Brain and Behavior Flashcards

Question

Amoxapine

Answer 1

Tetracyclic and Unicyclic Agents Rapidly absored with mean protein binding of 85%. **Its metabolite is a potent D2 blocker and has antipsychotic effects** NET inhibitor and less potent SERT inhibitor. Anticholinergic effects and moderate inhibitor of postsynaptic D2 receptor (antipsychotic properties) Adverse effects: **associated with parkinsoniam syndrome due to D2 block** Amoxapine and maprotiline are substrates to CYP2D6 and should not be used with inhibitors such as fluoxetine.

Answer 2

Tetracyclic/ Unicyclic

Answer 3

irreversible, nonselective MAOI More sedating than either selegiline or trancypromine

Answer 4

irreversible, nonselective MAOI prolonged inhibition

Answer 5

irreversible MAO-B agent at low doses Treat Parkinson's disease at low doses and becomes nonselective MAOI at higher doses.

Answer 6

Antidepressant action: hyperforin inhibits reuptake of serotonin, NE, and DA in vitro. Also upregulates the 5-HT2 receptor in rodent model. IL-6 production is reduced and GABA binding using commercial extract. Also used for Premenstrual dysphoric disorder, climacter complaints, somatoform disorders, and anxiety. Photoacticated hypericin used to investigationally treat HIV and basal/ squamous cell carcinoma and inhibits other virus Adverse: photosensitization due to hypericin and pseudohypericin so sunscreen and eyewear should be used. Hypomania, mania, arousal.

Answer 7

SSRI Relatively free of pharmacokinetic interactions enatiomer of Citalopram

Answer 8

local anesthetic with peripheral sympathomimetic action via inhibition of transmitter reuptake at noradrenergic synapse amphetamine-like psychological effect that is shorter lasting and more intense than amphetamine Inhibits DA reuptake into neurons in the "pleasure centers" of the brain giving you a wild ride Cocaine is a hell of a drug Highly addictive (relative risk of 5/5). heated in an alkaline base to become "crack cocaine" which can be smoked producing an instant "rush" In PNS, inhibits voltage gated Na channels. In CNS, cocaine blocks reuptake of DA, NE, serotonin. The DAT block increases DA in nucleus accumbens is the rewarding aspect of the drug By blocking NET, causes increase in arterial pressure, tachycardia, ventricular arrhythmia Toxicities: intracranial hemorrhage, ischemic stroke, MI, seizures, coma, death

Answer 9

Indirect-Acting Sympathomimetic Displasces stored catecholamine transmitters. Important chiefly because of its use and misuse as a CNS stimulant Readily enters the CNS; effects mediated through the release of norepinephrine and dopamine

Answer 10

Indirect-Acting sympathomimetic Similar to amphetamine with a higher ratio of central to peripheral effects

Answer 11

Indirect-Acting Sympathomimetic amphetamine variant used in treatment of ADHD Blocks the reuptake of DA and NE into presynaptic neuron d- enantiomer is more active and can be given in short (3-5), intermediate (3-8), and long-acting formulations (10-12) High propensity for diversion and abuse (schedule II controlled substance)

Answer 12

Mixed-Acting Sympathomimetic A B-receptor agonist Used in over the counter decongestant medicine and has been abused in the synthesis of methamphetamine

Answer 13

Amphetamine-like Indirect-Acting Sympathomimetic normal by product of tyrosine metabolism and produced from diets rich in proteins Readily metabolized by MAO in liver and inactive when taken orally due to first pass effect. MOA: causes release of stored catecholamines (similar to NE MOA) \*contraindicated with MAOIs

Answer 14

Indirect-Acting Sympathomimetic psychostimulant with unclear MOA; it inhibits NE and DA transporters and increases synaptic concentrations of NE, DA, serotonin, and glutamate, while decreasing GABA. Treatment for ADHD. Improves wakefulness in narcolepsy. Potential use for appetite suppressant. Fewer negative side effects than other amphetamines (no mood changes, insomnia, abuse potential) Adverse: increase in blood pressure and heart rate

Answer 15

Indirect-Acting Sympathomimetic Catecholamine reuptake inhibitor selective inhibitor of NET. **Non-stimulant compound**. No increase in psychomotor activity. Does not induce DA release in the nucleus accumbens (unlike methyphenidate/ amphetamine) so it has a low potential for abuse Used to treat ADHD little cardiovascular effects due to clonidine (alpha2) like effects in CNS, but NE effects in periphery. However, may increase blood pressure in some patients. Adverse: orthostatic tachycardia, abdominal pain, decreased appetite, vomiting, nausea, diarrhea, dizziness and somnolence, and height/ weight percentiles declined in children. Contraindications: **MAOIs should not be used within two weeks of taking atomoxetine (fatal hypertensive crisis). Metabolized by CYP2D6 so dont use with potent CYP2D6 inhibitors like paroxetine/ fluoxetine.** Not a controlled substance

Answer 16

The D-enantiomer of Methylphenidate Given in half the dose of the parent drug, a racemic mixture

Answer 17

The D-enantiomer of Amphetamine

Answer 18

Pro-drug amphetamine consisting of a d-amphetamine covalently bonded to L-lysine. Hydrolysis breaks the drug apart Less potential for abuse and toxicity than amphetamine, although still a schedule II

Answer 19

Indirect-Acting Sympathomimetic (this class of drugs enter the sympathetic nerve ending and displace stored catecholamines; they also can inhibit the reuptake of neurotransmitters by interfering with NET and DAT) Adderall is the racemic form of amphetamine whereas dextroamphetamine is the d- enantiomer. CNS stimulant, marked effects on mood and alertness, and appetite depressant. Effects are mediated through the release of NE and DA Adverse effects: insomnia, anorexia, weight loss, motor or vocal tics and headaches, visual hallucinations and emotional lability, growth retardation. Use caution in those with alcohol/ drug abuse. Contraindications: Don't use with sympathomimetic compounds (will increase heart rate and blood pressure). MAOIs will cause hypertensive crisis. Phenobarbital, phenytoin, TCAs (amphetamine will inhibit the metabolism of these drugs). Causes pupillary dilation (alpha receptor) so don't use in closed-angle glaucoma.

