Term
| Name one high potency typical antipsychotic |
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Definition
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Term
| Name one low potency typical antipsychotic |
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Definition
| Chlorpromazine (Thorazine) |
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Term
| Characteristics of high potency antipsychotics |
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Definition
– Lower mg doses
– Potent D2 antagonism
– Lower anticholinergic SE
– Higher risk of EPS
– Higher risk of TD
– Higher risk of NMS |
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Term
| Characteristics of low potency antipsychotics |
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Definition
– Higher mg doses
– Less potent D2 antagonism
– Significant anticholinergic SE
– Lower EPS risk
– Lower TD risk
– Lower risk of NMS |
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Term
| Characteristics of atypical antipsychotics |
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Definition
– Shorter binding time at D2 receptors
– 5HT2A antagonism |
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Term
| List the atypical antipsychotics we are responsible for |
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Definition
1. Clozapine (Clozaril)
2. Olanzapine (Zyprexa)
3. Risperidone (Risperdal)
4. Paliperidone (Invega)
5. Qeutiapine (Seroquel)
6. Ziprasidone (Geodon)
7. Aripiprazole (Abilify) |
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Term
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Definition
Atypical antipsychotic
Complex mechanism of action
First antipsychotic to be recognized that caused few extrapyramidal side effects, no tardive dyskinesia, no prolactin elevation
Possibly reduces the risk of suicide
Decreases violence and agression
May help with tardive dyskinesia
Most significant side effect is agranulocytosis (0.5-2%)
Other side effects
– Seizures
– Sedation
– Salivation
– Myocarditis
– Significant weight gain and cardiometabolic risk |
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Term
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Definition
Atypical antipsychotic
No EPS symptoms
Very sedating
Significant weight gain
High cardiometabolic risk |
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Term
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Definition
Acts as an atypical antipsychotic at lower doses
At high doses, tends to act more like a typical resulting in EPS and increases prolactin
Approved for pediatric use
Available in a two week depot injection
Lower risk of weight gain and cardiometabolic risk |
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Term
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Definition
Next generation of risperidone
Sustained release and more easily dosed
Lower EPS than risperidone
Weight gain, cardiometabolic syndrome
Increases the QTc interval |
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Term
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Definition
Virtually no EPS
No prolactin elevation
Preferentially used in patient’s with Parkinson’s
May have enhanced norepirnephrine activity and stronger antidepressant activity
Significant weight gain at high doses |
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Term
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Definition
Low symptoms of EPS
Low prolactin elevation
Significant QTc prolongation
Fewer propensities for weight gain
Lower cardiometabolic risk |
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Term
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Definition
Role for augmentation in depression
Not as sedating
Can cause agitation or akathesia
Significantly less weight gain, much lower CM risk |
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Term
| List the mood stabilizers we are responsible for |
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Definition
1. Lithium
2. Valproic Acid/ Divalproex (Depakote)
3. Lamotrigine (Lamictal)
4. Carbamazepine (Tegretol) and Oxcarbamazepine (Tripletal) |
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Term
| Lithium mechanisms of action |
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Definition
– Mechanism of action is not entirely clear
– Candidates for mechanism of action are various signal transduction sites beyond neurotransmitters
Second messengers such as the phoshatidyl inositol system (inhibits inositol monophosphate)
Modulation of G proteins
Regulation of gene expression for growth factors and neuronal plasticity (inhibition of glycogen synthetase kinase 3 and protein kinase C) |
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Term
| Use of Lithium in Mood Disorders |
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Definition
Proven effective for manic episodes and in the prevention of recurrence
Also effective in treating the depressive phase of bipolar disorder |
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Term
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Definition
Lithium is excreted exclusively through the kidney
Lithium is excreted along with sodium
Hyponatremia poses a risk of lithium toxicity
Patients should avoid becoming dehydrated during exercise
Sodium depleting diuretics should be avoided
