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Flashcards in Anti Anxiety Deck (16)
1

diazepam

Benzodiazepine

Antianxiety/Sedative-Hypnotic Drug

Therapeutic uses:
- Sedative/hypnotic: Treat Insomnia
- Anxiolytic: Anxiety (panic, obsessive compulsive disorder, phobias)
- Muscle Relaxant: Spasticity, dystonias
- Anticonvulsant: Absence, status epilepticus, generalized seizures (rapid tolerance develops)

Other Uses: Perioperative med and endoscopic procedures.
- Withdrawal from chronic use of ethanol and other CNS depressants

NOT ANESTHETICS OR ANALGESICS

Increasing doses produce sedation, hypnosis and stupor but NOT general anesthetics

Analgesias has been reported but after IV use due to anterograde amnesisa

Central Effects:
- Bind GABA receptors in the LIMBIC SYSTEM (amygdala, septum, hippocampus) involved in emotional processes

BZs enhance inhibition (Enhance GABA effect) of neurons in limbic system

Inhibition of limbic system produce anxiolytic effects of BZs

Mechanism: Bind to site on GABA (Cl) channel that ehnaces the CL influx (hyperpolarization

Increases the frequency of Cl channel opening in presence of GABA

Metabolism:
- Cytochrome p450
- CYP3A4
- CYP2C19
Adds a methyl to make
DESMETHYLDIAZEPAM the active metabolite
- Then adds a hydroxyl group to make OXAZEPAM which is put through glucuronide conjugation to make the inactive metabolite

Time to Peak Plasma: 1-2hr
HALF LIFE: Long 30-60h



2

chlordiazepoxide

Benzodiazepine

Antianxiety/Sedative-Hypnotic Drug

Therapeutic uses:
- Sedative/hypnotic: Treat Insomnia
- Anxiolytic: Anxiety (panic, obsessive compulsive disorder, phobias)
- Muscle Relaxant: Spasticity, dystonias
- Anticonvulsant: Absence, status epilepticus, generalized seizures (rapid tolerance develops)

Other Uses: Perioperative med and endoscopic procedures.
- Withdrawal from chronic use of ethanol and other CNS depressants

NOT ANESTHETICS OR ANALGESICS

Increasing doses produce sedation, hypnosis and stupor but NOT general anesthetics

Analgesias has been reported but after IV use due to anterograde amnesisa

Central Effects:
- Bind GABA receptors in the LIMBIC SYSTEM (amygdala, septum, hippocampus) involved in emotional processes

BZs enhance inhibition (Enhance GABA effect) of neurons in limbic system

Inhibition of limbic system produce anxiolytic effects of BZs

Mechanism: Bind to site on GABA (Cl) channel that ehnaces the CL influx (hyperpolarization

Increases the frequency of Cl channel opening in presence of GABA

3

alprazolam

Benzodiazepine

Antianxiety/Sedative-Hypnotic Drug

Therapeutic uses:
- Sedative/hypnotic: Treat Insomnia
- Anxiolytic: Anxiety (panic, obsessive compulsive disorder, phobias)
- Muscle Relaxant: Spasticity, dystonias
- Anticonvulsant: Absence, status epilepticus, generalized seizures (rapid tolerance develops)

Other Uses: Perioperative med and endoscopic procedures.
- Withdrawal from chronic use of ethanol and other CNS depressants

NOT ANESTHETICS OR ANALGESICS

Increasing doses produce sedation, hypnosis and stupor but NOT general anesthetics

Analgesias has been reported but after IV use due to anterograde amnesisa

Central Effects:
- Bind GABA receptors in the LIMBIC SYSTEM (amygdala, septum, hippocampus) involved in emotional processes

BZs enhance inhibition (Enhance GABA effect) of neurons in limbic system

Inhibition of limbic system produce anxiolytic effects of BZs

Mechanism: Bind to site on GABA (Cl) channel that ehnaces the CL influx (hyperpolarization

