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Pharmacology > Chapter 9 Nervous System (Anticonvulsants & Behavior Modifying Drugs) > Flashcards

Chapter 9 Nervous System (Anticonvulsants & Behavior Modifying Drugs) Flashcards

1
Q

Seizures

A

Periods of excessive brain electrical activity - can appear outwardly as a variety of signs depending on what area of the brain is affected

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2
Q

Focal Seizures

A

May appear as a muscle movement of one limb or area of the body - animal does not typically lose consciousness

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3
Q

Generalized Seizures

A

Involve all of the body and often are associated with loss of consciousness

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4
Q

Convulsions

A

Seizures that manifest themselves as spastic muscle movement caused by stimulation of motor nerves in the brain of spinal cord and are characterized into 3 categories (tonic, clonic and tonic-clonic seizures)

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5
Q

Tonic Seizures

A

Characterized by increased muscle tone and stiffening of the limbs

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6
Q

Clonic Seizures

A

Rare and are characterized by rapid contraction and relaxation of the muscles

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7
Q

Tonic-Clonic Seizures

A

(Grand Mal Seizures) Characterized by rapid alternation between tonic and clonic seizures

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8
Q

Epilepsy

A

Recurrent seizures originating from the brain - characterized by sudden loss of motor control, unconsciousness, and tonic-clonic seizures of relatively short duration (2-3 minutes)

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9
Q

Idiopathic Epilepsy

A

Has no known cause (even after diagnostic workup)

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10
Q

Genetic Epilepsy

A

Associated with familial genetic or breed predisposition

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11
Q

Structural Epilepsy

A

Occurs because of the presence of brain lesions

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12
Q

Prodrome/Prodromal Phase

A

Signs that occur prior to the onset of a seizure

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13
Q

Status Epilepticus

A

Refers to the state of being in the seizure - also used to describe the condition of animals with prolonged seizure activity

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14
Q

Ictus

A

Actual seizure itself

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15
Q

List at least 3 secondary pathologic conditions that can cause seizure activity

A 
Hypoxia
Hypocalcemia
Hypoglycemia
Toxicity (strychnine, lead, xylitol)
Canine Distemper
Brain migration of parasites
Brain tumors
Hypocephalus
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16
Q

Postictal Phase

A

Post-seizure period of confusion, anxiety, exhaustion and even blindness depending on nature and location of the seizure activity within the CNS - can last for seconds or hours

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17
Q

Epilepsy of Unknown Origin

A

When the cause of epilepsy has not been identified

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18
Q

Anticonvulsants

A

Drugs used to control seizures

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19
Q

Hyperthermia

A

Elevated body temperature

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20
Q

Hypoxia

A

Low blood oxygen level

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21
Q

Severe acidosis

A

pH of blood becomes more acidic

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22
Q

Phenobarbital

A

Barbiturate - Decreases likelihood of spontaneous depolarization in brain cells and reduces the spread of electrical activity throughout the brain from this seizure focus by enhancing the action of the GABA neurotransmitter

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23
Q

Mixed Function Oxidases (MFOs)

A

Family of enzymes primarily found in the liver

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24
Q

Cytochrome P-450 (CYP)

A

The MFO enzyme involved in phenobarbital metabolism (and also many other drugs as well)

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25
Q

Half life of Phenobarbital in dogs

A

30-90 hours

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26
Q

Therapeutic Monitoring

A

Evaluating the adequacy of a dosage regimen by checking blood concentrations of a drug

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27
Q

Refractory

A

Unable to be controlled

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28
Q

Why do animals started on Phenobarbital often exhibit signs of sedation and ataxia shortly after beginning the drug?

A

Initial high concentration of phenobarbital being achieved in the blood and body tissues - this initial effect usually diminishes in 2-3 weeks after therapy has been started (if symptoms persist serum levels should be checked for potential overdose)

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29
Q

List 2-4 other clinical signs of Phenobarbital therapy

A 
Polyphagia
Polydipsia
Polyuria
Inhibitory effect on the release of the antidiuretic hormone (which causes pu/pd)
Increase ALT and ALP serum levels
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30
Q

Phenobarbital-Induced Hepatotoxicity

A

Liver disease cause by a drug and is an idiosyncratic adverse reaction - can be fatal if not recognized and treated early enough

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31
Q

Idiosyncratic Adverse Reaction

A

Reaction that cannot be predicted

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32
Q

What is the infrequent side effect of Phenobarbital that is sometimes exhibited in dogs?

