Cns Drugs Week 7 PDF

PHARMACOLOGY FOR THE CENTRAL NERVOUS SYSTEM Prepared By: Justine Almodal, PTRP  CONTENTS SEDATIVE-HYPNOTIC ANTIPSYCHOTIC 1 AND ANTIANXIETY 3 DRUGS DRUGS DRUGS FOR AFFECTIVE ANTIEPILEPTIC 2 DISORDERS 4...

PHARMACOLOGY FOR THE CENTRAL NERVOUS SYSTEM Prepared By: Justine Almodal, PTRP  CONTENTS SEDATIVE-HYPNOTIC ANTIPSYCHOTIC 1 AND ANTIANXIETY 3 DRUGS DRUGS DRUGS FOR AFFECTIVE ANTIEPILEPTIC 2 DISORDERS 4 DRUGS DRUGS FOR CENTRAL NERVOUS SYSTEM Modify the activity of 01 neurons in order to treat specific disorders Alter the general 02 of arousal of the CNS  The largest and most rostral aspect CEREBRUM of the brain. The outer cerebrum or cerebral cortex is the highest order of conscious function and integration in the CNS. Most CNS therapeutic medications tend to affect cortical function indirectly by first altering the function of lower brain and spinal cord structures. An exemption to this are the drugs used to treat epilepsy and drugs that enhances cognitive function such as alzheimer’s disease. BASAL GANGLIA Primarily involved in the control of motor activities. Deficits in this area are seen in disorders such as Parkinson’s Disease and Huntington's chorea. Certain medications that treat these movement disorders exert their effects by interacting with basal ganglia structures. DIENCEPHALON THALAMUS HYPOTHALAMUS Contains distinct nuclei Involved in the control of that are crucial in the diverse body functions, including temperature integration of certain control, appetite, water types of sensations and balance and certain their relay to other areas emotional reactions. of the brain (Such as the Also significant in its somatosensory cortex). control over the function of hormonal release from the pituitary gland. RETICULAR ACTIVATING SYSTEM (RAS) Monitors and controls consciousness and is important in regulating the amount of arousal or alertness in the cerebral cortex. Sedative-Hypnotics and general anesthetics tend to exert their effects on the reticular formation. CNS stimulants (Caffeine and Amphetamines) may increase arousal through a stimulatory effect on reticular formation CEREBELLUM Interprets various sensory input and help modulate motor output. Also controls vestibular mechanisms responsible for balance and posture. Therapeutic medications are not usually targeted directly for the cerebellum, but incoordination and other other movement d/o may result if drug exerts toxic S/E on the cerebellum.  Involved in the control of LIMBIC SYSTEM emotional and behavioral activity. Motivation, aggression, sexual activity and instinctive responses may be influenced by activity within the limbic system. CNS drugs including some antianxiety and antipsychotic medications are believed to exert their beneficial effects primarily by altering activity in the limbic structures.  Consist of centrally located gray matter SPINAL CORD that is surrounded by white matter. ○ Gray matter: Synaptic transmission between various neurons. ○ White matter: for ascending and descending tracts. Certain CNS drugs such as narcotic and analgesic may exert an effect on synaptic transmission in the gray matter as well as synapses in other areas of the brain Drugs such as local anesthetics can block action potential propagation in white matter so that ascending and descending information is interrupted. BLOOD-BRAIN BARRIER Formed by highly specialized endothelial cells that line brain capillaries (Tight Junctions) Acts as a selective filter and seems to protect the CNS by limiting the harmful substances that enter brain and SC. In general, nonpolar, lipid soluble drugs are able to cross BBB by passive diffusion. Polar and lipophobic compounds are usually unable to enter the brain BLOOD-BRAIN BARRIER Ofloxacin Rifampin Moxifloxacin Doxycycline Isoniazid Metronidazole Cotrimoxazole Levofloxacin Minocycline CNS NEUROTRANSMITTERS Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse.  