Introduction to Central Nervous System Pharmacology

Drugs that inhibit DA breakdown: Selegiline- Prototype Rasagiline

Drug Interactions -Increases levels of drugs metabolized by COMT --Methyldopa --Dobutamine --Isoproterenol

Classification of Antiseizure Drugs: break them down by mechanisms of action

-Drugs that suppress sodium influx --shutting down -Drugs that suppress calcium influx --shutting down -Drugs that promote potassium efflux -Drugs that antagonize glutamate --turn lights on -Drugs that potentiate GABA --turn off

A patient with MS is prescribed interferon beta [Betaseron]. What is a priority for teaching at this time?

Educate about self-injection technique.

Definition of Seizure (epilepsy) Disorders

-Group of disorders characterized byexcessive excitability of neurons in the central nervous system: producing too much stimulation -Can produce a variety of symptoms that range from brief periods of unconsciousness to violent convulsions -May also cause problems with learning, memory, and mood

Dopamine Agonist vs. Levodopa

-Less effective than levodopa​ -Not dependent on enzymatic conversion to be active​ -Does not compete with dietary proteins​ -Lower incidence of response failure​ -Less likely to cause dyskinesias

Blood Brain Barrier (BBB)

-protects CNS -Impedes entry of drugs into the brain --Passage across the BBB limited to lipid-soluble drugs ---Protein-bound or highly ionized drugs cannot cross have to be lipofilic to cross BBB

The nurse is caring for a patient who is receiving pramipexole [Mirapex]. The nurse is most concerned if the patient makes which statement?

"Sometimes I just fall asleep without warning."

A patient has been taking a medication for 2 months. Which statement, if made by the patient, would indicate to the nurse that drug tolerance is occurring?

"The medication does not seem to be working as well."

The nurse receives a phone call from a patient who has been taking a CNS drug for 3 days. The patient tells the nurse that the medication causes nausea. Which response by the nurse is best?

"The nausea will most likely decrease over time."

Disease-Modifying Drugs II: Immunosuppressants: Mitoxantrone: prototype Cladribine

-More toxic than immunomodulators -Produce greater suppression of immune function -Chemotherapeutics are used off-label in the treatment of MS

How CNS Drugs Produce Therapeutic Effects

-Precise mechanism versus plausible hypotheses -We do not fully understand the brain in either health or disease -Although we cannot state with certainty how CNS drugs act, we do have sufficient data to permit the formulation of plausible hypotheses

Transmitters of the Central Nervous System

-There are at least 21 known transmitters, and more are likely to be discovered. -Some are unique to the CNS while others are also present in the periphery

CNS Adaptation to Prolonged Drug Exposure

-body adapts to new level of stimulation Different effects possible when drug is taken chronically versus the initial use of the drug due to brain adaptation -Increased therapeutic effects -Delayed beneficial responses -Delayed therapeutic responses Example: antidepressants typically require 2-3 weeks to show mood improvement Decreased side effects: When CNS drugs are taken chronically, the intensity of the side effects may decrease, but the therapeutic effects remain undiminished Example: -Morphine is taken to control pain -Nausea is a common side effect early on -Treatment continues, nausea diminishes, and analgesic effects persist

Neuronal Receptor Blocker for AD: Memantine

-for patients with COPD or asthma Mechanism of Action: -NMDA receptor antagonist -Indicated for moderate to severe AD Adverse effects -Dizziness -Headache -Confusion -Constipation Memantine restores natural excitatory signaling -In AD, glutamate "leaks" steadily, causing persistent activation. -Memantine blocks excitation when glutamate is low but allows it when glutamate is high. -MMAD receptor antagonist

Multiple Sclerosis (MS)

A chronic, inflammatory, autoimmune disorder that damages the myelin sheath of neurons in the CNS. Exact cause is unknown Disease presentation is due to damaged neuronal signaling: -Impaired vision -Slurred speech -Numbness -Muscle weakness -Cognitive changes -Back pain

A patient taking levodopa/carbidopa [Sinemet] for Parkinson disease experiences frequent "on-off" episodes (i.e., the abrupt loss of effect). Which action by the nurse is best?

A.Instruct the patient to avoid high-protein foods.