A

Hyperactive / more excitable instead of lethargic or sedated - idiosyncratic - often animals need to be switched to a different anticonvulsant

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33
Q

Approximately how many mg’s are in 1 grain

A

Approximately 60mg (64.8mg exactly)

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34
Q

True or False

Seizure conditions in horses and livestock are very easily and successfully medically managed

A

FALSE.
Seizure conditions in these animals often leads to humane euthanasia due to the danger of animals that large harming themselves, handlers or other animals near them when seizures occur

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35
Q

Induced Metabolism

A

Results in the concentrations of active drug in the blood decreasing as the body becomes more efficient at metabolizing the drug

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36
Q

What is ADH?

A

Anti-diuretic hormone is the hormone that usually helps the body conserve water by reducing water loss through the kidneys as urine

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37
Q

What does a decrease in ADH typically cause?

A

Polyuria and Polydipsia (compensating)

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38
Q

Benzodiazepine Tranquilizers for seizure control work by what method?

A

Controls seizures by rapidly penetrating the blood-brain barrier and enhancing the inhibitory effect of the CNS neurotransmitter GABA
GABA helps counter the effect of stimulation neurotransmitters in the brain (Acetylcholine and Norepinephrine) enhancing the GABA effect quiets the activity and excitability of the CNS

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39
Q

Diazepam (Valium)

A

Older bezodiazepine - Drug of choice for animals in status epilepticus - Not used for long term seizure control (develops tolerance very quickly)

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40
Q

Approximately how much Diazepam reaches systemic circulation when administered PO?

A

2-5% due to significant liver metabolism from the first-pass-effect - making it relatively ineffective

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41
Q

Why do Benzos cause ataxia and weakness?

A

Benzos are muscle relaxants

42
Q

What effects do Benzos have on learned behaviors?

A

The reduce the effects of training or learned behaviors, potentially allowing for more aggressive or territorial behaviors exhibited prior to training to be exhibited again

43
Q

True or False

Animals can just discontinue the use of benzos with no significant side effects

A

FALSE. This drug needs to be tapered!
Abrupt cessation of these drugs can lead to withdrawal signs: listlessness, decreased appetite, weight loss, fever and even recumbency

44
Q

What is Distat?

A

Gel formulation of Diazepam available in the US for rectal administration

45
Q

Midazolam

A

Benzodiazepine similar to Diazepam that can be used as a substitute for control of active seizures - similar significant first pass effect

46
Q

Clonazepam

A

Adjunct drug given PO to help control seizures on a long term basis
Significant first-pass-effect
Must be administered multiple times a day to maintain therapeutic concentrations
Most animals develop a significant tolerance to these drugs within a relatively short period of time (limiting their use long-term)

47
Q

Clorazepate

A

Adjunct drug given PO to help control seizures on a long term basis
Significant first-pass-effect
Must be administered multiple times a day to maintain therapeutic concentrations
Most animals develop a significant tolerance to these drugs within a relatively short period of time (limiting their use long term)

48
Q

How do Bromides control seizures?

A

Mechanism of Bromides is not clearly defined, but it may act like Chloride ions to change the resting membrane potential or neurons, making them more difficult to depolarize OR may enhance the activity of GABA neurotransmitters

49
Q

What is the net effect of Bromides?

A

A nervous system that is less likely to spontaneously discharge and produce a seizure

50
Q

How are Potassium and Sodium Bromide used in seizure control?

A

Adjunct therapies for dogs whose seizures are not well controlled by Phenobarbital alone

51
Q

It takes Potassium Bromide ___-___ months to reach a steady-state concentration

A

3-5 months

52
Q

Steady State concentration equation

A

Steady State = 5 x half life

53
Q

True or False

Potassium bromide has a long half life

A

TRUE.

Potassium bromides half life is 21-24 days in the dog

54
Q

What is the most common side effect of Potassium bromide?

