Nervous System Rx Flashcards
Name the neurotransmitters and whether they are excitory or inhibitory
Norepinephrine- primarily excitatory/ inhibitory in some areas
Serotonin- excitatory/inhibitory
Dopamine- primarily inhibitory
Gamma aminobutyric acid (GABA)- major inhibitory
Acetylcholine (ACh)- excitatory
Glutamate- major excitatory
What are the theories behind depression disorders?
older theory- decreased activity of monoamines (norepi, serotonin, dopa)
contemporary theory- neuroendocrine dysfunction leads to neuroplasticity, decreasing monoamin concentrations; chronically increased cortisol, dysregulation of brain derived neurotropic factor (BDNF)
What is the goal of antidepressive therapy?
complete remission without relapse or recurrence- often not achieved with 1st drug or takes combo Rx
What is the mechanism of action of SSRIs?
Selective Serotonin Reuptake Inhibitors
selectively blocks reuptake of serotonin by presynaptic terminal => increased serotonin available for neurotransmission
What are the indications for SSRIs?
1st line for Depression
Also OCD, panic disorders, anxiety, bulimia
NOT useful for pain disorders
Takes 2-12 weeks for effective treatment
Name common SSRIs
Cetalopram (Celexa) Escitalopram (Lexapro) Fluoxetine (Prozac) Fluvoxamine (Luvox) Paroxetine (Paxil) Sertraline (Zoloft)
What are adverse effects of SSRIs?
Akathisia (EPS)- inability to sit still, restlessness
Headache - common complaint early in Rx
Tinnitus
Sexual dysfunction
early wt loss followed by wt gain
serotonin syndrome-greatest risk if on >1 serotonergic drug
withdrawal if abruptly stopped (antidepressant discontinuation syndrome), esp. shorter half-life: HA, malaise, flu-like sx, agitation
What are the symptoms of serotonin syndrome?
mild- agitation, jitter, tremor; increased BP/pulse; diarrhea
severe- mydriasis (dilated pupils), diaphoresis, agitation, tachycardia, HTN, diarrhea, clonus/tremor/hyperreflexia (> in LE)
What are notable drug interaction for SSRIs?
Heterocyclics- increase levels
Warfarin- potentiates bleeding
Tamoxifen- decreases efficiency
Consider CYP450 with Paroxitine and Fluoxetine
Fluoxetine (Prozac)
SSRI- “activating”- good for lethargy
unique 5HT2c antagonist property
complements olanzapine - used together for bipolar
markedly long half-life => weekly dosing available
Sertraline (Zoloft)
SSRI
dopamine transport inihibition and sigma-1 receptor binding => produce activation in pts with low energy
frequently combined with bupropion
movre helpful in psychotic depression
Paroxetine (Paxil)
- SSRI - Anxiety (often 1st line)
- anticholinergic and norepi transmitter inhibition function => calming
- concern for rebound if withdrawn suddenly
- short half-life- often prescribed QHS
- Not good for breastcancer hx or high risk
- If used with pravastatin- increased serum glucose
- Do not take if pregnant
Fluvoxamine (Luvox)
SSRI
- potent sigma-1 binding
- used primarily for OCD, social anxiety, and panic disorder
- approved for children
- less sexual dysfunction
Citalopram (Celexa)
SSRI- anxiety/depression
mild antihistamine properties - good for anxiety
well tolerated in elderly
inconsistent response in lower doses, but concern for prolonged QT on higher doses (FDA- no >40 mg/day)
Escitalopram (Lexapro)
SSRI- anxiety/depression
- best tolerated SSRI, lower doses are usually effective
- few drug interactions
What are SPARIs?
