Anti Anxiety Flashcards
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
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
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
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
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
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
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
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
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
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
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)
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)
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)
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)
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
