CNS drugs

things CNS drugs treat

-psychiatric disorders

-CNS diseases

-suppression of seizures

-relief of pain

-anesthesia

CNS neurotransmitters

-contains dozens more than PNS

-serotonin

-gaba

-endorphins

-oxytocin

-dopamine

-norepinephrine

-epinephrine

blood brain barrier

-impeded entry of drugs into the brain

-lipid-soluble drugs and drugs that can use transport systems are able to cross

-protects the brain from injury & substances, can be an obstacle to the entry of therapeutic agents

-protein-bound drugs and highly ionized drugs cant cross

Therapeutic effects & the CNS

-uncertainty as to how CNS drugs act

-increase over time, sometimes it takes several weeks for a full therapeutic effect

-decreased side effects

-CNS drugs exhibit both tolerance & physical dependence

tolerance

-a person’s diminished response to a drug, which occurs when the drug is used repeatedly, and the body adapts to the continued presence of the drug

Parkinson’s Disease

-chronic progressive neurological disorder of the extrapyramidal system due to degeneration of the neurons in the substantia nigra

-loss of dopaminergic neurons & reduced concentration of dopamine

Parkinson’s symptoms

-dyskinesia

-bradykinesia

-akinesia

-tremor

-speech & writing changes

-impaired posture & balance

-arms hang heavily at sides

-voice is barely audible

-face almost void of emotion

dyskinesia

-abnormal involuntary movements

akinesia

-muscle rigidity

bradykinesia

-slowness of motion

tremor

-early sign of parkinson’s

-progressive

substantia nigra

-area of the brain that promotes balance and helped prevent unnecessary movement no

normal movement

-is normal when the inhibitory influence of dopamine and the excitatory influence of ACh are in balance

-dopamine is an inhibitory transmitter (less GABA)

ACh is excitatory (more GABA)

GABA

-inhibits the transmission of action potentials & slows down the brain by blocking specific signals in the CNS

-lessens the ability of a nerve cell to receive, create, or send chemical messages to other nerve cells

-regulates muscle tone daily and muscle relaxation during sleep

Dyskinesias of Parkinson’s disease

-tremor at rest

-rigidity

-postural instability

-bradykinesia

therapeutic goal of parkinson’s diease

-improve bradykinesia, gait problems, posture instability

-improve ability to perform ADLs

-drug selection & dosages are determined by ADL perfomances

classification of drug therapy for Parkinson’s Disease

-dopaminergic agents

-anticholinergic agents

dopaminergic agent

-promote activation of dopamine receptors

anticholinergic agents

-prevents activation of cholinergic receptors

dopaminergic drugs mechanisms of action

-promotion of dopamine synthesis

-prevention of dopamine degradation

-promotion of dopamine release

-direct activation of dopamine receptors

dopaminergic drug aim

-replenish supply of dopamine

methods of replenishing supply of dopamine in dopaminergic drugs

-administering exogenous dopamine in the form of a precursor

-stimulating dopamine receptors in the corpus striatum through use of dopamine agonists

-inhibiting the major metabolic pathways within the brain that are responsible for degradation of levodopa & its metabolites

dopaminergic agents to replace dopamine for parkinson’s disease drugs

-levodopa (Dopar)-PO

-carbidopa/levodopa (Sinemet; SInemet CR)- PO

dopaminergic agents to activate dopamine receptors for parkinson’s disease drugs

-ropinerole (Requip, Requip XL)- PO

-apomorphine (Apokyn SQ Pen, Kynmobi SL Strip)

levodopa (Dopar) PO action

-converted to dopamine in periphery & brain

-converted to dopamine via decarboxylase (helped by vit B6)

-dopamine itself doesn’t cross the blood brain barrier

-amino acids compete in intestine for absorption

levodopa (Dopar) PO patient response

-initially effective in 75% of patients w/ a 50% reduction in symptoms- full effect may take several months

