Central and Peripheral Nervous System Drugs PDF

Module 6 Central and Peripheral Nervous System Drugs MONECELLE JOY D. PESINABLE Instructor Lesson 1 Muscle Relaxants MONECELLE JOY D. PESINABLE Instructor Muscle Relaxants relieve musculoskeletal pain or spasm and severe musculoskeletal spasticity used to treat acute, painful musculoskelet...

Module 6 Central and Peripheral Nervous System Drugs MONECELLE JOY D. PESINABLE Instructor Lesson 1 Muscle Relaxants MONECELLE JOY D. PESINABLE Instructor Muscle Relaxants relieve musculoskeletal pain or spasm and severe musculoskeletal spasticity used to treat acute, painful musculoskeletal conditions and muscle spasticity associated with Multiple Sclerosis (MS), cerebral palsy, stroke, and spinal cord injuries 2 main classes centrally-acting peripherally-acting Centrally-Acting acts on the central nervous system used to treat acute spasms caused by anxiety, inflammation, pain and trauma a patient with acute muscle spasms may receive one of the following drugs baclofen carisoprodol chlorphenesin chlorzoxazone cyclobenzaprine metaxalone methocarbamol orphenadrine tizanidine Centrally-Acting Pharmacokinetics absorbed in the GIT widely distributed metabolized in the liver and excreted thru the kidneys onset: oral is 30 min to 1 hour; duration varies from 4 to 6 hours cyclobenzaprine has the longest duration of 12 to 25 hours Centrally-Acting Pharmacodynamics do not relax skeletal muscles directly or depress neuronal conduction, neuromuscular transmission, or muscle excitability depress the CNS* Pharmacotherapeutics treat acute, painful musculoskeletal conditions usually prescribed along with rest and physical therapy Centrally-Acting Drug Interactions interact with other CNS depressants causing increased sedation, impaired motor function and respiratory depression cyclobenzaprine interacts with MAOIs and can result in a high body temperature, excitation and seizures methocarbamol can antagonize the cholinergic effects of the anticholinesterase drugs used to treat myasthenia gravis 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 most common is dantrolene sodium* major effect is on the muscles** high therapeutic doses are toxic to the liver Pharmacokinetics peak is 5 hours after ingestion absorbed slowly in the GIT; highly plasma bound metabolized in the liver with a half life of 4 to 8 hours and excreted in the urine half life for healthy adults is 9 hours; maybe prolonged for patients with liver dysfunction 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 Pharmacotherapeutics 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 Lesson 2 Sedatives, Anxiolytics and Hypnotic Agents MONECELLE JOY D. PESINABLE Instructor 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 Pharmacokinetics absorbed well from the GIT and distributed widely in the body some may be given parenterally metabolized in the liver and excreted primarily in the urine Benzodiazepines Pharmacodynamics stimulate GABA receptors in the ascending reticular activating system (RAS) of the brain* low dose: decrease anxiety by acting on the limbic system and other areas of the brain that help regulate emotional activity; calm and sedate high dose: induce sleep** Pharmacotherapeutics Clinical indications include relaxing the patient during the day of before surgery, treating insomnia, producing IV anesthesia, treating alcohol withdrawal symptoms, treating anxiety and seizure disorders and producing skeletal muscle relaxation*** 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 Pharmacokinetics absorbed well from the GIT and distributed rapidly metabolized in the liver and excreted in the urine Pharmacodynamics depress sensory cortex of the brain, decrease major activity, alter cerebral function, and produce drowsiness, sedation and hypnosis Pharmacotherapeutics Clinical indications include daytime sedation*, hypnotic effects for patients with insomnia, preoperative sedation and anesthesia, relief of anxiety, anticonvulsant effects Prolonged use can lead to drug tolerance as well as psychological and physical dependence Nonbenzodiazepines-Nonbarbiturates act as hypnotics for short-treatment of simple insomnia no special advantages over other sedatives include chloral hydrate, ethchlorvynol and zolpidem Lose their effectiveness by the end of the 2nd week except zolpidem (35 