Anxiety, Insomnia, and Seizure Medications

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Systems Affecting Anxiety and Sleep

-Limbic System
and
-RAS System

Limbic System

- responsible for emotional expression, learning & memory
- Hypothalamus responsible for unconscious responses to extreme stress, & connects to the reticular formation (in brainstem)
- Stimulation of reticular formation- heightened alertness & arousal
- Inhibition of the reticular formation- general drowsiness & sleep

RAS

Reticular Activating System (RAS)
- the area where the reticular formation is located
- responsible for sleep & wakefulness
- if no signals pass through the RAS, no emotion-related signals get sent to the brain
- thought to be responsible for feelings: anxiety, fear & for sleep, restlessness

Common Causes of Anxiety

Phobias
Post-traumatic stress
Generalized anxiety
Obsessive-compulsive feelings
Panic

Anxiety

Anxiety- Common cold of psychiatric illness. 19 million Americans suffer from anxiety. Before you go to pharmacy you should: Counseling, relaxation techniques, guided imagery. You might want to look at the underlying problem first. If you're not targeting underlying problem, patient is gonna have symptom relief but the overall problem will not be fixed. Pharmacological help is proposed when it really affects your daily routines and the way you carry out your daily activity.

Anxiolytics

Drugs having the ability to relieve anxiety
Quite effective
Used when anxiety begins to significantly affect daily activities

Classes of Medications for Anxiety and Sleep Disorders

1) Antidepressants
2) Benzodiazepines
3) Barbiturates
4) Nonbenzodiazepine/nonbarbiturate CNS depressants

Antidepressants

Treat major depression and a range of anxiety conditions
Primary medications to reduce symptoms of panic and anxiety: TCAs, MAOIs, and SSRIs (see next slides)
Atypical antidepressants do not fall conveniently into the other categories
Adverse reactions make antidepressants unusable for some patients
example: Extra pyramidal side effects (EPS)

TCA- Tricyclic Antidepressants

TCA's will increase level of norepinephrine and serotonin, but may decrease your level of dopamine in the substancia negra (Black substance). Found in brain- decreased levels of substancia negra and dopamine will give Parkinson's symptoms.
-TCA's also give anti-cholinergic side affects (dried mouth, blurred vision, glaucoma, hyper/hypotension, cardiac arrhythmias, sedation- risk for falling and injuries)
-You cannot suddenly withdraw TCA's.
-Cannot take it together with Monoamine Oxidase Inhibitor); must wait atleast 2 weeks because they both increase the same neurotransmitter. It leads to hypertensive crisis. Alpha 1 is being increasingly stimulated.

MAOI (Monoamine Oxidase Inhibitor) Antidepressant

-prevent the breakdown of Norepinephrine which leads to an increase of norepinephrine in the synaptic cleft. If you, as a patient, take tyramine—amino acid, something to build norepinephrine, you can develop hypertensive crisis because there will be an increase of norepinephrine.

-Foods that contain tyramine: Red wine, chocolate, tuna, aged cheese. Taking this drug has lots of limitations.

-Do not take tyramine!

SSRI (Selective Serotonin Reuptake Inhibitor) Antidepressant

Inhibits the reuptake of serotonin and allows serotonin to remain longer in the synaptic cleft. SSRI's will take roughly 4 weeks to actually start working.... Benzodiapelines are given to allow SSRI's to work.
SSRI's will cause impotence. Will cause breast tissue to grow in males. Should not be taken with MAOI's because it will lead to hypertensive crisis.
Seratonin Syndrome
EPS—Extra pyramidal side effects (EPS)—decrease in dopamine: Parkisonian like syndrome.

