Download Free Medical Hypnotics and sedatives PowerPoint Presentation

Hypnotics and sedatives PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : This medical presentation titled ""Hypnotics and sedatives"" talks about the usage of hypnotics and sedatives.

Tags : Alternative Medicine, Hypnotics, sedatives, Non Benzodiazepine hypnotics, BARBITURATES, Bezodiazepines, Sedation, Relief of anxiety, Amnesia, Hypnosis, Anaesthesia, Coma, Respiratory depression

Published on : Apr 22, 2021 | Views : 2193 | Downloads : 10

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

HYPNOTICS AND SEDATIVES
Slide 2-

SEDATIVES – reduce anxiety and exert a calming effect HYPNOTICS - produces drowsiness and facilitates the onset and maintenance of a state of sleep.
Slide 3-

ppt slide no 3 content not found
Slide 4-

ppt slide no 4 content not found
Slide 5-

Non Benzodiazepine hypnotics ZOLPIDEM ZALEPLON ZOPICLONE (ESZOPICLONE) Miscellaneous MELATONIN RAMELTEON
Slide 6-

BARBITURATES CLASSIFIED ACCORDING TO THEIR DURATIONS OF ACTION
Slide 7-

ppt slide no 7 content not found
Slide 8-

ppt slide no 8 content not found
Slide 9-

ppt slide no 9 content not found
Slide 10-

ppt slide no 10 content not found
Slide 11-

Barbiturates enhance the binding of GABA to GABAA receptors Prolonging duration Only α and β (not ϒ ) subunits are required for barbiturate action Narrow therapeutic index in small doses, barbiturates increase reactions to painful stimuli. Hence, they cannot be relied on to produce sedation or sleep in the presence of even moderate pain. Bezodiazepines enhance the binding of GABA to GABAA receptors increasing the frequency Unlike barbiturates, benzodiazepines do not activate GABAA receptors directly
Slide 12-

BARBITURATES Mechanism of Action- Bind to specific GABAA receptor subunits at CNS neuronal synapses facilitating GABA-mediated chloride ion channel opening, enhance membrane hyperpolarization. Effects- Dose-dependent depressant effects on the CNS including Sedation Relief of anxiety Amnesia Hypnosis Anaesthesia Coma Respiratory depression steeper dose-response relationship than benzodiazepines
Slide 13-

BARBITURATES ACTIONS Depression of CNS: At low doses, the barbiturates produce sedation (calming effect, reducing excitement). 2. Respiratory depression: Barbiturates suppress the hypoxic and chemoreceptor response to CO2, and overdosage is followed by respiratory depression and death. 3. Enzyme induction: Barbiturates induce P450 microsomal enzymes in the liver.
Slide 14-

BARBITURATES PHARMACOKINETICS All barbiturates redistribute in the body. Barbiturates are metabolized in the liver, and inactive metabolites are excreted in the urine. They readily cross the placenta and can depress the fetus. Toxicity: Extensions of CNS depressant effects dependence liability > benzodiazepines. Interactions: Additive CNS depression with ethanol and many other drugs induction of hepatic drug-metabolizing enzymes.
Slide 15-

THERAPEUTIC USES ANESTHESIA (THIOPENTAL, METHOHEXITAL) Selection of a barbiturate is strongly influenced by the desired duration of action. The ultrashort-acting barbiturates, such as thiopental, are used intravenously to induce anesthesia. ANXIETY Barbiturates have been used as mild sedatives to relieve anxiety, nervous tension, and insomnia. When used as hypnotics, they suppress REM sleep more than other stages. However, most have been replaced by the benzodiazepines.
Slide 16-

THERAPEUTIC USES ANTICONVULSANT: (PHENOBARBITAL, MEPHOBARBITAL) Phenobarbital is used in long-term management of tonic-clonic seizures, status epilepticus, and eclampsia. Phenobarbital has been regarded as the drug of choice for treatment of young children with recurrent febrile seizures. However, phenobarbital can depress cognitive performance in children, and the drug should be used cautiously. Phenobarbital has specific anticonvulsant activity that is distinguished from the nonspecific CNS depression.
Slide 17-

