Psychobiology and Psychopharmacology Flashcards
(66 cards)
1
Q
Psychosis Psychobiology
A
- Elevated dopamine in basal ganglia
- Change is medolimbic-mesocortical circuits
- Decreased serotonin 5-HT receptor activity contributes to negative symptoms
2
Q
Depressive and Manic Symptoms Psychobiology
A
- Decreased levels of 5-HT and/or norepinephrine
- Most involved circuit is the locus coeruleus
- Bipolar disorder may be due to interactions between NE, DA, 5-HT, acetylcholine, GABA, and peptides
3
Q
Anxiety Disorders Psychobiology
A
- Elevated levels of 5-HT and NE; and decreased levels of GABA
- Raphe nucleus is the most involved circuit
4
Q
Cognitive/Attention Disorders Psychobiology
A
- Circuits involved: dorsal anterior cingulate cortex, dorsal lateral prefrontal cortex, orbital frontal cortex
- Dysregulation of dopamine, norepinephrine, and other neurotransmitters
5
Q
Dementia/Neurocognitive Psychobiology
A
*Multifactorial including amyloid plaques, tau protein tangles, metabolic and oxygenation issues
6
Q
Dopamine: D2 and D4 receptors
A
- Excitatory NT controls thoughts and emotions in frontal cortex; mesocortical tract involved in attention, focus, and depression
- Controls complex movement in nigrostriatal dopamine pathway
- Elevated dopamine in the mesolimbic dopamine pathway that projects into the nucleus accumbens (pleasure pathway) is associated with psychosis
- Influences in the tuberoinfundibular pathways controls prolactin secretion
- D2 receptors stimulated by dopaminergic agonists for Parkinsons treatment and blocked by dopamine agonists in treatment of psychosis
7
Q
Norepinephrine
A
*Excitatory NT elevates mood, modulates attention and fatigue; may contribute to anxiety
Located predominantly in the brainstem in the locus coeruleus
*Noradrenergic projections from the locus coeruleus to frontal cortex regulate mood (beta-1 receptors)
*Frontal cortex projections influence attention/concentration (alha-2 receptors)
*Projections in the limbic cortex influence emotions/energy; projections into the cerebellum mediate tremors
*Brain stem projections affect blood pressure and innervate heart via beta-1 receptors
*Innervation of the urinary tract via sympathetic neurons affect bladder emptying via alpha-1 receptors
8
Q
Serotonin 5-HT
A
- Located primarily in the raphe nucleus with projections ……
- Frontal lobe: affects mood and depression
- Basal ganglia: (5HT2A) control of movements and obsessions/compulsions
- Limbic: (5HT2A & 5HT2C) related to anxiety and panic
- Hypothalamus: (5HT3) appetite and sleep
- Brainstem: (5HT2A) sleep centers
- Spinal cord: sexual response and gut
- Peripheral: (5HT3 & 5HT4) receptors in gut regulate appetite and GI mobility
9
Q
GABA (gamma-amino-butyric acid)
A
- Inhibitory
* Works to sedate and calm
10
Q
Acetycholine (ACh)
A
- Play a role in memory and cognition
* Held in balance with dopamine in the substantia nigra
11
Q
Glutamate
A
*Excitatory
12
Q
Hypothalamus-Pituitary_Adrenal Axis (HPA)
A
- Hypothalamus releases corticotropin releasing hormone (CRH)
- CRH stimulates release of adrenocorticotropic hormone from the anterior pituitary
- Adrenocorticotropic stimulates release of cortisol from adrenals
- Cortisol: elevates blood glucose/fats; elevates BP; Suppresses immune response
- HPA axis may be abnormal in individuals with disorders of: circadian rhythm, stress disorders, depression, diabetes/hyperlipidemia
13
Q
Hypothalamus-Pituitary-Thyroid Axis
A
- Hypothalamus releases thyrotropin releasing hormone (TRH)
- TRH acts on the anterior pituitary to secrete thyroid stimulating hormone (TSH)
- TSH stimulates the thyroid to secrete T4
- T4 is converted to T3 through hepatic pathways: regulates basal metabolic rate, neurological function
- Deficiencies: Weight gain, depression, slow mentation
- Excess: Anxiety, Stress, Hypermetabolic state (Graves)
14
Q
Hypothalamus-Pituitary-Gonadal Axis (HPG)
A
- Hypothalamus releases gonadotropin releasing hormone (GnRH)
- GnRH acts on the pituitary to cause secretion of FSH & LH
- FSH stimulates: Ovarian follicle development, estrogen secretion, sperm production
- LH stimulates: estrogen and progesterone in females; testosterone in males
15
Q
CYP450 Enzymes
A
- Inducers: When used with another medication increases metabolism and reduces therapeutic effect
- Inhibitors: When used with another medication decreases metabolism and causes drug levels to rise
16
Q
CYP450 1A2
A
1A2 is inhibited by SSRIs. Increased levels of theophylline (e.g. smoking) induces 1A2, increasing the elimination of olanzepine.