days) Pharmacokinetics and Pharmacodynamics Absorbed rapidly from the GIT, metabolized in the liver and excreted in the urine MOA is not fully known but thought to produce depressant effects similar to barbiturates Nonbenzodiazepines-Nonbarbiturates Pharmacotherapeutics typically used for short term treatment of simple insomnia, sedation before surgery and sedation before EEG studies Drug Interactions common when given with other CNS depressants causing additive CNS depression resulting in drowsiness, respiratory depression, stupor, coma and death Antianxiety Drugs also known as anxiolytics used primarily to treat anxiety disorders 3 main types Benzodiazepines Barbiturates buspirone Buspirone buspirone hydrochloride is the first anxiolytic in a class of drugs known as azaspirodecanedione derivatives fewer side effects than some other common antianxiety drugs advantages less sedation no increase in CNS depressant effects when taken with alcohol or sedative-hypnotics low abuse potential Buspirone Pharmacokinetics absorbed rapidly; undergoes extensive first pass effect metabolized in the liver and eliminated in the urine and feces Pharmacodynamics MOA is unknown does not affect the GABA receptors produce various effects in the midbrain and act as a midbrain modulator, possibly due to its high affinity for serotonin receptors Buspirone Pharmacotherapeutics used to treat generalized anxiety states ineffective when quick relief from anxiety is needed because of its slow onset of action Drug Interactions does not interact with alcohol or other CNS depressants when given with MAOIs, hypertensive reaction may occur Lesson 3 Antidepressants MONECELLE JOY D. PESINABLE Instructor Antidepressants treat affective disorders* include Monoamine Oxidase Inhibitors (MAOIs) Tricyclic Antidepressants (TCAs) Selective Serotonin Reuptake Inhibitors (SSRIs) MAO Inhibitors 2 classifications based on chemical structure hydrazines, which include phenelzine sulfate nonhydrazines, comprised of a single drug, tranylcypromine sulfate Pharmacokinetics Absorbed rapidly and completely from the GIT Metabolized in the liver to inactive metabolites Excreted mainly by the GIT and to a lesser degree by the kidneys MAO Inhibitors Pharmacodynamics MOA is unclear work by inhibiting monoamine oxidase* making more norepinephrine and serotonin available to the receptors and thereby relieving the symptoms of depression Pharmacotherapeutics management of choice for atypical depression** may be used to treat typical depression resistant to other therapies or when other therapies are contraindicated other uses include* phobic anxieties, neurodermatitis, hypochondriasis and refractory narcolepsy MAO Inhibitors Food and Drug Interactions MAOI plus antidiabetics = may enhance hypoglycemic effects MAOI plus meperidine = excitation, hypertension or hypotension, extremely elevated body temperature and coma 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 Pharmacokinetics active pharmacologically, some of the metabolites are also active absorbed completely when taken orally but undergo first-pass effect metabolized extensively in the liver and eventually excreted as inactive compounds fat solubility makes these drugs widely distributed, excreted slowly and long half-lives Pharmacodynamics increase the amount of norepinephrine, serotonin or both by preventing their reuptake into the storage granules in the presynaptic nerves Tricyclic Antidepressants Pharmacotherapeutics 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 increase the catecholamine effects of amphetamines and sympathomimetics leading to hypertension barbiturates increase the metabolism of these drugs and decrease their blood levels 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 chemically different from TCAs and MAOIs include: citalopram hydrobromide fluoxetine hydrochloride fluvoxamine maleate paroxetine hydrochloride sertraline hydrochloride Selective Serotonin Reuptake Inhibitors (SSRIs) Pharmacokinetics absorbed almost completely after oral administration and are highly protein bound metabolized in the liver and excreted in the urine Pharmacodynamics inhibit the neuronal reuptake of the neurotransmitter serotonin* Selective Serotonin Reuptake Inhibitors (SSRIs) Pharmacotherapeutics 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 Selective Serotonin