Antianxiety and Antipsychotics Flashcards
Antianxiety medications are also called what 2 things?
- Sedative hyponotics
- Minor tranquilizers
**These are low potency compounds used to treat anxiety and neurosis
Which drugs account for 75% of 100 million prescriptions written for sedatives/tranquilizers?
1. dizepam (Valium)
- chlordizepoxide (Librium)
All benzodiazepines (BDZ) have same basic structure:
- 2 nitrogens “diazo”
- Benzene ring = binds to GABA receptors
Popular BDZ drugs =
- chlordiazepoxide (Librium)
2. diazepam (Valium)
3. lorazepam (Ativan)
- oxazepam (Serax)
5. alprazolam (Xanax)
- triazolam (Halcion)
7. midazolam (Versed) = “dazzle”
Which popular BDZ drug is used for preoperative sedation and inudction of general anesthesia?
midazolam (Versed)
T or F, Benzodiazepines were originally not thought of to be addictive. Now, these are known to be highly addictive
True
What schedule are Benzodiazepines?
Schedule IV/V opiates in the U.S. due to their abuse potential.
- Complicated by the fact that tolearnce develops to these drugs requiring increasingly higher doses = contributes to addiction
Benzodiazepines produce 3 distinct effects:
1. Effects on behavior
2. Anticonvulsant effects
3. Muscle relaxation
How do Benzodiazepines effect behavior
- Reduces aggression and hostility
- Reduce other symptoms of non-specific CNS depression
(Anxiety reduction, Drowsiness/depression)
Low doses of Benzodiazepines have what effect on behavior? High doses?
Anxiety reduction at low doses
Drowsiness/depression at high doses
Which two drugs prevent and arrest local anesthetic-induced seizures in dentistry?
1. diazepam (Valium)
2. midazolam (Versed)
How is diazepam and midazolam administered?
Slowly by IV (diazepam 5 mg/minute or midazolam 1 mg/minute)
Which drugs are most potent at muscle relaxation?
1. diazepam (Valium)
2. chlordiazepoxide (Librium)
Describe how Benzos cause muscle relaxation
Depresses motor nerve and muscle function in both healthy persons and in patients suffering from skeletal muscle disorders
Where are the receptor sites for BDZ found?
In the CNS
Describe the mechanism of action of BDZs
BDZ affect the concentration of most neurotransmitters, including GABA.
- When GABA receptor is activated, the Cl- channel opens, allowing Cl- influx, membrane hyperpolarization and neuronal inhibition. BDZ facilitate GABA action and “indirectly” increase inhibitory neurotransmission resulting from GABA
**Extra: BDZ increase frequency at which Cl- channels open in response to GABA
T or F, GABA receptor embedded in neuronal plasma membranes, locate at synapse = binds both GABA and BDZ
True - Presence of GABA enhances binding of BDZ
Binding to GABA receptor sites is:
- Rapid
- Reversible
- Stereospecific
- Saturable
Describe the body’s handling of BDZs
1. Most have very long half-lives
2. Most are metabolized to active compounds
BDZs have long half-lives so repeated dosing results in accumulation of the drug in the body. However, there is one drug that is metabolized rapidly to INACTIVE compounds = no significant accumulation. Which drug is it?
lorazepam (Ativan)
** A good choice for dentistry
Use of BDZs in Medicine
- Relief of anxiety
- Skeletal muscle relaxation = muscle strains
- Hypnotic to treat insomnia = induces sleep
- Treat withdrawal symptoms of alcoholism = helps alcoholic through initial withdrawal effects
- Pre-operative medication = used to decrease apprehension
Use of BDZs in Dentistry
- Reduce pre-operative anxiety
- diazepam (Valium), lorazepam (Ativan), alprazolam (Xanax), triazolam (Halcion) - IV sedative and amnesiac
- Emergency intervention for seizures
Adverse Effects of BDZs
- CNS depression (Fatigue, drowsiness
- Xerostomia
- Abuse and addiction
- Additive effects with other CNS depressants especially alcohol
- Dangerous drug interaction (Alcohol and BDZ)
If a patient is taking BDZs, how does this affect your dosage of opiates?
Reduce dose of opiates by 1/3 of normal dose when a BDZ is added (diazepam)
T or F, There is no drug interaction between BDZ and Alcohol. Patients are safe in consuming alcohol while on these medications
False, This is a dangerous drug interaction! Results in severe CNS depression that may be DEADLY. Results in significant respiratory depression.
- Because of the long half-life, teach your patients to avoid alcohol when using these medications.
What is buspirone (BuSpar) used for and its mechanism of action
- Used for management of generalized anxiety disorder
- Mechanism is unknown –> Binds serotonin receptors without affecting BDZ-GABA receptors
Many dental drug interactions increase the concentration of buspirone - what drugs should you avoid with concurrent use?
