MODULE 2 | CNS DEPRESSANTS Flashcards by CHESKA CIANNELLE FRANCISCO

are group of drugs that may enhance the activity of inhibitory neurotransmitters in the brain (GABA) and spinal cord (GLYCINE) or inhibit excitatory neurotransmitters (GLUTAMATE), and block the production of excitatory action potential

CNS depressants

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most common mental disorders

anxiety

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an unpleasant state of tension, apprehension, or uneasiness (a fear that arises from either a known or unknown source

ANXIETY

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drugs used to treat anxiety are called

anxiolytics

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induction of a relaxed easy state, i.e. allays irritability, nervousenss, or excitement

SEDATION

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SEDATIVES

reduce anxiety and exert a calming effect on motor and mental function

sedatives

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induction of sleep

HYPNOSIS

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HYPNOSIS

produce drowsiness and encourage the onset and maintenance of a state of sleep that as far as possible resembles the natural sleep

hypnotics

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inability to fall asleep and/or maintain a state of sleep

insomnia

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one of the applications of sedative-hypnotics

insomnia

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STAGES OF SLEEP

very light sleep
muscle activity slows down

stage 1

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STAGES OF SLEEP

breathing pattern and heart rate slows down
body temperature decreases slightly

stage 2

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STAGES OF SLEEP

deep sleep starts
brain starts to generate slow delta waves

sstage 3

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STAGES OF SLEEP

very deep sleep
muscle activity is limited

stage 4

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STAGES OF SLEEP

REM sleep
brainwaves speed up and dreams occur
heart rate increases

stage 5

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REM meaning

rapid eye movement

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the sleep cycle is divided into (2)

NREM
REM

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STAGES OF SLEEP

drowsy transition from waking to sleeping, still awake

stage 1 nrem

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STAGES OF SLEEP

no longer aware but are easily awakened

stage 2 NREM

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STAGES OF SLEEP

slow-wave sleep

stage 3 nrem

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STAGES OF SLEEP

deep sleep
brain acvitivity decreases
heart rate is slow
BP is decreased
breathing decreases

stage 4 NREM

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the NREM sleep usually takes how many mins

60-90mins

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STAGES OF SLEEP

increase autonomic activity
increase breathing, BP and HR
increase blood flow to the brain
dreaming episodes occur

stage 5 REM

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the REM sleep occupies how many % of the total sleep

20-25%

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# **BENZODIAZEPINES** **SHORT** ACTING (**2-8hrs**)

**O**xazepam **M**idazolam **T**riazolam

# **BENZODIAZEPINES** **INTERMEDIATE**-ACTING (**10-20hrs**)

**L**orazepam **A**lprazolam **T**emazepam **E**stazolam

# **BENZODIAZEPINES** **LONG**-ACTING (**1-3days**)

Chlordiazepoxide **DIAZEPAM** Flurazepam Chlorazepate Quazepam

an **active metabolite** of **Diazepam**, **Chlordiazepoxide**, and **Chlorazepate**

Nordazepam

**Benzodiazepines** support what GABA receptor

GABA A

**Barbiturates** support what GABA receptor

GABA B

# **BARBITURATES** **ULTRA SHORT**-ACTING (30mins)

**Thi**pental **Thi**amylal **M**ethohexital | ThiThiMo

# **BARBITURATES** **SHORT**-ACTING (**2 hours**)

**Pent**obarbital **Hex**obarbital **Sec**obarbital | 5-6-7

# **BARBITURATES** **INTERMEDIATE**-ACTING (**3-5hrs**)

**Amo**babital **Buta**barbital

# **BARBITURATES** **LONG**-ACTING (**>6hours**)

Phenobarbital Barbital

# **MISCELLANEOUS AGENTS** * 5-HT1A **partial agonist** * D2 **antagonist**

Buspirone

# **MISCELLANEOUS AGENTS** * **novel hypnotic** drug * **melatonin** receptor **agonist**

RAMELTEON

# **MISCELLANEOUS AGENTS** **melatonin** receptor **agonist**

TASIMELTEON

# **MISCELLANEOUS AGENTS** **orexin antagonist**

Almorexant Suvorexant

which has **extremely rapid absorption** TRAZOLAM or DIAZEPAM

TRIAZOLAM

the **absorption** of the **active metabolite** of ____ is **more rapid** than other common used benzodiazepens

clorazepate

**active form** of Clorazepate (a **prodrug**)

desmethyldiazepam (nordiazepam)

