Kk&s Ch.36 Biological Therapies S To Bsm

Front 1

What drugs are selective serotonin-norepinephrine reuptake inhibitors?

Back 1

Venlafaxine(Effexor) and Duloxetine (Cymbalta)

Front 2

Venlafaxine indications?

Back 2

dep
GAD ... XR
Social Phobia ... XR
Panic Ds ... XR

Front 3

Duloxetine indications?

Back 3

Duloxetine is indicated for the treatment of depression, generalized anxiety disorder, and painful diabetic neuropathy and is awaiting the indication for stress urinary incontinence

Front 4

Duloxetine and Venlafaxine vs TCA's?

Back 4

Venlafaxine and duloxetine are not unique with respect to their dual action. Tricyclic and tetracyclic antidepressants (TCAs) also inhibit reuptake of norepinephrine and serotonin. TCAs, however, also possess numerous other receptor
properties, such as muscarinic, adrenergic, and histaminergic effects, and thus are not considered selective.

Front 5

What is the metabolite of venlafaxine calle?

Back 5

O-des-methyl-venlafaxine = ODV

Front 6

Venlafaxine metab?

Back 6

2d6

Front 7

Thus, inhibitors of this venlafaxine isozyme, such reduce the formation of ODV.

Back 7

as quinidine or paroxetine,

Front 8

Venlafaxine NT's activity and where does it have non-activity?

Back 8

Venlafaxine is a potent inhibitor of serotonin and norepinephrine reuptake and a weak inhibitor of dopamine reuptake

It does not have activity at muscarinic, nicotinic, histaminergic, opioid, or adrenergic receptors, and it is not active as a monoamine oxidase inhibitor (MAOI).

Front 9

Most common venlafaxine side fx?

Back 9

Overall, the most common adverse reactions are nausea, somnolence, dry mouth, dizziness, nervousness, constipation, asthenia, anxiety, anorexia, blurred vision, abnormal ejaculation or orgasm, erectile disturbances, and impotenc

Front 10

Venlafaxine vs SSRI's : which has more sweating?

Back 10

Venlafaxine, treated with terazosin

Front 11

Stopping venlafaxine sx?

Back 11

Abrupt discontinuation of venlafaxine use can produce a discontinuation syndrome consisting of dizziness, anxiety, nausea, somnolence, paresthesias, and insomnia. Therefore, venlafaxine use should be tapered gradually over 2 to 4 weeks

Front 12

Venlafaxine relationship to BP?

Back 12

Venlafaxine can cause an increase in blood pressure (BP) in some persons. Diastolic hypertension was seen more often in patients treated with doses of venlafaxine greater than 300 mg per day, a dose higher than needed in most patients

Front 13

Venlafaxine can cause ?, so patients with ? eye problem should be monitored during venlafaxine treatment.

Back 13

Venlafaxine can cause mydriasis, so patients with raised intraocular pressure or those at risk for acute narrow-angle glaucoma should be monitored during venlafaxine treatment.

Front 14

Venlafaxine and bleeding risk?

Back 14

As in the case of SSRIs, abnormal bleeding or ecchymosis may be associated with venlafaxine use, the result of serotonin-related impairment of platelet aggregation

Front 15

What decreases venlafaxine clearance?

Back 15

The pharmacokinetic dispositions of both venlafaxine and ODV are altered in patients with hepatic cirrhosis. Venlafaxine elimination half-life is prolonged by about 30 percent and clearance decreased by about 50 percent. ODV elimination half-life is also prolonged (by about 60 percent) and its clearance decreased by about 30 percent. In patients with more severe cirrhosis, there may be a 90 percent decrease in venlafaxine clearance. Dosage adjustment, thus, is necessary in patients with liver disease.

Front 16

Venlafaxine and pregnancy risk?

Back 16

Information concerning use of venlafaxine by pregnant and nursing women is not available at this time. Venlafaxine and ODV are excreted in human milk. Clinicians should carefully weigh the risks and benefits of venlafaxine use by pregnant and nursing women.

Front 17

enlafaxine Drug INtx?

Back 17

Cimetidine (incr)
Bupropion incr V
V can increase haloperidol
V and MAOI bad

Front 18

Venlafaxine upper dosage?

Back 18

Although the recommended upper dosage of the extended-release preparation (Effexor XR) is 225 mg per day, it is approved by the FDA for use at dosages up to 375 mg a day. The dosage of venlafaxine should be halved in persons with significantly diminished hepatic or renal function. If discontinued, venlafaxine use should be gradually tapered over 2 to 4 weeks to avoid withdrawal symptoms.

Front 19

Dosing of Venlafaxine , depression versus anxiety?

Back 19

In depressed persons, venlafaxine demonstrates a dose-response curve.

In anxiety, a dose-response effect has not been found. In addition, lower mean dosages are typically used, with most patients taking 75 to 150 mg per day.

Front 20

Duloxetine peak? t half; metab by?

Back 20

6 hours, with food to 10hours
12 hours
2D6 and 3a4

Front 21

Duloxetine indications?

Back 21

GAD, DEpresesion,
Neuropathic pain associated with diabetes

Duloxetine is currently awaiting approval as a treatment for stress urinary incontinence, the inability to voluntarily control bladder voiding, which is the most frequent type of incontinence in women.

Front 22

Duloxetine most common side effect?

Back 22

Nausea was the most common side effect leading to treatment discontinuation in clinical trials

Front 23

Duloxetine most common side fx?

Back 23

The most common adverse reactions are nausea, dry mouth, dizziness, constipation, fatigue, decreased appetite, anorexia, somnolence, and increased sweating

Front 24

Patients with? use should not be treated with duloxetine because of possible hepatic effects

Back 24

Patients with substantial alcohol use should not be treated with duloxetine because of possible hepatic effects

Front 25

Duloxetine dosing?

Back 25

The recommended therapeutic, and maximal, dosage is 60 mg per day.

The 20- and 30-mg doses are useful for either initial therapy or for twice-daily use as strategies to reduce side effects. In clinical trials, dosages of up to 120 mg per day were studied, but no consistent advantage in efficacy was noted at dosages higher than 60 mg per day.

Front 26

What is Des-Venlafaxine? indication?

Back 26

DVS is the salt form of the isolated major active metabolite of venlafaxine, developed as separated drug. Like venlafaxine, DVS is mechanistically an SNRI.

Depression and for the alleviation vasomotor symptoms (VMS) associated with menopause.

Front 27

The first selective serotonin reuptake inhibitor (SSRI), which was introduced in 1987, altered attitudes about pharmacologic treatment of depression

Back 27

, fluoxetine (Prozac)

Front 28

SSRI indications?

Back 28

not only depression, but obsessive-compulsive disorder (OCD), panic disorder, generalized anxiety disorder, premenstrual dysphoric disorder, social anxiety disorder, and eating disorders (Table 36.29-1). All SSRIs appear to be equally effective in the treatment of these disorders.

Front 29

SSRI with longest half life? how long?

Back 29

Fluoxetine has the longest half-life: 4 to 6 days; its active metabolite has a half-life of 7 to 9 days

Front 30

other long half life SSRI?

Back 30

sertraline
The half-life of sertraline is 26 hours, and its less active metabolite has a half-life of 3 to 5 days.

Front 31

Half life of citalopram, paroxetine, fluvoxamine?

Back 31

The half-lives of the other three, which do not have metabolites with significant pharmacologic activity, are 35 hours for citalopram, 27 to 32 hours for escitalopram, 21 hours for paroxetine, and 15 hours for fluvoxamine.

Front 32

Plasma binding to proteins: compare ssri's

Back 32

Differences in plasma protein binding percentages are also found among the SSRIs, with sertraline, fluoxetine, and paroxetine being the most highly bound and escitalopram being the least bound

Front 33

SSRI with most drug drug intx?

Back 33

Fluvoxamine is the most problematic of the drugs in this respect. It has a marked effect on several of the CYP enzymes. Examples of clinically significant interactions include fluvoxamine and theophylline (Theo-Dur) through CYP 1A2 interaction; fluvoxamine and clozapine (Clozaril) through CYP 1A2 inhibition; and fluvoxamine with alprazolam (Xanax) or clonazepam (Klonopin) through CYP 3A4 inhibition.

Front 34

Which SSRI's majorly block 2D6 and what is resulting problem?

Back 34

Fluoxetine and paroxetine also possess significant effects on the CYP 2D6 isozyme, which may interfere with the efficacy of opiate analogs, such as codeine and hydrocodone, by blocking the conversion of these agents to their active form. Thus, coadministration of fluoxetine and paroxetine with an opiate interferes with its analgesic effects.

Front 35

SSRI are the most selective inhibitors of serotonin reuptake

Back 35

Citalopram and escitalopram are the most selective inhibitors of serotonin reuptake

with very little inhibition of norepinephrine or dopamine reuptake and very low affinities for histamine H1, γ-aminobutyric acid (GABA), or benzodiazepine receptors.

Front 36

Fluoxetine unique receptor property?

Back 36

fluoxetine weakly inhibits norepinephrine reuptake and binds to 5-HT2C receptors

Front 37

Sertraline unique receptor property?

Back 37

sertraline weakly inhibits norepinephrine and dopamine reuptake

Front 38

Paroxetine unique receptor property?

Back 38

paroxetine has significant anticholinergic activity at higher dosages and binds to nitric oxide synthase

Front 39

A pharmacodynamic interaction appears to underlie the antidepressant effects of combined fluoxetine–olanzapine. When taken together, these drugs increase brain concentrations of

Back 39

norepinephrine

Front 40

Concomitant use of SSRIs and drugs in the triptan class (sumatriptan [Imitrex], naratriptan [Amerge], rizatriptan [Maxalt], and zolmitriptan [Zomig]) may result

Back 40

in a serious pharmacodynamic interaction, the development of a serotonin syndrome

Front 41

SSRI + triptan or what other drug give serotonin syndrome

Back 41

A similar reaction may occur when SSRIs are combined with tramadol

Front 42

In the United States, all SSRIs other than ? have been approved by the US Food and Drug Administration (FDA) for treatment of depression

Back 42

fluvoxamine

Front 43

Several studies have found that antidepressants with ??? produce higher rates of remission than SSRIs in head-to-head studies

Back 43

serotonin–norepinephrine activity, drugs such as the MAOIs, TCAs, venlafaxine, and mirtazapine,

Front 44

more than XX percent of people who respond poorly to one SSRI will respond favorably to another

Back 44

50%

Front 45

When should all patients be especially monitored?

Back 45

Thus, all depressed patients should be closely monitored during the period of maximal risk, the first few days and weeks they are taking SSRIs

Front 46

Rates of relapse of major depression during pregnancy among women who discontinue, attempt to discontinue, or modify their antidepressant regimen are ???

Back 46

extremely high. Rates range from 68 percent to 100 percent of patients.

Front 47

The impact of maternal depression on infant development is

Back 47

unknown.

Front 48

Congential malform relation to SSRI during preg?

Back 48

No increased risk is seen for major congenital malformations following exposure to SSRIs during pregnancy

Front 49

Fluoxetine non-risks during preg?

Back 49

Studies that have followed children into their early school years have failed to find any perinatal complications, congenital fetal anomalies, decreases in global intelligence quotient (IQ), language delays, or specific behavioral problems attributable to the use of fluoxetine during pregnancy.

Front 50

SSRI concerns in elderly?

Back 50

Paroxetine does have some anticholinergic activity, which may lead to constipation and worsening of cognition. SSRIs can produce subtle cognitive deficits, prolonged bleeding time, and hyponatremia, all of which may have an impact on the health of this population. SSRIs are effective in poststroke depression and dramatically reduce the symptom of crying.

Front 51

Studies of SSRIs in depressed children and adolescents have generally failed to demonstrate the efficacy of SSRIs. Only ? has FDA approval for use as an antidepressant in this population

Back 51

fluoxetine

Front 52

Which antidepressants indicated in pediatric OCD?

Back 52

Fluvoxamine and sertraline have also been approved for treatment of pediatric OCD (ages 6 to 17

Front 53

OCD and SSRI's recommended?

Back 53

Fluvoxamine, paroxetine, sertraline, and fluoxetine are indicated for treatment of OCD in persons over the age of 18 years

Front 54

About XX percent of persons with OCD begin to show symptoms in childhood or adolescence, and more than half of these respond favorably to medication.

Back 54

50%

Front 55

Patients who fail to obtain adequate relief of their OCD symptoms with an SSRI often benefit from the addition of a

Back 55

small dose of risperidone (Risperdal

Front 56

Other diagnoses now considered part of OCD spectrum that benefit from SSRI?

Back 56

This includes a number of conditions and symptoms characterized by nonsuicidal self-mutilation, such as trichotillomania, eyebrow-picking, nose-picking, nail-biting, compulsive picking of skin blemishes, and cutting. Patients with these behaviors benefit from treatment with SSRIs. Other spectrum disorders include compulsive gambling, compulsive shopping, hypochondriasis, and body dysmorphic disorder.

Front 57

SSRI? are indicated for treatment of panic disorder, with or without agoraphobia

Back 57

Paroxetine and sertraline are indicated for treatment of panic disorder, with or without agoraphobia.
Citalopram, fluvoxamine, and fluoxetine also can reduce spontaneous or induced panic attacks.

Because fluoxetine can initially heighten anxiety symptoms, persons with panic disorder must begin taking small dosages (5 mg a day) and raise the dosage slowly.

Front 58

SSRIs are effective agents in the treatment of social phobia. They reduce both symptoms and disability. The response rate is comparable to that seen with the the previous standard treatment

Back 58

MAOI phenelzine (Nardil),

Front 59

PTSD: SSRIs are associated with marked improvement of

Back 59

both intrusive and avoidant symptoms
not so much hyperarousal I guess

Front 60

SSRI? is indicated for treatment of bulimia, which is best done in the context of psychotherapy. Dosages of XX mg a day are significantly more effective than XX mg a day.

Back 60

Fluoxetine is indicated for treatment of bulimia, which is best done in the context of psychotherapy. Dosages of 60 mg a day are significantly more effective than 20 mg a day.

Front 61

Fluoxetine role in Anorexia?

Back 61

Fluoxetine has been used in inpatient treatment of anorexia nervosa to attempt to control comorbid mood disturbances and obsessive-compulsive symptoms. At least two careful studies, one of 7 months and one of 24 months, however, failed to find that fluoxetine affected the overall outcome and the maintenance of weight. Effective treatments for anorexia include cognitive–behavioral, interpersonal, psychodynamic, and family therapies in addition to a trial with SSRIs.

