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NGR6172 WEEK 1 3
Drugs that Affect the Central
Nervous System: Part 2
Cholinesterase Inhibitors &
Dopamine Agonists;
Antiepileptic Agents
REVIEW POWER POINTS
Review Black Box Warnings / Practice Pearls / Clinical Reasoning /
Teaching Points
Tables with Medication Class categories/Indication/Comments and Monitoring from your Edmunds' textbook, and review Chapter Summaries and Study Questions found at the of the chapters in the Lippincott textbook. Antiepilepic Agents Ch. 29
- Review TABLE 29.2 MEDS/INDICATION/CONSIDERATIONS AND MONITORING
- Black box warning page 475 o Increased risk of suicidal ideation and behavior
- Review phenytoin o Practice Pearls page 475 o Oral formulation 90 – 100% bioavailable
o Ideal for newly diagnosed patients with seizures. Start with low dose and gradually increase. o Review dose-related adverse CNS effects o Gingival hyperplasia may happen with long treatment. o Monitoring for toxicity ▪ Nystagmus is an early manifestation, then ataxia and confusion o Review valproic acid ▪ GI adverse effects are common at initiation of therapy ▪ Serious adverse effects: ▪ Hepatic failure ▪ Hyperammonemia ▪ Hematologic adverse effects ▪ Platelet aggregation inhibition and thrombocytopenia ▪ Occurs with higher doses ▪ Coagulation tests and platelet counts should be performed prior to initiation of therapy and before any surgery. ▪ Practice Pearls page 476 ▪ Review symptoms of DRESS o Levetiracetam may be added as adjunct therapy to other antiepileptic drugs with no effect on pharmacokinetics. o Review carbamazepine ▪ Practice Pearls and Black box warning page 479 ▪ Monitor for signs and symptoms of hyponatremia. ▪ Headache, new or increased seizure frequency, concentration difficulty, memory impairment, confusion, weakness, or unsteadiness. Parkinson’s Disease Ch. 30
- Review TABLE 30.3 MEDS/INDICATION/CONSIDERATIONS AND MONITORING
- Review Practice Pearls page 488
- Anticholinergics such as benztropine can be use in Parkison’s patients experiencing excessive drooling. However, they are contraindicated in patients with glaucoma and emphysema. Which agent is safe for use in patients with glaucoma and emphysema?
- Understand the reasoning for combining carbidopa with levodopa
- The adjunct use of entacapone to carbidopa/levodopa combination allows for more levodopa to enter the brain.
- Review Black Box Warning page 492
o Valproic acid may cause thrombocytopenia and inhibition of platelet aggregation. Platelet counts and coagulation studies should be done before therapy is initiated, at regular intervals, and before any surgical procedure is performed. o Drug rash with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity, has been reported in patients taking valproic acid and its analogs. Common symptoms of DRESS are fever, serious rash, and/or lymphadenopathy in association with other organ system involvement. If DRESS is suspected, the patient should be evaluated immediately and valproic acid discontinued.
- Review gabapentin o Gabapentin is indicated as an adjunctive treatment for partial seizures with or without secondary generalized tonic-clonic seizures.
- According to the Beers Criteria, barbiturates are considered potentially inappropriate medications in geriatric patients, especially for those with a history of falls or fractures due to the effects of phenobarbital on gait and balance and the adverse effects of CNS.
- Review Carbamazepine o Although hematologic toxicity is relatively uncommon, transient leukopenia, neutropenia, thrombocytopenia, or more severe reactions such as agranulocytosis or aplastic anemia have been reported. WBC with differential would need to be performed if hematologic toxicity or more severe reactions are suspected. o The risk of Stevens-Johnson syndrome in Asian patients may be 10 times higher because of variants found in the immune system gene HLA-B 1502, which occur at a higher rate in Asian patients. It is recommended that Asian patients undergo a genetic blood test prior to the initiation of treatment.
- Patients receiving felbamate should be monitored for signs of hepatotoxicity, including periodic assessment of serum transaminase concentrations at baseline and regular intervals.
- Review carbidopa/levodopa o Combining carbidopa with levodopa results in increased concentrations of levodopa in the central nervous system and decreased conversion of levodopa to dopamine in the periphery, where it causes adverse effects. Carbidopa does not prolong the effects of levodopa. The combination is not synergistic and does not enhance passage across the blood-brain barrier.
o Levodopa use is contraindicated in patients currently taking nonselective monoamine oxidase inhibitor (MAOI) therapy or who have taken a nonselective MAOI within the previous 2 weeks. Hypertension can occur if these drugs are used concurrently. Nonselective MAOIs should be discontinued at least 2 weeks before initiation of oral or inhalational levodopa therapy.
- Patients who experience choreiform dyskinesias during their peak levodopa effect may benefit from substituting an immediate-release product for a sustained- release product.
- When an MAO-B is given, it appears to enhance and prolong the response to levodopa, reducing the wearing-off effect. Carbidopa does not alter this effect.
- Catecholamine O-methyl transferase inhibitors, such as entacapone, are used to prolong the effects of levodopa and help prevent breakthrough tremors that occur before the next dose of levodopa.
- Apomorphine injection is used for acute treatment of immobility related to difficulty with executing movement.
- Parkison’s disease and dieting recommendations o Recommend eating a balanced diet. Nerves and muscles govern the functioning of the GI system and may be adversely affected by PD. To prevent constipation and gastroparesis, a diet high in fiber and taking adequate hydration with water is recommended.
- Dopamine agonists are used in the treatment of patients with PD to increase the availability of dopamine in the CNS and are being used more frequently in early Parkinson’s disease to avoid using high doses of levodopa and in late stages of the disease to aid in the management of levodopa dose-response fluctuations.
- Transdermal selegiline is contraindicated in patients with pheochromocytoma due to the secretion of norepinephrine by the tumor potentially cause a hypertensive crisis.
- Ropinirole may be contraindicated in patients with sleep disorders (narcolepsy, sleep apnea) due to sudden somnolence that can occur.
- Rivastigmine has been shown to benefit patients with Lewy body dementia, a disease in which visual hallucinations are a hallmark feature.
- Donepezil is indicated as the first-line treatment for Alzheimer’s-type dementia.
- Olanzapine and risperidone are antipsychotics used to treat schizophrenia, which is not the cause of the patient’s hallucinations.
- Dementia treatment considerations o Current clinical practice guidelines encourage early initiation of treatment for dementia therapy to help the patient maintain independence longer,
- Accidental overdoses of donepezil can result in a cholinergic crisis; symptoms of this crisis include severe nausea, vomiting, bradycardia, sweating, convulsions, collapse, and even death. Patient experiencing these symptoms should call 911 for immediate emergency treatment, as the patient will require atropine for an antidote.
- Rivastigmine is a cholinesterase inhibitor indicated for patients with Lewy body dementia and dementia associated with Parkinson’s disease.