TCA's

Elavil (amitrytiline)
Anafranil (domipranine)

MAOI's

Nardil (phenelzine)

SSRI's

Lexapro (escitalopram oxalate)
Prozac (fluoxetine)

Atypical Antidepressant

Effexor (venlafaxine)

Insomnia

Tends to go with anxiety...
Insomnia is the inability to fall or stay asleep for 6-8 hours. Ages-
-Short Term Insomnia: Usually caused by stress
-Long-Term Insomnia: Chronic Pain
-Rebound Insomnia: When patient feels better, and then all of a sudden they discontinue medications they've been taking for a long time.
-Assessment for Sleep Apnea, EEG—will be able to differentiate between different stages of sleep.
-monitors brainwave activity
- looks at nonrapid eye movement (NREM) & rapid eye movement (REM)
- REM is where dreaming occurs; associated with memory, learning, & adaptation
- NREM is rest & restore

Stages of Sleep

-In sleep you have, your Non REM (Lightest of stages 7-10 minutes- Stage 1) (Stage 2- arousable but asleep, but it is the longest of the stages)(Stage 3—Parasympathetic kicks in. Blood pressure and heart rate decreases, as well as the temperature),(Stage 4- Deepest stage. Regeneration and restoration would take place)
-1 REM stage- Rapid Eye Movement. Body completely relaxes and the wavelengths in the brain are similar to the ones of when the patient is awake. A lot of dreaming takes place. Patient would have the development of memories and adaptation. If patient has trouble with REM stage, they will lose focus and can't concentrate really well.

Benzodiazepines and Barbs

-Normally used for short-term anxiety. Medications for people that have physiological and psychological dependency.
-Enhance GABA- GABA normally decreases brain activity. It is considered the main inhibitory nerve transmitter. This leads to sedation, drowsiness, respiratory depression, gonna decrease anxiety, insomnia. The real problem is that inhibits the non-REM stage for and the REM. So though the patient may sleep longer, they might not actually get a restful sleep. Also metabolized by the liver and may lead to toxicity if the patient has liver problems.
-Anxiolitic medication and Antidepressant
-Can also be used as muscle relaxant

Benzodiazepines

Ativan*
- drug of choice for anxiety & insomnia
- 1960's: Lithium & Valium
- All benzos have same action & side effects
- Differences are in onset & duration
- Schedule IV drugs
- Most are metabolized by the liver & excreted in urine
- shorten time to fall asleep
- may affect REM
- short-term use
- higher doses 'hypnotic' r/t sleep induction ability

Benzodiazepines

Diazapam (Valium), lorazepam (Ativan)
Drug of choice for status epilepticus
Can be used also as muscle relaxant, anxiolytic, sedative, for vertigo and entiemetic.
Adverse effect
CNS depression
Respiratory depression and drowsiness
Prolonged use
Physical and psychological dependence upon abrupt withdrawal
Symptoms of withdrawal
Convulsions, tremor, vomiting, & sweating

Alprazolam (Xanax) PO used often for anxiety PRN.
****Look for Pam ending to help you remember benzodiazepines.
****Romazicon (Flumazenil) IV for over-dose or sign of respiratory depression

Ativan (Benzodiazepine)

Sedative- Hypnotic- anxiolytic Benzodiazepine

Extended ½ life of 10-20 hours
Can be administered PO or IV, IM
Side effects of drowsiness, sedation
Adverse effects (high doses) weakness, disorientation, blurred vision
Don't give with other depressant drugs or alcohol
-Doesn't affect memory because it doesn't go into REM stage

Barbituates

Were the drug of choice until Benzos were discovered
Withdrawal can be life-threatening
Rarely prescribed for anxiety due to high abuse potential
Schedule II med
Can depress CNS functioning at all levels
In prolonged use, can stimulate their own metabolism (and other meds)
Tolerance does not include respiratory effects

Barbituates

Behave the same way that the Benzos
-CNS depressant through the GABA
At a low level, barbituates will give you:
Low Dose---> Relieve of Anxiety. As you increase dose to Mild/Moderate Dose---> Relieves insomnia. Moderate Dose-0-> Sedation. High Dose--->Adjunct to Anasthesia. --> Seizures because you become anoxic.
-Barbituates will increase CYP-450 enzymes-- enzymes that metabolize medications. Leads the patient to needing a higher dose of medication to achieve a therapeutic level.

Phenobarbitol and Tegretol

*Phenobarbitol--> Increases CYP-450.Tegretol  Medication is broken down by CYP-450. It will be broken down faster since phenobarbitol is creating more of the enzymes. Phenobarbitol is helping break down Tegretol. The sedation of the drug does not decrease though.