Drugs that suppress sodium influx: Phenytoin

Active against focal and tonic-clonic -Narrow therapeutic window due to strange kinetics (hard to maintain pt at dose that is effective without being toxic) --Poor liver metabolism -Half-life depends on the dose: --8 to 60 hours (10 - 20 mcg/mL therapeutic) Adverse effects -CNS: sedation, ataxia, diplopia (double vision), nystagmus -Gingival hyperplasia --Educate on oral hygiene and folic acid supplement -Skin rash -Effects in pregnancy --Teratogenic --Vitamin K can prevent bleeding in the infant -Cardiovascular effects: severe hypotension and dysrhythmia --Prevent with slow IV administration, cardiac monitoring Drug-Drug Interactions -Induces CYP liver enzymes (drug metabolism) --Decreases the effects of oral contraceptives, warfarin (narrow therapeutic level), and glucocorticoids -Drugs that alter phenytoin serum levels --↑ by diazepam, isoniazid, cimetidine (common antacid), alcohol (acute), and valproate --↓ by carbamazepine, phenobarbital, and alcohol (chronic) (precipitate a seizure)

Centrally Acting Muscle Relaxants for Spasm

Adverse effects -Generalized CNS depression & GI upset -Hepatic toxicity --Tizanidine -Physical dependence --Abstinence syndrome in babies --Withdrawal Contraindications -CNS Depressants: alcohol, opioids, and benzo's --b/c of respiratory depression

Classification of Antiseizure Drugs

Also known as anti-epileptic drugs (AEDs) Two major categories -Traditional AEDs --Phenytoin, fosphenytoin, carbamazepine, valproate, ethosuximide, phenobarbital and primidone -New Generation AEDs --Oxcarbazepine, gabapentin, zonisamide, and others (more selective)

The nurse prepares to administer dantrolene [Dantrium] to a patient. Before the administration of the drug, it is most important for the nurse to assess which laboratory value?

Aminotransferases

The nurse prepares to administer a cholinesterase inhibitor to a patient with AD. Which medication, if ordered by the healthcare provider, should the nurse question?

Amitriptyline (Tricyclic Antidepressant) -anticholinergic effects

An older patient with skin cancer and hypertension is prescribed levodopa/carbidopa [Sinemet] to treat Parkinson disease. Which action by the nurse is best?

Ask the patient about the type of skin cancer.

Centrally Acting Muscle Relaxers for Spasticity

Baclofen Mechanism of action: -Unknown, but in the CNS Preferred over dantrolene to preserve strength Diazepam Mechanism of action: -Benzodiazepine GABA agonist Adverse effects -Generalized CNS depression & GI upset -Urinary retention -Physical dependence --Withdrawal - must taper down -Overdose (respiratory depression) Contraindications -CNS Depressants: alcohol, opioids, and benzo's

Anticholinergics in PD

Benztropine, Trihexyphenidyl Mechanism of Action --Blockade of muscarinic receptors of the striatum centerally acting --Less effective, but better tolerated --BEERS Criteria: potentially inappropriate in geriatric patients Adverse Effects -Occur when peripheral cholinergic receptors are blocked hot, dry, blind, red, mad, cant pee and poop

Dopamine Receptor Agonists

Direct activation of dopamine receptors in the striatum Two types of dopamine agonists -Ergot derivatives (less selective) --Bromocriptine --Cabergoline -Non-ergot derivatives (highly selective) --Pramipexole --Ropinirole **First line of therapy in PD

Drug Therapy for MS

Disease-modifying drugs -Immunomodulators and Immunosuppressants -Can decrease the frequency and severity of relapses, reduce the development of brain lesions, decrease future disability, and help maintain quality of life -May prevent permanent damage to axons -Does not work for all patients -Not a cure

Cannabidiol as an AED

Cannabidiol (Epidiolex) -Does not contain THC so no "highs" -Given orally in liquid form -Adverse effects: drowsiness, dry mouth, low blood pressure, diarrhea -Therapeutic Uses --Dravet syndrome ---Fever sensitive myoclonic seizure in infants -Lennox-Gastaut syndrome --Seizures in children that start between 3 and 5 years of age --Patients also display intellectual and learning disabilities

Three Drug Classes

Centrally Acting Muscle Relaxer for Localized Muscle Spasm -Cyclobenzaprine: prototype -Diazepam! -Tizanamide Centrally Acting Muscle Relaxer for Spasticity -Baclofen: prototype -Diazepam! Direct-Acting Muscle Relaxer -Dantrolene: prototype

The nurse is caring for a patient who is taking phenytoin [Dilantin]. Which medication, if ordered by the physician, should the nurse question?