major requirement to **enter** BBB

lipophilic

all sedative-hypnotics cross the ____ during **pregnancy**

placental barrier

sedative-hypnotics are also detectable in ____ and may exert **depressant effeects** in the **nursing infant**

breast milk

# **BENZODIAZEPINES** are **metabolized** by ____ systems of the liver

microsomal drug-metabolizing enzyme

# **BENZODIAZEPINES** DESMETHYLDIAZEPAM: **elimination half life**

more than 40hrs

# **BENZODIAZEPINES** Alprazolam, Triazolam undergo ____

a-hydroxylation

# **BENZODIAZEPINES** **parent** drug or **active metabolites** with ____

long halflives

# **BENZODIAZEPINES** ESTAZOLAM ,OXAZEPAM, LORAZEPAM: are metabolized **directly** into ____

inactice glucuronides

# **BENZODIAZEPINES** affected by **inhibitors** and **inducers** of **hepatic P450 isozymes**

Diazepam Midazolam Triazolam

**Barbiturates** increase ____

bilirubin conjugation

# **BARBITURATES** **oxidation** by ____ to form **alcohols**, **acids**, and **ketones**

hepatic enzymes

# **BARBITURATES** metabolites appear in the **urine** as ____

glucoronide conjugates

# **BARBITURATES** **SECOBARBITAL** and **PHENOBARBITAL**: **elimination half lives**

18 - 48 hrs

# **BARBITURATES** **PHENOBARBITAL**: elimination half lives

4-5 days

# **ZOLPIDEM (NEWER HYPNOTICS)** reches **peak plasma levels** in ____

1-3 hrs

# **ZOLPIDEM (NEWER HYPNOTICS)** formulations available

sublingual & oral spray

# **ZOLPIDEM (NEWER HYPNOTICS)** **rapidly metabolized** to inactive metabolites via **oxiation** and **hydroxylation** by ____

hepatic CYP3A4

# **ZOLPIDEM (NEWER HYPNOTICS)** the **elimination half life** is **greater** in ____

women

# **ZOLPIDEM (NEWER HYPNOTICS)** the **elimination half life** is **increased significantly** in the ____

elderly

# **(NEWER HYPNOTICS)** is metabolized to inactive metabolites **mainly** by** hepatic aldehyde oxidase** and **partly** by the cytochrome P450 isoform **CYP3A4**

ZALEPLON

# **NEWER HYPNOTICS** * metabolized by **hepatic CYP450 (CYP3A4)** to form the inactive **N-oxidde derivative** and weakly active **demethyleszopiclone** * elimination half life is **prolonged** in the **elderly** and in the **presence** of **inhibitors** of **CYP3A4** (**ketoconazole**) * **inducers** of CYP3A4 (**rifampin**) **increase** its **hepatic metabolism**

ESZOPICLONE

excreted **unchanged** in the urine to a certain extent (20-30%) in humans

PHENOBARBITAL

# **PHENOBARBITAL** its **elimination rate** can be **increased** significantly by ____ of the urine | **mgmt. of phenobarbital toxicity**

alkalanization | bc phenobarb is a **weak acid**

# **PHENOBARBITAL** pKa

weak acid - 7.4

# **MOA OF SEDATIVE-HYPNOTICS** the **precursor** in the **synthesis of GABA**

GLUTAMINE

# **MOA OF SEDATIVE-HYPNOTICS** **GABA synthesis** is facilitated by what enzyme

GLUTAMIC ACID DECARBOXYLASE

# **MOA OF SEDATIVE-HYPNOTICS** prevention of metabolism/degradation of GABA

storage into vesicles

# **MOA OF SEDATIVE-HYPNOTICS** how will the GABA produce its effect

by binding to the **postsynaptic receptor**

# **MOA OF SEDATIVE-HYPNOTICS** GABA **inactivation** via

GABA transaminase

**key difference** between GABA **A** and GABA **B**

GABA A - ionotropic GABA B - metabotropic, GPRC

increase **frequency** of **chloride ion channel opening**

Benzodiazepines (Zolpidem)

* a **benzodiazepine** **antagonist** * can **reverse** the hypnotic effects of **zolpidem**

FLUMAZENIL

bind to other sites distinct from benzodiazepines and other sedatives increasing the **duration** of **chloride ion channel opening**

Barbiturates (Phenobarbital)

* a **negative mdoulator** * acts at the same site as BZDs through **competitive binding**

