Muscle Relaxants Substance Abuse and CNS Stimulants By

Muscle Relaxants, Substance Abuse and CNS Stimulants By Linda Self

Muscle Relaxants Used to decrease muscle spasms or the spasticity associated with certain neurologic and musculoskeletal disorders Muscle spasm—sudden, involuntary muscle contraction. Occurs with musculoskeletal trauma. Spasms may be tonic (sustained) or clonic (alternating) Spasticity—increased muscle tone or contraction, stiff, awkward movements. Caused by nerve damage in spinal cord and brain

Mechanisms of Action Centrally active except Dantrium Cause general depression of the CNS May block nerve impulses that cause increased muscle tone and contraction Lioresal and Valium increase GABA (gammaaminobutyric acid) Dantrolene acts directly on muscles inhibiting the release of calcium in skeletal muscle cells

Indications

Indications As adjuncts to other treatment measures such as physical therapy Spastic disorders which cause severe pain or inability to tolerate physical therapy, perform ADLs Dantrium in malignant hyperthermia

Skeletal Muscle Relaxants Used in patients with low back problems or be associated with sprains (ligaments), strains (muscle/tendon) , or other musculoskeletal injuries

Contraindications Caution in patients with liver or renal compromise Caution if must be alert Flexeril may have anticholinergic activity; caution in BPH, glaucoma and cardiac dysrhythmias

General Considerations No muscle relaxants are considered safe during pregnancy and lactation Lioresal (baclofen) approved for spasticity in patients with multiple sclerosis Flexeril (cyclobenzaprine) not recommended for more than three weeks

Age-Related Considerations Safety and effectiveness in children not established Caution in elderly because of anticholinergic effects and because of sedation

Individual Drugs Lioresal (baclofen) used in MS and SCI. PO or intrathecal (spinal). Decrease dose in renal impairment. Taper over 1 -2 weeks Soma (carisoprodol) indicated for acute, painful, musculoskeletal disorders. Can cause physical dependence. Withdrawal s/s if stopped suddenly. Half-life is 8 hours. Flexeril (cyclobenzaprine). Contraindicated in patients with CV disorders, recent MI and hyperthyroidism.

Individual Drugs Dantrium (dantrolene) Acts directly on skeletal muscle to inhibit muscle contraction. Used to relieve spasticity in neurologic disorders and in Tx of malignant hyperthermia. Use 1 -2 days before surgery in those w/documented MH Oral preparation has slow onset of action, IV is rapid Can cause fatal hepatitis if used on maintenance basis

Individual Drugs Zanaflex (tizanidine) Alpha 2 adrenergic agonist, similar to clonidine Given orally Can cause drowsiness, dizziness, constipation, dry mouth and hypotension Can cause psychoses and hallucinations

Individual Drugs Robaxin (methocarbamol) May be indicated to be used in tetanus (IV) Contraindicated with renal impairment Causes urine to have a green, brown or black color Skelaxin Painful, musculoskeletal disorders Contraindicated in anemias, renal or hepatic compromise

Interactions Caution with other CNS depressants MAOIs may potentiate effects by inhibiting metabolism of muscle relaxants Caution with antihypertensives as may increase effects of BP lowering

Substance Abuse Disorders Substance abuse is self-administration of a drug for prolonged periods or in excessive amounts resulting in physical and/or psychological dependence Most drugs of abuse affect the CNS Include: alcohol, CNS depressants (narcotic analgesics), CNS stimulants (cocaine, ecstasy, methamphetamine, nicotine) and others (marijuana)

Dependence Physical dependence whereby withdrawal symptoms will occur upon abrupt discontinuation Includes a “craving” for the drug Often will have unsuccessful attempts to decrease its use Continued use despite disruption in life (job loss, impaired relationships)

Dependence cont. Involves all socioeconomic levels School aged children to elderly Drug effects depend on the substance, route of administration, duration of use and phase of substance abuse Abusers are not reliable sources of information on their abuse Often will only present for medical care when situation mandates, e. g. withdrawal s/s or serious illness Used for mind-altering effects

CNS Depressants--Alcohol Considered to be most abused drug in the world Induces drug metabolizing enzymes that accelerate metabolism. Damages liver, increases production of lactate, decreases excretion of uric acid, increases production of lipids Results in irreversible changes in liver (necrosis, inflammation, fibrous scar tissue==cirrhosis)

