Mood Stabilizers & Antiepileptics Flashcards

1
Q

What is lithium used for

A

Bipolar disorder, especially to treat manic phase of bipolar disorder. It is used PROPHYLACTICALLY or acute mania and for maintenance

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2
Q

What is lithium classified as

A

Mood stabilizer

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3
Q

What is the most common side effect of lithium in terms of acute and chronic

A

Acute lithium toxicity begins with GI symptoms (nausea, vomiting, diarrhea). Chronic Lithium toxicity leads to development of neurologic symptoms including confusion, tremor, and ataxia.

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4
Q

What is a side effect off lithium even at therapeutic levels

A

Tremor

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5
Q

What are the 2 less common side effects of lithium?

A

(1) Nephrogenic diabetes insipidus(2) Hypothyroidism

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6
Q

What drugs can’t be taken with lithium and why?

A

NSAIDs and thiazides, since they reduce renal clearance of lithium, this can lead to diabetes insipidus

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7
Q

Can lithium be taken in pregnancy? Explain.

A

No, teratogenic as it leads to Ebstein abnormality

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8
Q

Explain Ebstein abnormalities

A

Atrial septal defect, an atrialized right ventricle and a malformed tricuspid

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9
Q

What tests can be done to check for ebstein abnormality and what is seen in it?

A

Echo, shows anatomic defects with tricuspid regurgitation

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10
Q

Summarize the side effects of lithium

A

Has a narrow therapeutic index so has many AE:(1) Acute AE are GI side effects, chronic are neurological AE(2) Tremor at therapeutic doses(3) Nephrogenic diabetes insipidus(4) Hypothyroidism(5) Teratogenic - Ebstein anomally(6) Cant be taken with NSAIDs and thiazides

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11
Q

What is the role of anti epileptic drugs in treating bipolar disorder?

A

The following are anti epileptic drugs that can be used as prophylaxis therapy for bipolar disorder:Valproate, carbamazepine and lamotrigine

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12
Q

What is a first line therapy for treating acute mania?

A

Valproate

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13
Q

What is the role of anti psychotics in treating bipolar disorder

A

1st generation (haloperidol) and 2nd generation (quetiapine) antipsychotics can be used to treat acute mania

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14
Q

Compare and contrast treatment of bipolar disorder with anti epileptics and anti psychotics

A

Anti epileptics for prophylaxis and anti psychotics for acute mania treatment

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15
Q

What are focal seizures

A

Seizure occurs at focal portion of brain

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16
Q

What are simple focal seizures

A

Focal seizures with NO loss of consciousness

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17
Q

What are complex focal seizures

A

Focal seizures with loss of consciousness

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18
Q

What are generalized seizures

A

Occurs in both hemispheres of the brain at onset

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19
Q

What can partial seizures progress to?

A

Can become generalized seizures

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20
Q

What is juvenile myoclonic epilepsy

A

a generalized seizure in kids with NO loss of consciousness

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21
Q

What is valproate, explain its MOA and use

A

Valproate is a broad spectrum antiepileptic drug that works by binding voltage gated-Na+ channels, thereby preventing the sustained high frequency firing of neurons -> extends the duration of inactivated phase of these channels

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22
Q

How does valproate effect GABA receptors in CNS?

A

Does not directly effect GABA receptors but may also cause an increase GABA levels in the CNS

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23
Q

AE of valproate

A

Most common side effects are nausea and vomiting, but it can also increase appetite and cause weight gain

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24
Q

AE of valproate at higher levels

A

Causes tremor, a rare but potentially fatal side effect is hepatoxicity.Also causes pancreatitis

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25
Q

Can valproate be taken in pregnancy?

A

No, its teratogenic, the babies have much higher risk of neural tube defects, including spina bifida

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26
Q

Summarize different types of seizures including JME

A

Focal Seizures = occurs at focal portion of brainSimple focal seizures = no loss of consciousnessComplex focal seizures = loss of consciousnessGeneralized Seizures = occurs in both hemispheres of the brain at onset.Juvenile myoclonic epilepsy (JME) - a generalized seizure in kids with no loss of consciousness

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27
Q

What is Topiramate, explain its MOA and its use

A

Topiramate - is a broad spectrum antiepileptic drug, works by binding voltage gated-Na+ channels, thereby preventing the sustained high frequency firing of neurons -> extends the inactivated phase of these channels

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28
Q

What is the mechanism of side effects associated with topiramate

A

Topiramate allosterically binds to the GABA-A receptor: cause dose-related somnolence, fatigue, confusion, and cognitive slowing.

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29
Q

What are other side effects of topiremate

A

Weight loss, Nephrolithiasis/urolithiasis, myopia and acute angle closure glaucoma

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30
Q

Lamotrigine

A

Lamotrigine is a broad spectrum antiepileptic works by binding VG-Na+ channels, thereby preventing the sustained high frequency firing of neurons -> extends the inactivated phase of these channels

31
Q

AE of Lamotrigine

A

Can cause skin rash, and more rarely SJS/TEN. Can also cause diplopia

32
Q

Levetiracetam and its AE

A

Levetiracetam - is a broad spectrum antiepileptic drug. Levetiracetam may cause somnolence

33
Q

Which of these broad spectrum drugs are more effective than others?

