Pharmacology Lecture Notes PDF

‫د‪.‬ي‬ ‫مواف التامنة فارما‬  CNS 01229984633 Anxiety Disorders & Anxiolytics  Classification of Anxiety D...

‫د‪.‬ي‬ ‫مواف التامنة فارما‬  CNS 01229984633 Anxiety Disorders & Anxiolytics  Classification of Anxiety Disorders 1. Generalized Anxiety Disorder (GAD) 2. Panic Disorder 3. Social Phobia 4. Obsessive Compulsive Disorder (OCD) 1) Generalized Anxiety Disorder (GAD) 2) Panic Disorder  It is characterized by an exaggerated autonomic response, irritability,  It is characterized by autonomic symptoms, hot flashes, and fear of dying difficulty in concentrating and swallowing, and insomnia. or going crazy. Classification of anxiolytic 1) Bezodiazepines 2) Nonbenzodiazepines, Zolpidem (only hypnotics) 3) buspirone (no hypnosis or dependance) 4) Barbiturates 5) Antihistaminics: H1 antagonists; Diphenhydramine, Doxylamine, Hydroxyzine, Promethazin Benzodiazepines  Benzodiazepines are the most widely used anxiolytic drugs. Introduction  They have largely replaced barbiturates because the benzodiazepines are safer and more effective  The targets for benzodiazepine actions are the gamma-aminobutyric acid (GABAA) Note: GABA is the major inhibitory neurotransmitter in the central nervous system  Benzodiazepines modulate the GABA effects by binding to a specific, high-affinity site.  The benzodiazepine receptor locations in the CNS parallel those of the GABA neurons.  Binding of GABA to its receptor triggers an opening of a chloride channel, which leads to an increase in chloride conductance. Mechanism of Benzodiazepines increase the frequency of channel openings produced by GABA. action  The influx of chloride ions causes a small hyperpolarization that moves the postsynaptic potential away from its firing threshold and, thus, inhibits the formation of action potentials.  Note: Binding of a benzodiazepine to its receptor site will increase the affinity of GABA for the GABA-binding site (and vice versa) without actually changing the total number of sites.  The clinical effects of the various benzodiazepines correlate well with each drug's binding affinity for the GABA receptor-chioride ion channel complex. Inhibitory Pathways 1. Reduction of anxiety: At low doses Actions 2. Sedative and hypnotic actions: can produce hypnosis (artificially produced sleep) at higher doses. 1 ‫ بارا‬/ ‫ فارما‬/ ‫ باثو‬/‫فسيولوجي‬ By/ Ali Elmewafy  CNS 01229984633 3. Anterograde amnesia: The temporary impairment of memory with use of the benzodiazepines. 4. Anticonvulsant: some are used to treat epilepsy (status epilepticus) 5. Muscle relaxant: Baclofen is a muscle relaxant as they affect the spinal cord. 1) Anxiolytic, anticonvulsant, and sedative 2) Anxiety disorders: These drugs should not be used to alleviate the normal stress of everyday life. They should be reserved for continued severe anxiety. and then should only be used for short periods of time because of their addiction potential. 3) Muscular disorders Therapeutic Uses 4) Amnesia: The shorter-acting agents are often employed as premedication for anxiety- provoking and unpleasant procedures, such as bronchoscopic, and certain dental procedures. Seizures - Sleep disorders 5) In the treatment of insomnia, it is important to balance the sedative effect needed at bedtime with the residual sedation (hangover) upon awakening.  Psychological and physical dependence on benzodiazepines can develop if high doses of the drugs are given over a prolonged period. Dependence  Abrupt discontinuation of the benzodiazepines results in withdrawal symptoms, including confusion, anxiety, restlessness, insomnia, tension, and rarely, seizures. Drugs  Midazolam , Nitrazepam , Triazolam , Estazolam  Higher therapeutic index than older drugs  No effect on liver enzyme Advantages  Less depressant effect on respiration  Lower abuse potential  Presence of specific antagonist  Drowsiness and confusion: These effects are the two most common side effects of the benzodiazepines. Adverse effects  Ataxia occurs at high doses and precludes activities that require fine motor coordination, such as driving an automöbile.  Cognitive impairment (decreased long-term recall and acquisition of new knowledge) can occur with use of benzodiazepines.  Benzodiazepines should be used cautiously in treating patients with liver disease.  Alcohol and other CNS depressants enhance the sedative-hypnotic effects of the benzodiazepines, Flumazenil Precautions ‫مهم‬  is a GABA-receptor antagonist that can rapidly reverse the effects of benzodiazepines,  The drug is available for intravenous administration only.  Onset is rapid but duration Is short, with a half-life of about 1 hour.  Frequent administration may be necessary to maintain reversal of a long-acting benzodiazepine. 2 ‫ بارا‬/ ‫ فارما‬/ ‫ باثو‬/‫فسيولوجي‬ By/ Ali Elmewafy