Answer 20

Mixed-Acting Sympathomimetic Over the counter appetite suppressants but has been removed due to hemorrhagic strokes in young women. Can increase blood pressure in patients with impaired autonomic reflexes. Also a decongestant

Answer 21

Effective against all types of partial and tonic-clonic seizures but not absence seizures. Exerts anti-seizure effects without causing general depression of the CNS. MOA: slows the rate of recovery of voltage-activated Na⁺channels from inactivation. At low doses it is very selective, at high doses it may reduce spontaneous activity and enhance responses to GABA Kinetics: bound (90%) by serum proteins (mainly albumin). Small variations in the percentage of phenytoin that is bound dramatically affect the absolute amount of free (active) drug (increased in neonates, patients with hypoalbuminemia, and uremic patients). Phenytoin has a non-linear rate of elimination and can overwhelm the capacity of the liver to metabolize it, leading to disproportionate increases in plasma drug concentration following a small increase in dose. This is due to changing of metabolism from first order to zero order. Interactions: Interacts with valproate (increases free conc. of phenytoin) and warfarin (inhibits breakdown leading to bleeding disorders) Toxicity: Can cause cardiac arrhythmias on rapid administration, also can effect cerebellum at higher doses

Answer 22

First effective organic anti-seizure agent; relatively low toxicity and is easily affordable. Effective for generalized tonic-clonic and partial seizures. Not effective for absence seizures. Used to be used for anxiolytic properties, but at high doses becomes a hypnotic MOA: works through potentiation of synaptic inhibition through an action on the B-subunit of GABA_A receptor (**increases duration of currents, not frequency of firing**). At high doses, GABA is not needed to activate receptor Kinetics: does not reach peak concentrations in plasma until several hours following administration. Induces UDP-glucuronosyltransferase as well as CYP2C and CYP3A Toxicity: Sedation is most frequenct, nystagmus and ataxia occur at excessive dosage. Can cause irritability and hyperactivity in children, agitation and confusion in elderly. Has a low therapeutic index half life of 4-5 days

Answer 23

A primary drug of treating both simple and complex partial and tonic-clonic seizures; also used for trigeminal neuralgia Related to the tricyclic antidepressants. MOA:Same as phenytoin, limits the repetitive firing of action potentials by slowing the rate of recovery of Na⁺channels from inactivation. Kinetics: Complex; influenced by limited aqueous solubility. Slowly and erratically absorbed after oral administration. Peak plasma concentrations can occur 24 hours following dosage. Induces CYP2c, CYP3A, and UGT (like phenobarbital) which induces its own breakdown Toxicity: Acute intoxication leads to stupor/coma, hyperirritability, convulsions, and respiratory depression. Long-term therapy lcan lead to drowsiness, vertigo, ataxia, diplopia, and blurred vision. Frequency of seizures may increase with overdosage. **Watch for aplastic anemia** Mood stabilizer: can be used as an alternative to lithium when it is not efficacious. MOA unclear

Answer 24

Primary agent for treatment of absence seizures MOA: reduces low threshold Ca2+ currents (T-type currents) in thalamic neurons (thalamus is important for absence seizures). Kinetics: Complete absorption, peak concentrations around 3 hours following dosage (more predictable than Carbamazepine) Toxicity: GI complaints and CNS effects (drowsiness, lethargy, euphoria, dizziness, headahe, and ?hiccough) Several deaths have resulted from bone marrow depression

Answer 25

Effective against **absence**, partial, and tonic-clonic seizures Drug of choice for myoclonic seizures MOA: slows recovery from inactivation of Na channels (like phenytoin) and at slightly higher doses produces reductions of T-type Ca²⁺ currents (like ethosuximide). It may also generally increase GABA levels by preventing breakdown Kinetics: Absorbed rapidly and completely, broken down by CYP2C9 and CYP2C19 Toxicity: Transient GI symptoms (anorexia, nausea, and vomiting) CNS (sedation, ataxia, tremor). A rare complication is potentially fatal fulminant hepatitis. Can also caused neural tube defects Interactions: Displaces phenytoin from albumin, slows metabolism of phenytoin and phenobarbital Mood stabilizer: antimanic effect like lithium. **First line treatment for mania although only lithium is used for maintenance therapy.**

Answer 26

Used primarily for sedative-anti-anxity drugs. MOA: enhance GABA-mediated synaptic inhibition by **increasing frequency, but not duration**, of GABA_A channel openings. Causes hyperpolarization of target neurons. Toxicity: drowsiness and lethargy occur in 50% of patients initially, but tolerance often develops. Used for treatment of absence seizures as well as myoclonic seizures in children. Diazepam is used for treatment of status epilepticus, not used for treatment of seizure disorders. Used for catatonic forms of schizophrenia. Clonazepam used for mild bipolar affective disorder. Allosteric modulators (GABA has to be present for this agonist to work)

Answer 27

Effective for partial seizures Gabapentin is also used for treatment of migraine, chronic pain, and bipolar disorder Anti-seizure drugs that consist of a GABA molecule covalently bound to a lipophilic cyclohexane ring or isobutane, respectively. Gabapentin was designed to cross the BBB MOA: Neither mimic GABA when iontophoretically applied to neurons in primary culture. Effects may be mediated by alpha2delta-1 protein Toxicity: well-tolerated, may lead to somnolence, dizziness, ataxia, and fatigue Kinetics: not metabolized, not protein bound, excreted unchanged in the urine

Answer 28

A phenytriazine derivative used for partial and secondarily generalized tonic-clonic seizures in adults and Lennox-Gastaut syndrome in both children and adults Like valproate, can be used for any type of seizure MOA: Same as phenytoin and carbamazepine, but is effective against a broader spectrum of seizures Toxicity: dizziness, ataxia, blurred or doublt vision, nausea, vomiting, and rash. A few cases of Stevens-Johnson syndrome and DIC have been reported

Answer 29

Used as add-on therapy of refractory partial seizures with or without secondary generalization MOA: inhibits the GABA transporter, GAT-1, and thereby reduces GABA uptake into neurons and glia Toxicity: can cause seizures in patients without seizure disorders. Principal adverse effects are dizziness, somnolence, and tremor Contraindicated in patients with generalized absence epilepsy

Answer 30

Used for partial-onset or primary generalized tonic-clonic seizures, for Lennox-Gastaut syndrome in patients 2 years of age and older, and for migraine headache prophylaxis in adults. MOA: Similar to phenytoin, plus it activates a hyperpolarizing K⁺ current, enhances postsynaptic GABA_A-receptor currents, and limits activation of the AMPA-kainate-subtypes of glutamate receptor. Can lead to increased breakdown of oral contraceptives (can cause unwanted pregnancies) Toxicity: well tolerated. Has been associated with cognitive impairment and patients may complain about a change in the taste of carbonated beverages

Answer 31

Approved as adjunctive therapy of partial seizures in adults, not effective against myoclonic seizures MOA: inhibits the T-type Ca2+ currents, also has a similar one to phenytoin and carbamazepine Well tolerated, but 1% of patients developed renal calculi

Answer 32

1. The less drugs, the better. Avoid multi-drug therapies if you can 2. After 2 years of being seizure free, taper off the drugs Failure can be brought by using the wrong drug for the type of siezure, drug interactions, drug induced toxicity leading to non-compliance, and unusual pharmacokinetics (like with phenytoin)