Non-Barb/Non-Benzo

Called 'miscellaneous agents'
Unrelated chemically to barbs or benzos
BuSpar & Ambien
BuSpar**
takes weeks to 'build up' level
Not for acute anxiety
Not a dependence issue
Ambien**
-Schedule IV med
High doses cause convulsions
Minor effect on REM sleep
Adverse Effects: amnesia, sleep-driving, daytime sedation

Ambien (Non-barb/non-benzo)

Behaves the same way that benzodiapezine does: Increases GABA and decreases neurological activity. It will give you sedation. Can give you respiratory depression, but is not likely. Normally used for insomnia, can be used for anxiety though you have to prescribe a bigger dose. Sleep walking can be common: have to monitor—Safety is a concern. Ambien is working if you are able to sleep for 7 hours with no interruption. Has little effect on REM cycle; less likelihood of having memory problem .

Sleep Assessment

Trouble falling to, staying, or both
Early morning waking
Stress situations
Length of time
Baseline sleep
Medical history
Pain assessment
Rituals
-Does the patient have pain? Do you have a cup of coffee right before you go to bed? Heavy meal right before going to bed will increase metabolism and not let patient go to sleep. Medications? Zudaphed (nasal decongestant that activates sympathetic )

Sleep Interventions

(Based on assessment.)
-Importance of drowsiness and safety.
-Need to assess if the medication is working.
Administer med just prior to going to bed
Avoid caffeine and other stimulants
Cool, dark environment
Establish ritual
Out of bed if not asleep within an hour
Only sleep in room- no tv
Monitor for side effects of meds
Educate on potential impairments of meds
driving
drowsiness

Seizures

Has an underlying cause
- trauma, fever (kids), drugs/alcohol, pregnancy
Different types of seizures
Some have convulsions
May have triggers
LYTEs Imbalance
GABA- the primary inhibitory neurotransmitter in the brain

Seizure Types

-Uncontrolled neuronal firing.
-Seizures can be divided into partial or generalized.
*Partial—Simple or Complex. Simple=patient does not have loss of consciousness(LOC). Movement is going to be focal. Can be still conscious, and then you forget what happens. *Complex= You do have LOC. Movement can be focal or you have a mannerism. Confirm them with an EEG.
*Abnormal firing comes from a focal area in the brain—Normally does not cross hemispheres.
*Generalize—Absent: Patient gets a blank stare... (petit) does not need to shake/convulse. They are unaware of their surroundings. Have loss of consciousness. *Grandmal: (Tonic Clonic), patient is shaking... Leading to Anoxia in the brain. Main goal: Give patient oxygen and suction after. Pat the side reels of the bed with blankets. Airway, Safety (Do not stick anything in their mouth to keep it open), Medications. Medications we give are benzos through IV. Airway, Breathing , and Circulation. Generalized seizures come from both hemispheres and always have LOC.

What can cause a seizure?

A E I O U TIPS:
ALCOHOL- Patient is either intoxicated or withdrawing from alcohol. ENDOCRINE/EXOCRINE/ELECTROLYTES- Hyperglycemia, Hypoglycemia, Ketoacidosis, Hyponatremia Hyperthyroidism, Hypothyroidism.... INFECTION/INSULIN—meningitis, encephalitis, systemic brain infections. OVERDOSE- Phenylbolbitol, narcotics, cocaine, drugs. UREMIA- Kidney problems, high level of ammonia. TRAUMA- Head injury. INSULIN. PSYCH- Pseudo seizure. SEPSIS/SHOCK

Anticonvulsants

Benzodiazepines first line for acute seizure episodes = Short term

Second line or maintenance

*Dilantin

*Tegretol

*Depakote

Seizure Medications

Goal of Seizure medication therapy is to decrease/alleviate seizures

New vs Old Seizure Medications
Newer meds have less troubling side effects
Newer tend to be better tolerated
Newer have less risk to pregnancy
Be careful in regards to suicidal risk with newer ones
Adding multiple meds can increase seizure activity

Understanding Seizure Meds

Correcting LYTEs Imbalance: Potassium (K+), Sodium (Na+), Chloride (Cl-), and Calcium (Ca+)
- delaying Ca &/or Na influx
- stimulating influx of Cl-
- kicking K+ out
GABA- the primary inhibitory neurotransmitter in the brain
- by increasing GABA effect, the impulse transmission is decreased = seizures

