1. Canadian National Institute of Health Inc.
Anti-anxiety agents
Chapter 11, pg
LO 14
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2. Canadian National Institute of Health Inc.
Anxiety
A state of uneasiness and apprehension, as about future uncertainties
Anxiety is a multisystem response to a perceived threat or danger. It reflects a combination of biochemical changes in the body, the patient's personal history and memory, and the social situation.
It is important to distinguish between anxiety as a feeling or experience, and an anxiety disorder as a psychiatric diagnosis. A person may feel anxious without having an anxiety disorder. In addition, anxiety frequently occurs as a symptom in other categories of psychiatric disturbance.
physical symptoms such as palpitation, sweating, and feelings of stress
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3. Sedatives and hypnotics
Benzodiazepines (minor tranquilizers)
Barbiturates
Non-benzodiazepine non-barbiturate sedative-hypnotics
Centrally acting muscle relaxants
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4. Sedative-hypnotic agents
Produce various degrees of CNS depression depending on the dose administered.
The same drug may be a sedative or a hypnotic, depending on the dose administered
A small dose produces sedation (reduction of activity and simple anxiety.) It is the result of a mild CNS depression. Usually anxiolytic effect
A larger dose of the same drug produces hypnoses(sleep), by a greater degree of CNS depression.
In even larger doses sedative-hypnotics will produce anesthesia and
finally death.
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Tranquilizers
Minor-tranquilizers:
used to treat anxiety
produce various degrees of depression (with anxiolytic effects) on CNS, similar to sedative-hypnotics and alcohol.
with larger and larger doses can produce coma and death.
relax voluntary muscles
potential for addiction
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Tranquilizers
Major- tranquilizers:
used to treat psychoses.
have strong anticholinergic effect: xerostomia
produce involuntary muscles movement and rigidity (extrapyramidal effect)
do not produce addictions.
do not produce death. Even with large doses the patient taking major tranquilizers can be easily aroused from the sedation
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The mostly used agents by the dental team are the oral drugs used to provide relaxation for the anxious patient. Benzodiazepines
i.v. administration is used in hospital settings or specially equipped, surgery practices.
Benzodiazepines, Barbiturates
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8. Canadian National Institute of Health Inc.
Benzodiazepines
Minor tranquilizers
Well absorbed when administered orally. Also administered i.v. for conscious sedation.
Dosage forms: tablets, capsules, oral solutions, rectal gel, injectable solutions
Mechanism of action: enhance or facilitate the action of GABA (gamma-aminobutiric acid)-a neurotransmitter in the CNS.
Classified according to their onset (rapid: min) and their ½ life (short: 2 hrs, intermediate: 4-10 hrs, long acting: hrs)
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Benzodiazepines
Metabolism:
Phase I, in the liver, might result in an active metabolite, that, with repeated administrations, can accumulate (diazepam ½ life is 20-50hrs, the active metabolite has a ½ life of hrs). It is affected by slowed or impaired liver function, as in aging, disease, interaction with other drugs metabolized in the liver.
Phase II requires the presence of an enzyme present in many tissues, so is not affected that much by other drugs or by age and slowed liver functions.
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Benzodiazepines
Pharmacologic effects:
Behavioral effects: reduce anxiety at low doses. Used in dentistry for nervous patients. Produce drowsiness and even sleep at higher doses (produce REM sleep, reduces deep sleep)
Anticonvulsant effects
Muscle relaxation of skeletal muscle. Relief of musculoskeletal pain, treatment of muscle spasticity secondary to pathologic states: cerebral palsy, paraplegia
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Benzodiazepines
Adverse reactions:
CNS effects: usually depression, manifested as fatigue, drowsiness, muscle weakness, ataxia. More evident in older persons. In psychiatric patients can produce CNS stimulation with talkativeness, anxiety, hyperactivity and increased muscle spasticity. Discontinue.