17
Q
CYP450 2D6
A
2D6 is most strongly inhibited by fluoxetine, paroxetine, and bupropion; If switching from a TCA to a serotonin agent, will have elevated levels of TCA. Affects metabolism of hydrocodone, morphine, and tramadol
18
Q
CYP450 3A4
A
- Inhibited by some SSRIs, nefazodone, and grapefruit juice; some benzo levels will rise when given with fluoxetine.
- Inhibited by erythromycin and will affect carbamazspine level or increase BZD levels. Use azithromycin instead of EES.
- Induced by carbamazepine affecting oral contraceptives, carbamazepine itself, and fluticasone.
- Induction greatly affects methadone, certain HIV meds will induce methadone, increase dose required
- Induced by St. John’s Wort, decreases cyclosporin levels
- Citalopram is a substrate for CYP 450 2C19 and 3A4, and therefore, poor metabolizer status could result in higher than predicted levels for the dosage
19
Q
Glucuronidation enzyme 1A4
A
Oral contraceptives in combination with lamotrigine induces the production of glucuronidation enzyme 1A4 increasing metabolism of lamotrigine by as much as 50%, leading to mood destablization
20
Q
Lithium levels
A
- Therapeutic level: .8 - 1.2
- Lithium levels increase the inhibition of prostglandins so common NSAID (ibuprofen) can lead to lithium toxicity; exceptions are ASA, Sulindac and tylenol
21
Q
CATIE Trial: Clinical Antipsychotic Trials of Intervention Effectiveness
A
- Olanzapine had the least amount of discontinuation; associated with weight gain, increase blood glucose, lipid metabolism
- Typical anti-psychotics are equally effective to atypical but more likely to be discontinued because of extrapyramidal symptoms
22
Q
STEP-BD Trial: Systematic Treatment Enhancement Program for Bipolar Disorder
A
In conjunction with mood stabilizing agents, intensive psychotherapy is more effective for depression than collaborative care treatment
23
Q
STAR-D Trial: Sequenced Treatment Alternatives to Relieve Depression
A
- Citalopram to another randomly selected SSRI/SNRI to TCA or MIrtazepine
- Pts with hard to treat depression can get better with step treatment but chance of recovery diminish with each step
24
Q
Typical Anitpsychotics (first generation)
A
- Phenothiazines: Chlorpromazine/Thorazine; Fluphebazine/Prolixin; *Trifluoperazine/Stelazine
- Butyrophenones: Halperidol/Haldol; Droperidol/Inaspine
- Thioxanthenes: Thiothixene/Navane
- Dihydroindolenes: Molindine/Moban
- Dibenzoazopines: Amoxapine/Asendin
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Typical Antipsychotics Effect
Bocks D2 receptors in the mesolimbic and mesocortical tract
26
Typical Antipsychotics Side Effects
* Sedation/weight gain from H1 blockade
* Orthostatic hypotension and drowsiness from alpha-1 adrenergic receptro blockade
* Increased prolactin from D2 blockade in the tuberoinfundibular tract
* Anticholinergic effects from Muscarinic blockade
* Extrapyramidal side effects from De blockade in the nigrostriatal tract
* Neuroleptic Malignant Syndrome
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Extrapyramidal Side Effects and Treatment
* Pseudoparkinsonism, dystonias, akathesia
* Change medication
* Lower dose
* Benzoptropine (Cogentin)
28
Atypical Antipsychotics
* Dibenzodiazepines: Clozapine/Clozaril
* Benzisoxazoles: Risperidone/Risperdal
* Thienobenzodiazepines: Olanzepine/Zyprexa
* Dibenzothiazepine: Quetiapine/Seroquel
* Benzisothiazolyl piperazines: Ziprasidne/Geodone
* Aripiprazole/Abilify
* Lurasidone/Latuda
* Asenapine/Saphis
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Atypical Antipsychotics Mechanism of Action
* Block D2 and 5HT receptors
* Relieves negative symptoms not seen with typical antipsychotics
* Decreased risk of extrapyramidal symptoms and tardive dyskinesias
30
Side Effects of Atypical Antipsychotics
```
Orthostatic hypotension
Dizziness