FLUMANEZIL

potentiate **GABAergic inhibition**

benzodiazepines

**enhance GABA's effects** allosterically **without directly** activating GABA A receptors or opening the associated Cl channels

benzodiazepenes

what will happen if GABA and benzodiazepine **interacts**

increase the frequencey of channel-opening events increase Cl conductane

increase the **duration** of the GABA-gated Cl channel openings

barbiturates

whis is **more toxic** BENZODIAZEPINE or BARBITURATES

barbiturates

# **ORGAN LEVEL EFFECTS OF SEDATIVE-HYPNOTICS** * **low** doses: BZDs, barbiturates, and older sedative-hypnotic drugs exert **calming effects** with concomitant reduction of anxiety * the **anxiolytic actions** are **accompanied** by some **depressant effects** on **psychomotor** and **cognitive functions** (side effects)

SEDATION

# **ORGAN LEVEL EFFECTS OF SEDATIVE-HYPNOTICS | SEDATION** exert **dose-dependent anterograde amnesic effects** (MIDAZOLIN) -- inability to **remember events** occuring during the durg's duration of action (used during surgeries, e.g. CS)

BENZODIAZEPINES

# **ORGAN LEVEL EFFECTS OF SEDATIVE-HYPNOTICS** * manifest when **high doses** are given

HYPNOSIS

# **EFFECTS OF BZDs AND SHs** the **latency of sleep onset** is ____ | time to fall asleep

decreased | can sleep faster

# **EFFECTS OF BZDs AND SHs** the duration of **stage 2 NREM** is ____

increased

# **EFFECTS OF BZDs AND SHs** the duration of **REM** sleep is ____

decreased

# **EFFECTS OF BZDs AND OLDER SHs** the duration of **stage 4 NREM** slow-wave sleep is ____

decreased

# **EFFECTS OF NEWER SHs** decreases **REM** sleep but has **minimal effect** on **slow-wave** sleep

ZOLPIDEM

# **EFFECTS OF NEWER SHs** decreases the **latency of sleep** onset with **little effect** on **total sleep time**, NREM, or REM sleep

ZALEPLON

# **EFFECTS OF NEWER SHs** **increases total sleep time** mainly via increases in **stage 2 NREM** sleep

ESZOPICLONE

# **EFFECTS OF NEWER SHs** ESZOPICLONE: **low** doses

little effect on sleep patterns

# **EFFECTS OF NEWER SHs** ESZOPICLONE: **highest** recommended dose

decreases REM sleep

all **hypnotics** can cause deliberate ____

interruption of REM sleep

**REM rebound** is commonly observed in what drug

TRIAZOLAM

**anxiety** and **irritability** followed by **REM rebound** is commonly associated with ____

older sedativehypnotics

occurs with both **Zolpidem** and **Zaleplon** at **higher doses**

rebound insomnia

use of sedative-hypnotics for **more than 1-2 weeks** leads to some ____ to their effcts on sleep patterns

tolerance

# **ORGAN LEVEL EFFECTS OF SEDATIVE-HYPNOTICS | ANESTHESIA** **high doses** of certain SHs **depress the CNS** to the point known as ____

STAGE III OF GENERAL ANESTHESI

# **ORGAN LEVEL EFFECTS OF SEDATIVE-HYPNOTICS | ANESTHESIA** * **very lipid-soluble**, penetrating brain tissue rapidly * makes them useful for the **induction** of anesthesia

THIOPENTAL & METHOHEXITAL

# **ORGAN LEVEL EFFECTS OF SEDATIVE-HYPNOTICS | ANESTHESIA** * used IV * given in **large doses** * **long half lives** and formation of **active metabolites** contributes to **post-anesthetic respiratory depression** * can be **reversed** by **Flumazenil**

BZDs

# **ORGAN LEVEL EFFECTS OF SEDATIVE-HYPNOTICS** * inhibit the development and spread of epileptiform electrical activity in the CNS

anticonvulsant effect

# **ORGAN LEVEL EFFECTS OF SEDATIVE-HYPNOTICS | ANTICONVULSANT** selective to be clinically useful in the management of **seizures**

BZDs

# **ORGAN LEVEL EFFECTS OF SEDATIVE-HYPNOTICS | ANTICONVULSANT** * effective in the treatment of **generalized tonic-clonic seizures** (not the drug of first choice)

BARBITURATES

# **ORGAN LEVEL EFFECTS OF SEDATIVE-HYPNOTICS | MUSCLE RELAXANT** * exert **inhibitory** effects * may **depress** transmission at the **skeletal** neuromuscular junction at **high doses**