Anti-Seizure Prototypes

Phenobarbital (Luminal)
- Barbituate; GABA A receptor agonist

Diazepam (Valium)
- Benzodiazapine; GABA A receptor agonist

Phenytoin (Dilantin)
- Hydantoin; Na+ Influx-suppressor

Valporic Acid (Depakote) works similar to hydatoin with influx of Na+
- Valproate

Luminal (Phenobarbital)

long-acting barbituate
PO, IM, IV routes
Category D
Schedule IV
Side effects: drowsiness, dizziness
Adverse effects: respiratory depression, increases pain
Multiple drug-drug interactions
-Used for seizures , insomnia, anxiety...

Valium (Diazepam)

Calming without strong sedation

Can take up to 4 weeks to get levels up (PO)

IV lasts for 20 minutes, rapid onset

Category D

Multiple drug-drug interactions

-Most used

Dilantin (Phenytoin)

Effective for most Sz types (except absence)
Has an anti-dysrhythmic property similar to lidocaine
- off-label use for digitalis-induced dysrhythmias
IV form only with saline
- can crystallize and become an embolism
- if IV in hand can have 'purple glove', exfoliative dermatitis
- monitor for Stevens-Johnson syndrome
IM has soft tissue irritants
Adverse effects: hyperglycemia, hypotension, v-fib, multiple blood dyscrasias
1930's med
Oral hygiene is a must
Narrow therapeutic range: 10-20 mcg/m L

Dilantin

most common for seizures; doesn't work right away. Need to know therapeutic level** 10-20. The way that it works is by desensitizing the influx of sodium into the neuron, consequently decreasing firing activity of the neuron. Can be given PO or IV. It should never be given IM because it will lead to necrosis of the tissue. If IV becomes dislodged, necrosis will developed in the tissue.


Once medication is taken, contraceptive measures do not work. When they do get pregnant, they are category D High likelihood that fetus will develop abnormalities.
Patient tends to develop suicidal ideations with this medication.
Some seizure medications can lead to arrhythmias of the heart, Dilantin is one of them.

Dilantin

-Teach oral hygiene. Patient may develop gingival hyperplasia—red gums.
-Always encourage fluids.
-Also considered an anti-arrhythmic. Have to monitor for arrhythmias because it has arrhythmic properties.
-May get drowsiness in the beginning, but eventually it wears out.
-Patient can develop aplastic anemia or agranular cytosis from bone marrow suppression: Bleeding from their mouth.

Dilantin Side Effects

Drowsiness, weakness & ataxia, insomnia, depression, headache, and psychosis
Gingival hyperplasia  overgrowth of gums
Practice good oral hygiene and regular dental visits
Androgen effect of excessive hair growth and development of acne
Encourage folic acid supplementation
**Drowsiness occurs initially, but decreases over time with use of medication

Depakote (valproic acid)

Used for a wide-range of Sz types & bipolar disorder
PO routes for administration
- GI irritation
- don't break/chew extended release
- don't mix liquid form with carbonated beverages
- can 'sprinkle' caplet beads if difficulty taking large pill
Adverse effects:
throat/mouth irritant, sedation, prolonged bleeding time, muscle weakness, weight gain, rash, photosensitivity
Interactions: drug-drug; increases dilantin and phenobarb levels

Depakote

-Hepato Toxic—can lead to liver failure. Patient must get their liver tested before and after they are given the meds.
-Assessment findings that patient has liver disease: They look swollen, jaundice (in the eyes especially- ictoris (sclera)
-Therapeutic Level: 50-100
Causes CNS depression

Hepatic dysfunction possible in first 6 months
**Monitor LFT's at 2 month intervals

*Therapeutic level 50-100mcg/mL

Tegretol

Adverse effects
Blood cell abnormalities/dyscrasias
Aplastic anemia, agranulocytosis
Monitor CBC routinely
Severely low sodium levels
Monitor drug levels as needed
**Normal Tegretol level is 4-12 mcg/mL
Take with food
Avoid grapefruit juice
. Patient will have toxic level and an increased amount of side effects.

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