CNS Flashcards
Anorexiant Use and Mode of Action
Short-term (8-12 weeks) drugs used for weight loss
Indicated for tx of morbid exogenous obesity
Mode of action: thought to stimulate the release of NE and/or dopamine from storage sites in nerve terminals in the lateral hypothalamic feeding center, thereby producing a decrease in appetite
Approved for those with a BMI of greater than or equal to 30 or for patients with BMI greater than or equal to 27 who have an obesity related condition such as HTN, type II diabetes, or dyslipidemia
-Anorexiant Pharmacokinetics and Pharmacotherapeutics
Lipid soluble, can cross blood-brain barrier
Metabolized by liver, excreted by kidneys; duration of action is 4-6 hours
Have risk of tolerance and dependence so avoid using in patients with hx of dependency
Contraindicated in patients who abuse cocaine, methamphetamine, etc.
Use of anorexiants should be limited to a maximum period of 6 months and discontinued at any sign of tolerance
Anorexiant ADRs
CNS overstimulation: agitation, confusion, insomnia dizziness, HTN, HA, palpitations, arrhythmias, dry mouth, N/V
Sudden w/drawal can cause w/drawal symptoms
Cautious use in patients with diabetes due to increased glucose uptake from skeletal muscles
Avoid use in patients with hx of cardiovascular disease
Anorexiant Drug Interactions
Careful use with serotonergic meds due to increased risk for serotonin syndrome
Avoid MAOIs due to increased risk of hypertensive crisis
Can cause lithium toxicity
Orlistat decreases level of levothyroxine and increases warfarin levels
Hydantoin Use and Pharmacodynamics
Anticonvulsant used for first-line tx for tonic-clonic & partial complex seizures
Pharmacodynamics: works by stabilizing neuronal membranes and decreasing seizure activity by increasing influx of sodium ions across membranes in motor cortex
Onset and duration varies
Hydantoin Pharmacokinetics
metabolized in liver: strong cytochrome P2C9 (CYP2C9) effects
Levels will increase with cimetidine, diazepam, acute alcohol intake, valproic acid, and allopurinol
Decreases effects with barbiturates, antacids, calcium, chronic alcohol use
Hydantoin Drug Interactions and ADRs
Concurrent administration causes decreased effect of carbamazepine, estrogens, acetaminophen, corticosteroids, levadopa, sulfonylureas, cardiac gylcosides
Many ADRs
Never give IV or IM in primary care setting
Watch patients with liver and renal disease closely
Phenytoin associated with hepatitis
Most Common ADRs:
Nystagmus, dizziness, pruritis, paresthesia, HA, somnolence, ataxia confusion, hypotension, tachycardia, constipation, n/v, anorexia, dry mouth, gingival hyperplasia, urinary retention, urine discoloration
Hydantoin Monitoring and Patient Education
Baseline lab values and plasma levels, along with TSH
Need to assess OTC drugs: ibuprofen, antacids
Pregnancy Category D- if pt. has to take it, add 400 IU folic acid daily
Has a Black Box warning for causing blood dyscrasias
Discuss risk factors for seizures, report ADRs, avoid driving if not seizure free for more than 1 year, oral hygiene
Carbamazepine Interactions and ADRs
Watch out for intake with grapefruit juice
ADRs:
Depression of bone marrow, liver damage, impairs thyroid function, drowsiness, dizziness, blurred vision, n/v, dry mouth, diplopia, HA
Carbamazepine Monitoring and Pt. Education
Baseline lab values: CBC, chemical panel, hepatic panel, TSH
Teach about symptoms of bone marrow depression (fatigue; pale skin, lips, & nail beds, faster HR, easy tiring w/ exertion, dizziness, SOB), careful use of medications, therapeutic dosing, kindling
Succinimide Use and Pharmacodynamics
Used for tx of absence seizures in children and adults
Suppresses seizures by delaying calcium influx into neurons
Decreases nerve impulses and transmission in the motor cortex
Absorbed in GI tract
Succinimide Pharmacokinetics and ADRs
Metabolized in liver
ADRs:
GI most common
CNS: somnolence, fatigue, ataxia
Agranulocytosis, aplastic anemia, granulocytopenia
Lamotrigine Use & Pharmacokinetics
Used in adjunctive tx of primary generalized tonic-clonic seizures and partial seizures in adults and children older than 2 years of age
