Drugs - Antipsychotics and Antidepressants (Linger)

Question 1

name some common atypical antipsychotics

Answer 1

“dones and pines”

and one prazole

a) Aripiprazole (Abilify)
b) Lurasidone (Latuda)
c) Olanzapine (Zyprexa)
d) Quetiapine (Seroquel)
e) Risperidone (Risperdal)
f) Ziprasidone

Question 2

special use atypical antipsychotic

Answer 2

colazpine (Clozaril)

Question 3

typical low potency antipsychotic agent

Answer 3

chlorpromazine

Question 4

typical high potency antipscyhotic agent

Answer 4

haloperidol and the azines

Question 5

why are they called atypical antipsychotics

Answer 5

b/c of the dramatic reduction in EPS at clinically effective doses

Question 6

what is the dopamine hypothesis in schizophrenia

Answer 6

(1) Antipsychotics block postsynaptic D2 receptors in the CNS, especially in the mesolimbic and striatal-frontal system; a few are partial dopamine agonists (e.g., aripiprazole and bifeprunox); D2 binding affinity correlates with antipsychotic potency
(2) Drugs that increase dopaminergic activity by activating receptors (apomorphine or bromocriptine), blocking dopamine reuptake (cocaine), stimulating dopamine release (amphetamines), or enhancing dopamine synthesis (levodopa) cause increased motor activity in rats, and can aggravate schizophrenia psychosis or cause psychosis de novo in humans
(3) Dopamine receptor density is increased in the brains of schizophrenics who have not been treated with antipsychotics
(4) Some (not all) post-mortem studies of schizophrenic subjects report increased dopamine levels and D2 receptor density in the nucleus accumbens, caudate, and putamen

Question 7

what evidence does NOT support the dopamine hypothesis

Answer 7

(1) Diminished cortical or hippocampal dopaminergic activity has been suggested to underlie the cognitive impairment and negative symptoms of schizophrenia
(2) Many atypical antipsychotics have much lower affinities for D2 receptors and yet are effective in schizophrenia; some of these drugs are even partial agonists at dopamine receptors
(3) These and other inconsistencies strongly suggest that the Dopamine Hypothesis is, at best, an over simplification

Question 8

what is the serotonin hypothesis in schizophrenia

Answer 8

i) Hallucinogenic drugs (LSD, mescaline) are serotonin receptor (5-HT2A and 5-HT2C) agonists
ii) Atypical antipsychotics are inverse agonists (block constitutive activity) of the 5-HT2A (and sometimes 5-HT2C) receptors

Question 9

what is the glutamate hypothesis of schizophrenia

Answer 9

i) Hypofunction of NMDA receptors, located on GABAergic interneurons, induces disinhibition of downstream glutamatergic activity and leads to hyperstimulation of cortical neurons through non-NMDA receptors
ii) Evidence for:
(1) Noncompetitive inhibitors of the NMDA receptor (e.g., phencyclidine and ketamine) exacerbate both psychosis and cognitive impairment in schizophrenics
(2) Ampakines (allosteric AMPA receptor agonists) have shown benefit in animal models of schizophrenia and depression, in part by increasing trophic factors such as BDNF

Question 10

chlorpromazine

Answer 10

prototype phenothiazine derivative

typical antipsychotic

Question 11

haloperidol

Answer 11

typical antipsychotic

prototype of the butyrophenone derivatives

(2) Tend to be more potent and have fewer autonomic effects but greater EPS than phenothiazines

Question 12

what is the prototype atypical antipsychotic

Answer 12

clozapine

Question 13

MOA of atypical antipsychotics

Answer 13

(4) Common pharmacologic attribute is that they exhibit greater effects at 5-HT2A receptors than at D2 receptors resulting in dissociation of EPS and antipsychotic efficacy
(5) Most are partial agonists of 5-HT1A receptors, which is synergistic with 5-HT2A receptor antagonism