-first 2 yrs promising, less after 5 year

-patients have “off” & “on” periods when drug is working on or not. may help to change dosing schedule

pt teaching for levadopa

-n/v (chemoreceptor zone in medulla is triggered by drug)

-give low dose or w/ food: caution that food decreases absorption

-involuntary movements (80% of people develop extra pyramidal symptoms ESP)

-postural hypotension

-confusion, paranoia, visual hallucination, nightmares etc; reduce dose

-darkens sweat & urine

HTN w/ monoamine oxidase (MAO)- inhibitors

-remember dopamine affects alpha 1, beta 1, and dopamine is later converted to norepinephrine by the body

levodopa/carbidopa (Sinemet)

-the carbidopa portion of the drug decreases destruction of peripheral levodopa by decarboxylase allowing more levodopa to cross BBB & gets to brain

-can reduce the actual dose of levodopa by 75%

-decrease the stimulation of medullary emetic center (less nausea)

-increase stability of symptom control

-greater degree of clinical improvement

Direct activation of dopamine receptor uses

-first line for mild/moderate symptoms, especially if younger patient

-can reserve levodopa/carbidopa for later

-used alone or with levodopa/carbidopa

advantages of drugs for parkinson’s disease activate dopamine receptors

-doesn’t compete w/ dietary protein

-less nausea

-no need for enzymatic conversion

-lower incidence of dyskinesias

-fewer response failures

disadvantages of drugs for parkinson’s disease activate dopamine receptors

-hallucinations “sleep attacks”

-postural hypotension if used with levodopa

apomorphine (Apokyn SQ Pen, Kynmobi SL Strip)

-test dose given during off period, if dose tolerated give 10mg PRN intermittent hypomobility

-titrate up by 5mg until adequate response achieved; then give PRN up to 5x a day

-must be tapered when discontinued

-trimethobenzamide premedication

-Check HR at baseline, can cause bradycardia

Catechol-O-methyltransferase inhibitor (COMT) drugs

-entacapone (Comtan)*

-tolcapone (Tasmar)- boxed warning liver failure risk

COMT inhibitors

-blocks degradation of levodopa in periphery, prolongs levodopa availability to cross the BBB & get to the brain (essentially increases ½ life of levodopa)

-similar to carbidopa, used in combination with levodopa

-causes yellow/orange colored urine

selective MAO-B inhibitors

-selegiline (Eldepryl, Zelepar)

-resagiline (Azilect)

-more dopamine from levodopa available

-may decrease progression of disease, if early

-effects may be brief

-must taper when discontinuing

selegiline (Eldepryl, Zelepar)

-inhibits monamine oxidase (MAO), another enzyme that breaks down dopamine

rasagiline (Azilect)

-inactivates MAO, less amphetamine (“speed”) characteristics than selegiline

2nd line anticholinergic agents drugs for parkinson’s disease

-benztropine PO/IM/IV

-trihexyphenidyl PO

Drugs for Parkinson’s Disease Anticholinergic agents 2nd line uses

-reduce tremor & rigidity, not bradykinesia

-used in the early stages of Parkinson’s Disease (esp. in younger pts)

-anticholinergic effects: antagonize ACh receptors

-also used for extrapyramidal symptoms (ESP) that caused by psych meds

-taper up, taper off

Alzheimer’s Disease pathophysiology

-hippocampus neurons degenerate- occurs early. short-term memory begins to fail

-cortical neurons degenerate; patients begin having difficulty with language

-reduced cholinergic transmission- in pt w/ advanced AD, levels of Ach are 90% below normal

-ACh is critical in forming memories

-neuritic plaques & beta-amyloid form on the outside of neurons; the hallmark of AD. These structural changes cause a loss in both the number & function of neurons

-neurofibrillary tangles and tau

-AD eventually destroys enough brain function to cause complete inability to care for self & eventually death

pharmacotherapy in the treatment of AD

-goal: to improve function in three domains: ADLs, behavior, and cognition. Therapy begins as soon as the diagnosis of AD is established

