NR546 psychopharmacology Final exam questions with complete verified solutions + rationales

monoamine hypothesis of depression

depression occurs as a result of deficiency of 1 or all 3 monoamine NT

-occurs due to too little positive affect or too much negative affect

(mania will occur from excess of all 3)

what are the three monoamine NT

NE, DA, 5HT

too little positive affect

-DA/NE dysfunction

-DA levels low = loss of pleasure, interest, alertness, self-confidence

-DA levels high = hallucinations seen in schizo

-NE (fight or flight) high = antsy, nervous, affects focus ability

-depressed mood, loss of joy, lack of interest, loss of energy, decreased alertness, decreased self-confidence, appetite changes

too much negative affect

-5HT = relaxation, comfort, decreases stress, regulates libido, arousal, sleep, aggression, pain perception

-5HT/NE dysfunction

-depressed mood, guilt, fear/anxiety, hostility, irritability, loneliness, appetite changes

prescribing considerations

-client preference

-prior treatment response

-anticipated adverse effects

-comorbidities

-half-life interactions

-cost

client preference

if no contraindication, then prescribe that med to improve adherence

prior treatment response

if patient had success with a previous med, prescribe that one first

anticipated adverse events

-consider age, family planning, and anticipated adverse effects.

-use adverse effects to pt's advantage (choose a known activating medication for a pt with atypical depression or choose a sedating medication for a patient with sleep disturbances)

Comorbidities

clients with comorbid anxiety may experience worsening symptoms when taking medications that target NE (SNRIs)

-fluoxetine is known to activate clients and cause panic attacks in clients with comorbid anxiety

half-life interactions

-choose a medication with a longer half life to avoid discontinuation syndrome if your client forgets to take it

-many antidepressants have significant interactions with other meds due to CYP450 enzyme involvement

cost

if client cant afford medication, they will not benefit. keep cost, insurance benefits, and pharmaceutical assistance programs in mind

goal of antidepressant medications

complete remission of symptoms

antidepressant prescribing schedule

-start on a single drug for 4-8 weeks

-if not working:

1. increase dose gradually until efficacy occurs

2. switch to different drug within same drug class after adequate trial which included higher dosing and a minimum of 8 weeks

3. switch to a drug in a different class after adequate trial and higher dosing

4. add a second med as adjunct

SSRI MOA

inhibit 5HT reuptake

first line of treatment for depression

SSRI s/e

7 S's of SSRIs

1. Stomach

2. sexual dysfunction

3. serotonin syndrome

4. sleep difficulties

5. suicidal thoughts

6. stress

7. size (weight)

serotonin s/e

head, red, fed

head = decreased anxiety, impulsivity, sex drive

red = platelets and bleeding

fed = gi motility and nausea

SSRI pt education

most adverse affects will subside after 4-5 days once body adjusts to increased serotonin levels

SSRI drugs

citalopram

fluoxetine

paroxetine

sertraline

fluvoxamine

bupropion

citalopram

*has a mild antihistamine effect

*causes QT prolongation

citalopram = celexa, think of cel LEXUS (car) = car - get an electrocardiogram if on this drug

escitalopram

*no known drug interactions, used with polypharmacy

*best tolerated SSRI

*27-32 hr half life

fluoxetine

*longest half life - prescribe to patient who may forget to take their meds

THINK fluoxetine - when you spent a long week in bed with the FLU (referring to the long half life)

*use with caution if pt has comorbid anxiety due to risk of activation and panic attacks

paroxetine

*also treats social anxiety disorder

*highest risk of discontinuation syndrome due to serotonin transporter inhibition and anticholinergic rebound

*patient will experience withdrawal symptoms if with a missed dose or late dose

*contraindicated in pregnancy due to risk of congenital defects

*avoid in hx of falls/fractures

*associated with weight gain

sertraline

*treats social anxiety

*27-36 hr half life

*THINK sertraline = "squirt" traline - harsher GI effects, safe for breastfeeding

fluvoxamine

treats anxious depression and smokers require increased dose

bupropion

fewer side effects, lowest risk for sexual side effects, use with caution if pt has comorbid anxiety

screening to be completed before prescribing SSRI

baseline and routine labs

age group most at risk when prescribed SSRI and why

antidepressant induced suicide is prevalent in children, adolescents, and adults younger than 25 years