ADVERSE EFFECTS CNS: Barbiturates cause drowsiness, impaired concentration. 2. Drug hangover: Hypnotic doses of barbiturates produce a feeling of tiredness well after the patient wakes. Barbiturates induce the P450 system. By inducing aminolevulinic acid (ALA) synthetase, barbiturates increase porphyrin synthesis, and are contraindicated in patients with acute intermittent porphyria.
Slide 18-

ADVERSE EFFECTS Physical dependence: Abrupt withdrawal from barbiturates may cause tremors, anxiety, weakness, restlessness, nausea and vomiting, seizures, delirium, and cardiac arrest. Poisoning: Barbiturate poisoning has been a leading cause of death resulting from drug overdoses for many decades. It may be due to automatism. Severe depression of respiration is coupled with central cardiovascular depression, and results in a shock-like condition with shallow, infrequent breathing.
Slide 19-

ADVERSE EFFECTS
Slide 20-

THE TREATMENT OF ACUTE BARBITURATE INTOXICATION Treatment includes artificial respiration and purging the stomach of its contents if the drug has been recently taken. No specific barbiturate antagonist is available. General supportive measures. Hemodialysis or hemoperfusion is necessary only rarely. Use of CNS stimulants is contraindicated because they increase the mortality rate.
Slide 21-

THE TREATMENT OF ACUTE BARBITURATE INTOXICATION If renal and cardiac functions are satisfactory, and the patient is hydrated, forced diuresis and alkalinization of the urine will hasten the excretion of phenobarbital. In the event of renal failure - hemodialysis circulatory collapse is a major threat. So hypovolemia must be corrected & blood pressure can be supported with dopamine. Acute renal failure consequent to shock and hypoxia accounts for perhaps one-sixth of the deaths.
Slide 22-

BENZODIAZEPINES
Slide 23-

COMPARISON OF THE DURATIONS OF ACTION OF THE BENZODIAZEPINES
Slide 24-

Effects of benzodiazepine On increasing the dose sedation progresses to hypnosis and then to stupor. But the drugs do not cause a true general anesthesia because -awareness usually persists -immobility sufficient to allow surgery cannot be achieved. However at "preanesthetic" doses, there is amnesia.
Slide 25-

Effects on the (EEG) and Sleep Stages ↓ sleep latency ↓ number of awakenings ↓ time spent in stage 0, 1, 3, 4 ↓ time spent in REM sleep (↑number of cycles of REM sleep) ↑ total sleep time (largely by increasing the time spent in stage 2)
Slide 26-

Respiration-Hypnotic doses of benzodiazepines are without effect on respiration in normal subjects CVS-In preanesthetic doses, all benzodiazepines decrease blood pressure and increase heart rate
Slide 27-

PHARMACOKINETICS A short elimination t1/2 is desirable for hypnotics, although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation. Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action). After metabolism these are conjugated and are excreted via kidney.
Slide 28-

ADVERSE EFFECTS Light-headedness Fatigue Increased reaction time Motor incoordination Impairment of mental and motor functions Confusion Antero-grade amnesia Cognition appears to be affected less than motor performance. All of these effects can greatly impair driving and other psychomotor skills, especially if combined with ethanol.
Slide 29-

FLUMAZENIL: A BENZODIAZEPINE RECEPTOR ANTAGONIST competitively antagonism Flumazenil antagonizes both the electrophysiological and behavioral effects of agonist and inverse-agonist benzodiazepines and β -carbolines. Flumazenil is available only for intravenous administration. On intravenous administration, flumazenil is eliminated almost entirely by hepatic metabolism to inactive products with a t1/2 of ~1 hour; the duration of clinical effects usually is only 30-60 minutes.
Slide 30-

FLUMAZENIL: A BENZODIAZEPINE RECEPTOR ANTAGONIST PRIMARY INDICATIONS FOR THE USE OF FLUMAZENIL ARE:- Management of suspected benzodiazepine overdose. Reversal of sedative effects produced by benzodiazepines administered during either general anesthesia. The administration of a series of small injections is preferred to a single bolus injection. A total of 1 mg flumazenil given over 1-3 minutes usually is sufficient to abolish the effects of therapeutic doses of benzodiazepines. Patients with suspected benzodiazepine overdose should respond adequately to a cumulative dose of 1-5 mg given over 2-10 minutes; A lack of response to 5 mg flumazenil strongly suggests that a benzodiazepine is not the major cause of sedation.
Slide 31-

