Transcript CNS Drugs Paul Algeo, PharmD/PA Candidate 2012 algeop@gmail

CNS Drugs
Paul Algeo, PharmD/PA Candidate 2012
[email protected]
2-26-10
Objectives
• Recall the bolded brand/generic names
for drugs under “Ranking of CNS drugs”
slide.
• Identify major indications (uses) for each
class of CNS drugs.
• List major counseling points for each
class of CNS drugs, including common
side effects.
• Describe the MOA for each class of CNS
drugs.
The Big Picture
• What are Central Nervous System (CNS)
drugs?
– Antidepressants, Anti-Psychotics, Anxiolytics, Antiepileptics, Stimulants, Skeletal Muscle Relaxants.
• How do these agents work?
– They alter or modulate the CNS via binding to receptors
and/or affecting neurotransmitter levels.
• What are they used for?
– Depression, schizophrenia, anxiety, seizures, ADHD,
neuropathy, muscle pain, and other mental health
disorders.
• Do they have side effects?
– Yes!
Non-Rx Treatment
• Eligible Indications:
– Depression
• Exercise!
• Light Therapy (SAD)
• Cognitive Behavioral
Therapy (CBT)!
• Avoid Stressors
• Communication
– Anxiety
•
•
•
•
CBT!
Sleep patterns
Avoid triggers
Communication
•Non-Eligible Indications:
•Psychosis
•Seizures
•ADHD?
•Muscle spasms?
Ranking of CNS drugs
•
•
•
SSRIs
•Anxiolytics/Hypnotics
•Skeletal Muscle Relaxants
10
•Xanax (alprazolam)
•Soma73 (carisoprodol)
– Celexa35 (citalopram)
•BuSpar155 (buspirone)
•Flexeril42 (cyclobenzaprine)
– Lexapro24 (escitalopram)
•Valium60 (diazepam)
•Robaxin190 (methocarbamol)
30
– Prozac (fluoxetine)
•Ativan33 (lorazepam)
20
– Zoloft (sertraline)
•Restoril106 (temazepam)
•TCAs
48
16
– Paxil (paroxetine)
•Ambien (zolpidem)
–Elavil63 (amitriptyline)
•Anticonvulsants
Other AntiDepressants
–Remeron143 (mirtazapine)
34
– Wellbutrin/Zyban36 (bupropion) •Klonopin 37(clonazepam)
–Pamelor219 (nortriptyline)
•Neurontin (gabapentin)
– Cymbalta59 (duloxetine)
•Lamictal103 (lamotrigine)
47
– Desyrel (trazodone)
•Keppra213 (levetiracetam)
– Effexor44 (venlafaxine)
•Dilantin147 (phenytoin)
•Lyrica93 (Pregabalin)
“Atypical” Anti-Pyschotics
•Topamax107 (topiramate)
– Abilify149 (aripiprazole)
•Depakote122 (Valproic Acid)
– Zyprexa185 (olanzapine)
•Stimulants
– Seroquel81 (quetiapine)
•Strattera216 (atomoxetine)
– Risperdal112 (risperidone)
•Concerta/Ritalin110 (methylphenidate)
•Adderall57 (dextro/amphetamine salts)
Antidepressants I
I. Selective Serotonin Reuptake Inhibitors (SSRIs)
•
•
•
•
•
Escitalopram (Lexapro)
Sertraline (Zoloft)
Fluoxetine (Prozac)
Paroxetine (Paxil)
Citalopram (Celexa)
Selective Serotonin
Reuptake Inhibitors (SSRIs)
• MOA - Block reuptake of
serotonin into nerve
terminal leading to
increased serotonin levels
at synapse
• Onset: 2-6 wks
• Admin:
– Same time each day, w/
or w/o food
– Titrate up when starting
and at high doses do not
d/c abruptly
• SE - Dry mouth, sexual
dysfunction, drowsiness,
sweating
• DDI - SSRIs are CYP2D6
inhibitors, therefore they
will increase the
concentration of drugs
metabolized by CYP2D6.
• Not for use with MAOIs 14 day washout period
required when switching.
• Serotonin Syndrome
Black Box Warning for (Lexapro)
•
Suicidality and antidepressant drugs: Antidepressants increased the
risk compared with placebo of suicidal thinking and behavior
(suicidality) in children, adolescents, and young adults in short-term
studies of major depressive disorder (MDD) and other psychiatric
disorders. Anyone considering the use of escitalopram or any other
antidepressant in a child, adolescent, or young adult must balance this
risk with the clinical need. Short-term studies did not show an increase
in the risk of suicidality with antidepressants compared with placebo in
adults older than 24 years of age; there was a reduction in risk with
antidepressants compared with placebo in adults 65 years of age and
older. Depression and certain other psychiatric disorders are
themselves associated with increases in the risk of suicide.