Weight gain
Tachycardia
Sleep disturbance
Constipation
Neuromalignant Syndrome
Agranulocytosis
EPS, TD
```
31
Clozapine/Clozaril
* May cause agranulocytosis
* 12.5 mg first dose, increase by 25-50 mg /day to 330-400 mg/ day
* 900 mg max per day; 450 mg max per dose
* CBC/Diff?ANC every week X 6 months then every 2 weeks x 6 months, then every 4 weeks
32
Risperidone/Risperdal
* May cause seizures
* Contraindicated in pregnancy
* Increased prolactin
33
Long Acting Injectable Antipsychotics
* Older: Fluphenazine/prollixin; Haloperidol
* Respiridone: q 2 weeks
* Paliperidone/Invega: q 4 weeks
* Olanzipine/Zyprexa: q 2-4 weeks; post injection delirium and extreme sedation
* Aripiprazole/Abilify: q 4 weeks
34
Neuroleptic Malignant Syndrome
* 0.2% - 2.4% incidence
Usually develops in first 2 weeks
* HOT, DTIFF and OUT OF IT: Mental status change, muscle rigidity, extreme autonomic instability/hyperthermia
* 10-20% mortality; Death from cardiac, respiratory, or renal failure
* Treatment with dopamine agonists: Amantadine, bromocriptine; Muscle relaxant: Dantrolene
35
Neuroleptic Syndrome Associated Symptoms
* Hyperthermia, confusion, muscle rigidity
* Diaphoresis, hypertension, tachycardia, irregular pulse, fasiculations
* elevated creatine kinase, elevated myoglobin, elevated WBC, Elevated AST/ALT, iron deficiency, proteinuria/myoglobinuria
36
Main medications for Bipolar Affective DIsorder
* Lithium
* Depakote
* Other agents include: antiepileptics, antipsychotics, sedatives
37
Lithium
* May work by affecting NE and DA but exact mechanism unknown
* Therapeutic levels .5 - 1.2 mmol/L
* Acute treatment: blood levels twice a week
* Chronic treatment: blood levels every 2-6 months
* Check serum levels 12 hours after last dose and after five days of steady dosing
38
Lithium Side Effects
* Muscle weakness
* Tiredness
* Slurred speech
* Fine hand tremor
* Thirst
* Nausea
* Diarrhea
* Vomiting
39
Lithium Cautions
* Concomitant use of haloperidol linked to encephalopathy
* IBU can increase serum lithium levels
* Calcium channel blockers are contraindicated
* Use diuretics with caution
40
Antiepileptics in Psychiatry
* Carbamazepine (Tegretol)
* Divalproex sodium (Depakote)
* Topiramate (Topamax): chronic headaches, alcohol craving
* Lamotrigine (Lamictal)
* Gabapentin (Neurontin)
* Pregabalin (Lyrica): alpha 2 delta ligands block voltage sensitive Ca channels, decreasing release of calcium, decreasing release of glutamate, decreasing AMPA activation, decreasing release of NE & Substance P
41
Antiepileptics in Psychiatry
* Decreases the firing of CNS nerves
| * Potentiating the effects of GABA in certain parts of the brain, reducing the number of action potentials
42
Antiepileptics Adverse Effects
* Sedation
* Fatigue
* Dizziness
* GI upset
* Phenobarbital: Induction of liver enzymes
* Phenytoin: Gingival hyperplasia
* Carbamazepine: Hepatitis and liver failure
* Divalproex sodium: Pancreatitis, hepatitis; MONITOR LIVER
* Lamotrigine: Serious skin rash
43
Tricyclic Antidepressants
* Amitriptyline (Elavil)
* Nortriptyline (Aventyl, Pamelor)
* Desipramine (Norpramine, Pertofrane)
* Imipramine (Tofranil)
* Doxepin (Sinequan)
* Protriptyline ( Vivactil)
* Amoxapine (Asendin)
* Trimipramine (Surmontil)
* Clomipramine (Anafranil)
44
Tetracycline Antidepressants
* Maprotiline (Ludiomil)
| * Mirtazapine (Remeron)
45
Tricyclic & Tetracyclic Antidepressants Side Effects
* Sedation
* Anticholinergic effects: dry mouth, mydriasis, hyperthermia, tachycardia
* Cognitive impairment
* Memory loss
* Weight gain
* Tetracyclic: Agranulocytosis
** Possible QT prolongation; baseline EKG
46
Tricyclic Antidepressant Pharmacokinetics
* Eliminated by 2D6
* If elimination is blocked by inhibition of 2D6 agents such as fluoxetine, risk of widening QTc interval allowing for Torsade de points arrhythmia/sudden death.