Reuptake Inhibitors (SSRIs) Drug Interactions associated with the drug’s ability to competitively inhibit a liver enzyme that is responsible for oxidation of numerous drugs use of drugs with MAOIs can cause serious potentially fatal reactions Lesson 4 Antiparkinsonian Agents MONECELLE JOY D. PESINABLE Instructor Antiparkinsonian Drugs 2 goals promote the secretion of dopamine (dopaminergic drugs) inhibit the cholinergic effects (anticholinergic drugs) Anticholinergic 2 chemical categories according to their chemical structure synthetic tertiary amines: benztropine, biperiden hydrochloride, biperiden lactate, procyclidine, and trihexyphenidyl antihistamines with anticholinergic properties such as diphenhydramine and orphenadrine Pharmacokinetics well absorbed from the GIT and cross the BBB to their action site in the brain most are metabolized in the liver and excreted by the kidneys as metabolites and unchanged drug unknown distribution 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 Pharmacotherapeutics all forms of parkinsonism most common in early stages of the disease when the symptoms are mild and do not have a major impact on the patient’s lifestyle effectively control sialorrhea and 20% effective in reducing incidence and severity of akinesia and rigidity Anticholinergic Drug Interactions antipsychotic drugs decrease the effectives of anticholinergics OTC cough and cold preparations increase the anticholinergic effects Dopaminergic Include drugs that are chemically unrelated levodopa, the metabolic precursor to dopamine carbidopa-levodopa, a combination drug composed of carbidopa* and levodopa amantadine, an antiviral drug bromocriptine, a semisynthetic ergot alkaloid pergolide and pramipexole, two dopamine agonists selegiline, a MAOI** Dopaminergic Pharmacokinetics absorbed from the GIT into the bloodstream and are delivered to their action site in the brain absorption is slowed and reduced when ingested with food levodopa is widely distributed in body tissues metabolized extensively in various areas of the body and eliminated by the liver, the kidneys or both Pharmacodynamics act in the brain to improve motor function in or two ways – increasing dopamine concentration and/or enhancing the neurotransmission of dopamine Dopaminergic Pharmacodynamics levodopa is inactive until it crosses the BBB and is converted to dopamine by enzymes in the brain, increasing dopamine concentration in the basal ganglia carbidopa enhances levodopa’s effectiveness amantines increase the amount of dopamine in the brain by increasing dopamine release or by blocking dopamine reuptake from presynaptic neurons bromocriptine and pramipexole stimulate dopamine receptors in the brain, producing effects that are similar to dopamine’s pergolide directly stimulates post synaptic dopamine receptors in the CNS selegiline can increase dopaminergic activity by inhibiting MAO activity Dopaminergic Pharmacotherapeutics 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 Lesson 5 Antiepileptic Agents MONECELLE JOY D. PESINABLE Instructor Anticonvulsant 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 Pharmacokinetics phenytoin is absorbed slowly after oral and IM while mephenytoin is absorbed rapidly after oral adminstration phenytoin is distributed rapidly in all tissues and fosphenytoin is widely distributed Pharmacodynamics 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 Pharmacokinetics phenobarbital is absorbed slowly but well from GIT 20-45% bound to serum proteins 75% is metabolized by the liver 25% is excreted in the urine unchanged Barbiturates Pharmacodynamics 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* Pharmacotherapeutics 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 Iminostilbenes most common example is carbamazepine therapeutic serum range is 5-12 mcg/ml effectively treats partial and generalized tonic-clonic seizures; mixed seizure types Pharmacokinetics absorbed slowly and erratically from the GIT distributed rapidly to all tissues 75-90% protein bound metabolized in the liver and excreted in the urine Pharmacodynamics inhibit the spread of seizure activity or neuromuscular transmission in general Iminostilbenes Pharmacotherapeutics carbamazepine is the drug of choice in adults and children for treating generalized tonic-clonic seizures and simple and complex