Week 4 (Quiz 3) (Antidepressants, antipsychotics, antiepileptic, headaches) Flashcards
1
Q
Monoamine Theory
A
deficiency of serotonin, NE, and dopamine at key sites in brain which control mood and emotions
2
Q
Major Depressive Disorder Criteria
A
Sleep Interest Guilt/Worthlessness Energy Concentration Appetite change Psychomotor retardation Suicide/Sex
3
Q
imipramine, desipramine, amitriptyline, nortriptyline, doxepin, clomipramine, amoxapine (Type)
A
Tricyclic Antidepressants
4
Q
fluoxetine, paroxetine, sertraline, citalopram, escitalopram, fluvoxamine (Types)
A
SSRIs
5
Q
venlafaxine, desvenlafaxine, duloxetine (Type)
A
SNRIs
6
Q
isocarboxazid, tranylcypromine, phenelzine, selegiline (Type)
A
Monoamine Oxidase Inhibitors (MAOIs)
7
Q
mirtazapine, bupropion, trazadone, nefazodone (Type)
A
Atypical Antidepressants
8
Q
Antidepressants metabolized by CYP2D6
A
All TCAs
All SSRIs
SNRIs (Except desvenlafaxine)
9
Q
Discontinuation syndrome (especially with SSRIs and SNRIs)
A
Abrupt discontinuation or reduction in dosage can result in:
anxiety, irritability, general malaise (flu-like), headache, insomnia, crying
10
Q
Reduce symptoms of discontinuation syndrome by:
A
- Tapering drugs over weeks or months
2. Switching to an SSRI with a longer half-life for a few weeks before discontinuing medication.
11
Q
Biopolar disorder drugs
A
Lithium (Main)
Anticonvulsants, Antipsychotics, Benzodiazepines
12
Q
Lithium mechanism
A
Unknown
13
Q
Lithium side effects (LMNOP)
A
Movement (tremor); Nephrogenic diabetes insipidus; HypOthyroidism; Pregnancy problems (Class D drug)
14
Q
TCAs that target 5-HT and NE (3 amine)
A
imipramine, doxepin, amitriptyline
15
Q
TCAs that target NE only
A
nortriptyline, desipramine, clomipramine, amoxapine
16
Q
TCA mechanism
A
Inhibits Uptake 1 (NE) and SERT (5-HT)
17
Q
TCA end effect
A
↑ neurotransmitter in synapse
18
Q
TCA use
A
Depression (all), nocturnal enuresis/bedwetting (imipramine), OCD (clomipramine), fibromyalgia/pain disorders
19
Q
What is imipramine specifically used for?
A
nocturnal enuresis/bedwetting
20
Q
What is comipramine specifically used for?
A
OCD
21
Q
Side effects of TCAs
A
anticholinergic (muscarinic) = block parasympathetics, delirium in elderly; blockade of α-adrenergic receptors = orthostatic hypotension, ↑HR; sedation; sexual SE, cardiac arrhythmias
22
Q
TCA Toxicity (3 Cs)
A
Convulsions
Coma
Cardiotoxic
23
Q
TCA Toxicity Treatment
A
Sodium bicarbonate
24
Q
Examples of SSRIs
A
fluoxetine [Prozac], paroxetine [Paxil], sertraline [Zoloft], citalopram [Celexa], escitalopram [Lexapro], fluvoxamine [Luvox]
25
Mechanism of SSRIs
inhibits SERT (5-HT)
26
SSRI use
Depression, panic disorder, generalized anxiety disorder, OCD, social phobia, PTSD, bulimia (fluoxetine), PMDD
27
SSRI side effects
headache, GI, sexual dysfunction (from receptors in spinal cord; most common reason for discontinuation), anxiety, insomnia, poss. increased bleed risk?
28
What is serotonin syndrome associated with SSRIs?
