Nursing CNS Pharmacology Notes

which FGA should be used in emergent situations?

Halparedol

Action of FGA
Block dopamine receptors on post synaptic neuron in brain

tardive kinesia
involuntary repetitive movements
EPS

FGA better for

positive symptoms of psychosis

SGA better for

negative symptoms of psychosis

MAO present
in presynaptic neuron
breaks down norepinephrine, seratonin, and dopamine

MAOI side effects

tyromines (precursor to monoamines) in diet may have toxic effects (excessive NE)
anticholinergic effects
hypertensive crisis (from excess NE)

tyramine rich foods

aged cheeses, figs, bananas, wine, aged meats, yeast

treat acute manic episode of BPD with (BPD)

lithium most effective

treat depressive phase with

valproic acid/ valproate most effective

concern for lithium toxicity has to do with

narrow therapeutic range

AE of lithium
GI, tremors, renal toxicity (excreted through the kidneys), imbalanced electrolytes (lithium retention
tied to sodium, low sodium: high lithium retention), needs to be monitored with labs
first line treatment for anxiety disorders
anti-depressant meds

dangerous lithium serum levels

> 1.5

lithium therapeutic index

0.6-0.8 (maintenance level)
0.8-1.4 (acute episode)

opoiod overdose symptoms

respiratory depression
coma
pinpoint pupils

treatment for OD of opioids

ventilatory support
opioid antagonist (naloxone)

cox 2 produces
painful response associated with inflammation

COX inhibitors (1 and 2)

inflammation, pain, fever reductions

AE of cox inhibitors
increase bleeding, gastric ulceration, and renal impairment

Acetaminophen
not an NSAID, does not act in periphery or have anti-inflammatory effects

aspirin vs ibuprofen
aspirin is not reversible

contraindications for aspirin

not for pregnancy (category D)
Reyes syndrome risk in children

to diagnose depression
symptoms must be present most of the day, nearly every day, for at least 2 weeks

monoamine transmitters
seratonin, norepinephrin
alternative depression therapies
vagus nerve stimulation, electroconvulsive therapy

action of TCAs
tricylcic antidepressents
block NE and 5-HT reuptake --> intensify transmission at noradrenergic and serotonergic synapses.
Over time this induces adaptive cellular responses relieve depression

TCA dosing
long half life, single daily dose
initial response takes 1-3 weeks
maximal response takes 1-2 months
continue for 6-12 months after symptoms abate

TCA adverse affects

common: sedation, orthostatic hypotension, and anticholinergic effects
serious: cardiotoxicity (possibly lethal OD)

What could happen if TCA is combined with MOAI?

hypertensive crisis

Other DDIs with TCAs

-intensify responses to direct-acting sympathomimetics (eg, epinephrine)
-diminish responses to indirect-acting sympathomimetics (eg, amphetamine).
-intensify the effects of other anticholinergic medications

action of SSRIs
block reuptake of serotonin --> intensify transmission at serotonergic synapses. Over time inducing
adaptive cellular responses that relieve depression

advantages of SSRIs over TCAs

-safer when overdosed
-fewer side effects

side effects of SSRIs that contrast to TCAs

SSRIs are more stimulating (insomnia, agitation)
TCAs are sedating

AE of SSRIs
sexual dysfunction, nausea, headache, weight gain, CNS stimulation: nervousness, insomnia, and
anxiety

serotonin syndrome
More likely when combined with MAOIs and other serotonergic drugs
Begin 2 to 72 hours after beginning SSRIs: agitation, confusion, hallucinations, hyperreflexia, tremor,
and fever

SSRI withdrawal syndrome

dizziness, headache, nausea, sensory disturbances, tremor, anxiety, and dysphoria
caused by abrupt discontinuation

SSRI risks during pregnancy

-neonatal abstinence syndrome
-persistent pulmonary hypertension (PPHN)

Warfarin and this SSRI have adverse DDI

Fluoxetine will displace warfarin and raise levels of warfarin in plasma

action of SNRIs
serotonin/norepinephrine reuptake inhibitors
similar to SSRIs

prototype SNRI
Venlafaxine: indicated for major depression, generalized anxiety disorder, social anxiety disorder

AE of venlafaxine
nausea, headache, anorexia, nervousness, sweating, somnolence, insomnia. Dose-dependent weight
loss per anorexia

Action of MOAIs
increase neuronal stores of NE and 5-HT -->intensify transmission at noradrenergic and serotonergic
synapses, inducing adaptive cellular responses that relieve depression

what does MAO do in organs?

the liver and intestine,inactivate tyramine and other biogenic amines in food. In addition, these
enzymes inactivate biogenic amines administered as drugs

MAOIs then, prevent inactivation of tyramine and biogenic amines and cause their increase

DDIs for MAOIs

avoid all drugs and OTC medications unless approved for safety by prescriber
combined with indirect sympathomimetics (ephedrine, amphetamine) - > hypertensive crisis
combined with other SSRIs -> serotonin syndrome

which antidepressant is unusual and similar to amphetamine?