partial seizures 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) Pharmacokinetics can be given orally or parenterally absorbed rapidly and almost completely from the GIT distributed at different rates 85-90% protein-bound Benzodiazepines Pharmacodynamics act as anticonvulsants, anxiolytics, sedative- hypnotics, muscle relaxants potentiate the effects of GABA* Stabilize nerve membranes throughout the CNS to decrease excitability and hyperexcitability to stimulation** Pharmacotherapeutics absence, atonic and myoclonic seizures Valproic Acid unrelated structurally to other anticonvulsants used cautiously when giving this drug to very young children and clients with liver disorders because hepatotoxicity is one of the possible adverse reaction* 2 major drugs: valproate (40-100 mcg/ml) and divalproex Pharmacokinetics valproate is converted rapidly to valproic acid in the stomach divalproex is a precursor of valproic acid and separates into valproic acid in the GIT absorbed well, strongly protein-bound metabolized in the liver and excreted in the urine Valproic Acid Pharmacodynamics unknown MOA but thought to increase the level of GABA Pharmacotherapeutics prescribed for long term treatment of absence, myoclonic and tonic-clonic seizures Lesson 6 Antipsychotic Agents MONECELLE JOY D. PESINABLE Instructor 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 3 distinct classes of phenothiazines according to adverse reactions that they can cause Aliphatics primarily cause sedation and anticholinergic effects and are moderately potent drugs that include chlorpromazine hydrochloride and promazine hydrochloride strong sedative effect, decrease BP and may cause moderate EPS (pseudoparkinsonism) Typical Antipsychotics Piperazines primarily cause extrapyramidal reactions and include acetophenazine maleate, fluphenazine decanoate, fluphenazine enanthate, fluphenazine hydrochloride, perphenazine and trifluoperazine hydrochloride low sedative effect, little effect on BP and strong antiemetic effect Piperidines primarily cause sedation, and include mesoridazine besylate and thioridazine hydrochloride strong sedative effect, cause few EPS, low to moderate effect on BP and have no antiemetic effect 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 Pharmacokinetics absorbed erratically; very lipid soluble and highly- protein bound distributed in many tissues and highly concentrated in the brain metabolized in the liver and excreted in the urine and bile Pharmacodynamics work by blocking postsynaptic dopaminergic receptors in the brain phenothiazines stimulate the extrapyramidal system* Typical Antipsychotics Pharmacotherapeutics Phenothiazines schizophrenia calm anxious or agitated patients improve patient’s thought process alleviate delusions and hallucinations Non-phenothiazines psychotic disorders thiothixene: controls acute agitation haloperidol and pimozide: Tourette’s Syndrome Typical Antipsychotics Drug Interactions increased CNS depressant effects such as stupor if phenothiazines are taken with CNS depressants; the drugs may also reduce the phenothiazine effectiveness resulting in increased psychotic behavior or agitation taking anticholinergic drugs with phenothiazines may result in increased anticholinergic effects such as dry mouth and constipation* phenothiazines may reduce the antiparkinsonian effects of levodopa, lower the threshold for seizures if taken with anticonvulsants, increase the serum levels of TCAs and beta blockers Nonphenothiazines’** dopamine blocking activity can inhibit levodopa and may cause disorientation in patients receiving both medications; haloperidol may boost the effects of lithium, producing encephalopathy 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 Pharmacokinetics absorbed after oral administration metabolized by the liver and highly protein-bound eliminated in the urine with a small portion in feces Pharmacodynamics block the dopamine receptors but not as effectively as the typical antipsychotics, in addition to blocking serotonin receptor activity* Atypical Antipsychotics Pharmacotherapeutics schizophrenic patients who are unresponsive to typical antipsychotics Pharmacodynamics drugs that alter the P-450 enzyme system will alter the metabolism of the atypical antipsychotics counteract the effects of levodopa and other dopamine agonists