Kk&s Ch.36 Biological Therapies

Front 1

Which drugs are SEROTONIN DOPAMINE antagonists?

Back 1

Atypicals
Antipyschotics and mood stabilizers

Front 2

Acebutolol m?

Back 2

β-Adrenergic Receptor Antagonists

Front 3

Acetophenazine m?

Back 3

Dopamine Receptor Antagonists (Typical Antipsychotics)

Front 4

Amantadine

Back 4

Anticholinergic

Front 5

Amitriptyline

Back 5

Tricyclics and Tetracyclics

Front 6

Amlodipine

Back 6

Calcium Channel Inhibitors

Front 7

Amobarbital

Back 7

Barbiturates and Similarly Acting Drugs

Trade: Amytal

Front 8

Amoxapine

Back 8

Asendin

Tricyclics and Tetracyclics

Front 9

Aripiprazole

Back 9

Abilify
Serotonin-Dopamine Antagonists (Atypical Antipsychotics)

Front 10

Atenolol

Back 10

β-Adrenergic Receptor Antagonists

Front 11

Atomoxetine

Back 11

Strattera
Sympathomimetics and Related Drugs

Front 12

Benztropine

Back 12

Cogentin

Anticholinergics and Amantadine

Front 13

Brofaromine

Back 13

Monoamine Oxidase Inhibitors

Front 14

Bromocriptine

Back 14

Dopamine Receptor Agonists and Precursors:

Front 15

Buprenorphine

Back 15

Opioid Receptor Agonists

Front 16

Chloral hydrate

Back 16

Barbiturates

Front 17

Chlorpromazine

Back 17

Thorazine

Dopamine Receptor Antagonists (Typical Antipsychotics)

Front 18

Clomipramine

Back 18

Tricyclics and Tetracyclics

Front 19

Clonidine

Back 19

α2-Adrenergic Receptor Agonists:

Front 20

Clorgyline

Back 20

Monoamine Oxidase Inhibitors

Front 21

Cyproheptadine

Back 21

Periactin

Anithistamine

Front 22

Desvenlafaxine

Back 22

Selective Serotonin-Norepinephrine Reuptake Inhibitors

Front 23

Diltiazem

Back 23

Calcium Channel Inhibitors

Front 24

Doxepin

Back 24

Tricyclics and Tetracyclics

Front 25

Droperidol

Back 25

Dopamine Receptor Antagonists (Typical Antipsychotics)

Front 26

Duloxetine

Back 26

Selective Serotonin–Norepinephrine Reuptake Inhibitors

Front 27

Estazolam

Back 27

Benzodiazepines and Drugs Acting at Benzodiazepine Receptors

ProSom

Front 28

Eszopiclone

Back 28

Benzodiazepines and Drugs Acting at Benzodiazepine Receptors

Front 29

Fenfluramne?

Back 29

Sympathomimetic

Front 30

Fexofenadine

Back 30

Allegra
Antihistamine

Front 31

Flumazenil

Back 31

Benzo related

Front 32

Fluphenazine

Back 32

DA Receptor Antagonist

Front 33

Hydroxyzine

Back 33

Atarax
Anti-histamine

Front 34

Isocarboxazid

Back 34

MAOI

Front 35

Labetalol

Back 35

B adrenergic receptor antagonist

Front 36

Levetiracetam

Back 36

Keppra

Front 37

Liothyronine

Back 37

Cytomel (Thyroid Horm)

Front 38

Maprotiline

Back 38

TCA

Front 39

Memantine

Back 39

Cholinesterase Inhibitors

Front 40

Metoprolol

Back 40

β-Adrenergic Receptor Antagonists

Front 41

Molindone

Back 41

Dopamine Receptor Antagonists (Typical Antipsychotics)

Front 42

Paliperidone

Back 42

Serotonin-Dopamine Antagonists (Atypical Antipsychotics)

Invega

Front 43

Pemoline

Back 43

Cylert
Sympathomimetic

Front 44

Pergolide

Back 44

Dopamine Receptor Agonists and Precursors

Front 45

Perphenazine

Back 45

Dopamine Receptor Antagonists (Typical Antipsychotics)

Front 46

Phenelzine

Back 46

MAOI
Nardil

Front 47

Pimozide

Back 47

Dopamine Receptor Antagonists (Typical Antipsychotics)

Orap

Front 48

Prochlorperazine

Back 48

Dopamine Receptor Antagonists (Typical Antipsychotics)

Front 49

Promazine

Back 49

Dopamine Receptor Antagonists (Typical Antipsychotics)

Front 50

Ramelteon

Back 50

Melatonin Agonists: Ramelteon and Melatonin

Front 51

Reboxetine

Back 51

SSRI

Front 52

Rivastigmine

Back 52

Cholinsterase Inhibitors
Exelon

Front 53

Selegiline

Back 53

MAOI

Front 54

Sulpiride

Back 54

Dopamine Receptor Antagonists (Typical Antipsychotics)

Front 55

Thiopental

Back 55

Barbiturates and Similarly Acting Drugs

Front 56

Thioridazine

Back 56

Dopamine Receptor Antagonists (Typical Antipsychotics)

Mellaril

Front 57

Thiothixene

Back 57

Navane

DA Recep Antag (Typical)

Front 58

Tranylcypromine

Back 58

Parnate (MAOI)

Front 59

Triazolam

Back 59

Halcion
Benzo

Front 60

Trifluoperazine

Back 60

DA Receptor Antagonists

Stelazine

Front 61

Triflupromazine

Back 61

Vesprin
Typical

Front 62

Trihexyphenidyl

Back 62

Artanae
Anticholinergics and amantadine

Front 63

Vardenafil

Back 63

Phosphodiesterase-5 Inhibitors
Levitra

Front 64

Ziprasidone

Back 64

Serotonin-Dopamine Antagonists (Atypical Antipsychotics)

Geodon

Front 65

Define Pharmacodynamics

Back 65

The time course and intensity of a drug's effects are referred to as its pharmacodynamics

Front 66

Give example of time limited side effects

Back 66

Nausea occurring with SSRIs or venlafaxine (Effexor) and sedation occurring with mirtazapine (Remeron) are good examples of early, time-limited side effects

Front 67

Early-onset, but persistent, side effects include

Back 67

dry mouth that is associated with noradrenergic reuptake inhibition or antimuscarinic activity

Front 68

Give e.g. of full agonist drug?

Back 68

opiods,
benzo's

Front 69

Antagnosit drug eg?

Back 69

Flumazenil
can be competitive or noncompetitive with agonist

Front 70

Partial agonist drug?

Back 70

Buprenorphine
affinitiy for receptor but makes only partial response

Front 71

Inverse agonist e.g.

Back 71

makese opposite effect,
R015-4513 which the inverse agonist of the benzodiazepine class of drugs R015-4513 and the benzodiazepines both utilize the same GABA binding site on neurons, yet R015-4513 has the opposite effect, producing severe anxiety rather than the sedative and anxiolytic effects associated with benzodiazepines.

Front 72

List examples of serious adverse drug effects ...

Back 72

agranulocytosis (clozapine [Clozaril]),
Stevens-Johnson syndrome (lamotrigine [Lamictal]),
hepatic failure (nefazodone [Serzone]),
stroke (phenelzine [Nardil]), and
heart block (thioridazine [Mellaril]

Front 73

Dopamine receptor antagonists, long term complications?

Back 73

TD,
small increase in the risk of breast cancer and that this is related to larger cumulative doses
warn, few long term studies

Front 74

The issue of antidepressant-associated suicide has become front-page news, the result of an analysis suggesting a link between medication use and suicidal ideation among children, adolescents, and adults up to age XX in short-term (YY to YY weeks), placebo-controlled trials of nine newer antidepressant drugs. The data from trials involving more than 4,400 patients suggested that the average risk of suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants was ZZ percent, AA the placebo risk of BB percent

Back 74

The issue of antidepressant-associated suicide has become front-page news, the result of an analysis suggesting a link between medication use and suicidal ideation among children, adolescents, and adults up to age 24 in short-term (4 to 16 weeks), placebo-controlled trials of nine newer antidepressant drugs. The data from trials involving more than 4,400 patients suggested that the average risk of suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants was 4 percent, twice the placebo risk of 2 percent

Front 75

The analysis also showed no increase in suicide risk among the XX to YY age group. Antidepressants reduced suicidality among those over age ZZ.

Back 75

The analysis also showed no increase in suicide risk among the 25 to 65 age group. Antidepressants reduced suicidality among those over age 65.

Front 76

A large study of real world patients published in the January 2006 issue of the American Journal of Psychiatry raises serious doubt about true antidepressants and suicidality, and about the wisdom of the FDA's decision to change the labeling. The study examined suicides and hospitalizations for suicide attempts in the medical records of 65,103 members of a nonprofit insurer in the Pacific Northwest that covers about 500,000 people who received antidepressants from 1992 to 2003. It found that

Back 76

(1) newer antidepressants were associated with a more rapid and greater reduction in risk than older types of antidepressants and

(2) patients were significantly more likely to attempt or commit suicide in the month before they began drug therapy than in the 6 months after starting it.

Front 77

John Mann, M.D., of Columbia University presented population data showing that since 1987, the year before fluoxetine (Prozac) became the first marketed SSRI, suicide rates in the United States began dropping, and that area in the United States with the highest SSRI prescription rates had the biggest decline in suicides. For every XX percent increase in prescription rates, the US suicide rate declined YY percent.

Back 77

every 10% increase in Rx,
3% decrase in Suicides

Front 78

Another study, a review of 588 case files of patients aged 10 to 19 (October 2003 Archives of General Psychiatry) found that a 1 percent increase in antidepressant use was associated with a decrease of X suicides per 100,000 adolescents per year

Back 78

0.23

Front 79

Management of unwanted somnolence includes:

Back 79

adjustment of dose or timing of administration,
switching to alternative medications,

addition of small doses of stimulants,

or the addition of modafanil (Provigil).

Front 80

The major gastrointestinal (GI) side effects of the older antidepressant and antipsychotic drugs consisted primarily of ????? a consequence of their ???? activity.

Back 80

constipation and dry mouth,
antimuscarinic

Front 81

Why do newer serotonergic drugs cause gi side effects?

Back 81

Most of the body's serotonin is in the GI tract, and serotonergic drugs often cause varying degrees of stomach pain, nausea, flatulence, and diarrhea. In most cases, these side effects are transient, but some persons never accommodate and must switch to another class of drugs. Initial use of

lower doses or use of

delayed release preparations are the most effective strategies for minimizing GI side effects.

Front 82

Which atypical closest to typical in terms of movement disorders?

Back 82

Risperidone,
Olanzapine also causes more EPS than suggested.

Front 83

SSRI and % of people with sexual dysfxn? managment

Back 83

between 35 and 75%
switch drug or if responding, augment with Bupropion.

Front 84

The evidence shows metformin helping out in patients using which Rx's to reduce weight?

Back 84

Metformin (Glucophage) has been reported to facilitate weight loss among patients whose weight gain is attributed to use of serotonin-dopamine reuptake inhibitors and valproic acid (Depakene).

Front 85

Valproate relatino to weight?

Back 85

alproate, as well as olanzapine, has been linked to the development of insulin resistance, which could induce appetite increase, with subsequent weight increase.

Front 86

Genetic factors that regulate body weight, as well as the related problem of diabetes mellitus, seem to involve the ????? receptor.

Back 86

5-HT2C

Front 87

Which drugs have been shown to cause modest weight loss that is sustained

Back 87

Bupropion, Wellbutrin
even more with diet and lifestyle change
Topiramate (Topamax) and zonisamide (Zonegran), marketed as treatments for epilepsy, sometimes produce substantial, sustained loss of weight

Front 88

Which drugs are associated with glucose changes?

Back 88

Clozapine and olanzapine are associated with a greater risk than other serotonin-dopamine antagonists of abnormalities in fasting glucose levels, as well as hyperosmolar diabetes and ketoacidosis

Front 89

Which drugs is associated with HYPOnatremia? Sx of hyponatremia?

Back 89

Hyponatremia is associated with oxcarbazepine (Trileptal) and SSRI treatment, especially in elderly patients. Confusion, agitation, and lethargy are common symptoms.

Front 90

Which drug causes anterograde amnesia?

Back 90

benzo's

Front 91

which drug usually most associated with cognitive impairment

Back 91

benzo's

Front 92

Which drugs are associated with absent-mindedness, word-finding difficulties

Back 92

the SSRIs,
lamotrigine (Lamictal),
gabapentin (Neurontin),
lithium (Eskalith),
TCAs, and
bupropion, however, are also associated with varying degrees of memory impairment and word-finding difficulties.

Front 93

Which class of drugs is likely to worsen memory?

Back 93

anticholinergics

Front 94

Severe perspiration unrelated to ambient temperature is associated with? how treat sweating?

Back 94

TCAs, SSRIs, and venlafaxine (noradrenergic agents)

alpha agents, such as terazosin (Hytrin) and oxybutynin (Ditropan)

Front 95

Which drugs are associated with cardiac effects?

Back 95

older phenothiazines,
thioridazie mellaril prolongs qtc in a DOSE depedent way
clozapine associated with myocarditis
ziprasidone prolongs qtc

Front 96

how does prolonged qtc cause problems?

Back 96

increases risk of sudden death by delayed ventricular repolarization causing torsades de pointes

Front 97

which drugs connected to stevens-johnson syndrome?

Back 97

Some psychotropics, such as carbamazepine (Equetro, Tegretol) and lamotrigine (Lamictal), have been linked to an increased risk of serious exfoliative dermatitis

Front 98

Stevens Johnson Syndrome describe

Back 98

Stevens-Johnson syndrome, this condition is a systemic, immune-mediated reaction that can prove fatal or result in permanent scarring or blindness. All patients should be informed about the potential seriousness of lesions that are widespread, that occur above the neck, that involve the mucous membranes, and that may be associated with fever and lymphadenopathy. If such symptoms manifest, a patient should be instructed at the time that the medication is prescribed to go immediately to an emergency department.

Front 99

Define therapeutic index

Back 99

Therapeutic index is a relative measure of the toxicity or safety of a drug and is defined as the ratio of the median toxic dose to the median effective dose.

