CNS Drugs - PDF

Module 6 Central and Peripheral Nervous System Drugs 1. Muscle Relaxant 2. Sedatives, Anxiolytics, Hypnotics 3. Antidepressants 4. Antiparkinsonian 5. Antiepileptic 6. Antipsychotics Lesson 1 Muscle Relaxants Muscle Relaxants 2 main classes centrally-acting peripherally-acting Centr...

Module 6 Central and Peripheral Nervous System Drugs 1. Muscle Relaxant 2. Sedatives, Anxiolytics, Hypnotics 3. Antidepressants 4. Antiparkinsonian 5. Antiepileptic 6. Antipsychotics Lesson 1 Muscle Relaxants Muscle Relaxants 2 main classes centrally-acting peripherally-acting Centrally-Acting baclofen carisoprodol chlorphenesin Centrally-Acting MOA GABA_B receptor agonist. GABA (gamma-aminobutyric acid) is an inhibitory neurotransmitter in the central nervous system. By stimulating GABA_B receptors, baclofen reduces the release of excitatory neurotransmitters and inhibits the transmission of nerve signals in the spinal cord and brain Indication treat acute, painful musculoskeletal conditions usually prescribed along with rest and physical therapy Centrally-Acting Indication Primarily indicated for the management of spasticity. It is commonly used to treat conditions like Multiple sclerosis (MS) Spinal cord injuries or diseases Cerebral palsy Stroke (to alleviate muscle spasms) It can also be used off-label for: Chronic hiccups Trigeminal neuralgia Centrally-Acting Adverse Reactions most frequently seen adverse effects relate to the associated CNS depression*, GI disturbances linked to CNS depression of the parasympathetic reflexes**, hypotension and arrythmias*, urinary frequency, enuresis, and feelings of urinary urgency chlorzoxazone may discolor the urine, becoming orange to purplish-red when metabolized and excreted** tizanidine has been associated with liver toxicity and hypotension in some patients Peripherally-Acting Dantrolene sodium* major effect is on the muscles** high therapeutic doses are toxic to the liver Peripherally-Acting Pharmacodynamics dantrolene works by acting on the muscle interferes with calcium ion release from the sarcoplasmic reticulum and weakens the force of contraction Indication helps manage spasticity especially in patients with cerebral palsy, MS, SCI, and stroke used to treat and prevent malignant hyperthermia Drug Interactions simultaneous use of dantrolene and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase CNS depression if given with estrogen, may lead to increased risk of liver toxicity Sedatives, Anxiolytics and Hypnotic Agents Sedatives and Hypnotics sedatives reduce activity or excitement* when given in large doses, sedatives are considered hypnotics** 3 main classes of synthetic drugs used as sedatives and hypnotics are benzodiazepines barbiturates nonbenzodiazepine-nonbarbiturate drugs Benzodiazepines minor tranquilizer; anxiolytic therapeutic effects include daytime sedation, sedation before anesthesia, sleep inducement, relief on anxiety and tension, skeletal muscle relaxation and anticonvulsant activity* estazolam, flurazepam, lorazepam, quazepam, temazepam, triazolam, (diazepam) VALIUM Benzodiazepines MOA stimulate GABA receptors in the ascending reticular activating system (RAS) of the brain* Act in the limbic system & the RAS to make GABA more effective, causing interference to neuron firing Indication Insomnia Alcohol withdrawal Anxiety Seizure disorders Barbiturates major pharmacologic action is to reduce the overall CNS alertness barbiturates that are used primarily as sedatives and hypnotics include amobarbital, aprobarbital, butabarbital sodium, mephobarbital, pentobarbital sodium, phenobarbital, secobarbital sodium low dose: depress sensory and motor cortex of the brain causing drowsiness high dose: cause respiratory depression and death because of their ability to depress all levels of the CNS Barbiturates Pharmacodynamics depress sensory cortex of the brain, decrease major activity, alter cerebral function, and produce drowsiness, sedation and hypnosis Inhibits neural impulse conduction in the ascending RAS, depress the cerebral cortex, alter cerebellar function & depresses motor output. Indication Insomnia Preoperative sedation and