ACETYLCHOLINE BLOCKING DRUGS AKA antimuscarinic drugs Improve the tremor and rigidity of parkinsonism. Antimuscarinic medicines: ○ Arpicolin (Procyclidine) ○ Biorphen (Orphenadrine) ○ Broflex (Trihexyphenidyl) ○ Cogentin (Benztropine) ○ Disipal (Orphenadrine) ○ Kemadrin (Procyclidine) SEDATIVE-HYPNOTIC AND ANTIANXIETY DRUGS SEDATIVE-HYPNOTIC & ANTIANXIETY AGENTS To relax the patient and to promote sleep At higher doses may produce: ○ Drowsiness and initiate a relatively normal state of sleep (Hypnosis) ○ General anesthesia (Barbiturates) Treating epilepsy or produce muscle relaxation  SEDATIVE-HYPNOTIC DRUGS Fall into two general categories: Benzodiazepines and Nonbenzodiazepines These agents are used to promote sleep.  BENZODIAZEPINE Used to treat anxiety (Diazepam) Promote sleep Generally regarded as safer because there is less of a chance for lethal overdose  BENZODIAZEPINE ANTIANXIETY DRUGS GENERIC NAME TRADE NAME RELATIVE HALF-LIFE Alprazolam Xanax Short-Intermediate Chlordiazepoxide Librium Long Clonazepam Klonopin Intermediate Clorazepate Tranxene Long Diazepam Valium Long Halazepam Paxipam Long Lorazepam Ativan Short-Intermediate Oxazepam Serax Short-Intermediate  MOA OF BENZODIAZEPINES Increase inhibitory effects at CNS synapses that uses NT GABA → Excitation level in RAS is decrease → relaxation and sleep are enhanced.  NON-BENZODIAZEPINE (BARBITURATES) Premier medication used to promote sleep. Disadvantages: ○ Relatively small TI ○ Prolonged use is often a problem in terms of abuse MOA ○ Depress the RAS as well as some areas of the limbic system ○ Also depresses neuronal excitability in other areas of brain and SC.  NEWER NONBENZODIAZEPINE SEDATIVE-HYPNOTICS Zolpidem (Ambien), Zaleplon (Sonata) and Eszopiclone (Lunesta) ○ Chemically different from benzodiazepines but still seem to affect the GABA-A receptors-> GABA bind more effectively -> Inc. chloride conductance and the level of inhibition in neuron -> Inc. inhibition in certain types of the brain results in less arousal and the promotion of sleep.  PROBLEMS WITH SEDATIVE-HYPNOTICS Residual effects that can occur the day after administration. Anterograde Amnesia ○ Pt may trouble recalling details of events that occurred for a certain period of time before the drug was taken. Tolerance and Physical dependence ○ Tapering off the dosage rather than abruptly stopping it has been recommended as a safer way to terminate administration.  OTHER SIDE EFFECTS GI Discomfort ○ Nausea and vomiting Dry mouth Sore throat Muscular incoordination  ANXIETY Described as fear or apprehension over a situation or event that an individual feel is threatening. Classified in several clinical categories: ○ Generalized anxiety d/o ○ Social Anxiety ○ Panic d/o ○ OCD ○ Posttraumatic stress syndrome Anti-anxiety drugs can help decrease the tension and nervousness assoc. with many of these syndromes until the situation is resolved.  BUSPIRONE An anti-anxiety agent used to treat general anxiety d/o Does not act on GABA receptor Increase the effects of 5-Hydroxytryptamine (Serotonin) in certain areas of the brain. Produces less sedation and psychomotor impairment than benzodiazepine agents. Has moderate efficacy for severe anxiety. USE OF ANTIDEPRESSANTS IN ANXIETY  OTHER ANTI-ANXIETY DRUGS Beta-blockers such as propranolol (Inderal) Antipsychotic (quetiapine) Anticonvulsants (Gabapentin and Pregabalin) Antihistamine (Hydroxyzine)  PROBLEMS AND ADVERSE EFFECTS OF ANXIOLYTICS Sedation: MC S/E Psychomotor impairments Addiction and Abuse Buspirone ○ Dizziness ○ HA ○ Nausea ○ Restlessness DRUGS FOR AFFECTIVE DISORDERS  MAJOR DEPRESSIVE DISORDERS Feeling of helplessness, hopelessness and worthlessness Depressed mood and fatigue Unintentional weight changes Change in sleep patterns Agitation or psychomotor retardation Difficulty thinking, focusing or decision making Suicidal ideation  PATHOPHYSIOLOGY OF DEPRESSION Disturbances in CNS neurotransmission involving certain chemicals known as amine neurotransmitters. These transmitters include 5-Hydroxytryptamine (Serotonin), NE and dopamine. Increase in Postsynaptic receptor sensitivity to amine NT particularly NE and Serotonin.  