Concurrent use with valproic acid, phenytoin
Metabolized in liver and kidneys
Lamotrigine ADRs and Pt. Education
ADRs:
GI- mostly n/v, constipation; somnolence, fatigue, dizziness, anxiety, insomnia, HA, amblyopia, nystagmus; dermatological- rashes
Patient Education:
Adherence, avoidance of alcohol, avoidance of OTC drugs, adequate hydration, reporting any new drugs, reporting ADRs
Discussion of risk factors that contribute to seizures; driving; controversy about discontinuing medications after a few years of being seizure free: neurologists to make decision
Rufinamide Use, Contraindications, ADRs, and Interactions
Adjunctive tx for Lennox-Gastaut Syndrome
Modulates the activity of sodium channels
Contraindicated in familial short QT syndrome
ADRs: increased suicide risk, DRESS (drug rash with eosinophilia & systemic symptoms)
Interactions: carbamazepine, phenobarbital, valproate
Tricyclic Antidepressants (TCA)- Uses & Pharmacodynamics
Imipramine (Tofranil)- Prototype: used for depression; can be used for nocturnal enuresis, intractable pain, anxiety disorders
Acts on neurotransmitters, serotonin, and NE, and histamine and acetylcholine
TCAs- Pharmacokinetics & ADRs
Have fairly long half-life of 6 to 18 hours
Liver metabolism strong CYP2D6
ADRs:
Paradoxical diaphoresis, causing anticholinergic effects, orthostatic hypotension, sedation, drowsiness
TCAs- Patient Education and Monitoring
Patient education:
Do not discontinue abruptly; avoid OTCs
Must let provider know if having MI, glaucoma
Monitoring:
Must report any chest pain
reassess patient after 2-4 weeks of starting medication: suicide, ADRs
Baseline EKG
Monoamine Oxidase Inhibitor (MAOIs) - Mechanism of Action
Inhibit monoamine oxidase, the enzyme that terminates the actions of neurotransmitters such as dopamine, NE, epinephrine, & serotonin
Have a low safety margin
Not a first-line drug
Have many drug-drug and food-drug interactions
MAOIs- ADRs, Pharmacodynamics, Pharmacokinetics
ADRs:
Orthostatic hypotension, HA, insomnia, diarrhea, hypertensive crisis when used with other antidepressants or sympathomimetic drugs or with drugs containing tyramine
Pharmacodynamics:
They inactivate the enzymes that metabolize NE, 5HT, dopamine
They prevent the breakdown of tyramine found in many foods
Pharmacokinetics:
There is a major first-pass effect of liver metabolism and most have CYP2D6 as a substrate
Quick onset: 1-2 weeks
Selective Serotonin Reuptake Inhibitors (SSRIs)- Pharmacodynamics & Pharmacokinetics
Pharmacodynamics:
All SSRIs have selective inhibitory effects on presynaptic serotonin reuptake and weak effects on NE and dopamine neuronal uptake
Pharmacokinetics:
Slow absorption, half-life: 26 hours, has extensive first-pass metabolism
- Fluoxetine half-life: 1-3 days and first metabolite 4 to 16 days
Liver metabolism may involve CYP2C19 and CYP2D6
SSRIs- ADRs, Patient Education, and Monitoring
ADRs:
CNS, GI, sexual dysfunction; serotonin syndrome
Patient Education:
Adherence, avoidance of alcohol, avoidance of OTC medications that stimulate, insomnia, or drowsiness, suicide ideation
Pregnancy: Category B, C, or D
Withdrawal symptoms if abruptly discontinued
Monitoring:
Never give more than 4 weeks on first prescription
Monitor target symptoms
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)- Use & Pharmacodynamics
Used for major depressive disorder, GAD, neuropathy pain, fibromyalgia; not FDA approved for use in children
Considered “atypical antidepressants”
Pharmacodynamics:
inhibit reuptake of both NE and serotonin
SNRIs- Pharmacokinetics & ADRs
Pharmacokinetics:
Half-life: 8-17 hours
Metabolized in liver via CYP1A2 and CYP2D6; forms multiple metabolites
Watch with abx: quinilones
ADRs:
HA, somnolence, dizziness, insomnia, fatigue, dry mouth, constipation, orthostatic hypotension, erectile dysfunction, ejaculation failure
SNRIs- Patient Education and Monitoring
Patient Edcuation:
Adherence, suicide ideation, avoidance of OTCs
Monitoring:
May increase serum transamine levels: watch in patients with liver disease
Monitor suicide risk, activation of hypomanic or manic symptoms
Atypical Antidepressants- MOA, PK, Contraindications