- ciprofloxacin
- clarithromycin
- erythromycin
- doxycycline
- systemic antifungals
- RED Flag Drugs in dentistry
Anti-anxiety medications together with what other drug class causes xerostomia?
Antidepressant
Older term for major tranquilizers or antipsychotic medications
neuroleptic drugs
Major Tranquilizers are used in the treatment of: (6)
- Psychotic disorders (Schizophrenia, paranoia)
- Acute delirium and dementia
- Manic episodes during induction of lithium
- Movement disorders - Huntington’s disease, Tourette’s syndrome, Ballismus
- Intractable hiccups
- Severe nausea and vomiting
Major Tranquilizers bind to a variety of receptors and act as what?
Antagonists
Name the 6 receptors that Major Tranquilizers bind to
- dopaminergic
- alpha1 and alpha2 adrenergic
- serotonergic (5-HT)
- muscarinic
- H1 histamine
- sigma opioid
Name the three major effects of major tranquilizers and how their effects are believed to occur?
- Antipsychotic action = blockage in prefrontal cortex and limbic areas
- Extrapyramidal side effects = blockade in basal ganglia
- Antiemetic effects = blockade in chemoreceptor trigger zone of the medulla
**Blockade of dopaminergic transmission in various areas of brain is thought to be responsible for their major effects
What is the Dopaminergic hypothesis of Schizophrenia?
Overactivity of dopaminergic system - thus, antipsychotic medications reduce dopaminergic activity by blocking D2 receptors
T or F, All major tranquilizers are strong D2 dopamine receptor antagonists and effective doses (potency) are indirectly proportional to their D2 antagonism
False, directly proportional
- Exception: cloxapine (Clozaril) = low D2 antagonism; effective dose is lower than is expected
Primary site for dopaminergic neurons
Striatum - Most tranquilizer drugs work here
- Antipsychotics occupy >70% of striatal D2 sites
- clozapine occupies only 30%
- **Also in Limbic system and prefrontal cortex - likely sites for curative actions of clozapine, where this drug occupies the same high percentage of D2 receptors as other antipsychotics.
What are the problems with the Dopaminergic Hypothesis of Schizophrenia
- Receptors are blocked within 2-4 hours after drug administration, but therapeutic activity requires several weeks of treatment to achieve full effect
- Therapeutic effects is related to slow-developing depolarization block of dopaminergic neurons
- Schizophrenia is also associated with alterations in structure of neurons in prefrontal cortex and limbic system
Dopamine is involved in:
- Neurotransmission
- Regulation of neuronal morpholoy
How are Major Tranquilizers administered?
Administered orally or by IM
Maximal concentration in blood for major tranquilizers occurs when? What is the half-life?
- Maximal concentration in blood is achieved 2-4 hours after oral adminsitration and within 30-4- minutes after IM
- Half-life = 18-40 hours
- Once daily dosing
- All durgs have similar efficacy
Side Effects of Major Tranquilizers:
- Akathisia = restless legs syndrome - caused by D2 receptor blockage in basal ganglia
- Dystonia = sustained muscular contraction
- Tardive Dyskinesia - abnormal movements, particularly of face and tongue, but may also be of trunk and limbs
Sedation and autonimc side effects of major tranquilizers are caused by what?
blockade of histamine, cholinergic and adrenergic receptors
- orthostatic hypotension, blurred vision, dry mouth, nasal congestion, constipation, urinary retention
T or F, Most extrapyramidal side effects of major tranquilizers are treatable with antiadrenergic drugs
False, anticholinergic drugs
Extrapyramidal side effects of antipsychotics
Parkinsonism - akinesia (difficulties in initiating movment), tremor, rigidity
Caused by blockage of D2 receptors in basal ganglia
T or F, Antipsychotics are highly addictive and have a low therapeutic index
False, Not addictive and have a HIGH therapeutic index
Antipsychotics potentiate CNS effects of :
Sedatives
Analgesics
Antihistamines
T or F, Antipsychotics potentiate the respiratory depression caused by opioids
True
Which other drug classes have this drug interaction with antipsychotics:
- Decrease absorption of antipsychotics
- Decrease plasma levels of antipsychotics
- Antipyschotics may alter efficacy of this medication
- Antacids
- Anticonvulsants
- Antihypertensive
Typical Antipsychotics:
clorpromazine (Thorazine)
haloperidol (Haldol)
prochlorperazine (Compro, Compazine)
Atypical Antipsychotics
- aripiprazole (Abilify)
- clozapine (Clozaril)
- risperdone (Risperdal)
3 Critical points for dentist regarding antipsychotics
- May cause hematologic disturbances = check white blood cell counts
- May alter QT interval of heart (caution with epinephrine; risk for arrhythmias)
- Cause extrapyramidal effects (movement disorders) - bruxism, Tardive dyskinesia