Front 62

Fluoxetine and obesity?

Back 62

Fluoxetine, in combination with a behavioral program, has been shown to be only modestly beneficial for weight loss.

A significant percentage of all persons who take SSRIs, including fluoxetine, lose weight initially, but later may gain weight.

Front 63

SSRI? have been reported to reduce the symptoms of premenstrual dysphoric disorder.

Back 63

Sertraline, paroxetine, fluoxetine, and fluvoxamine have been reported to reduce the symptoms of premenstrual dysphoric disorder.

An additional observation of unclear significance was that fluoxetine was associated with changing the duration of the menstrual period by more than 4 days, either lengthening or shortening. The effects of SSRIs on menstrual cycle length are mostly unknown and may warrant careful monitoring in women of reproductive age.

Front 64

Off-label uses SSRI's

Back 64

Premature Ejaculation,
Paraphilias,
Autism,
Sertraline and fluvoxamine have been shown in controlled and open-label trials to mitigate aggressiveness, self-injurious behavior, repetitive behaviors, some degree of language delay, and, rarely, lack of social relatedness in adults with autistic spectrum disorders. Fluoxetine has been reported to be effective for features of autism in children, adolescents, and adults.

Front 65

SSRI's and sexual dysfxn?

Back 65

All SSRIs cause sexual dysfunction, and it is the most common adverse effect of SSRIs associated with long-term treatment. It has an estimated incidence of between 50 percent and 80 percent.

The most common complaints are anorgasmia, inhibited orgasm, and decreased libido

Front 66

SSRI sexual dysfxn tx?

Back 66

Strategies to counteract SSRI-induced sexual dysfunction are too numerous to mention, and none has been proved to be very effective. Some reports suggest decreasing the dosage or adding bupropion. Reports have described successful treatment of SSRI-induced sexual dysfunction with agents such as sildenafil (Viagra), which are used to treat erectile dysfunction.

Ultimately, patients may need to be switched to antidepressants that do not interfere with sexual functioning, drugs such as mirtazapine or bupropion

Front 67

SSRI gi Gastrointestinal (GI) side effects, which are very common, are mediated largely through effects on the receptor

Back 67

serotonin 5HT3

Front 68

SSRI? produce the most intense GI symptoms

Back 68

Sertraline and fluvoxamine produce the most intense GI symptoms

Front 69

Up to ?of persons taking SSRIs will gain weight, sometimes more than 20 pounds

Back 69

Up to one third of persons taking SSRIs will gain weight, sometimes more than 20 pounds

Front 70

? is associated with more frequent and more pronounced weight gain than the other SSRIs, especially among young women.

Back 70

Paroxetine is associated with more frequent and more pronounced weight gain than the other SSRIs, especially among young women.

Front 71

The incidence of headache in SSRI trials was ? percentage point higher than the placebo rate. SSRI most likely to cause headache.

Back 71

1%
Fluoxetine is the SSRI most likely to cause headache.

Front 72

Increased anxiety is caused considerably less frequently by , which may be a better choice if sedation is desired, as in mixed anxiety and depressive disorders

Back 72

paroxetine or escitalopram

Front 73

SSRI's and sleep?

Back 73

The major effect SSRIs exert in the area of insomnia and sedation is improved sleep resulting from treatment of depression and anxiety

Front 74

As many as ? of persons taking SSRIs, however, note either trouble sleeping or excessive somnolence or overwhelming fatigue

Back 74

As many as one fourth of persons taking SSRIs, however, note either trouble sleeping or excessive somnolence or overwhelming fatigue

Front 75

? is the most SSRI likely to cause insomnia, for which reason it is often taken in the morning

Back 75

Fluoxetine is the most SSRI likely to cause insomnia, for which reason it is often taken in the morning

Front 76

? and ? are about equally likely to cause insomnia as somnolence, and ? and, especially, ? often cause somnolence

Back 76

Sertraline and fluvoxamine are about equally likely to cause insomnia as somnolence, and citalopram and, especially, paroxetine often cause somnolence

Front 77

Escitalopram is ? likely to interfere with sleep than its isomer, citalopram

Back 77

Escitalopram is more likely to interfere with sleep than its isomer, citalopram

Front 78

SSRI-induced insomnia can be treated with?

Back 78

SSRI-induced insomnia can be treated with benzodiazepines, trazodone (Desyrel) (clinicians must explain the risk of priapism), or other sedating medicines.

Front 79

SSRI other side fx?

Back 79

Emotional blunting, vivid dreams, yawning, seizures in up to 0.2%, EPS, Anticholinergic, Hematologic, Lytes, Endocrine, Serotonin Syndrome, Allergies

Front 80

Close clinical observation of patients taking SSRIs reveals an increase in yawning. This side effect is not a reflection of fatigue or of poor nocturnal sleep but is the result of SSRI effects on the

Back 80

hypothalamus.

Front 81

Can SSRI's cause EPS?

Back 81

Yes

Front 82

SSRI relation to hematology?

Back 82

The SSRIs can cause functional impairment of platelet aggregation, but not a reduction in platelet number. This is manifested by easy bruising and excessive or prolonged bleeding. When patients exhibit these signs, a test for bleeding time should be performed. Special monitoring is suggested when patients use SSRIs in conjunction with anticoagulants or aspirin.

Front 83

The SSRIs can acutely ? glucose concentrations

Back 83

decrease

Front 84

SSRI and lytes?

Back 84

Rare cases of SSRI-associated hyponatremia and the secretion of inappropriate antidiuretic hormone (SIADH) have been seen in patients treated with diuretics who are also water deprived

Front 85

The SSRIs can ? prolactin levels and cause mammoplasia and galactorrhea in both men and women

Back 85

decrease

Front 86

Concurrent administration of an SSRI with an ?, ?, or ? can raise plasma serotonin concentrations to toxic levels, producing a constellation of symptoms called the serotonin syndrome

Back 86

Concurrent administration of an SSRI with an MAOI, L-tryptophan, or lithium can raise plasma serotonin concentrations to toxic levels, producing a constellation of symptoms called the serotonin syndrome

Front 87

This serious and possibly fatal syndrome of serotonin overstimulation is composed, in order of appearance as the condition worsens, of (1 to 5)

Back 87

(1) diarrhea; (2) restlessness; (3) extreme agitation, hyperreflexia, and autonomic instability with possible rapid fluctuations in vital signs; (4) myoclonus, seizures, hyperthermia, uncontrollable shivering, and rigidity; and (5) delirium, coma, status epilepticus, cardiovascular collapse, and death.

Front 88

Some patients experience sweating while being treated with SSRIs. The sweating is unrelated to ambient temperature. Nocturnal sweating may drench bed sheets and require a change of night clothes. ?, 1 or 2 mg per day, is often dramatically effective in counteracting sweating

Back 88

Terazosin

Front 89

Which SSRI have worst withdrawal?

Back 89

shorter half-life drugs - paroxetine and fluvoxamine

Front 90

SSRI withdrawal sx? how much treatment is required, how long for it to resolve?

Back 90

withdrawal syndrome that can include dizziness, weakness, nausea, headache, rebound depression, anxiety, insomnia, poor concentration, upper respiratory symptoms, paresthesias, and migraine-like symptoms. It usually does not appear until after at least 6 weeks of treatment and usually resolves spontaneously in 3 week

Front 91

The combination of lithium and any serotonergic drug should be used with caution because of the possibility of

Back 91

precipitating seizures

Front 92

SSRIs, particularly fluvoxamine, should not be used with ? because it raises ? concentrations and seizures may result.

Back 92

CLOZAPINE

Front 93

Fluoxetine may slow the metabolism of

Back 93

carbamazepine (Tegretol), antineoplastic agents, diazepam (Valium), and phenytoin (Dilantin)

Front 94

Fluoxetine has ? interactions with warfarin (Coumadin), tolbutamide (Orinase), or chlorothiazide (Diuril).

Back 94

NO

Front 95

? may displace warfarin from plasma proteins and may increase the prothrombin time.

Back 95

Sertraline

Front 96

? has a higher risk for drug interactions than does either fluoxetine or sertraline because it is a more potent inhibitor of the CYP 2D6 enzyme

Back 96

Paroxetine

Front 97

Paroxetin relation to warfarin?

Back 97

Paroxetine can increase the anticoagulant effect of warfarin.

Front 98

Paroxetine and other drug interactins?

Back 98

Coadministration of paroxetine and tramadol (Ultram) may precipitate a serotonin syndrome in elderly persons.

Paroxetine has a higher risk for drug interactions than does either fluoxetine or sertraline because it is a more potent inhibitor of the CYP 2D6 enzyme. Cimetidine (Tagamet) can increase the concentration of sertraline and paroxetine, and phenobarbital (Luminal) and phenytoin can decrease the concentration of paroxetine. Because of the potential for interference with the CYP 2D6 enzyme, the coadministration of paroxetine with other antidepressants, phenothiazines, and antiarrhythmic drugs should be undertaken with caution

Front 99

Among the SSRIs, ? appears to present the most risk for drug–drug interactions

Back 99

FLUVOXAMINE

Front 100

Fluvoxamine is metabolized by the enzyme CYP ?, which may be inhibited by drug?

Back 100

Fluvoxamine is metabolized by the
enzyme CYP 3A4, which may be inhibited by ketoconazole (Nizoral).

Front 101

Fluvoxamine can increase the half-life of ?

Back 101

Fluvoxamine can increase the half-life of alprazolam (Xanax), triazolam (Halcion), and diazepam, and it should not be coadministered with these agents

Front 102

Fluvoxamine can increase ? levels threefold and ? levels twofold, with important clinical consequences; thus, the serum levels of the latter drugs should be closely monitored and the doses adjusted accordingly.

Back 102

Fluvoxamine can increase theophylline (Slo-bid, Theo-Dur) levels threefold and warfarin levels twofold, with important clinical consequences; thus, the serum levels of the latter drugs should be closely monitored and the doses adjusted accordingly.

Front 103

Fluvoxamine raises concentrations and may increase the activity of

Back 103

clozapine, carbamazepine, methadone (Dolophine, Methadose), propranolol (Inderal), and diltiazem (Cardizem). Fluvoxamine has no significant interactions with lorazepam (Ativan) or digoxin (Lanoxin).

Front 104

Citalopram and CYP enzymes ?

Back 104

Citalopram is not a potent inhibitor of any CYP enzymes.

Front 105

Concurrent administration of ? increases concentrations of citalopram by about 40 percent.

Back 105

cimetidine

Front 106

Escitalopram is a moderate inhibitor of ? and has been shown to significantly raise ? and ? concentrations.

Back 106

Escitalopram is a moderate inhibitor of CYP 2D6 and has been shown to significantly raise desipramine and metoprolol concentrations.

Front 107

Fluoxetine max dose?

Back 107

80mg

Front 108

Usual depression dosage?

Back 108

A 20 mg dose is often as effective as higher doses for treating depression.

Front 109

Sertraline dosing?

Back 109

For the initial treatment of depression, sertraline use should be initiated with a dosage of 50 mg once daily. To limit the GI effects, some clinicians begin at 25 mg a day and increase to 50 mg a day after 3 weeks. Patients who do not respond after 1 to 3 weeks may benefit from dosage increases of 50 mg every week up to a maximum of 200 mg, given once daily

Front 110

Paroxetine dosing?

Back 110

Paroxetine use for the treatment of depression is usually initiated at a dosage of 10 or 20 mg a day. An increase in the dosage should be considered when an adequate response is not seen in 1 to 3 weeks. At that point, the clinician can initiate upward dose titration in 10-mg increments at weekly intervals to a maximum of 50 mg a day.

A delayed-release formulation of paroxetine, (Paxil CR), is available in 12.5-, 25-, and 37.5-mg tablets.

Front 111

Fluvoxamine dosing?

Back 111

The effective daily dosage range is 50 to 300 mg a day. A usual starting dosage is 50 mg once a day at bedtime for the first week, after which the dosage can be adjusted according to the adverse effects and clinical response. Dosages above 100 mg a day can be divided into twice-daily dosing. A temporary dosage reduction or slower upward titration may be necessary if nausea develops over the first 2 weeks of therapy. Fluvoxamine can also be administered as a single evening dose to minimize its adverse effects. Tablets should be swallowed with food without chewing the tablet. Abrupt discontinuation of fluvoxamine can cause a discontinuation syndrome.

Front 112

Citalopram dosing?

Back 112

The usual starting dosage is 20 mg a day for the first week, after which it usually is increased to 40 mg a day. For elderly persons or persons with hepatic impairment, 20 mg a day is recommended, with an increase to 40 mg a day only with no response at 20 mg a day. Tablets should be taken once daily, in either the morning or the evening, with or without food.

Front 113

Escitalopram dosing? max?

Back 113

Escitalopram is available as 10- and 20-mg scored tablets, as well as an oral solution at a concentration of 5 mg/5 mL. The recommended dosage of escitalopram is 10 mg per day. In clinical trials, no additional benefit was noted when 20 mg per day was used.

Front 114

Some patients report a lessened response to SSRIs with recurrence of depressive symptoms after a period of time (e.g., 4 to 6 months). The exact mechanism is unknown. Potential remedies for the attenuation of response to SSRIs include

Back 114

increasing or decreasing the dosage;
tapering drug use and then rechallenging with the same medication;
switching to another SSRI or non-SSRI antidepressant;
and augmenting with bupropion or another augmentation agent.

Front 115

Why are atypicals called serotonin-dopamine antagonists?

Back 115

They are called SDAs because they have a higher ratio of serotonin type 2 (5-HT2) to D2 dopamine receptor blockades than the typical, or conventional, dopamine receptor antagonists (DRAs) that previously were the mainstay of treatment.

Front 116

The SDAs also appear to be more specific for the ? than ? dopamine system and, in some cases, are associated with (slow/rapid) dissociation from the D2 receptor.

Back 116

The SDAs also appear to be more specific for the mesolimbic than striatal dopamine system and, in some cases, are associated with rapid dissociation from the D2 receptor.

Front 117

List 4 key characterictics of SDAs

Back 117

(1) low D2 receptor blocking effects when compared with DRAs, which have high D2 receptor blockades;

(2) a reduced risk of extrapyramidal side effects compared with older agents, a reduced risk that probably extends to the occurrence of tardive dyskinesia as well;

(3) proved efficacy as treatments for schizophrenia; and

(4) proved efficacy as treatments for acute mania.