Serotonin partial agonist/reuptake inhibitors
Vilazodon (Viibryd) and Vortioxetine (Trintellix)
newest class of antidepressants
similar to SSRI, plus serotonin agonist
rapid onset, but worse GI side effects
lesser sexual side effects
What is the mechanism of action of SNRIs?
serotonin/norepinephrine reuptake inhibitors => increased serotonin and norepi available => effective against depression and neuropathic pain
Name SNRIs
Venlafaxin (Effexor)
Duloxitine (Symbalta)
Desvenlafaxine (Pristiq)
Levomilnacipran (Fetzima)
What are indications for SNRIs
Depression (2nd line)
Anxiety
depression with associated pain
*needs to be titrated down over >4 wks
What are adverse effects of SNRIs?
similar to SSRIs- nausea, anxiety, drowsiness, insomnia, sexual dysfunction
HTN (venlafaxin in high doses)
Buprion (Wellbutrin)
NDRI- norepi/dopamine reuptake inhibitor =>increased dopamine and norepi available
Used for depression and to inhibit cravings (smoking)
helpful for reduced positive affect/ anhedonia
less sexual side effects
Mirtazapine
Enhances noradrenergic and sertoninergic release by blocking presynaptic receptors
potent antihistimine effect => sedative
lesser sexual side effects
L-methylfolate (Deplin)
monoamine modulator- facilitates amine synthesis to make patients more responsive to antidepressants
available as “medical food”
What is the mechanism of action of Heterocyclics (TCAs)
block reuptake of norepi and serotonin
potent muscarinic antagonist (anticholinergic)
weak alpha1 receptor and histimine antagonist
Name heterocyclic drugs
Imipramin (Toranil)
Amitriptyline (Elavi)
Doxepin (Sinequin)
Trimipramine (Surmontil)
What are side effects of heterocyclics?
anticholinergic effects (dry mouth, constipation, urinary rentention, blurry vision, heart block, slowed gastric emptying
orthostatic hypotension, tachycardia
sedation, drowsiness
CNS hyperactivity- lower seizure threshold
What contraindications are there for heterocyclics?
acute MI recovery
conduction blocks
severe hepatic/renal impairment
What is the mechanism of action of MAOIs?
Monamine oxidase inhibitors => inhibit oxidation of monamines => decreases degradation of neurotransmitters => increased norepi, serotonin, and dopamine
*Especially helpful in anxiety, but often last line
Name MAOIs
Isocarboxazid (Marplan)
Phenelzine (Nardil)
Tranylcypromine (Parnate)
Selegiline patch (EMSAM)
What are side effects for MAOIs?
HTN
dysrhythmias
anticholinergic effectsd
many drug-drug and drug-food interactions: Tyramine-containing foods (cheese, beer, chocolate, red wine, aged meats)
How is unipolar depression Rx managed
1) SSRI
2) SNRI
3) reconsider diagnosis - bipolar could be worsened on antidepressants
4) expand from antidepressant spectrum
5) consider atypical antipsychotics- Abilify, Symbyax, Seroquel
6) consider alternative antidepressant- Lithium, Liothyronine, Buspiron
What are atypical antipsychotics
Ariprazole (Abilify)
Olanzapine/fluoxeitine (Symbyax)
Quetiapine (Seroquel)
Brexpiprazole (Rexulti)
*best for patients with treatment-resistant depression, bipolar, or depression with psychotic features
*may cause more adverse metabolic effects (obesity, hyperglycemia, dyslipidemia)
Lithium
atypical antidepressant
often used for bipolar disorder
demonstrates suicidality improvement
Liothyronine
Alternative antidepressant
“T3”- can be used for unipolar depression
pts need to have normal thyroid studies and agree to monitoring of TSH levels
Buspirone
- alternative antidepressant
- serotonin agonist that may also trigger oxytocin release
- Effective for generalized anxiety disorder - alternative to benzos as not addicting
- not meant for acute management of anxiety (delayed onset)
What is the difference between generalized and partial seizure disorders?
Generalized- diffuse, bilateral brain involvement
Partial- localized to one part of brain; manifestations depend on part of brain involved
How do antiseizure medications work?
decrease the neuronal excitability and raise the seizure threshold by inhibiting glutamate and/or potentiating GABA
Glutamate antagonist, GABA agonists, or SV2A binding
Name medications for seizure disorders
Brivaracetam (Briviact) Levetiracetam (Keppra) Phenytoin (Dilantin) Fosphenytoin (Cerebryx) Lamotrigine (Lamictal) Gabapentin (Neurontin) Divalproex (Depakote) Carbamazepine (Tegretol) Oxycarbamazepine (Trileptal) Benzodiazepines (Valium, Ativan) - acute management
How is treatment for seizure disorders managed?