Carbamate and BZDs

# **ORGAN LEVEL EFFECTS OF SHs | RESPIRATION & CARDIOVASCULAR** can produce significant **respiratory depression** in patients with ____ at **therapeutic doses**

pulmonary diseasse

# **ORGAN LEVEL EFFECTS OF SHs | RESPIRATION & CARDIOVASCULAR** usual **cause of death** due to **overdose** of SHs

depression od the medullary respiratory center

# **ORGAN LEVEL EFFECTS OF SHs | RESPIRATION & CARDIOVASCULAR** no significant effects in ____ of **healthy patients**

cardiovascular system

# **ORGAN LEVEL EFFECTS OF SHs | RESPIRATION & CARDIOVASCULAR** AT **NORMAL DOSE**: * in ____ states, **heart failure** and other disease that **impair CV function** may appear

HYPOVOLEMIC

# **ORGAN LEVEL EFFECTS OF SHs | RESPIRATION & CARDIOVASCULAR** AT **TOXIC** DOSE: * may cause **depression** of ____ and ____ leading to **circulatory collapse**

myocardial contractility & vascular tone

# **ORGAN LEVEL EFFECTS OF SHs | RESPIRATION & CARDIOVASCULAR** **respiratory** and **cardiovascular** effects are more marked when given ____

available in a **biphasic** release formulation that provides **sustained** drug levels for **sleep maintenance**

ZOLPIDEM

have value in the management of patients who **awaken early in the sleep cycle**

ZALEPLON

cause **less amnesia** or **day-after somnolence** than zolpidem / BZDs

Zaleplon & Eszopiclone

* orexin **antagonists** * **sleep enabling** drugs

Almorexant Suvorexant

* **agonist** at MT1 and MT2 melatonin receptors * have **no direct effects** on GABAergic neurotransmission in the CNS

Ramelteon Tasimelteon

approved for **non-24hr sleep-wake disorder**

Tasimelteon

* reduce the **latency** of **persistent sleep** * no rebound insomnia * no effect on sleep architecture * rapidly absorbed; undergoes extensive first pass metab

Ramelteon

useful **relaxant** effects in **skeletal muslces** spasticity of central origin

DIAZEPAM

# **CLINICAL USES OF BZDs** anesthesia

Midazolam | antegrade amnesia

# **CLINICAL USES OF BZDs** anxiety

BZD

# **CLINICAL USES OF BZDs** muscle relaxant **alcohol withdrawal**

DIAZEPAM

# **CLINICAL USES OF BZDs** anticonvulsant

Diazepam Clonazepam Clorazepate

# **CLINICAL USES OF BZDs** **panic** disorders

Alprazolam

# **CLINICAL USES OF BZDs** status epilepticus

Diazepam | seizure should be NMT 5 days

why is **MIDAZOLAM** preferred over other BZDs for **anesthesia**

* shorter onset of action * greater potency * more rapid elimination

# **CLINICAL USES OF BZDs** sleep disorders (**insomnia**)

lorazepam temazepam

# **CLINICAL USES OF BZDs** alcohol withdrawal

diazepam

# **CLINICAL USES OF BABRITURATES** anticonvulsant hypnosis

phenobarbital

# **CLINICAL USES OF BABRITURATES** anesthesia sedation

thiopental

# **CLINICAL TOXICOLOGY OF SHs** * **drowsiness**, **impaired judgement**, **diminished motor skills** * w impact on **driving ability**, **job performance**, **personal relationships** * **anterograde amnesia** * **hangover** effects

low doses

# **CLINICAL TOXICOLOGY OF SHs** * **lethargy** or state of **exhaustion** * as gross symptom equivalent to those of **ethanol intoxication** * exacerbate **breathing problems** in px w/ COPD

high doses

# **CLINICAL TOXICOLOGY OF SHs** a dose **as low as ten times the hypnotic dose** may be ____

fatal | except **BZDs** and **newer** hypnotics

# **TERATOGENECITY** individual BZDs category

D or X

# **TERATOGENECITY** **Barbiturates** are FDA pregnancy category ____

# **TERATOGENECITY** **Eszopiclone**, **Ramelteon**, **Zaleplon**, and **Zolpidem** are category

# **TERATOGENECITY** **Buspirone**, an **anxiolytic**, is caategory ____

# **ADVEERSE EFFECTS** **Barbiturates** enhance ____ synthesis * contraindicated in patients with **porphyria**

porphyrin

which drug does **tolerance** rapidly develops BARBITURATES or BZDs

barbiturates

____ usually develops when **used continuously at therapeutic doses**

PHYSICOLOGIC DEPENDENCE

____ may result to **abstinence** or **withdrawal syndrome**

abrupt withdrawal

it is advised that **withdrawal** should be done ____

gradually

which does have **high potential** for **physical dependence** and **abuse** BARBITURATES or BENZODIAZEPINES