The median toxic dose is the dose at which 50 percent of patients experience a specific toxic effect, and the median effective dose is the dose at which 50 percent of patients have a specified therapeutic effect. When the therapeutic index is high, as it is for haloperidol, it is reflected by the wide range of dosages in which that drug is prescribed. Conversely, the therapeutic index for lithium is quite low, thus requiring careful monitoring of serum lithium levels in patients for whom the drug is prescribed.

Front 100

a (time period) supply of TCAs could be fatal.

Back 100

1 month

Front 101

How deal with concern patient hoarding meds?

Back 101

Random pill counts or asking a family member to dispense daily doses may be helpful.
limit rx

Front 102

Hemodialysis for overdose works well for what drug but not another drug?

Back 102

it is generally presumed that drugs with low protein-binding are good candidates for dialysis. Venlafaxine, however, is only 27 percent protein bound and is too large as a molecule dialyzed. Hemodialysis is effective for treating overdose of valproic acid (Depakene).

Front 103

Which drugs decrease clearance of lithium by kidneys thus raising levels?

Back 103

angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and thiazides, decrease renal clearance of lithium

Front 104

A specific drug should be selected according?

Back 104

to the patient's history of drug response (compliance, therapeutic response, adverse effects),
the patient's family history of drug response,
the profile of adverse effects for that drug with regard to the particular patient, and the
prescribing clinician's usual practice.
NOT interact with medical disorders

Informed consent
Patient preference should be respected, unless a compelling advantage exists involving efficacy, tolerability, or safety with an alternative agen

Front 105

Do you need a signed conset form for rx?

Back 105

Discussions about drug selection should be documented in notes, but a signed informed consent is not needed. Surprisingly, patients who are informed of potential adverse effects report a higher incidence of side effects, but do not have higher rates of premature discontinuation.

Front 106

Difference between potency and efficacy?

Back 106

potency = relative dose required to achieve effect
efficacy: clinical response

Front 107

Anxiety , how is drug often misued?

Back 107

Used after experiencing sx?

Front 108

How are SSRI's taken in Premenstrual Dysphoric DisordeR?

Back 108

Intermittent dosing regimens of SSRIs have been found to be effective as a treatment for premenstrual dysphoric disorder. The drugs are taken daily during the 2-week luteal phase of the menstrual cycle.

Front 109

How would you decide duration of treatment in something like depression for eg.g

Back 109

Early-onset chronic major depression, for example, has a more severe course and greater comorbidity than late-onset chronic major depression. In addition to early onset, a history of multiple past episodes, and severity and length of current episode would make longer, even indefinite, treatment appropriate.

Front 110

Follow-up time for initial phase, maintenance phase, ?

Back 110

In severely ill patients, this might mean several times a week. Patients on maintenance therapy, even when stable, need monitoring, but no consensus exists on the frequency of follow-up therapy. Three months is a reasonable interval between visits, but 6 months may be adequate after long-standing treatment.

Front 111

Describe pretx labs ?

Back 111

r that might complicate treatment with drugs. Results of recently performed tests should be obtained. With agents known to cause cardiac conduction changes, a pretreatment electrocardiogram (ECG) should be obtained before initiating treatment. With lithium and clozapine, the possibility of serious changes in thyroid, renal, hepatic, or hematological functions requires pretreatment and ongoing monitoring with appropriate laboratory tests.

Front 112

This degree of improvement to below the syndromal threshold is defined as

Back 112

remission.

Front 113

In depression studies, response is usually defined as ....
Remission is defined as

Back 113

a 50 percent or greater decrease from baseline on a standard rating scale, such as the Hamilton Depression (HAM-D) Scale or the Montgomery-Asberg Depression Rating Scale (MADRS)

REmission ... an absolute score of seven or less on the HAM-D or ten or less on the MADRS.

Front 114

The probability of full remission from OCD with SSRI treatment alone over a 2-year period is XX? percent, and the probability of partial remission is approximately YY? percent

Back 114

less than 12
47%

Front 115

How manage Tx Failure

Back 115

1. Manage side fx: Most common reason for Tx failure: side effects
2. Correct Diagnosis? R/O GMC, SU
3. Side fx: due to rx or disoder
4. Drug Intx reducing efficacy
5. Pt take as directed (non adherence)
- complicated regimen (bubble pack); side effects; poor education about tx plan

Front 116

How manage treatment resistance?

Back 116

Strategies in these cases include the use of drug combinations, high-dose therapy, and use of unconventional drugs. Limited evidence is available on the comparative success rates associated with any given strategy.

Front 117

Which drug most associated with withdrawal?

Back 117

So-called sedative hypnotics and opiates are the agents most often associated with mentally and physically distressing discontinuation reactions

In some cases, such as barbiturate use, withdrawal can be fatal

Front 118

Most severe withdrawal drug in benzo's? ssri's?

Back 118

Benzo: alprazolam and triazolam
SSRI: paroxetine, venlafaxine

Front 119

Describe paroxetine metabolism?

Back 119

aroxetine is primarily metabolized by the cytochrome P450 (CYP) 2D6 isoenzyme. Paroxetine, however, is also a potent inhibitor of CYP 2D6. This results in autoinhibition, a dose-dependent inhibition of its own metabolism, with a subsequent increase in plasma concentrations of paroxetine.

Front 120

Has SR versions of alprazolam, paroxetine, venlafaxine help reduce severity of withdrawal?

Back 120

No,
The prolonged half-life of those agents results from delayed absorption rather than prolongation of the elimination phase. The frequency of drug dosing is reduced but not the rate of fall-off in plasma concentrations.

Front 121

Define augmentation and combination tx?

Back 121

When two psychotropics with the same approved indications are used concurrently, this is termed combination therapy. Adding a drug with another indication is termed augmentation. Augmentation often entails use of a drug that is not primarily considered a psychotropic. For example, in treating depression, it is not common to add thyroid hormone to an approved antidepressant.

Front 122

Which of the newer antidepressants has a FDA warning in pregnancy?

Back 122

Among the newer antidepressants, paroxetine is the only one to carry a warning from the FDA, the result of an increase risk of cardiac malformation.

Front 123

The agents with the most well-documented risk of specific birth defects are

Back 123

lithium, carbamazepine, and valproate

Front 124

Lithium and pregnancy?

Back 124

Lithium administration during pregnancy is associated with Ebstein's anomaly, a serious abnormality in cardiac development, although recent evidence suggests that the risk is not as great as previously believed.

Front 125

Carbamazepine and valproic acid and pregnancy?

Back 125

Carbamazepine and valproic acid are associated with neural tube defects, which can be prevented by use of folate during pregnancy

Front 126

Lamotrigine and pregnancy

Back 126

Lamotrigine can cause oral-clefts when used during the first trimester

Front 127

Rx to give during pregnancy

Back 127

folate

Front 128

SSRI used in third trimester, near birth associate with?

Back 128

Reports exist of a

neonatal withdrawal syndrome associated with third trimester use of SSRIs in pregnant women. They have also been implicated in producing

pulmonary hypertension in newborns

Front 129

Geri dosing recommendations?

Back 129

The two major concerns when treating geriatric patients with psychotherapeutic drugs are that elderly persons may be more susceptible to adverse effects (particularly, cardiac effects) and may metabolize and excrete drugs more slowly, thus requiring lower dosages of medication. In practice, clinicians should begin treating geriatric patients with a small dose, usually approximately one half of the usual starting dose. The dosage should be raised in small increments, more slowly than for middle-aged adults, until a clinical benefit is achieved or unacceptable adverse effects appear. Although many geriatric patients require a small dosage of medication, many others require a full therapeutic dosage.

Front 130

Discontinuation of psychotropic drugs results in an estimated XX percent risk reduction for falls

Back 130

40%

Front 131

Geriatrics and SSRI's associated with ?

Back 131

SIADH, hyponatremia

Front 132

Geri and other drug that can cause hyponatremia

Back 132

OXCARBazapine

Front 133

Which agents are associated with inducing mania?

Back 133

L-dopa
Cortico-steroids

Front 134

What kind of drug to use in patient with obstructive sleep apnea?

Back 134

avoid sedating drugs because that raises arousal threshold and suppresses respidration

Front 135

Give e.g. of drug drug interaction with paroxetine and fluoxetine?

Back 135

Use of drugs that inhibit CYP 2D6, agents such as paroxetine and fluoxetine, can prevent the conversion of hydrocodone (Robidone) and other opiates into an active analgesic form.

Front 136

Most commonly used legal drug? illegal?

Back 136

caffeine,
cannabis

Front 137

How is propranolol used clinically

Back 137

Social Anxiety
Lithium induced tremor

Front 138

verapamil use in psych?

Back 138

for mania and treatment of MAOI-induced hypertensive crisis

Front 139

levothyroxine

Back 139

antidepressant augmentation

Front 140

Clonidine, Guanfacine uses?

Back 140

ADHD and posttraumatic stress disorder

Front 141

dextroamphetamine (Dexedrine) also used for?

Back 141

antidepressant augmentation

Front 142

riluzole also used dor?

Back 142

self-injurious behavior

Front 143

For many psychiatric disorders, including mild to moderate depression and some anxiety disorders, well over XX percent of patients can exhibit significant improvement or remission of symptoms on a placebo

Back 143

30%

Front 144

For other conditions, such as schizophrenia, manic episodes, and psychotic depression, the placebo response rate is ?

Back 144

very low

Front 145

Do placebo have any biological effect?

Back 145

Whereas suggestion is undoubtedly important in the efficacy of placebos (and active drugs), placebos can produce biological effects. For example, placebo-induced analgesia may sometimes be blocked by naloxone (Narcan), which suggests that endorphins may mediate the analgesia derived from taking a placebo. It is conceivable that placebos may also stimulate endogenous anxiolytic and antidepressant factors, resulting in clinical improvement in patients with depression and anxiety disorders.

Front 146

The most common neuroleptic-related movement disorders are

Back 146

parkinsonism, acute dystonia, and acute akathisia

Front 147

Signs of neuroleptic induced parkinsonims?

Back 147

Symptoms include muscle stiffness (lead pipe rigidity), cogwheel rigidity, shuffling gait, stooped posture, and drooling. The pill-rolling tremor of idiopathic parkinsonism is rare, but a regular, coarse tremor similar to essential tremor may be present. The so-called rabbit syndrome, a tremor affecting the lips and perioral muscles, is another parkinsonian effect seen with antipsychotics, although perioral tremor is more likely than other tremors to occur late in the course of treatment.

Front 148

Parkinsonian adverse effects occur in about XX percent of patients who are treated with antipsychotics, usually within (time period) of the initiation of treatment.

Back 148

Parkinsonian adverse effects occur in about 15 percent of patients who are treated with antipsychotics, usually within 5 to 90 days of the initiation of treatment.

Front 149

Patients who are??? are at the highest risk for neuroleptic-induced parkinsonism, although the disorder can occur at all ages.

Back 149

elderly and female

Front 150

Neuroleptic-induced parkinsonism is caused by

Back 150

the blockade of dopamine type 2 (D2) receptors in the caudate at the termination of the nigrostriatal dopamine neurons

Front 151

All antipsychotics can cause the symptoms, especially

which rx not likely involved?

Back 151

high-potency drugs with low levels of anticholinergic activity (e.g., trifluoperazine [Stelazine])

Chlorpromazine (Thorazine) and thioridazine (Mellaril) are not likely to be involved

The newer, atypical antipsychotics (e.g., aripiprazole [Abilify], olanzapine [Zyprexa], and quetiapine [Seroquel]) are less likely to cause parkinsonism

Front 152

DDX of Neuroleptic Induced Parks?

Back 152

differential diagnosis are idiopathic parkinsonism, other organic causes of parkinsonism, and depression, which can also be associated with parkinsonian symptoms

Front 153

Parkinsonism can be tx with?

Back 153

anticholinergic agents, benztropine (Cogentin), amantadine (Symmetrel), or diphenhydramine (Benadryl)

Anticholinergics should be withdrawn after 4 to 6 weeks to assess whether tolerance to the parkinsonian effects has developed; about half of patients with neuroleptic-induced parkinsonism require continued treatment. Even after the antipsychotics are withdrawn, parkinsonian symptoms can last up to 2 weeks and even up to 3 months in elderly patients. With such patients, the clinician may continue the anticholinergic drug after the antipsychotic has been stopped until the parkinsonian symptoms resolve completely

Front 154

Neuroleptic-Induced Acute Dystonia Dx/Signs/Symptoms

Back 154

Dystonias are brief or prolonged contractions of muscles that result in obviously abnormal movements or postures, including oculogyric crises, tongue protrusion, trismus, torticollis, laryngeal–pharyngeal dystonias, and dystonic postures of the limbs and trunk.
Other dystonias include blepharospasm and glossopharyngeal dystonia; the latter results in dysarthria, dysphagia, and even difficulty in breathing, which can cause cyanosis.

Children are particularly likely to evidence opisthotonos, scoliosis, lordosis, and writhing movements. Dystonia can be painful and frightening and often results in noncompliance with future drug treatment regimens.

Front 155

Acute Dystonia higher risk?

Back 155

high incidence in men, in patients younger than age 30 years, and in patients given high dosages of high-potency medications.

Front 156

Acute dystonia mechanisms?

Back 156

The mechanism of action is thought to be dopaminergic hyperactivity in the basal ganglia that occurs when central nervous system (CNS) levels of the antipsychotic drug begin to fall between doses

Front 157

Benztropine dosing?

Back 157

PO 0.5 to 2 mg tid;

IM or IV 1 to 2 mg

Front 158

Diphenhydramine dosing acute?

Back 158

PO 25 mg qid;
IM or IV 25 mg
Benadryl

Front 159

DDX of acute dystonia?

Back 159

The differential diagnosis includes seizures and tardive dyskinesia.

Front 160

Neuroleptic-Induced Acute Akathisia Symptoms?

Back 160

Akathisia is subjective feelings of restlessness, objective signs of restlessness, or both.

Examples include a sense of anxiety, inability to relax, jitteriness, pacing, rocking motions while sitting, and rapid alternation of sitting and standing.

Akathisia has been associated with the use of a wide range of psychiatric drugs, including antipsychotics, antidepressants, and sympathomimetics. Once akathisia is recognized and diagnosed, the antipsychotic dose should be reduced to the minimal effective level. Akathisia may be associated with a poor treatment outcome.

Front 161

Which population is at risk for akasthisia? onset of akathisia?