A

Vomiting - it is thought that the potassium/sodium salts directly irritate the gastric lining

55
Q

True or False

Bromides are not used in cats

A

TRUE
Bromides can produce a respiratory syndrome that resembles Bronchial Asthma and it occurs commonly enough in cats on bromides to warrant avoiding the use of bromides for seizure control in cats

56
Q

Zonisamide

A 
Unique anticonvulsant because it belongs to the sulfa-antibiotic drug class 
Mechanism is unknown 
Used in dogs that are refractory to other anticonvulsants
57
Q

Levetiracetam (Keppra)

A

Adjunct anticonvulsant
Mechanism not completely understood and not similar to any of the other anticonvulsants discussed
(may interfere with the release of neurotransmitters from neurons, decreasing the ability of neurons to communicate with each other across synapses)

58
Q

Keppra is often advocated as

A

First-line drug for mild seizures in fairly low frequency due to its safety and availability

59
Q

How often does Keppra need to be administered?

A

Every 8 hours

60
Q

Can Keppra be used in both dogs and cats safely as an adjunct drug?

A

Yes

61
Q

Gabapentin’s use as an adjunct drug for seizure control

A

Used in the 1990’s and early 2000’s - has fallen out of use since it is NOT as effective as Leviteracitam or Zonisamide in helping control refractory seizures in dogs and has mixed reviews on its effectiveness

62
Q

Neuropathic Pain

A

Pain that originates not from a nociceptor but from the pain neurons themselves depolarizing and sending pain signals that confuse the brain into thinking there is a trauma or injury to the part if the body supplied by that particular pain sensory nerve

63
Q

Personality, emotions and fears are the result of what?

A

Complex, integrated balance (or imbalance) of a wide variety of chemical neurotransmitters. Demonstrating how readily normal brain function can be altered by even minor changes in concentrations of various neurotransmitters

64
Q

What are some side effects of neurotransmitter imbalances?

A 
Clinical depression
Behavior changes
Old-age memory changes
Self-destructive activities
Anxiety/fear
65
Q

Primidone

A

Approved drug for use as anticonvulsant for dogs - Alone it has some anticonvulsant activity but its efficacy mostly attributed to primidones metabolism of phenobarbital

66
Q

Behavior modifying drugs

A

Change the concentrations of selected neurotransmitters in the brain with the intent of decreasing or enhancing a specific mental activity and work by one of six mechanisms

67
Q

Enhancing the release of either inhibitory or excitatory neurotransmitters

A

One of the mechanisms of how behavior modifying drugs work

68
Q

Enhancing binding (affinity) or neurotransmitters to their receptors

A

One of the mechanisms of how behavior modifying drugs work

69
Q

Imitating the natural neurotransmitter and combining with the neurotransmitter’s receptor to stimulate the receptor (agonist effect)

A

One of the mechanisms of how behavior modifying drugs work

70
Q

Imitating the natural neurotransmitter and combining with the neurotransmitters receptor to reduce or prevent stimulation of the receptor (antagonist effect)

A

One of the mechanisms of how behavior modifying drugs work

71
Q

Prolonging the action of the neurotransmitter by decreasing the breakdown or slowing the rate of termination of the neurotransmitter itself

A

One of the mechanisms of how behavior modifying drugs work

72
Q

Shortening the action of the neurotransmitter and its activity in specific regions of the brain

A

One of the mechanisms of how behavior modifying drugs work

73
Q

Antipsychotic Drugs

A

Major tranquilizers and include Phenothiazine tranquilizers
Not commonly used in vet med (limited anxiolytic properties, abundant side effects and spontaneous muscle movement caused by blocking dopamine receptors in the brain)

74
Q

Limbic System

A

Parts of the brain involved with emotion

75
Q

What are antipsychotics most commonly used for in vet med?

A

To control learned fear responses associated with thunderstorms, fireworks and other stimuli (Acepromazine)

76
Q

Increased dopamine and stimulation of receptors in the limbic system have been shown to result in what?

A

Abnormal behaviors
Blocking dopamine receptors in this area of the brain allows other neurotransmitters to dominate and decreases the incidence of the abnormal behaviors related to emotions

77
Q

One major drawback Phenothiazine tranquilizers is…

A

Decreases LEARNED responses but NOT instinctual responses so treatment can sometimes uncover underlying inappropriate behaviors

78
Q

Antidepressant Drugs

A

Mood elevating drugs used in human therapy that consist of 3 classes used in vet med

79
Q

What are the 3 classes of antidepressants used in vet med?