The depressor effect on CNS is used in dentistry to produce conscious sedation. Diazepam, lorazepam iv reduces anxiety and alters patient’s perception of time. Amount is titrated to the patient’s response: appearance of ptosis.
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12. Canadian National Institute of Health Inc.
Benzodiazepines
Adverse reactions:
Amnesia. With i.v. administration, also oral. Because benzodiazepines interfere with the consolidation processes that store the information in the brain. Tell patient not to sign important papers or make important decisions after benzodiazepines are administered
Respiratory effects: occasionally respiratory depression. More common in elderly. The minimal respiratory depression produced by benzodiazepines is exacerbated by alcohol and opioids. In iv administration for conscious sedation can produce apnea.
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Benzodiazepines
Adverse reactions:
Cardiovascular effects: oral therapeutic doses have no effect on circulation. The relief of anxiety may result in a fall of blood pressure and pulse rate. Or the pulse rises and returns to normal in few minutes. Parenteral use may produce hypotention, bradycardia, cardiac arrest. Equipment for respiratory and cardiovascular assistance must be available if the dental office provides iv conscious sedation).
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Benzodiazepines
Adverse reactions:
Visual effects: diplopia, blurred vision, nystagmus, contraindicated in narrow-angle glaucoma, used to treat wide-angle glaucoma (the most common kind of glaucoma)
Dental effects: either xerostomia or increased salivation, swollen tongue, bitter or metallic taste
Thrombophlebitis: for iv use of diazepam.This is an effect of propylene glycol, a vehicle added to diazepam because diazepam has poor water solubility.
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Benzodiazepines
Adverse reactions:
GI tract: cramps, pain
Urinary tract: difficulty in urination
Allergy: skin rashes or itching
Pregnancy and lactation: do not administer. Produces congenital malformation if taken in first semester: cleft lip and palate, gi and cardiovascular abnormalities. If taken perinatally produces “floppy infant syndrome”: hypoactivity, hypotonia, hypothermia, apnea, feeding problems.
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Benzodiazepines
Abuse and tolerance:
Physical dependence and tolerance, especially with large doses over extended periods.
Less addiction potential than other sedative-hypnotics, like barbiturates.
Cross-tolerance in between benzodiazepines and other CNS depressants, like alcohol.
Wider therapeutic index than the barbiturates (large doses must be ingested to produce respiratory or vasomotor depression)
Their safety is reduced if combined with other CNS depressants: alcohol, resulting in coma, respiratory depression, hypotension, death.
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Benzodiazepines
Treatment of overdose:
The ingestion of benzodiazepines alone does not usually result in severe symptoms.
Emesis if recent ingestion,
Activated charcoal.
Monitor BP and respiration.
Chronic use of bezodiazepine for management of insomnia is not recommended.
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Benzodiazepines
Drug interactions:
Additive effect with other CNS depressants: alcohol, barbiturates, anticonvulsants, phenothiazines.
Smoking decreases their effectiveness.Tars in cigarettes stimulate hepatic enzymes, increasing the rate of metabolism of benzodiazepines, so a higher dose is required to produce same effect.
May reduce the effect of levodopa, and parkinsonism is exacerbated in these patients.
May increase the effect of digoxin, phenytoin and probenecid.
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Benzodiazepines
Uses:
Short term treatment of anxiety, insomnia (1month, limit to 10 tablets per month) Not long term because of potential for dependence, addiction, withdrawal
Treatment of alcohol withdrawal syndrome, to prevent agitation and tremor.
Acute treatment of seizures: iv in repetitive seizures.
Conscious sedation, general anesthesia
Control of muscle spasms in multiple sclerosis and cerebral palsy.
Relief of spasm and pain of back strain.
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Benzodiazepines
Dental use: Orally admin., preoperative, for relieve of apprehension for dental procedures.