Anxiety, agitation --> delirium; autonomic hyperactivity (vital sign changes, ↑BP, HR, temp); tremor/hyperreflexia --> rigidity/hypertonicity
29
Toxicity treatment for SSRIs
remove offending agent, control side effects, administer Cyproheptadine
30
SNRIs examples
venlafaxine, desvenlafaxine, duloxetine
31
Mechanism
inhibits SERT; inhibits NET (uptake-1) at higher doses
32
SNRIs use
depression, generalized anxiety disorder, panic disorder, social phobia, diabetic neuropathy, fibromyalgia
33
SE of SNRIs
same as SSRIs + sexual dysfunction, sedation (typically more than SSRIs), anorexia/weight loss, hypertension at higher doses
34
Examples of MAOIs
Isocarboxazid, tranylcypromine, phenelzine, selegiline
35
How can MAOIs be given to avoid rxns with tyramine?
transdermally
36
Mechanism of MAOIs
prevents neurotransmitter degradation inside neuron
37
MAO-A metabolizes:
5-HT and NE
38
MAO-B metabolizes:
Dopamine
39
End effect of MAOIs
increases amount of available neurotransmitter for release
40
Use of MAOIs
Depression
41
Off label uses of MAOIs
agoraphobia, bulimia, panic disorder, social phobia in conjunction with phenelzine
42
SE of MAOIs
orthostatic hypotension (displaces NE from synaptic vesicles); HA; GI problems; hepatic necrosis with phenelzine (rare); hypertension with tyramine
43
Mirtazapine mechanism
serotonin/NE disinhibitor; α2 receptor ANTAGONIST --> promotes release of NE and 5-HT (α2 receptor INHIBITS release of NE and 5-HT)
44
Mirtazapine use
major depressive disorder
45
Off label use of Mirazapine
due to weigh gain SE = cancer pts
46
SE of mirtazapine
weight gain, sedation, no significant sexual side effects
47
Bupropion mechanism
NE/DA reuptake inhibitor
48
Bupropion use
depression, smoking cessation
49
SE Bupropion
risk of seizures (contraindicated in pts with seizures); jitteriness; no weight gain; no significant sexual side effects
50
Toxicity of Bupropion
Seizure, psychosis
51
Trazadone/Nefazodone mechanism
5-HT antagonist/reuptake inhibitor
52
Trazadone/Nefazodone use
sedation, nausea, constipation, orthostatic hypotension, priapism
53
Trazadone/Nefazodone toxicity
ventricular arrhythmias, prolonged QT; nefazodone highly hepatotoxic
54
Positive symptoms
delusions, hallucinations, disorganized thought
55
Negative symptoms
withdrawl, flattening of emotional response
56
Cognitive impairments
pts lose on average of 10 IQ points during course of illness
57
Affective disturbance
affect is how you present your internal mood - schizophrenic patients are not very good at conveying their mood; depression after a psychotic episode
58
Four symptoms clusters
Positive, negative, cognitive, affective disturbances.
59
If pt. has high ration of + symptoms to - symptoms, then:
better prognosis
60
4 dopaminergic pathways in brain
1. mesolimbic
2. mesocortical
3. nigrostriatal
4. tuberohypophyseal
61
Too much dopamine in areas of brain:
positive symptoms
62
Too little dopamine in other parts of the brain:
negative symptoms
63
DOPAMINERGIC
| Mesolimbic is associated with what type of symptoms?
positive
64
DOPAMINERGIC
Location of mesolimbic
Midbrain ventral tegmental area (VTA) to Nucleus accumbens (NA)
65
DOPAMINERGIC
Pathophys of mesolimbic
↑ DA = auditory hallucinations, positive symptoms
66
DOPAMINERGIC
Effects of treatment in mesolimbic
↓ positive symptoms
67
DOPAMINERGIC
The limbic system is in charge of:
fear, anxiety, reward
68
DOPAMINERGIC
Mesocortical is associated with what type of symptoms?
negative symptoms
69
DOPAMINERGIC
Location of mesocortical
Midbrain VTA to limbic cortex (dorsolateral prefrontal cortex = DL PFC)
70
DOPAMINERGIC
Pathophys of mesocortical
cognitive deficits; + 5 As
71
DOPAMINERGIC
5As of mesocortical
- flat Affect
- Avolition (apathy)
- Alogia (lack words)
- Anhedonia (lack of enjoyment)
- Attention impairment
72
DOPAMINERGIC
Effects of treatment of mesocortical
↑ symptoms = "zombification"
73
DOPAMINERGIC
Where is 75% of the DA in the brain?