Back 161

Middle-aged women are at increased risk of akathisia, and the time course is similar to that for neuroleptic-induced parkinsonism.

Front 162

Tx of akathisia?

Back 162

Three basic steps in the treatment of akathisia are reducing medication dosage, attempting treatment with appropriate drugs, and considering changing the neuroleptic. The most efficacious drugs are β-adrenergic receptor antagonists, although anticholinergic drugs, benzodiazepines, and cyproheptadine (Periactin) may benefit some patients. In some cases of akathisia, no treatment seems to be effective.

Front 163

Neuroleptic-Induced Tardive Dyskinesia Dx, signs, sx? onset?

Back 163

Tardive dyskinesia is a delayed effect of antipsychotics; it rarely occurs until after 6 months of treatment. The disorder consists of abnormal, involuntary, irregular choreoathetoid movements of the muscles of the head, limbs, and trunk. The severity of the movements ranges from minimal—often missed by patients and their families—to grossly incapacitating. Perioral movements are the most common and include darting, twisting, and protruding movements of the tongue; chewing and lateral jaw movements; lip puckering; and facial grimacing. Finger movements and hand clenching are also common. Torticollis, retrocollis, trunk twisting, and pelvic thrusting occur in severe cases. In the most serious cases, patients may have breathing and swallowing irregularities that result in aerophagia, belching, and grunting. Respiratory dyskinesia has also been reported

Front 164

Dyskinesia relationship to stress and sleep?

Back 164

Dyskinesia is exacerbated by stress and disappears during sleep

Front 165

High risk groups for TD?

Back 165

Women are more likely to be affected than men. Children, patients who are more than 50 years of age, and patients with brain damage or mood disorders are also at high risk

Front 166

TD: course and prognosis?

Back 166

Between 5 percent and 40 percent of all cases of tardive dyskinesia eventually remit, and between 50 percent and 90 percent of all mild cases remit. Tardive dyskinesia is less likely to remit in elderly patients than in young patients, however.

Front 167

TD Tx approach?

Back 167

The three basic approaches to tardive dyskinesia are prevention, diagnosis, and management.

1. Prevention is best achieved by using antipsychotic medications only when clearly indicated and in the lowest effective doses. The atypical antipsychotics are associated with less tardive dyskinesia than the older antipsychotics.
2. Monitor with Scale; i.e., AIMS
3. educing the dose of the antipsychotic or even stopping the medication altogether. Alternatively, the clinician may switch the patient to clozapine or to one of the new SDAs. In patients who cannot continue taking any antipsychotic medication, lithium, carbamazepine (Tegretol), or benzodiazepines may effectively reduce the symptoms of both the movement disorder and the psychosis

Front 168

Rx with least TD chances?

Back 168

The atypical antipsychotics are associated with less tardive dyskinesia than the older antipsychotics.

Clozapine is the only antipsychotic to have minimal risk of tardive dyskinesia, and can even help improve preexisting symptoms of tardive dyskinesia. This has been attributed to its low affinity for D2 receptors and high affinity for 5-hydroxytryptamine (5HT) receptor antagonism

Front 169

In TD, what happens if stop DRA

Back 169

Patients frequently experience an exacerbation of their symptoms when the DRA is withheld, whereas substitution of an SDA may limit the abnormal movements without worsening the progression of the dyskinesia.

Front 170

AIMS: describe

Back 170

1. 0 None 4 = severe
2. Mouth: empty, dentures
3. ?Akathisia q
4. Observe sitting
5. Open mouth 2x
6. Protrude tongue 2x
7. Tap thumb with fingers fast
8. Flex arms
9. Extend arms palms down
10. Walk twice

Front 171

Describe NMS Dx, Signs, Sx

Back 171

Neuroleptic malignant syndrome is a life-threatening complication that can occur anytime during the course of antipsychotic treatment. The motor and behavioral symptoms include muscular rigidity and dystonia, akinesia, mutism, obtundation, and agitation. The autonomic symptoms include high fever, sweating, and increased pulse and blood pressure. Laboratory findings include an increased white blood cell count and increased levels of creatinine phosphokinase, liver enzymes, plasma myoglobin, and myoglobinuria, occasionally associated with renal failure.

Front 172

NMS and gender, mortality rate? prevalence?

Back 172

Men are affected more frequently than women, and
young patients are affected more commonly than elderly patients.

The mortality rate can reach 10 percent to 20 percent or even higher when depot antipsychotic medications are involved. The prevalence of the syndrome is estimated to be 0.02 percent to 2.4 percent of patients exposed to DRAs.

Front 173

NMS course?

Back 173

The symptoms usually evolve over 24 to 72 hours, and the untreated syndrome lasts 10 to 14 days. The diagnosis is often missed in the early stages, and the withdrawal or agitation may mistakenly be considered to reflect an exacerbation of the psychosis

Front 174

NMS Tx?

Back 174

Supportive: IV hydration, cooling blankets, ice packs, ice-water enema, oxygenation, antipyretics
Rx: Amantadine 200 to 400 mg PO/day in divided doses
Bromocriptine 2.5 mg PO bid or tid, may increase to a total of 45 mg/day
ECT: Effective when medications have failed; also may treat underlying psychiatric disorder
Dantrolene: 1 mg/kg/day for 8 days, then continue as PO for 7 additional days
Benzodiazepines: 1 to 2 mg IM as test dose; if effective, switch to PO; consider use if underlying disorder has catatonic symptoms, Has been reported effective when other agents have failed

Front 175

DDX for Drug Induced Hyperthermia

Back 175

Hyperthermia: Atropine, lidocaine, meperidine, NSAID toxicity, pheochromocytoma, thyrotoxicosis
Malignant hyperthermia: NMJ blockers (succinylcholine), halathone
Tricyclic overdose (increased heat production): Tricyclic, antidepressants, cocaine
Autonomic hyper-reflexia: CNS stimulants (amphetamines)
Lethal Catatonia: Lead poisoning

Front 176

Other drugs than can cause NMS?

Back 176

Antipsychotics (neuroleptics),
methyldopa,
reserpine

Front 177

Main Treatment of NMS?

Back 177

the most commonly used medications for the condition are dantrolene (Dantrium) and bromocriptine (Parlodel), although amantadine (Symmetrel) is sometimes used.

overcome the antipsychotic-induced dopamine receptor blockade


Bromocriptine (2–10 mg every 8 hrs orally or nsagastric tube),

lisuride (0.02–0.1 mg/hr IV infusion),

carbidopa-levodopa (Sinemet) (25/100 PO every 8 hrs),

dantrolene sodium (0.3–1 mg/kg IV every 6 hrs)

Front 178

NMS mortality untreated?

Back 178

20% mortality if untreated

Front 179

Medication-Induced Postural Tremor Dx, Signs, Symptoms, decreases, increases with?

Back 179

Tremor is a rhythmic alteration in movement that is usually faster than one beat per second.

Typically, tremors decrease during periods of relaxation and sleep and increase with stress or anxiety.

Front 180

Which drugs can produce tremor?

Back 180

Whereas all the above diagnoses specifically include an association with a neuroleptic, a range of psychiatric medications can produce tremor—most notably, lithium, antidepressants, and valproate (Depakene).

Front 181

Tremor treatment?

Back 181

1. The lowest possible dose of the psychiatric drug should be taken.
2. Patients should minimize caffeine consumption.
3. The psychiatric drug should be taken at bedtime to minimize the amount of daytime tremor.
4. β-adrenergic receptor antagonists (e.g., propranolol [Inderal]) can be given to treat drug-induced tremors.

Front 182

Nocturnal Myoclonus is what? associated (rarely) with what rx?

Back 182

Nocturnal myoclonus consists of highly stereotyped, abrupt contractions of certain leg muscles during sleep. Patients lack any subjective awareness of the leg jerks. The condition may be present in about 40 percent of persons over 65 years of age. The cause is unknown, but it is a rare side effect of selective serotonin reuptake inhibitors (SSRIs).

Front 183

Describe Noctural Myoclonus

Back 183

The repetitive leg movements occur every 20 to 60 seconds, with extensions of the large toe and flexion of the ankle, the knee, and the hips. Frequent awakenings, unrefreshing sleep, and daytime sleepiness are major symptoms.

Front 184

Treatment of Nocturnal Myoclonus?

Back 184

No treatment for nocturnal myoclonus is universally effective. Treatments that may be useful include benzodiazepines, levodopa (Larodopa), quinine, and, in rare cases, opioid

Front 185

Describe Restless Legs Syndrome, peak age, side effect of what?

Back 185

In restless leg syndrome, persons feel deep sensations of creeping inside the calves whenever sitting or lying down. The dysesthesias are rarely painful, but are agonizingly relentless and cause an almost irresistible urge to move the legs; thus, this syndrome interferes with sleep and with falling asleep.

It peaks in middle age and occurs in 5 percent of the population.

The cause is unknown, but it is a rare side effect of SSRIs.

Front 186

Restless Leg Syndrome treatment?

Back 186

Symptoms are relieved by movement and by leg massage. The dopamine receptor agonist ropinirole (Requip) is effective in treating this syndrome. Other treatments include the benzodiazepines, levodopa, quinine, opioids, propranolol (Inderal), valproate (Depakene), and carbamazepine (Tegretol).

Front 187

Clonidine is a what? primary indication?

Back 187

presynaptic α2-adrenergic receptor agonists approved for use as antihypertensive agents


Stimulation of α2-adrenergic receptors reduces the firing rate of noradrenergic neurons and of plasma concentrations of norepinephrine.

Front 188

Guanfacine mech? indication usual?

Back 188

presynaptic α2-adrenergic receptor agonists approved for use as antihypertensive agents

Stimulation of α2-adrenergic receptors reduces the firing rate of noradrenergic neurons and of plasma concentrations of norepinephrine.

Front 189

clonidine psychiatric use?

Back 189

when other rx not work ...
attention-deficit/hyperactivity disorder (ADHD),
opioid withdrawal,
Tourette's disorder, and
suppression of agitation in posttraumatic stress disorder

Front 190

Clonidine/Guanfacine half life?

Back 190

clonidine: 6 to 20 hours
guanfacine 10 to 30 hours

Front 191

Explain Clonidine/Guanfacine role?

Back 191

The agonist effects of clonidine and guanfacine on presynaptic α2-adrenergic receptors in the sympathetic nuclei of the brain result in a

decrease in the amount of norepinephrine released from the presynaptic nerve terminals.

This serves generally to reset the body's sympathetic tone at a lower level and decrease arousal

Front 192

Difference between clonidine and gaunfacine?

Back 192

Clinical psychiatry has considerably more experience with clonidine than with guanfacine. Recent interest in the use of guanfacine for the same indications that respond to clonidine centers on
guanfacine's longer half-life and
relative lack of sedative effects.

Front 193

Which part of opiate withdrawal does clonidine help with? not help with?

Back 193

Clonidine and guanfacine are effective in reducing the autonomic symptoms of rapid opioid withdrawal (e.g., hypertension, tachycardia, dilated pupils, sweating, lacrimation, and rhinorrhea), but not the associated subjective sensations.

Front 194

Clonidine dosing regimen?

Back 194

Clonidine administration (0.1 to 0.2 mg two to four times a day) is initiated before detoxification and is then tapered off over 1 to 2 weeks

Front 195

Clonidine also used in what kind of withdrawal?

Back 195

Clonidine and guanfacine can reduce symptoms of alcohol and benzodiazepine withdrawal, including anxiety, diarrhea, and tachycardia.
Clonidine and guanfacine can reduce craving, anxiety, and irritability symptoms of nicotine withdrawal.
Patch version more tolerated.

Front 196

Reasons to hold Clonidine?

Back 196

If get too much sympathetic blockade ... i.e., BP <90 (hypotension), bradycardia,

Front 197

Role of clonidine in Tourette's Ds? Tic Ds?

Back 197

Clonidine and guanfacine are effective drugs for the treatment of Tourette's disorder. Most clinicians begin treatment for Tourette's disorder with the standard dopamine receptor antagonists (DRAs), haloperidol (Haldol) and pimozide (Orap), and the serotonin-dopamine antagonists, risperidone (Risperdal) and olanzapine (Zyprexa). If concerned about the adverse effects of these drugs, the clinician, however, may begin treatment with clonidine or guanfacine.

The starting child dosage of clonidine is 0.05 mg a day; it can be raised to 0.3 mg a day in divided doses.

Three months are needed before the beneficial effects of clonidine can be seen in Tourette's disorder.

The response rate has been reported to be up to 70 percent.

Clonidine and guanfacine reduce the frequency and severity of tics in persons with tic disorder with or without comorbid ADHD symptoms.

Front 198

Role of clonidine, gaunfacine in ADHD?

Back 198

Clonidine and guanfacine can be useful alternatives for the treatment of ADHD. They are used in place of sympathomimetics and antidepressants, which can produce paradoxical worsening of hyperactivity in some children with mental retardation, aggression, or features on the spectrum of autism. Clonidine and guanfacine can improve mood, reduce activity level, and improve social adaptation. Some multiply impaired children may respond favorably to clonidine, whereas others may simply become sedated

Front 199

The efficacy of clonidine and guanfacine for control of hyperactivity and aggression ... what happens over time?

Back 199

often diminishes over several months of use

Front 200

Clonidine/Guanfacine in combo with methylphenidate/amphetamine? what do about using combo?

Back 200

Clonidine or guanfacine can be combined with methylphenidate (Ritalin) or amphetamine to treat hyperactivity and inattentiveness, respectively. A few cases have been reported of sudden death of children taking clonidine together with methylphenidate; however, it has not been conclusively demonstrated that these medications contributed to these deaths.

The clinician should explain to the family that the efficacy and safety of this combination have not been investigated in controlled trials. Periodic cardiovascular assessments, including vital signs and electrocardiograms, are warranted if this combination is used

Front 201

Clonidine patch and clozapine?

Back 201

A clonidine patch can reduce the hypersalivation and dysphagia caused by clozapine (Clozaril).

Front 202

Common side fx of clonidine?

Back 202

The most common adverse effects associated with clonidine are dry mouth and eyes, fatigue, sedation, dizziness, nausea, hypotension, and constipation, which result in discontinuation of therapy by about 10 percent of all persons taking the drug. Some persons also experience sexual dysfunction. Tolerance may develop to these adverse effects.

Front 203

Gaunfacine side fx?