Question 14

pharmacokinetics of most of most of the antipsychotics

Answer 14

i) Most are readily but incompletely absorbed and undergo significant first-pass metabolism
ii) Most are highly lipid soluble and protein bound

iii) Generally have a much longer clinical duration of action than would be estimated from their plasma half-lives (weeks to months after last dose depending on formulation)
vii) Metabolism of most antipsychotics is catalyzed by cytochrome P450 enzymes; drug-drug interactions should be considered when combining antipsychotic drugs (see below)

Question 15

clozapine discontinuation

Answer 15

iv) Discontinuation is generally well-tolerated, except for clozapine, which can cause cholinergic rebound and withdrawl-emergent movement disorders; chlorpromazine and thioridazine also cause cholinergic rebound

Question 16

in pt’s who discontinue their antipsychotics, what is the amount of time to relapse usually

Answer 16

6 months

EXCEPT for clozapine where relapse is rapid and severe

Question 17

MOA of typical antipsychotics

Answer 17

block D2 receptors and increase cAMP

Question 18

MOA of atypical antipsychotics

Answer 18

iii) Atypical antipsychotics tend to block 5-HT2A receptors more potently than they inhibit D2 receptors

Question 19

what is the mesolimbic mesocortical pathway

Answer 19

involved in behavior and cognitive function; cell bodies in the ventral tegmental area send projections to the limbic system and neocortex; inhibition of dopaminergic activity in this pathway is thought to play a key role in antipsychotic effects

Question 20

nigrostriatal pathway involves what?

what happens with inhibition of this system

Answer 20

(2) Nigrostriatal pathway is involved in coordination of voluntary movement; neurons project from the substantia nigra to the dorsal striatum (caudate/putamen); inhibition of dopaminergic activity in this pathway causes EPS

Question 21

tuberoinfundibular system

Answer 21

(3) Tuberoinfundibular system regulates prolactin release (dopamine is inhibitory); arcuate nucleus and periventricular neurons project to the hypothalamus and posterior pituitary; hyperprolactinemia can be a side effect of the older antipsychotics resulting from inhibition of this pathway (see “Adverse Effects” below)

Question 22

D1 like receptors (D1 and D5)

activation?
location?

Answer 22

increase cAMP via activation of Gs-coupled activation of adenylyl cyclase;

D1 receptors are mainly located in the putamen, nucleus accumbens, olfactory tubercle, and cortex;

D5 receptors are primarily localized in the hippocampus and hypothalamus

Question 23

D2 like receptors (D2, 3, 4)

Answer 23

decrease cAMP via Gi and inhibit Ca channels, open K channels

D2 receptors are found both pre- and post-synaptically in the caudate-putamen, nucleus accumbens, and olfactory tubercle

Question 24

which dopamine receptors are shown to play a role in the action of antipsychotics

Answer 24

(4) D2 receptors are the only dopamine receptors shown to play a role in the action of antipsychotics; selective antagonists of D1, D3, and D4 receptors have been extensively tested without producing evidence of antipsychotic action

Question 25

what percent occupancy of striatal D2 receptors by TYPICAL antipsychotics must be achieved to have antipsychotic efficacy what percent for EPS symptoms

Answer 25

60% EPS is produced when occupancy is ≥ 80%

Question 26

atypical antipscyhotics must have what percent occupancy of D2 receptors to be efficient

Answer 26

Atypical antipsychotic agents are effective at lower D2 receptor occupancy levels (30-50%), likely because of their concurrent high occupancy of 5-HT2A receptors

Question 27

primary use of antipscyhotics

Answer 27

schizophrenia ii) Also useful in management of other psychotic disorders including acute mania, bipolar disorder, schizoaffective disorders, behavioral disturbances in dementias, behavioral disturbances in children and adolescents, and disorders associated with problems of impulse control

Question 28

what are some non psychiatric uses of antipsychotics

Answer 28

(1) Antiemesis (due to dopamine receptor blockade in the medulla and stomach): Metoclopramide (Reglan), Prochlorperazine (Compazine), Chlorpromazine (Thorazin), Promethazine (Phenergan), Trimethobenzamide (Tigan) (2) Neuroleptanesthesia (analgesia & amnesia): Droperidol (a butyrophenone D2 blocker) + fentanyl + nitrous oxide (3) Low doses of some antipsychotics, particularly quetiapine, are commonly, but mistakenly prescribed to promote sleep onset and maintenance; there are safer sleep medications and these drug are not FDA-approved for sleep