Basal ganglia from substantia nigra to striatum
74
DOPAMINERGIC
Where is the Nigostriatial impacting?
extrapyramidal side effects
75
DOPAMINERGIC
Location of Nigostriatal
Basal ganglia from substantia nigra to striatum (extrapyramidal nervous system)
76
DOPAMINERGIC
Pathophys of nigostriatal
no major deficits
77
DOPAMINERGIC
Effects of treatment (nigostriatal)
↑ break on motor cortex
78
DOPAMINERGIC
4 hrs treatment ns
dystonia (sustained muscle contractions, esp. in young males, potentially lethal) [treat with anti-H or anti mACh]
79
DOPAMINERGIC
4 days treatment ns
Parkinsonism (more common in elderly)
80
DOPAMINERGIC
4 weeks treatment ns
akathisia (feeling of inner restlessness, dose related)
81
DOPAMINERGIC
4 months treatment ns
```
tardive dyskinesia (potentially
irreversible, women and elderly; delayed onset,
involuntary/repetitive body movements)
```
82
DOPAMINERGIC
Tuberohypophyseal ( location)
hypothalamus to anterior pituitary (tonic DA INHIBITS prolactin release)
83
DOPAMINERGIC
Tuberohypophyseal pathophys
no major deficits
84
DOPAMINERGIC
Tuberohypophyseal effects of treatment
↓DA = ↑ prolactin = galactorrhea (nipple discharge); amenorrhea; ↓ libido
85
4 seratonergic pathways in brain
1. mesolimbic
2. mesocortical
3. nigrostriatal
4. tuberohypophyseal
86
SEROTONERGIC
Mesolimbic location
Raphe (brain stem) to VTA
87
SEROTONERGIC
Mesolimbic effects of treatment
5HT blockade less robust than DA (DA blockade wins) = ↓ of positive symptoms preserved
88
SEROTONERGIC
Mesocortical location
raphe to DL PFC
89
SEROTONERGIC
Mesocortical effects of treatment
5HT blockade wins = relief of negative symptoms; blockade ↑ local DA levels
90
SEROTONERGIC
Nigrostriatial location
raphe to SN and striatum
91
SEROTONERGIC
Nicrostriatal effects of treatment
5HT block wins = reverses D2 block = ↓EPS
92
SEROTONERGIC
Tuberohypophyseal location
raphe to pituitary gland
93
SEROTONERGIC
Tuberohypophyseal pathophys
↑ 5HT inhibits prolactin
94
SEROTONERGIC
Tuberohypophyseal effects of treatment
DA blockade wins over 5HT = ↑ prolactin levels persist
95
Neuroleptics and antipsychotics absorption
oral at 30-90%
96
Neuroleptics and antipsychotics distribution
highly protein bound
97
Neuroleptics and antipsychotics metabolism
hepatic via CYP2D6 and CYP3A4
98
Neuroleptics and antipsychotics elimination
kidney and feces
99
Neuroleptics and antipsychotics site of action
D2, 5-HT2A, mACh, α-adrenergics
100
Neuroleptics and antipsychotics SE
2-fold increase in risk of sudden death
101
Neuroleptics and antipsychotics mACh off-target effects
dry mouth, blurred vision, constipation, urinary retention, cognitive blunting (anti-SLUDGE-y)
102
Neuroleptics and antipsychotics histaminergic off-target effects
weight gain, sedation
103
Neuroleptics and antipsychotics α1-adrenergic off-target effects
orthostatic hypotension, sedation also QT prolongation (esp. caused by Haloperidol)
104
Neuroleptics
Block D2 receptors, preferentially
105
Chlorpromazine
| D2 ___ 5-HT
>
106
SE of Chlorpromazine
obstructive jaundice
107
Haloperidol
| D2 ___ 5-HT
>>>>>>
108
SE of Haloperidol
QT prolongation
109
Clozapine
| 5-HT2A ___ D2
>
110
What symptoms does clozapine treat?