In all other respects, these agents differ markedly

Front 118

SDA versus DRAs for +/- sx comparison?

Back 118

SDAs are as good as, or better than, typical antipsychotics (DRAs) for the treatment of positive symptoms in schizophrenia and clearly superior to DRAs for the treatment of negative symptoms

Front 119

Clozapine indications?

Back 119

Because clozapine has potentially life-threatening adverse effects, it is appropriate only for patients with schizophrenia that is resistant to all other antipsychotics. Other indications for clozapine include treatment of persons with severe tardive dyskinesias—which can be reversed with high dosages in some cases—and those with a low threshold for extrapyramidal symptoms.

Front 120

Role of SDA's in mania?

Back 120

All of the SDAs are FDA-approved for treatment of acute mania.

Front 121

SDA role in depression?

Back 121

he SDAs improve depressive symptoms in schizophrenia, and both clinical experience and clinical trials show that all of the SDAs augment antidepressants in the acute management of major depression. A combination of SDAs and antidepressants is frequently used in treatment-resistant depression, and a fixed combination of olanzapine and fluoxetine (Symbyax) is approved by the FDA as a treatment for acute bipolar depression.

Front 122

Risperidone half life?

Back 122

The combined half-life of risperidone and 9-hydroxyrisperidone averages 20 hours, so it is effective in once-daily dosing.

Front 123

Risperidone receptor activity?

Back 123

Risperidone is an antagonist of the serotonin 5-HT2A, dopamine D2, α1- and α2-adrenergic, and histamine H1 receptors. It has a low affinity for α-adrenergic and muscarinic cholinergic receptors. Although it is as potent an antagonist of D2 receptors as is haloperidol (Haldol), risperidone is much less likely (except in high doses) than haloperidol to cause extrapyramidal symptoms in humans.

Front 124

Risperidone side fx?

Back 124

Extrapyramidal effects of risperidone are largely dosage dependent, and a trend is seen to using lower doses than initially recommended. Weight gain, anxiety, nausea and vomiting, rhinitis, erectile dysfunction, orgasmic dysfunction, and increased pigmentation are associated with risperidone use. The most common drug-related reasons for discontinuation of risperidone use are extrapyramidal symptoms, dizziness, hyperkinesias, somnolence, and nausea. Marked elevation of prolactin can occur. Weight gain occurs more commonly with risperidone use in children than in adults.

Front 125

Risperidone IM dosing?

Back 125

Risperidone (Risperdal Consta) is the only SDA currently available in a depot formulation. It is given as an intramuscular (IM) injection formulation every 2 weeks. The dose may be 25, 50, or 75 mg. Oral risperidone should be coadministered with Risperdal Consta for the first 3 weeks before being discontinued.

Front 126

Risp and Drug interaction?

Back 126

Inhibition of CYP 2D6 by drugs such as paroxetine and fluoxetine can block the formation of risperidone's active metabolite. Risperidone is a weak inhibitor of CYP 2D6 and has little effect on other drugs. Combined use of risperidone and selective serotonin reuptake inhibitors (SSRIs) can result in significant elevation of prolactin, with associated galactorrhea and breast enlargement.

Front 127

Olanzapine, peak, half-life?

Back 127

Approximately 85 percent of olanzapine is absorbed from the gastrointestinal (GI) tract, and about 40 percent of the dosage is inactivated by first-pass hepatic metabolism. Peak concentrations are reached in 5 hours, and the half-life averages 31 hours (range 21 to 54 hours).

Front 128

Olanzapine receptor activity?

Back 128

In addition to 5-HT2A and D2 antagonism, olanzapine is an antagonist of the D1, D4, α1, 5-HT1A, muscarinic M1 through M5, and H1 receptors.

Front 129

Other than ?, olanzapine consistently causes a greater amount and more frequent weight gain than other atypical antipsychotics which plateaus after about ? months

Back 129

Other than clozapine, olanzapine consistently causes a greater amount and more frequent weight gain than other atypical antipsychotics which plateaus after about 10 months

Front 130

Olanz and weight gain and dose?

Back 130

This effect is not dose related and continues over time.

Front 131

Olanz common side fx?

Back 131

Somnolence, dry mouth, dizziness, constipation, dyspepsia, increased appetite, akathisia, and tremor are associated with olanzapine use.

Front 132

Olanzapine and liver? EPS? blood sugar? elderly risks?

Back 132

A few patients (2 percent) may need to discontinue use of the drug because of transaminase elevation.

A dose-related risk exists of extrapyramidal side effects.

The manufacturer recommends “periodic” assessment of blood sugar and transaminases during treatment with olanzapine.

An FDA-mandate warns about an increased risk of stroke among patients with dementia treated with olanzapine and other SDA's but this risk is small and is outweighed by improved behavioral control that treatment may produce.

Front 133

Olanzapine dosing?

Back 133

A starting daily dose of 5 to 10 mg is recommended. After 1 week, the dosage can be raised to 10 mg a day. Given the long half-life, 1 week must be allowed to achieve each new steady-state blood level. Dosages in clinical use ranges vary, with 5 to 20 mg a day being most commonly used, but 30 to 40 mg a day being needed in treatment-resistant patients.

Front 134

Olanzapine and higher dosing

Back 134

A word of caution, however, is that the higher dosages are associated with increased extrapyramidal and other adverse effects and doses above 20 mg a day were not studied in the pivotal trials that led to the approval of olanzapine.

Front 135

Olanzapine drug interactions?

Back 135

Fluvoxamine (Luvox) and cimetidine (Tagamet) increase, whereas carbamazepine (Tegretol) and phenytoin decrease serum concentrations of olanzapine. Ethanol increases olanzapine absorption by more than 25 percent, leading to increased sedation. Olanzapine has little effect on the metabolism of other drugs.

Front 136

Quetiapine ... half life, receptor activity?

Back 136

It is rapidly absorbed from the GI tract, with peak plasma concentrations reached in 1 to 2 hours. Steady-state half-life is about 7 hours, and optimal dosing is two or three times per day. Quetiapine, in addition to being an antagonist of D2 and 5-HT2, also blocks 5-HT6, Dl and HI, and α1 and α2 receptors. It does not block muscarinic or benzodiazepine receptors. The receptor antagonism for quetiapine is generally lower than that for other antipsychotic drugs, and it is not associated with extrapyramidal symptoms.

Front 137

3 most common side fx of Quetiapine?

Back 137

Somnolence, postural hypotension, and dizziness are the most common adverse effects of quetiapin

Front 138

? is the SDA least likely to cause extrapyramidal side effects, regardless of dose

Back 138

Quetiapine is the SDA least likely to cause extrapyramidal side effects, regardless of dose

Front 139

Which Rx to use in Parkinson's?

Back 139

Quetiapine is particularly useful in treating patients with Parkinson's who develop dopamine agonist-induced psychosis because ... Quetiapine is the SDA least likely to cause extrapyramidal side effects, regardless of dose

Front 140

Quetiapine and weight, gi, cardio, lens problems?

Back 140

Prolactin elevation is rare and both transient and mild when it occurs. Quetiapine is associated with modest weight gain in some persons, but some patients occasionally gain a considerable amount of weight. Small increases in heart rate, constipation, and a transient rise in liver transaminases can also occur. Initial concerns about cataract formation, based on animal studies, have not been borne out since the drug has been in clinical use. Nevertheless, it might be prudent to test for lens abnormalities early in treatment and periodically thereafter.

Front 141

Quetiapine dose targets in sz, mania, bipolar depression

Back 141

In schizophrenia a target of 400 mg a day is desired and in mania and bipolar depression 800 mg and 300 mg respectively are desired. It has become evident that the target dose can be achieved rapidly and that some patients benefit from doses of as much as 1,200 to 1,600 mg a day. Despite its short elimination half-life, quetiapine can be given once a day to many patients. This is consistent with the observation that quetiapine receptor occupancy remains even when concentrations in the blood have markedly declined. Quetiapine in doses of 25 to 300 mg at night has been used for insomnia

Front 142

Quetiapine drug interaction?

Back 142

Other than a finding that phenytoin increases quetiapine clearance fivefold, no major pharmacokinetic interactions have been noted.

Front 143

Ziprasidone half life?

Back 143

The mean terminal half-life at steady state ranges from 5 to 10 hours, which accounts for the recommendation that twice-daily dosing is necessary

Front 144

Ziprasidone receptor activity?

Back 144

Ziprasidone, as with the other SDAs, blocks 5-HT2A and D2 receptors. It is also an antagonist of 5-HT1D, 5-HT2C, D3, D4, α1, and H1 receptors. It has very low affinity for D1, M1, and α2-receptors. Ziprasidone also has agonist activity at the serotonin 5-HT1A receptors and is a serotonin reuptake inhibitor and a norepinephrine reuptake inhibitor. This is consistent with clinical reports that ziprasidone has antidepressant-like effects in nonschizophrenic patients.

Front 145

Ziprasidone common side fx?

Back 145

Somnolence, headache, dizziness, nausea, and lightheadedness are the most common adverse effects in patients taking ziprasidone.

It has almost no significant effects outside the central nervous system (CNS) and is associated with almost no weight gain and does not cause sustained prolactin elevation.

Front 146

Ziprasidone and heart?

Back 146

Concerns about prolongation of the QTc complex have deterred some clinicians from using ziprasidone as a first choice. The QTc interval has been shown to increase by an average 4.7 to 1.4 milliseconds in patients treated with 40 and 120 mg per day, respectively. Ziprasidone is contraindicated in combination with other drugs known to prolong the QTc interval. These include, but are not limited to, dofetilide, sotalol, quinidine, other class Ia and III antiarrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, halofantrine, mefloquine, pentamidine, arsenic trioxide, levomethadyl acetate, dolasetron mesylate, probucol, or tacrolimus. Ziprasidone should be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias.

Front 147

Ziprasidone starting dose, max dose?

Back 147

Oral ziprasidone dosing should be initiated at 40 mg a day, divided into two daily doses. Studies have shown efficacy in the range of 80 to 160 mg a day, divided twice daily. In clinical practice, doses as high as 240 mg a day are being used. The recommended IM dosage is 10 to 20 mg every 2 hours for the 10-mg dose and every 4 hours for the 20-mg dose.

Front 148

Ziprasidone drug intx?

Back 148

Other than interactions with other drugs that prolong the QTc complex, ziprasidone appears to have low potential for clinically significant drug interactions.

Front 149

Clozapine .... half life, metabolites?

Back 149

Clozapine is a dibenzodiazepine. It is rapidly absorbed, with peak plasma levels reached in about 2 hours. Steady state is achieved in less than 1 week if twice-daily dosing is used. The elimination half-life is about 12 hours. Clozapine has two major metabolites, one of which, N-dimethyl clozapine, may have some pharmacologic activity.

Front 150

Clozapine receptor activity?

Back 150

Clozapine is an antagonist of 5-HT2A, D1, D3, D4, and α (especially α1) receptors. It has relatively low potency as a D2-receptor antagonist

Front 151

Why makes CLozapine so special in terms of MOA?

Back 151

ata from PET scanning show that 10 mg of haloperidol produces 80 percent occupancy of striatal D2 receptors, whereas clinically effective dosages of clozapine occupy only 40 to 50 percent of striatal D2 receptors. This difference in D2 receptor occupancy is probably why clozapine does not cause extrapyramidal adverse effects. It has also been postulated that clozapine, as well as other SDAs, bind more loosely to the D2 receptor, and as a result of this “fast dissociation,” more normal dopamine neurotransmission is possible.

Front 152

Clozapine and TD?

Back 152

clozapine has been shown to benefit patients with severe tardive dyskinesia. Clozapine suppresses these dyskinesias, but the abnormal movements return when clozapine is discontinued. This is true despite that clozapine, on rare occasions, can cause tardive dyskinesia.

Front 153

Clozapine and special indications?

Back 153

clinical situations where clozapine can be used include the treatment of psychotic patients who are intolerant of extrapyramidal side effects caused by other agents, treatment-resistant mania, severe psychotic depression, idiopathic Parkinson's disease, Huntington's disease, and suicidal patients with schizophrenia or schizoaffective disorder. Other treatment-resistant disorders that have demonstrated response to clozapine include pervasive developmental disorder, autism of childhood, or OCD (either alone or in combination with an SSRI). Used by itself, clozapine, very rarely, induces obsessive-compulsive symptoms.

Front 154

Most common Clozapine side fx?

Back 154

The most common drug-related adverse effects are sedation, dizziness, syncope, tachycardia, hypotension, electrocardiogram (ECG) changes, nausea, and vomiting.

Other common adverse effects include fatigue, weight gain, various GI symptoms (most commonly, constipation), anticholinergic effects, and subjective muscle weakness. Sialorrhea, or hypersalivation, is a side effect that begins early in treatment and is most evident at night. Patients report that their pillows are drenched with saliva. This side effect is most likely the result of impairment of swallowing. Although reports suggest that clonidine or amitriptyline may help reduce hypersalivation, the most practical solution is to put a towel over the pillow

Front 155

Clozapine seizure risk?

Back 155

The risk of seizures is about 4 percent in patients taking dosages above 600 mg a day.

Front 156

Clozapine and heme risks?

Back 156

Leukopenia, granulocytopenia, agranulocytosis, and fever occur in about 1 percent of patients. During the first year of treatment, a 0.73 percent risk is seen of clozapine-induced agranulocytosis. The risk during the second year is 0.07 percent. For neutropenia, the risk is 2.32 percent and 0.69 percent during the first and second years of treatment, respectively.

Front 157

he only contraindications to the use of clozapine are

Back 157

a white blood cell (WBC) count below 3,500/mm3 cells,
a previous bone marrow disorder,
a history of agranulocytosis during clozapine treatment,
or the use of another drug that is known to suppress the bone marrow, for example, carbamazepine.

Front 158

During the first 6 months of treatment, ? WBC counts are indicated to monitor the patient for the development of agranulocytosis.

Back 158

weekly.
If the WBC count remains normal, the frequency of testing can be decreased to every 2 weeks.

Front 159

Clozapine should be discontinued if the WBC count is below ?or the granulocyte count is below ?

Back 159

Clozapine should be discontinued if the WBC count is below 3,000/mm3 cells or the granulocyte count is below 1,500/mm3

Front 160

Clozapine and heart risk?

