Exam 2 (Pt. 13)

Question 1

Tolerance and Therapeutic Index - Top Panel

Answer 1

The top panel shows that with early drug use (non-tolerant) the individual experiences mood effects without significant respiratory depression.

Question 2

Tolerance and Therapeutic Index - Bottom Panel

Answer 2

However, as tolerance develops with repeated use (bottom panel), larger amounts of drug are needed to experience the mood change (the curve shifts to the right) but no change in the dose causing depression of respiration occurs.

Question 3

Tolerance and Therapeutic Index - Problem

Answer 3

The margin of safety (i.e., therapeutic index) shrinks dramatically in the tolerant individual.

Question 4

Effect of Chronic Barbiturate Administration on Sleep Architecture - Initial Effect

Answer 4

The panel shows the initial effects of pentobarbital, which include a short onset of sleep and few spontaneous awakenings.

Question 5

Effect of Chronic Barbiturate Administration on Sleep Architecture - Chronic-Use Effect

Answer 5

Effect The right panel shows the changes after chronic nightly use of the drug. Tolerance is shown by the long onset of sleep (1 hour) and the 12 spontaneously awakenings during the night. Both REM and stages 3 and 4 sleep are suppressed.

Question 6

Blood Levels of Secobarbital in Mothers and Newborn Infants

Answer 6

Effect of barbiturate on mothers in labor. Blood levels of secobarbital in mothers and their newborn infants after intravenous administration of the drug to the mothers. Each point represents one subject (circles, mothers; asterisks, infants)

Question 7

Benzodiazepine: Major Therapeutic Uses - Chlordiazepoxide

Answer 7

Question 8

Benzodiazepine: Major Therapeutic Uses - Diazepam

Answer 8

Question 9

Benzodiazepine: Major Therapeutic Uses - Oxazepam

Answer 9

Question 10

The Advantages of Drug “B” Over Drug “A” as Deduced From Dose-Response Curves

Answer 10

Question 11

Alcohol Content

Answer 11

There is the same amount of alcohol in one regular beer (340 ml/12 oz., 5% alcohol), one glass of wine (140 ml/5oz, 12% alcohol), one glass of fortified wine (85 ml/3oz, 20% alcohol) and one shot of spirits (45 ml/1.5 oz, 40% alcohol).

Question 12

Time Course of Brain and Venous Ethanol Concentrations

Answer 12

After administration of ethanol (2 g/kg i.p.) to mice, the brain ethanol concentration reached its peak in about 15 min, and did not equate with ethanol levels in venous blood taken from the tip of the tail until 60 min had passed.

Question 13

Relationship Between Blood Alcohol Concentration and Signs of Intoxication

Answer 13

After three doses of alcohol (1.0 g/kg at time a, and 0.25 g/kg at times b and c), signs of intoxication appeared during the rising phase of the blood alcohol concentration (BAC) curve when the BAC was about 200 mg/dl. However, when the BAC was declining, the subject became sober even though the BAC was about 265 mg/dl.

Question 14

Metabolism of Ethanol and the Use of the Aldehyde Dehydrogenase Inhibitor, Disulfiram

Answer 14

Ethanol is oxidated by the enzyme alcohol dehydrogenase using NAD+ as a cofactor to form acetaldehyde. A second oxidative step converts acetaldehyde to acetic acid, which, in turn, is broken down to carbon dioxide and water. The first step involving alcohol dehydrogenase is the rate-limiting step. The drug disulfiram (Antabuse) blocks the second step by blocking the activity of aldehyde dehydrogenase.

Question 15

Dose-Blood Level-Response for Alcohol

Answer 15

Question 19

Children with Fetal Alcohol Syndrome (FAS) Compared with a Mouse Model of FAS

Answer 19

Question 23

Normal EEG Patterns and Epileptic EEG Patterns

Answer 23

The top three traces represent normal a (left), q (middle, during drowsiness), and d (right, during deep sleep) activity recorded in the EEG. The bottom two traces illustrate a focal “spike discharge” (circled) and a sudden burst of spike-and-wave activity seen simultaneously in all the leads

Question 24

Relations Among Cortical EEG, Extracellular, and Intracellular Recordings in a Seizure

Answer 24

The extracellular recording was made through a high-pass filter. Note the high-frequency firing of the neuron evident in both extracellular and intracellular recording during the paroxysmal depolarization shift (PDS).