Answer 33

Primidone is metabolized to phenobarbital and phenylethylmalonamide. Although metabolized to phenobarbital, the MOA is closer to phenytoin It is used against partial seizures and generalized tonic-clonic seizures Drowsiness occurs when initial dose is too large

Answer 34

Dopamine-receptor antagonist Aliphatic derivative antipsychotic side effects: sedation and weight gain, orthostatic hypotension and tachycardia, seizures Pharmacokinetics: significant first pass metabolism. Oral doses have systemic availability of 25-35%. Metabolites may be excreted in urine weeks after last dose was administered. D2 blockade may occur 3-6 months after last injection. Adverse actions are traced to blocking effects at alpha adrenoceptors, muscarinic, H1, and 5-HT2 receptors. Least amount of EPS in the phenothiazine class Inexpensive

Answer 35

piperidine derivative antipsychotic (more potent than chlorpromazine, but not necessarily more efficacious) side effects: sedation and weight gain, orthostatic hypotension and tachycardia, abnormal EEG recordings, overdoses are fatal Pharmacokinetics: significant first pass metabolism. Oral doses have systemic availability of 25-35%

Answer 36

- Antipsychotic that blocks post-synaptic D2 receptors (D2 receptor antagonist)

Answer 37

Typical Anti-psychotic Dopamine-receptor antagonist decreased tardive dyskinesia (most important unwanted effect of antipsychotic drugs, similar to choreoathetosis). parenteral form also available

Answer 38

Dopamine-receptor antagonist Butyrophenone derivative antipsychotic most widely used typical antipsychotic drug, despite its **high level of EPS** (extrapyramidal side effects which is a blockade of D2 receptors in nigrostriatal pathway (voluntary movement) and typically EPS occurs when a DA antagonist binds to about 80% of D2 receptors ) **Used to treat Tourette's syndrome** more potent and fewer autonomic effects than phenothiazines (chlorpromazine and thioridazine) Pharmacokinetics: less first pass metabolism than chlorpromazine/ thioridazine; availability of 65%

Answer 39

Inverse agonist of 5-HT2A receptor (blocks consitutive activity); these receptors modulate the release of DA, NE, Glu, GABA in limbic, striatum, and cortex. Adverse: elevations of prolactin Can be used to treat Tourette's

Answer 40

Atypical Antipsychotic (generalization: most atypical antipsychotics inhibit 5-HT2A receptors just as well as they do D2) Clozapine is the prototype atypical antipsychotic: the class in general mostly act as partial agonist at 5-HT1A receptor which produces synergistic effects with the 5-HT2A receptor antagonism Relapse after discontinuation is rapid and severe. Should never be discontinued abruptly (adverse effects of myocarditis and **agranulocytosis**-must get blood counts every week for 6 months); seizures in 2-5%, **severe weight gain** only atypical antipsychotic used to reduce risk of suicide

Answer 41

Atypical Antipsychotic This goes for Clozapine as well: they both are more efficacious than other antipsychotics that block D2 because they only have to bind the about 30-50% of the receptors. Most others need to bind 60% of D2 receptors for effect. This may be due to their concurrent occupancy of 5-HT2A receptors. Olanzapine, quetiapine, and aripiprazole cause no increase in prolactin and less EPS, reflectinga diminished D2 antagonism adverse: **severe weight gain (like Clozapine)**; dose-related lowering of seizure threshold **treatment of bipolar disorder when used in combination with fluoxetine (SSRI)**

Answer 42

Atypical Antipsychotic low doses used to promote sleep short half life No weight gain

Answer 43

Atypical Antipsychotic Inverse agonist of 5-HT2A receptor (blocks consitutive activity); these receptors modulate the release of DA, NE, Glu, GABA in limbic, striatum, and cortex. **Can be used to treat bipolar disorder.** adverse: QT prolongation

Answer 44

Atypical Antipsychotic partial dopamine receptor agonist, but in the presence of endogenous DA it will act as a DA receptor *antagonist* Blocks postsynaptic D2 receptors in the CNS, especially in the the mesolimbic and striatal-frontal system. Does not cause EPS even though it binds D2 with high affinity- this is because it is a partial agonist.) Has been approved for treating bipolar disorder long half life and lower weight gain liability

Answer 45

ANS: loss of accommodation, dry mouth, difficulty urinating, constipation: muscarinic blockade. Also, because of alpha adrenergic blockade, orthostatic hypotension, impotence, failure to ejaculate. CNS: Parkinson's syndrome, akathisia, dystonia via DA receptor blockade. Endocrine: Amenorrhea-galactorrhea, infertility, impotence via DA receptor blockade (Dopamine keeps prolactin at low levels, an antagonist of dopamine leads to increased prolactin secretion) other: weight gain from H1 and 5-HT2 blockade

Answer 46

AKA Serotonin-DA Receptor Antagonists Includes: risperidone, olanzapine, quetiapine, clozapine, ziprasidone atypical because they have higher ratio of 5-HT2: D2 blockades than typicals. Blockade of 5-HT2 modulates DA neurons in nigrostriatal, mesolimbic, and mesocortical pathways. This is why there is less EPS and fixes negative symptoms of schizophrenia. any antipsychotic can treat positive symptoms (mesolimbic system) of schizophrenia, however, only atypicals can treat negative symptoms (mesocoritcal pathway) like inexpressive faces, blank looks, monotone and monosyllabic speech, few gestures, seeming lack of interest in the world and other people augments antidepressant effects in major depression used for acute mania and Tourette's disorder, reduces risk of suicide in schizophrenic patients suppresses the abnormal movements of tardive dyskinesia Interactions b/t DA and Serotonin systems: 2 mechanisms as to why there is less EPS. This is a summary of the mongraph: Mechanism 1: atypical antipsychotics bind D2 receptors with lower affinity than the typical antipsychotics so that when voluntary movement is initiated in nigrostriatal pathway, release of DA at synapse can outcompete the D2 receptor antagonists (atypical antipsychotic drugs) and stimulate the inhibitory DA neurons that will inhibit the indirect pathway so no parkinson's like symptoms and a net **excitation** will occur at caudate/ putamen) Mechanism 2: Serotonergic neurons in raphe nucleus talk to DA neurons of the substantia nigra pars compacta (part of the nigrostriatal pathway). These DA neurgons have 5-HT receptors on their dentrites/soma/ axon termimals. When serotonin binds these 5-HT receptors, an inhibitory effect is initiated so that less DA is released to the caudate/ putamen. Now, when atypical antipsychotics bind 5-HT receptor as an antagonist, this net inhibition is prevented and therefore a net **excitation** occurs.