anesthesia Relief of anxiety Anticonvulsant effects Antidepressants Antidepressants treat affective disorders* include Monoamine Oxidase Inhibitors (MAOIs) Tricyclic Antidepressants (TCAs) Selective Serotonin Reuptake Inhibitors (SSRIs) MAO Inhibitors Pharmacodynamics work by inhibiting monoamine oxidase* making more norepinephrine and serotonin available to the receptors and thereby relieving the symptoms of depression Indication Management of choice for atypical depression** Other uses include* phobic anxieties, hypochondriasis and refractory narcolepsy  MAO Inhibitors Food and Drug Interactions Severe reaction may occur if taken with tyramine* rich food such as red wines, aged cheese and fava beans, and sympathomimetic drugs Tricyclic Antidepressants treat major depression, effective and less expensive than SSRIs and other drugs block the uptake of the neurotransmitter norepinephrine and serotonin include amitriptyline hydrochloride, amitriptyline pamoate, amoxapine, clomipramine hydrochloride, desipramine hydrochloride, doxepin hydrochloride, imipramine pamoate, nortriptyline hydrochloride, protriptyline hydrochloride and trimipramine maleate Tricyclic Antidepressants Pharmacodynamics increase the amount of norepinephrine, serotonin or both by preventing their reuptake into the storage granules in the presynaptic nerves Tricyclic Antidepressants Indication Used to treat episodes of major depression effective in treating depression of insidious onset accompanied by weigh loss, anorexia or insomnia physical symptoms may respond after 1 to 2 weeks of therapy; psychological after 2 to 4 weeks Drug Interactions Concurrent use with MAOIs may cause an extremely elevated body temperature, excitation and seizures Increased anticholinergic effects when taken with anticholinergic drugs* reduce the antihypertensive effects of clonidine and guanethidine Selective Serotonin Reuptake Inhibitors (SSRIs) Formerly known as 2nd generation antidepressants* Developed to treat depression with fewer side effects Selective Serotonin Reuptake Inhibitors (SSRIs) Pharmacodynamics inhibit the neuronal reuptake of the neurotransmitter serotonin* Selective Serotonin Reuptake Inhibitors (SSRIs) Indication Used to treat the same major depressive episodes as TCAs and have the same degree of effectiveness Some are used to treat obsessive-compulsive disorder (OCD)* may also be useful in treating panic disorders, eating disorders, personality disorders, impulse control and premenstrual syndrome Antiparkinsonian Agents Antiparkinsonian Drugs 2 goals promote the secretion of dopamine (dopaminergic drugs) inhibit the cholinergic effects (anticholinergic drugs) Anticholinergic Pharmacodynamics high acetylcholine levels produce an excitatory effect on the CNS, which can cause parkinsonian tremors the drugs inhibit the action of acetylcholine at the receptor sites in the CNS and ANS, thus reducing tremors Dopaminergic Include drugs that are chemically unrelated levodopa, the metabolic precursor to dopamine carbidopa-levodopa, a combination drug composed of carbidopa* and levodopa Dopaminergic MOA act in the brain to improve motor function in or two ways – increasing dopamine concentration and/or enhancing the neurotransmission of dopamine Dopaminergic Pharmacodynamics Increase the amount of dopamine in the brain by increasing dopamine release or by blocking dopamine reuptake from presynaptic neurons Dopaminergic Indication to treat patients with severe parkinsonism or those who do not respond to anticholinergics alone levodopa is the most effective drug used to treat Parkinson’s disease* some (amantadine, pramipexole, bromocriptine) must be tapered to avoid precipitating parkinsonian crisis and possible life-threatening complications Dopaminergic Adverse Reactions levodopa: nausea and vomiting, orthostatic hypotension, anorexia, neuroleptic malignant syndrome*, arrythmias, irritability, confusion amantadine: orthostatic hypotension, constipation bromocriptine: persistent orthostatic hypotension, ventricular tachycardia, bradycardia, worsening angina pergolide: confusion, dyskinesia**, hallucinations, nausea pramipexole: orthostatic