psych drugs Flashcards
(71 cards)
1
Q
MOA of lithium
A
works on multiple NT (5-HT, NE, Glu, GABA, Da)
-modifies 2nd messenger system
2
Q
What conditions does lithium work for?
A
- Bipolar Mania (FDA)
- bipolar Prophylaxis (FDA)
- Adjunct to antidepressants to help treat MDD
- Acute tx of mania or agitation
- Better at preventing mania than depression but does help prevent depression
3
Q
What are the side effects of lithium
A
!!Dec. renal function!! (kidney drug!)
- tremor
- polyuria +/- polydipsia
- cognitive slow/memory probs
- hypothyroid
- acne
- N/V/D
4
Q
Can lithium be used in pregnancy?
A
- category D
- avoid in 1st trimester (Ebstein’s abnormality=congenital heart defect)
- can use after 1st trimester if benefts>risks
- do not use while breastfeeding
5
Q
Does lithium interact with any drugs?
A
- THINK KIDNEY
- diuretic–>inc. Li levels
- urinary alkalinizers–>dec. LI level
- iodide salts–>inc. hypothyroidism
- NSAIDS–>inc. Li levels
- sodium bicarb–>dec. Li levels
- antipsychotics–>inc. Li toxicity
- buproprion–>inc. sz risk
- inc. or dec. levels of verpamil
6
Q
does lithium interact with any foods?
A
inc. sodium–>dec Li level
inc. caffeine–>dec. Li level
7
Q
What are the sx of lithium toxicity?
A
- Coarse tremor, muscle fasciculations, confusion, stupor
- Slurred speech, ataxia (wobbly), vomiting, arrhythmia & seizures
8
Q
What things do you need to monitor in a patient taking lithium?
A
- narrow therapeutic window (blood level 0.8–1.2mmol/liter)
- monitor kidney function (Li excreted through the kidneys
- monitor TSH (worried about hypothyroid, though it is reversible if you discontinue Li)
9
Q
what is the MOA of anticonvulsants as mood stabilizers?
A
- Act on sodium, potassium and calcium ion channels in cell
- This modulation changes both excitatory (GLU) and inhibitory (GABA) neurotransmission
- Augment synthesis/release of GABA
- Inhibit reuptake and breakdown of GABA
- Decrease release of Glu
- ->work to dec. excitatory NT (glu) and inc. inhibitor NT (GABA)
10
Q
What drug class is valproic acid? What conditions can it be used to treat?
A
- Acute mania (FDA)
- Seizure d/o (FDA)
- Bipolar prophylaxis (may be effective)
11
Q
what are the side effects of valproic acid?
A
Scary side effects are:
- pancreatitis
- hepatitis (esp. children)
- thrombocytopenia
Less scary but undesirable side effects are:
- wt gain
- sedation
- GI upset (take w/ food)
- Dizziness
- hair loss
- polycystic ovaries
12
Q
Can you use valproic acid in pregnancy?
A
category D
inc. risk of NTD
13
Q
What sx will you see with valproic acid overdose?
A
N/V, CNS depression, seizures
check drug levels, target is 50-100g/mL
14
Q
Which drugs will inc. the serum level of valproic acid?
A
CAFE PI
- cemetidine (PPI)
- Aspirin
- Fluoxetine (antidepressant SSRI)
- Erythromycin
- Phenothiazines
- Ibuprofen
15
Q
Which drugs will dec. the serum level of valproic acid?
A
CREPes
- Carbamazepine
- Rifampin
- Ethosuximide
- Phenobarbitol
16
Q
Valproic acid inhibits the metabolism of which drugs?
A
I sAW LAND (I=inhibited by)
- Amitriptyline
- Warfarin (inc. risk bleeding)
- lamotrigine
- AZT
- Nortriptyline
- Diazepam (benzo)
17
Q
what is the MOA of carbamazepine?
A
Acts on Na and K channels to enhance GABA availability
18
Q
What conditions would you use carbamazepine with?
A
- trigeminal neuralgia
- seizures
- can use in bipolar but there are better drugs with fewer side Effx
19
Q
What are the side effects of carbamazepine?
A
HLA typing in asians
Scary ones are:
- thrombocytopenia and aplastic anemia
- hepatitis
- exfoliative dermatitis, toxic epidermal necrolysis
Less scary but unpleasant ones:
- sedation
- dizziness
- fatigue
- N/V, constipation or diarrhea
- ataxia (wobbly)
20
Q
carbamazepine and pregnancy?
