Holoprosencephaly Medication

Updated: Sep 07, 2017
  • Author: Jay Desai, MD; Chief Editor: Luis O Rohena, MD, FAAP, FACMG  more...
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Medication

Medication Summary

Anticonvulsants are used for treatment of seizures, as well as for long-term prophylaxis in patients with epilepsy.

Spasticity, choreoathetosis, and dystonia may require symptomatic treatment.

Hormone replacement therapy is used in cases of pituitary dysfunction.

H2 receptor antagonists, proton pump inhibitors (PPIs), and promotility agents are used for gastroesophageal reflux.

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Anticonvulsant Agents

Class Summary

These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.

Valproic acid (Depakote, Depakote ER, Depakene, Depacon, Stavzor)

Considered the drug of first choice for primary generalized epilepsy, valproate has a very wide spectrum and is effective in most seizure types, including myoclonic seizures. It has multiple mechanisms of anticonvulsant effects, including increasing gamma-aminobutyric acid (GABA) levels in brain, as well as T-type calcium channel activity. The extended-release (ER) formulation allows for once-a-day administration.

Phenytoin (Dilantin, Phenytek)

Phenytoin works for tonic-clonic seizures and is often used because it can be administered once a day. Long-term side effects of osteopenia and cerebellar ataxia now temper its use by neurologists. This agent is one of the most difficult antiepileptic drugs (AEDs) to use owing to its zero-order kinetics and narrow therapeutic index. In addition, it can have significant bidirectional drug interactions.

Carbamazepine (Tegretol, Tegretol XR, Carbatrol, Epitol, Equetro)

This older antiepileptic drug is used as a second-choice agent along with phenytoin. It has active metabolite 10-11 epoxide. Like phenytoin, carbamazepine has been associated with osteopenia.

Lamotrigine (Lamictal, Lamictal ODT, Lamictal XR)

Lamotrigine is a newer antiepileptic drug with a very broad spectrum of activity, like valproate. It is FDA approved for both primary generalized and partial-onset epilepsy.

Lamotrigine has several mechanisms of action that may account for its effectiveness. A major disadvantage is that the dose has to be increased very slowly over several weeks to minimize the chance of rash, especially if the patient is receiving valproic acid.

Zonisamide (Zonegran)

One of newer antiepileptics recently introduced in the US market, zonisamide has been studied extensively in Japan and Korea and seems to have broad-spectrum properties. It blocks T-type calcium channels, prolongs sodium channel inactivation, and inhibits carbonic anhydrase.

Felbamate (Felbatol)

Felbamate is approved by the FDA for medically refractory partial seizures and Lennox-Gastaut syndrome. This agent has multiple mechanisms of action, including (1) inhibition of NMDA-associated sodium channels, (2) potentiation of GABA-ergic activity, and (3) inhibition of voltage-sensitive sodium channels. It is used only as drug of last resort in medically refractory cases because of the risk of aplastic anemia and hepatic toxicity, which necessitates regular blood tests.

Topiramate (Topamax)

An AED with a broad spectrum of antiepileptic activity, topiramate is approved for generalized tonic-clonic seizures. It has multiple mechanisms of action, including state-dependent sodium channel–blocking action; it also potentiates inhibitory activity of the neurotransmitter GABA. It may block glutamate activity and is a carbonic anhydrase inhibitor.

Levetiracetam (Keppra, Keppra XR)

Levetiracetam is indicated for primary generalized tonic-clonic seizures in adults and children aged 6 years or older, as well as for use in juvenile myoclonic epilepsy and for partial seizures.

Rufinamide (Banzel)

An AED that is structurally unrelated to current antiepileptics, rufinamide modulates sodium channel activity, particularly prolongation of the channel's inactive state. It significantly slows sodium channel recovery and limits sustained repetitive firing of sodium-dependent action potentials. Rufinamide is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome.

Primidone (Mysoline)

Primidone decreases neuron excitability and increases seizure threshold.

Ethosuximide (Zarontin)

Ethosuximide is a succinimide AED that is effective only against absence seizures. It has no effect on generalized tonic-clonic, myoclonic, atonic, or partial seizures. Its mechanism of action is based on reducing current in T-type calcium channels on thalamic neurons. Spike-and-wave pattern during petit mal seizures are thought to be initiated in thalamocortical relays by activation of these channels.

Ethosuximide is available in large 250-mg capsules, which may be difficult for some children to swallow, and as a syrup (250 mg/5 mL).

Lamotrigine (Lamictal, Lamictal ODT, Lamictal XR)

Lamotrigine is a triazine derivative used in neuralgia. It inhibits release of glutamate and voltage-sensitive sodium channels, leading to stabilization of neuronal membrane.

Phenobarbital

Phenobarbital works at CNS GABA receptors to potentiate CNS inhibition. It exhibits anticonvulsant activity in anesthetic doses. Phenobarbital is the best-studied barbiturate in the treatment of status epilepticus (SE).

In SE, achieving therapeutic levels as quickly as possible is important. Intravenous doses may require approximately 15 min to attain peak levels in the brain. To terminate generalized convulsive SE, administer up to 15-20 mg/kg. If the patient has received a benzodiazepine, the potential for respiratory suppression significantly increases. Ventilation and intubation may be necessary. Hypotension may require treatment.

Phenobarbital is generally used after phenytoin or fosphenytoin fails. However, it can be used in lieu of phenytoin in certain circumstances.