Novel Benzodiazepine Receptor Agonists Z compounds zolpidem , zaleplon , zopiclone and eszopiclone structurally unrelated to each other and to benzodiazepines therapeutic efficacy as hypnotics is due to agonist effects on the benzodiazepine site of the GABAA receptor Compared to benzodiazepines, Z compounds are -less effective as anticonvulsants or muscle relaxants -which may be related to their relative selectivity for GABAA receptors containing the α1 subunit.
Slide 32-

Novel Benzodiazepine Receptor Agonists The clinical presentation of overdose with Z compounds is similar to that of benzodiazepine overdose and can be treated with the benzodiazepine antagonist flumazenil. Zaleplon and zolpidem are effective in relieving sleep-onset insomnia. Both drugs have been approved by the FDA for use for up to 7-10 days at a time. Zaleplon and zolpidem have sustained hypnotic efficacy without occurrence of rebound insomnia on abrupt discontinuation.
Slide 33-

ZALEPLON Its plasma t1/2 is ~1 hours approved for use immediately at bedtime or when the patient has difficulty falling asleep after bedtime. ZOLPIDEM Its plasma t1/2 is ~2 hours Cover most of a typical 8-hour sleep period, and is presently approved for bedtime use only.
Slide 34-

Eszopiclone Used for the long-term treatment of insomnia and for sleep maintenance. t1/2 of ~6 hours.
Slide 35-

MELATONIN CONGENERS RAMELTEON Synthetic tricyclic analog of MELATONIN. It was approved for the treatment of insomnia, specifically sleep onset difficulties. MECHANISM OF ACTION Melatonin levels in the suprachiastmatic nucleus rise and fall in a circadian fashion concentrations increasing in the evening as an individual prepares for sleep, and then reaching a plateau and ultimately decreasing as the night progresses.
Slide 36-

MELATONIN CONGENERS Mechanism of Action Two GPCRs for melatonin, MT1 and MT2, are found in the suprachiasmatic nucleus, each playing a different role in sleep. RAMELTEON binds to both MT1 and MT2 receptors with high affinity. Binding of Melatonin to MT1 receptors promotes the onset of sleep. Binding of Melatonin to MT2 receptors shifts the timing of the circadian system. RAMELTEON is efficacious in combating both transient and chronic insomnia
Slide 37-

Prescribing Guidelines for the Management of Insomnia Hypnotics that act at GABAA receptors, including the benzodiazepine hypnotics and the newer agents zolpidem, zopiclone, and zaleplon, are preferred to barbiturates because they have a Greater therapeutic index Less toxic in overdose Have smaller effects on sleep architecture Less abuse potential. Compounds with a shorter t1/2 are favored in patients with sleep-onset insomnia but without significant daytime anxiety who need to function at full effectiveness during the day. These compounds also appropriate for the elderly because of a decreased risk of falls and respiratory depression. One should be aware that early-morning awakening, rebound daytime anxiety, and amnestic episodes also may occur. These undesirable side effects are more common at higher doses of the benzodiazepines.
Slide 38-

Prescribing Guidelines for the Management of Insomnia Benzodiazepines with longer t1/2 are favored for patients - --- who have significant daytime anxiety and ----- who may be able to tolerate next-day sedation. However can be associated with -next-day cognitive impairment -delayed daytime cognitive impairment (after 2-4 weeks of treatment) as a result of drug accumulation with repeated administration. Older agents such as barbiturates, chloral hydrate, and meprobamate have high abuse potential and are dangerous in overdose.
Slide 39-

CATEGORIES OF INSOMNIA
Slide 40-

LONG-TERM INSOMNIA Nonpharmacological treatments are important for all patients with long-term insomnia.These include Reduced caffeine intake Avoidance of alcohol Adequate exercise Relaxation training Behavioral-modification approaches, such as sleep-restriction and stimulus-control therapies. Nonpharmacological treatments for insomnia have been found to be particularly effective in reducing sleep-onset latency and time awake after sleep onset.
Slide 41-