Buproprion (Wellbutrin, Zyban), and Mirtazapine (Remeron)
Exact Mechanism of Action unknown
- Mirtazapine is an antagonist of 5-HT2, 5-HT3, and histamine (H1) receptors
Pharmacokinetics:
Both extensively metabolized via CYP2D6
Contraindications:
Bupropion is contraindicated in seizure disorder
Atypical Antidepressants- ADRs, Monitoring, Patient Education
ADRs:
Bupropion may cause insomnia
Mirtazapine causes drowsiness, greater at 15 mg/day than at 30 mg/day
Monitoring:
Depression and suicidal ideation
Patient Education:
Take Mirtazapine before bedtime because it may cause drowsiness
Typical Antipsychotics- Pharmacodynamics
Phenothiazines: chlorpromazine (Thorazine)
Nonphenothiazine: Haloperidol (Haldol)
Pharmacodynamics:
Block dopamine receptors in the basal ganglia, hypothalamus, limbic system, and medulla
Side effects: parkinsonism, prolactin elevation, and extrapyramidal symptoms (EPS); concurrent therapy with anticholinergic
Typical Antipsychotics- Contraindications & ADRs
Contraindications:
Narrow-angle glaucoma, bone marrow depression, and severe liver or cardiovascular disease
Black box: increased mortality in older adult patients
ADRs:
neuroleptic malignant syndrome (NMS), EPS, sedation, weight gain
Typical Antipsychotics- Patient Education and Monitoring
Patient Education:
drug interactions, avoid sudden withdrawal, sun protection
Monitoring:
Abnormal involuntary movement scale (AIMS), prolactin levels
Atypical Antipsychotics- Use and Contraindications
Use:
Block serotonin receptors in cortex
Contraindications:
Hepatic or renal disease
Atypical Antipsychotics- ADRs, Patient Education, and Monitoring
ADRs:
Seizures, weight gain, diabetes, hyperprolactinemia, dizziness, orthostatic hypotension
Clozapine- fatal agranulocytosis
Patient Education:
ADRs; do not abruptly stop taking
Monitoring:
symptoms, ADRs
Dopaminergics- MOAs
These drugs attempt to restore the functional balance of dopamine and acetylcholine in the corpus striatum of the brain
Tx of choice for Parkinson’s Disease
- Amantadine (Symmetrel)
- Bromocriptine (Parlodel)
- Levodopa (L-Dopa, Larodopa); Carbidopa-levodopa (Sinemet)
- Pramipexole (mirapex)
- Ropinirole (Requip)
- Pergolide (Permax)
- Tolcapone (Tasmar)
Dopaminergics- Pharmacodynamics & ADRs
PD:
restore dopamine in areas of the brain
May need up to 6 mos. to achieve maximum therapeutic effects
ADRs:
N/V, hallucinations, dizziness; tolcapone may cause hepatocellular injury
Dopaminergics- Drug Interactions, Patient Education, & Monitoring
Many drug interactions
Patient education:
Avoidance of abrupt discontinuation
Drug interactions, TCAs, decrease effects, may increase effects of HTN drugs, avoid antacids
Monitoring:
Lab tests- hepatic panels
Anxiolytics and Hypnotics- Benzodiazepines & Serotonergic Anxiolytics
Benzodiazepines: for anxiety and insomnia (category IV)
- anxiety: lorazepam (ativan)
- insomnia: flurazepam (dalmane), temezepam (restoril)
Serotonergic anxiolytics: Buspirone
- Pharmacokinetics: reduced first-pass affect; has many metabolites; one has noradrenergic effects; NOT used with panic attacks
- Takes up to 2 weeks for onset to occur and up to 6 weeks for maximum effect
Anxiolytics & Hypnotics- Barbiturates Categories II to IV
Short-acting: pentobarbital (Nembutal), secobarbital (Seconal)
Intermediate-acting: amobarbital (Amytal), aprobarbital (Alurate), butabarbital sodium (Butisol)
Long-acting: mephobarbital (Mebaral), phenobarbital (Luminal)
- Half-life: in children 30 to 72 hours; in adults 50 to 150 hours
Anxiolytics & Hypnotics- Precautions/Contraindications
Dependence, withdrawal symptoms (need to be tapered)
Contraindicated in pregnancy and geriatric patients
Anxiolytics & Hypnotics- ADRs, Monitoring, Patient Education
ADRs:
CNS depression sedation
Monitoring:
Liver function if using long term
Patient Education:
Avoiding alcohol and CNS depressants, safety, driving concerns
Serotonergic Anxiolytics- Pharmacokinetics, ADRs, Drug Interactions, Monitoring, Patient Education
Busprione
PK: take 1-2 weeks for onset of anxiolytic effects, up to 6 weeks for maximum effects
ADRs: few
Drug interactions: MAOIs, SSRIs may cause serotonin syndrome, atypical antipsychotics
Monitoring: None needed
