Psychobiology and Psychopharmacology

Question 1

Mood Disorders/Depressed Symptoms

Answer 1

1. Depression may be due to decreased levels of 5HT and/or NE. Most involved circuit is the locus coeruleus.
2. Bipolar may be due to interactions between NE, DA, 5HT, ACh, GABA, and peptides

Question 2

Anxiety Disorders/Anxious Symptoms

Answer 2

1. Elevated 5HT and NE, and decreased GABA

2. Raphe Nucleus is most involved circuit

Question 3

Cognitive Disorders

Answer 3

1. ADHD: Dysregulation of attention, activity, and impulsivity. Circuits involved include dorsal anterior cingulate cortex, dorsal lateral prefrontal cortex, and orbital frontal cortex.
2. Dysregulation involves DA, NE, and other NTs

Question 4

Dementia Disorders

Answer 4

1. Multi-factorial contributors including amyloid plaques and tau, metabolic, and oxygenation issues

Question 5

Dopamine

Answer 5

1. Excitatory NT important in controlling thoughts and emotions, in frontal cortex, mesocortical tract, and are involved in attention, focus, and depression.
2. Controls complex movement in the nigrostriatal DA pathway
3. Mesolimbic DA to nucleus accumbens involved with pleasurable behaviors; elevated DA here associated with psychosis
4. Tuberoinfundibular pathway: prolactin secretion

Question 6

Norepinephrine

Answer 6

1. Located predominantly in the locus coeruleus
2. In frontal cortex regulates mood, attention, concentration (alpha-2 receptors)
3. In limbic cortex influences emotions and energy; into cerebellum mediates tremors
4. In Brainstem affects blood pressure and innervates heart
5. Excitatory NT that helps elevate mood, modulate attention and fatigue
6. May also contribute to anxiety disorders

Question 7

5HT receptors

Answer 7

1. Located mostly in the raphe nucleus with projections to:
   - Frontal Lobe: Affects mood and depression
   - Basal Ganglia: Especially 5HT2A, control of movements and obsessions/compulsions
   - Limbic Area: Especially 5HT2A and 5HT2C, related to anxiety and panic
   - Hypothalamus: 5HT3 receptors related to appetite and sleep (Mirtazipine)
   - Spinal Cord: Influence sexual response and gut
   - Peripheral: 5HT3 and 5HT4 receptors in the gut regulate appetite as well as GI motility (after a while, receptors down regulate and, nausea goes away)

Question 8

GABA

Answer 8

Inhibitory NT

Works to sedate and calm

Question 9

ACh

Answer 9

Plays a role in memory and cognition

Held in balance with dopamine in the substantia nigra

Question 10

Gutamate

Answer 10

Primary Excitatory NT

Question 11

CYP 450 1A2

Answer 11

• Inhibited by SSRI fluvoxamine; therefore increases the levels of theophylline.
• Cigarette smoking induces 1A2, increasing the elimination olanzapine; if pt decreases or quits smoking, dose adjustment needed (EXAM LOVES THIS QUESTION).

Question 12

CYP 2C19

Answer 12

Reduced activity in 20% of Asian persons, ~5% in Caucasians

Question 13

CYP 2D6

Answer 13

• Inhibited by fluoxetine, paroxetine, and bupropion.
• If switching from TCA to SSRI, it will have elevated blood levels of TCA who depend on 2D6 for metabolism
• Induction of metabolism of hydrocodone, morphine, and tramadol so will affect pain control.

Question 14

CYP 3A4 Inhibition

Answer 14

• Inhibited by some SSRIs, nefazodone, and grapefruit juice
• Some BZO levels will rise, such as alprazolam when given with fluoxetine
• Inhibited by erythromycin, will therefore affect carbamazepine level. Use zithromax instead

Question 15

CYP 3A4 Induction

Answer 15

• Carbamazepine, effecting oral contraceptive levels, as well as the level of carbamazepine itself.
• 3A4 induction greatly affects methadone
• Induced by St. John’s Wort

Question 16

Exogenous estrogen and Lamictal

Answer 16

-Exogenous estrogen in the form of oral contraception induces 1A4, cutting lamotrigine levels by 50%.

Question 17

Lithium and NSAIDs

Answer 17

Lithium levels increase with inhibition of prostaglandins, so Ibuprofen will effect levels, but ASA, Sulindac, and Tylenol will not.

Question 18

CATIE

Answer 18

Clinical Antipsychotic Trials in Intervention Effectiveness

• Patients were walking
• Atypicals are still good, but they weren’t the dream med that we thought they would be.

Question 19

STEP-BD

Answer 19

Treatment Enhancement Program for Bipolar Disorder

Question 20

Star-D

Answer 20

Sequenced Treatment Alternatives to Relieve Depression

-Still have a lot of residual depression that wasn’t getting treated.

Question 21

Typical Antipsychotics MOE

Answer 21

D2 blockade in the mesolimbic and mesocortical tract

Question 22

Typical Antipsychotics SEs

Answer 22

Sedation/wt gain: Histamine blockade
Orthostatic hypotension/drowsiness: Alpha 1 blockade
Increased Prolactin: D2 blockade in the tuberoinfundibular tract
Anti-Cholinergic effects: Muscarinic blockade
EPS: D2 blockade in nigrostriatal tract

Question 23

Treatments for EPS

Answer 23

Change med
Lower dose
Benztropine (Cogentin)

Question 24

Typical Antipsychotics Long-term SEs

Answer 24

Permanent effects on movement seen
TD not reversible
Neuroleptic Malignant Syndrome