SSRI with least CYP450 reactions

escitalopram

best tolerated SSRI

Escitalopram (Lexapro)

which meds are used as adjuncts

benzos, trazadone, antipsychotic meds sometimes prescribed at low doses for severe depression

which substances increase lithium levels

NSAIDS and ace inhibitors

which substances decrease lithium levels

caffeine

what is serotonin syndrome

potentially life threatening condition reported with the use of serotonergic antidepressants, especially when they are used concomitantly with other serotonergic drugs (such as triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, st john's wort) and with drugs that impair serotonin metabolism (MAOIs)

s/s serotonin syndrome

-mental status changes (agitation, hallucinations, delirium, coma)

-autonomic instability ( tachycardia, labile bp, dizziness, diaphoresis, flushing, hyperthermia)

-neuromuscular symptoms (tremor, rigidity, myoclonus, hyperreflexia, incoordination)

-seizures

-GI symptoms

if these s/s occur, discontinue medication and initiate treatment of symptoms

MAOI use

LAST choice for depression because of many potential, serious s/e

MAOI mech of action

block enzymes responsible for the breakdown of 5HT, NE, DA

- 2 primary forms of MAOI enzyme (MAOI-A and MAOI-B)

-both are located in brain

-MAOI-B is also located in gut

MAOI-A

A = Antidepressant and Axiolytic

MAOI-B

responsible for breakdown of DA, phenylephrine, and tyramine

-most MAOI-B meds are used in parkinsons

-high dose selegiline can be used in anxiety or depression

MAOI drugs

phenelzine

selegiline

tranylcypromine

isocarboxazid

MAOI s/e

confusion, dizziness, insomnia, sedation, vivid dreams

MAOI key points

-clients taking MAOIs are at high risk for hypertensive crisis if tyramine is ingested

-do not prescribe any serotonergic agents within 2 weeks of MAOI discontinuation due to increased risk of serotonin syndrome (wait at least 5 half lives)

MAOI pt edu

important dietary restrictions

-foods that contain tyramine should be avoided

---red wine, sauerkraut, aged cheese, soy, smoked meats, preserved foods, tap and unpasteurized beers, smoked fish, kimchee, tofu

- avoid these because MAOIs break down tyramine in the guy, ingesting extra tyramine can put pt at risk for hypertensive crisis

SARI mech of action

-serotonin antagonist and reuptake inhibitor

-potently blocks serotonin, allowing more 5HT to interact at postsynaptic sites

-trazadone

-trazadone also blocks histamine and alpha adrenergic receptors

trazadone

used as adjunct for clients with MDD who cannot sleep

short half life

traZZZZadone

trazadone s/e and edu

priapism (a medical emergency!), educate pt to take at bedtime bc of sedation

-off label use for insomnia and anxiety

TCAs MOA

possess both SRI and NRI properties but also block a-adrenergic, histamine, and muscarinic receptors

TCA adverse effects

-not 1st line treatment bc of high incidence of adverse rxns and potential risks of OD and death

-anticholinergic (cant see, cant pee, cant shit, cant spit)

-histamine effects (weight gain, sedation)

-alpha -1 adrenergic effects (orthostatic hypotension)

TCA drugs

amitriptyline

desipramine

doxepin

imipramine

nortriptyline

SNRI MOA

inhibits 5HT and NE reuptake (increasing energy and focus).

increase DA in the PFC (increasing cognition)

SNRI pt education

do not stop abruptly to avoid discontinuation symptoms.

