10/21 Flashcards
1
Q
List the main types of siezures
A
focal
complex focal
focal secondarily generalized
Generalized
generalized tonic-clonic
generalized absent
tonic
atonic
clonic and myoclonic
infantile spasms
2
Q
What are the symptoms of simple focal seizures?
A
Minimal spread of discharge
Does not affect consciousness or awareness
EEG may show normal discharge
3
Q
what is the difference between focal and generalized seizures?
A
focal begins and stays in one area of the brain
generalized covers the entire brain
4
Q
What are the symptoms of complex focal seizures?
Where do these originate?
A
May become unresponsive or lose consciousness
Most arise from temporal lobes
5
Q
What are the symptoms of focal seizures secondarily generalized?
A
Begin as simple or complex focal seizures, but then spread to rest of brain
Look like generalized tonic-clonic seizures
6
Q
What does generalized seizures have that focal seizures do not?
A
aura and post-ictal phase
7
Q
What are the symptoms of a generalized tonic-clonic (grand mal) seizure?
A
Person falls to ground
Entire body stiffens
Muscles jerk or spasm
Tongue or cheek may be bitten
Urinary incontinence
8
Q
What are the symptoms of a generalized absent seizure?
A
Stare into space
Wake-up, no notice of seizure
Some automatisms possible
9
Q
What are the symptoms of a generalized tonic seizure?
A
Muscles suddenly contract and stiffen (“sudden tone”)
Often causes falls
Another form of drop attack
10
Q
What are the symptoms of a generalized atonic seizure?
A
Sudden loss of muscle tone
Patient falls without warning
A drop attack
11
Q
What are the symptoms of a generalized clonic and myoclonic seizure?
A
Make the body jerk like it is being shocked
12
Q
What are the symptoms of infantile spasms?
A
Muscle spasms that affect a child’s head, torso, and limbs
Usually begins before age of 6 months
13
Q
what are the 3 general mechanisms of action that are targets for antiepileptic drugs?
A
- Modification of ion conductance
Na+, K+, Ca++ - Enhancing inhibition
Increasing inhibitory response by increasing activity at GABA receptors - Inhibiting excitation
Inhibit excitation response by inhibiting glutamate transmission, either at glutamate receptor or through release of glutamate itself
14
Q
What are the most common automatisms seen with seizures
A
Lip smacking
Rapid blinking of eyes
Swallowing
Fumbling
Scratching
Stumbling about
15
Q
What is tonic?
A
increase in tone of muscles; muscles contract and stiffen
16
Q
what is clonic?
A
muscle jerks/spasms; rapid movement back and forth
17
Q
What is the oldest non-sedative anti seizure drug?
A
phenytoin
18
Q
MOA of phenytoin?
A
alters sodium, GABA and Glutamate conductance
18
Q
what is the most effective drug for tonic-clonic seizures?
A
phenytoin
19
Q
What is important to know about the pharmacokinetics of phenytoin?
A
It is highly bound to albumin.
It is really easy to overdose on when in it’s free form
have to be careful with other drugs that compete for albumin or kick phenytoin off albumin
20
Q
What drug kicks phenytoin off of albumin?
A
valproic acid
21
Q
what is the therapeutic level of phenytoin?
A
10-20mcg/mL
only 10% is typically in the free form in the body
22
Q
what is the toxic and lethal level of phenytoin?
A
30-50mcg/mL
> 100mcg/mL
23
Q
what are drugs that compete for albumin binding sites?
A
carbamazepine
sulfonamides
Valproic acid
24
What are the toxicity symptoms of phenytoin?
vision changes
sedation
gingival hyperplasia
hirsuitism
25
what is the MOA of carbamazepine?
blocks Na+ channels
26
what drug class is carbamazepine?
TCA
27
what is the drug of choice for focal seizures?
carbamazepine (tegretol)
28
what does carbamazepine treat besides focal seizures?
trigeminal neuralgia
29
What is special about the pharmacokinetics of carbamazepine?