Back 160

Myocarditis is also a serious risk in the use of clozapine.

Front 161

Clozapine dosing?

Back 161

The initial dosage is usually 25 mg one or two times daily, although a conservative initial dosage is 12.5 mg twice daily. The dosage can then be raised gradually (25 mg a day every 2 or 3 days) to 300 mg a day in divided dosages, usually two or three times daily. Dosages up to 900 mg a day can be used. Testing for blood concentrations of clozapine may be helpful in patients who fail to respond. Studies have found that plasma concentrations greater than 350 mg/mL are associated with a better likelihood of response.

Front 162

Clozapine drug interactions?

Back 162

Clozapine should not be used with any other drug that is associated with the development of agranulocytosis or bone marrow suppression. Such drugs include carbamazepine, phenytoin, propylthiouracil, sulfonamides, and captopril (Capoten).

Lithium combined with clozapine can increase the risk of seizures, confusion, and movement disorders. Lithium should not be used in combination with clozapine by persons who have experienced an episode of neuroleptic malignant syndrome.

Clomipramine (Anafranil) can increase the risk of seizure by lowering the seizure threshold and by increasing clozapine plasma concentrations.

Risperidone, fluoxetine, paroxetine, and fluvoxamine increase serum concentrations of clozapine.

Addition of paroxetine may precipitate clozapine-associated neutropenia

Front 163

What is Bifeprunox?

Back 163

Bifeprunox, a dopamine partial agonist, is an investigational atypical antipsychotic for the treatment of schizophrenia.

Front 164

What is paliperidone?

Back 164

Paliperidone is the major active metabolite of the antipsychotic medication risperidone. It is a potent blocker of serotonin receptors, and partially blocks dopamine (D) 2 receptors. Published data suggest that efficacy and side effects are the same as those seen with risperidone. It is formulated to be a once-daily, extended release, oral medication. The recommended dose of paliperidone is 6 mg per day. with a dose range of 3 mg to 12 mg per day.

Front 165

Aripiprazole and MOA?

Back 165

s with the SDAs, aripiprazole is a potent 5-HT2A antagonist and is indicated for the treatment of both schizophrenia and acute mania. Unlike the SDAs, aripiprazole, however, is not a D2 antagonist, but is a partial D2 agonist. Partial D2 agonists compete at D2 receptors for endogenous dopamine, thereby producing a functional reduction of dopamine activity. Because schizophrenia and mania are disorders associated with increased dopamine activity, this reduction may account for its therapeutic effects.

Front 166

Aripiprazole side fx?

Back 166

Aripiprazole is usually nonsedating and has not been found to pose an increased risk of weight gain and diabetes. Aripiprazole is particularly effective in sparing, and possibly enhancing, neurocognitive functions. Use of aripiprazole is relatively new, so little off-label use has been described

Front 167

Aripiprazole half life? metab?

Back 167

Aripiprazole is well absorbed, reaching peak plasma concentrations after 3 to 5 hours. Absorption is not affected by food. The mean elimination half-life of aripiprazole is about 75 hours. It has a weakly active metabolite with a half-life of 96 hours. These relatively long half-lives make aripiprazole suitable for once-daily dosing. Clearance is reduced in the elderly. Aripiprazole exhibits linear pharmacokinetics and is primarily metabolized by CYP 3A4 and CYP 2D6 enzymes. It is 99 percent protein bound. Aripiprazole is excreted in breast milk in lactating rats

Front 168

Explain Aripiprazole MOA?

Back 168

Mechanistically, aripiprazole acts as a modulator, rather than a blocker, and acts on both postsynaptic D2 receptors and presynaptic autoreceptors. In theory, this mechanism addresses excessive limbic dopamine (hyperdopaminergic) activity, and decreased dopamine (hypodopaminergic) activity in frontal and prefrontal areas—abnormalities that are thought to be present in schizophrenia. The absence of complete D2 blockade in the striatal areas would be expected to minimize extrapyramidal side effects. Aripiprazole is an α1-adrenergic receptor antagonist, which can cause some patients to experience orthostatic hypotension. As with the so-called atypical antipsychotic agents, aripiprazole is a 5-HT2A antagonist.

Front 169

Aripiprazole indications?

Back 169

Sz, Mania,

Front 170

The most commonly reported adverse effects of aripiprazole are

Back 170

headache, somnolence, agitation, dyspepsia, anxiety, and nausea.

Although it is not a frequent cause of extrapyramidal side effects, aripiprazole does cause akathisia-like activation. Described as restlessness or agitation, it can be highly distressing and often leads to discontinuation of medication. Insomnia is another common complaint. Data so far do not indicate that weight gain or diabetes mellitus have an increased incidence with aripiprazole use. Prolactin elevation does not typically occur. Aripiprazole does not cause significant QTc interval changes. Seizures have been reported.

Front 171

Aripiprazole drug interactions?

Back 171

Carbamazepine and valproate reduce, whereas ketoconazole, fluoxetine, paroxetine, and quinidine increase aripiprazole serum concentrations. Lithium and valproic acid, two drugs likely to be combined with aripiprazole when treating bipolar disorder, do not affect the steady-state concentrations of aripiprazole. Combined use with antihypertensives can cause hypotension. Drugs that inhibit CYP 2D6 activity reduce aripiprazole elimination

Front 172

Aripiprazole dosing?

Back 172

The effective dosage range is 10 to 30 mg per day. Although the starting dosage is 10 to 15 mg per day, problems with nausea, insomnia, and akathisia have led to use of lower than recommended starting dosages of aripiprazole. Many clinicians find that an initial dose of 5 mg increases tolerability. It is too early to predict optimal dosing strategy for aripiprazole in clinical practice.

Front 173

SDAs usually require ? weeks to reach full effectiveness, and it may take up to ? weeks for the full clinical effects of an SDA to become apparent

Back 173

SDAs usually require 4 to 6 weeks to reach full effectiveness, and it may take up to 8 weeks for the full clinical effects of an SDA to become apparent.

Much of the observed initial clinical improvement, thus, may reflect nonspecific sedation.

Front 174

it is acceptable practice to augment an SDA with a ? in the first few weeks of use.

Back 174

it is acceptable practice to augment an SDA with a high-potency DRA or benzodiazepine in the first few weeks of use.

Front 175

How long to get clinical improvement?

Back 175

Clinical improvement may take 6 months of treatment with SDAs in some particularly treatment-refractory persons.

Front 176

What hx/lab exams to do prior to starting SDA?

Back 176

he patient's history should include information about
blood disorders, epilepsy, cardiovascular disease, hepatic and renal diseases, and drug abuse.

The presence of a hepatic or renal disease necessitates using low starting dosages of the drug.

Physical examination should include supine and standing blood pressure (BP) measurements to screen for orthostatic hypotension.

The laboratory examination should include an ECG; several complete blood counts (CBCs) with WBC counts, which can then be averaged; and liver and renal function tests. Periodic monitoring of blood glucose, lipids, and body weight is recommended.

Front 177

Which SDA are cholinergic?

Back 177

Risperidone, quetiapine, and ziprasidone lack anticholinergic effects, and the abrupt transition from a DRA, olanzapine, or clozapine to one of these agents can cause cholinergic rebound, which consists of excessive salivation, nausea, vomiting, and diarrhea.

The risk of cholinergic rebound can be mitigated by initially augmenting risperidone, quetiapine, or ziprasidone with an anticholinergic drug, which is then tapered off slowly.

Front 178

Cloza agranu ... can you then switch to olanz?

Back 178

Persons who developed agranulocytosis while taking clozapine can safely switch to olanzapine use, although initiation of olanzapine use in the midst of clozapine-induced agranulocytosis can prolong the time of recovery from the usual 3 to 4 days up to 11 to 12 days.

It is prudent to wait for resolution of agranulocytosis before initiating olanzapine use. Emergence or recurrence of agranulocytosis has not been reported with olanzapine, even in persons who developed it while taking clozapine.

Front 179

List common psychostimulants?

Back 179

ethylphenidate (Ritalin), dexmethylphenidate (Focalin), dextroamphetamine (Dexedrine), a combination of amphetamine and dextroamphetamine (Adderall), and pemoline (Cylert), now considered a second-line agent because of rare but potentially fatal hepatic toxicity

Front 180

Psycho stim indications?

Back 180

The drugs are indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) and narcolepsy and are also effective in the treatment of depression in some patients.

Both amphetamine and nonamphetamine sympathomimetics have been used as appetite suppressants

Front 181

Is atomoxetine a stimulant?

Back 181

no

Front 182

Half life of:
Amphetamine,

Back 182

Amphetamine reach peak plasma concentrations in 2 to 3 hours and have a half-life of about 6 hours, thereby necessitating once- or twice-daily dosing.

Front 183

Half life of dextroamphetamine?

Back 183

dextroamphetamine, Amphetamine reach peak plasma concentrations in 2 to 3 hours and have a half-life of about 6 hours, thereby necessitating once- or twice-daily dosing.

Front 184

Methylphenidate half-life,
(Ritalin), Ritalin-SR, extended (Concerta)

Back 184

Methylphenidate is available in immediate-release (Ritalin), sustained-release (Ritalin SR), and extended-release (Concerta) formulations. Immediate-release methylphenidate reaches peak plasma concentrations in 1 to 2 hours and has a short half-life of 2 to 3 hours, thereby necessitating multiple daily dosing. The sustained-release formulation reaches peak plasma concentrations in 4 to 5 hours and doubles the effective half-life of methylphenidate. The extended-release formulation reaches peak plasma concentrations in 6 to 8 hours and is designed to be effective for 12 hours in once-daily dosing.

Front 185

Dexmethylphenidate half-life

Back 185

reaches peak plasma concentration in about 3 hours and is prescribed twice daily.

Front 186

Pemoline peak concentration, half-life?

Back 186

Pemoline reaches peak plasma concentrations in 2 to 4 hours and has a half-life of about 12 hours,

Front 187

Modafinil, peak, t/12

Back 187

modafinil reaches peak plasma concentrations in 2 to 4 hours and has a half-life of 15 hours, thereby allowing once-daily dosing of these two agents.

Front 188

MOA of psychostimulants?

Back 188

Methylphenidate, dextroamphetamine, and amphetamine are indirectly acting sympathomimetics, with the primary effect of causing the release of catecholamines from presynaptic neurons. Clinical effectiveness is associated with increased release of both dopamine and norepinephrine. Dextroamphetamine and methylphenidate are also weak inhibitors of catecholamine reuptake and inhibitors of monoamine oxidase.
Pemoline may indirectly stimulate dopaminergic activity by a poorly understood mechanism, but it has little actual sympathomimetic activity

Front 189

Narcolepsy and modafinil MOA?

Back 189

The specific mechanism of action of modafinil is unknown. Narcolepsy–cataplexy results from deficiency of hypocretin, a hypothalamic neuropeptide. Hypocretin-producing neurons are activated after modafinil administration. Modafinil does not appear to work through a dopaminergic mechanism. It does have α1-adrenergic agonist properties, which may account for its alerting effects, because the wakefulness induced by modafinil can be attenuated by prazosin, an α1-adrenergic antagonist. Some evidence suggests that modafinil has some norepinephrine reuptake blocking effects.

Front 190

Sympathomimetics are the first-line drugs for treatment of ADHD in children and are effective about X percent of the time

Back 190

75%

Front 191

Methylphenidate and dextroamphetamine are ? effective for ADHD and work within ?

Back 191

Methylphenidate and dextroamphetamine are equally effective and work within 15 to 30 minutes

Front 192

? requires 3 to 4 weeks to reach its full efficacy; however, it is rarely used because of toxicity.

Back 192

Pemoline requires 3 to 4 weeks to reach its full efficacy; however, it is rarely used because of toxicity.

Front 193

Sympathomimetic drugs on ADHD sx? decrease hyperactivity, increase

Back 193

attentiveness, and reduce impulsivity,
They may also reduce comorbid oppositional behaviors associated with ADHD.
Sympathomimetics improve the core ADHD symptoms of hyperactivity, impulsivity, and inattentiveness and permit improved social interactions with teachers, family, other adults, and peers

Front 194

1st agent usually used in ADHD?

Back 194

Methylphenidate is the most commonly used initial agent, at a dosage of 5 to 10 mg every 3 to 4 hours. Dosages may be increased to a maximum of 20 mg four times daily or 1 mg/kg a day. Use of the 20-mg sustained-release formulation to achieve 6 hours of benefit and eliminate the need for dosing at school is supported by many experts, although other authorities feel it is less effective than the immediate-release formulation.

Front 195

Dextroamphetamine is ? potent vs methylphenidate on a per milligram basis and provides ? hours of benefit

Back 195

Dextroamphetamine is about twice as potent as methylphenidate on a per milligram basis and provides 6 to 8 hours of benefit

Front 196

Some X percent of nonresponders to one sympathomimetic may benefit from another.
All the sympathomimetic drugs should be tried before switching to drugs of a different class.

Back 196

70%

Front 197

Sympathomimetics and tics?

Back 197

The previous dictum that sympathomimetics worsen tics and, therefore, should be avoided by persons with comorbid ADHD and tic disorders has been questioned.

Small dosages of sympathomimetics do not appear to cause an increase in the frequency and severity of tics.

Front 198

Alternatives to treat ADHD that sympathomimetics?

Back 198

Alternatives to sympathomimetics for ADHD include bupropion (Wellbutrin), venlafaxine (Effexor), guanfacine (Tenex), clonidine (Catapres), and tricyclic drugs. Further studies are needed to determine whether modafinil decreases the symptoms of ADHD

Front 199

Sympathomimetics and tolerance?

Back 199

Short-term use of the sympathomimetics induces a euphoric feeling; however, tolerance develops for both the euphoric feeling and the sympathomimetic activity. Importantly, tolerance does not develop for the therapeutic effects in ADHD.

Front 200

Tx of narcolepsy, hypersomnolence?

Back 200

Narcolepsy consists of sudden sleep attacks (narcolepsy), sudden loss of postural tone (cataplexy), loss of voluntary motor control going into (hypnagogic) or coming out of (hypnopompic) sleep (sleep paralysis), and hypnagogic or hypnopompic hallucinations. Sympathomimetics reduce narcoleptic sleep attacks and also improve wakefulness in other types of hypersomnolent states. Modafinil is approved as an antisomnolence agent for treatment of narcolepsy, for people who cannot adjust to night shift work, and for those who do not sleep well because of obstructive sleep apnea.
Other sympathomimetics are also used to maintain wakefulness and accuracy of motor performance in persons subject to sleep deprivation, such as pilots and military personnel.
Persons with narcolepsy, unlike persons with ADHD, may develop tolerance for the therapeutic effects of the sympathomimetics.