NE effects of med may increase anxiety, report worseing anxiety

SNRI s/e

elevated bp, anxiety, insomnia, constipation

SHAT

same adverse effects as SSRIs +

Hypertension

Adrenergic effects (awake, anxious, agitated)

tachycardia

SNRI drugs

Vexed and depressed

vexed = venlafaxine (treats both depression and anxiety, ensure trial of higher dose before changing meds)

depressed = duloxetine (treats atypical pain at higher doses), desvenlafaxine (perimenopasual vasomotor symptoms - flushing and sweating)

NDRI mech of action

inhibits DA reuptake (increases alertness and motivation) and inhibits NE reuptake (increasing energy)

NDRI ot edu and s/e

edu: take in AM to avoid insomnia, stop if seizure occurs, stop if anxiety is noted

s/e: agitation, headache, dry mouth, constipation, weight loss

-bupropion (may improve energy, alertness, and motivation. NOT first line for anxiety, contraindicated with hx of seizures)

Mirtazipine (Remeron)

THINK...MEAL-tazapine = appetite stimulant, assist in weight gain

-serotonin/norepinephrine receptor agonist, alpha2 receptor agonist

-associated with sedation/drowsiness, this is useful for ppl with insomnia

-s/e increased appetite/weight gain, useful in pts with weight loss due to depression

Vortioxetine

can improve the speed of processing and cognitive function due to its unique MOA

-serotonin multimodal (SMM)

-acts as SSRI plus 5HT1A partial agonism

-improves depression related cognition

vilazodone

serotonin multimodal/serotonin partial agonist reuptake inhibitor (SPARI)

-inhibits serotonin reuptake with partial 5HT1A agonism

-use for depression/comorbid anxiety, similar to combo of SSRI and buspirone

Esketamine (Spravato)

nasal spray

use for MDD with acute suicidal behavior

peak onset 20-40 min

must be given in a supervised healthcare setting

ketamine

NMDA receptor inhibitor that results in downstream release of glutamate

in low doses, has a rapid effect on depression

dextromethorphan/quinidine

oral

approved for treatment of pseudobulbar affect (inappropriate involuntary laughing and crying)

pharmacologic treatment for bipolar disorder

lithium, anticonvulsants, second gen antipsychotics

lithium

used for euphoric mania, rapid cycling, or maintenance therapy

MOA: alters cation transport in the nerve and muscle

*1st line of treatment for new onset bipolar with acute mania

lithium labs

serum thyroid level, renal function, thyroid function

- can cause renal and thyroid tox

-monitor lithium levels 5 days after any dose adjustment

-monitor lithium levels regularly q6mo

starting dose should be decreased by 50% for pts with renal failure

-avoid in pregnancy and breast feeding

lamotrigine

maintenance therapy or monotherapy for bipolar

MOA: affects sodium ion transport and enhances the activity of y-aminobutyric acid (GABA)

- well tolerated but can cause a rash

- avoid in breast feeding

valproic acid

used for acute mania, mixed mood, multiple prior episodes, comorbid substance abuse

MOA: affects ion transport and enhances the activity of GABA

-teratogenic avoid in pregnancy

valproic acid labs

serum valproate level, liver fxn, cbc

-can cause thrombocytopenia, leukopenia, hepatotoxicity

-monitor labs q 3 mo for 1 yr ,then annually

SGAs

used in acute bipolar depression, acute mania or mixed episodes, or as bipolar maintenance/adjunct

MOA: DA, NE, 5HT receptor antagonists

labs: cbc, HgB A1C

-can increase bs and cause DMII, blood dyscrasias

-labs q 3 mo for 1 yr, then annually

SGA drugs

aripiprazole

cariprazine

lurasidone (take with food, safe for preg)

quetiapine

asenapine

risperidone

olanzapine

ziprazadone

carbamazepine

acute mania or mixed mood

-MOA; glutamate voltage gated sodium and calcium channel blocker

-teratogenic

-may cause stevens johnson syndrome in ppl of asian decent (genetic testing is helpful here)

-serum carbamazepine levels, renal and liver fxn, cbc

pregnancy

lithium, valproic acid, carbamazepine are teratogenic

lurasidone is safe

breast feeding

bottle feed for carbamazepine, lithium, lamotrigine

older adult

use caution

reduced renal and hepatic fxn may imoact metabolism and elimination. reduced doses