Alcohol Effects on CNS by enhancing activity of GABA (inhibitory) or inhibiting glutamate (excitatory) Women have less enzyme activity than men so absorb 30% more alcohol than men given comparable amounts based on weight and size Women become intoxicated more quickly from smaller amounts and develop cirrhosis earlier

Alcohol Causes increased intestinal motility Can damage intestinal mucosa resulting in nutritional deficiencies==thiamine, folic acid and Vitamin B 12 Damages myocardial cells resulting in cardiomyopathy Can affect bone marrow w/ resultant anemia May impair growth and development of fetus (fetal alcohol syndrome) Osteoporosis 2 ndary to hypocalcemia myopathies

Alcohol and Drug Interactions CNS depressants such as sedative-hypnotics, narcotic analgesics, antianxiety agents, general anesthetics Potentiates CNS depression so can cause excessive sedation, respiratory depression. Can be lethal.

Alcohol With antihypertensives, causes vasodilation and hypotensive effects With oral antidiabetic drugs, potentiates hypoglycemia With oral anticoagulants, variable depending on duration of alcohol ingestion

Alcohol With Antabuse (disulfiram), produces distress. Causes: flushing, tachycardia, bronchospasm, sweating, nausea and vomiting Disulfiram-like reaction may also occur with: Flagyl (metronidazole), Diabenese (chlorpropamide), Orinase (tolbutamide), others

Alcohol Dependence Occurs to extent of psychological dependence, physical dependence and cross tolerance w/other CNS depressants S/S of withdrawal include: agitation, tremors, sweating, tachycardia, fever, nausea, delirium, and convulsions Delirium Tremens Intensity of withdrawal depends on duration and amount of ingestion

Treatment of Alcohol Dependence Benzodiazepine antianxiety agents are drugs of choice for withdrawal syndromes Valium (diazepam) or Librium (chlordiazepoxide) Ativan (lorazepam) or Serax (oxazepam) better in elderly Antiseizure medications not usually needed postdetox

Alcohol Two drugs for maintenance of sobriety Antabuse (disulfiram)—interferes with metabolism of alcohol and allows accumulation of acetaldehyde. If alcohol ingested, acetaldehyde will cause n/v, syncope, hypotension, headache and confusion. Can affect cardiac functioning and even convulsions. Caution in OTC meds that contain etoh.

Alcohol Second drug used to maintain sobriety is Re. Via (naltrexone). Opiate antagonist that reduces craving for alcohol. Thought to be related to blockade of the endogenous opioid system which then decreases alcohol craving and consumption. Adverse effects include: anxiety, dizziness, drowsiness, headache, insomnia, and vomiting.

Alcohol Key to abstinence is desire to stop drinking Need support and psychiatric help Antidepressants appear to decrease alcohol intake as well

Barbiturate and Benzodiazepine Dependence Resembles alcohol dependence in symptoms of intoxication and withdrawal Includes physical dependence, psychologic dependence, tolerance, and cross tolerance Convulsions are more likely to occur during first 48 hours of withdrawal S/S of withdrawal are less severe with benzodiazepines than with barbiturates

Barbiturates largely replaced by benzodiazepines Examples: Luminal (phenobarbital), Pentothal (thiopental), Nembutal (pentobarbital), Seconal (secobarbital)

Barbiturate Dependence No antidote for overdose. Treatment is symptomatic and supportive. Withdrawal can be life-threatening May treat with gastric lavage if within 3 hours of ingestion If comatose, mechanical ventilation necessary Diuresis or hemodialysis clear the drug

Benzodiazepines May need to treat supportively as well Romazicon (flumazenil) is antidote, competes with benzodiazepine receptors Treatment of withdrawal involves administering benzodiazepines or phenobarbital in gradually tapering doses

Benzodiazepines Librium, Valium, Versed, Ativan, Xanax, Klonopin, Tranxene, Pro. Som, Serax, Restoril, Halcion Atypical benzodiazepine receptor ligands: Sonata (zalepon) and Ambien (zolpidem)

Opiates Commonly abused Produce tolerance and high degrees of psychological and physical dependence Not an issue when needed for pain management in terminal illnesses

Treatment of Opiate Dependence Overdose will require supportive care Giving narcotic antagonist can precipitate withdrawal s/s Can achieve therapeutic withdrawal by gradually tapering dose

Treatment of Opiate Dependence Methadone used in treatment Blocks euphoria, acts longer and reduces preoccupation with drug use LAAM (Orlaam) is synthetic, Schedule II narcotic used for treatment of opiate dependence. Can be given three times weekly (If M-W-F, Friday dosing needs to be larger to prevent withdrawal s/s over weekend)