-medications only have a modest impact

-meds are ineffective in treating the severe stages of this disorder; their therapeutic benefit does not outweigh their expense or the risk of side effects, so meds are usually discontinued in late stages

-agitation, anxiety, and depression are all common in AD & often require treatment

reversible cholinesterase inhibitors drugs

-donepezil (Aricept) PO, ODT

-rivastigmine (Exelon) PO patch

reversible cholinesterase inhibitors side/adverse effects

-cholinergic effects

-N/V

-dizziness

-headache

-bronchoconstriction

-bradycardia

Reversible cholinesterase inhibitor actions

-prevent breakdown of acetylcholine

-slows progression of disease (by a few months only)

NMDA receptor antagonist drug

-memantine (Namenda, Namenda XR) PO

-tolerated better than cholinesterase inhibitors

-comes in combination with donepezil (Namzaric) PO

memantine (Namenda, Namenda XR)

-binds N-methyl-D-aspartate receptors

-may slow calcium influx & nerve damage

-moderate or severe cases may slow decline and cause symptom improvement but does not change underlying disease process

Multiple Sclerosis (MS)

-myelin sheath on neurons in CNS destroyed by immune system; relapsing and non-relapsing forms (PNS spared)

-cells of the immune system mistakenly identify components of myelin as being foreign & attack

-affects brain, spinal cord, optic nerve; axonal conduction is slowed.

-drugs help to place MS in remission by reducing the severity & frequency of symptoms & slowing progression of the disease

Immunomodulators for MS drugs

-interferon beta 1B (Betaseron) SQ auto-injector

-glatiramer acetate (Copaxone, Glatopa)

-ocrelizumab (Ocrevus) every 6 months IV

-ocrelizumab/ hyaluronidase (Ocrevous Zunuvo) every 6 months SQ

ADRs of interferon beta 1b (Betaseron)

-flu symptoms

-liver toxicity

-blood cell suppression

-injection reaction

actions of interferon beta 1b (Betaseron)

-binds to Type 1 interferon receptors; thought to inhibit the migration of leukocytes across the BBB, preventing these cells from reaching neurons of the CNS & suppress T-helper cell activity

-decrease symptom severity & frequency, help prevent damage to axons, suppress destruction of myelin shealth, reduces relapse

glatiramer acetate (Copaxone, Glatopa)

-thought to act as a chemical decoy for T cells & block T cell damage

-affects immune system, suppresses inflammation

-decrease symptom severity & frequency, help prevent damage to axons, suppress destruction of myelin shealth

-well tolerated

-BBW: life threatening anaphylaxis risk even years after use

ocrelizumab (Ocrevus), ocrelizumab/ hyaluronidase action

-monoclonal antibody that specifically binds to a protein which is found on the surface of immature & mature B lymphocytes

-triggers the body’s immune system to destroy the B cells

immunomodulators

-safer than the immunosuppressants & generally preferred

-all pts w/ relapsing-remitting RRMS should receive an immunomodulator beginning as soon as possible after diagnosis & continuing indefinitely

-risks: infections, dangerous opportunistic infections, hypersensitivity reaction, anaphylaxis, hematologic changes

Chemotherapeutic immunosuppressant drugs

-mitoxantrone (Novantrone) every 3 months IV, interferes with RNA

mitoxantrone (Novantrone) action

-delays relapse & disability time, decreases autoimmune destruction of sheath, work against cells that grow & divide rapidly

-may have cardiotoxic effect (BBW) & harmless blue/green tint to skin, saliva, urine

-Severe ADR’s to rapidly producing cells & teratogen

cladribine

-MS chemotherapeutic immunosuppressants

-not to be used in pts w/ malignancy/cancer (BBW)

partial seizures

-focal (limited to one part of the brain)

Generalized seizures

-throughout the brain

-convulsive (tonic-clonic)

-nonconvulsive (absence)

action of antiepileptic drugs (AEDs)

-influence seizure activity by preventing spread of neuronal excitation, suppressing neuronal discharge so excessive discharge so excessive discharge is reduced or abolished thus reduced transmission through