Chose an agent with fast onset and short ½ life: triazolam (Halcion) (fast onset, short ½ life=3hrs), diazepam (Valium) (fast onset, long ½ life=50hrs), lorazepam (Ativan) (fast onset, intermed.1/2life=10hrs) or alprazolam (intermediate onset, short ½ life).
Short ½ life important especially in elderly. Patients should not be allowed to operate a motor vehicle, must be accompanied to/from the office.
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Benzodiazepines
Dental use:
Premedication prior to surgical procedure. PO or iv. If iv. produces amnesia, beneficial in stressful dental procedures.
Diazepam is used as a premedication before general anesthesia, endoscopy, gastroscopy, etc.
Conscious sedation (reflexes are maintained): iv administration of diazepam, lorazepam or midazolam to provide antianxiety effect, muscle relaxation and amnesia. Because amnesia may last 45 min., postop. instructions should be provided in writing. Continuous monitoring of vital signs. Emergency equipment and drugs a must.
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Barbiturates
Were the original sedative-hypnotic agents.
Barbiturates have almost completely been replaced by benzodiazepines in clinical use.
Exception:
-the barbiturates used as anticonvulsants
-the barbiturates used to induce general anesthesia.
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Barbiturates
Well absorbed orally and rectally. Also used iv.
Metabolism: in the liver for short-acting and intermediate-acting, the long-acting are excreted as free drug. Patients with liver damage may have exaggerated response to short-and intermediate- acting barbiturates and people with renal impairments may have an accumulation of long-acting agents.
Mechanism of action; enhance GABA receptor binding.
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Barbiturates
Pharmacologic effects:
CNS depression, additive with other agents that produce CNS depression, like alcohol and opioids.
Depression is progressive, following the same path as many CNS depressors, including general anesthetics:
At normal doses: relaxation and anxiety relief.
Higher doses: disinhibition and euphoria.
Higher doses: hypnosis.
Higher doses: anesthesia with respiratory and cardiovascular depression and finally arrest.
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Barbiturates
Pharmacologic effects:
Do not pprovide analgesia: barbiturates do not block the reflex response to pain. Must be accompanied by an analgesic.
Anticonvulsant effect. Used to treat epilepsy (long-acting agents, e.g. phenobarbital)
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Barbiturates
Adverse reactions:
Sedative and hypnotic doses:
Usually safe, but CNS depression is exaggerated in elderly and patients with liver or renal impairments.
Do not administer in pregnancy, as they cause fetal harm
Anesthetic doses: used for intubation or very short procedures. At high doses and iv, concentrations attained in the blood can be lethal. Coughing, laringospasm.
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Barbiturates
Adverse reactions:
Acute poisoning: at ingestion of 10 times the hypnotic dose. At 15 times the hypnotic dose life is seriously endangered. Death by respiratory failure.
Treatment: treatment of specific symptoms. Conservative management of barbiturates to avoid overdose.
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Barbiturates
Chronic long-term use:
can lead to physical and psychologic dependence.
Produces tolerance, so a larger and larger dose is needed to produce an effect and this can approximate the lethal dose.
There is cross-tolerance among different barbiturates and between barbiturates and non-barbiturates sedative-hypnotics.
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Barbiturates
Contraindications:
Absolute contraindication in patients with intermitent porphyria or a positive family history of porphyria( metabolic disease that leads to accumulation of porphirin with clinical manifestation of skin or neurological problems).
Barbiturates precipitate an acute attack of porphyria
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Barbiturates
Drug interaction:
Are numerous, because barbiturates are potent stimulators of liver enzymes production, influencing the metabolism of many other drugs metabolized in the liver.
Enhanced or additive CNS depressant effect with alcohol, other CNS depressants and opioids.
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Barbiturates
Uses:
The therapeutic uses of barbiturates are determined by their duration of action:
Ultrashort-acting (thiopental): iv. For induction of general anesthesia
Short-and intermediate-acting have been replaced by benzodiazepines for insomnia and anxiety relief.