ANTIDEPRESSANT DRUGS Tricyclics Monoamine Oxidase (MAO) Inhibitors Second Generation Drugs (SSRI/SNRI) Other Compounds TRICYCLIC ANTIDEPRESSANTS (TCA) GENERIC NAME TRADE NAME Amitriptyline Elavil, Endep Amoxapine Asendin Clomipramine Anafranil Desipramine Norpramin Doxepin Sinequan Imipramine Norfranil, Tofranil Nortriptyline Aventyl, Pamelor Protriptyline Vivactil Trimipramine Surmontil  ADVERSE EFFECT “HATS” ○ Hypotension ○ Anticholinergic effect ○ Tachycardia ○ Sedation MONOAMINE OXIDASE INHIBITORS (MAOI) Monoamine Oxidase (MAO) is an enzyme located at amine synapses and helps removed released transmitters through enzyme destruction. MAOI allow more NT to remain in the synaptic cleft and continue to exert an effect. MONOAMINE OXIDASE INHIBITORS (MAOI) GENERIC NAME TRADE NAME Isocarboxazid Marplan Phenelzine Nardil Tranylcypromine Parnate  SECOND-GENERATION ANTIDEPRESSANTS SELECTIVE-SEROTONIN REUPTAKE INHIBITORS (SSRI) ○ Selectively block the reuptake of 5-Hydroxytryptamine (Serotonin) SEROTONIN/NOREPINEPHRINE REUPTAKE INHIBITORS (SNRI) ○ Reboxetine Selectively inhibit transmitter reuptake at NE synapses ○ Venlafaxine Selectively decrease serotonin and NE reuptake without an appreciable effect of dopamine synapses. SECOND-GENERATION ANTIDEPRESSANTS SNRI GENERIC NAME TRADE NAME Citalopram Celexa Escitalopram Lexapro Fluoxetine** Prozac Fluvoxamine Luvox Paroxetine Paxil Sertraline Zoloft  SNRI GENERIC NAME AMINE SELECTIVITY Bupropion Primarily inhibits dopamine reuptake; Little effect on NE or serotonin Maprotiline Mod. Inhibition of NE reuptake Mirtazapine Inc. NE and Serotonin activity by blocking inhibitory presynaptic autoreceptors Nefazodone Slight Inhibition of serotonin and NE reuptake Trazodone Slight inhibition of serotonin reuptake Venlafaxine Strong inhibition of NE and serotonin reuptake  PROBLEMS AND ADVERSE EFFECTS OF ANTIDEPRESSANTS TCA ○ HATS MAOI ○ CNS excitation, less anticholinergic effect, hypertensive crisis SSRI and SNRI ○ “Serotonin Syndrome” Sweating, shivering, movement d/o (Severe restlessness, dystonias, dyskinesia), muscle fasciculation and other neuromuscular symptoms.  BIPOLAR DISORDER: ANTIMANIC DRUGS Bipolar syndrome is associated with mood swings from one extreme (Mania) to the other (Depression).  BIPOLAR DISORDER: PATHOPHYSIOLOGY Genetic and environmental factors conspire to increase NE and possibly serotonin influence. ○ Inc. NT activity= Manic episode ○ Dec. NT activity= Depression  ANTIMANIC DRUGS Lithium ○ Directly decrease the release of certain amine NT (NE and Dopamine) and increase the effects of other NT (Serotonin, Acetylcholine and GABA) ANTIPSYCHOTIC/ NEUROLEPTIC DRUGS  SCHIZOPHRENIA Thought disorder/Disruption of thought pattern Increased Dopamine “The Withdrawn” Behavior Cancer of the Mental Illness  SCHIZOPHRENIA Eugen Bleuler ○ Schizin *Split* ○ Phren *Mind* ○ Schism between thought, emotion and behavior ○ Described the fundamental Sx (4 A’s) Affect Autism Associative Looseness Ambivalence ○ Described the Secondary Sx Delusions Hallucinations  PATHOPHYSIOLOGY OF SCHIZOPHRENIA Genetic factors (i.e chromosomal abnormalities that cause deviations in brain structure and function) Environmental factors (Social stresses, prenatal or childhood brain injury ) Schizophrenia appears to be caused an over activity of dopamine pathways in certain parts of the brain such as the limbic system.  