Cimetidine [Tagamet] inhibits metabolism of phenytoin

Tolerance

Decreased response occurring during the course of prolonged drug use

In addition to motor symptoms

Depression Psychosis and dementia Autonomic disturbances

Alzheimer's Disease

Devastating illness -Progressive memory loss -Neuropsychiatric symptoms -Inability to perform routine tasks of daily living -AD affects 4.5 million Americans Degeneration of neurons -Early in hippocampus --Memory -Later in cerebral cortex --Speech, perception, reasoning, and other higher functions

Nursing Considerations

Diagnosis and Therapeutic Evaluation -Takes time and requires a lot of record keeping --Seizure frequency charts --Medication schedules --Serum plasma levels --Maintenance -Patient compliance is critical --Drugs need to be taken at regular intervals --Stopping treatment is a decision made by the prescriber and must be done slowly

Antiseizure Drugs

Effects -Suppress discharge of neurons within a seizure focus -Suppress propagation of seizure activity from the focus to other areas of the brain Mechanisms of action -Suppression of sodium influx -Suppression of calcium influx -Promote potassium efflux -Potentiation of gamma-aminobutyric acid (GABA) -Antagonism of glutamate Goal: Decrease hyperexcitability by decreasing neuronal activity (suppress signaling) -Suppression of sodium influx -Suppression of calcium influx -Promote potassium efflux -Potentiation of GABA -Antagonism of glutamate Glutamate- increase excitability, want to block with seizure, on signaling in brain GABA- increase effects of GABA, turns off, decrease excitability

Dopamine Receptor Agonist

Ergot Derivatives: Bromocriptine, Cabergoline Mechanism of Action -DA receptor agonist. Also mildly block serotonin and alpha receptors. Adverse Effects -Nausea Psychosis (confusion, nightmares, hallucinations) Non-ergot Derivatives: Pramipexole, Ropinirole Mechanism of Action -Selective DA receptor agonist. Adverse Effects -Monotherapy: Nausea, dizziness, insomnia, hallucinations, and constipation. -Combined: orthostatic hypotension, dyskinesia, hallucinations Sleep attacks -not as many adverse effects because direct actions -can be combines with levadopa

Levodopa/Carbidopa/Entacapone

Fixed-dose combinations sold as Stalevo More convenient than taking separate doses Costs a little less Disadvantage -Only available in immediate-release tablets Only available in three strengths

Types of Seizures

Focal-onset seizures (small areas of the brain) -Focal aware -Focal impaired awareness -Focal to bilateral tonic-clonic seizures Generalized-onset seizures -Tonic-clonic -Absence -Atonic (loose all muscle rigidity) -Myoclonic -Status epilepticus Febrile

A patient is newly prescribed carbamazepine [Tegretol] for seizure control. It is most important for the nurse to teach the patient to avoid which food?

Grapefruit juice

PD Dopamine/ACh Imbalance in Striatum

In Parkinson's dopaminergic neurons degenerate -Decreasing dopamine output -Acetylcholine signaling predominates -increased ach creates disturbed movements -decreased dopamine output

Generation of Seizures

Initiated by synchronous, high-frequency discharge from a group of hyperexcitable neurons called a focus Focus may result from the following: -Congenital defects -Hypoxia at birth -Head trauma -Brain infection -Stroke -Cancer Genetic disorders

Drugs that inhibit DA breakdown

Levadopa given with: DOPA Decarboxylase Inhibitors -Carbidopa (prevents levadopas breakdown in periphery) COMT Inhibitors -Entacapone -Tolcapone MAO-B Inhibitors -Selegiline -Rasagiline ** Used to enhance levodopa

Drugs that promote DA synthesis

Levodopa- prototype Mechanism of Action -Increase DA synthesis Adverse Effects -Diminishing effect (used with other meds because of this) -Nausea & vomiting (CTZ) (chemo receptor trigger zone) -Dyskinesia -Psychosis -Darkens sweat & urine -Activates malignant melanoma PK/PD-pharmacokinetic -Orally administered and absorbed in the small intestine -Delayed by food DDI (↓)- delayed by -High-protein foods -DA antagonist -Non-Selective MAOI