It increases it's own metabolism by increasing CYP450
named autoinducer
This increased metabolism also increases the metabolism of other drugs:
phenytoin
phenobarbital
ethosuxemide
valproic acid
clonazepam
30
locasamide(Vimpat) is widely used for what?
focal seizures
31
what is the MOA of lacosamide(Vimpat)?
blocks Na+ channels
32
toxicity of lacosamide (Vimpat)?
HA, nausea, dizziness
33
what is the safest sedative anti epileptic drug?
phenobarbital
34
what is the MOA of phenobarbital?
unknown
may enhance GABA
35
what is the drug of choice for seizures in infants?
phenobarbital
36
which anti seizure drug is the closest to the "miracle drug" that works for most seizures?
what types of seizures is it not useful to give for and may actually worsen them?
phenobarbital
Absence, atonic attacks, infantile spasms
37
what is the toxicity of phenobarbital?
sedation
38
What is fosphenytoin?
More soluble prodrug of phenytoin
“Better” than phenytoin because can be given IV
39
What are the drugs used for Focal and generalized tonic-clonic seizures?
phenytoin (Dilantin)
Carbamazepine
Lacosamide (Vimpat)
Phenobarbital
40
What are the drugs used for generalized seizures (not tonic-clonic)
ethosuximide
valproic acid(depakene)
41
what is the drug of choice for absence seizures?
ethosuximide
42
Ethosuximide has a good safety and efficacy index which is why it is often used for
children
43
what is the MOA of ethosuximide?
Ca++ channel inhibition
44
what is the MOA of valproic acid?
unknown
some effects on Na+ currents
increases GABA
Increases K+ conductance at high levels
45
what is known as a "broad spectrum AED"?
valproic acid (Depakene)
46
What is the drug interactions to know for valproic acid (depakene)?
**Displaces Phenytoin from proteins**
inhibits metabolism of many other drugs:
phenobarbital
phenytoin
carbamazepine
47
what are some common benzodiazepines?
Diazepam (valium)
Lorazepam (ativan)
Clonazepam (klonipin)
Chlorazepate dipotassium (tranxene)
48
what is the MOA of benzodiazepines?
Increases GABA action to depress all levels of CNS
49
clonazepam (klonipin) is only available in the _______ form.
It is good for
oral
absence seizures and myoclonic seizures
50
diazepam (Valium) is effective in stopping _______ but ________ therapy is not considered effective
continuous seizure activity
chronic
51
Lorazepam (ativan) is more effective than diazepam for ________
status epilepticus
52
what is the treatment options for infantile spasms?
palliative (keep sedated)
Prednisone
Vigabatrin (GABA analog)
53
what are the treatment options for epilepsy?
AED
resection of foci
vagus nerve stimulation
ketogenic diet (children)
medical marijuana
54
Status epilepticus is a
medical emergency.
55
treatment for status epilepticus
IV antiseizure meds
ABC's
Possibly intubation and sedation
56
chronic phenytoin therapy makes patients resistant to ___________
neuromuscular blocking agent
57
phenytoin can enhance neuromuscular blockades when
there is a high level in the system at the time the NMB is given
58
what is the only narcotic drug that can stimulate seizure activity?
Meperidine (demerol)
59
What is the MOA of Lamotrigine (Lamictal)
ion channel blocker
60
What is Lamotrigine (Lamictal) used for?
focal seizures
61
what is the MOA of GABA analogs?
increase GABA
62
what drugs are known as GABA Analogs?
gabapentin
pregabalin
vigabatrin
63
what are gaba analogs used for?
adjunct, neuralgia, infantile spasms
64
which category does GABA analogs fall under on the major seizure drugs chart?
focal and generalized tonic-clonic
65
Why are benzodiazepines rarely used in chronic therapy of seizure states but are valuable in status epilepticus?
They are sedative hypnotics which is great for stopping a seizure but you don't want the patient to be sleepy or sedated all the time
66
what is the difference between sedation and hypnosis?
Sedation:
Calming effect, decreased anxiety
Depressant effects on psycho-motor function
Hypnosis:
Deep sleep
Lack of memory
67
What are the major subgroups of sedative-hypnotics?