BARBITURATES

Due to **high abuse potential**, most sedative-hypnotic drugs are classified as ____ or ____ drugs

schedule III or IV

over how many % of **alcohol** is **oxidized** in the **liver**

90%

the rate of oxidation of **alcohol** follows ____

ZERO-ORDER KINETICS

inhibits **alcohol dehydrogenase**

Fomepizole

inhibits **aldehyde dehydrogenase**

Disulfiram

**alcohol** produces ____

dose-dependent depression

**primary mechanism** to account for the **CNS depressant property** of **alcohol**

**enhance** the action of GABA at GABA A receptor

**alcohol** inhibits the ability of ____ to open the **cation channel**

glutamate | accounts for the **blackouts** episodes

# **EFFECTS OF ALCHOL** induces ____ in the skin resulting to **flushed sensation**

dilation of blood vessels

# **EFFECTS OF ALCHOL** stimulates **secretion** of ____ and ____

saliva and gastric juices

# **EFFECTS OF ALCHOL** **blocks** secreetion of ____

ADH - antidiuretic hormone

antidiuretic hormone

vasopressin

# **CONSEQUENCES OF CHRONIC ALCOHOLISM** Alcoholics suffer from ____ resulting to **WERNICKES-KORSAKOFF'S SYNDROME**

thiamine deficiency

# **CONSEQUENCES OF CHRONIC ALCOHOLISM** characterized by **paralysis** of the **external eye muscles**, **ataxia** and **confused state** than can progress to **coma** & **death**

WERNICKES-KROSAKOFF'S SYNDROME

**chronic** alcoholinsm causes enzyme ____

induction

**acute** alcoholinsm causes enzyme

inhibition

# **TREATMENT OF ALCOHOLISM** opioid antagonists can cause **dose-dependent hepatotoxicity**, thus should be used with caution in patients with eviidence of **abnormalities** in **serum aminotransferase** activity

NALTREXONE

# **TREATMENT OF ALCOHOLISM** reduces **short term** and **long term** (more than 6mos) **relapse** rates when combined with psychotherapy

Acamprostate

* should be **taken with alcohol**; has little effect when given alone * **inhibits aldehyde dehydrogenase** resulting accumulation of acetaldehyde causing **extreme discomfort** in patients * this causes **flushing**, **throbbing headache**, **N&V**, **sweating**, **hypotnesion**, and **confusion** -- may last for **30mins** in **mild** cases and **several hours** in **severe** ones

Disulfiram

# **TREATMENT OF ALCOHOLISM** 5 HT3 **antagonist**

Ondansetron

# **TREATMENT OF ALCOHOLISM** antiseizure

Topiramate

employed in conditions collectively known as **neurosis**

anxiolytics

an **accumulation** of **anxiety** and **tension** which leads to emotional changes and abnormal behavior

neurosis

commonly used **anxiolytic**

Buspirone

# **ANXIETY STATES** * psychic **awareness** of anxiety * accompanied by **enhanced vigilance**, **motor tension**, and **autonomic hyperactivity**

PRIMARY

# **ANXIETY STATES** * results from **circumstances** that may** have to be dealt with only once or a few times**

Situational anxiety

* **excessive** or **unreasonable** anxiety about life circumstances * managed by drug therapy, sometimes in conjunction with psychotherapy

GENERALIZED ANXIETY DISORDER

**Triggered** by **certain circumstances**, such as open spaces, social interactions or spiders

Phobic anxiety

**Attacks** of **overwhelming fear** occur in association with **marked somatic symptoms**, such as sweating, tachycardia, chest pain, trembling, choking, etc

Panic disorder

* **Widely used** for the management of **acute anxiety** states and for rapid control of panic attacks * Also used, though **less commonly**, in the **long-term management of GAD** and **panic disorders**

BZDs

selectively used for the treatment of **panic disorders** and **agoraphobia**

Alprazolam

preferred for patients with anxiety that may require treatment for **prolonged period of time**

Diazepam

* **5HT1A partial agonist**, **D2 antagonist ** * Has **selective anxiolytic effect** without causing marked sedative, hypnotic, or euphoric effects * **Mainly** for **generalized anxiety states**, **less effective in panic disorders**

BUSPIRONE

* Used mainly to **reduce physical symptoms** of anxiety (tremors, palpitations, etc.) * **No effect** on affective component

BETA BLOCKERS

MODULE 2 | CNS DEPRESSANTS Flashcards

(177 cards)