Drugs that inhibit DA breakdown: Entacapone- prototype Tolcapone- better activty

Mechanism of Action -Inhibits COMT to enhance levodopa effects Adverse Effects -Can enhance levodopa effects -E: vomiting, diarrhea, constipation, yellow-orange discoloration of the urine Drug Interactions -Increases levels of drugs metabolized by COMT --Methyldopa --Dobutamine --Isoproterenol ---levels increase with these 3

Drugs that inhibit DA breakdown: Carbidopa

Mechanism of Action -Inhibits DOPA decarboxylase in the periphery to enhance Levodopa effects Adverse Effects -Can enhance levodopa effects **Levodopa + Carbidopa considered most effective therapy for PD

Drugs that inhibit DA breakdown: Selegiline- prototype Rasagiline

Mechanism of Action -Inhibits MAO-B to enhance levodopa effects (respomsible for breakdown of DA in periphery) -Monotherapy or Combined Adverse Effects -Can enhance levodopa effects -Benefits decline in 1-2 years -Hypertensive crisis (high doses) S: Insomnia (selegiline) **Preferred combination over COMT inhibitors Hypertensive crisis: sudden, severe increase in blood pressure

Drugs that antagonize glutamate: New Generation Topiramate Perampanel

Mechanism of Action: -Antagonize glutamate receptors or decrease glutamate activity (primary works to) glutamate- lights on, increase excitation

Mitoxantrone

Mechanism of Action: -Chemotherapeutic agent (DNA synthesis & topoisomerase inhibitor) Adverse effects -Myelosuppression -Cardiotoxicity -Fetal harm -Alopecia -GI upset -Blue-green tint to urine and skin

Immunomodulators for MS: Glatiramer Acetate

Mechanism of Action: -Inhibits immune response to myelin basic protein Adverse effects -Injection-site reactions -Better tolerated than IFN-b: no flu-like symptoms, myelosuppression, or liver toxicity

Immunomodulators for MS: Interferon beta-1a

Mechanism of Action: -Naturally occurring immunomodulator. -Inhibits migration of pro-inflammatory leukocytes across BBB and suppresses helper T-cells. --pro-inflammatory immune cells --reduces overall inflammations Adverse effects -Flu-like reactions -Hepatotoxicity -Myelosuppression: happens when something interferes with immune response -Injection-site reactions -Depression, Suicidal thoughts -Neutralizing antibodies Administration -Single-use syringes and vials

Cholinesterase Inhibitors for AD: Donepezil- prototype Rivastigmine Galantamine

Mechanism of Action: -Prevent breakdown of acetylcholine -Used for mild to moderate AD Adverse Effects: SLUDGE -Cholinergic effects -Headache, dizziness -bradycardia related falls -Bronchoconstriction --Caution with COPD and asthma! Drug-Drug Interactions -Drugs that block cholinergic receptors (anti-cholinergic agents, 1st-generation antihistamines, tricyclic antidepressants) can reduce responses to cholinesterase inhibitors

Drugs that promote DA release: Amantadine- prototype

Mechanism of action -Poorly Understood. Inhibition of dopamine uptake, stimulation of dopamine release, cholinergic antagonist Adverse effects -CNS effects: Confusion, lightheadedness, and anxiety -Peripheral effects: Blurred vision, urinary retention, dry mouth, and constipation -Livedo reticularis: A condition characterized by mottled discoloration of the skin

Centrally Acting Muscle Relaxants for Spasm: Tizanidine

Mechanism of action: -Alpha2 agonist

Centrally Acting Muscle Relaxants for Spasm: Diazepam!

Mechanism of action: -Benzodiazepine GABA (lights off) agonist

Centrally Acting Muscle Relaxants for Spasm: Cyclobenzaprine- prototype

Mechanism of action: -Unknown, but in the CNS

Risk Factors and Symptoms

Mild Symptoms -Confusion and memory loss -Feeling disoriented -Problems with routine tasks -Changes in personality and judgement Moderate Symptoms -Difficulty with self-care (ADLs) -Anxiety, suspiciousness, agitation -Sleep disturbances -Behavior problems (wandering, pacing, agitation, screaming) -"Sundowning" -Inability to recognize family members and friends "sundowning" confusion that occurs in late afternoon and persists into the night Severe Symptoms -Inability to communicate -Loss of weight and appetite -Loss of bladder and bowel control -Total dependence on care giver

Drugs for Muscle Spasm

Muscle spasm: involuntary contraction of muscle or muscle group -Causes --Epilepsy --Hypocalcemia --Pain syndromes: adult and chronic --Trauma: localized skeletal muscle injury Treatment of spasm -Physical measures: immobilization, cold compress, physical therapy -Drug Therapy: Centrally acting skeletal muscle relaxant