Benzodiazepines
barbituates
sleep aids
anxiolytics
ehtanol
68
What are the major drugs in the Benzodiazepine sedative-hypnotic subgroup?
diazepam
midazolam
69
What are the major drugs in the Barbituates sedative-hypnotic subgroup?
phenobarbital
70
What are the major drugs in the sleep aids sedative-hypnotic subgroup?
zolpidem
71
What are the major drugs in the anxiolytic sedative-hypnotic subgroup?
buspirone
72
what receptor does sedative-hypnotic drugs work on and what does it do?
what is special about ethanol in this regard?
GABA
it increases permeability to Chloride
ethanol enhances GABA as well as inhibits glutamate from opening cation channels.
73
what are the 4 phases of sleep and the important changes seen when taking sedative-hypnotics.
* Stage 1 (NREM): when we are first going to sleep
* Stage 2 (NREM): with hypnotics, there is an increase in this stage. This is desirable
* Stage 3 (NREM, used to be known as stage 3 and 4): this is our deepest sleep
**undesirable effects is a decrease stage 4 NREM slow-wave sleep**
* REM sleep. associated with dreaming. We are close to being awake at this point.
**undesirable effect is decreased REM**
The time it takes for us to actually go to sleep is known as SOL (sleep onset latency). The last desirable effect that hypnotics have is it decreases the time it takes for us to go to sleep
74
Describe ethanols effects on sleep
* Gives us more vivid dreams
* Not sleeping good
* Fall asleep faster and sleep longer but the sleep is not as restful as it could be because they do not spend as much time in REM sleep
75
Describe the Alcohol dehydrogenase pathway (AD)
Ethanol is broken down by alcohol dehydrogenase (ADH) into acetaldehyde.
If we are drinking at moderate levels, acetaldehyde is broken down by aldehyde dehydrogenase → then produced into acetate → acetate can be broken down into lipids/glucose or it can be breathed out
Alcohol dehydrogenase and Acetaldehyde both utilizes NAD (nicotinamide adenine dinucleotide) → NAD is converted into NADH → NADH goes through electron transport chain to make ATP/energy
76
what drug can inhibit alcohol dehydrogenase?
What is the result of this?
Fomepizole
increases our ethanol levels
77
Because you can get energy/calories from alcohol, it is viewed as similar to which biomolecule?
More similar to lipids than it is to glucose
78
Acetaldehyde is a toxic compound that produces what symptoms?
headaches, N/V
Associate acetaldehyde with hangover symptoms
79
Why do people get a "beer belly"?
This alcohol dehydrogenase pathway causes more calorie intake d/t the biproducts of acetaldehyde being broken down by aldehyde dehydrogenase to produce acetate
then acetate being broken down into lipids/glucose
80
Disulfiram (antabuse) MOA
Who is a target for this drug and why?
inhibits aldehyde dehydrogenase that converts acetaldehyde into acetate (so you’ll have more acetaldehyde in the body)
This can be given to chronic alcoholics. Within minutes of drinking alcohol, they have these hangover symptoms
The goal is to make them feel bad so they stop drinking
81
Which ethanol breakdown pathway is the common pathway?
Why is it called common?
alcohol dehydrogenase pathway
It is used by most people who are **not** chronic alcoholics
82
If someone drinks a wood alcohol (methanol: can cause death) which drug do you want to give?
Fomepizole.
Can block wood alcohol metabolism by blocking Alcohol dehydrogenase converting Ethanol into acetaldehyde.
83
Associate fomepizole with
toxic concentrations of poisonous alcohol, as opposed to ethanol
84
Describe the Microsomal ethanol-oxidizing system (MEOS) pathway
This pathway produces NADPH as a byproduct, instead of NAD/NADH
These individuals get less calories from alcohol. They tend to be thinner as well (this is because they aren’t having the conversion of NAD → ATP → calories)
This pathway still produces acetaldehyde
85
Which pathway is going to increase in activity with people who have **chronic** alcohol use?
Microsomal ethanol-oxidizing system (MEOS)
86
What percent of alcohol is metabolized by the liver?