Answer 47

Treatment for bipolar disorder and recurrent endogenous depression, schizoaffective disorder, and unipolar depression Inhibits inositol signaling and glycogen synthase kinase-3. Reduction in PIP2 so not IP3 and DAG made. Manic episodes are associated with an increase in these messengers. Also has been shown to inhibit NE sensitive adenylyl cyclase attributing to its antidepressant/ antimanic effects. pharmacokinetics: 6-8 hours for full absorption. no metabolism and virtually all of it is extreted in urine. half life of 20 hours. Renal clearance is reduced by about 25% by diretics (thiazide), newer NSAIDS adverse: nausea and tremor, ataxia, aphasia, decreased thyroid function (take serum TSH conc. every 6-12 months), diabetes insipidus (polydipsia), edema, bradycardia-tachycardia (contra-indicated due to T-wave flattening), acne Recurrent endogenous depression is controlled by lithium or imipramine

Answer 48

- Benzodiazepine used to treat Delirium Tremens in alcohol withdrawl emergencies

Answer 49

Benzodiazepine More of a sedative Active form of diazepam, prazapam, and chlorazepate half life of over 40 hrs is an active metabolite of diazepam

Answer 50

Benzodiazepine used for alchohol withdrawals causes less drowsiness due to short half life

Answer 51

used as sleep aid but causes daytime sleepiness due to biotransformation to active metabolites hypnotic Benzodiazepines decrease REM, stage 3 and 4 sleep and increase stage 2 (decreases latency)

Answer 52

rapid oral absorption. undergoes alpha hydroxylation and metabolites are metabolized rapidly. short half life of 3 hrs accounts for its use as hypnotic rather than sedative, but because of short half life, withdrawals occur the next day. Binds to GABA A receptor (like all **benzodiazepines**). Binds the BZ site which is between the alpha and gamma subunits. \*\*Very important concept about benzodiazepines: they do not substitute for GABA; they allosterically enhance GABA's effects resulting in an increase in the *frequency* of channel opening events.

Answer 53

anxiolytic drug used for treatment of panic disorder and agoraphobia more toxic in overdose than other benzodiazepines

Answer 54

Hypnotic lipophilicity allows entry into CNS. Rapidly metabolized to inactive metabolites via CYP450. half life of 1.5- 3.5 hrs A nonbenzodiazepine that binds GABA A receptor causing Chloride to rush in causing an IPSP. Binds at BZ site that has alpha 1 subunit decreases REM sleep but minimal effects (increases) on slow-wave sleep. Shortens sleep latency and increases total time spent in sleep. Abrupt discontinuation causes rebound insomnia. Less risk of tolerance and dependence

Answer 55

Hypnotic lipophilicity allows entry into CNS. shorter half life than Zolpidem (1 hr) A nonbenzodiazepine that binds GABA A receptor causing Chloride to rush in causing an IPSP, GABA does not have to be present. Binds at BZ site that has alpha 1 subunit decreases latency of sleep with no effect on total sleep time. less amnesia or day after somnolence than zolpidem or benzodiazepines.

Answer 56

herbal remedy useful as sedative-hypnotic and anxiolytic most biological activity is attributed to sesquiterpene Used for treating *mild* insomnia by reducing sleep latency (time it takes to fall asleep) adverse: withdrawals similar to benzodiazepines when taken long term in high doses, migraine and GI effects, dizziness (these adverse were only seen in a few patients from small trials) more effective when used over the course of time instead of acutely

Answer 57

melatonin receptor agonist used as a hypnotic. Binds MT1 and 2 receptors in suprachiasmatic nuclei No associated dependence Associated with endocrine changes rapidly absorbed orally and undergoes extensive first pass metabolism Contraindicated with inhibitors of CYP1A2 (ciprofloxacin, fluvoxamine) or fluconazole. CYP inducer Rifampin will reduce its levels.

Answer 58

Hypnotic absorbed rapidly into blood following oral administration. lipophilicity allows entry into CNS. half life of 6 hours and metabolized by CYP3A4 A nonbenzodiazepine that binds GABA A receptor causing Chloride to rush in causing an IPSP. Binds at BZ site that has alpha 1 subunit increases total sleep time. less amnesia or day after somnolence than zolpidem or benzodiazepines (unusual because it can increase stage 2 sleep). At high doses it decreases REM sleep

Answer 59

barbituate very lipid-soluble, penetrates brain and useful for anesthesia but has been largely replaced by propofol. Should not be used in patients with acute intermittent porphyria Does not produces analgesia (might even cause hyperalgesia) Decreases blood pressure on infusion (but not as bad as propofol) Accidental injection into arterial circulation results in excrutiating pain, intense vasoconstriction, and can lead to gangrene

Answer 60

Like most **barbituates**, they get metabolized by hepatic enzymes and little drug remaines unchanged when excreted half life of 18-48 hours In normal barbituate fashion, Secobarbital binds GABA A receptor but barbituates only bind to alpha 1 receptor so they are more selective in action. \*\*Very important concept for barbituates: they increase the *duration* of GABA channel openings, They can activate the channels at high concentrations. \*Absolutely contraindicated in patients with porphyrias due to enhancement of porphyrin synthesis. - Used to treat insomnia and make one sleepy/less anxious before surgical procedures

Answer 61

slow-onset anxiolytic agent No sedative, hypnotic or euphoric effects. Unlike benzodiazepines, Buspirone has no anticonvulsant or muscle relaxant properties. Acts on 5-HT1A and D2 receptors No rebound anxiety or withdrawal from discontinuance. Used in general anxiety states but not in panic disorders Rapidly absorbed orally and undergoes extensive first pass metabolism. half life of 2-4 hours. Toxicities: chest pain, tachycardia, palpitations, dizziness, nervousness, tinnitus, GI distress, paresthesias, pupillary constriction.

Answer 62

synthetic benzodiazephine derivative. Serves as an antagonist at GABA A receptor, blocking the actions of benzodiazepines, eszopiclone, zaleplon, and zolpidem; does not block effects of barbituates and alcohol. used as treatment of benzodiazepine overdose acts rapidly but has short half life of about an hour due to hepatic clearance, this is important for getting people awake from benzodiazepine anesthetics. Adverse effects: agitation, confusion, dizziness, nausea. seizures and cardiac arrhythmias if previously taken TCAs + benzodiazepines

Answer 63

Sedative: antianxiety and calming effects Hypnotic: drowsiness and state of sleepiness These agents cross placenta and cause respiratory depression in fetus

Answer 64

Most frequently administered drug for induction of anesthesia (has replaced barbituates) Kinetics: allows for continuous infusions, used during maintenance of anesthesia. Poorly water soluble, formulated as an oil emulsion that can lead to allergic reactions. Rapidly metablized in the liver, metabolites excreted in kidneys. Extrahepatic metabolism is thought to occur in the lungs (up to 30%). Elimination is like other IV anesthetics: redistributed from highly perfused (brain) to less-well-perfused (skeletal muscle) compartments. MOA potentiation of the chloride current mediated through the GABA_A receptor complex Acts as a hypnotic without analgesic properties, causes pronounced decrease in systemic blood pressure due to vasodilation in both arterial and venous circulations, causes apnea after an induction dose, and can lead to tachycardia in the case of propofol infusion syndrome.

