CNS stimulants

CNS stimulants

sypathomimetic drugs

classified according to:

• chemical structural similarities: amphetamines, serotnonin agonists, sympathimimetics, xanthines

• site of therapeutic action

• major therapeutic uses: ADHD, antinarcoleptic, antimigraine

ADHD

• affects 3-10% of children

• boys affected 2 to 9 times more than girls

Narcolepsy

• incurable neurological condition where pts unexpedectly fall asleep in middle of normal daily activities

• cataplexy: sudden acute skeletal muscle weakness

  • commonly affects knees

obesity

expected to rise 4-5% each year

migraine

• lasts 4to 72 hours

• pulsatile quality with pain that worsens with each pulse

• unilateral but may occur on both sides

• assc. symptoms: nausea, vomitting, photophobia, phonophobia

analeptic responsive respiratory depression syndromes

• neonatal apnea

• bronchopulmonary dysplasia

• postanasthetic resp dep

  • drugs: analeptic drugs like aminiphylline, caffeine, oxygen

drugs for ADHD and narcolepsy

• amphetamines: methylphenidate

• non-amphetamine stimulant

  • modafinil - less cardiac stimulant

• nonstimulants

  • atomoxetine; also for ADHD

Amphetamine MOA

stimulate areas of brain assc. with mental alertness

Amphetamines CNS effects

• euphoria

• increased mental alertness and capacity for work

• decreased fatigue and drowsiness

• prolonged wakefulness

Amphetamines Resp effects

• relaxation of bronchial smooth muscle

• incr respiration

• dilation of pulmonary arteries

amphetamine adverse effects

• speed up body systems

• Palpitations, tachycardia, hypertension, angina, anxiety, insomnia, headache, tremor, nausea, vomiting, diarrhea, dry mouth, increased metabolic rate

Principal Drugs Used to Treat ADHD and
Narcolepsy

• Amphetamine derivatives
• Nonamphetamine stimulants
• Atomoxetine: nonstimulant drug also used for ADHD

Amphetamine drugs

dextroamphetamine sulphate (Dexedrine®)
• dextroamphetamine saccharate
• amphetamine sulphate
• amphetamine aspartate (Adderall®): one of the most
prescribed drugs for ADHD

atomoxetine hydrochloride (strattera)

• tx adults and children older than 6

• may cause suicidal thinking in adolescents

methylphenidate hydrochloride (ritaline)

• first prescription drug for adhd

• also for narcolepsy

• extended dosage forms:

• • Ritalin SR®
  • Concerta®
  • Biphentin

modafinil (alertec)

• Use: improvement of wakefulness in patients with
excessive daytime sleepiness associated with
narcolepsy and with “shift work” sleep disorder
• Less potential for misuse than amphetamines and
methylphenidate
• Available with a prescription

anorexiants

• tx obesity

• effictiveness not proven lmao

• not avail in canada

• orlistat (xenical) nonstimulant: inhibits absorption o caloric intake from any fatty foods

Orlistat AE

• headache

• upper resp infection

• GI distress, fecal incontinence

Antimigraine drugs

serotonin agonists (aka triptans)

• sumatriptan (Imitrex®)
• almotriptan (Axert®)
• eletriptan (Relpax®)
• naratriptan (Amerge®)
• rizatriptan (Maxalt®)
• zolmitriptan (Zomig®)
• frovatriptan (Frova®)

Triptan MoA

• stimulate 5HT receptors in cerebral arteries, cause vasoconstriction and reduce headache symptoms

• reduce prod. of inflammatory neuropeptides

Ergot alkaloids MoA

constrict or narrow BVs in the brain

AE of triptans

• vasoconstriction

• irritation at inj site

• tingling, flushing, congestion

ergot alkaloids AE

• nausea or vomiting

• cold or clammy hands

• muscle pain

• dizziness

analeptics

• not used frequently

• neonatal apnea

• ex: Methylxanthines, such as aminophylline, theophylline, and caffeine

caffeine

• OTC

• use in caution in pts with: peptic ulcer, recent myocardial infarction, dysrhythmias

analeptics MoA

• stim cns that control respiration

• methylxanthines: inhibit phosphodiesterase, leading to buildup of cyclic adenosine monophosphate

