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Block 15 > Pharmacology II > Flashcards

Pharmacology II Flashcards

1
Q

Disorder of brain function characterized by the periodic and unpredictable occurrences of seizures

A

Epilepsy

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2
Q

What is epilepsy characterized by?

A

Periodic and unpredictable occurrence of seizures

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3
Q

Transient alteration of behaviors due to excessive discharge of population of brain neurons

A

Seizure

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4
Q

Two types of epilepsy

A

Partial/focal

Generalized

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5
Q

Partial/focal epilepsy has neuronal discharge onset in what part of the brain

A

Localized area of the cerebral cortex, beginning in only one hemisphere of the brain

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6
Q

In generalized epilepsy, neuronal discharge is _____ at the onset

A

Widespread

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7
Q

Where in the brain does generalized epilepsy begin?

A

Both hemispheres of the brain

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8
Q

Seizures where consciousness is preserved

A

Simple partial seizures

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9
Q

Seizure greater than 5 minutes, needing medication

A

Status epilepticus

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10
Q

Seizures where consciousness is impaired and preceded by psychological symptoms

A

Complex partial seizures

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11
Q

3 types of generalized seizures

A

Tonic-clonic
Absence
Myoclonic

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12
Q

First phase of tonic-clonic seizures

A

Tonic phase (less than 1 minute) = sudden loss of consciousness, muscle rigidity, and respiration arrest

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13
Q

Second phase of tonic-clonic seizures

A

Clonic phase (2-3 minutes) - jerking of body muscles, with lip or tongue biting, and focal and urinary incontinence (relaxation and contraction)

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14
Q

Seizures with impaired consciousness (sudden onset and abrupt cessation duration < 10 seconds)

A

Absence seizures

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15
Q

What ages usually have absence seizures

A

Childhood, usually cease by age 20 yrs

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16
Q

Seizures with single or multiple myoclonic muscle jerks (to a greater or lesser extent, in a wide variety of seizures) no loss of consciousness

A

Myoclonic seizures

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17
Q

What happens to the neurons in epilepsy?

A

During a seizure, a small number of hyperexcitable neurons fire abnormally in synchrony
Normal membrane conductances
Inhibitory synaptic currents break down

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18
Q

Mechanism of epilepsy

A

Alteration in number, type and biophysical properties of voltage or ligand-gated K, Na, or Ca ion channels in neuronal membranes

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19
Q

What happens to the GABA(a) receptors in epilepsy?

A

Breakdown of GABA(a) receptor mediates an increase in chloride ion conductance and inhibition of action potentials

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20
Q

Synaptic excitation in epilepsy is mediated by what?

A

Ionotropic glutamate receptors

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21
Q

Na channel modulator drugs for epilepsy that enhance the fast inactivation

A

Phenytoin, carbamazepine, valproate (Mixed MOA)

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22
Q

Na channel modulator drugs for epilepsy that enhance slow inactivation

A

Lacosamide

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23
Q

Calcium channel blocker (T-type) drug for epilepsy

A

Ethosuximide

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24
Q

Calcium channel modulator (alpha2gama ligands) drug for epilepsy

A

Gabapentin

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25
Q

GABA-enhancing drug for epilepsy

A

Diazepam

26
Q

Glutamate receptor antagonist drug for epilepsy

A

Perampanel

27
Q

MOA for sodium channel modulators that enhance fast inactivation in epilepsy

A

Decreasing sodium influx into neurons by prolonging the existence of the inactivated state

28
Q

How do you take phenytoin?

A

Intravenous use only fosphenytoin (water soluble prodrugs)

29
Q

Phenytoin is metabolized by what?

A

CYP2C9; metabolism is nonlinear; elimination kinetics shift from first-order to zero-order at moderate to high dose lovels

30
Q

How are phenytoin plasma levels increased?

A

Transiently by drugs that compete for binding (carbamazepine, sulfonamides, valproic acid)

31
Q

What does phenytoin do to the metabolism of other drugs?

A

Increases the metabolism of other drugs, leading to decreases of their actions (contraceptives - can lead to pregnancy)

32
Q

Side effects of phenytoin

A

Gingival hyperplasia (gums grow over teeth)
Coarsening of facial features
Decreased bone density due to increased vitamin D metabolism
Cardiac arrhythmias

33
Q

How should you treat patients who are taking phenytoin?