Back 203

similar to clonidine side fx but milder adverse effect profile is seen with guanfacine, especially at doses of 3 mg or more per day

Front 204

Clonidine to be avoided in who?

Back 204

Clonidine and guanfacine should not be taken by adults with blood pressure (BP) below 90/60 or with cardiac arrhythmias, especially bradycardia

Front 205

What do you do if get clonidine withdrawal bradycardia?

Back 205

Development of bradycardia warrants gradual, tapered discontinuation of the drug.

Front 206

relationship of clonidine and sedation

Back 206

Clonidine, in particular, is associated with sedation, and tolerance does not usually develop to this adverse effect

Front 207

Presentation of clonidine/guanfacine overdose?

Back 207

an overdose of clonidine can present with coma and constricted pupils, symptoms similar to those of an opioid overdose. Other symptoms of overdose are decreased BP, pulse, and respiratory rates.
Guanfacine ... milder sx

Front 208

GMC's to watch out for with Clonidine

Back 208

Clonidine and guanfacine should be used with caution in persons with heart disease, any type of vascular disease, renal disease, Raynaud's syndrome, or a history of depression. Clonidine and guanfacine should be avoided during pregnancy and by nursing mothers. Elderly persons are more sensitive to the drug than are younger adults. Children are susceptible to the same adverse effects as are adults.

Front 209

Clonidine/Guanfacine withdrawal ... what and when sx seen?

Back 209

Abrupt discontinuation of clonidine can cause anxiety, restlessness, perspiration, tremor, abdominal pain, palpitations, headache, and a dramatic rise in BP. These symptoms may appear about 20 hours after the last dose of clonidine and, thus, may be seen if one or two doses are skipped. A similar set of symptoms occasionally occurs 2 to 4 days after discontinuation of guanfacine, but the usual course is a gradual return to baseline BP over 2 to 4 days. Because of the possibility of discontinuation symptoms, dosages of clonidine and guanfacine should be tapered slowly.

Front 210

Drug Interactions with Clonidine/Guanfacine?

Back 210

Coadministration of clonidine and tricyclic drugs can reduce the hypotensive effects of clonidine.

Clonidine and guanfacine may enhance the CNS depressive effects of barbiturates, alcohol, other sedative-hypnotics, and trazodone (Desyrel).

Clonidine and guanfacine can have an unwanted synergistic hypotensive effect if coadministered with other antihypertensive drugs.

The α2-adrenergic receptor antagonist yohimbine (Yocon) blocks the effects of clonidine and guanfacine.

The concomitant use of β-adrenergic receptor antagonists can increase the severity of rebound phenomena when clonidine and guanfacine are discontinued.

Front 211

Clonidine dosage?

Back 211

The usual starting dosage is 0.1 mg orally twice a day; the dosage can be raised by 0.1 mg a day to an appropriate level (up to 1.2 mg per day)

Front 212

Clonidine patch dosing?

Back 212

The usual starting dosage is the 0.1-mg-a-day patch, which is changed each week for adults and every 5 days for children; the dose can be increased, as needed, every 1 to 2 weeks.

Front 213

Guanfacine dosing? caution?

Back 213

Guanfacine is available in 1- and 2-mg tablets. The usual starting dose is 1 mg before sleep, and this can be increased to 2 mg before sleep after 3 to 4 weeks, if necessary. Regardless of the indication for which clonidine or guanfacine is being used, the drug should be withheld if a person becomes hypotensive (BP below 90/60)

Front 214

Beta blocker use medically, psych?

Back 214

he β-adrenergic receptor antagonists, which are variously referred to as β-blockers and β-antagonists, are commonly used in medical practice for their peripheral effects in the treatment of hypertension, angina, certain cardiac arrhythmias, and migraine.

Their effectiveness as peripherally and centrally acting agents has been well demonstrated for
social phobia (e.g., performance anxiety),
lithium-induced postural tremor,

control of aggressive behavior, and

neuroleptic-induced akathisia

Front 215

Beta blockers used in psych?

Back 215

The β-receptor antagonists most commonly used in psychiatry are propranolol (Inderal), nadolol (Corgard), pindolol (Visken), labetalol (Normodyne, Trandate), atenolol (Tenormin), metoprolol (Lopressor, Toprol), and acebutolol (Sectral)

Front 216

Give effectiveness for beta blockers
Definite, probable, possible

Back 216

Definitely effective
Performance anxiety
Lithium-induced tremor
Neuroleptic-induced akathisia

Probably effective
Adjunctive therapy for alcohol withdrawal and other substance-related disorders
Adjunctive therapy for aggressive or violent behavior

Possibly effective
Antipsychotic augmentation
Antidepressant augmentation

Front 217

Which beta blockers most likely to be central acting?

Back 217

The agents that are most soluble in lipids (i.e., are lipophilic) are likely to cross the blood–brain barrier and enter the brain; those agents that are least lipophilic are less likely to enter the brain. When central nervous system (CNS) effects are desired, a lipophilic drug may be
preferred; when only peripheral effects are desired, a less lipophilic drug may be indicated.

Front 218

Which beta blockers have greater b1 blockade?

Back 218

Propranolol, nadolol, pindolol, and labetalol have essentially equal potency at both the β1- and β2-receptors, whereas

metoprolol,
atenolol, and
acebutolol have greater affinity for the β1-receptor than for the β2-receptor. Relative β1-selectivity confers few pulmonary and vascular effects on these drugs, although they must be used with caution in asthmatic persons, because the drugs retain some activity at the β2-receptors.

Front 219

Which Beta Blockers possess some antagonist activity at the serotonin 5-HT1A receptors

Back 219

Pindolol, propranolol, and nadolol possess some antagonist activity at the serotonin 5-HT1A receptors

Front 220

Role of beta blockers in Anxiety Ds?

Back 220

Propranolol is useful for the treatment of social phobia, primarily of the performance type (e.g., disabling anxiety before a musical performance).

Data are also available for its use in treatment of panic disorder, posttraumatic stress disorder (PTSD), and generalized anxiety disorder

Front 221

Social phobia Beta blocker dosing?

Back 221

take 10 to 40 mg of propranolol 20 to 30 minutes before the anxiety-provoking situation. A test run of the β-receptor antagonist can be tried before using it before an anxiety-provoking situation to be sure that the patient does not experience any adverse effects from the drug or the dosage.

Front 222

Beta blocker role in other conditions than anxiety?

Back 222

Lithium/Valproate tremor, (propranolol)
Aggression
Alcohol withdrawal:no propranolol for a pulse rate below 50; 50 mg propranolol for a pulse rate between 50 and 79; and 100 mg propranolol for a pulse rate of 80 or above.

Front 223

Which beta blocker used in mood ds and role?

Back 223

Pindolol has been used to augment and hasten the antidepressant effects of SSRIs, tricyclic drugs, and electroconvulsive therapy. Small studies have shown that pindolol administered at the onset of antidepressant therapy may shorten the usual 2- to 4-week latency of antidepressant response by several days. Because the β-receptor antagonists may possibly induce depression in some persons, augmentation strategies with these drugs need to be further clarified in controlled trials.

Front 224

The β-receptor antagonists are contraindicated for use in people with

Back 224

asthma,
insulin-dependent diabetes, congestive heart failure,
significant vascular disease,
persistent angina, and
hyperthyroidism

The contraindication in diabetic persons is because of the drugs' antagonizing the normal physiologic response to hypoglycemia. The β-receptor antagonists can worsen atrioventricular (AV) conduction defects and lead to complete AV heart block and death. If the clinician decides that the risk-to-benefit ratio warrants a trial of a β-receptor antagonist in a person with one of these coexisting medical conditions, a β1-selective agent should be the first choice. All currently available β-receptor antagonists are excreted in breast milk and should be administered with caution to nursing women

Front 225

The most common adverse effects of β-receptor antagonists are ?

Back 225

hypotension and bradycardia

Front 226

Concomitant administration of propranolol results in increases in plasma concentrations of

Back 226

antipsychotics,
anticonvulsants, theophylline (Theo-Dur, Slo-bid), and
levothyroxine (Synthroid)

Front 227

Propranolol dosing?

Back 227

For the treatment of chronic disorders, propranolol administration is usually initiated at 10 mg by mouth three times a day or 20 mg by mouth twice daily. The dosage can be raised by 20 to 30 mg a day until a therapeutic effect begins to emerge. The dosage should be leveled off at the appropriate range for the disorder under treatment. The treatment of aggressive behavior sometimes requires dosages up to 800 mg a day, and therapeutic effects may not be seen until the person has been receiving the maximal dosage for 4 to 8 weeks. For the treatment of social phobia, primarily the performance type, the patient should take 10 to 40 mg of propranolol 20 to 30 minutes before the performance.

Front 228

Cautions with Beta blockers? How to discontinue?

Back 228

Pulse and BP readings should be taken regularly, and the drug should be withheld if the pulse rate is below 50 or the systolic BP is below 90. The drug should be temporarily discontinued if it produces severe dizziness, ataxia, or wheezing. Treatment with β-receptor antagonists should never be discontinued abruptly. Propranolol should be tapered by 60 mg a day until a dosage of 60 mg a day is reached, after which the drug should be tapered by 10 to 20 mg a day every 3 or 4 days

Front 229

In the clinical practice of psychiatry, the anticholinergic drugs are primarily used to treat

Back 229

medication-induced movement disorders,
particularly neuroleptic-induced parkinsonism,
neuroleptic-induced acute dystonia, and
medication-induced postural tremor

Front 230

Amantadine (Symmetrel) is used primarily for the treatment of

Back 230

medication-induced movement disorders, such as neuroleptic-induced parkinsonism. It is also used as an antiviral agent for the prophylaxis and treatment of influenza A infection.

Front 231

Trihexyphenidyl (Artane) and benztropine (Cogentin) reach peak plasma concentrations in X hours after oral administration and their duration of action is Y hours

Back 231

Trihexyphenidyl (Artane) and benztropine (Cogentin) reach peak plasma concentrations in 2 to 3 hours after oral administration and their duration of action is 1 to 12 hours

Front 232

Anticholinergic block which receptors?

Back 232

block muscarinic acetylcholine receptors, and benztropine also has some antihistaminergic effects.

None of the available anticholinergic drugs has any effects on the nicotinic acetylcholine receptors.

Front 233

Most stimulating anticholinergic?

Back 233

trihexyphenidyl is the most stimulating agent, perhaps acting through dopaminergic neurons

Front 234

Least stimulating anticholinergic?

Back 234

benztropine is the least stimulating and, thus, is least associated with abuse potential.

Front 235

The primary indication for the use of anticholinergics in psychiatric practice is

Back 235

for the treatment of neuroleptic-induced parkinsonism

Front 236

Other uses of anticholinergics?

Back 236

neuroleptic-induced acute dystonia

Front 237

Role of anticholinergics in akathisia?

Back 237

Although a trial of anticholinergics for the treatment of neuroleptic-induced acute akathisia is reasonable, these drugs are not generally considered as effective as the
β-adrenergic receptor antagonists,

the benzodiazepines, and
clonidine

Front 238

The adverse effects of the anticholinergic drugs result from blockade of

Back 238

muscarinic acetylcholine receptors

Front 239

Anticholinergic drugs should be used cautiously, if at all, by persons with

Back 239

prostatic hypertrophy,
urinary retention, and
narrow-angle glaucoma

Front 240

The anticholinergics are occasionally used as drugs of abuse because of

Back 240

their mild mood-elevating properties, most notably, trihexyphenidyl.

Front 241

The most serious adverse effect associated with anticholinergic toxicity is anticholinergic intoxication, which can be characterized by

Back 241

delirium, coma, seizures, agitation, hallucinations, severe hypotension, supraventricular tachycardia, and peripheral manifestations—flushing, mydriasis, dry skin, hyperthermia, and decreased bowel sounds.

Front 242

Tx of anticholinergic tox?

Back 242

Treatment should begin with the immediate discontinuation of all anticholinergic drugs. The syndrome of anticholinergic intoxication can be diagnosed and treated with physostigmine (Antilirium, Eserine), an inhibitor of anticholinesterase,

1 to 2 mg IV (1 mg every 2 minutes) or IM every 30 or 60 minutes.

Treatment with physostigmine should be used only in severe cases and only when emergency cardiac monitoring and life-support services are available, because physostigmine can lead to severe hypotension and bronchial constriction

Front 243

The most common drug–drug interactions with the anticholinergics occur when they are coadministered with psychotropics that also have high anticholinergic activity, such as

Back 243

DRAs,
tricyclic and tetracyclic drugs, and
monoamine oxidase inhibitors (MAOIs)

Front 244

How tx Parkinsonism with anticholinergic?

Back 244

For the treatment of neuroleptic-induced parkinsonism, the equivalent of 1 to 3 mg of benztropine should be given one to two times daily. The anticholinergic drug should be administered for 4 to 8 weeks, and then it should be discontinued to assess whether the person still requires the drug. Anticholinergic drugs should be tapered over a period of 1 to 2 weeks.

Front 245

For the short-term treatment and prophylaxis of neuroleptic-induced acute dystonia, tx?

Back 245

1 to 2 mg of benztropine or its equivalent in another drug should be given IM.

The dose can be repeated in 20 to 30 minutes, as needed.

If the person still does not improve in another 20 to 30 minutes, a benzodiazepine (e.g., 1 mg IM or IV lorazepam [Ativan]) should be given.

Laryngeal dystonia is a medical emergency and should be treated with benztropine, up to 4 mg in a 10-minute period, followed by 1 to 2 mg of lorazepam, administered slowly by the IV route.

Front 246

The primary indication for amantadine use in psychiatry is to treat

Back 246

extrapyramidal signs and symptoms, such as parkinsonism, akinesia, and so-called rabbit syndrome (focal perioral tremor of the choreoathetoid type) caused by the administration of DRA or SDA drugs

Front 247

Amantadine is as effective as the anticholinergics (e.g., benztropine [Cogentin]) for these indications and results in improvement in approximately ???persons who take it

Back 247

one half of all

Front 248

Amantadine, however, is not generally considered as effective as the anticholinergics for the treatment of

Back 248

acute dystonic reactions and is not effective in treating tardive dyskinesia and akathisia

Front 249

Amantadine and renal failure?

Back 249

Amantadine is excreted unmetabolized in the urine. Amantadine plasma concentrations can be twice as high in elderly persons as in younger adults.