• caffeine: antagonizes adenosine receptors

Analeptics AE

vagal: stim of gastic secretions, diarrhea, and reflex tachycardia

vasomotor: flushing, sweating

resp: elevated resp rate

musculoskeletal: muscular tension and tremors

analeptic nursing implications

Assess for
• Potential contraindications
• Potential interactions, including with herbal therapies
• Conditions such as abnormal cardiac rhythms, seizures, palpitations, liver
problems
• For children, baseline height and weight

drugs for ADHD nursing implications

• Last daily dose should be given 4 to 6 hours before bedtime to reduce
insomnia.
• Take on an empty stomach 30 to 45 minutes before meals.
• Medication-free times may be ordered.
• Instruct parents to keep a journal to monitor the child’s response to therapy.
• Monitor the child for continued physical growth, including height and weight.

anorexiants nursing implications

• Follow instructions for diet and exercise.
• Take in the morning.
• Avoid caffeine.
• Fat-soluble vitamin supplementation may be needed

ergot alkaloid nursing implications

• Pay close attention to airway, breathing, and circulation because of the patient’s diminished sensorium.

primary epilepsy (idiosyncratic)

• 50% of cases

secondary epilepsy (symptomatic)

distinct cause identified

• trauma, infection, cerebrovascular disease

classification of epilepsy

• Generalized onset seizures
• Tonic-clonic seizures
• Atonic seizures
• Partial onset seizures
• Localized or focal region
• Simple
• Complex
• Secondary generalized tonic-clonic
• Unclassified seizure

status epilepticus

• Multiple seizures occur that last 5 minutes or longer of continuous or electrographic seizure activity or recurrent seizure activity without recovery between seizures
• Result: hypotension, hypoxia, brain damage, and possibly death
• True medical emergency

antiepileptic drugs

• Antiepileptic drug (AED) therapy is usually lifelong

• To control or prevent seizures while maintaining a reasonable quality of life

• To minimize adverse effects and drug-induced toxicity

• Barbiturates
• Hydantoins
• Iminostilbenes plus valproic acid
• Second- and third-generation antiepileptics

Long term therapy with phenytoin (dilantin) may cause…

gingival hyperplasia, acne, hirsutism, and dilantin facies

antiepileptic drugs

• carbamazepine (Mazepine®)
• ethosuximide (Zarontin®)
• fosphenytoin (Cerebyx®)
• gabapentin (Neurontin®)
• lamotrigine (Lamictal®)
• levetiracetam (Keppra®)
• oxcarbazepine (Trileptal®)

• phenobarbital
• phenytoin (Dilantin)
• perampanel (Fycompa®)
• pregabalin (Lyrica®)
• Primidone (Mysoline®)
• topiramate (Topamax®)
• valproic acid (Depakene®)

barbituates: phenobarbital and primidone

• Primidone is metabolized in the liver to
phenobarbital.
• Most common adverse effect is sedation.
• Therapeutic effects: serum drug levels of 15 to 40
mcg/mL

phenobarbital and primidone contrainidications

known drug allergy, porphyria, liver
or kidney impairment, respiratory illness

phenobarbital and primidone AE

cardiovascular, central nervous
system (CNS), gastrointestinal (GI), and
dermatological reactions

Hydantoins: phenytoin sodium

• Used as a first-line drug for many years and is the prototypical drug.
• Long-term therapy adverse effects: gingival hyperplasia, acne, hirsutism, Dilantin facies, and osteoporosis
• Therapeutic drug levels are usually 10 to 20 mcg/mL

• Intravenous (IV) administration
• Very irritating to veins
• Slow IV directly into a large vein through a large-gauge (20-gauge or larger) venous catheter
• Diluted in normal saline for IV infusion
• Filter must be used
• Saline flush

carbamazepine

• Second most commonly prescribed antiepileptic drug in Canada after phenytoin
• Autoinduction of hepatic enzymes

gabapentin

• Chemical analogue of gamma-aminobutyric acid (GABA), a neurotransmitter that inhibits brain activity
• Believed to work by increasing the synthesis and synaptic accumulation of GABA between neurons
• Contraindication: known drug allergy
• Adverse effects: CNS and GI symptoms
• Oral use only

levetiracetam (Keppra®)