A
category D
-assoc. w/ congenital malformations (spina bifida)
21
Q
What are the important clinical take-home points concerning carbamazepine?
A
- Avoid in patients with cardiac, hematological, liver or kidney disease
- Think of it as a drug that interacts with almost everything
- If you ever rx must check it doesn’t interact with other meds pt is taking (it interacts with itself)
- Must have 14 day washout period before initiate MAOI—can have serotonin syndrome
22
Q
what is the MOA for lamotrigine?
A
dec the excitatory actions of Glu via interference with Na channels
23
Q
what disorders can you treat with lamotrigine?
A
bipolar d/o (mania, hypomania, and depression)
24
Q
what are the side effects of lamotrigine?
A
scary:
-toxic epidermal necrolysis (10% pt’s get rash but only small subset progress)
less scary but unpleasant:
- sedation
- dizziness
- ataxia
- dec. coordination
- headache
- N/V
25
lamotrigine in pregnancy?
Category C
Avoid in first trimester
Use after first trimester if other meds don’t work
Avoid in breast feeding – risks unknown
26
When can you use antipsychotics?
Psychotic illness – unable to distinguish unreality from reality
-Schizophrenia, Bipolar Mania, Depression w/psychosis, drugs (eg. Cocaine)
Augmentation of antidepressant (eg SSRI)—makes them work better
-Aripiprazole & Quetiapine
Mood Stabilizer – Acute Mania
-Quetiapine, olanzepine, aripiprazole, ziprasidone & risperidone
Mood Stabilizer – Maintenance
-Olanzapine & aripiprazole
27
What are the typical first generation antipsychotics?
dopamine antagonists:
- chlorpromazine
- thiordazine
- prochlorperazine
- trifluoperazine
- haloperidol
28
What are the second generation atypical antipsychotics?
serotonin/dopamine antagonists:
- Clozapine
- Risperidone
- Olanzapine
- Quetiapine
- Ziprasidone
dopamine agonist/antagonist:
-arpiprazole
29
what is the mesolimbic pathway? What does this pathway control?
- Midbrain ventral tegmental area -->nucleus accmbens
- Pathway of all things pleasurable
- Pathways for drugs of abuse to create “high” feeling
- Pathway of delusions and hallucinations of pscyhosis
30
What is the mesocortical pathway? What does this pathway control?
- Midbrain ventral tegmental area --> limbic cortex
- May have role in mediating +/- psychotic symptoms
- May have role in cognitive side effects of FGA’s
31
what is the nigrostriatal pathway? what does this pathway control?
- Substantia nigra --> basal ganglia
| - Controls movement
32
What ist he tubuloinfundibular pathway? What does this pathway control?
- Hypothalamus --> anterior pituitary gland
- Controls prolactin secretion
- Dopamine & prolactin have an inversely proportionate relationship (i.e. inc of one =dec of the other)
- Lower dopamine-->inc. prolactin-->galactorrhea/gynecomastia
33
what is the dopamine hypothesis of schizophrenia?
```
-Hyperdopaminergic activity in mesolimbic system -->positive sx
Delusions
Hallucinations
Catatonia
Thought disorder
```
-Hypodopaminergic activity in mesocortical system -->neg sx
Apathy
Motor retardation
Social withdrawal
34
what is the MOA of FGA dopamine antagonists?
- Competitively block Da receptors (D2, D3 & D4 subtypes)
- D2 receptors located in limbic, extrapyramidal & endocrine structures
- D3 & D4 subtypes located primarily in limbic structures
- Receptors linked to enzyme adenyl cyclase via G protein which inhibits activation of enzyme
- Blocking receptors decreases +sx (mesolimbic pathway)
- Bind to D2 receptors 10-50x more avidly than D3 receptors
35
Which FGAs are high potency? What profile will they have?
haloperidol & fluphenazine
- Low anticholinergic & low sedating properties
- Fewer CV abnormalities
- Higher rate of EPS
36
Which FGAs are low potency? What profile will they have?
chlorpromazine and thioridazine
- high anticholinergic and high sedating properties
- more pronounced CV abnormalities
- low incidence of EPS
37
What is the MOA of dopamine/serotonin antagonists (SGAs)?
clozapine, risperidole, olanzapine, quetiapine, ziprasidone
More selective for mesolimbic Da pathway (origin + symptoms)
Less active on nigrostriatal pathway (origin EPS)
Competitively block serotonin receptors (5-HT2 subtype)
Have >5x binding affinity for 5-HT2 than D2
-5-HT2 located in cortical structures where neg sx thought to originate
Higher degree of binding/blockade of D4 & D3 receptors vs D2
-D4 & D3 receptors located in limbic structures where + sx thought to originate
Blockade of 5-HT receptors therefore-->
- Improves negative & positive sx
- Dec EPS
38
what is the MOA of dopamine agonist/antagonist?