Question 29

what are the advantages of the new atypical antipsychotics

Answer 29

ii) The major advantage of these newer agents is their much lower tendency to cause the severe extrapyramidal symptoms and tardive dyskinesia associated with the typical antipsychotics iii) Atypical antipsychotics have been shown in some studies to be more effective than older drugs for treating negative symptoms

Question 30

which two drugs are the exception to the statement that all antipsychs are equally effective for reducing psychosis

Answer 30

i) Broadly, all the antipsychotics, except clozapine and olanzapine, are considered equally effective for reducing psychosis; 30-50% of patients refractory to standard doses of other antipsychotics respond to clozapine or high-dose olanzapine

Question 31

ADR's of clozapine and what pt's is it used in

Answer 31

iv) Because of its potential serious side effects (agranulocytosis, myocarditis), clozapine is generally reserved for use with patients who have become refractory to high doses of other agents or who have made life-threatening suicide attempts

Question 32

how long does it take for antipscyh's to start working

Answer 32

v) Psychotic symptoms can improve within 1 week; treatment for 16-20 weeks is often required before full effect is observed; the drugs are usually tried for at least 4-6 weeks or longer; maintenance therapy may last a lifetime; these drugs are not “habit forming”

Question 33

is polypharmacys in psychotic treatment ok?

Answer 33

i) Polypharmacy (treatment with more than one drug), is the norm for treatment of psychotic disorders, as it is often difficult to fully control symptoms with one medication alone

Question 34

what are some behavioral effects of older (typical) antipsychs

Answer 34

anhedonia- inability to experience pleasure akinesia toxic confusional states (high doses) sedatino

Question 35

what are some side effects of the high potency typical pscyh meds (haloperidol)

Answer 35

HIgh EPS

Question 36

what are some side effects of the low potency psych meds (chlorpromazine)

Answer 36

cause lots of nonspecific side effects -orthostatic hypotension male sexual dysfunction (alpha blockade) constipation, dry mouth, urinary retention (treat with antimuscarinic - benztropine or benadryl antihistamine ) sedation

Question 37

what are some early onset and reversible Extrapyrimidal side effects

Answer 37

dystonia - involuntary contraction of face, neck, tongue, EOM's - responds to anticholinergics - peak at 1 week parkinsonism - akinesia (2 weeks), muscle rigidity (3 weeks), tremor 6 weeks, shuffling gait akathisia - motor restlessness and urge to move give benzodiazepine -peak at 10 weeks

Question 38

what are some late onset and irreversible extrapyramidal side effects of antipsychs

Answer 38

tardive dyskinesia - involuntary repetitive movements (tongue, face, body) - due to supersensitivity of dopamine receptors worsened by anticholinergics

Question 39

which agents have the lowest risk for tardive dyskinesia

Answer 39

quetiapine or clozapine

Question 40

why does weight gain occur with antipsychs

Answer 40

possibly combined H1 and 5 HT2 blockade

Question 41

what happens with sexual function with antipsychs

Answer 41

Orthostatic hypotension, impotence, failure to ejaculate, sedation, dizziness due to alpha block

Question 42

which antipsych meds have significant affinity for muscarinic cholinergic receptors and alpha receptors and what happens when bound?

Answer 42

Older typical antipsychotics have significant affinity for muscarinic cholinergic and α1-adrenergic receptors (as well as histamine H1 and 5-HT2 receptors). Blockade of these receptors can lead to anti-parasympathetic (anti-muscarinic) side effects such as loss of accommodation, dry mouth, difficulty urinating, and constipation and anti-α-adrenergic side effects such as orthostatic hypotension, dizziness, sedation, impotence, and failure to ejaculate. Patients who present with these symptoms should be switched to a newer atypical agent.

Question 43

what are two big metabolic/endocrine effects of antipsychs

Answer 43

weight gain -hyperglycemia hyperprolactinemia

Question 44

which drugs have the highest potential for causing weight gain lowest risk?