Answer 65

Unique among the group of IV anesthetics in that their action can readily be terminated by adminstration of their selective antagonist, flumazenil Highly lipid-solube; rapidly enter CNS Midazolam is considered to have a slower effect-site equilibration than propofol. It also has the shortest context-sensitive half-life, meaning it is the only one of the three benzodiazepines suitable for continuous infusion. Cuases decrease in systemic blood pressure, minimal depression of ventilation (although transient apnea may follow rapid IV administration), may produce pain on injection Lorazepam has a slow onset and prolonged duration that limit its usefulness for preop medication or induction of anesthesia Midazolam is the most commonly used oral premedication for children

Answer 66

IV anesthetic with hypnotic but not analgesic effects and is often chosen for its minimal hemodynamic effects. Endocrine side-effects limit its use for continuous infusions MOA: appears to have GABA-like effects and seems to act primarily through potentiation of GABA_A mediated chloride currents, like most other IV anesthetics. Because of etomidate's minimal effects on hemodynamics and short context-sensitive half-time, larger doses, repeated boluses, or continuous infusions can safely be administered May cause myoclonic activity in 50% of patients, causes cardiovascular stability after bolus injection, less pronounced respiratory depressive effects compared to barbituates, but causes adrenocortical suppression by inhibiting 11B-hydroxylase, an enzyme necessary for the conversion of cholesterol to cortisol Not used as a continuous infusion Often used in patients with compromised myocardial contractility

Answer 67

IV anesthetic that produces significant analgesia. MOA: complex, but associated with inhibition of the NMDA receptor complex Ketamine is the only IV anesthetic that has low protein binding. When using this drug, the patient's eyes remain open and they drool. Ketamine increases cerebral blood flow, and can increase systemic blood pressure, heart rate, and cardiac output Can be administered by multiple routes (IV, IM, oral, rectal, epidural) which is good for uncooperative patients

Answer 68

Prototypical opiod agonist. Full agonist at the mu opioid receptor, the major analgesic receptor. * generally*, opioids act at receptor coupled to G proteins; they inhibit the influx of Calcium and reduce neurotransmitter release; secondly, they hyperpolarize and thus inhibit postsynaptic neurons by opening potassium channels. Most opioids are well absored in all routes, but b/c of first-pass effect, a higher oral dose needs to be given Conjugated into morphine-3-glucoronide and has neuroexceitatory effects at GABA/glycinergic system. 10% gets converted to morphine-6-glucoronide which has potent analgesic properties. These metabolites dont cross BBB and do not contribute to CNS effects of morphine slow release morphine (oxycontin) is good for treating chronic constant pain Tolerance and dependence MOA: Simple up-regulation of cAMP system doesn't explain it, so two hypothesis are presented; 1.) **Receptor recycling**: endogenous opioids bind their receptors and cause endocytosis and eventual recycling to plasma membrane. Morphine doesn't result in endocytosis whereas methadone does (which is used in treating opioid dependence. 2.) **Receptor Uncoupling: ** binding of opioid to receptor is normally linked to G protein. When this is no longer the case, tolerance and dependence can result. NMDA antagonists like ketamine can block this tolance mechanism. CI: kidney failure, Probenecid can increase metabolites and cause unwanted effects Adverse (for most opioids): disrupts REM and non-REM sleep, respiratory depression, sedation, euphoria, cough suppression, nausea/vomiting, temperature disregulation, miosis

Answer 69

diacetylmorphine is metabolized to morphine rapidly hydrolyzed by esterases to monoacetylmorphine and then morphine which is then conjugated to glucoronic acid when given intramuscularly, more effective in relieving severe chronic pain than morphine. potent and fast acting, but prohibited in USA Users describe a "rush" comparable to sexual orgasm, taste, warmth. Cant distinguish between effects of hydromorphone adverse: hypothalamic-pituitary tract messed up, abnormal menstruation, withdrawal symptoms in between dose Toxicities: death, endocarditis, pulm infections like TB

Answer 70

Oxycodone + Aspirin = **Percodan** Oxycodone + Acetominophen = **Percocet** partial mu opioid receptor agonist reduced first pass metabolism (oral) metabolism by CYP2D6, resulting in strong metabolites; codeine is demethylated to morphine. Oxycodone metabolites can accumulated in patients with renal failure. Antitussive: suppress cough

Answer 71

Hydrocodone + Acetaminophen = Vicodin or Lortab Hydrocodone + Ibuprofen = Vicoprofen metabolism by CYP2D6, resulting in strong metabolites

Answer 72

Opioid gets metabolized by conjugation to H3G which has CNS excitatory properties rectal suppositories are available Hydrocodone is metabolized into hydromorphone via CYP2D6

Answer 73

strong opioid agonist used in treating severe pain. Oxycodone is metabolized via CYP2D6 into oxymorphone and so ultra rapid metabolizers need less of a dose.

Answer 74

Adverse: truncal rigidity is especiially prominent If GI disturbances prevent the use of sustained release morphine (oxycontin), Fentanyl transdermal patch can be used. available via buccal transmucosal route, as a lollipop lozenge Can be used as a primary anesthetic for surgical procedures

Answer 75

Opioid MOR agonist yielding strong analgesic effects. Hepatic oxidative metabolism is main route kinetics. first-pass metabolism results in 50% of dose having an effect. Adverse: A demethylated metabolite, normerperidine, can cause seizures; negative ionotropic action of the heart; tachycardia; peak respiratory depression 1 hr after administration; tremors. Can block reuptake of serotonin so can cause serotonin syndrome if used with some drugs. CI: SSRI, TCAs, MAO, Chlorpromazine less neonatal depression when used during labor

Answer 76

- Opiod agonist: weak opioid agonist, binding primarily to mu opiod receptors, producing analgesia and other CNS effects

Answer 77

Centrally acting analgesic. MOA based on blockade of serotonin reuptake. inhibits NET weak mu receptor agonist adverse: seizures, serotonin syndrome (esp with SSRI) May serve as an adjunct with pure opioid agonist in the treatment of chronic neuropathic pain CI in patients taking SSRIs for same reason as meperidine (SERT)

Answer 78

mixed opioid agonist-antagonist; agonist effect at one receptor and an *antagonist* effect at another strong kappa receptor agonist and mu antagonist. At higher doses, there appears to be a ceiling to the respiratory depressant effect although it is resistant to naloxone reversal