Patients with renal failure accumulate amantadine in their bodies

Front 250

Amantadine mechanism of action?

Back 250

Amantadine augments dopaminergic neurotransmission in the CNS; however, the precise mechanism for the effect is unknown.

The mechanism may involve dopamine release from presynaptic vesicles, blocking reuptake of dopamine into presynaptic nerve terminals, or an agonist effect on postsynaptic dopamine receptors.

Front 251

Amantadine is associated with ?More or less? memory impairment than are the anticholinergics.

Back 251

Less

Front 252

Amantadine is a reasonable compromise for persons with

Back 252

extrapyramidal symptoms who would be sensitive to additional anticholinergic effects, particularly those taking a low-potency DRA or the elderly

Front 253

Amantadine has been reported to be of benefit in treating some selective serotonin reuptake inhibitor (SSRI)-associated side effects, such a

Back 253

lethargy, fatigue, anorgasmia, and ejaculatory inhibition.

Front 254

Amantadine mech

Back 254

Amantadine augments dopaminergic neurotransmission in the CNS

Front 255

The most common CNS effects of amantadine are

Back 255

mild dizziness,
insomnia, and
impaired concentration (dosage related), which occur in 5 percent to 10 percent of all persons

Front 256

? is the most common peripheral adverse effect of amantadine

Back 256

Nausea is the most common peripheral adverse effect of amantadine

Front 257

Livedo reticularis of the legs (a purple discoloration of the skin, caused by dilation of blood vessels) has been reported in up to 5 percent of persons who take the drug for over a month. It usually diminishes with elevation of the legs and resolves in almost all cases when drug use is terminated.

Which drug?

Back 257

Amantadine

Front 258

Amantadine is relatively contraindicated in persons with

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renal disease or a seizure disorder.

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Amantadine should be used with caution in persons with

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edema or cardiovascular disease.

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Amantadine and pregnancy?

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Some evidence indicates that amantadine is teratogenic and, therefore, should not be taken by pregnant women.

it is excreted in milk, women who are breast-feeding should not take the drug.

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Amantadine and over dose threat?

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Suicide attempts with amantadine overdosages are life threatening.

Symptoms can include toxic psychoses (confusion, hallucinations, aggressiveness) and cardiopulmonary arrest.

Emergency treatment beginning with gastric lavage is indicated

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Coadministration of amantadine with ??? can result in a significant increase in resting blood pressure (BP).

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phenelzine (Nardil) or other MAOIs

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The coadministration of amantadine with CNS stimulants can result in

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insomnia, irritability, nervousness, and possibly seizures or irregular heartbeat.

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Amantadine should not be coadministered with anticholinergics because

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unwanted side effects—such as confusion, hallucinations, nightmares, dry mouth, and blurred vision—may be exacerbated.

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Amantadine dosing?

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Amantadine is available in 100-mg capsules and as a 50-mg/5 mL syrup. The usual starting dosage of amantadine is 100 mg given orally twice a day, although the dosage can be cautiously increased up to 200 mg given orally twice a day if indicated

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Amantadine cautions?

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Amantadine should be used in persons with renal impairment only in consultation with the physician treating the renal condition.

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How manage Amantadine as treatment for EPS?

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If amantadine is successful in the treatment of the drug-induced extrapyramidal symptoms, it should be continued for 4 to 6 weeks and then discontinued to see whether the person has become tolerant to the neurologic adverse effects of the antipsychotic medication

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Amantadine taper plan? cautions

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Amantadine should be tapered over 1 to 2 weeks once a decision has been made to discontinue the drug. Persons taking amantadine should not drink alcoholic beverages.

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Gabapentin MOA?

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Gabapentin indirectly increases brain γ-aminobutyric acid (GABA) levels.

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Gabapentin dosing?

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Because higher amounts are not absorbed, doses should not exceed 1,800 mg per single dose or 5,400 mg a day

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Gabapentin half-life

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Gabapentin absorption is unaffected by food. Steady-state half-life of 5 to 9 hours is reached in 2 days when taken three times a day.

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Gabapentin metabolism?

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Gabapentin does not bind to plasma proteins and is not metabolized. It is excreted unchanged in the urine.

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Tx uses of gabapentin?

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Gabapentin is used as a hypnotic agent, because of its sedating effects.

It also has anxiolytic properties, providing benefit to patients with panic attacks and social anxiety disorder.

Gabapentin decreases craving for alcohol, helping patients to remain abstinent, and facilitates detoxification. In some cases, patients can be switched to gabapentin following benzodiazepine-facilitated alcohol detoxification.

Because gabapentin is renally excreted, it is well suited for use among patients with liver disease.

To the extent that gabapentin reduces alcohol use among patients with bipolar disorder, it may prove useful as an adjunct to standard mood stabilizer regimens.

Gabapentin is approved by the US Food and Drug Administration (FDA) for the treatment of postherpetic neuralgia. Other pain conditions responsive to gabapentin

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. Pregabalin, an analog of gabapentin, has been approved for the management of

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neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia

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Dose related gabapentin side effect?

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sedation

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Gabapentin side fx?

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Other frequent adverse effects of gabapentin are dizziness, ataxia, fatigue, and nystagmus, which are usually transient. Some patients experience peripheral edema, memory impairment, weight gain, and orgasmic dysfunction

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Gabapentin P450 interaction? Drug interactions?

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Gabapentin has no significant hepatic cytochrome P450 or pharmacodynamic interactions. Antacids containing aluminum hydroxide and magnesium hydroxide (Maalox) decrease gabapentin absorption by 20 percent if administered concurrently, but negligibly if administered 2 hours before taking the dose of gabapentin. Gabapentin can cause false-positive readings with the Ames N-Multistix SG dipstick test for urinary protein.

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Gapentin should be used cautiously in patients with

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renal disease or on dialysis.

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Gabapentin dosing?

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Gabapentin is available as 100-, 300-, and 400-mg capsules and as 600- and 800-mg tablets. The starting dosage of gabapentin is 300 mg three times a day, and the dosage can be rapidly titrated up to a maximum of 1,800 mg three times a day over a period of a few days. Most people achieve satisfactory benefit within the range of 600 to 900 mg three times a day. Although abrupt discontinuation of gabapentin does not cause withdrawal effects, use of all anticonvulsant drugs should be gradually tapered

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Pregabalin MOA? Comparison to gabapentin?

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Pregabalin is pharmacologically similar to gabapentin. It is believed to work by inhibiting the release of excess excitatory neurotransmitters, presumably by binding to the α-2-Δ subunit protein of voltage-dependent calcium channels in the brain and spinal cord. It also increases neurnal γ-aminobutyric acid (GABA) levels. The binding affinity of pregabalin for the α-2-Δ subunit is six times more potent than gabapentin and has a longer half-life

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Pregabalin efficacy in psych?

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Pregabalin has been found to be of benefit to some patients with generalized anxiety disorder. In studies, no consistent dose response relationship was found, although 300-mg pregabalin per day was more effective than 150 mg or 450 mg.
Although rejected for that indication by the FDA, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency issued a positive opinion recommending marketing authorization of pregabalin. Some patients with panic disorder or social anxiety disorder may benefit from pregabalin, but little evidence supports its routine use in treating those disorders.

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Pregabalin metabolism?

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It is not subject to hepatic metabolism and does not induce or inhibit liver enzymes such as the cytochrome P450 system. Dose adjustment may be necessary in patients with creatinine clearance (CLcr) less than 60 mL per minute. A 50 percent reduction in pregabalin daily dose is recommended for patients with CLcr between 30 and 60 mL per minute compared with those with CLcr greater than 60 mL per minute. Daily doses should be further reduced by approximately 50 percent for each additional 50 percent decrease in CLcr. Pregabalin is highly cleared by hemodialysis, so additional doses may be needed for patients on chronic hemodialysis treatment after each hemodialysis treatment.

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The most common adverse events associated with pregabalin use are

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dizziness, somnolence, blurred vision, peripheral edema, amnesia or loss of memory, and tremors.

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Pregabalin potentiates sedating effects of

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alcohol, antihistamines, benzodiazepines, and other central nervous system (CNS) depressants.

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Topiramate MOA?

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Topiramate is a selective inhibitor of Glu AMPA receptors, blocks Na+ receptors, and has indirect GABAergic activity. It potentiates the action of GABA at a non–benzodiazepine-, non–barbiturate-sensitive GABAA receptor

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Topiramate and absorption, half life?

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is rapidly and completely absorbed, and has a steady-state half-life of 21 hours. Food does not affect its absorption.

Front 287

Topiramate elimination?

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It is 15 percent protein bound in the plasma and 70 percent of an oral dose of topiramate is excreted unchanged in the urine, together with small amounts of several inactive metabolites

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Topiramate has been shown to benefit patients with

Back 288

primary alcoholism and
posttraumatic stress disorder.
weight loss
reduce the frequency of cutting and other forms of self-mutilating behavior in patients with borderline personality disorder.

It is effective in treating neuropathic pain and migraine and is also highly effective in treating
binge-eating disorder.

Front 289

The most common non–dose-related adverse effects of topiramate used in combination with other antiepileptic drugs include ?
How about alone as dose increases?

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psychomotor slowing; speech and language problems, especially word-finding difficulties; somnolence; dizziness; ataxia; nystagmus; and paresthesias. The most common dose-related adverse effects are fatigue, nervousness, poor concentration, confusion, taste perversion, depression, anorexia, anxiety, mood problems, weight loss, and tremor.

Some 1.5 percent of persons taking topiramate develop renal calculi, a rate ten times that associated with placebo. Patients at risk for calculi should be encouraged to drink plenty of fluids

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Topiramate relation to other anticonvulsants?

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Topiramate can increase phenytoin concentrations up to 25 percent and valproic acid concentrations 11 percent;
it does not affect the concentrations of carbamazepine or its epoxide, phenobarbital (Luminal), or primidone.

Topiramate concentrations are decreased by 40 percent to 48 percent with concomitant administration of carbamazepine or phenytoin and by 14 percent with concurrent administration of valproic acid.

Topiramate also slightly decreases digoxin (Lanoxin) bioavailability and the efficacy of estrogenic oral contraceptives.

Addition of topiramate, a weak inhibitor of carbonic anhydrase, to other inhibitors of carbonic anhydrase, such as acetazolamide (Diamox) or dichlorphenamide (Daranide), may promote development of renal calculi and is to be avoided

Front 291

Topiramate dosing?

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Topiramate is available as unscored 25-, 100-, and 200-mg tablets. To reduce the risk of adverse cognitive and sedative effects, topiramate dosage is titrated gradually over 8 weeks to a maximum of 200 mg twice a day. Higher doses are not associated with increased efficacy. Persons with renal insufficiency should reduce doses by half.

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Tiagabine MOA?

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Tiagabine is a potent and selective reuptake inhibitor of GABA. It also has mild blocking effects of H1, serotonin IB, benzodiazepine, and chloride channel receptors

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Tiagabine use?

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Tiagabine is occasionally used as an anxiolytic or hypnotic agent in patients who have not responded to, or tolerated, standard treatments. It has not been found to be useful in treating manic symptoms, whether used alone or as adjunctive therapy.

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Tiagabine side fx?

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Animal studies have found teratogenic effects in rats.

Ophthalmic changes can occur with chronic use. CNS side effects include sedation, cognitive impairment, ataxia, dizziness, tremor, paresthesias, confusion, and depression.

Other side effects include ecchymosis, nausea, abdominal pain, muscle weakness, and flushing.

Cases of serious rash can occur, including Stevens-Johnson syndrome. Lower doses of tiagabine should be used in patients with hepatic impairment.

Patients being treated with tiagabine for bipolar disorder have experienced new-onset seizures.

Reports of seizures in patients without epilepsy being treated with tiagabine have prompted an FDA warning about its use. Consequently, this drug should not be considered for off-label psychiatric use.

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Zonisamide is sometimes used as an alternative treatment for

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acute mania and as a weight loss agent for drug-induced weight gain.

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Zonisamide MOA?

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Zonisamide blocks sodium channels and may weakly potentiate dopamine and serotonin activity. It also inhibits carbonic anhydrase. Some evidence suggests that it might block calcium channels.

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Zonisamide metabolism?

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Zonisamide is metabolized by the hepatic CYP450 3A system

Front 298

Zonisamide metabolism impact?

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enzyme-inducing agents, such as carbamazepine, alcohol, and phenobarbital, increase the clearance and reduce the availability of the drug

Front 299

Levetiracetam has been used to treat

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acute mania,
as add-on therapy to antidepressants to prevent the emergence of mania or cycling, and as an
anxiolytic.

Front 300

Levetiracetam MOA?

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The CNS effects of levetiracetam are poorly understood, but it appears to indirectly enhance GABA inhibition. It is rapidly and completely absorbed.

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The most common side effects of levetiracetam are :

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The most common side effects of levetiracetam are drowsiness, dizziness, ataxia, diplopia, memory impairment, apathy, and paresthesia. More notably, some patients develop behavioral disturbances during treatment, and hallucinations can occur. Suicidality was noted in a few patients during clinical trials

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Levetiracetam dosing?

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Levetiracetam is available as 250-, 500-, and 750-mg tablets.
In epilepsy, it is given twice a day, with daily dosage ranging from 500 mg to 3,000 mg. The typical daily dose in epilepsy is 1,000 mg.

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Which antihistamines used in psych?

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antagonists of H1 receptor

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In clinical psychiatry, certain antihistamines (antagonists of histamine H1 receptors) are used to treat

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neuroleptic-induced parkinsonism and neuroleptic-induced acute dystonia

and also as hypnotics and
anxiolytics.

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Diphenhydramine (Benadryl) is used to treat

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neuroleptic-induced parkinsonism and

neuroleptic-induced acute dystonia and sometimes as a hypnotic

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Hydroxyzine hydrochloride (Atarax) and hydroxyzine pamoate (Vistaril) are used as

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anxiolytics

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Promethazine (Phenergan) is used for its

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sedative and anxiolytic effects

Front 308

Cyproheptadine (Periactin) has been used for the treatment of

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anorexia nervosa and
inhibited male and female orgasm caused by serotonergic agents

Front 309

Which antihist less used in psych?