Drugs that increase potassium efflux

New Generation: Ezogabine- only one in this class Mechanism of Action: -Increases potassium efflux to reduce neuronal firing Adverse Effects: -CNS: dizziness, fatigue, confusion, vertigo, memory impairment, diplopia, etc. -Retinal abnormalities -Urinary retention and red-orange colored urine -Skin discoloration Drug-Drug Interactions: -↓ by carbamazepine and phenytoin (serum levels and effectiveness)

A patient is concerned about developing AD. What should the nurse include in the teaching plan?

No solid evidence supports the use of drugs to prevent AD.

Normal Dopamine/ACh Balance in Striatum

Normal movement requires balance between dopamine and acetylcholine -GABA signaling allows for controlled movement -Dopamine suppresses GABA Acetylcholine promotes GABA Ach activate GABA DA shut down GABA

Parkinson's Disease (PD)

PD is a neurodegenerative disorder of the extrapyramidal system associated with disruption of neurotransmission in the striatum -decreased amount of dopamine being released

Disease-Modifying Drugs I: Immunomodulators

Preferred agents over immunosuppressants Immunomodulators currently available -Interferon beta -Dimethyl fumarate -Diroximel Fumarate -Glatiramer acetate -Natalizumab -Fingolimod -Teriflunomide -Alemtuzumab prevent immune response to myelin sheath Common immunomodulator concerns -Neutralizing antibodies decreasing drug effects -Hypersensitivity reactions --Hives, itching, chest pain, rash, hypotension -Opportunistic Infections --Progressive multifocal leukoencephalopathy (PML) -Natalizumab (BBW): most prone to producing PML -Hematologic changes -Liver injury --Monitor elevations in ALT and AST: get baseline levels before treatment given -Vaccine risk -Drug interactions-mostly unknown Generally, not safe in children and pregnant women

Antiseizure Drugs and Pregnancy

Pregnant women MUST continue their antiseizure medications -Fetal risk from seizure > risk from the drug Some antiseizure drugs decrease the efficacy of birth control -Carbamazepine -Eslicarbazepine -Oxcarbazepine -Lamotrigine -Phenytoin -Phenobarbital -Rufinamide -Topiramate important that mothers know they must continue taking medicine

Drug Therapy for Parkinson's Disease

Therapeutic goals -Ideally: Reverse neuronal degeneration. -Realistically: Improve ability to perform daily tasks (supplement dopamine) -overall goal is to increase dopamine Two major categories -Dopaminergic agents (promote dopamine) --Promotes dopamine synthesis --Inhibits dopamine breakdown --Dopamine receptor agonist --Promotes dopamine release -Anticholinergic agents (to much ach- prevent activation of anticholinergic) --Prevent activation of cholinergic receptors

Drugs that suppress calcium influx

Traditional Ethosuximide!- absent seizures New Generation Pregabalin Topiramate Zonisamide Mechanism of Action: -Reduce seizures by decreasing calcium influx in hyperexcitable neurons

Drugs that potentiate GABA

Traditional Valproate! Phenobarbital Primodone New Generation Topiramate Tiagabine Vigabatrin Mechanism of Action: -Increase GABA activity GABA shuts down everything want to increase

Pathophysiology of AD

Reduced cholinergic transmission - ACh 90% below normal Beta-amyloid and neuritic plaques -Form outside of neurons Neurofibrillary tangles and tau protein -Form inside neurons Apolipoprotein E4 Basically, we don't know.

Drugs for Spasticity

Spasticity: movement disorders of CNS origin -Causes: --multiple sclerosis --cerebral palsy -Characteristics include: --Heightened muscle tone --Spasm --Loss of dexterity

Physical dependence

State in which abrupt discontinuation of drug use will precipitate a withdrawal syndrome

A patient with multiple sclerosis is prescribed baclofen [Lioresal, Gablofen]. Which assessment by the nurse indicates that the medication is exerting its desired effect?

Suppression of spasticity

A patient is prescribed phenytoin [Dilantin] for epileptic seizures. Which of the following is the priority for patient teaching?

Teach the patient to avoid the abrupt cessation of treatment.