90%
87
How much alcohol does the adult metabolize in 1 hr to prevent going into zero order kinetics?
7-10grams/hr
(1 standard drink)
88
What are the toxic effects of chronic ethanol ingestion?
Fatty liver → hepatitis → cirrhosis → liver failure
Neurotoxicity
Symmetrical peripheral nerve injury
Gait disturbances, ataxia
Optic nerve degeneration
Dementia, demyelinating disease
Wernicke-Korsakoff syndrome
Thiamine deficiency
Treatment: replenish thiamine
Paralysis of external eye muscles, ataxia, confusion, psychosis
89
What are the molecular targets of ethanol?
GABA (gamma-aminobutyric acid): main brain inhibitory neurotransmitter
Alcohol enhances the action of GABA at GABAA receptors
Glutamate NMDA: (from a&p) one of our pain receptors. Remember we talked about how alcohol is one of the things that can inhibit NMDA!
Ethanol inhibits the ability of glutamate to open this channel
Glutamate is excitatory, so ethanol inhibits this action
90
What is the difference between physiologic and psychological dependence?
Alcohol dependence (physiologic):
Body is now reliant on the drug - if you stop taking it you’ll have withdrawals
Addiction (psychological dependence)
Will seek out the drug regardless of negative consequences
Associated with dopamine
91
What is alcohol abuse?
Alcohol abuse- Use in dangerous situations and despite adverse consequences
92
How to manage acute alcohol intoxication?
Goal= patient safety
Prevent respiratory depression and aspiration of vomit
correct electrolyte imbalance and hypoglycemia
(banana bag for chronic alcoholics)
93
What are the treatment options for alcohol withdrawal syndrome and alcohol-use disorders?
Detoxification: Taper sedative to benzodiazepines
Alcohol counseling
Meds:
Naltrexone
Acamprosate
Disulfiram
94
How does Naltrexone work?
Long acting opioid antagonist
Patients must be opioid free before initiating because it could cause acute withdrawal syndrome from opioids
95
How does Acamprosate work?
Deals with the desire for alcohol
GABA channels in CNS decrease over time → patient has withdrawals and does not have normal brain function → acamprosate increases GABA activity
Adjunct therapy, not effective alone
96
How does Disulfiram work?
Inhibits aldehyde dehydrogenase - acetaldehyde accumulation
Causes extreme discomfort in patients that drink alcohol
97
What is the treatment for acute anxiety?
treat underlying causes first (disease, situational)
benzodiazepines (sedative/hypnotic)
98
What is the treatment for chronic anxiety?
buspirone (5-HT1A receptor agonist, which is G inhibitory and decreases cAMP)
99
What is the treatment for sleep disorders?
Non pharmacologic first: proper diet/exercise, stimulant (caffeine) avoidance, comfortable sleep environment
Pharmacologic:
Benzos/barbiturates: this is less effective sleep because you have decreased REM sleep and decreased stage 4 NREM sleep
Zolpidem (ambien) and eszopiclone (lunesta): helpful for sleep but high abuse potential
OTC: most are histamines (benadryl)
100
What is the major routes that sedative-hypnotic drugs are excreted?
Some of the sedative-hypnotics are excreted through the liver via alcohol dehydrogenase pathway (AD) and microsomal ethanol-oxidizing system (MEOS)
Others are excreted through the urine unchanged.
101
Where do most sedative-hypnotics work?
GABAA
102
How does a GABAA work?
GABA binds to receptor (has two binding sites for GABA)→ channel opens and chloride comes into the cell → hyperpolarized cell → harder to excite
103
What is the proposed mechanisms of action of benzodiazepines, barbiturates, and zolpidem?
GABAA
activation
104
What are some cautions associated with sedative-hypnotic drugs?
Drowsiness, impaired judgment, diminished motor skills
Somnambulism (sleep walking): with ambien and lunesta
“Date-rape “ drugs: benzos
In elderly pts, possibly use half dose to avoid overdose
Intentional overdose with these drugs: coma/death
Interactions with other CNS depressants can cause poor outcomes (coma/death): including alcohol and ambien