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Fexofenadine (Allegra), loratadine (Claritin), and cetirizine (Zyrtec) are less commonly used in psychiatric practice

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Why were Terfenadine (Seldane) and astemizole (Hismanal) removed from market?

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because they were associated with serious cardiac arrhythmias when coadministered with some drugs (e.g., nefazodone [Serzone], selective serotonin reuptake inhibitors [SSRIs]).

Front 311

Diphenhydramine onset? peak?

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intramuscular (IM) diphenhydramine have their onset in 15 to 30 minutes, and the sedative effects of diphenhydramine peak in 1 to 3 hours

Front 312

Antihistamine MOA?

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Activation of H1 receptors stimulates wakefulness; therefore, receptor antagonism causes sedation.

Front 313

Cyproheptadine is unique among the antihistamine drugs, because

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it has both potent antihistamine and serotonin 5-HT2 receptor antagonist properties.

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Antihistamines are useful as a treatment for

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neuroleptic-induced parkinsonism, neuroleptic-induced acute dystonia, and neuroleptic-induced akathisia

They are an alternative to anticholinergics and amantadine for these purposes.

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The antihistamines are relatively safe hypnotics, but they are not superior to the

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benzodiazepines, which have been much better studied in terms of efficacy and safety

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??? is sometimes used to treat impaired orgasms, especially delayed orgasm resulting from treatment with serotonergic drugs

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Cyproheptadine

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Because it promotes weight gain, ??? may be of some use in the treatment of eating disorders, such as anorexia nervosa

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cyproheptadine

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??? can reduce recurrent nightmares with posttraumatic themes.

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Cyproheptadine can reduce recurrent nightmares with posttraumatic themes.

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Relationship of cyproheptadine and psych drugs?

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The antiserotonergic activity of cyproheptadine may counteract the serotonin syndrome caused by concomitant use of multiple serotonin-activating drugs, such as SSRIs and monoamine oxidase inhibitors (MAOIs)

Front 320

Antihistamine adverse fx?

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Antihistamines are commonly associated with sedation, dizziness, and hypotension, all of which can be severe in elderly persons, who are also likely to be affected by the anticholinergic effects of those drugs

Paradoxical excitement and agitation are adverse effects seen in a small number of persons. Poor motor coordination can result in accidents; therefore, persons should be warned about driving and operating dangerous machinery. Other common adverse effects include epigastric distress, nausea, vomiting, diarrhea, and constipation. Because of mild anticholinergic activity, some people experience dry mouth, urinary retention, blurred vision, and constipation. For this reason also, antihistamines should be used only at very low doses, if at all, by persons with narrow-angle glaucoma or obstructive GI, prostate, or bladder conditions

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A central anticholinergic syndrome with psychosis may be induced by either

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cyproheptadine or diphenhydramine

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Antihistamines and abuse potential?

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In addition to the above adverse effects, antihistamines have some potential for abuse. The coadministration of antihistamines and opioids can increase the euphoria experienced by persons with substance dependence.

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Antihistamine overdose risk?

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Overdoses of antihistamines can be fatal.

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Antihistamines are excreted in breast milk, so their use should be avoided by nursing mothers. Because of some potential for teratogenicity, the use of antihistamines should also be avoided by pregnant women

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Antihistamines and pregnant women?

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Diphenhydramine dosing?

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Adults: 25 to 50 mg three to four times per day
Children: 5 mg/kg three to four times per day, not to exceed 300 mg/day

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Cyproheptadine (Periactin) dosing?

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Adults: 4 to 20 mg/day
Children 2 to 7 yrs of age: 2 mg two to three times daily (maximum of 12 mg/day)
Children 7 to 14 yrs of age: 4 mg two to three times daily (maximum of 16 mg/day)

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The sedative property of antihistamines can be additive with other central nervous system (CNS) depressants, such as

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alcohol, other sedative-hypnotic drugs, and many psychotropic drugs, including tricyclic drugs and dopamine receptor antagonists (DRAs

Front 328

The beneficial effects of ?? can be antagonized by cyproheptadine.

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SSRIs

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Dosing of antihistamine for parkinsonism, akinesia, buccal movements?

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Intravenous (IV) administration of 25 to 50 mg of diphenhydramine is an effective treatment for neuroleptic-induced acute dystonia, which may immediately disappear. Treatment with 25 mg three times a day—up to 50 mg four times a day, if necessary—can be used to treat neuroleptic-induced parkinsonism, akinesia, and buccal movements

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Diphenhydramine can be used as a hypnotic at a ?? dose for mild transient insomnia

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50-mg
Doses of 100 mg have not been shown to be superior to doses of 50 mg, but they produce more anticholinergic effects than doses of 50 m

Front 331

Hydroxyzine is most commonly used as a

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short-term anxiolytic.

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Hydroxyzine should not be given

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IV, because it is irritating to the blood vessels

Front 333

Anorgasmia induced by SSRIs may sometimes be reversed with anticipated sexual activity

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4 to 16 mg a day of cyproheptadine taken by mouth 1 or 2 hours before

Front 334

Major side effects of barbiturates?

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Many problems are associated with these drugs, including high abuse and addiction potential, a narrow therapeutic range with low therapeutic index, and unfavorable side effects.

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The mechanism of action of barbiturates involves

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the γ-aminobutyric acid (GABA) receptor–benzodiazepine receptor–chloride ion channel complex.

Front 336

?, the most commonly used barbiturate for treatment of seizures, has indications for the treatment of generalized tonic-clonic and simple partial seizures

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Phenobarbital (Solfoton, Luminal)

Front 337

? has been used historically as a diagnostic aid in a number of clinical conditions, including conversion reactions, catatonia, hysterical stupor, and unexplained muteness, and to differentiate stupor of depression, schizophrenia, and structural brain lesions.

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Amobarbital (Amytal)

Front 338

Barbiturates vs benzodiazepines?

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A major difference between the barbiturates and the benzodiazepines is the low therapeutic index of the barbiturates. An overdose of barbiturates can easily prove fatal. In addition to narrow therapeutic indexes, the barbiturates are associated with a significant risk of abuse potential and the development of tolerance and dependence. Barbiturate intoxication is manifested by confusion, drowsiness, irritability, hyporeflexia or areflexia, ataxia, and nystagmus. The symptoms of barbiturate withdrawal are similar to, but more marked than, those of benzodiazepine withdrawal.

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Barbiturates are also contraindicated in patients with

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acute intermittent porphyria, impaired respiratory drive, or limited respiratory reserve.

Front 340

The primary area for concern about drug interactions with barbiturates is the potentially additive effects of

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respiratory depression.

Front 341

The therapeutic blood concentrations for phenobarbital in this indication range from XXX mg/L, although some patients may experience significant adverse effects in that range.

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15 to 40

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Meprobamate is indicated for

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short-term treatment of anxiety disorders. It has also been used as a hypnotic and is prescribed as a muscle relaxant.

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Meprobamate side effects?

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Meprobamate can cause CNS depression and death in overdose and carries the risk of abuse by patients with drug or alcohol dependence. Abrupt cessation following long-term use can lead to withdrawal syndrome, including seizures and hallucinations. Meprobamate can exacerbate acute intermittent porphyria. Other rare side effects include hypersensitivity reactions, wheezing, hives, paradoxical excitement, and leukopenia. It should not be used in patients with hepatic compromise.

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The major indication for chloral hydrate is

Back 344

to induce sleep
The benzodiazepines are superior to chloral hydrate for all psychiatric uses

Front 345

Drug Intx of chloral hydrate?

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It is because of metabolic interference that chloral hydrate should be strictly avoided with alcohol, a notorious concoction known as a Mickey Finn. Chloral hydrate may displace warfarin (Coumadin) from plasma proteins and enhance anticoagulant activity; this combination should be avoide

Front 346

Benzo MOA?

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hey share a common effect on receptors that have been termed benzodiazepine receptors, which in turn modulate γ-aminobutyric acid (GABA) activity

Front 347

Flumazenil (Romazicon) role and MOA?

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, a benzodiazepine receptor antagonist used to reverse benzodiazepine-induced sedation and in emergency care of benzodiazepine overdosage,

Front 348

Benzo use?

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Because benzodiazepines have a rapid anxiolytic sedative effect, they are most commonly used for immediate treatment of
insomnia,
acute anxiety, and
agitation or anxiety associated with any psychiatric disorder. In addition, the benzodiazepines are used as
anesthetics,
anticonvulsants, and
muscle relaxants.

Front 349

The absorption, the attainment of peak concentrations, and the onset of action are quickest for (which benzo's)

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iazepam (Valium),
lorazepam (Ativan),
alprazolam (Xanax),
triazolam (Halcion), and estazolam (ProSom)

Front 350

whereas only (benzo) have rapid and reliable absorption following intramuscular (IM) administration

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lorazepam and midazolam

Front 351

which benzo's have longest half life?

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Diazepam, chlordiazepoxide, clonazepam (Klonopin), clorazepate, flurazepam (Dalmane), prazepam (Centrax), quazepam (Doral), and halazepam (Paxipam) have plasma half-lives of 30 to more than 100 hours and, therefore, are the longest-acting benzodiazepines

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Advantages of long acting half life drugs?

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The advantages of long half-life drugs over short half-life drugs include
less-frequent dosing,
less variation in plasma concentration, and
less-severe withdrawal phenomena.

The disadvantages include drug accumulation,
increased risk of daytime psychomotor impairment, and

increased daytime sedation

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The advantages of the short half-life drugs over the long half-life drugs (benzo's)

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include no drug accumulation and less daytime sedation
The disadvantages include more-frequent dosing and earlier and more-severe withdrawal syndromes.
Rebound insomnia and anterograde amnesia are thought to be more of a problem with the short half-life drugs than with the long half-life drugs

Front 354

Difference in MOA of benzo's and Z drugs?

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Benzodiazepines activate all three specific GABA–benzodiazepine (GABA–BZ) binding sites of the GABA type a (GABAA)-receptor, which opens chloride channels and reduces the rate of neuronal and muscle firing.

Zolpidem, zaleplon, and eszopiclone have selectivity for certain subunits of the GABA receptor. This may account for their selective sedative effects and relative lack of muscle relaxant and anticonvulsant effects

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Benzo's are benzodiazepines with a sole indication for insomnia

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Temazepam, flurazepam, and triazolam

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? are the benzodiazepines approved for use as hypnotics

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Flurazepam, temazepam, quazepam, estazolam, and triazolam

Front 357

Compare : Flurazepam, temazepam, quazepam, estazolam, and triazolam

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The benzodiazepine hypnotics differ principally in their half-lives; flurazepam has the longest half-life, and triazolam has the shortest. Flurazepam may be associated with minor cognitive impairment on the day after its administration, and triazolam may be associated with mild rebound anxiety and anterograde amnesia. Quazepam may be associated with daytime impairment when used for a long time. Temazepam or estazolam may be a reasonable compromise for most adults. Estazolam produces rapid onset of sleep and a hypnotic effect for 6 to 8 hours

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Benzo's and Anxiety Ds?

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Panic: Alpraz, Clonazep
Social Phobia: Clonaz
GAD: yes

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Benzo for anxiety with depression?

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Alprazolam

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Benzo's and BP1?

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Clonazepam, lorazepam, and alprazolam are effective in the management of acute manic episodes and as an adjuvant to maintenance therapy in lieu of antipsychotics. As an adjuvant to lithium (Eskalith) or lamotrigine (Lamictal), clonazepam may result in an increased time between cycles and fewer depressive episodes.

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The first-line drug for akathisia is most commonly

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a β-adrenergic receptor antagonist.

Front 362

A few persons with idiopathic Parkinson's disease will respond to long-term use of ? with reduced bradykinesia and rigidity.

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zolpidem

Front 363

DRUG is used to manage the symptoms of alcohol withdrawal

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Chlordiazepoxide (Librium)

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Flumazenil is used to

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reverse the adverse psychomotor, amnesic, and sedative effects of benzodiazepine receptor agonists

Front 365

Flumazenil dosing?

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For the initial management of a known or suspected benzodiazepine overdosage, the recommended initial dosage of flumazenil is 0.2 mg (2 mL) administered IV over 30 seconds. If the desired consciousness is not obtained after 30 seconds, a further dose of 0.3 mg (3 mL) can be administered over 30 seconds. Further doses of 0.5 mg (5 mL) can be administered over 30 seconds at 1-minute intervals up to a cumulative dose of 3.0 mg. The clinician should not rush the administration of flumazenil. A secure airway and IV access should be established before the administration of the drug. Persons should be awakened gradually.

Most persons with a benzodiazepine overdosage respond to a cumulative dose of 1 to 3 mg of flumazenil; doses above 3 mg of flumazenil do not reliably produce additional effects. If a person has not responded 5 minutes after receiving a cumulative dose of 5 mg of flumazenil, the major cause of sedation is probably not benzodiazepine receptor agonists, and additional flumazenil is unlikely to have an effect.

Sedation can return in 1 to 3 percent of persons treated with flumazenil. It can be prevented or treated by giving repeated dosages of flumazenil at 20-minute intervals. For repeat treatment, no more than 1 mg (given as 0.5 mg a minute) should be given at any one time, and no more than 3 mg should be given in any 1 hour

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The most common adverse effect of benzodiazepines is

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drowsiness, which occurs in about 10 percent of all persons

Front 367

Benzo: Some persons also experience ataxia (less than XX percent) and dizziness (less than YY percent).

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Some persons also experience ataxia (less than 2 percent) and dizziness (less than 1 percent).

Front 368

High-potency benzodiazepines, especially? can cause anterograde amnesia.

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triazolam, and zolpidem

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An unusual, paradoxical increase in aggression has been reported in persons given benzodiazepines, although this effect may be most common in persons with

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preexisting brain damage.

Front 370

The symptoms of benzodiazepine intoxication include

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confusion, slurred speech, ataxia, drowsiness, dyspnea, and hyporeflexia

Front 371

Triazolam side fx?

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Triazolam has received significant attention in the media because of an alleged association with serious aggressive behavioral manifestations. The manufacturer, therefore, recommends that the drug be used for no more than 10 days for treatment of insomnia and that physicians carefully evaluate the emergence of any abnormal thinking or behavioral
changes in persons treated with triazolam, giving appropriate consideration to all potential causes. Triazolam was banned in Great Britain in 1991.

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Benzodiazepines can produce clinically significant impairment of respiration in persons with

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chronic obstructive pulmonary disease and sleep apnea.