Increases the frequency of Cl channel opening in presence of GABA

Metabolism:
- Cytochrome p450
- CYP3A4
- CYP2C19
Adds a Hydroxyl to make a alpha-hydroxy metabolite
- Then it is Fast to make a Glucoronide Conjugation

Time to Peak Plasma: 1-2hr
HALF LIFE: Short 12-15 hr

Insomnia/Anxiety

4

What to do in case of Benzodiazepine Acute Toxicity

BZs have very high therapeutic index
: TI= LD/ED= 100s

Overdose not life threatening

Treatment: Support Respiration/ Blood Pressure
- Gastric Lavage, activated charcoal, cathartic (sorbitol)

Give Antagonist: Flumazenil
- Short Acting (5 min-2 hr)- multiple dose
- Injected IV gives quick reversal of BZ respiratory depression

5

oxazepam

Benzodiazepine

Antianxiety/Sedative-Hypnotic Drug

Therapeutic uses:
- Sedative/hypnotic: Treat Insomnia
- Anxiolytic: Anxiety (panic, obsessive compulsive disorder, phobias)
- Muscle Relaxant: Spasticity, dystonias
- Anticonvulsant: Absence, status epilepticus, generalized seizures (rapid tolerance develops)

Other Uses: Perioperative med and endoscopic procedures.
- Withdrawal from chronic use of ethanol and other CNS depressants

NOT ANESTHETICS OR ANALGESICS

Increasing doses produce sedation, hypnosis and stupor but NOT general anesthetics

Analgesias has been reported but after IV use due to anterograde amnesisa

Central Effects:
- Bind GABA receptors in the LIMBIC SYSTEM (amygdala, septum, hippocampus) involved in emotional processes

BZs enhance inhibition (Enhance GABA effect) of neurons in limbic system

Inhibition of limbic system produce anxiolytic effects of BZs

Mechanism: Bind to site on GABA (Cl) channel that ehnaces the CL influx (hyperpolarization

Increases the frequency of Cl channel opening in presence of GABA

Metabolism:
- Cytochrome p450
- CYP3A4
- CYP2C19
From Diazepam: Adds a methyl to make
DESMETHYLDIAZEPAM the active metabolite
- Then adds a hydroxyl group to make OXAZEPAM which is put through glucuronide conjugation to make the inactive metabolite

Time to Peak Plasma: 1-2hr
HALF LIFE: Long 30-60h

6

lorazepam

Benzodiazepine

Antianxiety/Sedative-Hypnotic Drug

Therapeutic uses:
- Sedative/hypnotic: Treat Insomnia
- Anxiolytic: Anxiety (panic, obsessive compulsive disorder, phobias)
- Muscle Relaxant: Spasticity, dystonias
- Anticonvulsant: Absence, status epilepticus, generalized seizures (rapid tolerance develops)

Other Uses: Perioperative med and endoscopic procedures.
- Withdrawal from chronic use of ethanol and other CNS depressants

NOT ANESTHETICS OR ANALGESICS

Increasing doses produce sedation, hypnosis and stupor but NOT general anesthetics

Analgesias has been reported but after IV use due to anterograde amnesisa

Central Effects:
- Bind GABA receptors in the LIMBIC SYSTEM (amygdala, septum, hippocampus) involved in emotional processes

BZs enhance inhibition (Enhance GABA effect) of neurons in limbic system

Inhibition of limbic system produce anxiolytic effects of BZs

Mechanism: Bind to site on GABA (Cl) channel that ehnaces the CL influx (hyperpolarization

Increases the frequency of Cl channel opening in presence of GABA

Metabolism:
- Cytochrome p450
- CYP3A4
- CYP2C19
- Directly Glucoronide Conjugated to be excreted in the Urine