A

Topiramate is not as affective as valproate or Lamotrigine

34
Q

What is the cause of possible drug interactions of generalized anti epileptics

A

Many antileptics are metabolized by CYP450.

35
Q

When are topiramate, lamotrigine, valproate and levetircetam used?

A

Only used to treat generalized seizures

36
Q

What class of drugs are used to treat focal seizures

A

Narrow spectrum anti epileptics

37
Q

Explain the indications and contraindications of narrow spectrum antiepileptics

A

Only used for treating focal seizures, some of these agents can be used to treat generalized tonic serizures but they should be avoided in other generalized seizures such as JME as they can exacerbate seizures in these patients

38
Q

Carbamazepine drug class and MOA

A

Carbamazepine - is a narrow spectrum antiepileptic that works by binding to VG-Na+ channels, extending their inactivated state

39
Q

When is carbamazepine used? What is it first line of treatment for?

A

Used primarily for focal seizures and are ineffective against absence seizuresCarbamazepine is the 1st-line agent for treatment of Trigeminal Neuralgia (which typically affects V2 & V3)

40
Q

What are the most common AE of carbamazepine that are especially common in the elderly?

A

Diplopia and ataxia

41
Q

How does carbamazepine body’s electrolytes?

A

SIADH which can lead to hyponatremia

42
Q

What are hematologic AE of carbamazepine

A

Leukopenia, agranulocytosis, and aplastic anemia

43
Q

How do we treat carbamazepine induced leukopenia and other hematologic AE?

A

If Carbamazepine induces leukopenia, the drug does not necessarily need to be discontinued as it may only be transient, however, agranulocytosis (may warrant) or aplastic anemia warrant discontinuation of the drug.

44
Q

Drug interactions of carbamazepine?

A

Potent INDUCER of CYP450

45
Q

What is a potential life threatening side effect of carbamazepine.Explain this adverse effect.

A

Carbamazepine can cause a potentially life-threatening reaction called DRESS syndrome - a drug reaction characterized by eosinophilia and systemic symptoms - occurs 2 to 8 weeks after exposure with fever, generalized lymphadenopathy, facial edema and diffuse morbilliform skin rash

46
Q

Explain the teratogenic effects of carbamazepine

A

Neural tube defects.There are also major fetal malformations such as hyperplasia of the nails and distal phalanges, hypertelorism, characteristic facial features such as distal phalanges, broad upper lip and maxillary hypoplasia

47
Q

What is a dermatologic AE of carbamazepine? What gene is it associated with?

A

SJS/TENHLA-B1502 allele which occurs almost exclusively in Asians Need to screen patients for this.

48
Q

Summarize the AE of carbamazepine

A

The most common side effects of Carbamazepine are diplopia and ataxia this is especially important in older patients. Carbamazepine can also cause hyponatremia due to excessive ADH production (SIADH) due to increased responsiveness of the collecting tubules to ADH. Leukopenia, agranulocytosis, and aplastic anemia may also occur. If Carbamazepine induces leukopenia, the drug does not necessarily need to be discontinued as it may only be transient, however, agranulocytosis (may warrant) or aplastic anemia warrant discontinuation of the drug. Carbamazepine is a potent broad spectrum inducer of CYP450. Carbamazepine can cause a potentially life-threatening reaction called DRESS syndrome - a drug reaction characterized by eosinophilia and systemic symptoms - occurs 2 to 8 weeks after exposure with fever, generalized lymphadenopathy, facial edema and diffuse morbilliform skin rash. Carbamazepine is also teratogenic, able to cause neural tube defects like spina bifida, there are also major fetal malformations such as hyperplasia of the nails and distal phalanges, hypertelorism, characteristic facial features such as distal phalanges, broad upper lip and maxillary hypoplasia . A skin condition that can occur due to Carbamazepine is SJS/TEN, which is significantly more likely to occur in patients with the HLA-B1502 allele which occurs almost exclusively in Asians -> should screen patients for Asian ancestry prior to Carbamazepine therapy.

49
Q

Phenytoin use and MOAWhat is it ineffective at?

A

Phenytoin is a narrow spectrum antiepileptic drug that is used for focal seizures Phenytoin works by binding to VG-Na+ channels, extending their inactivated stateIneffective towards absence seizures.

50
Q

What are the CNS side effects of Phenytoin?

A

Diplopia, nystagmus, and ataxia

51
Q

What are the hematologic side effects of Phenytoin?

A

Phenytoin can cause a drop in folate, leading to megaloblastic anemia

52
Q

How does phenytoin cause gingival hyperplasia

A

Gingival hyperplasia is known to occur in 50% of patients that have been on 3-4months of Fenytoin therapy. The mechanism of Fenytoin-induced gingival hyperplasia is due to expression of Platelet-Derived GF, leading to the proliferation of gingival cells and alveolar bone

53
Q

What is an aesthetically unpleasant side effect of Phenytoin

A

hirsutism & coarse features

54
Q

What are the teratogenic effects of phenytoin

A

cardiac malformations, genitourinary defects, and cleft palate

55
Q

What are the effects of phenytoin on bone?

