Anxiolytic and Hypnotic Drugs Lec 1 PDF

PHARMACOLOGY CNS Lec 1 Dr. Anxiolytic and Hypnotic drugs Benzodiazepines − Group of drugs that are widely used anxiolytic drugs. Benzodiazepine are safe and effective. Mechanism of a...

PHARMACOLOGY CNS Lec 1 Dr. Anxiolytic and Hypnotic drugs Benzodiazepines − Group of drugs that are widely used anxiolytic drugs. Benzodiazepine are safe and effective. Mechanism of action − Benzodiazepines act on γ-aminobutyric acid (GABA) receptors, they are safer and more effective.  GABA is the major inhibitory neurotransmitter in the central nervous system(CNS)  GABA receptors are composed of ve subunits α, β and γ that span the postsynaptic membrane.  Binding of GABA to its receptor triggers an opening of the central ion fi channel, allowing chloride through the pore. The influx of chloride ions causes hyperpolarization of the neuron and decreases neurotransmission by inhibiting the formation of action potentials. 1  PHARMACOLOGY CNS Lec 1 Dr. Therapeutic Uses ‫من اسئلة املد‬ 1- anxiety disorders ‫أﺿﻄﺮاﺑﺎت اﻟﻘﻠﻖ‬ ‫اﻻﻛﺘﺌﺎب‬ ‫اﻧﻔﺼﺎم اﻟﺸﺨﺼﯿﺔ‬ − Anxiety with depression and schizophrenia − Should not be used to alleviate the normal stress of everyday life. ‫ﻻ ﯾﻨﺒﻐﻲ اﺳﺘﺨﺪاﻣﮫ ﻟﻠﺘﺨﻔﯿﻒ ﻣﻦ اﻟﺘﻮﺗﺮ اﻟﻄﺒﯿﻌﻲ ﻟﻠﺤﯿﺎة اﻟﯿﻮﻣﯿﺔ‬ − Reserved for continued severe anxiety and used for short period, tolerance occur when use it 1-2 Wks. anti-anxiety less subject to tolerance ‫اﻟﻤﮭﺪء‬ ‫اﻟﻤﻨﻮم‬ than sedative & hypnotic effect. Long-acting agent prefer than short acting ‫ﻣﻔﺎﺟﻰء‬ ‫ﺷﺪﯾﺪ‬ agent it induce more abrupt and sever withdrawal reaction. Tolerance (decreased responsive to repeated 2- Muscular disorders doses of the drug) ‫إﺟﮭﺎد ﻋﻀﻠﻲ‬ − Diazepam is useful in muscular spasm such as muscle strain. − Muscle spasticity as in multiple sclerosis and cerebral palsy. 3- Amnesia ‫ﻓﻘﺪان اﻟﺬاﻛﺮة‬ ‫ﺗﺸﻨﺞ اﻟﻌﻀﻼت ﻛﻤﺎ ھﻮ اﻟﺤﺎل ﻓﻲ اﻟﺘﺼﻠﺐ اﻟﻤﺘﻌﺪد واﻟﺸﻠﻞ اﻟﺪﻣﺎﻏﻲ‬ − Premedication for endoscopic and bronchoscopy procedure as well as ‫ﻗﺴﻄﺮة اﻟﻘﻠﺐ‬ angioplasty use short acting agent. 2  PHARMACOLOGY CNS Lec 1 Dr. 4- Seizures ‫ﻧﻮﺑﺎت اﻟﺼﺮع‬ ( ‫اﻟﺼﺮع اﻟﻐﯿﺎﺑﻲ )اﻟﻤﺮﯾﺾ ﯾﺼﻔﻦ‬ − Clonazepam useful in abscent epelipsy. − Diazepam is used in grand mal and status epilepticus & acute alcohol withdrawal. Reduce withdrawal related seizure. 5- sleep disorder − All benzodiazepines have sedative and calming effects but not all of them have hypnotic effects..‫ﻟﮭﺎ ﺗﺄﺛﯿﺮات ﻣﺴﻜﻨﺔ وﻣﮭﺪﺋﺔ وﻟﻜﻦ ﻟﯿﺲ ﻛﻠﮭﺎ ﻟﮭﺎ ﺗﺄﺛﯿﺮات ﻣﻨﻮﻣﺔ‬ ‫اﻟﻜﻤﻮن‬ − They decrease the latency to sleep onset and increase stage two of non- REM sleep. − Diazepam, clonazepam, chlordiazepoxide, clorazepate, C l a s s i f i c a t i o n Flurazepam. [klor-di-az-ePOX-ide] [klor-AZ-e-pate] 1. L o n g - a c t i n g b e n z o d i a z e p i n e s 2. Intermediate acting Lorazepam, Alprazolam, Temazepam. [al-PRAY-zoe-lam] − − Triazolam, midazolam, Oxazepam 3. S h o r t a c t i n g D e p e n d e n c e  P s y c h o l o g i c a l a n d p h y s i c a l d e p e n d e n c e f o r h i g h d o s e s a n d f o r ‫اﻻرﺗﺒﺎك‬ ‫واﻟﻘﻠﻖ‬ ‫واﻹﺛﺎرة‬  Withdrawal symptoms include confusion, anxiety, agitation, p r o l o n g e d t i m e. ‫واﻷرق‬ ‫اﻟﺘﻮﺗﺮ‬ restlessness, insomnia, and tension 3  PHARMACOLOGY CNS Lec 1 Dr. Adverse Effects ‫اﻟﻨﻌﺎس‬ ‫االرتباك‬ 1- Drowsiness and Confusion- Most Common − Ataxia- at high dose- precludes activities that require fine motor loss of full control of body movements coordination