+ and - (efficacious in treatment resistant pts)
111
Metabolism of clozapine
CYP1A2 (some 2D6 and 3A4)
112
CYP1A2*1F and clozapine... associated with what?
rapid drug metabolism, decreased efficacy
113
Smokers with *1F/*1F and clozapine
ultrarapid metabolizers
114
Omeprazole and Clozapine
omeprazole induces CYP1A2*1C and *1F, even more decreased drug efficacy
115
Clozapine SE
weight gain, agranulocytosis risk for those with HLA-DQB1 genotype
116
Risperidone
| 5-HT ___ D2
>
117
SE of Risperidone
Weight gain, hypotension, EPS with high dose
118
Aripiprazole
| D2 ____ 5-Ht
>
119
SE of Aripiprazole
Some sedation, low SE profile may be due to partial DA agonism
120
Metabolism of chlorpromazine
2D6
121
Metabolism of haloperidol
2D6, 34A
122
Metabolism of clozapine
1A2, 2D6, 3A4
123
Metabolism of risperidone
2D6
124
Metabolism of ariprazole
2D6, 3A4
125
Epilepsy co-morbidities
memory loss; depression/anxiety; psychosocial debilitation; ↑ risk of morbidity and mortality
126
Two causes of epilepsy
Idiopathic v. symptomatic
127
Idiopathic epilepsy
no specific anatomic cause - may result from inherited abnormality in CNS, patients are treated chronically; accounts
for most cases of epilepsy
128
Symptomatic epilepsy
due to illicit drug use, tumors, trauma, infection, etc.; may or may not require therapy
129
Partial epilepsy
Simple or complex
only involve one portion of the brain; consciousness is usually preserved; may progress to tonic-clonic
130
Simple partial epilepsy
a group of hyperactive neurons with abnormal activity --> single locus in brain (usually involves one musclegroup)
131
Complex partial epilepsy
complex sensory hallucination, mental distortion, LOC; altered consciousness
132
Generalized epilepsy
abnormal electrical discharges in both hemispheres of brain
133
Tonic-clonic generalized epilepsy
LOC; continuous contraction followed by rapid contraction/relaxation (clonic)
134
Absence generalized epilepsy
brief, abrupt, self-limiting LOC (generally in children)
135
Myoclonic generalized epilepsy
short episodes of muscle contractions (begin around puberty)
136
Febrile generalized epilepsy
seizures as a result of high fever (tonic-clonic)
137
Status epilepticus
two or more seizures occur without full recovery of consciousness between them; prolonged period
of seizures; life-threatening; requires emergency treatment
138
Three classifications of epilepsy
1. Partial
2. Generalized
3. Focal
139
Carbamazepine
Phenytoin
Oxcarbazepine
Lamotrigine
Type of drug? (epilepsy)
Sodium channel blocker
140
Toxicity of carbamazepine
metabolic bone disease (↓ vitamin D); diplopia, leukopenia
141
Toxicity of phenytoin
metabolic bone disease (↓ vitamin D);
| hirsutism, neuropathy, ataxia, gingival hyperplasia
142
Toxicity of oxcarbazepine
low NA, neurotoxicity, drug interactions, rash
143
Toxicity of lamotrigine
rash, drug interactions, headache
144
Benzodiazepines
Barbiturates (penobarbital)
What type of drug? (epilepsy)
GABA receptor agonists
145
Toxicity of barbiturates
metabolic bone disease; cognitive decline, sedation
146
What two drugs block excitatory synaptic binding of glutamate receptor?
Felbamate
| Tiagabine
147
What does Felbamate target?
Targets NMDA
148
What does Tiagabine target?
kainate receptors
149
T calcium current suppressor
Ethosuximide
150
Gabapentin
Pregabalin
What do they do? (Epilepsy)
Bind alpha-2-delta subunit of voltage-gated Ca++ channels
151
Gabapentin toxicity
weight changes, neurotoxicity
152
Pregabalin toxicity
weight gain, mild neurotoxicity
153
Which drug works on the presynaptic protein on synaptic vesicles?
Levetiracetam
154
Mechanism of Topiramate (epilepsy)
sodium blocker, GABA agonist
155
Toxicity of Topiramate
weight loss, kidney stones, glaucoma
156
Mechanism of Propofol (epilepsy)
sodium blocker, GABA agonist
157
Propofol-infusion syndrome
prolonged infusion; hyperlipemia, metabolic acidosis, rhabdomyolysis; renal/heart failure
158
Toxicity of propofol
apnea, hypotension, bradycardia