Drug Therapy

Therapeutic Goals -Ideally: Improve symptoms and reverse cognitive decline. -Realistically: Marginally improve cognition and independence. Two Major Categories -Cholinesterase inhibitors (increase PNS activity) --Donepezil --Rivastigmine --Galantamine -Neuronal NMDA receptor antagonist --Memantine

Drugs that suppress sodium influx

Traditional Phenytoin-prototype Fosphenytoin Carbamazepine- frequently used New Generation Oxcarbazepine-prototype Topiramate Zonisamide Lacosamide Rufinamide Mechanism of Action: -Reduce seizures by decreasing sodium influx in hyperexcitable neurons

TRAP

Tremor: shaking, usually starting on one side Rigidity: stiffness of the limbs, neck, or trunk (cogwheel) Akinesia: loss or impairment in power of voluntary movement Posture and balance

Drugs for Muscle Spasm and Spasticity

Two groups of drugs that cause skeletal muscle relaxation -One group for localized muscle spasm -One group for spasticity Most drugs produce their effects through actions in the CNS -Exception: Dantrolene These drugs are not interchangeable -Exception: Diazepam (either spasm/spacitity)

Pathophysiology of MS

What we do know: autoimmunity against myelin sheath -Multifocal regions of inflammation and myelin destruction of axon membrane and nearby oligodendrocytes. -Demyelination: Axonal conduction is slowed or blocked. -Inflammation subsides; damaged tissue replaced by astrocyte-derived filaments that form scars known as scleroses. -Subsequent inflammation injures underlying axon and damages oligodendrocytes. What we do know: autoimmunity against myelin sheath -Result is an inflammatory cascade that destroys myelin and that may also injure the axonal membrane and nearby oligodendrocytes. Therapeutic goal: -Reduce the frequency and severity of attacks to prevent further damage interrupted neural signals

Drugs that suppress sodium influx Oxcarbazepine (new)

a derivative of carbamazepine Adverse effects -CNS: dizziness, drowsiness, ataxia, diplopia, nystagmus, headache, nausea, and vomiting -Hyponatremia -Skin Reactions, Stevens Johnson Syndrome & Toxic Epidermal Necrolysis Drug-Drug Interactions -Sodium Depleting Drugs -Alcohol -Oral Contraceptives (induced metabolism) -Other AEDs --↓ by phenytoin, valproate, phenobarbital --↑ by perampanel

Drugs that potentiate GABA: Valproate

also suppresses Na+ and Ca2+ channels Adverse effects -Hepatotoxicity - liver failure -Pancreatitis -Teratogenic (4x other AEDs) Drug-Drug Interactions -Phenobarbital, phenytoin, topiramate - monitor plasma levels carefully -Avoid meropenem and imipenem/cilastatin antibiotics

Drugs that antagonize glutamate: Topiramate

also suppresses Na+ and Ca2+ channels potentiates GABA Adverse effects -CNS: dizziness, ataxia, nervousness, diplopia -Nausea -Anorexia and weight loss -Metabolic acidosis --Measure serum bicarb and monitor changes Drug-Drug Interactions Phenytoin and carbamazepine

Drugs that suppress sodium influx: Carbamazepine

preferred agent Adverse effects -CNS: ataxia and nystagmus -Hematologic: leukopenia, anemia, thrombocytopenia -Skin rash, Stevens Johnson Syndrome, Toxic Epidermal Necrolysis -Effects in pregnancy --Teratogenic Drug-Drug Interactions -Induces CYP liver enzymes --Decreases the effects of oral contraceptives, warfarin, and glucocorticoids -Drugs that alter carbamzepine serum levels --↑ by grapefruit juice --↓by phenytoin and phenobarbital

Drugs that suppress calcium influx: Ethosuxamide

preferred agent in absence seizures -common in children that they out grow Adverse effects -Early on: drowsiness, dizziness, and lethargy -No other significant adverse effects

Direct Acting Muscle Relaxers for Spasticity: Dantrolene

specific for spasticity (local) Mechanism of action: -Blocks Calcium release from the sarcoplasmic reticulum to reduce skeletal muscle contraction Adverse effects -Muscle Weakness -Drowsiness -Diarrhea -Hepatotoxicity -Acne-like rash

CNS Pharmacology

•CNS Drugs -Agents that act on the brain and spinal cord -Medical uses --Psychiatric disorders, suppression of seizures, pain relief, production of anesthesia -Nonmedical uses --Stimulant, depressant, euphoriant, and other "mind-altering" abilities