such as driving ‫ﯾﻤﻨﻊ اﻷﻧﺸﻄﺔ اﻟﺘﻲ ﺗﺘﻄﻠﺐ ﺗﻨﺴﯿﻘﺎ ﺣﺮﻛﺎ دﻗﯿﻘﺎ ﻣﺜﻞ اﻟﻘﯿﺎدة‬ − cognitive impairment ‫ﺿﻌﻒ إدراﻛﻲ‬ (decreased long-term recall and retention of new knowledge) − Triazolam show rapid tolerance. ‫من اسئلة املد‬ 2- Precautions ‫اﻻﺣﺘﯿﺎطﺎت اﻟﻼزﻣﺔ‬ − Liver disease (metabolism in liver) Acute narrow angle glaucoma avoided − Alcohol and other CNS depressant enhance benzodiazepine effects − Not used in pregnancy & breast milk. Other Anxiolytic and Hypnotic Agents Zolpidem: [ZOL-pi-dem] − It is not a benzodiazepine but it acts on BZ receptor − It has short duration of action and exhibit minimal rebound withdrawal effects. Hydroxyzine: ‫ﻣﻀﺎد ﻟﻠﺘﻘﻲء‬ − It is antihistamine with antiemetic activity. ‫ﻣﮭﺪء‬ − It is used for sedation prior to surgery. Benzodiazepine antagonist Flumazenil [floo-MAZ-eh-nill] ‫من اسئلة املد‬ ‫ﯾﻌﻜﺲ‬ − It is GABA receptor antagonist that can rapidly reverse the effects of benzodiazepine ‫اﻟﺠﺮﻋﺔ اﻟﻤﺘﻜﺮرة‬ − It has short half-life; therefore, repeated doses should be given to ‫ﯾﻌﻜﺲ‬ maintain reversal of long-acting benzodiazepine IV administration only. 4  PHARMACOLOGY CNS Lec 1 Dr. They were formerly the mainstay of treatment used to sedate the patient or to maintain sleep Today they have been largely replaced by benzodiazepines for the following 1. Causes enzyme induction ‫من اسئلة املد‬ 2. Induces tolerance 3. Causes Physical dependence and severe withdrawal symptoms 4. Narrow margin of safety. Mechanism of action − Interaction with GABA receptors which enhances GABAergic transmission, the binding site of barbiturates on GABA distinct from BZD. − Barbiturate can block excitatory glutamate receptors. Individual drugs ‫اﻟﺘﺨﺪﯾﺮ‬ Thiopental: Ultra short acting barbiturate used to induce anaesthesia Phenobarbitone: Long-acting barbiturate used in tonic clonic convulsion, status ‫ﺗﺴﻤﻢ اﻟﺤﻤﻞ‬ ‫اﻟﺘﺸﻨﺞ اﻟﺤﻤﻮي‬ epilepticus, and eclampsia, febrile convulsion. Non barbiturate sedatives Chloral hydrate − It is pro-drug, it is converted to active metabolite, trichloro ethanol. − It is effective as sedative and hypnotics. − It is irritating to the gastrointestinal tract and causes epigastric distress. 5  PHARMACOLOGY CNS Lec 1 Dr. − Diphenhydramine ‫ارق‬ − It has sedating properties and used in mild insomnia − Other antihistamines chlorpheniramine Ethanol − It has anti-anxiety and sedative effects but its toxic potential out weights its benefits..‫ﻟﮫ ﺗﺄﺛﯿﺮات ﻣﻀﺎدة ﻟﻠﻘﻠﻖ وﻣﮭﺪﺋﺔ وﻟﻜﻦ إﻣﻜﺎﻧﺎﺗﮫ اﻟﺴﺎﻣﺔ ﺗﻔﻮق ﻓﻮاﺋﺪه‬ − Chronic consumption lead to sever liver disease, gastritis and nutritional deficiency. − Cardiotoxicity is also a consequence of heavy drinking. − Benzodiazepines are the treatment of choice for alcohol withdrawal syndrome. Disulfiram [dye-SUL-fi-ram] − It blocks the oxidation of acetaldehyde to acetic acid. The result is accumulation of acetaldehyde and causing flushing, tachycardia, hyperventilation and nausea. Disulfiram is used in patients want to stop alcohol ingestion ‫من اسئلة املد‬ Buspirone [Byoo-SPYE-rone] Antianxiety partial agonist act on serotonine receptor used in elderly age not cause dependance because not act on GABA − Melatonin Secrete from pineal gland cause sleep Ramelteon act on MT1, MT2 cause sleep Side effects: GIT disturbances ‫ ﯾﺸﺎر إﻟﯿﮫ ﺧﺼﯿﺼﺎ ﻟﻌﻼج‬.‫دواء ﻧﺎھﺾ اﻟﻤﯿﻼﺗﻮﻧﯿﻦ ﯾﺴﺘﺨﺪم ﻟﻌﻼج اﻷرق‬.‫اﻷرق اﻟﺬي ﯾﺘﻤﯿﺰ ﺑﺼﻌﻮﺑﺎت ﻣﻊ ﺑﺪاﯾﺔ اﻟﻨﻮم‬ 6 PHARMACOLOGY CNS Lec 1 Dr. 7