Anxiolytics

Question 1

What are the two classes of anxiolytics?

Answer 1

benzos

buspirone

Question 2

Benzodiazepine pharmacokinetics

Answer 2

• highly pb
• high lipid solubility
• hepatic metabolism by cyp450
• eliminated via the kidneys

Question 3

What is alprazolam used for?

(zanax)

Answer 3

• significant anxiety reducing effect
• used for primary anxiety and panic attacks
• can depress cortisol secretion

Question 4

What are the different classes of antipsychotic drugs?

what do they treat?

Answer 4

• phenothiazines
• thioxanthenes
• butyrophenones
• atypical
• treatment of schizophrenia, mania/depression with psychotic features, psychoses, tourettes syndrome
• may be used as antiemetic at low doses

Question 5

What are the Phenothiazine and Thioxanthene drugs?

Answer 5

• Phenothiazines
  
  • Chlorpromazine (thorazine)
  • Thioridazine (Mellaril)
  • perphenazine (trilafon)
  • Trifluoperazine (stelazine)
• Thioxanthene
  
  • Thiothixene (navane)

Question 6

What is the MOA of phenothiazines and thioxanthene?

MOA for antiemetic effects?

Answer 6

• blocks dopamine receptors (especially dopamine 2) in the basal ganglia and limbic portions of the forebrain
• interferes with dopamine, causing extrapyramidal side effects
• antiemetic: blocks dopamine receptors in chemoreceptor trigger zone of medulla

Question 7

Phenothiazines and thioxanthene pharmacokinetics

Answer 7

• erratic patterns of absorption after po administration
• highly lipid soluble
• highly PB

Question 8

Phenothiazines and Thioxanthene

Metabolism

Answer 8

• oxidation in liver with conjugation
• most have inactive metabolites
• E1/2t 10-20 hours
  
  • prolonged in the elderly or those with decreased capacity to metabolize drugs

Question 9

Phenothiazines and Thioxanthene

Side effects

Answer 9

• decreased BP- b/c of alpha block
• direct cardiac depression
• Extrapyramidal effects
  
  • tardive dyskinesia
• Acute dystonic reactions
• sedation- from antagonism of alpha 1, muscarinic, and histamine receptors
• decrease in sz threshold
• decrease in sensory evoked potentials
• skeletal muscle relaxation
• neuroleptic syndrome

Question 10

what is tardive dyskinesia?

Answer 10

tardive dyskinesia- abnormal involunarty movements involving the tongue, facial/neck muscles, extremeties, and occasionally skeletal muscle groups used in breathing/swallowing

occurs in 20% of pts receiving theapy for >1 year

elderly and women more susceptible

permanent

Question 11

what is acute dystonia?

Answer 11

acute skeletal muscle rigidity and cramping in neck, tongue, face or back

usually within first few weeks of therapy

respiratory distress from laryngeal dyskinesia (laryngospasm)

responds well to diphenhydramine

Question 12

How do the antiemetic effects of phenothiazines and thioxanthene work?

Answer 12

• interacts with dopaminergic receptors in chemoreceptor trigger zone
• effective in preventing opioid induced N/V
  
  • no sedation or hypotensive effects and rarely cause extrapyramidal symptoms

Question 13

What is neuroleptic malignant syndrome?

How is it treated?

Answer 13

• hyperthermia
• hypertonicity of skeletal muscles
  
  • myogloinuria
• instability of autonomic NS
• fluctuation LOC
• Treatment:
  
  • supportive care
  • dantrolene
  • dopamine agonists

Question 14

What drugs do phenothizines and thioxanthen interact with?

Answer 14

• Opioids
  
  • potentiation of sedation
  • respiratory depression
  • analgesic properties

Question 15

How are Butyrophenones similar to phenothiazines?

What are the two medications?

Answer 15

• structurally similar
• similar side effects
• Droperidol
• haloperidol

Question 16

Droperidol

pharmacokinetics

Answer 16

• clearance is perfusion dependent
  
  • hepatic metabolism not reliant on hepatic enzyme activity
• accumulation of drug with decreased hepatic blood flow
• maximal excretion of metabolites in first 24 hours

Question 17

Droperidol

side effects

Answer 17

• CNS effects
  
  • extrapyramidal
  • cerebral vasoconstrictor- decreased cerebral blood flow but not CMRO2
  • Dysphoria
• CV
  
  • decreased BP from alpha block
  • antidysrhythmic
  • large doses decrease conduction along accessory pathways responsible for tacky dysrhythmias
  • Prolonged QT interval
  • torsades de pointes

Question 18

What special care do patients receiving droperidol require?

Answer 18

• 12 lead ekg before administration
• must be monitored for 2-3 hours
• may develop QT syndrome

Question 19

What is droperidol used for?

Answer 19

• Neurolept analgesia
  
  • combined with fentanyl and prepared commercially
    
    • prolonged action of fentanyl
• antiemetic
  
  • very successful, cheaper than zofran

Question 20

What are the 2nd generation antipsychotics?

Answer 20

• Risperidone
  
  • can cause severe hypotension
  • active metabolite
  • half life 12 hrs
  • effects last 7-8 weeks
• Ziprasidone
  
  • prolonged QT; torsades
• Olanzapine (zyprexa)
  
  • severe hypotension, thrombocytopenia
  • half life 21-54 hours

Question 21

2nd generation Antipsychotics

MOA

Metabolization

side effects

Answer 21

• MOA- antagonize D2 and Serotonin receptors
• metabolized in CYP450
• all cause extrapyramidal side effects