Answer 79

mixed opioid agonist-antagonist, kappa agonist; weak mu antagonist/ partial agonist Contraindication: weak partial agonist like pentazocine should never be used in a patient receiving a full agonist (morphine); diminishes analgesia and induces a state of withdrawal the oldest mixed agent around. used orally or parenterally. Injection not recommended due to irritant properties

Answer 80

preference for kappa opioid receptor; may cause greater analgesia in women; can cause dyphoric reactions and reduced potency from other opioids Currently, the only opioid available in USA in a nasal formulation produces more sedation than nalbuphine/ buprenorphine but similar analgesia

Answer 81

mixed agonist-antagonist: binds mu receptor with high affinity and possibly used to treat withdrawal, and it also binds kappa and delta receptors antagonistically. partial mu agonist/ kappa antagonist Combined with naloxone as a treatment plan for addiction. In high doses, it acts as a mu antagonist, limiting its analgesic properties; extremely dangerous to combine this with benzodiazepines or other CNS depressants sublingual administration is favored to avoid first-pass metabolism. long duration of action due to slow dissociation from mu receptors and resistant to naloxone reversal Subutex is sublingual buprenorphine. Suboxone is buprenorphine combined with Naloxone, which inhibits patients from crushing up the Buprenorphine and injecting it. Naloxone blocks subjective high, but not when taken orally as perscribed. Buprenorphine produces minimal withdrawal symptoms when suddenly discontinued and has a low potential for overdose, long duration of action, and can block heroin's effects. Good long-term treatment plan.

Answer 82

NMDA receptor antagonist free of addictive properties and produces less constipation than codeine. Antitussive and available in over the counter preps Enhances the angalgesic effects of morphine and lowers the tolerance associated with opiates. d,m Toxicities: powdered form can be abused and leads to death Dissociative drug:

Answer 83

allyl substitution and hydroxylation of a full opioid agonist results in this strong mu receptor *antagonist* Antagonist precipitated withdrawal: administer naloxone and within 3 minutes, signs and symptoms similar to those seen in abrupt discontinuance of opiates appear for about an hour IV injection reverses coma due to opioid overdose when administered to a morphine-treated paitent, the antagonist effects reverse morphine in 1-3 minutes. Short acting effects so need to monitor patient for relapse a few hours later.

Answer 84

CNS depressant, but also a stimulant in terms of suppression of inhibitory systems adverse: impairs recent memory, blackouts, etc cross-tolerance with benzodiazepines is important to know: high blood alcohol levels + benzos can be life threatening. Acts on many receptors including GABA_A and NMDA. ENT1 receptor may be involved in dependence Withdrawal: 6-12 hours after heavy drinking may have tremor of hands, nausea, vomiting, sweating, anxiety. 12-24 hours manifest generalized seizures. 48-72 hours delirium tremens-person hallucinates and shows evidence of autonomic instability and death in 5-15% treatment: benzodiazepines like oxazepam/ lorazepam

Answer 85

agonist at nicotinic acetylcholine receptor Rewarding aspect of nicotine due to nAChR expressed on DA neurons in VTA and DA is released into nucleus accumbens and prefrontal cortex. Nicotine withdrawal is mild compared to opioids and involves irritability and sleep problems. Relapse very common. Treatment: cystine and **Varenicline** work by occupying nAChRs on DA neurons of the VTA, thus preventing nicotine from exerting its action. Varenicline may impair ability to drive and cause suicidal ideation. Buproprion also approved for nicotine cessation, but seems less effective than Varenicline

Answer 86

"Ecstasy" produces feelings of intimacy and empathy without impairing intellectual capacities distributed in "raves" and taken orally Causes release of biogenic amines by reversing the pumps, especially SERT (similar moa to amphetamines). With repeated doses serotonin may become permanently depleted toxicities: hyperthermia + dehydration (due to dancing at the rave) may be fatal, serotonin syndrome (mental status change, ANS hyperactivity, neuromuscular abnormalities), seizures. To compensate for dehydration, dancers will drink too much water and cause hyponatremia, seizures, and death.

Answer 87

activates G_IO coupled receptors mu receptors are on and inhibit GABAergic neurons causing euphoria whereas kappa receptors inhibit dopaminergic neurons and so cause dysphoria. Treat withdrawals with clonidine and methadone. Methadone is a long acting agonist

Answer 88

Exogenous cannabinoids. THC is the main psychoactive substance. Disinhibition of DA neurons, by presynaptic inhibition of GABA in the VTA. half life is 4 hours Hashish is super potent and you can hallucinate there are withdrawals to marijuana: relessness, irritability Dronabinol and Nabilone (older) are THC analogs

Answer 89

chemical vapors like nitrates, ketones, aliphatic/ aromatic hydrocarbons. agents inhaled by "sniffling" "huffing" or "bagging" Sniffing is inhaling an open container; huffing refers to soaking a cloth in volatile substance before inhalation; bagging to breathing in and out of a paper or plastic bag filled with fumes Nitrous oxide binds NMDA receptors and fuel additives enhance GABA_A produces euphoria; increased VTA excitation is reason for toluene addiction risk. amyl nitrite "poppers" produce smooth muscle relaxation Toxicities: lesions in white matter of CNS

Answer 90

dissociative anesthetic. only ketamine is still used as anesthetic feeling of separation of mind and body. Psychedelic effects last for about an hour at high doses, out of body "near death" experiences, causes stupor and coma, hypertension, impaired memory, visual alterations "club drug" PCP goes by "angel dust" "Hog" and Ketamine by "special K" non-competitive antagonist at NMDA receptor, which is present on inhibitory neurons white crystal powders but in streets they are sold in liquid, capsules, pills which can be snorted, ingested, injected, or smoked.

Answer 91

hallucinogens; they alter consciousness and induce perceptual symtoms, including color and shape distortion Causes dizziness, nausea, paresthesias, blurred vision, and flashbacks from previous drug exposures Not associated with dependence or addiction. Doesn't target mesolimbic DA system; it hits the cortical and thalamic circuites . MOA: activates serotonic 5-HT_2A receptor in prefrontal cortex, enhancing glutamatergic signals onto pyramidal neurons, enhancing perception. LSD can induce abortion

Answer 92

Club drug, roofies A benzodiazepine that binds GABA_Areceptor and causes sedating effects. When combined with ethanol, anterograde amnesia occurs as well as an inability to protect from sexual assault. Commonly used in raves. Associated with the same level of tolerance as other benzodiazepines

Answer 93

produced during the metabolism of GABA used to treat narcolepsy; GHB decreases daytime sleepiness causes euphoria, enhanced sensory perceptions, social closeness, amnesia so its a popular "club drug" "liquid ecstasy" "grievous bodily harm" "date rape drug" reaches maximal concnetration after 30 minutes and half life is 30 min addictive

Answer 94

Also known as Antabuse Treatment of alochol dependence by inhibiting acetaldehyde dehydrogenase and therefore preventing alcohol metabolism. Unpleasant rxn if alcohol is consumed. Patient compliance is the hardest part of treatment. Alcohol isn't fun while taking Disulfuram, so why am I taking it?