Front 201

When would you use sympathomimetic monotherapy in depression?

Back 201

Possible indications for use of sympathomimetics as monotherapy include depression in the elderly, who are at increased risk for adverse effects from standard antidepressant drugs;
depression in medically ill persons, especially persons with acquired immunodeficiency syndrome (AIDS);

obtundation because of chronic use of opioids; and
clinical situations in which a rapid response is important but for which electroconvulsive therapy (ECT) is contraindicated.

Depressed patients with abulia and anergia may also benefit.

Front 202

Sympathomimetics and dementia?

Back 202

Dextroamphetamine may be useful in differentiating pseudodementia of depression from dementia.

A depressed person generally responds to a 5-mg dose with increased alertness and improved cognition. Sympathomimetics are thought to provide only short-term benefit (2 to 4 weeks) for depression, because most persons rapidly develop tolerance for the antidepressant effects of the drugs. Some clinicians, however report that long-term treatment with sympathomimetics can benefit some persons.

Front 203

Sympathomimetics and encephalopathy?

Back 203

Sympathomimetics increase alertness, cognition, motivation, and motor performance in persons with neurologic deficits caused by strokes, trauma, tumors, or chronic infections. Treatment with sympathomimetics may permit earlier and more robust participation in rehabilitative programs. Poststroke lethargy and apathy may respond to long-term use of sympathomimetics

Front 204

Sympathomimetics and weight?

Back 204

Sympathomimetics are used in the treatment of obesity because of their anorexia-inducing effects. Because tolerance develops for the anorectic effects and because of the drugs' high abuse potential, their use for this indication is limited.

Front 205

Psychostims and energy levels?

Back 205

Between 70 percent and 90 percent of individuals with multiple sclerosis experience fatigue. Modafinil, amphetamines, methylphenidate, and the dopamine receptor agonist amantadine (Symmetral) are sometimes effective in combating this symptom. Other causes of fatigue, such as chronic fatigue syndrome, respond to stimulants in many cases.

Front 206

How manage the following stim side fx in adhd? Anorexia, N, Weight loss

Back 206

* Administer stimulant with meals.
* Use caloric-enhanced supplements. Discourage forcing meals.
* If using pemoline, check liver function tests.

Front 207

How manage the following stim side fx in adhd?
Insomnia, nightmares

Back 207

* Administer stimulants earlier in day.
* Change to short-acting preparations.
* Discontinue afternoon or evening dosing.
* Consider adjunctive treatment (e.g., antihistamines, clonidine, antidepressants).

Front 208

How manage the following stim side fx in adhd? Dizziness

Back 208

# Monitor BP.
# Encourage fluid intake.
# Change to long-acting form

Front 209

How manage the following stim side fx in adhd? Rebound phenomena

Back 209

* Overlap stimulant dosing.
* Change to long-acting preparation or combine long- and short-acting preparations.
* Consider adjunctive or alternative treatment (e.g., clonidine, antidepressants).

Front 210

How manage the following stim side fx in adhd? Irritability

Back 210

* Assess timing of phenomena (during peak or withdrawal phase).
* Evaluate comorbid symptoms.
* Reduce dose.
* Consider adjunctive or alternative treatment (e.g., lithium, antidepressants, anticonvulsants).

Front 211

How manage the following stim side fx in adhd?
Dysphoria, moodiness, agitation

Back 211

* Consider comorbid diagnosis (e.g., mood disorder).
* Reduce dosage or change to long-acting preparation.
* Consider adjunctive or alternative treatment (e.g., lithium, anticonvulsants, antidepressants).

Front 212

Amphetamine side fx?

Back 212

The most common adverse effects associated with amphetamine-like drugs are stomach pain, anxiety, irritability, insomnia, tachycardia, cardiac arrhythmias, and dysphoria
Decrease Appetite (but get tolerance)
Increase HR/BP/Pa
self-limited to 10 days dyskinesia

Front 213

Methylphenidate may ? tics in one % person

Back 213

Methylphenidate may worsen tics in one third of person.

these persons fall into two groups: those whose methylphenidate-induced tics resolve immediately on metabolism of the dosage and a smaller group in whom methylphenidate appears to trigger tics that persist for several months, but eventually resolve spontaneously.

Front 214

Sympathomimetics and growth?

Back 214

Longitudinal studies do not indicate that sympathomimetics cause growth suppression

Front 215

Sympathomimetics can exacerbate

Back 215

glaucoma, hypertension, cardiovascular disorders, hyperthyroidism, anxiety disorders, psychotic disorders, and seizure disorders.

Front 216

Sympathomimetics ... overdose sx and management?

Back 216

High dosages of sympathomimetics can cause dry mouth, pupillary dilation, bruxism, formication, excessive ebullience, restlessness, and emotional lability. Long-term use of high dosages can cause a delusional disorder that resembles paranoid schizophrenia. Overdosages of sympathomimetics result in hypertension, tachycardia, hyperthermia, toxic psychosis, delirium, and occasionally seizures. Overdosages of sympathomimetics can also result in death, often caused by cardiac arrhythmias.

Seizures can be treated with benzodiazepines, cardiac effects with β-adrenergic receptor antagonists, fever with cooling blankets, and delirium with dopamine receptor antagonists (DRAs)

Front 217

Sympathomimetics and dependence risk?

Back 217

The most limiting adverse effect of sympathomimetics is their association with psychological and physical dependence. At the doses used for treatment of ADHD, psychological dependence virtually never develops.
A greater concern is the presence of adolescent or adult cohabitants who might confiscate the supply of sympathomimetics for abuse or sale.

Front 218

Why pemoline no longer used?

Back 218

A review of postmarketing experience with pemoline found several cases of acute hepatic failure, some of which were in children. This prompted the US Food and Drug Administration (FDA) to change the package insert to recommend that pemoline no longer be considered first-line therapy for ADHD. It is now rarely used.

Front 219

Sympathomimetic drug interaction?

Back 219

The coadministration of sympathomimetics and tricyclic or tetracyclic antidepressants, warfarin (Coumadin), primidone (Mysoline), phenobarbital (Luminal), phenytoin (Dilantin), or phenylbutazone (Butazolidin) decreases the metabolism of these compounds, resulting in increased plasma levels. Sympathomimetics decrease the therapeutic efficacy of many antihypertensive drugs, especially guanethidine (Esimil, Ismelin). The sympathomimetics should be used with extreme caution with monoamine oxidase inhibitors (MAOIs).

Front 220

Dextro-amphetamine and lab interference?

Back 220

Dextroamphetamine can elevate plasma corticosteroid levels and interfere with some assay methods for urinary corticosteroids.

Front 221

Sympathomimetic pre-tx evaluation?

Back 221

Pretreatment evaluation should include an evaluation of the person's cardiac function, with particular attention to the presence of hypertension or tachyarrhythmias.

The clinician should also examine the person for the presence of movement disorders, such as tics and dyskinesia, because these conditions can be exacerbated by the administration of sympathomimetics.

If tics are present, many experts will not use sympathomimetics, but will instead choose clonidine or antidepressants.

Recent data, however, indicate that sympathomimetics may cause only a mild increase in motor tics and may actually suppress vocal tics.

Liver function and renal function should be assessed, and dosages of sympathomimetics should be reduced for persons with impaired metabolism.

In the case of pemoline, any elevation of liver enzymes is a compelling reason to discontinue the medication.

Front 222

Methylphenidate dosing?

Back 222

Persons with ADHD can take immediate-release methylphenidate at 8 AM, 12 noon, and 4 PM. Dextroamphetamine, sustained-release methylphenidate, or 18 mg of extended-release methylphenidate may be taken once at 8 AM. Pemoline is taken at 8 AM. The starting dose of methylphenidate ranges from 2.5 mg of regular to 20 mg of sustained-release in children and 90 mg daily in adults. If this is inadequate, the dosage may be increased to a maximal dosage of 80 mg.

Front 223

Dextroamphetamine dosing?

Back 223

The dosage of dextroamphetamine is 2.5 to 40 mg a day up to 0.5 mg/kg a day.

Front 224

Modafinil dosing?

Back 224

The starting dosage of modafinil is 200 mg in the morning in medically healthy individuals and 100 mg in the morning in persons with hepatic impairment.

Some persons take a second 100- or 200-mg dose in the afternoon.

The maximal recommended daily dosage is 400 mg, although dosages of 600 to 1,200 mg a day have been used safely.

Adverse effects become prominent at dosages above 400 mg a day.

Compared with amphetamine-like drugs, modafinil promotes wakefulness, but produces less attentiveness and less irritability. Some persons with excessive
daytime sleepiness extend the activity of the morning modafinil dose with an afternoon dose of methylphenidate.

Front 225

Atomoxetine MOA?

Back 225

Atomoxetine is believed to produce a therapeutic effect through selective inhibition of the presynaptic norepinephrine transporter.

Front 226

Atomoxetine, peak, half life, metab

Back 226

It is well absorbed after oral administration and is minimally affected by food. High-fat meals may decrease the rate but not the extent of absorption.

Maximal plasma concentrations are reached after approximately 1 to 2 hours. At therapeutic concentrations, 98 percent of atomoxetine in plasma is bound to protein, mainly albumin.

Atomoxetine has a half-life of approximately 5 hours and is metabolized principally by the cytochrome P450 (CYP) 2D6 pathway. Poor metabolizers of this compound reach a fivefold higher area under the curve and fivefold higher peak plasma concentration than normal or extensive metabolizers. This is important to consider in patients receiving medications that inhibit the CYP 2D6 enzyme.

Front 227

Drugs such as fluoxetine (Prozac), paroxetine (Paxil), or bupropion are CYP 2D6 inhibitors and may ? atomoxetine levels.

Back 227

raise

Front 228

Atomoxetine indication?

Back 228

tomoxetine is used for the treatment of ADHD. It should be considered for use in patients who find stimulants too activating or who experience other intolerable side effects. Because atomoxetine has no abuse potential, it a reasonable choice in the treatment of patients with both ADHD and substance abuse, patients who complain of ADHD symptoms but are suspected of seeking stimulant drugs, or patients who are in recovery.
Atomoxetine may enhance cognition when used to treat patients with schizophrenia. It also can be used as an alternative or add-on to antidepressants in patients who fail to respond to standard therapies.

Front 229

Atomoxetine side fx?

Back 229

Common side effects of atomoxetine include abdominal discomfort, decreased appetite with resulting weight loss, sexual dysfunction, dizziness, vertigo, irritability, and mood swings. Minor increases in BP and heart rate have also been observed. Cases have been seen of severe liver injury in a few patients taking atomoxetine. The drug should be discontinued in patients with jaundice (yellowing of the skin or whites of the eyes, itching) or laboratory evidence of liver injury. Atomoxetine should not be taken at the same time as, or within 2 weeks of taking, a MAOI or by patients with narrow-angle glaucoma.

Front 230

Atomoxetine dosing?

Back 230

In children and adolescents up to 70 kg in body weight, atomoxetine should be initiated at a total daily dose of approximately 0.5 mg/kg and increased after a minimum of 3 days to a target total daily dose of approximately 1.2 mg/kg administered either as a single daily dose in the morning or as evenly divided doses in the morning and late afternoon or early evening. The total daily dose in smaller children and adolescents should not exceed 1.4 mg/kg or 100 mg—whichever is less. Dosing of children and adolescents over 70 kg in body weight and adults should start at a total daily dose of 40 mg and then be increased after a minimum of 3 days to a target total daily dose of approximately 80 mg. The doses can be administered either as a single daily dose in the morning or as evenly divided doses in the morning and late afternoon or early evening. After 2 to 4 additional weeks, the dose may be increased to a maximum of 100 mg in patients who have not achieved an optimal response.

The maximal recommended total daily dose in children and adolescents over 70 kg and adults is 100 mg.

Front 231

Thyroid hormone indications in psych?

Back 231

Thyroid hormones—levothyroxine (Synthroid, Levothroid, Levoxine) and liothyronine (Cytomel)—are used in psychiatry, either alone or as augmentation to
1)treat persons with depression or
2)rapid-cycling bipolar I disorder. 3) They can convert an antidepressant-nonresponsive person into an antidepressant-responsive person. 4)Thyroid hormones are also used as
replacement therapy for persons treated with lithium (Eskalith) who have developed a hypothyroid state.

Front 232

MOA of T3/T4, half life

Back 232

The mechanism of action for thyroid hormone effects on antidepressant efficacy is unknown. Thyroid hormone binds to intracellular receptors that regulate the transcription of a wide range of genes, including several receptors for neurotransmitters

Thyroid hormones are administered orally, and their absorption from the gastrointestinal (GI) tract is variable. Absorption is increased if the drug is administered on an empty stomach. In the brain, T4 crosses the blood–brain barrier and diffuses into neurons, where it is converted into T3, which is the physiologically active form. The half-life of T4 is 6 to 7 days and that of T3 is 1 to 2 days.

Front 233

The major indication for thyroid hormones in psychiatry is as ?.

Back 233

an adjuvant to antidepressants

Front 234

If a patient has not responded to a ?-week course of antidepressants at appropriate dosages, adjuvant therapy with either lithium or a thyroid hormone is an alternative.

Back 234

6

Front 235

Several controlled trials have indicated that liothyronine use converts about ? percent of antidepressant nonresponders to responders

Back 235

50%

Front 236

Liothyronine dosing?

Back 236

The dosage of liothyronine is 25 or 50 µg a day added to the patient's antidepressant regimen. Liothyronine has been used primarily as an adjuvant for tricyclic drugs; however, evidence suggests that liothyronine augments the effects of all the antidepressant drugs.

Front 237

Thyroid hormone Contra in?

Back 237

Thyroid hormones should not be taken by persons with cardiac disease, angina, or hypertension. The hormones are contraindicated in thyrotoxicosis and uncorrected adrenal insufficiency and in persons with acute myocardial infarctions.

Front 238

Thyroid horm and pregnacy

Back 238

Thyroid hormones can be administered safely to pregnant
Thyroid hormones are minimally excreted in the breast milk and have not been shown to cause problems in nursing babies.