Appropriately monitor patients of all ages who are started on
antidepressant therapy and closely observe for clinical worsening,
suicidality, or unusual changes in behavior. Advise families and
caregivers of the need for close observation and communication with
the prescriber. Escitalopram is not approved for use in children younger
than 12 years of age.
Antidepressants II
II. Tricyclic Antidepressants (TCAs)
–Amitriptyline (Elavil)
–Nortriptyline (Pamelor)
Tricyclic
Antidepressants(TCAs)
• While labeled for depression,
off-label uses can include:
– Peripheral neuropathy
– Pain/Fibromyalgia
– Migraine prophylaxis
– Irritable Bowel Syndrome
(IBS)
• MOA: Increases the synaptic
concentration of serotonin
and/or norepinephrine by
inhibition of their reuptake by
the nerve terminal.
• Admin - Best at night due to
drowsiness
•Onset: up to 4 weeks.
•SE - Sedation, weight gain, AntiChol effects.
•DDI: CYP2D6 inhibitors (i.e.
SSRIs), aspirin, phenytoin and
other CNS agents.
•Not to be used with MAOIs - 14
day washout period required
•Monitoring: 30 day supply
enough to fatally overdose (don’t
tell pt this). Overdose can lead to
the 3 “C”s: Coma, Convulsions,
Cardiotoxicity.
Antidepressants III
• III. Miscellaneous Antidepressants:
– Venlafaxine (Effexor)
– Mirtazapine (Remeron)
– Duloxetine (Cymbalta)
– Bupropion (Wellbutrin/Zyban)
– Trazodone (Desyrel)
Drug
MOA
S/E
Admin/Notes
re-uptake inhibitor of
5HT, NE, DA
Anti-Chol, insomnia,
HTN, NMS, some
sexual dysfunction.
W/food; XR capsules
may be sprinkled on
applesauce and
swallow whole.
Increased appetite, dry
mouth, constipation,
drowsiness
At bed time
Mirtazapine
(Remeron)
Antagonizes alpha-2
receptors centrally,
which increases [5HT]
and [NE].
Duloxetine
(Cymbalta)
SNRI: Re-uptake
inhibitor of 5HT and
NE.
Anti-Chol,  appetite,
fatigue, risk of
bleeding, hepatitis.
W/ or w/o food.
Dual DA/NE reuptake
inhibitor, with NO
serotonin activity.
Insomnia, Anti-Chol,
seizures (w/high dose).
C/I in pts w/bulimia and
anorexia.
W/ or w/o food.
Lacks 5HT activity,
therefore, no sex
dysf, weight gain,
excessive sedation.
Probably a serotonin
reuptake inhibitor.
Drowsiness, Anti-Chol
At bedtime.
Commonly used as a
non-habit forming
sleep aid.
Venlafaxine
(Effexor)
Bupropion
(Wellbutrin/
Zyban)
Trazodone
(Desyrel)
Miscellaneous
Antidepressants (con’t)
• General Themes for drugs from Prior Slide:
– Onset: 2-6 weeks
– Not to be used with MAOIs: 14 day washout period
required.
– Suicidal Risk for all antidepressants
– Less sexual side effects (except for Effexor)
– Should NOT d/c drug abruptly; need to taper down (or up).
•Other indications/uses:
•Duloxetine (neuropathic pain)
•Zyban (smoking cessation)
•Trazodone (sleep aid)
“Atypical” Antipsychotics
• Quetiapine (Seroquel)
• Risperidone (Risperdal)
• Olanzapine (Zyprexa)
• Aripiprazole (Abilify)
“Atypical” Antipsychotics I
• MOA - All work to
antagonize dopamine
(DA) receptors, which 
[DA] centrally. (Some are
mixed DA/5HT antagonists).
• Onset: 3-6 weeks
• Uses: Schizophrenia,
Bipolar Disorder, even
depression and sleep
disorders.
• Admin: w/ or w/o food.
• “Typical” Antipsychotics:
drugs developed prior to the
“atypicals” with higher incidence
of serious s/e such as:
– Extra-pyramidal Symptoms
(EPS)
– Tardive Dyskinesia (TD)
– Neuroleptic Malignant
Syndrome (NMS).
