CNS Depressants, CNS Stimulants, and Anticonvulsants Notes

Central Nervous System Depressants, Stimulants, and Anticonvulsants

Central Nervous System Depressants

  • Nonpharmacologic Management of Insomnia:

  • Rise at the same time each morning.

  • No naps during the day.

  • Consider warm fluids before bed.

  • Avoid caffeine 6 hours prior to sleep.

  • Heavy meals and vigorous exercise should be avoided before bedtime.

  • Reduce exposure to noise.

  • Engage in activities like warm baths, reading, or listening to music to promote relaxation.

Benzodiazepines: “Pam’s and Lam’s”

  • Examples: Flurazepam, diazepam, clonazepam, alprazolam, temazepam, triazolam, estazolam

  • Mechanism of Action:

  • Depress CNS activity by stimulating GABA receptors, the main inhibitory neurotransmitter in the brain.

  • Indications:

  • Insomnia, anxiety, seizures, muscle spasms, anesthesia, status epilepticus.

  • Contraindications:

  • Allergy, pregnancy, narrow-angle glaucoma.

  • Side Effects:

  • Drowsiness, dizziness, cognitive impairment, lethargy, amnesia, confusion, hangover-like effects.

  • Toxicity and Management:

  • Increased risk with other CNS depressants (e.g. alcohol, opioids).

  • Management is symptomatic; flumazenil is an antidote but poses risks of seizures.

  • Interactions:

  • Other CNS depressants increase sedation.

  • Possible interactions with herbal supplements (e.g. valerian, kava kava) and grapefruit juice (prolongs effects).

Non-Benzodiazepines

  • Example: Zolpidem

  • Mechanism of Action:

  • CNS depression through GABA receptor binding.

  • Pharmacokinetics:

  • Duration of action: 6-8 hours, half-life: 2-3 hours.

  • Indications:

  • Insomnia.

  • Side effects:

  • Similar to benzodiazepines: drowsiness, dizziness, amnesia, agitation, dependence, hangover effect, binge eating.

  • Interactions:

  • Alcohol and other CNS depressants.

Barbiturates

  • Examples: Secobarbital, butobarbital, phenobarbital.

  • Mechanism of Action:

  • Work in the brain stem, reduce nerve impulses to cerebral cortex, potentiating GABA's effects.

  • Indications:

  • Insomnia, anesthesia, seizure disorders.

  • Side Effects:

  • Drowsiness, dizziness, hangover, REM sleep deprivation, hypotension, respiratory depression.

  • Toxicity and Management:

  • Similar symptomatology; treatment is supportive (airway, ventilation, fluids).

  • Interactions:

  • Alcohol, opioids, other CNS depressants, kava kava, and valerian (additive sedation).

Sedatives and Hypnotics in Older Adults

  • Identify root causes of insomnia.

  • Prioritize non-pharmacologic strategies.

  • Use short-acting benzodiazepines (e.g. estazolam, temazepam, triazolam) at the lowest effective dose to avoid agitation and confusion.

  • Avoid long-acting benzodiazepines such as flurazepam, quazepam, and diazepam.

Centrally-Acting Muscle Relaxants

  • Example: Cyclobenzaprine.

  • Mechanism of Action:

  • Relaxes skeletal muscles via CNS depression; no direct effect on muscle fibers.

  • Indications:

  • Alleviates muscle spasms from acute painful musculoskeletal conditions.

  • Contraindications:

  • Severe cardiovascular disease; hyperthyroidism.

  • Side Effects:

  • Anticholinergic effects, dizziness, drowsiness, confusion, fatigue, hallucinations, orthostatic hypotension.

  • Interactions:

  • Including CNS depressants, alcohol, and MAOIs (similar structure to tricyclic antidepressants).

Direct Acting Muscle Relaxants

  • Example: Dantrolene.

  • Mechanism of Action:

  • Acts directly on muscle fibers rather than the CNS.

  • Indications:

  • Malignant hyperthermia, neuroleptic malignant syndrome.

Drugs Used to Treat ADHD

Amphetamines

  • Mechanism of Action:

  • Stimulate norepinephrine and dopamine release.