Time to Peak Plasma: 1-6hr
HALF LIFE: Intermediate 10-18 hour

Treatment for:
- Insomnia
- Anxiety
- Muscle Relaxant

7

midazolams

Benzodiazepine

Antianxiety/Sedative-Hypnotic Drug

Therapeutic uses:
- Sedative/hypnotic: Treat Insomnia
- Anxiolytic: Anxiety (panic, obsessive compulsive disorder, phobias)
- Muscle Relaxant: Spasticity, dystonias
- Anticonvulsant: Absence, status epilepticus, generalized seizures (rapid tolerance develops)

Other Uses: Perioperative med and endoscopic procedures.
- Withdrawal from chronic use of ethanol and other CNS depressants

NOT ANESTHETICS OR ANALGESICS

Increasing doses produce sedation, hypnosis and stupor but NOT general anesthetics

Analgesias has been reported but after IV use due to anterograde amnesisa

Central Effects:
- Bind GABA receptors in the LIMBIC SYSTEM (amygdala, septum, hippocampus) involved in emotional processes

BZs enhance inhibition (Enhance GABA effect) of neurons in limbic system

Inhibition of limbic system produce anxiolytic effects of BZs

Mechanism: Bind to site on GABA (Cl) channel that ehnaces the CL influx (hyperpolarization

Increases the frequency of Cl channel opening in presence of GABA

Metabolism:
- Cytochrome p450
- CYP3A4
- CYP2C19
- Directly Glucoronide
- Hydroxyl group added (Quick) to make alpha hydroxy metabolite
- Fast: Glucoronide Conjugation to inactive metabolite

Time to Peak Plasma: 0.2-1 hr
HALF LIFE: Ultra Short (2-5 hr)

Treatment for:
- Pre-anesthetic Medication

8

flumazenil

Antagonist of BZs/GABA receptor
- Blocks effect of both agonists and inverse agonists

Has not biologic effect by itself
- Can precipitate withdrawal in BZ or BARB dependent Persons

Treatment for BZ toxicity

Short acting (5 min- 2hr)
Multiple doses/IV

9

zolpidem

Non- Benzodiazepine antianxiety/sedative-hypnotic Drugs

Act on BZ binding site of GABA receptor

Increase frequency of GABA mediated Cl channel opening

Peak Plasma via Oral: 1-2 hr

Metabolized: CYP3A4 (oxidation and hydroxylation)
- Partially by hepatic aldehyde oxidase as well to form inactive metabolite
- Eliminated (half life 1.5-3hr)

Induce sleep: decease in latency of onset of sleep/increase in duration of sleep

Hypnotic Dose: No respiratory or cardiovascular effects under normal conditions
- Heart failure/disease states that impair CV function there is CV depression

IV administration has marked CV and resp depressant effects


10

Zaleplon

Non- Benzodiazepine antianxiety/sedative-hypnotic Drugs

Act on BZ binding site of GABA receptor

Increase frequency of GABA mediated Cl channel opening

Peak Plasma via Oral: 1-2 hr

Metabolized: CYP3A4 (oxidation and hydroxylation)
- Partially by hepatic aldehyde oxidase as well to form inactive metabolite
- Eliminated (half life 1.5-3hr)

Induce sleep: decease in latency of onset of sleep/increase in duration of sleep

Hypnotic Dose: No respiratory or cardiovascular effects under normal conditions
- Heart failure/disease states that impair CV function there is CV depression

IV administration has marked CV and resp depressant effects

11

pentobarbital

Barbituate
- Plasma Half Life determine usage

Onset of Effect: Short to Intermediate (0.5-1h)

Half Life: Intermediate (15-50hr)

Uses: Preoperative Sedation

Have been replaced by BZs for sedation and antianxiety due to toxicity

Advantages: Effective/inexpensive
Extensively studied

Disadvantaged:
- Respiration depression
- CV Depression at sedative hynoptic doses
- Liver: Influence cyto p450, induce drug metabolism and other enzymes