PE: prolonged onset, drowsiness
Barbiturates- Use, MOA, ADRs, Interactions, Monitoring
Limited to: preanesthesia sedation, short-term tx of insomnia, status epilepticus
CNS depressants; bing ot GABA receptors
Contraindications: alcohol, hx of depression or suicide attempts
ADRs: CNS depression, agitation, confusion, HA
Drug interactions: CNS depressants
Monitoring: therapeutic levels, narrow therapeutic range
Sedative-Hypnotics- Use, Contraindications, ADRs, Patient Education
Insomnia
Benzodiazepine hypnotics
Nonbenzodiazepine hypnotics
Contraindications: pregnancy, children, older adults, long-term use
ADRs: somnolence, abnormal behaviors
Patient Education: avoid CNS depressants, take immediately before bedtime, and get 6-7 hours of sleep
Mood Stabilizers- Lithium Carbonate (Lithobid, Eskalith): MOA, Half-life, Therapeutic index, ADRs
MOA- unknown
Absorbed in GI tract, has no protein-binding, NOT metabolized in liver, excreted by kidney
Long half-life: 15-36 hours; steady state: 5-7 days
Very narrow therapeutic index (0.6-1.5 mEq/L): monitor levels every 10-14 days after initiating, and then every 2-3 mos. thereafter
ADRs
narrow therapeutic index, toxicity, ECG changes
Mood Stabilizers- Lithium Carbonate: Monitoring and Patient Education
Monitoring:
Blood levels every 14 days after starting, 14 days after dosage changes, and then every 3-6 months
Patient Education:
Maintain adequate salt intake
Mood Stabilizers- Valproates: Pharmacodynamics, Pharmacokinetics, Contraindications
PD:
Blocks GABA
PK:
metabolized by CYP2C9, 2C19, and 2A6; possibly induces 2C9 and 2C19; and inhibits 2C9, 2D6, and 3A4
Contraindications: pregnancy category D
Mood Stabilizers- Valproates: Interactions, Monitoring, Patient Education
Many drug interactions
Monitoring:
Monitor plasma levels every 3 months
Patient Education:
Bruising and delayed clotting
Nonclassified Mood Stabilizers- Nonbenzdiazepines: ADRs, Patient Education
Lamotrigine (Lamictal), Gabapentin (Neurontin), and topiramate (topamax)
ADRs:
somnolence, dizziness, weight changes
topiramate has 1% chance of renal calculi
Patient Education: ADRs
Muscle Relaxants & Antispasmodics: Centrally Acting & Direct Acting
Centrally acting:
baclofen (Lioresal), carisoprodol (Soma), chloroxazone (Paraflex, Parafon Forte), cyclobenzaprine (Flexeril), metaxalone (Skelaxin), methocarbamol (Robaxin), orphenadrine (Banflex, Norflex), and tizanidine (Zanaflex)
Direct acting:
dantrolene (Dantrium) and botulinum toxin type A (Botox)
Centrally Acting Muscle Relaxants and Antispasmodics: MOA, Contraindications, ADRs, Interactions, Patient Education
MOA: exact action unknown
Contraindications: specific for each drug; all are contraindicated in pregnancy
ADRs: CNS sedation, respiratory depression; chloroxazone may be hepatotoxic
Drug interactions: additive sedation with CNS depressants
Patient Education: appropriate use, CNS sedation
Direct-Acting Antispasmodics: Dantrolene & Botulinum toxin type A
Dantrolene: used to treat spasticity associated with upper neuron disorders
- Contraindications in active liver disease
- ADRs: CNS depression, confusion
- Patient Education: titration schedule
Botulinum toxin type A: injected to provide localized reduction in muscle activity
- May spread from site of injection to mimic botulism; may require mechanical ventilation
Opioids: Types, Pharmacodynamics, Pharmacokinetics
Morphine- prototype
- all opioids rated against morphine
Single agent products: oxycodone, morphine
Combination products: Vicodin, Percocet, Percodan, Tylenol with Codeine
PD: bind to opioid receptors in CNS
PK: vary
Opioids: ADRs, Patient Education, Monitoring
ADRs:
CNS sedation, constipation, euphoria
Patient Education:
ADRs, drug interactions
Monitoring:
ADRs, withdrawal, refills
Stimulants- Amphetamine: Pharmacodynamics, Contraindications, ADRs
PD:
CNS stimulation, reward centers
Contraindications:
Heart disease, HTN, pregnancy
ADRs:
Insomnia, weight loss, palpitations, HA
Stimulants- Amphetamines: Patient Education, Monitoring; Nonamphetamine
Patient Education:
ADRs, drug interactions
Monitoring:
Monitor ADRs, amount of drug used, refills
Nonamphetamine
Atomoxetine (Strattera)