Answer 44

clozapine and olanzapine Lowest risk: Aripiprazole, Lurasidone, Ziprasidone

Question 45

what are complications of weight gain with antipsychs

Answer 45

(1) Weight gain is very common, especially with clozapine and olanzapine and requires monitoring food intake, BMI, and fasting blood sugar and lipids. Hyperglycemia may develop, can be serious (ketoacidosis) and definitely complicates pre-existing diabetes. Whether hyperglycemia is secondary to weight gain-associated insulin resistance or other potential mechanism is unknown. Hyperlipidemia can also be a problem.

Question 46

why does hyperprolactinemia occur and what are the complications which drugs cause this

Answer 46

(2) Hyperprolactinemia (due to loss of dopamine inhibition of prolactin secretion) can cause an amenorrhea-galactorrhea syndrome, infertility, and possibly osteoporosis in women; in men, this effect leads to infertility, loss of libido, impotence, and breast enlargement (gynecomastia). Most pronounced with older typical antipsychotics as well as risperidone and paliperidone. Atypical antipsychotics with reduced D2 antagonism, such as olanzapine, quetiapine, and aripiprazole, cause no or minimal increases in prolactin.

Question 47

which three atypicals have minimal or no increases in prolactin

Answer 47

Atypical antipsychotics with reduced D2 antagonism, such as olanzapine, quetiapine, and aripiprazole, cause no or minimal increases in prolactin.

Question 48

ADR's of clozapine

Answer 48

agranulocytosis - reversible - must get weekly blood counts for first 6 months and every 3 weeks after

Question 49

effects of antipsychs on CV system

Answer 49

vi) Cardiac Toxicity: Several antipsychotics can cause QT prolongation, leading to increased risk of sudden death; ECG monitoring can identify QT prolongation, but unknown whether this will identify patients at high risk for sudden death; other medications that prolong QT interval (e.g., antiarrhythmics and erythromycin) should be avoided in patients taking antipsychotics

Question 50

antipsychs' in pregnancy?

Answer 50

Atypical antipsychotics are preferred over conventional drugs if treatment is required during pregnancy. Most of these drugs are considered relatively safe during pregnancy, but definitive data are lacking. Most are Risk Category C [some animal studies show adverse effects; no controlled studies in humans].

Question 51

``` rigidity myoglobinuria autonomic instability hyperperpyrexia hypertension ```

Answer 51

neuroleptic malignant syndrome treatment includes dantrolene and dopamine agonists (bromocriptine) hyperthermia and stress leukocytosis may lead to misdiagnosis as an infection; onset over 1-3 days; can be treated with supportive care and physical cooling if body temperature becomes excessive;

Question 52

``` rigidity myoglobinuria autonomic instability hyperperpyrexia hypertension ```

Answer 52

neuroleptic malignant syndrome treatment includes dantrolene and dopamine agonists (bromocriptine) hyperthermia and stress leukocytosis may lead to misdiagnosis as an infection; onset over 1-3 days; can be treated with supportive care and physical cooling if body temperature becomes excessive;

Question 53

1. List the six major classes of drugs used to treat depression.

Answer 53

SSRI's Selective serotonin norepinephrine reuptake inhibitors (SNRI's) Tricyclic antidepressants (TCA's) 5HT2 antagonists tetracyclic and unicyclic agents Monoamine oxidase inhibitors (MAOI's)

Question 54

Citalopram

Answer 54

SSRI

Question 55

Escitalopram

Answer 55

SSRI

Question 56

Fluoxetine

Answer 56

SSRI

Question 57

Fluvoxamine

Answer 57

SSRI

Question 58

Paroxetine

Answer 58

SSRI

Question 59

Sertraline

Answer 59

SSRI

Question 60

Duloxetine

Answer 60

SNRI

Question 61

Venlafaxine

Answer 61

SNRI

Question 62

Amitriptyline

Answer 62

TCA

Question 63

Desipramine

Answer 63

TCA

Question 64

Imipramine

Answer 64

TCA

Question 65

Nortriptyline

Answer 65

TCA

Question 66

Trazodone

Answer 66

5HT 2 Antagonist

Question 67

Bupropion

Answer 67

Tetracyclic and Unicyclic Agent

Question 68

Mirtazapine

Answer 68

Tetracyclic and Unicyclic Agent

Question 69

Selegiline

Answer 69

Monoamine Oxidase Inhibitor (4) Selegiline is a selective irreversible MAO-B inhibitor at low doses (useful in Parkinson’s disease) and nonselective MAO-A/B inhibitor at higher doses (used to treat refractory depression)