Mechanism of Action:
- Significantly depress neuronal activity in reticular formation (pons, medulla) and cortex
- Binds to pentameric GABA receptor macromolecular complex
to enhance GABA effect\

Mechanisms of Action 2:
- Increase open time of CL channel
- Enhance inhibitory effects of GABA
- HIGH CONC directly increases Cl conductance in absence of GABA

Barbiturate Metabolism
- Liver p450 enzyme: many complex reactions
- Most induce activity/expression of CYPs
- Are dealkylated
- Glucoronidated to make inactive
- RENAL EXCRETION

Side Effects:
- Drowsiness, confusion, diminished motor skills, impaired judgement

Contraindication
- Pain: can increase pain
- Pulmonary Insufficiency: Respiratory depression

Drug Interaction:
- Enhance CNS depressive effects of:
- Antipsychotic
- Antihistamines
- Ethanol

Enhance Metabolism of (via CYP):
- Beta blockers, Ca channel blockers, corticosteroids, estrogens, phenothiazines, valproic acid, and theophylline

Acute Toxicity
- Poisioning: major problem, serious toxicity at only 10X hypnotic dose
- Respiratory depression, circulatory collapse, renal failure, and pulmonary complications, can be life threatening

Symptoms:
- Severe respiratory depression, coma, sever hypotension, hypothermia

Treatment:
- Support respiration and BP
- Gastric Lavage: recent ingestion, activated charcoal, and cathartic (sorbitol)

12

phenobarbital

Barbituate
- Plasma Half Life determine usage

Onset of Effect: Long (1-3h)

Half Life: Long (80-120h)

Uses: Anticonvulsant

Have been replaced by BZs for sedation and antianxiety due to toxicity

Advantages: Effective/inexpensive
Extensively studied

Disadvantaged:
- Respiration depression
- CV Depression at sedative hynoptic doses
- Liver: Influence cyto p450, induce drug metabolism and other enzymes

Mechanism of Action:
- Significantly depress neuronal activity in reticular formation (pons, medulla) and cortex
- Binds to pentameric GABA receptor macromolecular complex
to enhance GABA effect\

Mechanisms of Action 2:
- Increase open time of CL channel
- Enhance inhibitory effects of GABA
- HIGH CONC directly increases Cl conductance in absence of GABA

Barbiturate Metabolism
- Liver p450 enzyme: many complex reactions
- Most induce activity/expression of CYPs
- Are dealkylated
- Glucoronidated to make inactive
- RENAL EXCRETION

Side Effects:
- Drowsiness, confusion, diminished motor skills, impaired judgement

Contraindication
- Pain: can increase pain
- Pulmonary Insufficiency: Respiratory depression

Drug Interaction:
- Enhance CNS depressive effects of:
- Antipsychotic
- Antihistamines
- Ethanol

Enhance Metabolism of (via CYP):
- Beta blockers, Ca channel blockers, corticosteroids, estrogens, phenothiazines, valproic acid, and theophylline

Acute Toxicity
- Poisioning: major problem, serious toxicity at only 10X hypnotic dose
- Respiratory depression, circulatory collapse, renal failure, and pulmonary complications, can be life threatening

Symptoms:
- Severe respiratory depression, coma, sever hypotension, hypothermia

Treatment:
- Support respiration and BP
- Gastric Lavage: recent ingestion, activated charcoal, and cathartic (sorbitol)

13

amobarbital

Barbituate
- Plasma Half Life determine usage

Onset of Effect: Ultra short/immediate

Half Life: Ultra-short (~10h)

Uses: Preoperative sedation

Have been replaced by BZs for sedation and antianxiety due to toxicity

Advantages: Effective/inexpensive
Extensively studied

Disadvantaged:
- Respiration depression
- CV Depression at sedative hynoptic doses
- Liver: Influence cyto p450, induce drug metabolism and other enzymes