*Establishes balanced dopamine availability
```
-Acts as antagonist when there is excess Da
Mesolimbic pathway (positive sx-delusions)
```
-Acts as agonist when there is too little Da
Nigrostriatal pathway & frontal lobes (negative sx)
-Aripiprazole (abilify) only drug in this class
39
What other receptors can antipsychotics act on? What are the side effects based on these receptors?
Anticholinergic (M1)
- Dry mouth
- Mydriasis
- Urinary retention
- Constipation
Antihistaminergic (H1)
- Weight gain (can be VERY significant)
- diabetes
- sedation
Alpha Adrenergic Blockade
- Orthostatic (postural) hypotension
- sedation
Dopaminergic Blockade
-EPS
40
what are the extrapyramidal side effects of antipsychotics?
- Parkinsonian syndrome (blockage of D2 receptors in striatum-->muscle rigidity, slow movements, shuffling gait, resting tremor, mask like facies, cogwheel rigidity)
- acute dystonia (prolonged muscle spasm tx'ed with dephenhydramine or benztropine)
- tardive dyskinesia (more common with FGAs, abnormal writing movement of tongue, face, limbs, trunk; D2 blockade in hypothalamus and striatum, may not go away with discontinuation of meds)
- Neuroleptic malignant syndrome: life threatening, more common in men, hyperthermia, hypertension, tachycardia, tremor, sz, dyskinesias, STOP antipsychotic
- akithisia: subject feeling of motor restlessness, give patient dephenhydramine, propanolol, benzodiazepine
41
what are the endocrine side effects of antipsychotics?
Blockade of D2 in hypothalamus &/or anterior pituitary
- Inc prolactin -->gynecomastia in men and galactorrhea in women
- Dec gonadotropin--> amenorrhea
- Dec growth hormone, Luteinizing hormone & ACTH
42
what are the cardiovacular side effects of antipsychotics?
- Prolongation of QT interval on EKG (Torsades)
| - Can result in potentially lethal cardiac -arrhythmia
43
What is metabolic syndrome? Which has more risk FGA or SGA? What should you monitor in patients taking antipsychotics?
Group of findings--> inc risk of heart disease, stroke & diabetes
-Inc BP, inc insulin, xs abdominal fat or inc cholesterol
- SGAs have inc. risk
- Monitor: weight, waist circumference, fasting glucose, fasting lipids, BP
44
What are the general clinical guidelines for antipsychotics?
- Choose based on past response and side effects
- SGA’s generally 1st line, especially if past tardive dyskinesia
- Avoid SGA’s for behavioral disorders in patients with dementia--> inc mortality
-Pregnancy category C
FGA’s – slight inc in anomalies
SGA’s – need inc data
- Smoking increases metabolism of antipsychotics
- Must adjust dose for patients with liver or kidney disease
45
When would you use clozapine? What are the side effects?
-For patients who have failed 2+ other antipsychotic agents
- Risk of agranulocytosis & neutropenia must monitor CBC
- Risk seizures on doses > 600mg/day
- Myocarditis – rare
- Low association with TD
- For patients who have failed 2+ other antipsychotic agents
- Sedation, orthostatic hypotension & hypersalivation
- Decreased risk of suicide in patients with schizophrenia (FDA approval)
46
which 2 antipsychotics are less likely to cause weight gain?