* Can lower seizure threshold
47
Monoamine Oxidase Inhibitors (MAOI)
* Phenelzine (Nardil)
* Tranylcypromine (Parnate)
* Isocarboxazid (Marplan)
* Selegiline (patch Emsam, buccal Zelapar, capsule Eldepryl)
48
MAOI Side Effects
* Dizziness
* Vertigo
* Headache
* Insomnia
* Memory impairment
* Hypertensive crisis: precipitated by tyramine rich foods, sympathomimetic drugs, meperidine
49
Norepinephrine-Dopamine Reuptake Inhibitor (NDRI) Antidepressants
* Buproprion (Wellbutrin)
50
Selective Reuptake Inhibitor Antidepressants
* Nefazodone (Serzone)
| * Trazodone (Desyrel)
51
Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants
* Fluoxetine (Prozac)
* Paroxetine (Paxil): known for withdrawal symptoms
* Citalopram (Celexa): cardiac effects may require decreased doses
* Sertraline (Zoloft)
* Escitalopram (Lexapro)
* Vilazodone (Viibryd): 5HT1A partial agonism
* Vortioxetine (Brintellix): 5HT1A partial agonism
52
Serotonin Norepinephrine Reuptake Inhibitor (SNRI) Antidepressants
* Venlafaxine (Effexor) : increased BP
* Duloxetine (Cymbalta)
* Desvenlaxafine (Pristiq)
53
SRI and SSRI Side Effects
* Nervousness
* Insomnia
* Sedation (Paroxetine)
* Headache
* Sweating
* Dry mouth
* Teeth clenching
* Sexual dysfunction
* Initially: Nausea, weight loss
* Prolonged use: weight gain
54
Antidepressants which cause lower sexual dysfunction
* Bupropion (Wellbutrin)
* Mirtazapine (Remeron)
* Vilazodone (Viibryd)
* Virtioxetine (Trintellix)
* Erectile dysfunction caused by inhibition of alpha 1 adrenergic receptors
55
Pediatric Antidepressants
* Fluoxetine (Prozac): FDA indicated for MDD 6+; OCD & PTSD 7+; cataplexy ages 7+
* Escitalopram (Lexapro): FDA indicated for MDD 7+; autism 6+
56
Serotonin Syndrome Symptoms
* Agitation
* Confusion
* Hallucinations
* Tachycardia
* Fever
* Muscle rigidity
* Hyperrelexia
* Tremors
* Diarrhea
* Hypo/hypertension
* Myoclonus
57
Serotonin Syndrome cause/treatment
* Use of more than one SSRI or St. John's Wort
* Withdraw from SSRI
* Stabilize temperature with antipyretics
* Benzodiazepine, dantrolene for muscle relaxation
* Beta blocker for tachycardia
* Cyproheptadine (Periactin): Binds to serotonin (5HT1A & 5HT2A) and histamine receptors
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Discontinuation of SSRIs: FINISH
* Flue like symptoms
* Insomnia
* Nausea
* Imbalance (dizziness)
* Sensory disturbance
* Hyperarousal (anxiety); Headache
59
Anxiolytic Side Effects
* lethargy
* sedation
* depression
* dizziness
* lightheadedness
* anticholinergic effects
* addiction
** Avoid in acute narrow angle glaucoma
60
Side Effects of ADHD Medications
* Weight loss
* Hypertension
* Insomnia
* Irritability
* Nervousness
* Palpitations
* Tachycardia
* Monitor growth
* Pros and cons of drug holidays
61
Anxiolytics/Hypnotics
* Diazepam (Valium)
* Lorazepam (Ativan)
* Alprazolam (Xanax)
* Clonazepam (Klonopin)
* Chlordiazepoxide (Librium)
* Buspirone (Buspar): Nonbenzo
* Zaleplon (Sonata): Nonbenzo
* Zolpidem (Ambien): Nonbenzo
62
Anxiolytic withdrawal
* * withdraw slowly
* irritability
* anxiety
* insomnia
* depression
* seizures
63
Stimulant Medications
* Accelerate "slow rate" behaviors; Suppress "fast rate" behaviors
* Blockade of DA
Contraindications: glaucoma, motor tics, tourette's syndrome, caution with seizure disorder
64
ADHD Medications
* Methylphenidate: Ritalin, Concerta, Focalin
* Dextroamphetamine: Adderall, Vyvanse
* Non-stimulant
* * Atomoxetine (Strattera): Blocks reuptake of NE
* * Guanfacine (Intuniv)
* * Catapres (Clonidine)
65
Anti-Parkinsonian Drugs
* Parkinson's is the result of loss of dopaminergic neurons in the substantia nigra and cholinergic deficits
* Levodopa is the gold standard
* Acetylcholine antagonists (first line therapy): Benzotropin (Cogentin); Trihexyphenidyl (Artane); Amantadine (Symmetrel); Selegine (Eldepryl): MAOI
* Dopamine agonists added: pramipexole, ropinirole, pergolide
66
Side Effects of Anti-Cholinergic anti-Parkinsons Drugs
* Tachycardia
* Confusion
* Agitation
* Constipation
* Urinary Retention
* Blurred Vision
* Dry mouth; Dry skin
**Tolcapone (Tasmar) and Entacapone (Comtan); Catechol-)-methyl (COMT) enzyme inhibitors help reduce levodopa drug induced dyskinesias
