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Flashcards in Psychobiology and Psychopharmacology Deck (62):
1

Mood Disorders/Depressed Symptoms

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

2

Anxiety Disorders/Anxious Symptoms

1. Elevated 5HT and NE, and decreased GABA
2. Raphe Nucleus is most involved circuit

3

Cognitive Disorders

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

4

Dementia Disorders

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

5

Dopamine

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

6

Norepinephrine

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

7

5HT receptors

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)

8

GABA

Inhibitory NT
Works to sedate and calm

9

ACh

Plays a role in memory and cognition
Held in balance with dopamine in the substantia nigra

10

Gutamate

Primary Excitatory NT

11

CYP 450 1A2

-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).

12

CYP 2C19

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

13

CYP 2D6

-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.

14

CYP 3A4 Inhibition

-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

15

CYP 3A4 Induction

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

16

Exogenous estrogen and Lamictal

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

17

Lithium and NSAIDs

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

18

CATIE

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.

19

STEP-BD

Treatment Enhancement Program for Bipolar Disorder

20

Star-D

Sequenced Treatment Alternatives to Relieve Depression
-Still have a lot of residual depression that wasn't getting treated.

21

Typical Antipsychotics MOE

D2 blockade in the mesolimbic and mesocortical tract

22

Typical Antipsychotics SEs

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

23

Treatments for EPS

Change med
Lower dose
Benztropine (Cogentin)

24

Typical Antipsychotics Long-term SEs

Permanent effects on movement seen
TD not reversible
Neuroleptic Malignant Syndrome

25

Neuroleptic Malignant Syndrome

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

26

Atypical Antipsychotics MOA

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

27

Dosing Clozapine

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

28

Monitoring with Clozapine

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

29

Clozapine Testing Thresholds

If WBC 2.0 or Neuts

30

Unique to Risperdal

May cause szr
Contraindicated in preggers
Increased prolactin
Sexual SEs

31

Risperidone Depot

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

32

Paliperidone (Invega) Depot

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

33

Olanzapine Depot

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

34

Abilify Depot

Q4Weeks
Costs problematic
gluteal only

35

Metabolic Goals with Antipsychotics

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

36

Diagnostics for Metabolic Syndrome

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

37

HEAT MADE HI

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

38

Treatment for NMS

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

39

Hot, Stiff, and out of it

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

40

Tricyclic eliminated by:

2D6

41

SRI: Selective Reuptake Inhibitors

Nefazodone
Trazodone
Bupropion

42

Viibryd and Brintellix

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

43

SNRIs

Venlafaxine: Inc in BP at higher doses
Duloxetine
Desvenlafaxine

44

SRIs and SSRI class side effects and clinical pearls

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

45

Prozac clinical pearls

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

46

Paxil (Paroxetine)

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

47

Citalopram (Celexa)

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

48

Sertraline (Zoloft)

Great for elderly
Easily titrated

49

Escitalopram (Lexapro)

More effective than Citalopram, fewer side effects

50

Best medication for bipolar maintenance

Lithium

51

Exam wants to know firsts

Clozaril first SGA
Lithium first treatment for bipolar
Prozac first SSRI

52

Therapeutic blood level for acute treatment

1.2 mEq/L

53

When to check Li level

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

54

Cautions with Li

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

55

LFTs with Depakote

Before first dose
3 and 6 months out

56

BuSpar shortcomings

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

57

Drugs for Parkinson's

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

58

Acetylcholine antagonists for Parkinson's

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

59

Drugs to reduce levodopa-induced dyskinesias

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

60

Sleep Regulator

Ventrolateral preoptic nucleus in the hypothalamus inhibits brainstem arousal

61

When does REM start?

REM starts 80-100 minutes after sleep initiation

62

Sleep hygiene points

No screens
Dark and cool
Routine
No caffeine