• Adjunct therapy for partial seizures with and without secondary generalization
• Contraindication: known drug allergy
• Mechanism of action: unknown
• Adverse effects: generally well tolerated, CNS effects
• No drug interactions
• Oral and injectable forms

pregabalin (lyrica)

• Structurally related to GABA
• Indication: partial seizures
• Most common uses: adjunct therapy for neuropathic pain, postherpetic neuralgia
• Contraindication: known drug allergy
• Adverse drug reactions: primarily CNS related
• Oral use only

Parkinson’s

• Symptoms occur when about 80% of the dopamine stored in the substantia nigra of the basal ganglia is depleted.
• Symptoms can be partially controlled as long as there are functioning nerve terminals that can take up dopamine.

• PD assc. dementia

parkinson’s S+S

• Bradykinesia

• TRAP

  • tremor

  • rigidity

  • akinesia

  • postural instability

what happens when dopamine is too little in parkinsons?

worsens

what happens when dopamine is too much in parkinsons?

dyskinesia

dyskinesia: Chorea

irregular, spasmodic, involuntary movements of the limbs or facial muscles

dyskinesia: dystonia

abnormal muscle tone leading to impaired or abnormal movements

PD cause

thought to be caused by an imbalance of dopamine and ACh with a deficiency of dopamine in certain brain areas

Selective monoamine oxidase inhibitor therapy

MAO breaks down catecholamines in the CNS

Selegiline hydrochloride and rasagiline mesylate (Azilect®) are selective
MAO-B inhibitors.
• Cause an increase in levels of dopaminergic stimulation in the CNS
• Do not elicit the “cheese effect” of the nonselective MAOIs used to treat depression (if 10 mg or less is used)

cheese effect

hypertensive reaction caused by high tyramine intake

rasaglinine and selegiline

Used as adjuncts with levodopa
• Contraindications
• Known drug allergy
• Concurrent use with meperidine

Dopamine Modulator: amantadine hydrochloride

• antiviral drug for tx of influenza early on

• also tx dyskinesia assc. w/ carbidopa-levodopa

• effective only for 6-12 months

• indirect acting

• cause release of catecholamines from storage sites in presynaptic fibres of nerve cells in basal ganglia that have not been destroyed by disease yet

• blocks dopamine reuptake into nerves

• results in higher lvls of dopamine

amantadine AE

mild and include dizziness, insomnia, and nausea.

amantadine interactions

increased anticholinergic adverse effects when given with
anticholinergic drugs

Catechol Ortho-Methyltransferase Inhibitors

entacapone (Comtan®)
• Block catechol ortho-methyltransferase (COMT), the enzyme that catalyzes the breakdown of the body’s catecholamines
• Prolong the duration of action of levodopa; reduce wearing-off phenomenon

Catechol Ortho-Methyltransferase Inhibitors AE

GI upset, urine discolouration; can WORSEN PRESENT DYSKINESIA

Levodopa Therapy

precursor of dopamine

BBB does not allow exogenously supplied dopamine to enter but allows levodopa

As a result, neurotransmitter imbalance is controlled in patients with
early PD who still have functioning nerve terminals.

• As PD progresses, it becomes more difficult to control it with levodopa.
• Ultimately, levodopa no longer controls the PD, and the patient is
seriously debilitated.
• This generally occurs between 5 and
10 years after the start of levodopa therapy.

nondopamine dopamine receptor agonists

• Ergot derivatives: bromocriptine
• Nonergot drugs: pramipexole (Mirapex®), ropinirole (ReQuip®)
• Work by direct stimulation of presynaptic dopamine receptors or postsynaptic dopamine receptors or both in the brain

bromocriptine

• activates presynaptic dopamine receptors to stim prod of more dopamine

• inhibits prolactin, which stimulates normal lactation and can also be used to tx galactorrhea

bromocriptine caution

in pts with peripheral vascular disease

bromocriptine AE

GI upset, dyskinesia, sleep disturbances

bromocriptine interactions

eythromycin and adrenergic drugs

presynaptic dopamine replacement drugs

carbidopa given with levodopa

as a result, large doses of levodopa can get across the BBB to get dopamine to the brain

levodopa AE

confusiom, involunatary mvmts, GI distress, hypotension, dysrhythmias

levodopa carbidopa therapy contraindication

closed angle glaucoma,

use WITH CAUTION IN OPEN ANGLE

Levodopa carbidopa therapy AE

dysrhythmias, hypotension, chorea, muscle
cramps, GI distress

Levodopa carbidopa interctions

pyridoxine, nonselective MAOIs, benzodiazepines,
antipsychotics, dietary protein

Carbidopa–Levodopa (Sinemet®)