Question 70

what is the depression monoamine hypothesis

Answer 70

i) Depression is caused by a decrease in biogenic amines (primarily NE and 5-HT, but also DA); excess biogenic amines results in mania and psychotic states ii) All currently available antidepressant drugs are classified as having as their primary mechanism of actions on the metabolism, reuptake, or selective receptor antagonism of serotonin, norepinephrine, or both iii) Depletion of biogenic amines with reserpine, which blocks vesicular uptake of monoamines and depletes their concentration in nerve endings, can induce depression in normal individuals iv) LSD is a 5-HT2A receptor agonist that causes hallucinations and altered mental states v) Anti-adrenergic drugs can induce depression

Question 71

Receptor hypothesis of depression

Answer 71

i) Some antidepressants decrease NE and/or 5-HT receptor density in particular brain regions or decrease the sensitivity of these receptors to stimulation ii) Antidepressants may take 1-4 weeks to produce any improvement and 6-8 weeks to achieve substantial benefit; The acute pharmacological effects of these drugs on neurotransmitter levels and subsequent receptor activation are immediate (minutes) iii) This lag in onset of clinical efficacy implies that dynamic changes in neural circuits must occur before benefits can be realized; This probably involves regulation of receptor signaling, cellular sensitivity to signals, and trophic factor-induced changes in neuronal plasticity

Question 72

what is the hypothesis of depression that involves brain-derived neurotrophic factor (BDNF)

Answer 72

BDNF), a critical growth factor involved with neurogenesis and neural plasticity, as a key modulator of mood and depression (1) Depression is associated with a drop in BDNF levels; Antidepressants are associated with increased BDNF levels with chronic administration (2) Electroconvulsive therapy also stimulates BDNF production in animal models (3) Synthesis of neurotrophic factors has been proposed as an explanation for the delay in clinical efficacy of antidepressants; appreciable protein synthesis of BDNF typically takes 2 weeks or longer and coincides with the clinical course of antidepressant treatment

Question 73

what endocrine problems are associated with depression

Answer 73

A number of hormonal abnormalities are associated with depression including changes in the hypothalamic-pituitary-adrenal (HPA) axis, thryoid dysregulation, and sex steriod deficiencies

Question 74

SSRI's MOA

Answer 74

i) Selective Serotonin Reuptake Inhibitors (SSRIs): Allosterically inhibit the serotonin transporter (SERT) effectively increasing the concentration of serotonin in the synaptic cleft; about 80% of SERT activity is blocked at therapeutic doses; downregulation of postsynaptic 5-HT2A receptor density has been proposed as an adaptive process provoked by chronic administration of SSRIs

Question 75

TCA's

Answer 75

Both classes inhibit SERT and NET, the norepinephrine reuptake transporter, effectively increasing the concentration of both neurotransmitters in the synaptic cleft (1) The affinity of most SNRIs tends to be greater for SERT than for NET (2) Different TCAs have different relative affinities for either NET or SERT (3) Many TCAs also exhibit high affinity for muscarinic receptors, H1 histamine receptors, and α-adrenergic receptors, which account for many of the side effects of these drugs

Question 76

SNRI's

Answer 76

Both classes inhibit SERT and NET, the norepinephrine reuptake transporter, effectively increasing the concentration of both neurotransmitters in the synaptic cleft (1) The affinity of most SNRIs tends to be greater for SERT than for NET (2) Different TCAs have different relative affinities for either NET or SERT (4) SNRIs differ from TCAs in that they do not have high affinity for adrenergic, cholinergic, or histamine receptors resulting in more favorable side effect profiles