• -decreased NA influx

• -decrease CA influx

• -stimulate chloride influx

• -antagonize glutamate (an excitatory transmitter)

  • -potentiate GABA (an inhibitory transmitter)

Common AED Drugs class

-hydantoins

-barbiturates

-benzodiazepines

-succinimides

traditional AED drugs vs. Newer AED drugs

-traditional; more familiarity, less $$$

-newer: fewer ADRs, fewer interactions

Nursing implications of AEDs

-provider must know seizure type & appropriate drug

-test drug for sufficient time, sufficient does

-keep chart of seizure activity & frequency

-serum level: helps achieve effective drug levels, aids adherence

-chronic problem: requires continual treatment

discontinuation of AED therapy

-not necessarily life-long

-AED may be withdrawn from most patients after a 2-5 yr seizure-free period

-withdraw gradually

-may have seizures during withdrawal

pregnancy & epilepsy

-all traditional antiseizure meds can harm the developing fetus, particularly in the first trimester

-fetus & mother are at greater risk from uncontrolled seizures than from antiseizure meds

-women w/ major seizure disorders should continue taking antiseizure drugs throughout pregnancy

-fetal risk can be minimized by avoiding valproate & by using just one antiseizure drug in the lowest effective dosage

hydantoins drugs

-phenytoin (Dilantin, Phenytek ) PO, IV

-fosphenytoin (Cerebyx) IM IV staus epilepticus or short term

hydantoins actions

-inhibit sodium entry into hyperactive neurons

uses of hydantoins

-all seizures except absence

nursing implications of hydantoins

-CNS depressant, pregnancy teratogen (avoid)

-gingival hyperplasia: prevent/decrease w/ flossing/gum massage

-monitor for toxicity: narrow therapeutic range (nystagmus, ataxia, lethargy, sedation)

-various oral preparations or phenytoin are not bio-equivalent

-BBW- risk for severe hypotension is IV given too rapidly

phenytoin (Dilantin) interactions

-high potential

-stimulates metabolism of other drugs: esp. warfarin, oral contraceptives, glucocorticoids

-effects of alcohol & other CNS depressants are intensified: avoid

-several drugs can increase or decrease levels of phenytoin, monitor serum levels closely: remember the therapeutic range risk

-can use by optimally avoid in pregnancy

phenytoin side effects

p-450 inducer, purple glove syndrome

-hair growth

-enlarged gums

-nystagmus

-yucky skin rashes

-teratogenic

-osteoporosis

-interferes w/ folic acid (anemia)

-neuropathies

carbamazepine (Tegretol) uses

-epilepsy: cornerstone of therapya

action of cabamazepine (Tegretol)

-similar to phenytoin

-active against partial seizures & tonic-clonic types but not absencce

-suppresses neuronal discharge, decreases spread of seizure

adverse effects of carbamazepine

-CNS symptoms -minimal compared to phenytoin

-BBW: rare but serious anemias, teach pt to report flu like symptoms, monitor CBCs

-birth defects

-interactions: grapefruit juice (decreases metabolism= more Tegretol= toxic)

oxcarbazepine (Trileptal, Oxtellar XR)

-similar to carbamazepine, blocks neuronal Na channels

-used for partial seizures & trigeminal neuralgia

-more $$, better tolerated, as effective

-ADRs: dizziness, drowsiness, double vision

-teratogenic: teach use birth control

-interaction: decrease oral contraceptives effect

-can increase phenytoin’s level

Valproic acid (Depakene, Stavzaor) & divalproex sodium ( Depakote, Depakote ER)

-blocks Na & Ca channels & increase GABA influence (may also inhibit glutamate/ NMDA receptor-medicated neuronal excitation)

uses of Valproic acid (Depakene, Stavzaor) & divalproex sodium ( Depakote, Depakote ER)

-all types of seizures

-preferred drug for absence & myoclonic seizures & is used in combination with other drugs for partial seizures