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Benzodiazepines should be used with caution by

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persons with a history of substance abuse, cognitive disorders, renal disease, hepatic disease, porphyria, central nervous system (CNS) depression, or myasthenia gravis

Front 374

Benzo's and pregnancy?

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Some data indicate that benzodiazepines are teratogenic; therefore, their use during pregnancy is not advised.

Moreover, the use of benzodiazepines in the third trimester can precipitate a withdrawal syndrome in the newborn. The drugs are secreted in breast milk in sufficient concentrations to affect the newborn.

Benzodiazepines can cause dyspnea, bradycardia, and drowsiness in nursing babies.

Front 375

In rare cases, ? can cause hallucinations and behavioral changes. The coadministration of ? and SSRIs can extend the duration of hallucinations in susceptible patients

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zolpidem

Front 376

When benzodiazepines are used for short periods (1 to 2 weeks) in moderate dosages, they usually cause no significant tolerance, dependence, or withdrawal effects. The ??? may be an exception to this rule, because some persons have reported increased anxiety the day after taking a single dosage of the drug.

Back 376

short-acting benzodiazepines (e.g., triazolam)

Front 377

Benzodiazepine withdrawal syndrome consists of

Back 377

anxiety, nervousness, diaphoresis, restlessness, irritability, fatigue, light-headedness, tremor, insomnia, and weakness

Front 378

Abrupt discontinuation of benzodiazepines, particularly those with short half-lives, is associated with severe withdrawal symptoms, which can include

Back 378

depression, paranoia, delirium, and seizures.

Front 379

Benzo withdrawal: how to do?

Back 379

When the medication is to be discontinued, the drug must be tapered slowly (25 percent a week); otherwise, recurrence or rebound of symptoms is likely.

Front 380

Concurrent use of ?? during benzodiazepine discontinuation has been reported to permit a more rapid and better-tolerated withdrawal than does a gradual taper alone.

Back 380

carbamazepine (Tegretol)

The dosage range of carbamazepine used to facilitate withdrawal is 400 to 500 mg a day.

Front 381

How d/c alprazolam?

Back 381

There have been reports of successful discontinuation of alprazolam by switching to clonazepam, which is then gradually withdrawn.

Front 382

Benzo intx? most serious intx?

Back 382

The most common and potentially serious benzodiazepine receptor agonist interaction results in excessive sedation and respiratory depression occurring when benzodiazepines, zolpidem, or zaleplon are administered concomitantly with other CNS depressants, such as alcohol, barbiturates, tricyclic and tetracyclic drugs, dopamine receptor antagonists (DRAs), opioids, and antihistamines.

Front 383

Ataxia and dysarthria may likely occur when??are combined.

Back 383

lithium, antipsychotics, and clonazepam

Front 384

The combination of benzodiazepines and ??? has been reported to cause delirium and should be avoided.

Back 384

clozapine (Clozaril)

Front 385

Cimetidine (Tagamet), disulfiram (Antabuse), isoniazid, estrogen, and oral contraceptives increase the plasma concentrations of

Back 385

diazepam, chlordiazepoxide, clorazepate, flurazepam, prazepam, and halazepam.

Front 386

The plasma concentrations of triazolam and alprazolam are increased to potentially toxic concentrations by

Back 386

nefazodone (Serzone) and fluvoxamine (Luvox)

Front 387

Over-the-counter preparations of ???? can potentiate the action of benzodiazepine receptor agonists through synergistic overactivation of GABA receptors

Back 387

kava plant, advertised as a “natural tranquilizer,”

Front 388

? can lower the plasma concentration of alprazolam.

Back 388

Carbamazepine

Front 389

Antacids and food can ?Inc or decrease the plasma concentrations of benzodiazepines, and smoking can increase or decrease the metabolism of benzodiazepines.

Back 389

Antacids and food can decrease the plasma concentrations of benzodiazepines, and smoking can increase the metabolism of benzodiazepines.

Front 390

Rifampin (Rifadin), phenytoin (Dilantin), carbamazepine, and phenobarbital (Solfoton, Luminal) significantly change how? the metabolism of zaleplon

Back 390

increase

Front 391

The benzodiazepines can ? the plasma concentrations of phenytoin and digoxin (Lanoxin).

Back 391

increase

Front 392

SSRIs may prolong and exacerbate the severity of ????-induced hallucinations

Back 392

zolpidem

Front 393

Name a high and low potency beno

Back 393

clonazepam : 0.25 mg = 5mg diazepam
low potency: 15mg = above, oxazepam

Front 394

Zaleplon ???mg is the usual adult dose.

Back 394

is available in 5- and 10-mg capsules. A single 10-mg dose

Front 395

Eszopiclone and relation to sleep?

Back 395

Eszopiclone is available in 1-, 2-, and 3-mg tablets. The starting dose should not exceed 1 mg in patients with severe hepatic impairment or those taking potent CYP 3A4 inhibitors. The recommended dosing to improve sleep onset or maintenance is 2 or 3 mg for adult patients (ages 18 to 64) and 2 mg for older adult patients (ages 65 and older).

Front 396

Ramelteon MOA?

Back 396

Unlike the other hypnotic agents discussed in this section, ramelteon does not act on the benzodiazepine or GABA system. It specifically targets the melatonin MT1 and MT2 receptors in the brain's suprachiasmatic nucleus (SCN). The SCN regulates 24-hour, or circadian, rhythms including the sleep–wake cycle.

Front 397

Ramelteon is indicated for the treatment of

Back 397

insomnia characterized by difficulty with sleep onset.

Front 398

Ramelteon side fx?

Back 398

The most common adverse events seen with ramelteon were somnolence, dizziness, and fatigue. Ramelteon has been associated with decreased testosterone levels and increased prolactin levels. No evidence suggests abuse or dependence, and the drug is not designated as a controlled substance

Front 399

Ramelteon dosage? avoid combining with? cautin with ?

Back 399

The recommended dose for long-term use in adults is 8 mg taken within 30 minutes before going to bed. Ramelteon should not be combined with fluvoxamine and should not be used by patients with severe hepatic impairment.

Front 400

Unlike other currently used antidepressants, bupropion (Wellbutrin, Wellbutrin SR, Wellbutrin XL) does not act on the

Back 400

serotonin system

Front 401

Wellbutrin MOA?

Back 401

It is a norepinephrine and dopamine reuptake inhibitor.

The mechanism of action for the antidepressant effects of bupropion is poorly understood, although it presumably involves inhibition of dopamine and norepinephrine reuptake. Bupropion binds to the dopamine transporter in the brain. The effects of bupropion on smoking cessation may be related to its effects on dopamine reward pathways or to inhibition of nicotinic acetylcholine receptors.

Front 402

Bupropion is the only medication approved by the US Food and Drug Administration (FDA) for the prevention of

Back 402

seasonal depressive episodes of patients with seasonal affective disorder (SAD

Front 403

Bupropion and depression tx?

Back 403

Although overshadowed by the SSRIs as first-line treatment for major depression, the therapeutic efficacy of bupropion in depression is well established in both outpatient and inpatient settings. Observed rates of response and remission are comparable to those seen with SSRIs.

Front 404

Bupropion is most effective when combined with (to tx neonatical) for cigarette soessions

Back 404

nicotine substitutes (NicoDerm, Nicotrol).

Front 405

Buprion role ADHD

Back 405

Bupropion is used as a second-line agent, after the sympathomimetics, for treatment of attention-deficit/hyperactivity disorder (ADHD). It has not been compared with proved ADHD medications, such as methylphenidate (Ritalin) or atomoxetine (Strattera), for childhood and adult ADHD. Bupropion is an appropriate choice for persons with comorbid ADHD and depression or persons with comorbid ADHD, conduct disorder, or substance abuse. It may also be considered for use in patients who develop tics when treated with psychostimulants.

Front 406

Buproprion indications?

Back 406

Depression, Seasonal Affective Ds, Smoking Cessation, Bipolar Disorder, ADHD, Cocaine Detoxification, Hypoactive Sexual Desire

Front 407

Bupropion most common side effects?

Back 407

Headache, insomnia, dry mouth, tremor, and nausea are the most common side effects of bupropion use. Restlessness, agitation, and irritability may also occur

Front 408

Bupropion ... which disorders not to use in?

Back 408

Patients with severe anxiety or panic disorder should not be started on bupropion.

Most likely because of its potentiating effects on dopaminergic neurotransmission, bupropion can cause psychotic symptoms, including hallucinations, delusions, and catatonia, as well as delirium.

Front 409

What side effects do you NOT get with bupropion?

Back 409

Most notable about bupropion is the
absence of significant drug-induced orthostatic hypotension,
weight gain, daytime drowsiness, and anticholinergic effects.

Front 410

Bupropion cardiovasc changes?

Back 410

Hypertension can occur in some patients, but bupropion causes no other significant cardiovascular or clinical laboratory changes. Bupropion exerts indirect sympathomimetic activity, producing positive inotropic effects in human myocardium, an effect that may reflect catecholamine release.

Front 411

What is the risk of seizures with Bupropion?

Back 411

Concern about seizure has deterred some physicians from prescribing bupropion. Studies show that at dosages of 300 mg a day or less of sustained-release bupropion, the incidence of seizures is 0.05 percent, which is no worse than the incidence of seizures with other antidepressants. The risk of seizures increases to about 0.1 percent with dosages of 400 mg a day.

Front 412

What are risk factors for a seizure?

Back 412

Risk factors for seizures include a history of seizures, use of alcohol, recent benzodiazepine withdrawal, organic brain disease, head trauma, or epileptiform discharges on electroencephalogram (EEG).

Front 413

Bupropion and pregnancy/breast feeding?

Back 413

The use of bupropion by pregnant women is not associated with specific risk of increased rate of birth defects. Bupropion is secreted in breast milk, so the use of bupropion in nursing women should be based on the clinical circumstances of the patient and the judgment of the clinician.

Front 414

Bupropion safety compared to other antidepressants?

Back 414

In general, however, bupropion is safer in overdose cases than are other antidepressants, except perhaps SSRIs

Front 415

Bupropion drug interactions?

Back 415

Bupropion has been found to have an effect on the pharmacokinetics of venlafaxine. One study noted a significant increase in venlafaxine levels

No significant changes in plasma levels of the SSRIs paroxetine and fluoxetine have been reported. A few case reports, however, indicate that the combination of bupropion and fluoxetine (Prozac) may be associated with panic, delirium, or seizures.

Bupropion in combination with lithium (Eskalith) may rarely cause CNS toxicity, including seizures

Because of the possibility of inducing a hypertensive crisis, bupropion should not be used concurrently with monoamine oxidase inhibitors (MAOIs)

Delirium, psychotic symptoms, and dyskinetic movements may, however, be associated with the coadministration of bupropion and dopaminergic agents such as levodopa (

Sinus bradycardia may occur when bupropion is combined with metoprolol.

bupropion may increase plasma concentrations of valproic acid (Depakene)

Bupropion has some inhibitory effect on CYP 2D6

Front 416

Why must you spread Bupropion dosing? max dosing?

Back 416

To decrease risk of seizure.

A single dose of sustained-release bupropion should never exceed 300 mg. The maximal dose is 200 mg twice a day of the immediate-release or extended-release formulations.

An advantage of the extended-release preparation is that, after appropriate titration, a total of 450 mg can be given all at once in the morning

Front 417

Smoking cessation planning with bupropion?

Back 417

For smoking cessation, the patient should start taking 150 mg a day of sustained-release bupropion 10 to 14 days before quitting smoking. On the fourth day, the dosage should be increased to 150 mg twice daily. Treatment generally lasts 7 to 12 weeks

Front 418

Buspirone (BuSpar) was introduced in 1986 as the first nonsedating drug specifically indicated for the treatment of

Back 418

generalized anxiety disorder.

Front 419

Buspirone dosing properties

Back 419

At doses of 10 to 40 mg, single-dose linear pharmacokinetics are observed. Nonlinear pharmacokinetics are observed after multiple doses

Front 420

Buspirone half-life

Back 420

Because of a short half-life (2 to 11 hours), buspirone is dosed three times daily.

Front 421

Buspirone MOA?

Back 421

Buspirone acts as an agonist, partial agonist, or antagonist on serotonin 5-HT1A receptors. Its most pronounced action, as a presynaptic agonist at these receptors, inhibits release of serotonin, with consequent antianxiety effects. Action as an agonist at postsynaptic receptors appears to account for antidepressant activity.

Buspirone also has activity at 5-HT2 and dopamine type 2 (D2) receptors, although the significance of the effects at these receptors is unknown. At D2 receptors, it has properties of both an agonist and an antagonist.

Front 422

Buspirone MOA compared to SSRI/Benzo

Back 422

Buspirone has no effect on the γ-aminobutyric acid (GABA)-associated chloride ion channel on that receptor mechanism or the serotonin reuptake transporter, targets of other drugs that are effective in generalized anxiety disorder.

Front 423

Buspirone response takes how long?

Back 423

buspirone takes 2 to 3 weeks to exert its therapeutic effects implies that, whatever its initial effects, they involve the modulation of several neurotransmitters and intraneuronal mechanisms

Front 424

Buspirone is a narrow-spectrum antianxiety agent, with demonstrated efficacy only in the treatment of

Back 424

generalized anxiety disorder

Front 425

Buspirone advantage to other antidep? disadvantage?

Back 425

Buspirone, however, has an advantage over these agents in that it does not typically cause sexual dysfunction or weight gain.

In contrast to the SSRIs or venlafaxine (Effexor), buspirone is not effective in the treatment of panic disorder, obsessive-compulsive disorder (OCD), or social phobia

Front 426

Benzo vs buspirone?

Back 426

Some evidence suggests that, compared with benzodiazepines, buspirone is generally more effective for symptoms of anger and hostility, equally effective for psychic symptoms of anxiety, and less effective for somatic symptoms of anxiety.

Front 427

The full benefit of buspirone is evident only at dosages above

Back 427

30 mg a day.

Front 428

Benzo vs buspirone?

Back 428

Compared with the benzodiazepines, buspirone has a delayed onset of action and lacks any euphoric effect. Unlike benzodiazepines, buspirone has no immediate effects, and the patient should be told that a full clinical response may take 2 to 4 weeks. If an immediate response is needed, the patient can be started on a benzodiazepine and then withdrawn from the drug after buspirone's effects begin. Sometimes the sedative effects of benzodiazepines, which are not found with buspirone, are desirable; however, these sedative effects can cause impaired motor performance and cognitive deficits.