Front 239

Thyroid horm and drug interactions?

Back 239

Thyroid hormones can potentiate the effects of warfarin (Coumadin) and other anticoagulants by increasing the catabolism of clotting factors. They may increase the insulin requirement for diabetic persons and the digitalis requirement for persons with cardiac disease. Thyroid hormones should not be coadministered with sympathomimetics, ketamine (Ketalar), or maprotiline (Ludiomil) because of the risk of cardiac decompensation. Administration of selective serotonin reuptake inhibitors (SSRIs), tricyclic and tetracyclic drugs, lithium, or carbamazepine (Tegretol) can mildly lower serum thyroxine and raise serum thyrotropin concentrations in euthyroid persons or persons taking thyroid replacements. This interaction warrants close serum monitoring and may require an increase in the dosage or initiation of thyroid hormone supplementation.

Front 240

T4 relation to TSH?

Back 240

More than 90 percent of T4 is bound to serum protein and is responsible for thyroid-stimulating hormone (TSH) secretion and cellular metabolism

Front 241

THyroid hormone and depression?

Back 241

hose tests are used to rule out hypothyroidism, which can be associated with symptoms of depression. In some studies, up to 10 percent of patients complaining of depression and associated fatigue had incipient hypothyroid disease

Front 242

Neonatal hypothyroidism results in ?

Back 242

Neonatal hypothyroidism results in mental retardation and is preventable if the diagnosis is made at birth.

Front 243

Describe TRH test normal

Back 243

injection of 500 mg of protirelin (TRH), which produces a sharp rise in serum TSH levels, which are measured at 15, 30, 60, and 90 minutes. An increase in serum TSH of 5 to 25 mIU/mL above the baseline is normal.

Front 244

TRH test abnormal?

Back 244

An increase of less than 7 mIU/mL is considered a blunted response, which may correlate with a diagnosis of depression. Of all patients with depression, 8 percent have some thyroid illness

Front 245

T3/Liothyronine dosing?

Back 245

The dosage of liothyronine is 25 or 50 µg a day added to the person's antidepressant regimen. Liothyronine has been used as an adjuvant for all the available antidepressant drugs. An adequate trial of liothyronine supplementation should last 2 to 3 weeks. If liothyronine supplementation is successful, it should be continued for 2 months and then tapered off at the rate of 12.5 µg a day every 3 to 7 days.

Front 246

Trazodone use?

Back 246

Depression and insomnia

Front 247

Trazodone peak, half life, metab?

Back 247

Trazodone is readily absorbed from the gastrointestinal (GI) tract and reaches peak plasma levels in about 1 hour. It has a half-life of 5 to 9 hours. Trazodone is metabolized in the liver, and 75 percent of its metabolites are excreted in the urine.

Front 248

Trazodone MOA?

Back 248

Trazodone is a weak inhibitor of serotonin reuptake and a potent antagonist of serotonin 5-HT2A and 5-HT2C receptors. The active metabolite of trazodone is m-chlorophenylpiperazine (mCPP), which is an agonist at 5-HT2C receptors and has a half-life of 14 hours. mCPP has been associated with migraine, anxiety, and weight loss. The adverse effects of trazodone are partially mediated by α1-adrenergic receptor antagonism.

Front 249

Trazodone and depression, dosing? parameters improved

Back 249

The main indication for the use of trazodone is major depressive disorder. A clear dose–response relationship is seen, with dosages of 250 to 600 mg a day being necessary for trazodone to have therapeutic benefit. Trazodone increases total sleep time, decreases the number and the duration of nighttime awakenings, and decreases the amount of rapid eye movement (REM) sleep. Unlike tricyclic drugs, trazodone does not decrease stage 4 sleep. Trazodone, thus, is useful for depressed persons with anxiety and insomnia

Front 250

Why trazodone used for sleep and dosing?

Back 250

Trazodone is a first-line agent for the treatment of insomnia because of its marked sedative qualities and favorable effects on sleep architecture (see above), combined with its lack of anticholinergic effects. Trazodone is effective for insomnia caused both by depression and by use of drugs. When used as a hypnotic, the usual initial dosage is 25 to 100 mg at bedtime

Front 251

Trazodone and sexual fxn?

Back 251

Trazodone is associated with an increased risk of priapism. Trazodone can potentiate erections resulting from sexual stimulation, thus it has been used to prolong erectile time and turgidity in some men with erectile disorder. The dosage for this indication is 150 to 200 mg a day. Trazodone-triggered priapism (an erection lasting more than 3 hours with pain) is a medical emergency. The use of trazodone for treatment of male erectile dysfunction has diminished considerably since the introduction of phosphodiesterase (PDE)-5 agents

Front 252

Trazodone and agitation? anxiety? sz?

Back 252

Trazodone may be useful in low dosages (50 mg a day) to control severe agitation in children with developmental disabilities and elderly persons with dementia. At dosages above 250 mg a day, trazodone reduces the tension and apprehension associated with generalized anxiety disorder. Trazodone may have a beneficial effect on insomnia and nightmares in posttraumatic stress disorder (PTSD).

It has been used to treat depression in patients with schizophrenia.

Front 253

Trazodone common side fx? other?

Back 253

The most common adverse effects associated with trazodone are sedation, orthostatic hypotension, dizziness, headache, and nausea. Some persons experience dry mouth or gastric irritation. The drug is not associated with anticholinergic adverse effects, such as urinary retention, weight gain, and constipation. A few case reports have noted an association between trazodone and arrhythmias in persons with preexisting, premature ventricular contractions or mitral valve prolapse. Neutropenia, usually not of clinical significance, can develop, which should be considered if persons have fever or sore throat.

Trazodone can cause significant orthostatic hypotension 4 to 6 hours after a dose is taken, especially if taken concurrently with antihypertensive agents or if a large dose is taken without food. Administration of trazodone with food slows absorption and reduces the peak plasma concentration, thus reducing the risk of orthostatic hypotension.

Trazodone causes priapism, prolonged erection in the absence of sexual stimuli, in 1 of every 10,000 men.

Front 254

Trazodone and priapism? and management?

Back 254

Trazodone causes priapism, prolonged erection in the absence of sexual stimuli, in 1 of every 10,000 men. Trazodone-induced priapism usually appears in the first 4 weeks of treatment, but can occur as late as 18 months into treatment. It can appear at any dose. In such cases, trazodone use should be discontinued and another antidepressant should be used. Painful erections or erections lasting more than 1 hour are warning signs that warrant immediate discontinuation of the drug and medical evaluation. The first step in the emergency management of priapism is intracavernosal injection of an α1-adrenergic agonist pressor agent, such as metaraminol (Aramine) or epinephrine.

Front 255

Trazodone and mania?

Back 255

Trazodone is less likely to precipitate mania in vulnerable persons than are other antidepressant drugs.

Front 256

Trazodone and preg?

Back 256

Trazodone use is contraindicated in pregnant and nursing women. Trazodone should be used with caution in persons with hepatic and renal diseases.

Front 257

Trazodone drug interactions?

Back 257

Trazodone potentiates the central nervous system (CNS) depressant effects of other centrally acting drugs and alcohol. Concurrent use of trazodone and antihypertensives can cause hypotension. No cases of hypertensive crisis have been reported when trazodone has been used to treat monoamine oxidase inhibitor (MAOI)-associated insomnia. Trazodone can increase levels of digoxin and phenytoin. Trazodone should be used with caution in combination with warfarin. Drugs that inhibit CYP 3A4 can increase levels of trazodone's major metabolite, mCPP, leading to an increase in side effects.

Front 258

Trazodone dosing?

Back 258

The usual starting dose is 50 mg before sleep. The dosage can be increased in increments of 50 mg every 3 days if sedation or orthostatic hypotension does not become a problem. The therapeutic range for trazodone is 200 to 600 mg a day in divided doses. Some reports indicate that dosages of 400 to 600 mg a day are required for maximal therapeutic effects; other reports indicate that 250 to 400 mg a day is sufficient. The dosage can be titrated up to 300 mg a day; then, the person can be evaluated for the need for further dosage increases on the basis of the presence or the absence of signs of clinical improvement.

Front 259

TCA indications?

Back 259

Introduced as antidepressants, their therapeutic indications now also

include panic disorder, generalized anxiety disorder, posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and pain syndromes.

Front 260

TCA's with longer half lives?

Back 260

Peak plasma concentrations occur within 2 to 8 hours, and the half-lives of the TCAs vary from 10 to 70 hours; nortriptyline (Aventyl, Pamelor), maprotiline (Ludiomil), and, particularly, protriptyline (Vivactil) can have longer half-lives.

Front 261

Clinically relevant drug interactions can result from competition for enzyme CYP ? between TCAs and

Back 261

Clinically relevant drug interactions can result from competition for enzyme CYP 2D6 between TCAs and quinidine, cimetidine (Tagamet), fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), phenothiazines, carbamazepine (Tegretol), and the type IC antiarrhythmics propafenone (Rythmol) and flecainide (Tambocor). Concomitant administration of TCAs and these inhibitors may slow the metabolism and raise the plasma concentrations of TCAs. Additionally, genetic variations in the activity of CYP 2D6 may account for up to a 40 times difference in plasma TCA concentrations in different persons. The dosage of the TCA may need to be adjusted to correct changes in the rate of hepatic TCA metabolism.

Front 262

The TCAs ?MOA, thus increasing synaptic concentrations of these neurotransmitters

Back 262

The TCAs block the transporter site for norepinephrine and serotonin, thus increasing synaptic concentrations of these neurotransmitters

Front 263

Each drug differs in its affinity for each of these transporters, with ? being the most serotonin selective and ? the most norepinephrine selective of the TCAs

Back 263

Each drug differs in its affinity for each of these transporters, with clomipramine (Anafranil) being the most serotonin selective and desipramine (Norpramin, Pertofrane) the most norepinephrine selective of the TCAs

Front 264

Secondary effects of the TCAs include

Back 264

antagonism at the muscarinic acetylcholine, histamine H1, and α1- and α2-adrenergic receptors (Table 36.34-1). It is the potency of these effects on other receptors that largely determines the side-effect profile of each drug

Front 265

Least antichol TCA

Back 265

Amoxapine (Asendin), nortriptyline, desipramine, and maprotiline have the least anticholinergic activity;

Front 266

most antihistaminic TCA

Back 266

doxepin (Adapin, Sinequan) has the most antihistaminergic activity.

Front 267

TCA vs SSRI side fx

Back 267

Although they are more likely to cause constipation, sedation, dry mouth, or lightheadedness than the SSRIs, the TCAs are less likely to cause sexual dysfunction, significant long-term weight gain, and sleep disturbances than the SSRIs

Front 268

TCA vs SSRI in mania induction?

Back 268

Whereas the TCAs are effective in the treatment of depression in persons with bipolar I disorder,
P.1108
they are more likely to induce mania, hypomania, or cycling than newer antidepressants, most notably the SSRIs and bupropion. Thus, it is not advised that TCAs be routinely used to treat depression associated with bipolar I or bipolar II disorder.

Front 269

What depressive features increase likelihood of TCA response?

Back 269

Melancholic features, prior major depressive episodes, and a family history of depressive disorders increase the likelihood of a therapeutic response.

Front 270

TCA ... which ones superior for depression?

Back 270

all =

Front 271

Clomipramine approved for?

Back 271

Although it is used worldwide as an antidepressant, clomipramine is only approved in the United States for the treatment of OCD.

Front 272

? is the TCA most studied for panic disorder with agoraphobia, but other TCAs are also effective when taken at the usual antidepressant dosages

Back 272

Imipramine is the TCA most studied for panic disorder with agoraphobia, but other TCAs are also effective when taken at the usual antidepressant dosages

Front 273

The use of ? for the treatment of anxiety disorders is approved by the US Food and Drug Administration (FDA). Some research data show that ? may also be useful. Although rarely used anymore, a ? is available for mixed anxiety and depressive disorders

Back 273

The use of doxepin for the treatment of anxiety disorders is approved by the US Food and Drug Administration (FDA). Some research data show that imipramine may also be useful. Although rarely used anymore, a chlordiazepoxide–amitriptyline combination (Limbitrol) is available for mixed anxiety and depressive disorders

Front 274

Obsessive-compulsive disorder appears to respond specifically to ?, as well as the SSRIs.

Back 274

Obsessive-compulsive disorder appears to respond specifically to clomipramine, as well as the SSRIs.

Front 275

OCD and treatment response time usually with TCA? None of the other TCAs appears to be nearly as effective as ? for treatment of this disorde

Back 275

Some improvement is usually seen in 2 to 4 weeks, but a further reduction in symptoms may continue for the first 4 to 5 months of treatment.
Clomipramine

Front 276

? may also be a drug of choice for depressed persons with marked obsessive features

Back 276

Clomipramine may also be a drug of choice for depressed persons with marked obsessive features

Front 277

The TCAs are widely used to treat chronic ? pain and in prophylaxis of ? headache. ? is the TCA most often used in this role.
Dosing in pain?

Back 277

The TCAs are widely used to treat chronic neuropathic pain and in prophylaxis of migraine headache. Amitriptyline is the TCA most often used in this role.

During treatment of pain, doses are generally lower than those used in depression, for example, 75 mg of amitriptyline may be effective. These effects also appear more rapidly

Front 278

Childhood enuresis is often treated with ?

Back 278

Childhood enuresis is often treated with imipramine

Front 279

Peptic ulcer disease can be treated with ?, which has marked antihistaminergic effects.

Back 279

Peptic ulcer disease can be treated with doxepin, which has marked antihistaminergic effects.

Front 280

? has also been used to treat premature ejaculation, movement disorders, and compulsive behavior in children with autistic disorders

Back 280

Clomipramine has also been used to treat premature ejaculation, movement disorders, and compulsive behavior in children with autistic disorders

Front 281

TCs in children and teens?

Back 281

because TCAs have caused sudden death in several children and adolescents, their use is best avoided in this population.

Front 282

TCA side fx categories?

Back 282

Psychiatric (switch to mania), Anticholinergic effects, cardiac, autonomic, sedation, neurological, allergic, hematologic, hepatic, other adverse

Front 283

TCA and mood ds?

Back 283

switch to mania
worsen psychosis

Front 284

TCA anticholinergic effects?