hypotension, dizziness, confusion, insomnia Antiepileptic Agents Anticonvulsant / Anti- epileptic Drugs also, antiepileptic drugs usually prescribed for long term management of chronic epilepsy (recurrent seizures) or short-term management of acute isolated seizures not caused by epilepsy, such as after trauma or brain injury five major classes hydantoins barbiturates iminostilbenes benzodiazepines valproic acid Hydantoins the first anticonvulsant used to treat seizures include phenytoin (10-20 mcg/ml), phenytoin sodium, fosphenytoin, mephenytoin MOA: stabilize nerve cells to keep them from overexcited phenytoin works in the motor cortex of the brain where it stops the spread of seizure activity Hydantoins Pharmacotherapeutics phenytoin is the most commonly prescribed anticonvulsant drug because of its effectiveness and low toxicity also acts as an antidysrhythmic by increasing the electrical stimulation threshold in cardiac tissue non-addicting but has teratogenic effects on the fetus it’s one of the drugs of choice to manage complex partial seizure (psychomotor or temporal lobe seizures) tonic-clonic seizures Hydantoins Adverse Effects May cause severe liver toxicity, bone marrow suppression, gingival hyperplasia*, potentially serious dermatological reactions**, bone marrow suppression Barbiturates long-acting barbiturate phenobarbital was formerly one of the most widely used anticonvulsants, now less frequent due to the adverse effects therapeutic serum range for phenobarbital is 15-40 mcg/ml Barbiturates MOA inhibit impulse conduction in the ascending RAS, depress the cerebral cortex, alter cerebellar function, and depress motor nerve output stabilize nerve membranes throughout the CNS directly by influencing ion channels in the cell membrane* Indication effective in treating partial, tonic-clonic and febrile seizures Adverse Effects most common adverse effects relate to CNS depression and its effects on body function** can produce sedation, hypnosis, and deep coma*** may be associated with physical dependence and withdrawal syndrome Benzodiazepines drugs that provide anticonvulsant effects include diazepam (parenteral form) clonazepam (recommended for long term treatment of epilepsy; 20-80 ng/ml) clorazepate (adjunct therapy in treating partial seizures) Benzodiazepines MOA potentiate the effects of GABA* Stabilize nerve membranes throughout the CNS to decrease excitability and hyperexcitability to stimulation** Indication absence, atonic and myoclonic seizures Antipsychotic Agents Antipsychotic Agents control psychotic symptoms such as delusion, hallucinations and though disorders that can occur with schizophrenia, mania and other psychoses* Various Names antipsychotics: eliminate the signs and symptoms of psychoses major tranquilizer: calm an agitated patient neuroleptic: can cause an adverse neurobiological effect that causes abnormal body movements Major Groups** typical antipsychotics: phenothiazines and nonphenothiazines atypical antipsychotics: clozapine, olanzapine and risperidone Typical Antipsychotics drug classes of non phenothiazines according to chemical structure butyrophenones: haloperidol and haloperidol decanoate dibenzoxazepines: loxapine succinate dihydroindolones: molindone hydrochloride diphenylbutylpiperidines: pimozide thioxanthenes: chlorprothixene, thiothixene and thiothixene hydrochloride Typical Antipsychotics Pharmacodynamics work by blocking postsynaptic dopaminergic receptors in the brain phenothiazines stimulate the extrapyramidal system* Typical Antipsychotics Indication Phenothiazines schizophrenia calm anxious or agitated patients improve patient’s thought process alleviate delusions and hallucinations Atypical Antipsychotics lesser side effects; most common is weight gain 2 advantages over typical antipsychotics effective in treating negative symptoms not likely to cause EPS include clozapine olanzapine risperidone  Atypical Antipsychotics MOA block the dopamine receptors but not as effectively as the typical antipsychotics, in addition to blocking serotonin receptor activity* Atypical Antipsychotics Indication Schizophrenic patients who are unresponsive to typical antipsychotics