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Medication Review Central Nervous System (CNS).

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Medication Review, Central Nervous System

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Medication Review Central Nervous System (CNS)

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Dependence Sedative Hypnotics Antidepressants Skeletal Muscle Relaxants Antianxiety Agents (Anxiolytics) Anticonvulsants CNS Stimulants Narcotic Analgesics Anti-Parkinson's Agents Antipsychotics Smoking Deterrents

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Medication Review Central Nervous System (CNS)

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Dependence  An altered state where continued administration of the drug is necessary to prevent physical and psychological withdrawal systems

Addiction  A pattern of compulsive use characterized by overwhelming involvement with drug use and abuse Example:  Opiates,  Alcohol  Nicotine

Tolerance  The need for larger doses or an increase in the number of doses to achieve the desired response  May develop after repeated or chronic administration of the drugs Example:  Some with chronic pain will increase dose of analgesics

Physiology  The CNS is composed of the brain and spinal cord Example:  Burn your finger, goes to spinal cord to brain, brain says "move finger"

 Involved in integrating and deciphering all incoming messages and sending responses to the organs and tissues of the body  Coordinates muscle movements, visualization, temperature regulation, pain and sensation

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Sedative Hypnotics

Uses  Short-term use (days to a few weeks) for insomnia; not for long term use  Long-term use (months or years); long-term use can cause drug-induced abnormalities in the patient's sleep cycle  Antidotes for overdoses of stimulants  In combination with analgesics in painful situations  Preoperative anesthetics

Mechanism of Action  Not sure, but is thought to reduce the activity of the brain and spinal cord

Side Effects  Drowsiness  Addiction  Tolerance and dependence  Respiratory and cardiac depression (with high doses)

Examples  Benzodiazepines: o Flurazepam (Dalmane), Legend Drug, Schedule IV o Alprazolam (Xanax), Legend Drug, Schedule IV o Lorazepam (Ativan), Legend Drug, Schedule IV o Diazepam (Valium) Legend Drug, Schedule IV, o Oxazepam (Serax), Legend Drug, Schedule IV o Midazolam (Versed), Legend Drug, Schedule IV o Temazepam (Restoril), Legend Drug, Schedule IV o Triazolam (Halcion), Legend Drug, Schedule IV o Estazolam (ProSom), Legend Drug, Schedule IV o Clonazepam (Klonopin) (used to treat epilepsy seizures), Legend Drug, Schedule IV o Quzaepam (Doral), Legend Drug, Schedule IV o Clorazepate (Tranxene), Legend Drug, Schedule IV o Chlordiazepoxide (Librium), Legend Drug, Schedule IV

 Barbiturates:

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o Secobarbital (Seconal), Legend Drug, Schedule IV o Amobarbital (Amytal), Legend Drug, Schedule IV o Pentobarbitol (Nembutal) Legend Drug, Schedule IV, o Primidone (Mysoline), Legend Drug, Schedule IV

 Miscellaneous  Z Drugs are a group of nonbenzodiazepine drugs with effects similar to benzodiazepines which are used in the treatment of insomnia and whose names mostly start with the letter “Z”. Some “Z” drugs may have advantages over benzodiazepines.: o Zolpidem (Ambien), Legend Drug, Schedule IV o Eszopiclone (Lunesta), Legend Drug, Schedule IV o Zaleplon (Sonata), Legend Drug, Schedule IV o Ramelteon (Rozerem), Legend Drug, is a melatonin receptor agonist-mimics the action of melatonin  Antihistamines o Diphenhydramine (Benadryl, Compoz, Nytol, Sominex), Over the counter 25 mg / Legend Drug 50 mg

 Other o Chloral Hydrate (Noctec), Legend Drug, Schedule IV o Alcohol

Skeletal Muscle Relaxants

Uses  Relieve muscle spasm associated with muscle inflammation and injury  Useful in neuromuscular disorders such as Multiple Sclerosis and Cerebral Palsy

Mechanism of Action  Not understood, but may block nerve response within the spinal column. This has an effect of reducing muscle tone and relieving muscle spasm and tension

Side Effects  Drowsiness  Addiction  Tolerance and dependence

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 Respiratory and cardiac depression (with high doses)