Often only requires one drug
If first drug does not work at max doses, gradually add another and then taper off the first
*concern for increased risk of suicidal thoughts on AEDs
Phenytoin (Dilantin)
Antiepileptic
has zero order kinetics- it saturates its routes of elimination, so the higher the concentration of drug, the longer the half-life
Carbamazepine (Tegretol)
Antiepileptic
- causes auto-induction of its own metabolism- may need dose increases throughout therapy
- may cause hypersensitivity reaction in certain patients, esp of Asian descent- test for HLA-B1502 gene
Fosphenytoin (Cerebryx)
Antiepileptic
prodrug that is rapidly converted to phenytoin
given parenterally
Topiramate (Topamax) and Zonisamide (Zonegran)
Antiepileptics
Carbonic anhydrase inhibitors
increased risk for metabolic acidosis- early in rx, monitor HCO3 prior to treatment
Valproic Acid (Depakote)
Antiepileptic
pts may develop pancreatitis
What is the pathophysiology of Parkinson disease?
Loss of dopamine-containing neurons in substantia nigra => ACh (excitatory) is uninhibited and overactive => loss of control over muscle movements
Levodopa/Carbidopa
Drugs for Parkinson disease
- Levodopa- dopamine precursor that crosses blood-brain barrier and breaks down into dopamine
- Carbidopa- dopamine decarboxylase inhibitor that reduces metabolism of dopamine
- Adverse effects- anorexia, nausea, tachycardia, hypotension, flushing, hallucinations
- on-off phenomena- symptoms worsen throughout day
Name Dopamine receptor agonists
*Parkinson disease* Bromocriptine (Parlodel) Pramipexole (Mirapex) Ropinirole (Requip) Cabergoline (Dostinex) Rotigotine patch (Neupro)
What is the mechanism of action of Dopamine receptor agonists?
stimulate dopamine receptors in basal ganglia
used to treat parkinson’s disease- most useful early in treatment
1st line in younger patients (<70) to delay symptoms for 5 years
What are adverse effects of Dopamine receptor agonists?
anorexia, N/V postural hypotension HA cardiac dysrhythmia drowsiness
What is the use of anticholinergics in managing parkinsons?
- reduces the impact of unihibited ACh release
- Benztropine and Trihexyphenidyl
- typical anticholinergic side effects
What are COMT inhibitors?
- for parkinson’s disease
- Catechol-O-methyl transferase inhibitors => blocks breakdown of dopamine
- Entacapone (Comtan) and tolcapone (Tasmar)
- tolcapone associated with hepatotoxicity (check LFTs)
- used if not responding to other treatment- discontinue if not working in 3 weeks
What are MAO-B inhibitors?
- for parkinson’s disease
- inhibits breakdown of dopamine
- should be given with Levodopa
- Selegiline (deprenyl)
What are side effects of COMT and MAO-B inhibitors?
orthostatic hypotension HTN dysrhythmia psychotic symptoms *not to be used with heterocyclics
What is the patho of Alzheimer’s disease?
production of apolipoprotein E => accumulation of amyloid plaques in brain => loss of neurons in limbic pathway that drives memory => decreased ACh activity
What is the focus of pharmacologic treatment of Alzheimer’s?
prolonging ACh breakdown to allow for greater opportunity for ACh binding at receptor sites
What are adverse effects of AChE inhibitors?
- inhibit breakdown of ACh by acetylcholinesterase =>cholinergic stimulation => modest reduction in Alzheimers sx
- bradycardia, tremors, myalgia, syncope, N/V, diarrhea
Donepezil (Aricept)
AChE inhibitor- Alzheimers Rx
CYP450 metabolism, but no hepatotoxicity
Galantamine (Razadyne)
AChE inhibitor- Alzheimers Rx
CYP450 metabolism
available in ER, IR, and liquid forms
Rivastigmine (Exelon)
AChE inhibitor- Alzheimers Rx
available PO and as patch- take with food
fewer drug interactions (no CYP450)
Memantine HCl (Namenda)
- NMDA receptor antagonist - Alzheimers Rx
- blocks overactive glutamate from binding to NMDA receptors, preventing cognitive damage
- Minimal side effects and drug interactions
- For moderate-severe AD
- often given as in combo with AChE inhibitor
How is hypersexuality associated with Alzheimer’s managed?