“Atypical” Antipsychotics II:
Side Effects
Drug
Glucose
Weight Gain Intolerance/
DM II
Quetiapine
(Seroquel)
X
X
Risperidone
(Risperdal)
X
X
Olanzapine
(Zyprexa)
X
X
Aripiprazole
(Abilify)
Abnormal
Lipids
Cardiac
Dysfunction
(arrhythmia)
X
X
X
•General S/E: GI upset, hypotension, NMS!
Anxiolytics,
Sedative Hypnotics
• Zolpidem (Ambien)
• Buspirone (BuSpar)
• Benzodiazepines (“Benzos”):
– Temazepam (Restoril)
– Alprazolam (Xanax)
– Diazepam (Valium)
– Lorazepam (Ativan)
Anxiolytics,
Sedative Hypnotics
•
•
MOA:
– Benzos: bind to the GABA
receptor, which leads to a less
excitable neuronal state (less
anxiety, more sedation).
– Zolpidem: binds to a different
site on the GABA receptor,
eliciting only sedation effects
(and not anxiolytic effects).
– Buspirone: does not interact
with with the GABA receptor, but
rather is an agonist for a
serotonin receptor.
Uses:
– Anxiety (Benzos)
– Insomnia (Zolpidem)
– Off Label uses include phobias,
OCD, panic disorders
•Onset: hours (benzos, zolpidem),
weeks (buspirone).
•Admin - At bedtime for insomnia,
before anxiety promoting activity
(flights, dental appt, etc).
•SE - drowsiness, hypotension,
bradycardia, non-EtOH hangover
effect, CNS depressive effects
•Notes
–Alcohol intensifies effects**
–Caution with falls in elderly
–Dependence is possible**
–All are scheduled (C-IV/V)
drugs**
**Not with buspirone
Anticonvulsants
• Antiepileptics:
–
–
–
–
–
–
–
–
Lamotrigine (Lamictal)
Gabapentin (Neurontin)
Valproic Acid (Depakote)
Topiramate (Topamax)
Levetiracetam (Keppra)
Pregabalin (Lyrica)
Phenytoin (Dilantin)
Clonazepam (Klonipin)
Anticonvulsants I
• MOA: Prevents/antagonizes seizure activity via multiple
mechanisms including decreasing the release of
excitatory neurotransmitters (NT), increasing the activity
of inhibitory NTs, keeping cells depolarized and/or
stabilizing their membranes.
• Primary Use: prevent/treat seizures.
• Other uses:
– Peripheral neuropathy (Gabapentin)
– Prophylaxis for migraines (Topamax)
– Bipolar I disorder (Lamotrigine & Valproic Acid)
– Fibromyalgia (Lyrica)
Anticonvulsants II
• Onset: hours (most) to
•SE - drowsiness, fatigue, N/V(most)
weeks (Lyrica)
– rash (Lamictal)
• Admin:
– weight gain (Depakote)
– If GI upset a risk - take w/
– weight loss (Topamax)
food
–Phenytoin:
– Titrate dose up to
–Gingival hyperplasia
therapeutic effect
–Nystagmus
• Notes:
–Steven-Johnson Syndrome
– Often have narrow
therapeutic index (NTI) for
•More Notes:
seizures.
•Keppra is the most benign
– Many DDIs
newer agent (less sedation).
– Take meds regularly;
interruptions can cause
seizures.
Stimulants
• Dextro/Amphetamine (Adderall)
• Methylphenidate (Concerta, Ritalin)
• Atomoxetine (Strattera)
Stimulants
• MOA: Block the reuptake of
NE or NE/DA. Brings ADHD
pts “down”, but brings nonADHD pts “up”
• Uses - ADD, ADHD,
Narcolepsy
• Onset: hours
• Admin:
– Prefer taken in AM
– W/ or w/o food (food
delays onset).
•S/E (dangerous) - tachycardia,
HTN, hallucinations, insomnia,
decreased appetite (esp kids)
•Not to be used with MAOIs:
•14 day washout period
required.
•Notes:
–All are C-II, except Strattera,
which is NOT a controlled drug.
–Concerta: ADHD, Narcolepsy
–Ritalin: ADHD only
–Commonly abused by college
students as study aid
Skeletal Muscle Relaxants
• Cyclobenzaprine (Flexeril)
• Methocarbamol (Robaxin)
• Carisoprodol (Soma)
Skeletal Muscle Relaxers
(CNS Acting)
• MOA: Causes CNS
depression, which leads
to skeletal muscle
relaxation.