Examples  Diazepam (Valium), Legend Drug, Schedule IV  Cyclobenzaprine (Flexeril), Legend Drug  Methocarbamol (Robaxin), Legend Drug  Baclofen (Lioresal), Legend Drug  Chlorzoxazone (Parafon Forte), Legend Drug  Carisoprodol (Soma), Legend Drug  Metaxalone (Skelaxin), Legend Drug  Tizanidine (Zanaflex), Legend Drug  Orphenadrine (Norflex), Legend Drug

Anticonvulsants

Uses Epilepsy:  Seizures accompanied by loss or disturbance of consciousness and possibly abnormal body movements (convulsions)  Needs to be individualized by dose and addition of other anticonvulsant agents  Prevent the occurrence of seizures; they do not cure the disease

Mechanism of Action  Control the excessive discharge of signals from the brain (seizures)

Side Effects  Drowsiness  Slurred speech  Addiction  Tolerance and dependence  Respiratory and cardiac depression (with high doses)

Examples The anticonvulsant drug chosen depends on the type of seizure the patient has (e.g. partial vs. generalized onset seizures). Valium and Ativan are the drugs of choice to treat a life threatening seizure disorder called Status Epilepticus

 Phenobarbital (available in tablets, capsules, oral suspension and I.V. injection p6 ______© PassAssured, LLC - Serving the Pharmacy Technician Commuinty www.passassured.com PassAssured's Pharmacy Technician Training Systems

dosage), Legend Drug, Schedule IV  Phenytoin (Dilantin) (available in tablets, capsules, oral suspension and I.V. injection dosage), Legend Drug  Carbamazepine (Tegretol) (available in tablets, oral suspension), Legend Drug, Schedule IV  Valproic acid and its derivatives (Depakene, Depakote) (available in tablets, capsules, oral syrup and I.V. injection dosage), Legend Drug  Gabapentin (Neurontin) newer compound (available in capsules), Legend Drug  Lamotrigine (Lamictal) (available in tablets), Legend Drug  Clonazepam (Klonopin) (available in tablets), Legend Drug, Schedule IV  Clorazepate (Tranxene) (available in tablets), Legend Drug, Schedule IV  Ethosuximide (Zarontin) (available in capsules and oral syrup), Legend Drug  Oxcarbazepine (Trileptal) (available in tablets), Legend Drug  Felbamate (Felbatol) (available in tablets, oral suspension), Legend Drug  Lamotrigine (Lamicta) (available in tablets), Legend Drug  Levetiracetam (Keppra) (available in tablets), Legend Drug  Tiagabine (Gabitril Filmtabs) (available in tablets), Legend Drug  Topiramate (Topamax) (available in tablets), Legend Drug  Primidone (Mysoline) (available in tablets), Legend Drug, Schedule IV  Trimethadione (Tridione) (available in tablets), Legend Drug  Lacosamide (Vimpat)(available in tablets), Legend Drug, Schedule V, Used in the treatment of partial-onset seizures and diabetic neuropathic pain.  Pregabalin (Lyrica)(available in capsules and oral solution), Legend Drug, Schedule V  Ruginamide (Banzel), (available in tablets), Legend Drug  Vigabatrin (Sabril), (available in tablets), Legend Drug

Narcotic Analgesics

Uses  Relief of moderate to severe pain  Cough suppressant (Antitussives). Antitussives are often combined with Expectorants to decrease viscosity of respiratory tract secretions. Expectorants helps the patient cough up phlegm.  Severe diarrhea

Mechanism of Action  Bind to specific receptors within the brain and depress certain parts of the CNS to cause pain relief, respiratory depression, decreased GI motility, and suppression of cough

Side Effects  Drowsiness

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 Constipation  Nausea/vomiting  Addiction, tolerance and physical psychological dependence  Overdoses can cause respiratory depression, profound coma, and pinpoint pupils (narcotic antagonists are used to treat overdoses - Naloxone (Narcan)

Examples

Single Agents:  Codeine, Legend Drug, Schedule II  Morphine Sulfate (MS Contin, Roxanol), Legend Drug, Schedule II  Oxycodone (Roxicodone), Legend Drug, Schedule II  Nalbuphine (Nubain), Legend Drug, Schedule II  Meperidine (Demerol) , Legend Drug, Schedule II  Fentanyl (Duragesic) available in a patch, injection and Lozenges, not a tablet. Legend Drug, Schedule II  Hydromorphone (Dilaudid) , Legend Drug, Schedule II  Remifentanil (Ultiva) , Legend Drug, Schedule IV  Pentazocine (Talwin) , Legend Drug, Schedule IV  Levorphanol (Levo-Dromoran) , Legend Drug, Schedule IV  Propoxyphene (Darvon) , Legend Drug, Schedule IV  Butorphanol (Stadol) , Legend Drug, Schedule IV