Front 429

Buspirone role in other disorders?

Back 429

Many other clinical uses of buspirone have been reported, but most have not been confirmed in controlled trials. Evidence of the efficacy of high-dosage buspirone (30 to 90 mg a day) for depressive disorders is mixed. Buspirone appears to have weak antidepressant activity, which has led to its use as an augmenting agent in patients who have failed standard antidepressant therapy. Buspirone is sometimes used to augment SSRIs in the treatment of OCD. Some reports indicate that buspirone may be beneficial against the increased arousal and flashbacks associated with posttraumatic stress disorder.
Because buspirone does not act on the GABA–chloride ion channel complex, the drug is not recommended for the treatment of withdrawal from benzodiazepines, alcohol, or sedative-hypnotic drugs, except as treatment of comorbid anxiety symptoms.
Scattered trials suggests that buspirone reduces aggression and anxiety in persons with organic brain disease or traumatic brain injury, SSRI-induced bruxism and sexual dysfunction, and nicotine craving, and in attention-deficit/hyperactivity disorder (ADHD)

Front 430

Buspirone Precautions and Adverse Effects?

Back 430

The most common adverse effects of buspirone are headache, nausea, dizziness, and, rarely, insomnia. No sedation is associated with buspirone

Front 431

Buspirone Drug Interactions?

Back 431

The coadministration of buspirone and haloperidol (Haldol) results in increased blood concentrations of haloperidol. Buspirone should not be used with monoamine oxidase inhibitors (MAOIs) to avoid hypertensive episodes, and a 2-week washout period should pass between the discontinuation of MAOI use and the initiation of treatment with buspirone. Drugs or foods that inhibit CYP450 3A4, for example, erythromycin (E-mycin), itraconazole (Sporanox), nefazodone (Serzone), and grapefruit juice, increase buspirone plasma concentrations

Front 432

Buspirone lab effects?

Back 432

Single doses of buspirone can cause transient elevations in growth hormone, prolactin, and cortisol concentrations, although the effects are not clinically significant.

Front 433

Buspirone dosing?

Back 433

treatment is usually initiated with either 5 mg orally three times daily or 7.5 mg orally twice daily. The dosage can be raised 5 mg every 2 to 4 days to the usual dosage range of 15 to 60 mg a day.

Front 434

Calcium channel inhibitors are used in psychiatry as

Back 434

antimanic agents for persons who are refractory to, or cannot tolerate, treatment with first-line mood-stabilizing agents

Front 435

MOA of Calcium Channel Blockers in Bipolar Disorder?

Back 435

The primary mechanism of action of calcium channel blockers in bipolar illness is not known. The calcium channel inhibitors discussed in this section inhibit the influx of calcium into neurons through L-type (long-acting) voltage-dependent calcium channels

Front 436

These 2 Ca Channel blockers have been demonstrated to be effective as maintenance therapy in bipolar illness.

Back 436

Nimodipine and verapamil have been demonstrated to be effective as maintenance therapy in bipolar illness.

Front 437

The most common adverse effects associated with calcium channel inhibitors are those caused by

Back 437

vasodilation: dizziness, headache, tachycardia, nausea, dysesthesias, and peripheral edema

Front 438

Despite its proved efficacy, carbamazepine was not approved as a treatment for bipolar disorder by the US Food and Drug Administration (FDA) until ???? and only in the ? form

Back 438

2004
extended release

Front 439

Both carbamazepine and oxcarbazepine are iminostilbenes. As seen in Figure 36.13-1, both drugs are almost structurally identical and are similar to the

Back 439

tricyclic antidepressants.

Front 440

The therapeutic effects of carbamazepine have been linked

Back 440

to blockade of type 2 or batrachotoxin-sensitive sodium channels, action on mitochondrial receptors, and activity at adenosine A1 receptors

Front 441

The primary biochemical effect of oxcarbazepine is

Back 441

potent blockade of sodium channels

Front 442

The half-life of carbamazepine ranges from

Back 442

18 to 54 hours, with an average of 26 hours.
With chronic administration, however, the half-life of carbamazepine decreases to an average of 12 hours.

This results from induction of hepatic CYP450 enzymes by carbamazepine, and specifically autoinduction of carbamazepine metabolism. The induction of hepatic enzymes reaches its maximal level after about 3 to 5 weeks of therapy

Front 443

The acute antimanic effects of carbamazepine are typically evident within

Back 443

the first several days of treatment. A 50 percent to 70 percent response is seen within 2 to 3 weeks of initiation

Front 444

Studies suggest that carbamazepine may be especially effective in persons who

Back 444

are not responsive to lithium, such as persons with dysphoric mania, rapid cycling, or a negative family history of mood disorders

Front 445

The antimanic effects of carbamazepine can be, and often are, augmented by concomitant administration of

Back 445

lithium, valproic acid, thyroid hormones, dopamine receptor antagonists, or serotonin-dopamine antagonists

Front 446

Carbamazepine use in other psych disorders?

Back 446

Carbamazepine helps to control symptoms associated with acute alcohol withdrawal. Although lacking the abuse potential of benzodiazepines in this population, the lack of any advantage of carbamazepine over the benzodiazepines for alcohol withdrawal and the potential risk of adverse effects with carbamazepine limit use in this role. Carbamazepine has been suggested as a treatment for the paroxysmal recurrent component of posttraumatic stress disorder. Uncontrolled studies suggest that carbamazepine is effective in controlling impulsive, aggressive behavior in persons of all ages who are not psychotic, including children and the elderly. Carbamazepine is also effective in controlling nonacute agitation and aggressive behavior in patients with schizophrenia and schizoaffective disorder. Persons with prominent positive symptoms (e.g., hallucinations) may likely respond, as are persons who display impulsive aggressive outbursts.

Front 447

Carbamazepine dose related side fx?

Back 447

Double or blurred vision
Vertigo
Gastrointestinal (GI) disturbances
Task performance impairment
Hematologic effects
Rash

Front 448

Carbamazepine idiosyncratic side effects?

Back 448

Agranulocytosis
Stevens-Johnson

Aplastic anemia

Hepatic failure

Rash
Pancreatitis

Front 449

The rarest but most serious adverse effects of carbamazepine are

Back 449

blood dyscrasias,
hepatitis, and
serious skin reactions

Front 450

Most of the adverse effects of carbamazepine are correlated with plasma concentrations above

Back 450

9 µg/mL

Front 451

Carbamazepine Main Side effects?

Back 451

Mild GI (nausea, vomiting, gastric distress, constipation, diarrhea, and anorexia) and
CNS (ataxia, drowsiness) are the most common side effects

Front 452

Carbamazepine unique property compared to other anticonvulsants?

Back 452

In contrast to lithium and valproate, other drugs used to manage bipolar disorder, carbamazepine does not appear to cause weight gain.

Front 453

Explain carb blood dyscrasia

Back 453

The drug's hematologic effects are not dose related. Severe blood dyscrasias (aplastic anemia, agranulocytosis) occur in about 1 in 125,000 persons treated with carbamazepine.

A correlation does not appear to exist between the degree of benign white blood cell suppression (leukopenia), which is seen in 1 percent to 2 percent of persons, and the emergence of life-threatening blood dyscrasias

Front 454

Warning signs of blood dyscrasia?

Back 454

Persons should be warned that the emergence of such symptoms as fever, sore throat, rash, petechiae, bruising, and easy bleeding can potentially herald a serious dyscrasia and the person should seek medical evaluation immediately

Front 455

Routine hematologic monitoring in carbamazepine-treated persons is recommended at ? months?

Back 455

3, 6, 9, and 12 months.

Front 456

Carb: Mild transaminase elevations warrant observation only, but persistent elevations more than X times the upper limit of normal indicate the need to discontinue the drug

Back 456

three
Hepatitis can recur if the drug is reintroduced to the person and can result in death.

Front 457

Carb and derm effects?

Back 457

About 10 percent to 15 percent of persons treated with carbamazepine develop a benign maculopapular rash within the first 3 weeks of treatment. Stopping the medication usually leads to resolution of the rash. Some patients may experience life-threatening dermatologic syndromes, including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The possible emergence of these serious dermatologic problems causes most clinicians to discontinue carbamazepine use in a person who develops any type of rash. The risk of drug rash is about equal between valproic acid and carbamazepine in the first 2 months of use, but is subsequently much higher for carbamazepine. If carbamazepine seems to be the only effective drug for a person who has a benign rash with carbamazepine treatment, a retrial of the drug can be undertaken. Many patients can be rechallenged without re-emergence of the rash. Pretreatment with prednisone (40 mg a day) may suppress the rash, although other symptoms of an allergic reaction (e.g., fever and pneumonitis) may develop, even with steroid pretreatment

Front 458

Carb and renal effects?

Back 458

Carbamazepine is occasionally used to treat diabetes insipidus not associated with lithium use. This activity results from direct or indirect effects at the vasopressin receptor. It also can lead to the development of hyponatremia and water intoxication in some patients, particularly the elderly or when used in high doses.

Front 459

Other carb side effects?

Back 459

Carbamazepine decreases cardiac conduction (although less than the tricyclic drugs do) and, thus, can exacerbate preexisting cardiac disease. Carbamazepine should be used with caution in persons with glaucoma, prostatic hypertrophy, diabetes, or a history of alcohol abuse. Carbamazepine occasionally activates vasopressin receptor function, which results in a condition resembling the syndrome of secretion of inappropriate antidiuretic hormone (SIADH), characterized by hyponatremia and, rarely, water intoxication.

Front 460

carb and preg?

Back 460

Minor cranial facial abnormalities, fingernail hypoplasia, and spina bifida in infants may be associated with the maternal use of carbamazepine during pregnancy.

Pregnant women should not use carbamazepine unless absolutely necessary.

All women with childbearing potential should take 1 to 4 mg of folic acid daily, even if they are not trying to conceive. Carbamazepine is secreted in breast milk.

Carbamazepine can decrease the blood concentrations of oral contraceptives, resulting in breakthrough bleeding and uncertain prophylaxis against pregnancy.

Front 461

Carb and drug intx?

Back 461

Carbamazepine decreases serum concentrations of numerous drugs as a result of prominent induction of hepatic CYP 3A4

Grapefruit juice inhibits the hepatic metabolism of carbamazepine.

Front 462

carb and valproate dosing?

Back 462

When carbamazepine and valproate are used in combination, the dosage of carbamazepine should be decreased, because valproate displaces carbamazepine binding on proteins, and the dosage of valproate may need to be increased.

Front 463

carb and lab values?

Back 463

Circulating increased levels of thyroxine (T4) and triiodothyronine (T3) without an associated increase in thyroid-stimulating hormone (TSH) may be associated with carbamazepine.

Carbamazepine is also associated with an increase in total serum cholesterol, primarily by increasing high-density lipoproteins.

Front 464

Carb dosing?

Back 464

The target dose for antimanic activity is 1,200 mg a day, although this varies considerably.

Front 465

GMC's can be relative contraindications for carbamazepine treatment

Back 465

Preexisting hematologic, hepatic, and cardiac diseases

Front 466

carb and liver disease: how dose?

Back 466

Persons with hepatic disease require only one third to one half the usual dosage; the clinician should be cautious about raising the dosage in such persons and should do so only slowly and gradually.

Front 467

carb and labs to order when starting?

Back 467

The laboratory examination should include a complete blood count with platelet count, liver function tests, serum electrolytes, and an electrocardiogram in persons more than 40 years of age or those with a preexisting cardiac disease. An electroencephalogram (EEG) is not necessary before the initiation of treatment, but it may be helpful in some cases for the documentation of objective changes correlated with clinical improvement.

Front 468

carb and drug level?

Back 468

Serum levels for antimanic efficacy have not been established. The anticonvulsant blood concentration range for carbamazepine is 4 to 12 µg/mL and this range should be reached before determining that carbamazepine is not effective in the treatment of a mood disorder.

Front 469

carb and warnings

Back 469

Patients should be informed that fever, sore throat, rash, petechiae, bruising, or unusual bleeding may indicate a hematologic problem and should prompt immediate notification of a physician.

This approach is probably more effective than is frequent blood monitoring during long-term treatment

Front 470

Carb and heme values to watch out for?

Back 470

Carbamazepine treatment should be discontinued, and a consult with a hematologist be obtained, if the following laboratory values are found: total white blood cell count below 3,000/mm3, erythrocytes below 4.0 × 106/mm3, neutrophils below 1,500/mm3, hematocrit less than 32 percent, hemoglobin less than 11 g/100 mL, platelet count below 100,000/mm3,

reticulocyte count below 0.3 percent, and a serum iron concentration below 150 mg/100 mL

Front 471

OXcarbamazepine: comparison of side effects to carb?

Back 471

The most common side effects are sedation and nausea. Less frequent side effects are cognitive impairment, ataxia, diplopia, nystagmus, dizziness, and tremor. In contrast to carbamazepine, oxcarbazepine does not have an increased risk of serious blood dyscrasias, so hematologic monitoring is not necessary. The frequency of benign rash is lower than observed with carbamazepine, and serious rashes are extremely rare. About 25 percent to 30 percent of patients who develop an allergic rash on carbamazepine also, however, develop a rash with oxcarbazepine. Oxcarbazepine is more likely to cause hyponatremia than carbamazepine. Approximately 3 percent to 5 percent of patients taking oxcarbazepine develop this side effect. It is advisable to obtain serum sodium concentrations early in the course of treatment, because hyponatremia may be clinically silent. In severe cases, confusion and seizure may occur

Front 472

Oxcarbazepine dosing?

Back 472

In clinical trials for mania, the doses typically used were from 900 to 1,200 mg per day, with a starting dose of 150 or 300 mg at night.

Front 473

Oxcarbazepine drug interactions?

Back 473

Drugs such as phenobarbital and alcohol, which induce CYP 3A4, increase the clearance and reduce oxcarbazepine concentrations.

Oxcarbazepine
induces CYP 3A4/5
and inhibits CYP 2C19,
which may affect the metabolism of drugs that utilize that pathway.

Women taking oral contraceptives should be told to consult with their gynecologist because oxcarbazepine may reduce concentrations of their contraceptive and, thus, decrease its efficacy.