• -also bipolar, migraines

adverse effects of Valproic acid (Depakene, Stavzaor) & divalproex sodium ( Depakote, Depakote ER)

-GI effects: take with food, try coated formulas

-BBW:

• -hepatotoxic (monitor LFTs)

• -Pancreatitis (rare)

• -Teratogenic effects

phenobarbital (Sezaby) action

-barbiurate

-potentiates GABA & binds to GABA receptors (slows)

phenobarbital (Sezaby) uses

-generalized & partial seizures

• -promotes sleep & sedation

  • -IV for status epilepticus

Nursing implications for phenobarbital (Sezaby)

-ADR: neurotoxicity, drowsiness, depression, inattention, confusion

BBW caution for risk of profound sedation w/ concomitant opioid use

-monitor serum levels

-use is now limited as other drugs have fewer & less severe ADRs

gabapentin (Neurontin) action

-thought to enhance GABA release

uses of gabapentin (Neurontin0

-absence seizures & other seizures

-post-herpetic neuralgia, neuropathy

-ADR: confusion, depression, drowsiness

pregabalin (Lyrica) action

-chemical analog

-thought to enhance GABA release

uses of pregabalin (Lyrica)

-neuropathic pain

-postherpetic neuropathy

-partial seizure adjunct

-fibromyalgia

side effects of pregabalin (Lyrica)

-dizziness, sleepiness,

-blurred vision

-weight gain

-trouble concentrating

-swelling of hands & feet

-dry mouth

patient information for pregabalin (Lyrica)

-discontinue gradually

-abrupt discontinuation may cause insomnia, nausea, headache, and diarrhea

benzodiazepine drugs

-diazepam (Valium) PO adjunct; IV status epilepticus

-clonazepam (Klonopin) PO tid

uses of benzodiazepine anticonvuslants

-status epilepticus (diazepam, midazolam)

-absence (clonazepam)

-simple partial (clorazepate)

-general (diazepam, clonazepam)

AEDs newer drugs

-lacosamide (Vimpat) PO & IV (Motpoly XR) PO- Schedule V

action of newer AED drugs

-thought to stabilize neuronal membranes & inhibit repetitive firing

uses of newer AED

-tonic-clonic & partial seizures (used as adjuncts for both)

-administered IV lacosamide slowly over 15-60 mins

-renal & hepatic dosing

-monitor for skin rashes & hypersensitivity reactions (DRESS), as lacosamide can cause serious skin reactions

DRESS

-severe type of skin reaction that many drugs can cause

-considered an ADR & a toxicity

Signs and symptoms of DRESS

-pruritic, maculopapular rash

-facial swelling

-hematological abnormalities

-fever

-fatigue

-painless enlarged lymph nodes

-myocarditis

-interstitial pneumonitis

-interstitial nephritis

-encephalitis

hematological abnormalities of DRESS

—eosinophilia

-leukocytosis

-neutrophiliapru

pruritic, maculopapular rash of DRESS

-morbilliform, or measles like

-symmetrical over torso & extremities

-darker skin colors: deep red, maroon, violaceous, or brown

-lighter skin colors: pink or red, & fading eruptions may appear violaceous

DRESS background

-drug reaction w/ eosinophilia & systemic symptoms syndrome

-severe dermatologic emergency characterized by rash, fever, & internal organ involvement

causes of DRESS

-anticonvulsants

-antibiotics

-allopurinol

-anti-viral agents

-NSAIDs

-anti-platelet medication

diagnosis of DRESS

-clinical evaluation

-labroatory testing

• -liver function tests

• -CBC

• -urinalysis

• -renal function tests

• -skin biopsy

levetiracetam (Keppra, Keppra XR) PO & IV, (Elepsia XR, Spirtam) PO

-thought to prevent synchronization of seizure burst firing (eliptiform)

-used with tonic-clonic & partial seiazures or adjunct

-administer w/ meals if PO

-use w/ caution in pregnancy

-monitor for behavior changes, depression, suicidal thoughts