Question 77

5 HT 2 antagonists isn't this counterintuitive?

Answer 77

act via antagonism of 5-HT2A receptors (1) It is counterintuitive how antagonism of a postsynaptic 5-HT receptor can enhance monoamine tone; nevertheless, both animal and human studies have shown that 5-HT2A receptor inhibition is associated with substantial antianxiety, antipsychotic, and antidepressant effects (2) Deceased suicidal and otherwise depressed patients have had more 5-HT2A receptors than normal patients, suggesting that postsynaptic 5-HT2A overdensity is involved in the pathogenesis of depression

Question 78

MOA of bupriopion

Answer 78

The mechanism of action is incompletely understood; a selective inhibitor of the dopamine transporter (DAT) and stimulates presynaptic release of NE and DA; virtually no direct effect on serotonin reuptake or receptors

Question 79

Monoamine oxidase inhibitors

Answer 79

Monoamine oxidase (MAO) is mitochondrial enzyme that metabolizes monoamines to inactive metabolites (1) Two major enzyme isoforms: MAO-A and MAO-B (2) MAO-A is primarily responsible for metabolism of NE and 5-HT; Tyramine (a naturally occurring monoamine found in a variety of foods) is metabolized by MAO-A and MAO-B (see “Adverse Effects” below); Dopamine is metabolized by both isoenzyme forms (3) MAOIs cause accumulation of NE, 5-HT, and/or DA in vesicular storage in nerve endings and enhance neurotransmitter concentrations in the synaptic cleft

