use alone. It has low solubility and low potency.
Effect of nitrous oxide on BP?
Maintains blood pressure through sympathetic discharge
Effect of nitrous oxide on skeletal muscle?
No skeletal muscle relaxation
Possible complication from nitrous oxide?
Pockets of trapped gas may reside after anesthesia
Solubility of ether, and implications of that?
High solubility (12). So, it has to be administered at high doses at first in order to speed induction, but slow recovery because so much accumulation.
Effect of ether on cardiovascular system?
Circulatory stability, no CV depression.
Side effects of ether?
Irritating, produces N/V
Stages of anesthesia induced by ether?
Has a classic timeframe for each stage of anesthesia
Efficacy of ether for muscle relaxation?
Very good
Efficacy of ether for analgesia?
Very good
Possible problems with ether?
Peroxides formed by ether evaporation are explosive. It causes irritation to respiratory tract, increases secretions and bronchoconstriction. Ether is not used in U.S. and other developed countries, but mainstay in third world countries. It has high solubility
Solubility of halothane?
2.3. no longer used, but is standard to which all other gas anesthetics are compared.
Effect of halothane on analgesia?
Poor analgesia.
Effect of halothane on CV system?
Depresses myocardium and baroreceptor reflexes, sensitizes ventricular tissues to catecholamines (but does not stimulate sympathetic output). Circulatory depression
What is the most important risk of halothane?
1:10,000 cases it can cause halothane hepatitis. 15-20% of halothane is metabolized by P450, and a free radical intermediate is formed from that.
Solubility of isoflurane?
Intermediate solubility (1.4). has more rapid onset and recovery than halothane
Effect of isoflurane on CV system?
Less cardiac depression than halothane
Effect of isoflurane on skeletal muscles?
Good muscle relaxation
Problems with isoflurane?
Can cause uterine contractions, is slightly irritating, and stimulated airway reflexes.
Solubility of desflurane?
0.45, most rapid onset and recovery. Good in outpatient setting. Recovery is 5-10 minutes after discontinuation
Effects of desflurane on CV system?
Same as isoflurane (less cardiac depression than halothane), may have some benefit in CAD pts
Effect of desflurane on skeletal muscle?
Good muscle relaxation (like isoflurane and ether, but not Nitrous oxide)
Metabolic degradation of desflurane?
Very little. Only about 0.02%, which is similar to isoflurane (0.2%).
Problems with desflurane?
More irritating on the airways, induction more difficult. It’s use is increasing in the U.S.
Solubility of sevoflurane?
0.65, so it has rapid onset and recovery like desflurane.
Advantage of sevflurane over desflurane?
Less irritating.
Metabolic degradation of sevflurane?
3% (as opposed to 0.02% for desflurane and 0.2% for isoflurane)
Problems with sevflurane?
Chemically unstable in the presence of absorbants of CO2
How do anesthetic agents reach their site of action?
Local diffusion (after direct delivery), or movement though the IV route
Consistency of structure between volatile and injectable agents?
Injectable agents have consistent structure similarity, which is an independent predictor of bioactivity. But volatile agents have no EVIDENT structure similarity.
GABA receptors for injectable anesthetics?
They are highly concentrated in neuraxis. They are inhibitory at virtually every neuron in the CNS, and inhibition can be mediated by specific subclasses of receptors
GABA A and GABA B receptors ionotophic or metabotrophic?
GABA A is ionotrophic. GABA B is metabotrophic. Anesthetics target the GABA A receptors
Structure of GABA A receptors?
Pentamer of subunits, creating a gated Cl- channel. Each subunit has 4 transmembrane regions. There are four families of subunits, alpha, beta, gamma, and delta. And several versions of each subunit
What happens at the GABA-A receptor when GABA binds?
Opens the channel to Cl-conductance, which either depolarizes or hyperpolarizes the membrane depending on the Cl equilibrium potential
what’s thiopental?
A barbiturate like phenobarbital. It targets the GABA-A receptor to increase affinity for GABA and Cl conductance
What is alphaxone?
A steroid that targets the GABA-A receptor
What is midazolam?
A BDZ, like alprazolam that targets the GABA-A receptor. Short duration of action
What is alprazolam?
A BDZ like midazolam that targets the GABA-A receptor.
What is propofol?
IV Anesthetic that targets the GABA-A receptor to increase its affinity for GABA and increase Cl conductance
What is etomidate?