Combination Products:  Acetaminophen with Codeine (Tylenol with Codeine) (No. 2 has 15mg codeine, No. 3 has 30mg of codeine and No. 4 has 60mg codeine) , Legend Drug, Schedule III  Hydrocodone and Acetaminophen (Lorcet, Lortab, Vicodin) , Legend Drug, Schedule III  Propoxyphene and Acetaminophen (Darvocet-N, Propacet, Wygesic) , Legend Drug, Schedule IV  Oxycodone and Acetaminophen (Percocet, Roxicet) , Legend Drug, Schedule II  Oxycodone and Aspirin (Percodan) , Legend Drug, Schedule II

Antipsychotics

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Uses  Relieve the signs and symptoms of psychosis (e.g. Schizophrenia)  Have a much better effect on the positive symptoms of psychosis:  Auditory and visual hallucinations, agitation, suspiciousness, feeling of persecution, ideas of reference, and intrusion of unwanted thoughts  Noncompliance is the leading cause of recurrent positive psychotic symptoms in those patients who initially responded

 Negative symptoms include emotional apathy, extreme inattentiveness, and social withdrawal  Some analgesic, antiemetic, antinausea, and antihistaminic effects

Mechanism of Action  Originally, it was proposed that these drugs block dopamine (a chemical in the brain) receptors in the brain  Chemically effects unknown

Side Effects Sedation  Extrapyramidal symptoms (abnormal body movements) - with typicals  Anticholinergic symptoms  Orthostatic hypotension  Abnormal heart rhythms (arrhythmia's)

Examples Typical: (also known as first generation antipsychotics)  Haloperidol (Haldol), Legend Drug  Chlorpromazine (Thorazine) , Legend Drug  Prochlorperazine (Compazine) , Legend Drug  Fluphenazine (Prolixin - Permitil) , Legend Drug  Thioridazine (Mellaril) , Legend Drug  Thiothixene (Navane) , Legend Drug  Trifluoperazine (Stelazine) , Legend Drug

Atypical:(also known as second generation antipsychotics)  Clozapine (Clozaril) , Legend Drug  Risperidone (Risperdal ) , Legend Drug

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 Olanzapine (Zyprexa) , Legend Drug  Antipiprazole (Abilify) , Legend Drug  Quetiapine (Seqroquel) , Legend Drug

Third Generation antipsychotics:  Antipiprazole (Abilify), Legend Drug 

Antidepressants

Uses  Treat severe depression

Mechanism of Action  Exact mechanism unknown  Appear to increase neurotransmitters in the brain (Norepinephrine and serotonin)  Usually takes 3-6 weeks for these drugs to relieve the depression

Side Effects  Sedation  Anticholinergic  Abnormal heart rhythm  Seizures

Examples Tricyclic antidepressants (TCAs):  Amitriptyline (Elavil) , Legend Drug  Desipramine (Norpramin) , Legend Drug  Imipramine (Tofranil) , Legend Drug  Nortriptyline (Pamelor) , Legend Drug  Trimipramine (Surmontil) , Legend Drug  Clomipramine (Anafranil) , Legend Drug  Mirtazpine (Remeron) , Legend Drug  Doxepin (Adapin, Sinequan) , Legend Drug  Protriptyline (Vivactil) , Legend Drug

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Serotonin-reuptake inhibitors:  Fluoxetine (Prozac) , Legend Drug  Venlafaxine (Effexor) , Legend Drug  Paroxetine (Paxil) , Legend Drug  Sertraline (Zoloft) , Legend Drug  Fluvoxamine (Luvox) , Legend Drug  Citalopram (Celexa) , Legend Drug  Escitalopram (Lexapro) , Legend Drug

Serotonin and Norepinephrine reuptake inhibitors  Duloxetine (Cymbalta) , Legend Drug

Miscellaneous:  Trazodone (Desyrel) , Legend Drug  Nefazodone (Serzone) , Legend Drug  Bupropion (Wellbutrin) , Legend Drug  Lithium (Eskalith, Lithobid, Lithonate) , Legend Drug

Monoamine oxidase inhibitors:  Phenelzine (Nardil) , Legend Drug  Tranylcypromine (Parnate) , Legend Drug

Important to do a drug interaction check

Manic-depressive disorder:  Periods of elation, followed by periods of depression  Drugs used to moderate mood swings Example:  Lithium Carbonate (Eskalith, Lithonate) , Legend Drug

Alzheimer disease:  Alzheimer's disease is a form of dementia, a term used to describe a group of brain disorders that cause memory loss and a decline in mental function over time.