A

TCA’s (Tricyclic Antidepressants), SSRI’s (Selective Serotonin Reuptake Inhibitors), and MAOI’s (Monoamine Oxidase Inhibitors)

80
Q

Describe TCA’s (Tricyclic Antidepressants) Mechanism

A

Works by decreasing the reuptake of serotonin and norepinephrine from the synaptic cleft, which allows the neurotransmitter to accumulate and prolongs its stimulatory activity

81
Q

SSRI’s (Selective Serotonin Reuptake Inhibitors Mechanism

A

Antidepressants derived from TCA drugs - they share the same mechanism but SSRI’s are more selective for blocking only serotonin reuptake instead of both serotonin and norepinephrine like TCA’s

82
Q

MAOI’s (Monoamine Oxidase Inhibitors) Mechanism

A

Inhibits the enzyme monoamine oxidase (whose purpose is to catabolize serotonin, dopamine, and norepinephrine) allowing for additional accumulation of these neurotransmitters, stimulating the CNS in general

83
Q

Synaptic Cleft

A

Space in the synapse between two communicating neurons

84
Q

List 2-5 TCA drugs commonly used in vet med

A
  • Clomipramine (Clomicalm)
  • Amitriptyline
  • Doxepin
  • Imipramine
  • Desipramine
  • Nortriptyline
85
Q

Reconcile

A

FDA approved version of Fluoxetine for use in dogs to treat separation anxiety

86
Q

What are TCAs used to treat in vet med?

A

Generalized anxiety
Separation anxiety behaviors in dogs and cats
Reduce excessive feather plucking in birds

87
Q

True of False

Evaluation of treatment with TCAs can be immediately observed within a few days of starting administration

A

FALSE

  • TCA drugs MUST be administered every day to work appropriately
  • Changes will not be observed right away because the brain biochemistry takes time to adjust to the drugs effects
  • 2-4 weeks minimum for effects to be evaluated
88
Q

True or False

Serotonin is a neurotransmitter identified as playing a significant role in determining mood and behavior

A

TRUE

89
Q

What behaviors are SSRIs used to treat in vet med?

A
  • OCD
  • Anxiety
  • Aggression
  • Fear of people
90
Q

What drug class should never be administered with SSRIs?

A

MAOIs - because they inhibit the breakdown of precursors for several catecholamine compounds, including serotonin

91
Q

Serotonin Syndrome

A
  • Caused by combination of excessive production and release of serotonin by MAOIs and inhibition of serotonin and removal from the synapse by SSRIs
  • Potentially fatal
92
Q

What symptoms are observed in a patient experiencing serotonin syndrome?

A 
Hypertension
Hyperthermia
Tremors
Seizures 
Altered mental status
93
Q

What are 2 SSRI drugs used in vet med to treat separation anxiety and fear of people (specifically)

A

Fluoxetine

Sertraline

94
Q

What is the only MAOI used to any extent in vet med?

A

Selegiline (Deprenyl) or Anipryl

95
Q

What is Selegiline used to treat in animals?

A

Cushings disease

Canine Cognitive Dysfunction (old dog senility)

96
Q

Anxiolytic Drugs

A

Drugs the lyse anxiety or decrease fear responses

97
Q

Benzodiazipines work by:

A

Facilitating stimulation of the Gamma (y)-aminobutyric acid A (GABAA) receptors by the inhibitory neurotransmitter GABA, depressing the neurons of the CNS

98
Q

What are anxiolytic drugs used to treat in vet med?

A
  • Generalized anxiety
  • Compulsive licking
  • Aggression
  • Canine cognitive dysfunction syndrome in geriatric dogs
99
Q

Cannabidiol (CBD)

A

Clinical studies in humans using CBD (non-psychoactive cannabinoid derived from cannabis) for the treatment of seizures
Veterinarians cannot currently legally prescribe CBD

100
Q

What are the 3 most important things that are absolutely REQUIRED when it comes to behavior modification in pets?

A

1) TRAINING TECHNIQUES
2) Persistence on the part of the pet owner
3) Possibility of medication to assist with the behavior modifying process
* * There is NO MAGIC BULLET drug that exists for behavior therapy ***

Pharmacology (13 decks)

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