Question 25

Pharmacological Treatment of Epilepsy

Answer 25

Question 26

Antiseizure Drug-Enhanced Na+ Channel Inactivation

Answer 26

Some antiseizure drugs (shown in blue text) prolong the inactivation of the Na+ channels, thereby reducing the ability of neurons to fire at high frequencies. Note that the inactivated channel itself appears to remain open, but is blocked by the inactivation gate (I). A, activation gate.

Question 27

Drug-Induced Reduction of Current Through T-Type Ca2+ Channels

Answer 27

Some antiseizure drugs (shown in blue text) reduce the flow of Ca2+ through T-type Ca2+ channels, thus reducing the pacemaker current that underlies the thalamic rhythm in spikes and waves seen in generalized absence seizures.

Question 28

Enhanced GABA Synaptic Transmission

Answer 28

In the presence of GABA, the GABA_A receptor (structure on left) is following an influx of Cl-, which in turn increases membrane polarization.

Some antiseizure drugs act by reducing the metabolism of GABA. Others act at the GABAA receptor, enhancing Cl- influx.

Gabapentin acts presynaptically to promote GABA release; its molecular target is currently under investigation. GABA-T, GABA transaminase; GAT-1, GABA transporter.

Question 29

Categorization of Sleep Disorders - Dysomnias

Answer 29

Question 30

Categorization of Sleep Disorders - Parasomnias

Answer 30

Question 31

Comparison of Representative Benzodiazepines for Insomnia Therapy

Answer 31

Question 32

Non-Benzodiazepine Therapy for Insomnia

Answer 32

Question 33

Neurotransmitter Systems Affected by General Anesthetics

Answer 33

The main point is only to recognize that different anesthetics act on a wide variety of different neurochemical systems and that they affect these systems in different ways.

Question 43

Alcohol (ETOH) Use and Abuse

Answer 43

* In U.S. nearly 75% of all adults drink ETOH. * 15% of ETOH users in the U.S. are considered to have a drinking problem or are subject to alcoholism. * 10 million Americans are classified as alcoholics. * Alcoholism is most severe of all substance abuse in USA. * More people become dependent on ETOH, become psychotic through excessive use of it and are killed or disabled by it than by all other abused drugs (except nicotine via tobacco) put together. * 11 million accidents each year are ETOH-related. * Alcoholism costs the U.S. economy $136 billion.

Question 44

American Medical Association Definition of Alcoholism

Answer 44

Alcoholism is an illness characterized by preoccupation with alcohol and loss of control over its consumption such as to lead usually to intoxication if drinking is begun; the condition is chronic, progressive, and has a tendency toward relapse. It is typically associated with physical disability and impaired emotional, occupational, and/or social adjustments as a direct consequence of persistent and excessive use of alcohol.

Question 45

Children with Fetal Alcohol Syndrome (FAS)

Answer 45

* Mental retardation and developmental delays * Low birthweight * Neurological disorders (tremor, irritability auditory hypersensitivity, etc.) * Craniofacial malformations * Assorted physical abnormalities

Question 47

Nature of Epilepsy (Pt. 1)

Answer 47

* Epilepsy affects about 0.5% of the population. * The characteristic event is the seizure, which is often associated with convulsions, but may occur in many other forms. * The seizure is caused by an abnormal high frequency discharge of a group of neurons, starting locally and spreading to a varying extent to affect other parts of the brain.

Question 48

Nature of Epilepsy (Pt. 2)

Answer 48

* Seizures may be partial or generalized depending on the location and spread of the abnormal neuronal discharge. The attack may involve mainly motor, sensory or behavioral phenomena. Unconsciousness occurs when the reticular formation is involved. * Partial seizures are often associated with damage to the brain, whereas generalized seizures occur without obvious cause. * Two common forms of generalized epilepsy are the tonic-clonic fit (grand mal) and the absence seizure (petit mal).

Question 49

Nature of Epilepsy (Pt. 2)

Answer 49

* The neurochemical basis of the abnormal discharge is not well understood. It may be associated with enhanced excitatory amino acid transmission, impaired inhibitory transmission, or abnormal electrical properties of the affected cells. * Prolonged epileptic discharge (status epilepticus) can cause neuronal death (excitotoxicity). * Current drug therapy is effective in 70-80% of epileptic patients.