A

Consistency treated with the same drugs from a single manufacturer. However, if switch to other product, care must be taken to select a therapeutically equivalent product.

34
Q

Sodium channel modulator for enhancing fast inactivation that has hepatic CYP3A4, which is responsible for its metabolism

A

Carbamazepine

35
Q

Carbamazepine has what for it’s active metabolite?

A

10,11 epoxied

36
Q

Adverse effects of carbamazepine

A

Stupor, coma, and respiratory depression

Blurred vision

37
Q

Sodium channel modulator for enhancing fast inactivation that is a broad spectrum ASD (anti-seizure drug)

A

Valproate

38
Q

MOA for valproate

A

Increase inactivated state of sodium channels at different sites than phenytoin or carbamazepine
Produces small reductions of low-threshold (T) calcium currents in thalamic neurons
Increases GABA concentration (Inactivating GABA-T transaminase)

39
Q

Adverse effects of valproate

A

Elevated hepatic enzymes (hepatitis, especially in children < 2 years old)

40
Q

Sodium channel modulator for enhancing slow inactivation that is used to limit sustained repetitive firing

A

Lacosamide

41
Q

Adverse effects of lacosamide

A

Double vision

Among all ASD, lacosamide may contribute to suicidal ideation. The FDA has mandate a black-bock warning for this agents

42
Q

Calcium channel blocker (T-type) that is the drug of choice for the treatment of absence seizures

A

Ethosuximide

43
Q

MOA for ethosuximide

A

Reduces low threshold T-type calcium currents in thalamic neurons; inhibits absence seizures

44
Q

Adverse effects of ethosuximide

A

Nausea
Vomiting
Anorexia
Photophobia

45
Q

Calcium channel modulators (alpha2gama ligands) that are designed as GABA agonists

A

Gabapentin

46
Q

MOA for gabapentin

A

GABA agonist

Bin with high affinity to alpha2gama subunit of calcium channels, resulting in decreasing calcium entry

47
Q

Adverse effects of gabapentin

A

No significant drug interaction which makes it idea to be used with other ASD’s

48
Q

GABA-receptor enhancing drug for epilepsy that increase the frequency, but not duration of opening at GABA activated chloride channels

A

Diazepam

49
Q

Therapeutic use for diazepam

A

In therapy of absence seizures and myoclonic seizures in children

50
Q

What is diazepam an effective agent for?

A

Status epilepticus

51
Q

What is status epilepticus?

A

A dangerous condition in which epileptic seizures follow one another without recovery of consciousness between them)
Treated with diazepam

52
Q

GABA-receptor enhancing drug that increases the duration of bursts of GABA(a) receptors on chloride channels without changing the frequency of the burst

A

Phenobarbital

53
Q

Adverse effects of phenobarbital

A

Sedation
Ataxia
Vertigo
Morbilliform rash in sensitive individuals (rash on back)

54
Q

Glutamate receptor antagonist that is metabolized by hepatic CYP3A, possibly decreasing the effectiveness of hormonal contraceptives, carbamazepine.

A

Perampanel

55
Q

MOA for perampanel

A

Selective, non competitive antagonist of the AMPA-type ionotropic glutamate receptor
AMPA receptor antagonists prevent repetitive neuronal firing

56
Q

Adverse effects of perampanel

A

Anxiety

Double vision

57
Q

Commonly used drugs for focal/partial seizures

A

Carbamazepine
Phenytoin
(Also phenobarbital, topiramate, and valproic acid)

58
Q

Commonly used drugs for generalized tonic-clonic (grand mal) seizures

A

Carbamazepine
Phenytoin
Valproic acid
(Alternative agent in adults = phenobarbital)

59
Q

Commonly used drugs for generalized absence seizures

A

Ethosuximide (DOC)

Valproic acid

60
Q

Ethosuximide is the preferred drug for what type of seizure because it causes minimal sedation

A

Generalized absence seizures

61
Q

DOC for myoclonic seizures

A

Valproic acid

62
Q

DOC for status epilepticus

A

IV diazepam

Block 15 (4 decks)

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