buproprion (wellbutrin): stimulant actions, appetite suppression

action of buproprion
Antidepressant effects begin in 1 to 3 weeks, equal to TCA
mechanism but may be related to dopamine uptake blockade
AE of Buproprion
Agitation, headache, dry mouth, constipation, weight loss, GI upset, dizziness, tremor, insomnia,
blurred vision, tachycardia, seizures

vagus nerve stimulation and electroconvulsant therapies used when

other therapies do not work

Bipolar disorder is treated with what kinds of drugs

mood stabilizers, antipsychotic drugs, and antidepressants

For acute BPD therapy

mood stabilizers or mood stabilizer plus antidepressant are used

for long term BPD therapy

one or more mood stabilizers are used

preferred mood stabilizers for BPD

Lithium and valproic acid

cautions for lithium use

low therapeautic index, mandatory to monitor lithium levels
target trough level, measured 12 hours after pm dose <1.5 mEq/L
serious toxicities > 1.5 mEq/L, death > 2.5 mEq/L
low sodium levels will cause body to retain lithium
diuretics (thiazides) and NSAIDs can increase lithium levels

patients with classic (euphoric) mania are prescribed

acute or maintenance (with euphoric BPD)
lithium
Antimanic effects begin 5 to 7 days after treatment onset— full benefits after 2 to 3 weeks

patients without euphoric manic BPD are prescribed which medication for long term therapy?
valproic acid

NSAIDs and lithium

suppress renal synthesis of prostaglandins and increase lithium levels

this drug controls symptoms in acute manic episodes and prophylaxis against recurrent episodes of
mania and depression
Valproic acid

differences between lithium and valproic acid

lithium is reserved for euphoric BPD
higher therapeutic index than lithium but better tolerated
May cause serious toxicity: (rarely) thrombocytopenia, pancreatitis, and liver failure
antipsychotics and BPD
to treat manic episodes and long term to help prevent mood episodes
benefits those w/ and w/out psychotic symptoms

can you use antidepressants for BPD?

not exclusively as they will cause mania
use with a mood stabilizing drug

physical components of anxiety disorders

tachycardia, palpitations, trembling, dry mouth, sweating, weakness, fatigue, and shortness of breath

first-line choices for GAD

benzodiazepines, buspirone, and three antidepressants: venlafaxine, paroxetine, and escitalopram

what drugs are preferred for acute general anxiety disorder

benzodiazepines

preferred drugs for long term management of GAD

buspirone and the antidepressants are preferred (SSRI)

how do benzodiazepines work?

enhance response to gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter
immediate onset
high margin of safety

AE of benzos (BZD)
sedation, psychomotor slowing (subside in 7-10 days)
risk for physical dependency

most prescribed benzos for GAD

alprazolam (Xanax, Xanax XR, Niravam) and lorazepam (Ativan)

non BZD anxiolytic

Buspirone (BuSpar)
not a CNS depressant
as effective as BZD
No sedation, no abuse potential, and no increased interaction CNS depressants

AE Buspirone
dizziness, nausea, headache, nervousness, lightheadedness, and excitement

cons of buspirone for GAD

develops slowly (initial response takes 1 week, several weeks for response peaks)
levels of buspirone can be increased by
grapefruit juice, erythromycin, and ketoconazole

which antidepressants can be used to treat generalized anxiety?

venlafaxine (Effexor XR), paroxetine (Paxil), and escitalopram (Lexapro)

which SSRIs are used for GAD?

Paroxetine and escitalopram, as effective as BZDs, less well tolerated

panic attacks involve

-palpitations, pounding heart, chest pain, sensations of shortness of breath, dizziness, nausea,
derealization or depersonalization, and fear of dying or going crazy
-usually <30 minutes
-may also suffer from agoraphobia (avoidance behavior)

first line drugs for panic disorder

SSRI

treatment of panic disorder

should continue for 6-9 months
best in conjunction with CBT
any of the three major antidepressant classes (SSRIs, TCAs, MAOIs) 6-12 weeks to achieve full benefits

second line drugs for panic disorder

BZDs

minimum for OCD diagnosis

persistent obsessions and compulsions that cause marked distress, consume at least 1 hour per day,
and significantly interfere with daily living

drugs used for OCD

four SSRIs and one TCA (clomipramine)
enhance serotonergic transmission
SSRIs better tolerated
take several months to become maximal

side effects of OCD drugs

nausea, headache, insomnia, sexual dysfunction, weight gain

First line drugs for social phobia disorder

SSRIs

second line drugs for SPD or for nongeneralized SPD

BZDs
symptoms of PTSD
re-experiencing, avoidance/emotional numbing, and hyperarousal

treatment of PTSD
no drugs are proven to be effective
SSRIs—paroxetine and sertraline

what families of peptides has opioid like properties

enkephalins, endorphins, and dynorphins

Endogenous opioid peptides are found

CNS, peripheral tissue

significance of mu receptors
Opioid analgesics act primarily by activating these

groups of drugs that bind opioid receptors

(1)pure opioid agonists,
(2) agonist-antagonist opioids
(3) pure opioid antagonists

opioid agonists relieve pain by

mimicking the actions of endogenous opioid peptides.