Back 284

nticholinergic effects often limit the tolerable dosage to relatively low ranges. Some persons may develop a tolerance for the anticholinergic effects with continued treatment. Anticholinergic effects include dry mouth, constipation, blurred vision, delirium, and urinary retention. Sugarless gum, candy, or fluoride lozenges can alleviate the dry mouth. Bethanechol (Urecholine), 25 to 50 mg three or four times a day, may reduce urinary hesitancy and may be helpful in erectile dysfunction when the drug is taken 30 minutes before sexual intercourse. Narrow-angle glaucoma can also be aggravated by anticholinergic drugs, and the precipitation of glaucoma requires emergency treatment with a miotic agent. TCAs should be avoided in persons with narrow-angle glaucoma, and an SSRI should be substituted. Severe anticholinergic effects can lead to a central nervous system (CNS) anticholinergic syndrome with confusion and delirium, especially if TCAs are administered with dopamine receptor antagonists (DRAs) or anticholinergic drugs. IM or intravenous (IV) physostigmine (Antilirium, Eserine) is used to diagnose and treat anticholinergic delirium.

Front 285

TCAs and Cardiac Effects?

Back 285

nticholinergic effects often limit the tolerable dosage to relatively low ranges. Some persons may develop a tolerance for the anticholinergic effects with continued treatment. Anticholinergic effects include dry mouth, constipation, blurred vision, delirium, and urinary retention. Sugarless gum, candy, or fluoride lozenges can alleviate the dry mouth. Bethanechol (Urecholine), 25 to 50 mg three or four times a day, may reduce urinary hesitancy and may be helpful in erectile dysfunction when the drug is taken 30 minutes before sexual intercourse. Narrow-angle glaucoma can also be aggravated by anticholinergic drugs, and the precipitation of glaucoma requires emergency treatment with a miotic agent. TCAs should be avoided in persons with narrow-angle glaucoma, and an SSRI should be substituted. Severe anticholinergic effects can lead to a central nervous system (CNS) anticholinergic syndrome with confusion and delirium, especially if TCAs are administered with dopamine receptor antagonists (DRAs) or anticholinergic drugs. IM or intravenous (IV) physostigmine (Antilirium, Eserine) is used to diagnose and treat anticholinergic delirium.
Because the drugs prolong conduction time, their use is contraindicated in persons with preexisting conduction defects. In persons with a history of any type of heart disease, TCAs should be used only after SSRIs or other newer antidepressants have been found ineffective, and if used, they should be introduced at low dosages, with gradual increases in dosage and monitoring of cardiac functions. All TCAs can cause tachycardia, which may persist for months and is one of the most common reasons for drug discontinuation, especially in younger persons. At high plasma concentrations, as seen in overdoses, the drugs become arrhythmogenic.

Front 286

?n is the most common cardiovascular autonomic adverse effect, and the most common reason TCAs are discontinued.

Back 286

Orthostatic hypotension is the most common cardiovascular autonomic adverse effect, and the most common reason TCAs are discontinued.

Front 287

? may be the drug least likely to cause orthostatic hypotension?

Back 287

Nortriptyline may be the drug least likely to cause this problem

Front 288

Tx of orthostatic HTN?

Back 288

Orthostatic hypotension is treated with avoidance of caffeine, intake of at least 2 L of fluid per day, and addition of salt to the diet unless the person is being treated for hypertension. In persons taking antihypertensive agents, a dosage reduction may reduce the risk of orthostatic hypotension.

Front 289

TCA and autonomic side fx?

Back 289

Other possible autonomic effects are profuse sweating, palpitations, and increased blood pressure (BP). Although some persons respond to fludrocortisone (Florinef), 0.02 to 0.05 mg twice a day, substitution of an SSRI is preferable to addition of a potentially toxic mineralocorticoid such as fludrocortisone.

Front 290

TCAs and surgery?

Back 290

TCA use should be discontinued several days before elective surgery because of the occurrence of hypertensive episodes during surgery in persons receiving TCAs

Front 291

Rank TCA interms of most sedating to least?

Back 291

Amitriptyline, trimipramine, and doxepin are the most sedating agents; imipramine, amoxapine, nortriptyline, and maprotiline are less sedating; and desipramine and protriptyline are the least sedating agents.

Front 292

TCA and neurologic side fx?

Back 292

A fine rapid tremor may occur. Myoclonic twitches and tremors of the tongue and the upper extremities are common. Rare effects include speech blockage, paresthesia, peroneal palsies, and ataxia.

Front 293

Amoxapine side fx?

Back 293

Amoxapine is unique in causing parkinsonian symptoms, akathisia, and even dyskinesia because of the dopaminergic blocking activity of one of its metabolites. Amoxapine can also cause neuroleptic malignant syndrome in rare cases.

Front 294

TCA? can cause seizures when the dosage is increased too quickly or is kept at high levels for too long.

Back 294

Maprotiline can cause seizures when the dosage is increased too quickly or is kept at high levels for too long.

Front 295

? and amoxapine may lower the seizure threshold more than other drugs in the class

Back 295

Clomipramine and amoxapine may lower the seizure threshold more than other drugs in the class

Front 296

TCA hepatitic effects?

Back 296

Mild and self-limited rise in serum transaminase concentrations can occur and should be monitored. TCAs can also produce a fulminant acute hepatitis in 0.1 percent to 1 percent of persons. This can be life threatening and the antidepressant should be discontinued

Front 297

TCAs and newborn withdrawal sx?

Back 297

The TCAs can cause a withdrawal syndrome in newborns, consisting of tachypnea, cyanosis, irritability, and poor sucking reflex. The drugs do pass into breast milk, but at concentrations that are usually undetectable in the infant's plasma.

Front 298

TCA and GMC cautions?

Back 298

The drugs should be used with caution in persons with hepatic and renal diseases.

Front 299

TCA's and ECT?

Back 299

TCAs should not be administered during a course of electroconvulsive therapy (ECT), primarily because of the risk of serious adverse cardiac effects.

Front 300

TCA and drug interactions?

Back 300

MOAI, AntiHTN, Antiarrhythmic Drugs, DRA, CNS, Sympathomimetics, OCPs,

Front 301

TCA and antihypertensives?

Back 301

The TCAs block the neuronal reuptake of guanethidine (Esimil, Ismelin), which is required for antihypertensive activity. The antihypertensive effects of β-adrenergic receptor antagonists (e.g., propranolol [Inderal] and clonidine [Catapres]) can also be blocked by TCAs. The coadministration of a TCA and α-methyldopa (Aldomet) can cause behavioral agitation

Front 302

The antiarrhythmic properties of TCAs can be additive to those of ?, an effect that is further exacerbated by the inhibition of TCA metabolism by ?.

Back 302

The antiarrhythmic properties of TCAs can be additive to those of quinidine, an effect that is further exacerbated by the inhibition of TCA metabolism by quinidine.

Front 303

TCA's with typicals?

Back 303

Concurrent administration of TCAs and DRAs increases the plasma concentrations of both drugs. Desipramine plasma concentrations can rise twofold during concurrent administration with perphenazine (Trilafon). DRAs also add to the anticholinergic and sedative effects of the TCAs

Front 304

TCA's and CNS depressants?

Back 304

Opioids, alcohol, anxiolytics, hypnotics, and over-the-counter cold medications have additive effects by causing CNS depression when coadministered with TCAs. Persons should be advised to avoid driving or using dangerous equipment if sedated by TCAs.

Front 305

Tricyclic drug use with ? drugs can cause serious cardiovascular effects.

Back 305

Tricyclic drug use with sympathomimetic drugs can cause serious cardiovascular effects.

Front 306

Birth control pills can ? TCA plasma concentrations

Back 306

Birth control pills can decrease TCA plasma concentrations through the induction of hepatic enzyme

Front 307

TCA drug interactions, what decreases TCA []

Back 307

Nicotine can reduce TCA concentrations. Plasma concentrations can also be lowered by ascorbic acid, ammonium chloride, barbiturates, cigarette smoking, carbamazepine, chloral hydrate, lithium (Eskalith), and primidone (Mysoline).

Front 308

TCA Rx intx, what increases []

Back 308

TCA plasma concentrations can be increased by concurrent use of acetazolamide (Diamox), sodium bicarbonate, acetylsalicylic acid, cimetidine, thiazide diuretics, fluoxetine, paroxetine, and fluvoxamine (Luvox). Plasma concentrations of TCAs can rise threefold to fourfold when administered concurrently with fluoxetine, fluvoxamine, and paroxetine

Front 309

Pre-TCA lab workup?

Back 309

Persons who intend to take TCAs should have a routine physical and laboratory examination, including a complete blood count (CBC), a white blood cell (WBC) count with differential, and serum electrolytes with liver function tests. An ECG should be obtained for all persons, especially women over 40 years of age and men over 30 years of age. TCAs are contraindicated in persons with a QTc greater than 450 milliseconds. The initial dose should be small and should be raised gradually. Because of the availability of highly effective alternatives to TCAs, a newer agent should be used in the presence of any medical condition that could interact adversely with the TCAs.
The elderly and children are more sensitive to TCA adverse effects than are young adults. In children, the ECG should be regularly monitored during use of a TCA.

Front 310

With the exception of protriptyline, all TCAs can be started at ? mg a day and increased as tolerated.

Back 310

With the exception of protriptyline, all TCAs can be started at 25 mg a day and increased as tolerated.

Front 311

A common clinical mistake is to stop increasing the dosage when the person is tolerating the drug but taking less than

Back 311

the maximal therapeutic dose and does not show clinical improvement.

Front 312

TCA for chronic pain?

Back 312

Persons with chronic pain can be particularly sensitive to adverse effects when TCA use is started. Therefore, treatment should begin with low dosages that are raised in small increments. Persons with chronic pain may experience relief, however, on long-term low-dosage therapy, such as amitriptyline or nortriptyline at 10 to 75 mg a day.

Front 313

TCAs and children?

Back 313

The TCAs should be avoided in children, except as a last resort. Dosing guidelines in children for imipramine include initiation at 1.5 mg/kg a day. The dosage can be titrated to no more than 5 mg/kg a day. In enuresis, the dosage is usually 50 to 100 mg a day taken at bedtime. Clomipramine use can be initiated at 50 mg a day and increased to no more than 3 mg/kg a day or 200 mg a day.

Front 314

TCA tapering?

Back 314

When TCA treatment is discontinued, the dosage should first be decreased to three fourths the maximal dosage for a month. At that time, if no symptoms are present, drug use can be tapered by 25 mg (5 mg for protriptyline) every 4 to 7 days. Slow tapering avoids a cholinergic rebound syndrome consisting of nausea, upset stomach, sweating, headache, neck pain, and vomiting. This syndrome can be treated by reinstituting a small dosage of the drug and tapering more slowly than before. Several case reports note the appearance of rebound mania or hypomania after the abrupt discontinuation of TCA use.

Front 315

? is unique in its association with a therapeutic window; that is, plasma concentrations below ? ng/mL or above ? ng/mL may reduce its efficacy

Back 315

Nortriptyline is unique in its association with a therapeutic window; that is, plasma concentrations below 50 ng/mL or above 150 ng/mL may reduce its efficacy

Front 316

Prescriptions for TCA drugs should be nonrefillable and for no longer than a ? at a time for patients at risk for suicide.

Back 316

a week

Front 317

? may be more likely than the other TCAs to result in death when taken in overdose

Back 317

Amoxapine may be more likely than the other TCAs to result in death when taken in overdose

Front 318

Sx of TCA overdose?

Back 318

Symptoms of overdose include agitation, delirium, convulsions, hyperactive deep tendon reflexes, bowel and bladder paralysis, dysregulation of BP and temperature, and mydriasis. The patient then progresses to coma and perhaps respiratory depression. Cardiac arrhythmias may not respond to treatment. Because of the long half-lives of TCAs, the patients are at risk of cardiac arrhythmias for 3 to 4 days after the overdose, so they should be monitored in an intensive care medical setting.

Front 319

Valproate indications?

Back 319

Valproate (Depakene, Depakote), or valproic acid, is used for the treatment of acute manic or mixed episodes associated with bipolar I disorder. Other indications include seizure disorder and migraine prophylaxis.

Front 320

Valproate peak, half life

Back 320

Regardless of how it is formulated, valproate is rapidly and completely absorbed 1 to 2 hours after oral administration, with peak concentrations occurring 4 to 5 hours after oral administration. The plasma half-life of valproate is 10 to 16 hours. Valproate is highly protein bound. Protein binding becomes saturated and concentrations of therapeutically effective free valproate increase at serum concentrations above 50 to 100 µg/mL. The extended-release preparation produces lower peak concentrations and higher minimal concentrations and can be given once a day.

Front 321

Valproate metabolism?

Back 321

Valproate is metabolized primarily by hepatic glucuronidation and mitochondrial β oxidation

Front 322

Valproate mech?

Back 322

The biochemical basis of valproate's therapeutic effects remains poorly understood. Postulated mechanisms include enhancement of γ-aminobutyric acid (GABA) activity, modulation of voltage-sensitive sodium channels, and action on extrahypothalamic neuropeptides.

Front 323

About ?of persons with acute mania respond to valproate

Back 323

About two thirds of persons with acute mania respond to valproate

Front 324

Most patients with mania usually respond within time? after achieving valproate serum concentrations above ? µg/mL

Back 324

Most patients with mania usually respond within 1 to 4 days after achieving valproate serum concentrations above 50 µg/mL

Front 325

Antimanic valproate response is generally associated with levels ?

Back 325

Antimanic response is generally associated with levels greater than 50 µg/mL, in a range of 50 to 150 µg/mL

Front 326

Valproate Time to control mania?

Back 326

Using gradual dosing strategies, this serum concentration can be achieved within 1 week of initiation of dosing, but newer, rapid oral loading strategies achieve therapeutic serum concentrations in 1 day and can control manic symptoms within 5 days

Front 327

Because of its more favorable profile of ? adverse effects, valproate is preferred to lithium for treatment of acute mania in children and elderly persons

Back 327

cognitive, dermatologic, thyroid, and renal

Front 328

Rx? approved for the treatment of acute manic or mixed episodes associated with bipolar disorder, with or without psychotic feature

Back 328

Divalproex sodium extended-release tablets are approved for the treatment of acute manic or mixed episodes associated with bipolar disorder, with or without psychotic feature

Front 329

Among depressive symptoms, valproate is more effective for treatment of ? than ?.

Back 329

Among depressive symptoms, valproate is more effective for treatment of agitation than dysphoria.