If the intramuscular route is chosen, administer this agent into a large muscle such as the gluteus maximus or vastus lateralis or other areas where the risk of encountering nerve trunk or major artery is low. Permanent neurologic deficit may result from injection into or near peripheral nerves.

Restrict IV use to conditions in which other routes are not possible, either because patient is unconscious or because prompt action is required.

A trend is to recommend agents other than phenobarbital (propofol, midazolam, other barbiturates) for refractory SE.

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Decarboxylase Inhibitors

Class Summary

In order for a dopamine agonist to offer clinical benefit, it must stimulate D2 receptors. The role of other dopamine-receptor subtypes is currently unclear.

Levodopa/Carbidopa (Sinemet, Parcopa)

The active component is an L-isomer of dopamine (ie, L-dopa). Carbidopa is a peripheral DOPA hydroxylase inhibitor; by preventing peripheral metabolism, it increases the concentration of dopamine in the central nervous system (CNS). The total L-dopa dose required varies from person to person.

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Anticholinergic Agents

Class Summary

These agents are thought to work centrally by suppressing conduction in the vestibular cerebellar pathways. They may have an inhibitory effect on the parasympathetic nervous system.

Trihexyphenidyl

Trihexyphenidyl is a synthetic anticholinergic noted to have a marked benefit in muscle spasm conditions, such as dystonia.

Benztropine (Cogentin)

By blocking striatal cholinergic receptors, benztropine may help balance cholinergic and dopaminergic activity in striatum. This agent can be used as an alternative to trihexyphenidyl.

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Skeletal Muscle Relaxants

Class Summary

These agents may be used in any dystonia but most commonly in the childhood-onset type.

Baclofen (Lioresal, Gablofen)

Baclofen is a centrally acting muscle relaxant; its precise mechanism of action is unknown. It is a GABA analog and may exert its effects by stimulation of GABA-beta receptors. Baclofen inhibits monosynaptic and polysynaptic reflexes at the spinal level by hyperpolarization of afferent terminals.

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Histamine H2 Antagonists

Class Summary

H2 blockers are reversible competitive blockers of histamine at H2 receptors, particularly those in the gastric parietal cells (where they inhibit acid secretion). The H2 antagonists are highly selective, they do not affect the H1 receptors, and they are not anticholinergic agents.

Some gastroenterologists recommend PPIs as being more effective than H2 blockers in promoting lesion cicatrization for hemorrhagic esophagitis and gastroesophageal reflux. Studies with omeprazole (Prilosec) and pantoprazole (Protonix) in IV forms have been encouraging, but they are not yet approved by the FDA for use in children.

Ranitidine (Zantac)

This agent inhibits histamine stimulation of H2 receptors in gastric parietal cells, which reduces gastric acid secretion, gastric volume, and hydrogen ion concentrations.

Famotidine (Pepcid)

Famotidine competitively inhibits histamine at the H2 receptors in gastric parietal cells, reducing gastric acid secretion, gastric volume, and hydrogen concentrations.

Nizatidine (Axid, Axid AR)

This agent competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.

Cimetidine (Tagamet HB 200)

This agent inhibits histamine at H2 receptors of gastric parietal cells, which results in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.

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Proton Pump Inhibitors

Class Summary

PPIs are used to reduce gastric acid hypersecretion. Dosing should be adequate to achieve a basal acid output (BAO) of less than 10 mEq/h. Dosing may vary in each patient. Children may require relatively higher doses per kilogram than adults.

Lansoprazole (Prevacid)

Lansoprazole is a substituted benzimidazole that covalently and irreversibly binds the hydrogen potassium/ATPase, thereby inhibiting acid secretion. This agent is available as an IV formulation, oral (PO) caps, or solutabs. Strawberry-flavored solutabs can be dissolved in water for easy administration to children. Dissolve the 15-mg solutab in 4 mL of water and the 30-mg solutab in 10 mL of water.

Omeprazole (Prilosec)

Omeprazole is a substituted benzimidazole that suppresses acid secretion by specific inhibition of hydrogen potassium/ATPase at the secretory surface of the parietal cell.

Pantoprazole (Protonix)

Pantoprazole is a substituted benzimidazole that suppresses acid secretion by specific inhibition of hydrogen potassium/ATPase at the secretory surface of the parietal cell.

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Prokinetic Agents

Class Summary

Prokinetics are promotility agents, proposed for use in severe constipation-predominant symptoms.

Metoclopramide (Reglan, Metozolv)

Metoclopramide is characterized by remarkable coordination of gastric and duodenal motility.

Cisapride (Propulsid)

Cisapride indirectly improves GI motility by promoting acetylcholine release from postganglionic nerve endings in the myenteric plexus. It was withdrawn from the US market on July 14, 2000, but the manufacturer will make it available to certain patients meeting clinical eligibility criteria for a limited-access protocol only.

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Estrogens/Progestins

Class Summary

Contraceptives reduce secretion of LH and FSH from the pituitary by decreasing the amount of gonadotropin-releasing hormone (GnRH).

Ethinyl estradiol and drospirenone (YAZ, Zarah, Ocella, Loryna, Gianvi)

This formulation is an oral contraceptive that contains ethinyl estradiol 20 µg and drospirenone 3 mg. It is indicated for PMDD in women who choose to use an oral contraceptive as their method of contraception.

Norethindrone acetate/ethinyl estradiol (Ortho-Novum, Nortrel, Cyclafem)

Norethindrone acetate and ethinyl estradiol are used as an oral contraceptive in women who choose to use an oral contraceptive as their method of contraception.

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