Uses

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 Treat Alzheimer disease

Mechanism of Action  NMDA Receptor antagonists  Cholinesterase inhibitors

Side Effects  Dizziness  Confusion  Insomnia  Nausea  Agitation  Coughing  Fatique  Abdnormal thinking

NMDA Receptor antagonists Example:  Memantine (Namenda) , Legend Drug

Cholinesterase inhibitors Examples:  Tacrine (Cognex) , Legend Drug The use of Tacrine is limited by poor oral bioavailability, the necessity for four-times daily dosing and considerable adverse drug reactions (including nausea, diarrhea, urinary incontinence and hepa toxicity) such that few patients could tolerate therapeutic doses.

Newer cholinsterase inhibitors:  Donepezil (Aricept) , Legend Drug  Rivastigmine (Exelon) , Legend Drug

Antianxiety Agents (Anxiolytics)

Uses  To relieve nervousness and tension in normal or neurotic patients  Have muscle-relaxing capabilities  Some have anticonvulsant activity

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Mechanism of Action  Benzodiazepines work by binding to and affecting certain receptors and neurotransmitters (GABA) in the brain  The second-generation drug, Buspirone, has an effect at the serotonin and dopamine receptors.

Side Effects  Drowsiness  Dizziness  Fatigue  Abrupt termination of high dosages can cause coma, convulsions, and death

Examples Benzodiazepines:  Alprazolam (Xanax) , Legend Drug, Schedule IV  Lorazepam (Ativan) , Legend Drug, Schedule IV  Diazepam (Valium) , Legend Drug, Schedule IV  Oxazepam (Serax) , Legend Drug, Schedule IV  Flurazepam (Dalmane) , Legend Drug, Schedule IV  Midazolam (Versed) , Legend Drug, Schedule IV

Miscellaneous:  Buspirone (BuSpar), Legend Drug  Doxepin (Sinequan) , Legend Drug  Hydroxyzine (Atarax) , Legend Drug

CNS Stimulants

Uses  To improve mental function, elevate mood, overcome fatigue, and produce a general feeling of well being  Narcolepsy  Hyperkinesis (Attention Deficit Hyperactivity Disorder - ADHD in children)  Anorexiants ( Management of Obesity)

Mechanism of Action

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 Amphetamines stimulate activity and are mediated by the release of Norepinephrine and Dopamine in the brain  Pemoline and Methylphenidate's action is unknown

Side Effects  Dependence  Increased blood pressure  Increased respiratory rate  Stomach upset

Examples  Caffeine  Methylphenidate (Ritalin) , Legend Drug, Schedule II  Dextroamphetamine (Dexadrine) , Legend Drug, Schedule II  Pemoline (Cylert) , Legend Drug, Schedule II  Adderall (Amphetamine Mixture) , Legend Drug, Schedule II  Modafinil (Provigil) , Legend Drug, Schedule IV Modafinil is a “wakefulness promoting agent” rather than a classic amphetamine-like stimulant.  Dexmethylphenidate (Focalin) , Legend Drug, Schedule II  Lisdexamphetamine, (Vyvanse) was developed for the intention of creating a longer lasting and more difficult to abuse version of dextroamphetamine. Legend Drug, Schedule II  Armodafinil (Nuvigil), Legend Drug, Schedule IV Armodafinil is a ‘wakefulness promoting agent” rather than a classic amphetamine-like stimulant. Armodafinil and Modafinil are mirror images of each other.