- discontinue benzodiazepines
- consider Cimetidine- has antiandrogen effect
- consider SSRIs
- consider Seroquel
What part of the brain is highly involved in anxiety disorders?
The Amygdala - flight, fight, or freeze (fear/anxiety)
The CSTC Loop- apprehension/worry
What neurotransmitters are involved in anxiety?
GABA
Norepinephrine
dopamine
Serotonin
What medication classes are often used for treatment of chronic anxiety?
- SSRIs/SNRIs- often require higher doses than for depression
- Buspirone
- Benzodiazepines
- Alpha2 ligands
What are Alpha2-delta Ligands?
- Gabapentin (Neurontin) and Pregabalin (Lyrica)
- block excitatory neurotransmitters- glutamate
- effective for social anxiety and panic disorder
What are first line therapies for generalized anxiety disorder?
SSRI/SNRI
Buspirone
Alpha2-delta ligands
benzodiazepines
What are first line therapies for PTSD?
SSRI/SNRI
*pharmacotherapy not preferred
What are first line therapies for Panic disorder?
SSRI/SNRI
Benzodiazepines
Alpha-2-delta ligands
What are first line therapies for social anxiety?
SSRI/SNRI Alpha-2-delta ligands beta blockers (alternative option)
What is the drug of choice for acute anxiety?
Benzodiazepines
What are Benzodiazepines?
- Very effective for acute anxiety- subject to abuse
- metabolized by liver
- Function as GABA agonists => inhibits motor responses triggered by amygdala => CNS depressant
- used for acute anxiety, panic attacks
- should be tapered off slowly
Name benzodiazepines
- Alprazolam (Xanax) (panic disorders)
• Diazepam (Valium) (generalized anxiety)
• Chlordiazepoxide (Librium) (alcohol w/d)
• Lorazepam (Ativan) (generalized anxiety)
• Temazepam (Restoril) (sleep disorder)
• Clonazepam (Klonopin) (maintenance)
• Oxazepam (Serax) (may be safer in liver dz)
What alternatives are there to benzodiazepines for acute anxiety?
First generation antihistamines (hydroxyzine) Antiadrenergic agonists (clonidine) Beta blockers (propranolol) * useful in cases of addictive behaviors
What is insomnia?
Difficulty falling asleep or staying asleep, waking early morning, non-restorative sleep
often undertreated
What is acute vs chronic insomnia?
Acute- identifiable trigger, doesn’t last >4 mnths
Chronic- predisposing factors, multifactorial, > 4 mnths
What is associated insomnia?
related to underlying mood disorder
How is insomnia therapy managed?
- BzRAs or melatonin agonist
- Sedating antidepressants
- Antiepileptics
- 2nd Generation antipsychotics
What are Benzodiazepine receptor agonists (BzRAs)?
- used for insomnia, not intended for long-term
- Triazolam
- Estazolam
- Temazepam
- Flurazepam
What are non-benzodiazepine receptor agonists?
For insomnia, The “Z” drugs:
- Zolpidem (Ambien)
- Zaleplon (Sonata)
- Eszopiclone (Lunesta)
- minimize adverse effects and abuse potential
Zolpidem (Ambien)
Insomnia
- adverse effects- AM hangover, anterograde amnesia
- CYP450 considerations
Zaleplon (Sonata)
Insomnia- esp middle-of-night awakenings
Rapid onset/short half-life
no issue with morning grogginess
Eszopiclone (Lunesta)
Insomnia
- longer half-life
- CYP450 considerations
- AM hangover
Ramelteon (Rozarem)
Insomnia- difficulty falling asleep
- Melatonin agonist
- no fall risk or cognitive impairment
- CYP450 considerations
Doxepin (Silenor)
Tricyclic antidepressant approved for insomnia
- do not take with food
Suvorexant (Belsomra)
Insomnia
Orexin receptor antagonist- improves total sleep time and sleep onset
need planned >7 hrs of sleep