A

Phenytoin can decrease bone density due to induction increased Vitamin D metabolism - monitoring of Ca2+ and VitD levels is recommended for patients on prolonged Phenytoin therapy

56
Q

Drug interactions of phenytoin

A

Potent INDUCER of CYP450

57
Q

What AE are shared by Phenytoin and carbamazepine

A

Lupus like syndromeDRESS syndromeSJS/TEN in HLA-B1502 patients (Asian ancestory)

58
Q

Summarize the AE of phenytoin

A

CAUTION: Phenytoin can cause diplopia, nystagmus, and ataxia. Phenytoin can cause a drop in folate, leading to megaloblastic anemia. Gingival hyperplasia is known to occur in 50% of patients that have been on 3-4months of Phenytoin therapy. The mechanism of Phenytoin-induced gingival hyperplasia is due to expression of Platelet-Derived GF, leading to the proliferation of gingival cells and alveolar bone “bubble-gum”. An aesthetically unpleasant side effect of Phenytoin is hirsutism & coarse features “beard”. Phenytoin is teratogenic and can result in cardiac malformations, genitourinary defects, and cleft palate “cleft hat”. Like Carbamazepine, Phenytoin is a potent inducer of CYP450. Phenytoin can decrease bone density due to induction increased Vitamin D metabolism - monitoring of Ca2+ and VitD levels is recommended for patients on prolonged Phenytoin therapy.CAUTION: Phenytoin and Carbamazepine can both cause drug-induced Lupus “wolf”. Phenytoin and Carbamazepine can both cause DRESS syndrome - a drug reaction characterized by eosinophilia and systemic symptoms. Phenytoin and Carbamazepine can both induce SJS/TEN, especially in Asian patients with the HLA-B1502 allele.

59
Q

Explain status epilepticus

A

Status Epilepticus is when a patient has generalized tonic clonic seizures that last for more than a few minutes without recovery in between events - a life-threatening emergency

60
Q

What is the most effective treatment of status epilepticus

A

IV benzodiazepines

61
Q

Explain the treatment of status epilepticus

A

IV benzodiazepines to stop status epilepticus, then give phenytoin for maintenance therapy, if the patient doesn’t respond to phenytoin then give a barbiturate such as phenobarbital but that would run the risks of sedation and respiratory & cardiac depression

62
Q

When are gabapentine and pregabaline used?

A

Gabapentine & Pregabaline are narrow spectrum antiepileptics that are sometimes used as add-on therapy for refractory focal seizures

63
Q

Explain Gabapentin MOA

A

Gabapentin works by blocking VG-Ca2+ channels and inhibits neurotransmitter releaseIt does not bind to GABA receptors

64
Q

When are gabapentine and pregabaline used by themselves?

A

Diabetic neuropathy, fibromyalgia, and post-herpetic neuralgia d/t VZV

65
Q

AE of gabapentine and pregabaline

A

Gabapentin and pregabalin can cause dose dependent sedation, dizziness and can cause ataxia. These side effects are more common in older adults.

66
Q

Vigabatrin

A

Vigabatrin is a narrow spectrum antiepileptic drug that irreversibly inhibits GABA-transaminase (the enzyme responsible for degradation of GABA); this produces a sustained increase in the amount of GABA in the CNS, providing tonic inhibition

67
Q

Tiagabine

A

Tiagabine is a narrow spectrum antiepileptic drug that inhibits GABA reuptake, increasing the amount of GABA in the CNS and providing tonic inhibition

68
Q

Explain absence seizures

A

Absence seizures most commonly occur in children and are characterized by sudden momentary lapse in awareness accompanied by staring, rhythmic blinking, or small clonic jerks. Following attack, the patient returns to normal but usually has no recollection that the seizure occurred

69
Q

How does absence seizures manifest in EEG?

A

3 Hz spike wave complexes on EEG

70
Q

How do you treat absence seizures

A

Ethosuximide

71
Q

Explain use, MOA of Ethosuximide

A

Ethosuximide is a very narrow spectrum antiepileptic because it is only good for the treatment of absence seizures. Ethosuximide is the 1st line treatment for patients experiencing only absence seizures. Ethosuximide works by blocking T-type Ca2+ channels in Thalamic neurons

72
Q

AE of Ethosuximide

A

Ethosuximide can cause GI distress (e.g. pain, nausea, and vomiting) and lethargy or fatigue

73
Q

What are other drugs that can be used to treat absence seizures

A

Valproate & Lamotrigine

74
Q

When are valproate and lamotrigine used for absence seizures instead of ethosuximide.

A

Valproate &Lamotrigine should be used instead of Ethosuximide if a patient has a history of other types of seizures accompanying their absence seizures