Low sodium diets can increase lithium levels
NSAIDS should be avoided because of their effect on renal prostaglandin synthesis and sodium excretion
Serum levels of lithium are monitored through treatment and there is a narrow therapeutic index between normal levels a toxicity |
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Term
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Definition
Tremor
Nausea and diarrhea
Nephrogenic diabetes insipidus
Hypothyroidism (5-15% of patients)
Weight gain
Alopecia
Interference of conduction in the SA node (benign)
Ebstein’s anomaly (triscuspid valve defect) in the first trimester of pregnancy
Avoid in patients with cardiac conduction problems
Avoid in patients with impaired renal function and use cautiously in those at risk for impaired renal function
Benign and reversible leukocytosis |
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Term
| Tests to do before starting Lithium |
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Definition
Check renal function by checking BUN and creatinine
Baseline thyroid function tests
Urine pregnancy test
EKG
Baseline blood counts |
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Term
| Tests while monitoring Lithium |
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Definition
Renal function
Thyroid function
Lithium levels
Always ask about possibility of pregnancy |
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Term
| Symptoms of Lithium Toxicity |
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Definition
Coarse tremor
Vomiting
Ataxia
Dysarthria
Confusion
Seizures
May require dialysis if severe |
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Term
| Valproic Acid/ Divalproex (Depakote) Mechanism |
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Definition
– Anticonvulsant
– Exact mechanism of action is unknown but may be
Inhibiting voltage sensitive sodium channels
Increasing the action of GABA
Regulating downstream signal cascades
– Uses of Valproic Acid/ Divalproex (Depakote) in Mood Episodes
Effective in the acute phase of mania
Effective at the prevention of recurrence of mania
Effectiveness as an antidepressant is not established
May more effective than other agents in rapid cycling |
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Term
| Metabolism of Valproic Acid/ Divalproex (Depakote) |
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Definition
Hepatic metabolism
Inhibits P450 enzymes |
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Term
| Side Effects of Valproic Acid/ Divalproex (Depakote) |
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Definition
Sedation
Weight gain (in females – PCOS, insulin resistance) * Compliance issue
Alopecia
Tremor
Thrombocytopenia (Do NOT use in patients with clotting abnormalities)
Hepatotoxicity (Do NOT use in patients with liver disease)
Rare cases of pancreatitis
1-2% chance of neural tube defects in the first trimester of pregnancy |
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Term
| Lamotrigine (Lamictal) Mechanism |
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Definition
Inhibits voltage sensitive sodium channels
Inhibits glutamate release
Possible effects on blocking calcium channels |
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Term
| Uses of Lamotrigine (Lamictal) in Mood Episodes |
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Definition
Used off label (not FDA approved) for depressed phase but generally accepted by clinicians as effective
Unique in that it is one of the few agents showing clinical effectiveness for the depressed phase
Not appropriate for mania |
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Term
| Lamotrigine (Lamictal) metabolism |
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Definition
Primarily hepatic
Levels are affected by other medications
Increased by valproic acid/divalproex
Decreased by carbamazepine |
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Term
| Side Effects of Lamotrigine (Lamictal) |
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Definition
Relatively few side effects except sedation
No labs to monitor
Must be started slowly and titrated
1 in 1000 risk of Stevens-Johnson syndrome and toxic epidermal necrolysis (risk is increased with combined with valproic acid/divalproex) |
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Term
| Carbamazepine (Tegretol) and Oxcarbamazepine (Tripletal) Mechanism |
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Definition
– Anticonvulsant
– Mechanism of action
Blocks voltage sensitive sodium channels
Enhances GABA function |
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Term
| Uses of Carbamazepine (Tegretol) and Oxcarbamazepine (Tripletal) in Mood Episodes |
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Definition
Carbamazepine is effective in the treatment of mania
Effective to prevent mania
Not studied in bipolar depression
Oxcarbamazepine has never been proven to work as a mood stabilizer but is used “off label” for mania |
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Term
| Metabolism of Carbamazepine (Tegretol) and Oxcarbamazepine (Tripletal) |
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Definition
Both hepatically metabolized
Cabamazepine induces hepatic enzymes increasing its own metabolism and the metabolism of other drugs over a about a two week period (Oxcarbamazepine does not induce hepatic enzymes) |