TRADITIONAL ANTIPSYCHOTICS GENERIC NAME TRADE NAME Chlorpromazine** Thorazine Fluphenazine Permitil, Prolixin Haloperidol ** Haldol Thioridazine Mellaril Trifluoperazine Stelazine Mesoridazine Serentil Loxapine Loxitane Perphenazine Trilafon, Triavil  ATYPICAL ANTIPSYCHOTICS GENERIC NAME TRADE NAME Ziprasidone Geodon Risperidone Risperdal Quetiapine Seroquel Olanzapine** Zyprexa Clozapine Clozaril Aripiprazole Abilify  PROBLEMS AND ADVERSE EFFECT OF ANTIPSYCHOTICS 1. Extrapyramidal Sx a. Acute Dystonic Reactions i. Torticollis ii. Facial grimacing iii. Abn. Eye Movement iv. Involuntary Muscle Mov’t b. Akathisia i. Restlessness ii. Difficulty in sitting still iii. Strong urge to move about PROBLEMS AND ADVERSE EFFECT OF ANTIPSYCHOTICS C. Pseudoparkinsonism D. Tardive Dyskinesia i. Motor retardation i. Protrusion of ii. Mask-like facies tongue iii. Tremor ii. Puffing of cheeks iv. “Pill rolling” iii. Chewing v. Rigidity movements vi. Salivation iv. Involuntary mov’t of vii. Shuffling gait trunk and extremities.  PROBLEMS AND ADVERSE EFFECT OF ANTIPSYCHOTICS 2. Sedation 3. Anticholinergic effects 4. OH 5. Photosensitivity 6. Weight gain, increase plasma lipids and DM (Newer and Atypical drugs) ANTIEPILEPTIC DRUGS  EPILEPSY Is a chronic neurologic disorder characterized by recurrent seizures. ○ Seizures: Episodes of sudden, transient disturbances in cerebral excitation that occur when a sufficient number of cerebral neurons begin to fire rapidly and in synchronized burst. CLASSIFICATION OF EPILEPTIC SEIZURES CLASSIFICATION OF EPILEPTIC SEIZURES  DRUGS USED TO TREAT EPILEPSY These drugs generally try to inhibit firing of certain cerebral neurons. ○ Inc. the inhibitory effects of GABA ○ Dec. the effects of excitatory amino acids (Glutamate and Aspartate) ○ Alter the movement of ions (Sodium, calcium) across the the neuronal membrane.  BARBITURATES Phenobarbital: Prescribed in virtually all types of adult seizures but seem to be especially effective in generalized tonic-clonic and simple complex partial seizures. A/E ○ Sedation (Primary problem) ○ Nystagmus ○ Ataxia ○ Folate/ Vit. K deficiency ○ Paradoxical inc. in seizures and inc in hyperactivity may occur in some children.  BENZODIAZEPINES Diazepam and Lorazepam: Used in the acute treatment of status epilepticus. Clonazepam: Recommended in specific forms of absence seizure and may also be useful in minor generalized seizures such as akinetic spells and myoclonic jerks. Clorazepate: Used as an adjunct in certain partial seizures.  HYDANTOINS Phenytoin: First drug considered in treating many types of epilepsy and especially effective in treating partial seizures and generalized tonic-clonic seizures. Fosphenytoin: Administered IV used to treat continuous uncontrolled seizures. A/E: ○ Gastric irritation ○ Confusion ○ Sedation ○ Dizziness ○ HA ○ Cerebellar signs ○ Gingival hyperplasia ○ Hirsutism ○ Skin d/o  IMINOSTILBENES Carbamazepine: Shown to be effective in treating all types of epilepsy except absence seizure and it is often considered as the primary agent for treating partial and tonic-clonic seizures. A/E ○ Dizziness ○ Drowsiness ○ Ataxia ○ Blurred vision ○ Anemia ○ Water retention ○ Cardiac arrhythmias and CHF  SUCCINIMIDES Ethosuximide, Methsuximide and Phensuximide: Primary agents in the treatment of absence (Petit mal) seizures A/E ○ GI distress ○ HA ○ Dizziness ○ Fatigue ○ Lethargy ○ Movement d/o ○ Skin rashes and itching  VALPROIC ACID Used primarily to treat absence seizures or as secondary agent in generalized tonic-clonic forms of epilepsy This drug is also used to treat bipolar d/o especially during the acute manic state. A/E: ○ GI distress ○ Temporary hair loss ○ Weight gain ○ Impaired platelet function  TREATMENT OF STATUS EPILEPTICUS Status Epilepticus ○ Series of seizures occurring without any appreciable period between individual seizures ○ Regarded as MEDICAL EMERGENCY!! ○ Treatment begins with standard emergency procedures such as maintaining airway and starting an IV line for blood sampling and drug administration.  TREATMENT OF STATUS EPILEPTICUS First drugs administered are usually Benzodiazepines (Lorazepam or Diazepam) given IV. Followed by Phenytoin If seizures continue despite these drugs Phenobarbital is given IV. If all other attempts fail, General Anesthesia (Halothane) may be used as a last resort. THE END THANK YOU FOR LISTENING!