IV anesthetic than targets the GABA-A receptor to increase its affinity for GABA and increase Cl conductance. It can cause post-op N/V and temporary Addison’s.
Ethanol and GABA-A?
Ethanol targets the GABA-A receptor to increase its affinity for GABA and increase Cl conductance.
Effect of GABA-A-targeted drugs at low vs. high concentration?
At low conc, they increase the receptor’s affinity for GABA and therefore increase Cl conductance. At high concentration, they alone increase Cl conductance at GABA receptors
Onset and duration of thiopental?
10-20sec and 20-30 minutes. Short duration due to redistribution of drug from brain to other tissues like fat (not because of metabolism)
What is the half-life of thiopental?
Very fast, but not due to metabolism. It has a “context-sensitive half-life” because chronic exposure can lead to accumulation and extended recovery.
What is thiopental good for?
Induction (fast onset), followed by other, longer-acting agents.
Effects of thiopental on pain?
No analgesia, in fact, causes hyperalgesia (like other barbiturates) during recovery.
Effects of thiopental on CV system?
Minimal CV effects
Effects of thiopental on respiratory system?
Depressed respiratory response to to hypercarbia/hypoxia, bronchospasm
Contraindication for thiopental?
Porphyrias
Onset and duration of propofol?
Rapid acting IV anesthetic, more rapid emergence than thiopental after bolus. Duration depends on how long pt has been exposed. Immediately half-life is 2-4 minutes. After 1 hr, 5 minutes. After 10 hrs, 7 minutes.
CV effects of propofol?
Initial apnea and fall in BP. (causes vasodilation and reduced myocontractility). These are the same effects as for etomidate.
What’s propofol good for?
Good for induction of anesthesia, (same as etomidate)
Problems with propofol?
Prepared in fat emulsion base, associated with bacteremia. Dose is reduced in elderly
Onset and duration of etomidate?
Rapid acting IV anesthetic. But, recovery is less affected by prolonged exposure than with propofol
CV effects of etomidate?
Initial apnea and fall in BP. (causes vasodilation and reduced myocontractility). These are the same effects as for propofol. However, there are “minimal effects upon CV, no hypotension, best for cardiac stability”
What’s etomidate good for?
Good for induction of anesthesia, (same as etomidate)
Which injected anesthetic is best for cardiac stability?
Etomidate
Problems with etomidate?
N/V, stongly suppresses adrenocortical stress response
Utility of BDZs in anesthetics?
Diazepam and midazolam are good for preanesthetic agents or anesthesia supplements.
Onset of BDZs compared to barbiturates?
BDZs slower than barbiturates, and drowsiness continues after plasma levels fall. Midazolam has the shortest duration of action
Problems with BDZs in anesthesia?
All except midazolam cause vascular irritation if injected rapidly, will not produce anesthesia alone, but good for diagnostic procedures not requiring analgesia (“conscious sedation”)
What’s flumazenil?
Competitive antagonist at the BDZ binding site, used to reverse BDZ-induced sedation.
Use of opioids in anesthesia?
Opiates like fentayl and sufentanil are used widely as induction agents. And as supplements to general anesthetics to reduce anethetic requirements. Has a MAC-sparing effect
Cardiac effects of opioids in anesthesia?
Bradycardia, but CO and organ perfusion still maintained.
Respiratory effects of opioids in anesthesia?
High doses result in respiratory depression and significant chest wall and jaw rigidity, so severe that usually requires muscle relaxant to permit intubation
Which glutamate receptor do some anesthetics target?
NMDA (as opposed to AMPA and Kainate, which are also ionotropic), and not metabotropic glutamate receptors either.
Structure of the NMDA receptor?
Transmembrane, glutamate-activated, calcium channel, a pentamer of NR1 (2) and NR2 (3) subunits.
How do anesthetics targeted at NMDA receptor control pain?
They are antagonists at the NMDA receptors which are associated with many systems including learning and memory, and in spinal cord, help pain transmission.
What clinical effects to NMDA antagonists have in anesthesia?
Sedation, immobility, amnesia, analgesia, feeling of disociation from environment. Hence the name “dissociative anesthetics”
What is Ketamine?
IV anesthetic. A dissociative anesthetic (NMDA antagonist, like PCP). Has pressor effects, and only IV total anesthetic.
Onset and duration of action of ketamine?
NMDA antagonist. 45 seconds, lasting 10-15 minutes. Analgesia lasts 40 minutes and is accompanied by amnesia.
Cardiac effects of Ketamine?
Increased BP, cardiac output.

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