• Onset: 30-60min
• Uses - Acute muscle
spasms, muscle pain,
supportive therapy in
tetanus (Robaxin)
• Admin - Generally 3-4x
daily, for acute use.
•S/E: Anti-Chol effects,
drowsiness, dizziness, vertigo
(whirling).
•Notes:
•Alcohol will intensify effects
•Soma is now a C-IV in WA!
•S/E are similar to other CNS
drugs, be aware.
•Flexeril LOT NTE 2-4 wks.
Let’s Recap!
“I know that I have told you a lot of information, so to make sure I
didn’t forget anything important, can you tell me about…”
•Brand/generic names for:
•Lexapro, Zyban/Wellbutrin, Cymbalta, Abilify, Zyprexa, Ambien,
Keppra, Lyrica, Strattera, Effexor.
•Major indication (uses) for all the classes of drugs we discussed
today.
•i.e. TCAs can be used for depression and neuropathy (off-label).
•Describe major counseling points and common side effects for
each class of drugs (and HOW you would articulate these points).
•i.e. suicidal risk for antidepressants, alcohol-intensifying effects of
benzos, anti-cholinergic effects, admin PM vs AM, etc.
•Know, in general, the major MOAs for these CNS drus classes.
•i.e. antidepressants inhibit reuptake of certain NTs.
More Recap!
General Themes:
1. Time to effect for many of the
classes of drugs is weeks.
Which classes take days?
Which take hours?
2. Potentially long washout
periods when switching from
a MAOI to certain drugs, viceversa.
3. Suicidal Risk.
4. Many of these drugs have
Anti-Chol effects, sedation,
and sexual dysfunction s/e.
Which drugs/classes do not?
Some quick Pearls:
•TCA overdose
•Phenytoin S/E
•Keppra = benign
anticonvulsant.
•Strattera is only stimulant that is
NOT controlled.
•Soma recently became a
controlled drug in WA.
“FYI” Slides
The following slides are for YOUR
INFORMATION, in other words, they
will NOT show up on any exam
question!
“What am I suppose to learn from this
lecture? What are the expectations?!”
Bloom’s Taxonomy
Neurotransmitters:
Brain’s Chemical Messengers
Neurotransmitter
Normal Function
Malfunction
Dopamine
Mood, energy level, and
ability to feel pleasure
Depression
Serotonin
5 senses (touch, hearing, Depression,
sight, taste, smell), sleep, aggressive or mellow
aggression, and hunger
behavior, altered
sleep pattern, and
altered hunger
GABA
Seizures threshold, and
depression
Seizures, and
depression
Norepinephrine
Heart, respiration, body
temperature, and blood
pressure
Classic withdrawal
symptoms, and
hallucination
Glossary I
•5HT: serotonin.
•ADHD: Attention Deficit Hyperactivity Disorder
•Antiepileptic: anti seizure drug
•Anxiolytic: anti anxiety drug
•DDI: drug-drug interaction
•EPS (extra-pyramidal symptoms): includes dystonic (twitching, repetitive
movements) reactions and akathisia (can’t sit still).
•Fibromyalgia: chronic widespread pain and allodynia, a heightened and
painful response to pressure.
•Hypnotic: a sleep-inducing drug.
•LOT: length of therapy.
•MAOI: monoamine oxidase inhibitor
•MOA: mechanism of action
•NE: norepinephrine
•Neurotransmitters: serotonin (5HT), (GABA), Dopamine (DA),
Norepinephrine (NE).
Glossary II
•NMS (neuroleptic malignant syndrome): consists of high fever, muscle
rigidity, delirium. Can be life threatening; 10-20% mortality.
•Nystagmus: involuntary eye movement.
•OCD: obsessive compulsive disorder.
•SSRI: selective serotonin reuptake inhibitor
•Serotonin Syndrome: can be life threatening. Classically described as the
triad of:
(1) mental status changes: anxiety, agitated delirium, restlessness, and
disorientation
(2) autonomic hyperactivity: excessive sweating, tachycardia, hyperthermia,
hypertension, vomiting, and diarrhea
(3) neuromuscular abnormalities: tremor, muscle rigidity, myoclonus
(involuntary muscle twitching), hyperreflexia.
•SNRI: serotonin (5HT) and noradrenergic (NE) reuptake inhibitor.
•TCA: tricyclic antidepressant
•TDS (tardive dyskinesia syndrome): Tardive dyskinesia is characterized by
repetitive, involuntary, purposeless movements.