Long-acting (phenobarbital): treatment of epilepsy.
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32. Non-barbiturates sedative-hypnotics
Chloral Hydrate:
PO (flavored syrup, c.h.has unpleasant taste), rapid onset (30 min), short duration of action (4hrs.).
Therapeutic doses do not produce respiratory or cardiac depression. Higher doses do .
Can produce addiction if used for long periods of time
Used in dentistry for preoperative sedation of children.
Benzodiazepines are a safer choice for sedation in children.
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33. Non-barbiturates sedative-hypnotics
Meprobamate:
Sedative and anticonvulsant properties, some muscle-relaxant properties
Few side effects in the therapeutic doses.
Overdoses produce excessive CNS depression
Chronic long-term use can lead to tolerance and dependence. Also cross-tolerance with other sedative-hypnotics, including alcohol.
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34. Non-barbiturates sedative-hypnotics
Meprobamate:
Additive depressing effect on CNS with other CNS depressants.
Do not use in pregnancy.
Uses in dentistry: antianxiety agent and muscle relaxant in preparations that combine aspirin or other agents.
Medical uses: occasionally used as treatment of anxiety, as a daytime sedative or nighttime hypnotic.
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35. Centrally acting muscle relaxants
Produce muscle relaxation by producing CNS depression.
Produce some degree of sedative effects because they are CNS depressants.
Xerostomia is a common side effect.
Use: adjunct to rest and physical therapy for relief of muscle spasm in acute painful musculoskeletal conditions.
Dental use: treatment of TMD to decrease symptoms.
Diazepam, methocarbamol.
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Other agents
Buspirone:
Has an unique structure and action. Has only anxiolytic but not hypnotic, anticonvulsant or muscle relaxant. (Selective anxiolytic, anxioselective)
Onset: 1 week.
Use: treat anxiety.
Does not produce tolerance or dependence.
Produces much less CNS depression and does not affect driving skills
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37. General comments about antianxiety agents
Drugs are not to be used as a substitute for patient management, for patient education or for proper psychologic approach to patient care. The dental practitioner should not rely exclusively on drugs to provide a calm and cooperative patient. The dental team should exhibit a confident and relaxed manner, a pleasant, soothing office atmosphere.
When an agent for anxiety relief is deemed necessary, the selection of the drug is made according to its advantages and disadvantages and according to the needs and contraindications for the patient.
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38. General comments about antianxiety agents
Sedatives do not provide analgesia. Use of a sedative without proper pain control may cause the patient to become highly excited and act irrationally.
Sedatives potentiate the effect of an analgesic taken concomitantly.
Patients with impaired renal or hepatic function may experience exaggerated effects: the young, elderly, debilitated patients, liver and kidney diseases.
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39. General comments about antianxiety agents
CNS depression is additive with alcohol and over the counter sleeping medications. Caution the patient.
Patient must be accompanied by a responsible adult who can drive the patient home. Caution the patient he will not be able to drive himself, to sign important documents, to perform any activity that requires full alertness and muscle coordination.
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40. General comments about antianxiety agents
Keep in mind that almost all antianxiety drugs can produce dependence
Suicide may be attempted by taking sedative-hypnotic drugs, so prescription should be limited to the minimum required for therapeutic effects.
Benzodiazepines have a wide therapeutic index, unless mixed with alcohol.
Do not administer in pregnancy.
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41. Analgesic-sedative combinations
The use of analgesic and a sedative-hypnotic concomitantly is useful because:
-Relief of both pain and anxiety is required frequently in the same patient. Anxiety can lower the pain threshold
-Sedatives potentate the effect of analgesic agents
-If sedatives are given without analgesics, they may produce excitation.
Sedative+opioid or non-opioid analgesic can be prescribed separately
Fixed dose combinations: butalbital/ASA/caffeine (Fiorinal); b/aceta (Fioricet)
b/ASA/Caffeine/codeine (Fiorinal#3)
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