Question 25

Neuroleptic Malignant Syndrome

Answer 25

Life threatening complication of antipsychotics Usually develops within the first 2 weeks of use (90%) Also seen in Parkinson's with abrupt levodopa withdrawal S & S: (HOT, STIFF and OUT OF IT) -Autonomic instability with hyperthermia -Muscle rigidity/dystonia -Extreme mental status change/confusion

Question 26

Atypical Antipsychotics MOA

Answer 26

D2 and 5HT blockade in brain - Decreased risk of EPS - Decreased emergence rates of long-term side effects, including tardive dyskinesias

Question 27

Dosing Clozapine

Answer 27

May cause agranulocytosis Rigorous dosing and monitoring 12.5 mg for first dose; thereafter, divided dose Increase by 25-50 mg per day as tolerated, to 300 to 400 mg per day; maximum is 900 mg per day

Question 28

Monitoring with Clozapine

Answer 28

Weekly CBC x 6 months Biweekly x 6 months monthly after that for rest of life

Question 29

Clozapine Testing Thresholds

Answer 29

If WBC 2.0 or Neuts

Question 30

Unique to Risperdal

Answer 30

May cause szr Contraindicated in preggers Increased prolactin Sexual SEs

Question 31

Risperidone Depot

Answer 31

Every 2 weeks; must be reconsituted and refrigeration | No loading dose option; 3 weeks to max effect

Question 32

Paliperidone (Invega) Depot

Answer 32

No need for po formulations Loading dose options Small needle and volume q4week inj; costs, injection site reaction

Question 33

Olanzapine Depot

Answer 33

- Loading dose options - Cost and needle size are problems - Post injection delirium (pt should wait around for 3 hours post-injection

Question 34

Abilify Depot

Answer 34

Q4Weeks Costs problematic gluteal only

Question 35

Metabolic Goals with Antipsychotics

Answer 35

LDLs 60 for men, > 50 for women | BP goal is 120/80

Question 36

Diagnostics for Metabolic Syndrome

Answer 36

``` Any 3: Abdominal girth: > 37 in males and >31.5 for women or TG > 150 or HDL 130/85 or on current HTN med or FBG > 100, or prior type II DM diagnosis ```

Question 37

HEAT MADE HI

Answer 37

``` Symptoms of NMS: Hyperthermia Elevated CK Altered Mental Status Tachycardia Mutism Akinesia Diaphoresis Elevated myoglobin Hypertension Irregular pulse ```

Question 38

Treatment for NMS

Answer 38

``` Fatal if left untreated: D/C neuroleptics Hydrate O2 Cooling blanket DANTROLENE (EXAM WANTS THIS ANSWER) ```

Question 39

Hot, Stiff, and out of it

Answer 39

Classic Triad for NMS: Mental status change/confusion Muscle rigidity/dystonia Autonomic Instability

Question 40

Tricyclic eliminated by:

Answer 40

2D6

Question 41

SRI: Selective Reuptake Inhibitors

Answer 41

Nefazodone Trazodone Bupropion

Question 42

Viibryd and Brintellix

Answer 42

5HT1A partial agonist - They turn the dopamine brake off - -Allows patient to feel pleasure - Gets rid of need for Abilify and BuSpar to enhance your antidepressant

Question 43

SNRIs

Answer 43

Venlafaxine: Inc in BP at higher doses Duloxetine Desvenlafaxine

Question 44

SRIs and SSRI class side effects and clinical pearls

Answer 44

Never give at night Sexual dysfunction Initial nausea subsided with receptor downregulation

Question 45

Prozac clinical pearls

Answer 45

Long half-life Stimulating Younger people mania? Sexual side effects

Question 46

Paxil (Paroxetine)

Answer 46

Great for anxiety Only SSRI in Cat D, no use in preggers Horrible withdrawal syndrome

Question 47

Citalopram (Celexa)

Answer 47

Cardiac effects necessitate decreased doses | Prolonged QTc leading to Torsades de pointes and sudden death

Question 48

Sertraline (Zoloft)

Answer 48

Great for elderly | Easily titrated

Question 49

Escitalopram (Lexapro)

Answer 49

More effective than Citalopram, fewer side effects

Question 50

Best medication for bipolar maintenance

Answer 50

Lithium

Question 51

Exam wants to know firsts

Answer 51

Clozaril first SGA Lithium first treatment for bipolar Prozac first SSRI

Question 52

Therapeutic blood level for acute treatment

Answer 52

1.2 mEq/L

Question 53

When to check Li level

Answer 53

12 hours after the last dose after 5 days of stable dosing

Question 54

Cautions with Li

Answer 54

``` ASA or APAP for over the counter analgesic Ibuprofen can increase serum levels Ca channel blockers are contraindicated Use diuretics with caution Maintain steady hydration levels ```

Question 55

LFTs with Depakote

Answer 55

Before first dose | 3 and 6 months out

Question 56

BuSpar shortcomings

Answer 56

Dosed tid or bid, and takes a long time to get going

Question 57

Drugs for Parkinson's

Answer 57

``` 1st line: Levodopa is gold standard 2nd line: Acetylcholine antagonists 3rd line: Dopamine agonists -pramipexole -ropinirole -pergolide ```

Question 58

Acetylcholine antagonists for Parkinson's

Answer 58

Benztropine (Cogentin) Trihexyphenidyl (Artane) Amantadine (Symmetrel) Selegline (Eldepryl)

Question 59

Drugs to reduce levodopa-induced dyskinesias

Answer 59

COMT enzyme inhibitors: - Tolcapone (Tasmar) - Entacapone (Comtan)

Question 60

Sleep Regulator

Answer 60

Ventrolateral preoptic nucleus in the hypothalamus inhibits brainstem arousal

Question 61

When does REM start?

Answer 61

REM starts 80-100 minutes after sleep initiation

Question 62

Sleep hygiene points

Answer 62

No screens Dark and cool Routine No caffeine