major effects of opioids

Analgesia
Sedation
Respiratory depression (most serious AE)
Cough suppression
Suppression of bowel movements

AE of opioids
Respiratory depression
constipation, urinary retention, orthostatic hypotension, emesis, intracranial pressure (ICP) elevation

in order to relieve pain morphine must be able to

cross BBB

morphine routes
many routes
oral: must give higher dose due to first pass metabolism

opioid tolerance
analgesia, euphoria, sedation, and respiratory depression but not to constipation and miosis
opioid cross tolerance
occurs among the various opioid agonists but not between opioid agonists and general CNS
depressants

opioid dependence
is physical (abstinence syndrome occurs with acute withdrawal)
withdrawal is unpleasant but not dangerous

withdrawal syndrome for CNS depressants

is dangerous

precautions to opioid use include

pregnancy, labor and delivery, head injury, and decreased respiratory reserve

DDIs for opioids

-alcohol and other CNS depressants may intensify opioid-induced sedation and respiratory depression
-anticholinergic drugs (antihistamines, tricyclic antidepressants, atropine-like)— can exacerbate
opioid-induced constipation and urinary retention

opioid overdose symptoms

coma, pinpoint pupils, respiratory depression

role of opioid antagonists

-mostly to treat opioid OD
-reverse respiratory depression, coma, analgesia, and most other effects
- methylnaltrexone (exception) does not cross the blood-brain barrier & treats opioid-induced
constipation

should opioids be administered PRN?

no, on fixed schedule

what is COX (cyclooxygenase inhibitors)?

an enzyme that is involve in production of prostaglandins
Cox 1 = good prostaglandins (stomach protective), platelet aggregation, kidney function
COX 2 = associated with pain, inflammation, fever

types of cox inhibitors

NSAIDs
acetaminophen

benefits of aspirin
suppresses inflammation, relieves mild to moderate pain, reduces fever, prevents MI and stroke (by
suppressing platelet aggregation)

risks of aspirin
gastric ulceration, bleeding, and renal impairment (Cox 1 inhibition)

what happens when you take aspirin and ibuprofen together?

Blocks the cardiovascular protective effects of aspirin (ibuprofen can antagonize antiplatelet actions)

differences between aspirin and ibuprofen

-NSAIDs reversibly inhibit COX
-both suppress platelet aggregation, but nonaspirin NSAIDS increase risk of MI and stroke: use lowest
effective dose for shortest possible time

because of its anti-inflammatory properties, aspirin is the initial drug of choice for
rheumatoid arthritis, osteoarthritis, and juvenile arthritis

how long is aspirin's antiplatelet effect?

8 days/ life of the platelet because aspirin irreversibly inhibits COX

aspirin dosing
use much higher dose for anti-inflammatory than for analgesic or antipyretic

two ways to prevent gastric bleeding when beginning aspirin use

test for h. pylori
give proton pump inhibitor

what effects can aspirin have on kidneys and thus body?

impaired renal function -> sodium, H2O retention, edema, elevated BP (not likely without risk factors)

giving aspirin to children may cause

Reyes syndrome: swelling in liver and brain
confusion, seizures, loss of consciousness
especially when recovering from flu or chickenpox

effects of non-aspirin NSAIDs

suppress inflammation, pain, and fever; and they all can cause gastric ulceration, renal impairment,
and bleeding

second generation NSAIDS

(coxibs/ celecoxib)
Selectively inhibit COX 2
may cause less gastric ulceration, do not inhibit platelet aggregation
pose a risk of MI and stroke

acetaminophen uses
-analgesic & antipyretic properties equivalent to aspirin -no anti-inflammatory and antirheumatic
actions
acetaminophen actions
inhibits prostaglandin synthesis in (CNS), not periphery
- differs from the NSAIDs: (1) lacks anti-inflammatory actions (2) no gastric ulceration (3) no platelet
aggregation suppression (4) no renal impairment

concerns about acetaminophen and alcohol

chronic alcohol consumption and tylenol OD is a problem for liver due to cytochrome P450 induction
(increase production of toxic metabolite of acetaminophen) & depletes glutathione stores (which
reduces detoxification of the metabolite)

acetaminophen may increase the risk of warfarin-induced bleeding

by inhibiting the metabolism of warfarin

tylenol OD can cause

liver injury and death (leading cause of acute liver failure)

acetaminophen poisoning is treated with

PO or IV acetylcysteine: substitutes for depleted glutathione & removes the toxic metabolite of
acetaminophen