Answer 95

Used to reduce cravings of opioid addicts mu opioid receptor antagonist and partial agonist is FDA aproved for both opioid and alcohol addiction by modulating endogenous opioid system. Makes drinking alcohol less rewarding

Answer 96

Antagonist of NMDA glutamate receptors May interfere with synaptic plasticity that depend on NMDA receptors and useful for treating alcoholism. Toxicities: allergic rxn, arrhythmia, change in blood pressure, impotence Somehow acts on the GABA system. Used to get alcoholics off alcohol without withdrawals

Answer 97

Used to treat opioid dependence slow acting agonist of mu opioid receptor similar effects to morphine/heroin but less psychoactive, and still has potential for abuse and overdose half life ranges 4-130 hours toxicities: respiratory depression, constipation, depression, withdrawal symptoms (but not as severe as other opioids)

Answer 98

**dependence** is physical dependence. Withdrawal syndrome defines dependence. Tolerance and withdrawal are associated terms with dependence. * Tolerence:* doses of drugs have to be increased over time as the patient gets used to them. Can occur by reduction of drug concentration or mu receptor functional changes. Unfortuante because undersirable side effects like respiratory depression dont show tolerance. * Withdrawal:* adaptive changes once drug exposure is terminated. mu receptor activation causes inhibition of adenylyl cyclase. once drug is terminated, compensatory increase in cyclases causes negative dysporia. Also, overproduction of cAMP causes increase CREB, causing increased transcription of dynorphin. This dynorphin then leads to decreased DA release in Ventral tegmentum. **addiction** is psychological dependence. Consists of compulsive, relapsing drug use despite engative consequences, triggered by cravings and cues. MOA: mesolimbic dopamine system. VTA projects to nucleus accumbens, amygdala, hippocampus, and prefrontal cortex. Drugs of abuse cause DA release into these areas and activate the mesolimbic system. Relapse is much more common in addicts after a successful withdrawal when they are no longer dependent. Basically, addiction is much more harder to fix than dependence

Answer 99

alpha 2 adrenergic agonist that decreases NE from locus ceruleus the withdrawals effects seen from opioid addiction stems from the loss of suppression of the locus ceruleus: vomiting, cramps, sweating, tachycardia, hypertension. clonidine reverses this

Answer 100

Phenytoin: CNS depression, arrhythmias Carbemazepine: Drowsiness, stupor, coma, convulsions, respiratory depression, aplastic anemia Valproate: GI symptoms, sedation Ethosuximide: GI symptoms, drowsiness, lethargy Primidone, Clonazepam, Diazepam, Phenobarbital: drowsiness Gabapentin: somnolence, fatigue (mild) Lamotrigine: Dizziness, GI symptoms (mild) Topiramate: somnolence, weight loss (mild) Tiagabine: dizziness, tremor, somnolence (mild) Zonisamide: somnolence, fatigue (mild)

Answer 101

5-HT_1B/1Dreceptor-selective agonist Constriction of incranial blood vessels is effective in treating **acute** migraine attacks (with or w/ out aura) Decreases nausea and vomiting of migraine Classified as a triptan (indole derived) which is limited to 5-HT₁ receptors MOA: By constricting blood vessels of the arteriovenous anastomoses, shunts are closed and cerebral hypoxia and ischemia is mitigated. May also block the release of proinflammatory neuropeptides in the nerve terminal of perivascular space. Reaches peak concentration in 12 minutes (subcutaneously) or 1-2 hours (orally). Bioavailability of 97% subQ. Half life of 1-2 hours. Metabolized by MAO-A Adverse: coronary artery vasospasm, myocardial ischemia, MI, irritation at site of injection, bitter taste (nasal spray). Orally: paresthesia, fatigue, pain in chest, drowsy, dizzy, nausea Contraindicated in serious cardiovascular diseases, hemiplegic or basilar migraines, hypertension

Answer 102

Ergot and Ergot alkaloids in general are partial agonists or antagonists at DA, adrenergic, serotonergic receptors Ergot is from a fungus that grows on rye/ other grains Extensive first-pass metabolism. Oral administeration may result in undetectable levels. 90% of metabolites are excreted in bile. half life of 2 hours and vasoconstriction lasting 24 hours. Acute anti-migraine effects by acting as 5-HT_1B/1D agonists, similarly to Sumatriptan Not to be used in patients with frequent, moderate migraine or infrequent, severe attacks. Only for acute migraines Sublingual tablet, nasal spray, solution for injection, and ergotamine with caffeine as both oral and rectal suppositories. Adverse: nausea, vomiting (CNS emetic centers), leg weakness, muscle pain, numbness/ tingling in fingers and toes, coronary vasospasm, edema and itching in hypertensive patient. CI in pregnant women, peripheral vascular disease, coronary artery disease, hypertension, impaired renal or liver function, sepsis. Don't use within 24 hrs of sumatriptan.

Answer 103

Muscarinic Receptor Antagonist Benztropine: antagonist at M receptor in basal ganglia Improves the rigidity and tremor of parkinsonism but has little effect on bradykinesia Start at low dose and gradually increase until therapeutic effects are noticed. When coming off the medication, do it slowly to prevent acute exacerbation of parkinsonism. Adverse: Poorly tolerated by the elderly, dyskinesia, acute suppourative parotitis due to dryness of the mouth, and other typical antimuscarinic effects.

Answer 104

Acyclic guanosine derivative used against HSV-1, HSV-2, and VZV but 10X more potent against Herpes Simplex than Varicella. MOA: requires 3 phosphorylation steps for activation: converted to monophosphate by **viral** thymidine kinase, then to the di- and triphosphate compounds by **host** cell enzymes. Acyclovir triphosphate then inhibits viral DNA by competing with deoxyGTP for viral DNA polymerase (makes an irreversible complex), and chain termination following incorporation of acyclovir into viral DNA. low oral bioavailability. Cleared by kidney. half life of 2.5- 3hrs in normal renal function shortens duration of genital herpes by 2 days, time of lesion healing takes 4 days, duration of viral shedding is 7 days, and decreases sexual transmission. In VZV, high doses required to decrease number of lesions IV route is used for herpes simplex encephalitis, neonatal HSV Resistance: viral alteration of thymidine kinase of DNA polymerase Adverse: nausea, diarrhea, heache, IV associated with reversible renal toxicity, tremors, delirium, seizures

Answer 105

Passive Immunization protection usually lasts for 1-3 months Largely IgG (95%) Specific immune globulin ("hyperimmune") preparations are available for rabies. Pooled from donors who are selected for high titers of desired antibodies.