• Carbidopa alone: adjunct to treat nausea associated with Sinemet
• Sinemet CR: increases “on” time and decreases “off” time
• Drug interactions occur with tricyclic antidepressants and other drugs.
• Carbidopa–levodopa is best taken on an empty stomach; to minimize GI adverse effects, it can be taken with food

anticholinergic therapy

blocks effects of Ach

• Used to treat muscle tremors and muscle rigidity associated with PD
• These two symptoms are caused by excessive cholinergic activity.
• Does not relieve bradykinesia (extremely slow movements).

anticholinergic AE

oppostie of SLUDGE

dry mouth or decreased
salivation, urinary retention, decreased GI motility (constipation), dilated
pupils (mydriasis), and smooth muscle relaxation

benztropine mesylate

• Anticholinergic drug used for PD and extrapyramidal
symptoms from antipsychotic drugs
• Caution during hot weather or exercise because it
may cause hyperthermia

• Anticholinergic syndrome
• Avoid alcohol

benztropine mesylate

tachycardia, confusion, disorientation, toxic psychosis, urinary retention, drythroat, constipation, nausea, vomiting

nursing implications for PD drugs

When starting dopaminergic drugs, assist patient with walking, because dizziness may occur.
• Administer oral doses with food to minimize GI upset.
• Encourage patient to take in at least 3 000 mL of fluids per day (unless contraindicated).
• Taking levodopa with MAOIs may result in hypertensive crisis.

• Entacapone may darken the patient’s urine and sweat

benzodiazepine ex

• alprazolam (Xanax®)
• diazepam (Valium®)
• lorazepam (Ativan®)

benzo AE

Benzodiazepines’ adverse effects are an overexpression of their
therapeutic effects.
• Decreased CNS activity, sedation, amnesia
• Hypotension
• Drowsiness, loss of coordination, dizziness, headaches
• Nausea, vomiting, dry mouth, constipation

benzo overdose

dangerous when taken with other sedatives or alcohol

FLUMAZENIL tx

diazepam (valium) indications

Indications: relief of anxiety, management of alcohol withdrawal,
reversal of status epilepticus, preoperative sedation, and as an
adjunct for the relief of skeletal muscle spasms

lithium

• Drug of choice for the treatment of mania
• Thought to potentiate serotonergic neurotransmission
• Narrow therapeutic range: acute mania—lithium serum
level of 1 to 1.5 mmol/L. Maintenance serum levels should
range between 0.6 mmol/L and 1.2 mmol/L.
• Levels exceeding 1.5 to 2.0 mmol/L begin to produce
toxicity (severe reaction exceeding 2.0 mmol/L), including
gastrointestinal (GI) discomfort, tremor, confusion,
somnolence, seizures, and possibly death.
• Keeping the sodium level in the normal range (135 to 145 mmol/L) helps maintain therapeutic lithium levels.

Lithium AE

• Most serious adverse effect is cardiac dysrhythmia.
• Other effects: drowsiness, slurred speech, epilepsy-type seizures, choreoathetotic movements (involuntary wavelike movements of the extremities), ataxia (generalized disturbance of muscular coordination), and hypotension
• Long-term treatment may cause hypothyroidism.

First gen antidepressants

• tricyclics

• tetracyclics

• MAOI’s

second gen antidepressants

• SSRIs

• SNRIs

• Misc

tricylics

replaced by SSRI’s

considered second line

amitriptyline (elavil)

tricyclics MoA

blocks reuptake of neurotransmitters causes accum. at nerve endings

may help regulate malfunctioning neurons

tricylics indications

• neuropathic pain insomnia

• childhood enuresis (bedwetting) (imipramine)

• OCDs (clomipramine)

• sometimes, anorexia

tricyclic antidepressants AE

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