Management of Patients after Long-Term Treatment with Hypnotic Agents If a benzodiazepine has been used regularly for >2 weeks, it should be tapered rather than discontinued abruptly. In some patients on hypnotics with a short t1/2, it is easier to switch first to a hypnotic with a long t1/2 and then to taper. The onset of withdrawal symptoms from medications with a long t1/2 may be delayed. Consequently, the patient should be warned about the symptoms associated with withdrawal effects.
Slide 42-

Atypical Anxiolytics Buspiron Ipsapirone Gepirone Buspirone relieves anxiety -without causing marked sedative, hypnotic, or euphoric effects. - no anticonvulsant or muscle relaxant properties. Buspirone does not interact directly with GABAergic systems. Anxiolytic effects of buspirone is by acting as a partial agonist at brain 5-HT1A receptors.
Slide 43-

the anxiolytic effects of buspirone may take more than a week unsuitable for management of acute anxiety states no rebound anxiety or withdrawal signs on abrupt discontinuance The drug is not effective in blocking the acute withdrawal syndrome resulting from abrupt cessation of use of benzodiazepines or other sedative-hypnotics Buspirone has minimal abuse liability The drug is used in generalized anxiety states but is less effective in panic disorders
Slide 44-

MCQs Q1. Sleep promoting effect of ramelteon is mediated by receptor: A. GABAA receptor B. Opiate receptors C. GABAB receptor D. Melatonin receptors MT1 and MT2 Ans- D
Slide 45-

Q2. Which one of the following effects is NOT seen with barbiturates? A. Analgesic B. Anticonvulsant C. Induction and maintenance of anaesthesia D. Sedation Ans- A
Slide 46-

Q3. An ideal hypnotic drug should NOT have: A. rapid onset of action B. sustained effect throughout the night C. without any residual effect in the following morning D. increase in sleep latency Ans- D
Slide 47-

Q4. True statement about effect of bezodiazepines on sleep is: A. Time spent in stage 2 is decreased B. Time spent in stages 1, 3 and 4 is increased C. Shortening of REM sleep D. Increase sleep latency Ans- C
Slide 48-

Q5. Beta carboline at benzodiazepine receptor act as: A. Agonist B. Inverse agonist C. Antagonist D. Partial agonist Ans- B
Slide 49-

Q6. Benzodiazepine antagonist is: A. Naloxone B. Zolpidem C. Nalorphine D. Flumazenil Ans- D
Slide 50-

Q7. Benzodiazepines act by: A. Activating GABAA receptors directly B. Modulating the effects of GABA on GABAA receptors C. Antagonistic effect on GABAA receptors D. GABA mimetic effect Ans- B
Slide 51-

Q8. Administration of barbiturate is contraindicated in: A. Kernicterus B. Anxiety C. Epilepsy D. Acute Intermittant porphyria Ans-D
Slide 52-

Q9. Which is NOT true about Flumazenil? A. Acts on GABAA receptor B. Specific antagonist of benzodiazepine C. Given intravenously D. May be used in barbiturate poisoning Ans- D
Slide 53-

Q10. True statement about zolpidem: A. Relieve sleep onset insomnia B. Cause profound rebound insomnia C. Cause profound REM suppression D. Has strong anticonvulsant effect Ans- A
Slide 54-

Bibliography Essentials of Medical Pharmacology -7th edition by KD Tripathi Goodman & Gilman's the Pharmacological Basis of Therapeutics 12th edition by Laurence Brunton (Editor) Lippincott's Illustrated Reviews: Pharmacology - 6th edition by Richard A. Harvey Basic and Clinical pharmacology 11th edition by Bertram G Katzung Rang & Dale's Pharmacology -7th edition by Humphrey P. Rang Clinical Pharmacology 11th edition By Bennett and Brown, Churchill Livingstone Principles of Pharmacology 2nd edition by HL Sharma and KK Sharma Review of Pharmacology by Gobind Sparsh
Slide 55-

THANKS