Question 80

Indications for use of antidepressants

Answer 80

``` Depression Anxiety pain disorders Premenstrual dysphoric disorder smoking cessation eating disorders- bulimia NOT anorexia ``` Others include insomnia, headache, pruitis

Question 81

which pt's should be considered for long term maintenance antidepressants

Answer 81

(7) Patients should be considered for long-term maintenance (years) treatment if they have had ≥2 serious MDD episodes in the previous 5 years or ≥3 episodes in a lifetime

Question 82

what agents are used for premenstrual dysphoric disorder

Answer 82

fluoxetine and sertraline (SSRI's) (2) Treating for 2 weeks out of the month during the luteal phase may be as effective as continuous treatment

Question 83

which agent is used for smoking cessation

Answer 83

v) Smoking Cessation: Bupropion reduces the urge to smoke, reduces the number of mood swings, and reduces the amount of weight gain experienced by patients withdrawing from nicotine dependence; the mechanism of action for this application is unknown

Question 84

what agents are possibly used for pruitis

Answer 84

TCA's such as doxepin b/c of antihistamine effects

Question 85

often times what must be done to find the right drug

Answer 85

trial and error

Question 86

most commonly prescribed first-line agents in the treatment of MDD and anxiety; they have fewer antimuscarinic side effects and are less cardiotoxic in overdose

Answer 86

SSRI's vii) SNRIs, bupropion, and mirtazapine are also reasonable first-line agents for MDD

Question 87

in what pt's is bupropion useful for

Answer 87

viii) Bupropion is a useful alternative for treating depression in patients who cannot tolerate the sexual dysfunction, weight gain, and sedation that may occur with other antidepressants, but generally is not effective for treatment of anxiety ix) Bupropion, and less frequently mirtazapine, is commonly combined with other antidepressants to augment therapeutic response

Question 88

CAs and MAOIs are relegated to second- or third-line treatments for MDD why ?

Answer 88

they are potentially lethal in overdose, require titration to achieve therapeutic dose, have serious drug interactions, and have many adverse effects; However, these drugs remain valuable alternatives for patients with moderate to severe depression who do not respond to an SSRI or SNRI

Question 89

what is a major concern of all antidepressants (ADR)

Answer 89

suicidality (1) All antidepressants carry a warning of increased suicidality (suicidal ideation and gestures, but not completion) in patients under age 25; there is no increased risk or reduced risk in those over age 25 (2) The benefits of antidepressant use seem to outweigh the risks; the absence of treatment of a major depressive episode in all age groups is an important risk factor in completed suicides

Question 90

what are the ADR's of SSRI's

Answer 90

(2) Gastrointestinal side effects such as nausea, vomiting, upset stomach, and constipation are quite common; these effects may diminish after the first week of treatment (3) Diminished sexual function, loss of libido, delayed orgasm, diminished arousal are common; these effects often persist for the duration of therapy (4) Headaches, insomnia or hypersomnia, and weight gain (1) Minor sedation and antimuscarinic side effects may occur but are usually less frequent and less troublesome than with the TCAs serotonin syndrome with use of MAOI's (5) Discontinuation syndrome, causing dizziness and parethesia, can occur after sudden discontinuation of agents with short half-lives (e.g., paroxetine and sertraline)

Question 91

Contraindications for SSRI's

Answer 91

(7) Contraindications: SSRIs should be discontinued or avoided in patients displaying active manic symptoms; paroxetine is contraindicated in pregnant patients

Question 92

ADR's of SNRI's

Answer 92

(1) SNRIs have the serotonergic side effects exhibited by SSRIs but also have noradrenergic side effects including insomnia, anxiety, and agitation increase in BP most common (3) Venlafaxine may increase the risk of bleeding via an antiplatelet aggregation effect; this agent is also more frequently associated with cardiac toxicity in overdose relative to other SNRIs or SSRIs

Question 93

ADR's of TCA's

Answer 93

(1) Anticholinergic effects including drowsiness, dry mouth, constipation, urinary retention, blurred vision, and confusion (2) Orthostatic hypotension due to α-adrenergic receptor blockade, especially in the elderly (3) Weight gain and sedation due to H1 histamine receptor antagonism (4) Cardiotoxicity, arrhythmias and heart block; Convulsions; hepatic dysfunction; Hyponatremia, which may lead to confusion in the elderly (5) Hematological abnormalities (e.g., leucopenia, thrombocytopenia and agranulocytosis) (6) Sexual side effects similar to those seen with SSRIs (7) Imipramine and amitriptyline exhibit marked antimuscarinic and cardiac side effects (8) Discontinuation syndrome like that seen with SSRIs

Question 94

Contraindications of TCA"

Answer 94

(9) Contraindications: Arrhythmias, recent myocardial infarction, liver disease, glaucoma, mania

Question 95

ADR's of 5 HT2 antagonists

Answer 95

(1) Most common adverse effects are sedation and gastrointestinal disturbances (2) Sexual side effects are uncommon (3) Orthostatic hypotension due to α-adrenergic receptor blockade (4) Nefazodone carries a black box warning for hepatotoxicity and potentially lethal hepatic failure; it is still available generically but rarely prescribed

Question 96