-avoid carbamazepine (may cause SIADH)

-use caution with antipsychotics (may increase risk of falls)

-antipsychotics may increase risk of stroke, cognitive decline, and death in dementia pts

-avoid lithium in clients taking ACE inhibitors or loop diuretics

medications approved for children

age 10+

lurasidone (bipolar)

aripiprazole (acute and mixed mania)

quetiapine (monotherapy and adjunct for acute mania)

asenapine (acute and mixed mania)

risperidone (monotherapy and adjunct for acute and mixed mania)

olanzapine age 13+ (acute and mixed mania)

1st line combination therapy for bipolar 1

some clients are not candidates due to lack of med adherence

lithium or valproic acid + lamotrigine or aripiprazole or risperidol

whos your daddy and wheres your mama

does anyone in family have hx of unipolar depression or bipolar disorder

need pt hx before they come into office, may need to find out from family members - they are often reluctant to report mania or hypomania

distinction is important because treatment is different!

antidepressants can make someone manic or cause rapid cycling and increase suicide risk

** antidepressant sparing strategy is to use sparingly or never at all. exhaust mood stabilizers first!

bipolar type 1

at least 1 episode of mania for at least one week OR any duration of hospitalization due to symptoms

bipolar type 2

current or past hypomanic episode and current or pasr MDD

symptoms last at least 4 days but less than 7

symptoms of MDD linked to prefrontal cortex

concentration

mental fatigue

mood

symproms of MDD linked to PFC and amygdala

guilt, suicidality, worthlessness

symptoms of MDD related to striatum

physical fatigue

symptoms of MDD related to nucleus accumbens

pleasure interests

symptoms of MDD related to hypothalamus

sleep

appetite

symptoms of mania linked to thalamus and hypothalamus

decreased sleep/arousal

symptoms of mania linked to striatum

motor/agitation

symptoms of mania linked toPFC

risk taking

talkative/pressured speech

symptoms of mania linked to nucleus accumbens and PFC

racing thoughts, grandiosity

symptoms of mania linked to PFC and amygdala

mood

which medication cannot be increased in the elderly

citalopram and escitalopram should be dosed at 1/2 due to QTC

L-methylfolate

derived from folate

enters brain and works as methyl donor and monamine synthesis modulator

regulates tetrahydrobiopritin (a critical enxyme factor for trimanoamine neurotransmitter synthesis)

essential for producing NTs such as 5HT, DA, NE

adjunct to standard treatments for depression and schizophrenia at the initaition of treatment or to augment partial response

very safe

genetics of SUD

-may impact a person's experience of a drug as pleasurable or not

-may impact how long drug remains in the body

-specific genetic factors predispose a person to alcohol dependence and tobacco use

neuroanatomy of SUD

mesolimbic pathway and DA production

neural networks

drugs and alcohol act directly on the brain receptors leading to a release of dopamine which fires up the reward center

neural signaling

when dopamine is released in surges in response to drugs

changes in brain circulatory can occur, leading to cravings, addiction, dependence, and withdrawal

tolerance

with repeated ingestion of a drug, the drug shows decreased effect. increasing doses are required to achieve effects noted with the original administration

dependence

state of adaptation produced with repeated administration of certain drugs so that physical symptoms occur when the drug is discontinued abruptly

addiction

a change in behavior caused by biochemical changes in the brain after continued substance use characterized by preoccupation with and repeated use of a substance despite negative outcomes.

withdrwal

physiological and psychological reactions that occur when the use of a substance is stopped abruptly

intoxication

condition following the ingestion of a substance resulting in changes in level of consciousness, cognition, perception, judgement, behavior

symptoms of opioid withdrawal

-N/V

-diarrhea

-runny nose

-sweating

-tremor

-irritability

-muscle spasms

medication assisted therapy

1st line of treatment for opioid use disorder

MAT works by substituting the substance being abused with a prescription med that targets the same receptor

-can reduce cravings

-improve relapse

-reduce mortality from OD

-increase likelihood of abstinence