Front 330

Which type of BP1 Valproate better in?

Back 330

It may be particularly effective in persons with rapid-cycling and ultrarapid-cycling bipolar disorders, dysphoric or
mixed mania, and
mania due to a general medical condition as well as in persons who have
comorbid substance abuse or panic attacks and in persons who have not had complete favorable responses to lithium treatment.

Front 331

The two most serious adverse effects of valproate treatment affect the ? organs?

Back 331

The two most serious adverse effects of valproate treatment affect the pancreas and the liver

Front 332

Factors that increase risk with valp for fatal hepatox include? rate ?

Back 332

Risk factors for potentially fatal hepatotoxicity include young age (less than 3 years), concurrent use of phenobarbital, and the presence of neurologic disorders, especially inborn errors of metabolism.

The rate of fatal hepatotoxicity in persons who have been treated with only valproate is 0.85 per 100,000 persons; no persons over the age of 10 years are reported to have died from hepatotoxicity. Therefore, the risk of this adverse reaction in adult psychiatric patients seems low

Front 333

Hepatoxicity sx?

Back 333

Nevertheless, if symptoms of lethargy, malaise, anorexia, nausea and vomiting, edema, and abdominal pain occur in a person treated with valproate, the clinician must consider the possibility of severe hepatotoxicity. A modest increase in liver function test results does not correlate with the development of serious hepatotoxicity.

Front 334

Valproate and pancreatitis risk?

Back 334

Rare cases of pancreatitis have been reported; they occur most often in the first 6 months of treatment, and the condition occasionally results in death. Pancreatic function can be assessed and followed with serum amylase concentrations

Front 335

Besides liver and pancreas, other serious side fx?

Back 335

Other potentially serious consequences of treatment include hyperammonemia-induced encephalopathy and thrombocytopenia. Thrombocytopenia and platelet dysfunction occur most commonly at high dosages and result in the prolongation of bleeding times.

Front 336

Valproate and pregnancy?

Back 336

If at all possible, valproate should not be used by pregnant women. Women who require valproate therapy, therefore, should inform their physicians if they intend to become pregnant. The drug is associated with neural tube defects (e.g., spina bifida) in about 1 percent to 4 percent of all women who take valproate during the first trimester of the pregnancy.

Front 337

What helps to reduce Neural tube defects

Back 337

he risk of valproate-induced neural tube defects can be reduced with daily folic acid supplements (1 to 4 mg a day). All women on the drug with childbearing potential should be given folic acid supplements

Front 338

Valproate and breast-feeing?

Back 338

Infants breast-fed by mothers taking valproate develop serum valproate concentrations 1 percent to 10 percent of maternal serum concentrations, and no data suggest that this poses a risk to the infant. Valproate is not contraindicated in nursing mothers

Front 339

Cases of polycystic ovary disease have been reported in women using ?.

Back 339

valproate.
Even when the full syndromal criteria for this syndrome are not met, many of these women develop menstrual irregularities, hair loss, and hirsutism. These effects are thought to result from a metabolic syndrome that is driven by insulin resistance and hyperinsulinemia.

Front 340

Describe valproate hepatoxicity risk?

Back 340

Rare, idiosyncratic event
Estimated risk 1:118,000 (adults)
Greatest risk profile (polypharmacy, younger than 2 yr of age, mental retardation) → 1:800

Front 341

Pancreatitis valproate risk?

Back 341

are, similar pattern to hepatotoxicity
Incidence in clinical trials data is 2 of 2,416 (0.0008%)
Postmarketing surveillance shows no increased incidence
Relapse with rechallenge
Asymptomatic amylase not predictive

Front 342

Valproate and hyperammonemia risk?

Back 342

Rare—more common in combination with carbamazepine (Tegretol)
Associated with coarse tremor and may respond to L-carnitine administration

Front 343

Valproate and urea cycle disorders: how manage?

Back 343

Discontinue valproate and protein intake
Assess underlying urea cycle disorder
Divalproex is contraindicated in patients with urea cycle disorders

Front 344

Valproate and teratogenicity risk?

Back 344

Neural tube defect: 1% to 4% with valproate
Preconceptual education and folate–vitamin B complex supplementation for all young women of child-bearing potential

Front 345

How manage elderly valproate somnolence?

Back 345

Slower titration than conventional doses
Regular monitoring of fluid and nutritional intake

Front 346

Valproate and Thrombocytopenia management?

Back 346

Decrease dose if clinically symptomatic (i.e., bruising, bleeding gums)
Thrombocytopenia more likely with valproate levels ≥ 110 µg/mL (women) and ≥ 135 µg/mL (men)

Front 347

Valproate, how minimize GI side fx?

Back 347

The common adverse effects associated with valproate (Table 36.35-2) are those affecting the gastrointestinal (GI) system, such as nausea, vomiting, dyspepsia, and diarrhea. The GI effects are generally most common in the first month of treatment, particularly if the dosage is increased rapidly. Unbuffered valproic acid (Depakene) is more likely to cause GI symptoms than are the enteric-coated “sprinkle” or the delayed-release divalproex sodium formulations.

Front 348

Other common adverse effects involve the nervous system of valproate:

Back 348

, such as sedation, ataxia, dysarthria, and tremor. Valproate-induced tremor may respond well to treatment with β-adrenergic receptor antagonists or gabapentin. Treatment of the other neurologic adverse effects usually requires lowering the valproate dosage

Front 349

Common adverse effects of valproate?

Back 349

Common
GI irritation
Nausea
Sedation
Tremor
Weight gain
Hair loss

Front 350

Uncommon side fx of valporate?

Back 350

Uncommon
Vomiting
Diarrhea
Ataxia
Dysarthria
Persistent elevation of hepatic transaminases

Front 351

Valproate Rare but deadly side fx?

Back 351

Rare
Fatal hepatotoxicity (primarily in pediatric patients)
Reversible thrombocytopenia
Platelet dysfunction
Coagulation disturbances
Edema
Hemorrhagic pancreatitis
Agranulocytosis
Encephalopathy and coma
Respiratory muscle weakness and respiratory failure

Front 352

How manage valproate weight gain?

Back 352

reduce calories

Front 353

how manage valproate hair loss?

Back 353

zinc, selenium

Front 354

valproate and liver enz?

Back 354

Of persons taking valproate, 5 to 40 percent experience a persistent but clinically insignificant elevation in liver transaminases up to three times the upper limit of normal, which is usually asymptomatic and resolves after discontinuation of the drug.

Front 355

valproate and lytes?

Back 355

High dosages of valproate (above 1,000 mg a day) may rarely produce mild to moderate hyponatremia, most likely because of some degree of the syndrome of secretion of inappropriate antidiuretic hormone (SIADH), which is reversible on lowering of the dosage

Front 356

valproate overdose concern?

Back 356

Overdoses of valproate can lead to coma and death.

Front 357

Valproate is commonly prescribed as part of a regimen involving other psychotropic agents. The only consistent drug interaction with lithium, if both drugs are maintained in their respective therapeutic ranges, is

Back 357

the exacerbation of drug-induced tremors, which can usually be treated with β-receptor antagonists.

Front 358

The combination of valproate and DRAs can result in increased ? ?

Back 358

sedation
as can be seen when valproate is added to any central nervous system (CNS) depressant (e.g., alcohol), and increased severity of extrapyramidal symptoms, which usually respond to treatment with antiparkinsonian drugs.

Front 359

Perhaps the most worrisome interaction of valproate and a psychotropic drug involves ?.

Back 359

Perhaps the most worrisome interaction of valproate and a psychotropic drug involves lamotrigine.

Since the approval of lamotrigine for the treatment of bipolar disorder, the likelihood that patients will be treated with both agents has increased. Valproate more than doubles lamotrigine concentrations, increasing the risk of a serious rash.

Front 360

Recommended Laboratory Tests During Valproate Therapy
Prior to Treatment?

Back 360

Standard chemistry screen with special attention to liver function tests
CBC, including white cell and platelet count

Front 361

Recommended Laboratory Tests During Valproate Therapy
During Treatment?

Back 361

Liver function tests at 1 month, then every 6 to 24 months if no abnormalities are found
Complete blood work with platelet count at 1 month, then every 6 to 24 months if findings are normal
Liver function test results become abnormal
Mild transaminase elevation (less than three times normal): monitoring every 1 to 2 weeks: if stable and patient is responding to valproate, results are monitored monthly to every 3 months
Pronounced transaminase elevation (more than three times normal): dosage reduction or discontinuation of valproate; increase dose or rechallenge if transaminases normalize and if the patient is a valproate responder

Front 362

Which drugs are increased in [] when given with valproate?

Back 362

The plasma concentrations of carbamazepine, diazepam (Valium), amitriptyline (Elavil), nortriptyline (Pamelor), and phenobarbital (Luminal) can also be increased when these drugs are coadministered with valproat

Front 363

Which drugs decrease when given with valproate?

Back 363

the plasma concentrations of phenytoin (Dilantin) and desipramine (Norpramin) can be decreased when they are combined with valproate.

Front 364

What drugs lower valproate levels?

Back 364

The plasma concentrations of valproate may be decreased when the drug is coadministered with carbamazepine

Front 365

What drugs increase valproate []

Back 365

may be increased when coadministered with guanfacine (Tenex), amitriptyline, or fluoxetine (Prozac)

Front 366

valproate and warfarin?

Back 366

Persons who are treated with anticoagulants (e.g., aspirin and warfarin [Coumadin]) should also be monitored when valproate use is initiated to assess the development of any undesired augmentation of the anticoagulation effects

Front 367

Valproate can cause what interference in lab results?

Back 367

Valproate can cause laboratory increase of serum free fatty acids. Valproate metabolites can produce a false-positive test result for urinary ketones as well as falsely abnormal thyroid function test results.

Front 368

Labs to order with valproate?

Back 368

When starting valproate therapy, a baseline hepatic panel, complete blood cell (CBC) and platelet counts, and pregnancy testing should be ordered. Additional testing should include amylase and coagulation studies, if baseline pancreatic disease or coagulopathy is suspected. In addition to baseline laboratory tests, white blood cell (WBC) and platelet counts and hepatic transaminase concentrations should be obtained 1 month after initiation of therapy and every 6 to 24 months thereafter. Because even frequent monitoring may not predict serious organ toxicity, it is more prudent, however, to reinforce the need for prompt evaluation of any illnesses when reviewing the instructions with patients. Asymptomatic elevation of transaminase concentrations up to three times the upper limit of normal are common and do not require any change in dosage.

Front 369

Valproate dosing for acute mania?

Back 369

For treatment of acute mania, an oral loading strategy of initiation with 20 to 30 mg/kg a day can be used to accelerate control of symptoms. This is usually well tolerated, but can cause excessive sedation and tremor in elderly persons. Agitated behavior can be rapidly stabilized with intravenous (IV) infusion of valproate. If acute mania is absent, it is best to initiate drug treatment gradually to minimize the common adverse effects of nausea, vomiting, and sedation. The dose on the first day should be 250 mg administered with a meal. The dosage can be raised up to 250 mg orally three times daily over the course of 3 to 6 days. The plasma concentrations can be assessed in the morning before the first daily dose is administered.

Front 370

Therapeutic plasma concentrations for the control of seizures range between ? and ? µg/mL, but concentrations up to ? µg/mL are usually well tolerated. It is reasonable to use the same range for the treatment of mental disorders; most of the controlled studies have used ? to ? µg/mL.

Back 370

Therapeutic plasma concentrations for the control of seizures range between 50 and 150 µg/mL, but concentrations up to 200 µg/mL are usually well tolerated.

It is reasonable to use the same range for the treatment of mental disorders; most of the controlled studies have used 50 to 125 µg/mL.

Front 371

Most persons attain therapeutic plasma concentrations on a dosage between ? and ? mg a day in divided doses.

Back 371

Most persons attain therapeutic plasma concentrations on a dosage between 1,200 and 1,500 mg a day in divided doses.

Once a person's symptoms are well controlled, the full daily dose can be taken all at once before sleep

Front 372

What is yohimbine, moa, and indication?

Back 372

Yohimbine (Yocon) is an α2-adrenergic receptor antagonist that is sometimes used as a treatment for both idiopathic and medication-induced erectile disorder. Currently, sildenafil (Viagra) and its congeners (see Section 36.27) and alprostadil (Impulse, Caverject) are considered more efficacious for this indication than yohimbine

Front 373

How does yohimbine compare to viagra?

Back 373

Currently, sildenafil (Viagra) and its congeners (see Section 36.27) and alprostadil (Impulse, Caverject) are considered more efficacious for this indication than yohimbine

Front 374

Yohimbine MOA?

Back 374

Yohimbine is an antagonist of α2-receptors located both presynaptically and postsynaptically on noradrenergic neurons. The α2-receptors are also located on synaptic terminals of some serotonergic neurons. Stimulation of presynaptic α2-receptors results in a decrease in the release of neurotransmitters from the neuron; therefore, blockade of the receptors results in an increase in the release of neurotransmitters. Both norepinephrine and serotonin are involved in the physiology of male sexual response. Clinically, yohimbine produces increased parasympathetic (cholinergic) tone.

Front 375

Patients with ? disorder show heightened sensitivity to yohimbine and experience increased

Back 375

anxiety, increased BP, and increased plasma 3-methoxy-4-hydroxyphenylglycol (MHPG)

Front 376

Yohimbine side fx?

Back 376

The side effects of yohimbine include anxiety, elevated blood pressure (BP) and heart rate, increased psychomotor activity, irritability, tremor, headache, skin flushing, dizziness, urinary frequency, nausea, vomiting, and sweating.

Yohimbine should be used with caution in female patients and should not be used in patients with renal disease, cardiac disease, glaucoma, or a history of gastric or duodenal ulcer.

Front 377

Yohimbine drug intx?

Back 377

Yohimbine blocks the effects of clonidine (Catapres), guanfacine (Tenex), and other α2-receptor agonists.

Front 378

Yohimbine dosing?

Back 378

The dosage of yohimbine in the treatment of erectile disorder is approximately 18 mg a day given in dosages that range from 2.7 to 5.4 mg three times a day.

Front 379

Problems with using yohimbine?

Back 379

Yohimbine should be used judiciously in psychiatric patients because it may have an adverse effect on their mental status. Because yohimbine has no consistent effect on erectile dysfunction, its use remains controversial. Phosphodiesterase-5 inhibitors are the preferred medication for this disorder.