Mechanism of Action:
- Significantly depress neuronal activity in reticular formation (pons, medulla) and cortex
- Binds to pentameric GABA receptor macromolecular complex
to enhance GABA effect\

Mechanisms of Action 2:
- Increase open time of CL channel
- Enhance inhibitory effects of GABA
- HIGH CONC directly increases Cl conductance in absence of GABA

Barbiturate Metabolism
- Liver p450 enzyme: many complex reactions
- Most induce activity/expression of CYPs
- Are dealkylated
- Glucoronidated to make inactive
- RENAL EXCRETION

Side Effects:
- Drowsiness, confusion, diminished motor skills, impaired judgement

Contraindication
- Pain: can increase pain
- Pulmonary Insufficiency: Respiratory depression

Drug Interaction:
- Enhance CNS depressive effects of:
- Antipsychotic
- Antihistamines
- Ethanol

Enhance Metabolism of (via CYP):
- Beta blockers, Ca channel blockers, corticosteroids, estrogens, phenothiazines, valproic acid, and theophylline

Acute Toxicity
- Poisioning: major problem, serious toxicity at only 10X hypnotic dose
- Respiratory depression, circulatory collapse, renal failure, and pulmonary complications, can be life threatening

Symptoms:
- Severe respiratory depression, coma, sever hypotension, hypothermia

Treatment:
- Support respiration and BP
- Gastric Lavage: recent ingestion, activated charcoal, and cathartic (sorbitol)

14

thiopental

Barbituate
- Plasma Half Life determine usage

Onset of Effect: Ultra Short

Half Life: Ultra Short (3-10h)

Uses: Anesthesia Induction

Have been replaced by BZs for sedation and antianxiety due to toxicity

Advantages: Effective/inexpensive
Extensively studied

Disadvantaged:
- Respiration depression
- CV Depression at sedative hynoptic doses
- Liver: Influence cyto p450, induce drug metabolism and other enzymes

Mechanism of Action:
- Significantly depress neuronal activity in reticular formation (pons, medulla) and cortex
- Binds to pentameric GABA receptor macromolecular complex
to enhance GABA effect\

Mechanisms of Action 2:
- Increase open time of CL channel
- Enhance inhibitory effects of GABA
- HIGH CONC directly increases Cl conductance in absence of GABA

Barbiturate Metabolism
- Liver p450 enzyme: many complex reactions
- Most induce activity/expression of CYPs
- Are dealkylated
- Glucoronidated to make inactive
- RENAL EXCRETION

Side Effects:
- Drowsiness, confusion, diminished motor skills, impaired judgement

Contraindication
- Pain: can increase pain
- Pulmonary Insufficiency: Respiratory depression

Drug Interaction:
- Enhance CNS depressive effects of:
- Antipsychotic
- Antihistamines
- Ethanol

Enhance Metabolism of (via CYP):
- Beta blockers, Ca channel blockers, corticosteroids, estrogens, phenothiazines, valproic acid, and theophylline

Acute Toxicity
- Poisioning: major problem, serious toxicity at only 10X hypnotic dose
- Respiratory depression, circulatory collapse, renal failure, and pulmonary complications, can be life threatening

Symptoms:
- Severe respiratory depression, coma, sever hypotension, hypothermia

Treatment:
- Support respiration and BP
- Gastric Lavage: recent ingestion, activated charcoal, and cathartic (sorbitol)

15

buspirone

Antianxiety/sedative-hypnotic drug

Partial agonist for serotonin receptor (5HT1A)

Metabolized (hydroxylation/dealkylation by CYP3A4)

Produces only anxiolytic effects

No CNS depression

NO physical dependence

No rebound anxiety or withdrawal signs

No additive depression with EtOH

Onset of action 1 to 3 weeks: limits usefulness in acute anxiety states

16

Propranolol

Beta Adrenoceptor blocker

Blocks autonomic effect (palpitation, sweating, shaking)
Used for disabling situational anxiety (stage fright)