aripiprazole
| ziprasidone
47
all addictive drugs activate what part of the brain
the mesolimbic dopamine system
| this originates in the VTA-->nucleus accumbens, amygdala, hippocampus, prefrotnal cortex
48
SSRIs
- Sertraline, paroxetine, citalopram, escitalopram, fluvoxamine
- Good b/c decr. wt. gain, decr. sedation, decr. orthostatic hypotn
- Biggest drawback is decrease sex drive
49
SNRIs
- serotonin and norepi reuptake inhibitors
- Venlafaxine, duloxetine
- Duloxetine can be used for DM peripheral neuropathy
50
tricyclic antidepressants
- Desipramine, Imipramine, Nortriptyline, Amitriptyline
- Block reuptake of NE & Serotonin
- Yes they’re efficacious but they come with a whole host of AE’s
- CARDIAC – arrhythmias, prolonged QT
- ANTI – histaminergic, - cholinergic, - adrenergic
- Still sexual AEs
- OD will KILL you
51
MAOIs
-Phenelzine, Tranylcypromine
Not use as much because…
-Foods that contain TYRAMINE -->stroke
-Mixing with drugs can --> HTN crisis
-React with other medications, including anesthetics so have to go off 2 weeks before surgery
-SEROTONIN SYNDROME – do not mix w/ SSRIs**
52
buproprion
- Only one, along with mirtazapine, that doesn’t cause sexual side effects
- Can also be used to help quit smoking – marketed as Zyban for that
- NDRI (norepi and dopamine reuptake inhibitors)
53
Why are SSRI's better than Tricyclics?
a. Do NOT block cholinergic receptors, histamine receptors (less sedation) or a1-adrenergic receptors (less orthostatic hypotension)
b. Do NOT have quinidine-like action on the heart
c. Do NOT cause significant weight gain
d. Do NOT require monitoring of blood levels
e. Have higher safety margins in overdose
54
Serotonin syndrome occurs when SSRIs are combined with which drugs?
a. MAOIs
b. Tricyclic antidepressants
c. Lithium
d. Carbamazepine
55
What are the indications for using SSRIs
```
o Depression (1st line)
o OCD, panic disorders, posttraumatic stress disorder, eating disorders, generalized anxiety disorder, premenstrual syndrome
```
56
which SSRI has the longest half-life?
fluoxetine
57
what are the indications for using Tricylcics?
```
o Depression (resistant to SSRIs)
o Childhood enuresis, chronic pain, neuralgias, migraine, diabetic neuropathy
```
58
What is the MOA of benzodiazepines?
enhance frequency of GABA mediated Cl- channel opening
59
what is the MOA of barbituates?
enhance duration of GABA mediated Cl- channel opening
60
What drug classes and drug names can you use to treat insomnia?
1. antihistamines (diphenhydramine)
2 . antidepressants w/ sedative activity (trazodone)
3. melatonin receptor agonists (ramelteon)
4. benzo's (temazepam, estazolam, flurazepam, quazepam, triazolam)
5. non-benzo hypnotics (zolpidem, zaleplon)
61
What are the adverse effects when using benzodiazepines?
o Sedation (ALL benzodiazepines are sedating)
o Daytime drowsiness
o Dizziness and ataxia (<2%), can lead to falls and hip fractures in the elderly
o Amnesia and memory impairment
o Rebound insomnia upon discontinuation
caution in patients with COPD, sleep apnea and cognitivie deficits
teratogenic in pregnancy
other issues: abuse, withdrawal
62
what are the best drugs to use to treat insomnia?
zolpidem
zaleplon
act on subunit of GABA receptor and inc. Cl- channel opening
63
All addictive drugs activate what
mesolimbic dopamine system
| VTA=addiction center
64
Which drugs of abuse work on GPCR pathways?
1. opioids
2. cannabinoids
3. GHB
4. LSD
65
which drugs of abuse work on ion channels?
nicotine
alcohol
benzo's
phencyclidine, ketamine
66
Which drugs of abuse work on dopamine transporters?
cocaine, amphetamine
| ecstasy
67
tolerance
escalation in dose to maintain comparable effect
1. PK changes (eg. enzyme induction--barbituates)
2. pharmacodynamic changes (receptor change in number--morphine)
3. immunological changes (antibody formation--insulin)
4. behavioral changes (compensation--alcohol)
68
physical dependence
drug need to prevent withdrawal syndrome
alcohol,barbituates=severe
narcotic analgesics=moderate
stimulants=mild
69
you suspect drug toxicity. Patient presents with respiratory depression, mental status depression, miosis. What drug?what is the treatment?
opioid
| naloxone
70
patient is drug addict going through withdrawal. He presents with lacrimation, rhinorrhea, mydriasis, N/V/D, diaphoresis, insomnia, piloerection. What drug is he withdrawing from?
heroind
71
how do you treat benzo toxicity?
flumazenil