Answer 106

Volatile anesthetic (has low vapor pressure and thus high boiling points so that liquid at room temperature/ sea-level pressure) The driving force for an inhaled anesthetic is the alveolar concentration. This concentration changes based on *inspired concentration or partial pressure,* and *alveolar ventilation* Medium rate of onset and recovery Solubility is 2X and 10X more than nitrous oxide in brain tissue and blood, respectively. Therefore, elimiantion and recovery is less rapid. Hepatotoxicity (halothane hepatitis): adverse: more severe depression of normal cardiac contractility than others 40% of halothane is metabolized so that elimination occurs more quickly than would be be expected based on tissue solubility.

Answer 107

Volatile anesthetic Medium rate of onset and recovery Not really metabolized unlike halothane. Even though enflurane's solubility is lower, it's eliminated more slowly. adverse: more severe depression of normal cardiac contractility than others. Only inhaled anesthetic with frank clinical seizures Toxicities: metabolites are nephrotoxic

Answer 108

Volatile anesthetic Medium rate of onset and recovery Isoflurane, sevoflurane, halothane, enflurane produce initial activation of EEG at low doses and subsequent slowing when given doses of 1.0-1.5 MAC. Isoflurane EEG is silenced at 2.0-2.5 MAC. Pungency makes it less suitable for patients with active bronchospasm better choice for patients with impaired myocardial function

Answer 109

Volatile anesthetic Rapid onset and recovery; unstable in soda-lime better choice for patients with impaired myocardial function Toxicities: metabolites are nephrotoxic

Answer 110

Gaseous anesthetic (high vapor pressure and low boiling point so gas at room temperature) No metabolism; incomplete anesthetic; rapid onset and recovery Can increase cerebral blood flow and increase intracranial pressure (SNS) Adverse: Reduces myocardial function in a concentration dependent manner. Toxicities: decreases methionine synthase, potentially causing megaloblastic anemia

Answer 111

Anesthetic potency is described by the minimum alveolar concentration (MAC) required to prevent a response to a surgical incision. Inhaled anesthetics decrease metabolic activity in the brain. Decreasing cerebral metabolic rate (CMR) reduces blood flow in the brain. Some volatile anesthetics actually increase blood flow in the brain. The net effect of either increased or decreased blood flow is what we are interested in. At 0.5 MAC, the reduction in CMR is greater than the vasodilation caused by the anesthetic, so net cerebral blood flow is decreased, a desirable effect. Increasing blood flow can be undesirable in patients with increased intracranial pressure. Anesthetics in general either cause increased *inhibition* by acting on GABA/ K channels, or they can decrease *excitation* through AMPA/ Kainate/ etc Three prinicipal components of anesthetics; immobility, amnesia, and consciousness

Answer 112

Stage 1-analgesia: the patient experiences analgesia without amnesia. Later on in stage 1, amnesia is produced Stage 2- excitement: patient appears delirous, may vocalize but is amnestic. Rapid respiration, heart rate and blood pressure increase. Duration and severity of this stage is shortened by rapidly increasing concentration of anesthetic. Stage 3- surgical anesthesia: slowing of respiration and heart rate and extends to complete cessation of spontaneous respiration (apnea). Planes of stage 3 are described based on ocular movements, eye reflexes, pupil size. Stage 4- medullary depression: severe depression of CNS, including vasomotor center in medulla and respiratory center in brainstem. Without support, death would ensue.

Answer 113

Malignant hyperthermia: genetic disorder of skeletal muscle occurs while undergoing general anesthesia. Succinylcholine may trigger it. Consists of muscle rigidity, hyperthermia, tachycardia, hypercapnia, hyperkalemia, acidoses. Rare cause of anesthetic morbidity and mortality. Treatment includes dantrolene (reduces calcium release from sarcoplasmic reticulum). Ryanodine receptor (calcium release channel in SR) mutations associated with disease. Hepatotoxicity (halothane hepatitis): 1 in 20,000 to 35,000 get this after taking halothane. MOA is unclear but potentially caused by free radicals directly wreaking havoc. Hepatitis following enflurane and isoflurane have rarely been reported.

Answer 114

Used to treat Alzheimer's Disease Does not modify the disease, they only alleviate symtoms Reversible antagonists of cholinesterases (AD have deficiency of cholinergic neurons in the nucleus basalis of Meynert) Can treat Behavioral symtoms associated with AD (paranoia, delusional thinking, anxiety, depression) Also used to treat other neurodegenerative diseases such as dementia with Lewy bodies and vascular dementia Well tolerated, with most common side effect being GI distress, muscle cramping, abnormal dreams.

Answer 115

Adjunct therapy or alternative to cholinesterase inhibitors in Alzheimer's Disease. Typically added on later in disease progression. Noncompetitive antagonist of NMDA-type glutamate receptor (interacts with Mg⁺ binding site). Does not compete with glutamate directly! It interacts with the channel in a voltage-dependent manner. When the channel is depolarized, Mg is kicked out and the channel is open, allowing Memantine to enter. Has a lower affinity than drugs such as PCP, so doesnt interfere with normal function of NMDA receptors when high concentrations of glutamate are released. Less adverse effects. Reduces the rate of clinical deterioration in patients with moderate to severe AD. May be beneficial treatment for vascular dementia Can treat Behavioral symtoms associated with AD (paranoia, delusional thinking, anxiety, depression) but doesn't treat agitation. **To treat agitation, use Risperidone or Olanzapine**. Adverse: headache, dizziness Excreted in kidneys (in pH dependent manner) and should be reduced in patients with severe renal impairment. Administered orally and not metabolized by CYP450 so not many contraindications. Amantadine, dextromethorphan, and ketamine are all known to act as antagonists at the NMDA receptor and should not be co administered to patients receiving memantine Also a 5-HT₃ antagonist- beneficial for memory

Answer 116

Mild to lethal Delerium, coma, hypertension, tachycardia, hyperreflexia, tremor TCA, SSRI, SNRI + MOA-I leads to this

Answer 117

1) Mesolimbic: source of positive symptoms, too much dopamine/ Mesocortical: source of negative symptoms, too little dopamine 2) Nigrostriatal: Substantia nigra to dorsal striatum involved in coordination of voluntary movement (source of EPS through blockage of D2 receptors) 3) Tuberoinfundibular system: HPA axis, when you inhibit D2 receptors, you activate prolactin hormone secretion 4) Medullary-Periventricular: related to the vagas nerve, may be invovled in eating behaviors 5) Incertohypothalamic: hypothalamus and amygdala that have to do with regulating copulation

Answer 118

Neuroleptanalgesia: produce intense analgesia and amnesia. Neuroleptic (droperidol) + analgesic (fentanyl) Neuroletanesthesia: produces unconciousness. Neuroleptic (droperidol)+ analgesic (fentanyl) + Nitrous oxide