ADR's of bupriopion (Tetracyclics and unicyclics)

Answer 96

(1) Bupropion has CNS activating properties, it is occasionally associated with agitation, insomnia, and anorexia (2) Bupropion and mirtazapine are two of the few antidepressants not commonly associated with sexual side effects

Question 97

MAOI's ADR's

Answer 97

(1) Orthostatic hypotension and weight gain (2) Highest rates of sexual side effects of all the antidepressants; anorgasmia is common (3) May cause dangerous interactions with certain tyramine-containing foods and with serotonergic drugs (see “Drug Interactions” below) (4) Sudden discontinuation syndrome manifested in delirium-like presentation with psychosis, excitement, and confusion

Question 98

Overdose of TCA's

Answer 98

i) TCAs are the most toxic of all the antidepressants, particularly amitriptyline, especially when taken in overdose, which can lead to arrhythmias, altered mental status, and seizures ii) 1 in 40 patients who overdose on a TCA will die; serious complications tend to occur within 12h of ingestion; gastric decontamination is helpful for up to about 8h post ingestion

Question 99

MAOI overdose

Answer 99

iii) MAOIs are also potentially lethal in overdose producing autonomic instability, hyperadrenergic symptoms, psychotic symptoms, confusion, delirium, fever, and seizures

Question 100

St. John's wort

Answer 100

(2) St. John’s wort, an herbal medicine used to treat depression, induces CYP450 enzymes

Question 101

what is serotonin syndrome

Answer 101

(a) Life-threatening pharmacodynamic interaction of MAOIs with serotonergic agents including SSRIs, SNRIs, most TCAs, and some analgesics (b) Thought to be caused by overstimulation of 5-HT receptors in the central gray nuclei and the medulla (c) Symptoms range from mild to lethal: (i) Cognitive: delirium, agitation, coma (ii) Autonomic: hypertension, tachycardia, hyperthermia, diaphoreses (iii) Somatic: myoclonus, hyperreflexia, tremor

Question 102

how can serotonin syndrome be prevented and what is the treatment

Answer 102

(d) When a patient is switched from an SSRI (or other serotonergic agent) to an MAOI (or vice versa), the current therapy should be discontinued for at least 2 weeks (6 weeks for fluoxetine due to longer half-life) prior to initiation of the new therapy (e) Treatment: withdraw the offending drug, sedation with benzodiazepines, paralysis, intubation, and ventilation; consider 5-HT2 block with cyproheptadine or chlorpromazine

Question 103

what is the tyramine effect

Answer 103

(a) Tyramine is a naturally occurring monoamine compound that acts as a catecholamine releasing agent (b) In foods, it is often produced by decarboxylation of tyrosine during fermentation or decay (c) Foods containing considerable amounts of tyramine include foods that are pickled, aged, smoked, marinated, or meats that are potentially spoiled; chocolate; alcoholic beverages; and fermented foods, such as most cheeses, etc. (d) Tyramine is normally metabolized by MAO; when large amounts of tyramine are ingested and MAOIs reduce metabolism, hypertensive crisis can occur – tyramine induces NE release from peripheral nerve terminals and subsequent dramatic (and potentially fatal) rise in heart rate and blood pressure

Question 104

D1 like receptors (D1 and D5) activation? location?

Answer 104

increase cAMP via activation of Gs-coupled activation of adenylyl cyclase --> excitatory D1 receptors are mainly located in the putamen, nucleus accumbens, olfactory tubercle, and cortex; D5 receptors are primarily localized in the hippocampus and hypothalamus

Question 105

D2 like receptors (D2, 3, 4)

Answer 105

decrease cAMP via Gi and inhibit Ca channels, open K channels D2 receptors are found both pre- and post-synaptically in the caudate-putamen, nucleus accumbens, and olfactory tubercle inhibitory these are responsible for the positive symptoms in schizophrenia

Question 106

what is the tyramine effect

Answer 106

(a) Tyramine is a naturally occurring monoamine compound that acts as a catecholamine releasing agent (b) In foods, it is often produced by decarboxylation of tyrosine during fermentation or decay (c) Foods containing considerable amounts of tyramine include foods that are pickled, aged, smoked, marinated, or meats that are potentially spoiled; chocolate; alcoholic beverages; and fermented foods, such as most cheeses, etc. (d) Tyramine is normally metabolized by MAO; when large amounts of tyramine are ingested and MAOIs reduce metabolism, hypertensive crisis can occur – tyramine induces NE release from peripheral nerve terminals and subsequent dramatic (and potentially fatal) rise in heart rate and blood pressure

Question 107

all five subtypes of dopamine receptors are what

Answer 107

metabotropic GPCR's

Question 108

all five subtypes of dopamine receptors are what

Answer 108

metabotropic GPCR's

Question 109

which drug has side effect of priapism

Answer 109

trazadone (5HT2 antagonists)

Question 110

what percentage of pt's achieve remission of depression with a single trial of 8-12 weeks

Answer 110

30-40 percent 70-80 achieve remission by switching to another agent or augmentation by addition of another drug

Question 111

what percentage of pt's achieve remission of depression with a single trial of 8-12 weeks

Answer 111

30-40 percent 70-80 achieve remission by switching to another agent or augmentation by addition of another drug

Question 112

Enuresis treatment

Answer 112

TCA's

Question 113

insomnia treatment using antidepressants

Answer 113

amitryptiline and trazodone