LAAM Can overdose if patient takes this medication and other opiates Has prodysrhythmic effects so need baseline ECG. Can use Re. Via (naltrexone) but then have to give alternative non-narcotic analgesic. If undergoing elective surgery, must stop taking Re. Via 72 h before procedure

CNS Stimulants Not recommended in children under 6 years of age May affect growth Ritalin (methylphenidate) is most commonly used drug for children with ADHD

Amphetamines Increase amounts of norepinephrine, dopamine and serotonin Are Schedule II drugs under Controlled Substances Act High potential for addiction and abuse Concerta, Focalin, Ritalin, Daytrana, Adderall, Metadate, Vyvanse

Amphetamine Dependence Produce stimulation and euphoria Effects are dose related Small amounts cause mental alertness, wakefulness and increased energy Large amounts can cause psychoses Tolerance develops

Methamphetamine Psychostimulant Increases levels of norepinephrine, serotonin and dopamine Extremely neurotoxic—can result in a secondary Parkinsonism. Causes dopaminergic degeneration. “Meth mouth” Patriot Act 2005 removed active ingredients, ephedrine or pseudoephedrine, were removed from regular OTC access

Xanthines Caffeine Stimulates cerebral cortex thus increasing alertness and decreasing fatigue Cause myocardial stimulation, diuresis, and increased sescretion of pepsin and HCL, cerebrovascular constriction, bronchodilation Can cause restlessness, nervousness, anxiety, agitation, insomnia, cardiac dysrhythmias and gastritis

Xanthines Frequently ingested stimulant in form of coffee, tea, cola drinks Develop tolerance and habituation Combined with other medications to enhance absorption and work as an additive with ergots, oxycodone, OTC pain and cold remedies

Cocaine Powerful CNS stimulant Prevents reuptake of dopamine, norepinephrine and serotonin and prolongs neurotransmitter effects Inhalation Produces euphoria, increased energy and alertness, sexual arousal, tachycardia, increased blood pressure and restlessness

Cocaine As drug wears off, patient will feel depressed, fatigued and drowsy Can cause cardiac dysrhythmias, MI, convulsions, stroke and death Not physically addictive but cause psychologic dependence “Crack” cocaine highly addictive after first dose

Treatment Treat with Haldol or other antipsychotics Treat cardiac dysrhythmias with antidysrhythmics Need detox and psychiatric counseling

Nicotine Promotes compulsive use, abuse and dependence Inhaling smoke from cigarrette delivers 1 mg of nicotine Readily absorbed through the lungs, skin, mucous membranes Metabolized by liver, excreted by kidneys GI effects: n/v, increases muscle tone and motility, aggravates GERD and PUD

Nicotine Toxic effects include hypertension, cardiac dysrhythmias, convulsions, coma, respiratory arrest, paralysis of skeletal muscle With chronic use, implicated in vascular disease and sudden cardiac death

Nicotine Dependence is characterized by compulsive use and development of tolerance and physical dependence Compulsion when nicotine levels become low S/S of withdrawal include: anxiety, irritability, difficulty concentrating, restlessness, headache, increased appetite, weight gain, and sleep disturbances

Treatment of Nicotine Addiction Wellbutrin or Zyban (buproprion) OR Nicotine replacement in form of patches or gum; inhaler and nasal spray by prescription Intended for use no longer than 3 -6 months Contraindicated in CAD May use buproprion and nicotine in concert

MDMA Psychoactive similar to methamphetamine Stimulant and psychedelic, create energizing effect Causes distortion in perception of time Affects primarily serotonin Neurotoxic addictive

MDMA Can affect with body temperature regulation Cognitive impairment Causes tachycardia, elevated BP, involuntary teeth clenching, chills or sweating

Analeptics CNS stimulants Provigil (modafinil) for narcolepsy Mechanism of action unclear Not recommended in patients with LVH or ischemic changes on ECG Adverse effects include: chest pain, dizziness, dyspnea, dysrhythmias, headache, nausea, nervousness, palpitations

Toxicity of CNS stimulants s/s agitation, dysrhythmias, combativeness, confusion, hyperactivity, insomnia, irritability, nervousness, panic states, restlessness, tremors, seizures, coma, circulatory collapse and death Tx is supportive. Gastric lavage within 4 h of ingestion. Activated charcoal (1 g/kg). IV Valium

Others Ketamine Rohypnol (flunitrazepam) GHB (gamma hydroxybutyric acid) Dextromethorphan THC Absinthe