Examples of Anorexiants:  Benzphetamine (Didrex) , Legend Drug, Schedule III  Phentermine (Adipex-P) , Legend Drug, Schedule III  Diethylpropion, Legend Drug, Schedule III  Phendimetrazine (Bontril, Melfiat, Prelu-2), Legend Drug, Schedule III

Anti-Parkinson's Agents

Uses  To treat the shaking, rigidity, salvation, and slowing of initial movements associated with Parkinson's disease

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Mechanism of Action  Parkinson's is a disease characterized by loss of dopamine manufacturing neurons. There is an imbalance in the brain between Acetylcholine (increased) and dopamine (decreased).  Anticholinergics decrease the amount of CNS Acetylcholine  Drugs such as Levodopa increase the amount of dopamine in the CNS  Amantadine augments dopamine release from presynaptic nerve terminals and inhibits dopamine reuptake  Dopamine agonist is a compound that activates dopamine receptors in the absence of dopamine.  Monomine oxidase B inhibitors (MAO-B inhibitor) prevent the metabolism of dopamine by MAOB and hence increase its brain levels.  Catechol-O-methyl transferase (COMT) inhibitor: COMT is an enzyme that degrades dopamine.

Side Effects Anticholinergics:  Dry mouth  Blurred vision  Constipation  Hallucinations  Memory impairment

Amantadine:  Dizziness  Insomnia  Nervousness  Irritability  Confusion  Nausea and vomiting  Constipation

Levodopa:  Nausea and vomiting  Confusion  Depression  Restlessness

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 Postural hypotension  Arrhythmias

Dopamine agonist:  Euphoria  Hallucinations  Weight Loss  Nausea  Insomnia  Unusual tiredness or weakness  Dizziness

Examples  Levodopa/Carbidopa (Sinemet), Legend Drug L-DOPA enters the brain and is convertied into dopamine; Carbidopa prevents the peripheral synthesis of dopamine from L-DOPA to prevent undesirable sympathomimetic side effects.  Bromocriptine (Parlodel), Legend Drug, are dopamine receptor agonists which directly increase the activity of the dopamine system.  Pramipexole (Mirapex), Legend Drug, are dopamine receptor agonists which directly increase the activity of the dopamine system.  Ropinirole (Requip), Legend Drug, are dopamine receptor agonists which directly increase the activity of the dopamine system.  Amantadine (Symmetrel), Legend Drug, augments dopamine release from presynaptic nerve terminals and inhibits dopamine reuptake.  Selegiline (Eldepryl), Legend Drug, prevent the metabolism of dopamine by MAOB and hence increase its brain levels.  Rasagiline (Azilect), Legend Drug, prevent the metabolism of dopamine by MAOB and hence increase its brain levels.  Benztropine (Cogentin), Legend Drug, is to prevent hyperkinesia (a state of overactive restlessness).  Entacapone (COMTan®), Legend Drug Used to prevent the metabolism of dopamine by COMT and hence increase dopamine brain levels.  Tolcapone (TASMAR), Legend Drug, Used to prevent the metabolism of dopamine by COMT and hence increase dopamine brain levels. Special Note Alcohol and other CNS depressants can have additive CNS depressant effects and concomitant use should be avoided.

Levodopa is considered the “gold standard” of treatment of Parkinson’s disease.

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Levodopa can also have negative effects when used long-term. Because of this, dopamine agonists such as pramipexole and ropinirole often are used first. Other non-dopamine drugs may be used early in the course of the disease. These include amantadine, monoamine oxidase inhibitors (such as selegiline) and anticholenergics (such as trihexyphenidyl). As the disease progresses levodopa will likely need to be added.

Smoking Deterrents

Nicotine

Use  It is an aid in nicotine replacement therapy (NRT), a process for smoking cessation.

Mechanism of Action  Release nicotine into the body

Side Effects  Dizziness  Drowsiness  Headache  Irritability  Sleep disturbances  Vivid Dreams  Mild Hallucinations  Depression

Examples:  Nicotine patch (Nicoderm CQ)  Nicotine gum (Nicorette Gum)  Nicotine MD (Nicotrol Inhaler)  Nicotine Nasal Spray (Nicotrol NS)

Alternative to NRTs

Use

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 Varenicline is indicated for smoking cessation

Mechanism of Action  Varenicline tartrate mimics the actions of nicotine on the brain and can help both in easing nicotine withdrawal symptons and blocking the reinforcing effects of nicotine if smoking is resumed.

Side Effects  Nausea was the most common side effect  Headache  Vomiting  Flatulence (gas)  Insomnia  Abnormal dreams  Changes in taste perception

Example:  Vareniciline (trade name Chantix)

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