  • Contraindications:

  • Cardiac abnormalities, glaucoma, hyperthyroidism, parkinsonism.

  • Side Effects:

  • Tachycardia, palpitations, hypertension, irritability, nausea, insomnia, weight loss.

  • Interactions:

  • Decreased effects with CNS depressants; increased with stimulant drugs; MAOIs can cause severe hypertension.

Methylphenidate

  • Mechanism of Action:

  • Modulates serotonergic pathways affecting dopamine transport.

  • Side Effects:

  • Similar to amphetamines, including hypertension, sleeplessness, restlessness, and potential growth suppression.

  • Interactions:

  • With CNS depressants, other stimulants, and MAOIs.

Anticonvulsants

Phenytoin

  • Mechanism of Action:

  • Suppresses abnormal neuronal firing by inhibiting sodium influx.

  • Indication:

  • To prevent tonic-clonic seizures or complex partial seizures; status epilepticus.

  • Contraindications:

  • Caution in pregnancy due to teratogenic risk.

  • Side effects:

  • Gingival hyperplasia, dizziness, ataxia, rash, hypotension.

  • Interactions:

  • With CNS depressants, warfarin, oral contraceptives (may decrease effectiveness), and decreases folate absorption.

  • Dosage:

  • Therapeutic level of 10-20 mcg/mL; can only be administered in NS IV slowly (max 50 mg/min).

Phenobarbital

  • Long-acting Barbiturate

  • Indications:

  • For partial seizures, grand mal seizures, and status epilepticus.

  • Therapeutic range:

  • 10-40 mcg/mL.

  • Important:

  • Do not discontinue abruptly due to potential withdrawal seizures.

Carbamazepine

  • Indication:

  • Tonic-clonic and partial seizures; also used in psychiatric disorders and trigeminal neuralgia.

  • Side Effects:

  • Drowsiness, ataxia, possible blood dyscrasias.

  • Interactions:

  • Grapefruit juice can cause toxicity.

  • Dosages:

  • Therapeutic level of 4-12 mcg/mL.

Topiramate

  • Indications:

  • For partial and tonic-clonic seizures; also migraine and bipolar disorder.

  • Mechanism of Action:

  • Block sodium channels, enhance GABA, inhibit excitatory receptors.

  • Side Effects:

  • Cognitive difficulties, dizziness, sedation, potential for weight loss.

  • Dosage Range:

  • 5-20 mcg/mL therapeutic serum range.

Valproic Acid

  • Indication:

  • Myoclonic, tonic clonic, and mixed seizures.

  • Contraindications:

  • Use caution with liver disorders; contraindicated in children under 2.

  • Side Effects:

  • Range from agitation to hepatotoxicity; should monitor liver enzymes.

  • Therapeutic range:

  • 50-100 mcg/mL.

Considerations in Pregnancy

  • Increased seizure frequency in pregnant women with epilepsy (25% increase).

  • Anticonvulsants may pose risks of fetal malformations; they are vitamin K inhibitors.

  • Increased folate loss can occur; prenatal care is critical for pregnant patients on anticonvulsants.

Anticonvulsants & Febrile Seizures

  • Febrile seizures occur in children aged 3 months to 5 years.

  • About 2.5% may develop epilepsy post-seizure.

  • Prophylactic treatment (e.g., phenobarbital or diazepam) may be required for high-risk children.

  • Avoid medications like valproic acid in children under 2 due to hepatotoxicity.

Status Epilepticus

  • Defined as a continuous seizure lasting more than 5 minutes; a medical emergency.

  • Immediate administration of diazepam or lorazepam IV, followed by phenytoin for continued seizures.

  • Advanced treatment includes midazolam or propofol, possibly high-dose long-acting barbiturates.

Practice Questions

  1. Temazepam Intervention:

  • Option to tell the patient to seek help before standing.

  1. Sedative-Hypnotic Teaching:

  • Assess whether the patient requests kava kava tea for relaxation.

  1. Older Adult Insomnia:

  • Suggest drinking warm milk or chamomile tea before bed as an initial method.

  1. Phenytoin Levels:

  • Always check phenytoin levels before administration to ensure safety.

Note: Always consider patient assessment and potential drug interactions for effective medication management.