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Term
| Side Effects of Carbamazepine (Tegretol) and Oxcarbamazepine (Tripletal) |
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Definition
Carbamazepine
Sedation
Rash progress to Stevens-Johnson
Agranulocytosis
Ataxia
SIADH (hyponatremia)
Elevated liver enzymes
Do NOT use in patients with liver disease or neutropenia
Can cause neural tube defects, craniofacial defects and microcephaly in pregnancy
Decreases the effectiveness of oral contraceptives
Oxcarbamazepine
Fewer side effects, mainly sedation
Higher risk of SIADH |
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Term
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Definition
| Common side effects include anxiety, restlessness, sleep disturbance, nausea, and loose stools (transient). Sexual dysfunction related to SSRIs is a major side effect and can impact a patient’s quality of life. Men commonly experience delayed ejaculation (SSRIs are also used in the treatment of premature ejaculation). Women often experience anorgasmia. Either gender may experience a general loss of libido. Patients are often reluctant to self disclose these side effects. Other side effects include headache, tremor, increased perspiration, and dry mouth. |
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Term
| Serotonin Discontinuation Symptoms |
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Definition
| Nausea, irritability, tearfulness, fatigue, and dizziness when SSRIs (except Fluoxetine) are discontinued abruptly. |
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Term
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Definition
SSRI
•Dose range is 20 to 40 mg per day, up to 80 mg.
•Half life of fluoxetine is 2-3 days, half life of norfluoexine is up to two weeks
•Weekly formulation available |
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Term
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Definition
SSRI
• Dose range is usually 50 to 150 mg
• Half life is 24 hours
• Doses start at 25 mg and must be titrated up
• Some dopamine activity, may be useful in brain injured patients |
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Term
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Definition
SSRI
• Dose range is 20 to 40 mg
• Half life is 24 hours
• Somewhat sedating, useful in anxiety disorders
• Significant 2D6 inhibition
• Anticholinergic side effects |
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Term
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Definition
SSRI
• Dose range 20 to 60 mg
• Half life of 24 hours
• Fewer drug interactions, useful when someone is on numerous medications
• Newly introduced enantiomer, escitalopram (Lexapro), with similar profile and dose ranges of 10 to 30 mg a day |
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Term
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Definition
SSRI
• Can be used for depression but only approved to treat OCD
• 50-150 mg dose range |
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Term
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Definition
• Characterized by fever, delirium, hypertension, hypotension, neuromuscular excitability but is uncommon
• Risk increases when using more than one serotonergic drug
• Can result in death |
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Term
| List the SSRIs we are responsible for |
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Definition
1. Fluoxetine (Prozac)
2. Sertraline (Zoloft)
3. Paroxetine (Paxil)
4. Citalopram (Celexa)
5. Fluvoxamine (Luvox) |
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Term
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Definition
Primarily used in depression.
• Mechanism of action not entirely understood but likely increases dopamine and norepinephrine
• Few side effects
• Some seizure risk, contraindicated if history of seizures or any conditions with electrolyte imbalance (eating disorders, dialysis) which might lower the seizure threshold
• Used in smoking cessation
• No sexual side effects
• Effective in decreasing sexual side effects when given with an SSRI
• Increasing evidence that may be useful in treating ADHD
• Sustained release usually 150mg twice a day, max dose is 200mg twice a day; extended release can be taken once a day |
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Term
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Definition
• Serotonin presynaptic reuptake inhibitor (like and SSRI)
• Postsynaptic 5HT 2 receptor antagonism
• Sedating
• Fewer sexual side effects
• Has fairly significant 3A3/4 inhibition, use carefully in individuals on multiple medications
• Slow titration of dose, usually starting at 100mg at bedtime, increasing every few days, to a dose range of 400mg to 600mg per day
• Can be divided into two doses or given all at bedtime |
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Term
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Definition
• Norepinephrine and serotonin reuptake inhibition
• Side effect profile similar to SSRIs
• Dose related increase in blood pressure
• Very few drug interactions, very useful in patient on numerous medications
• Dose range is 75mg to 225 mg
• Also approved for the treatment of Generalized Anxiety Disorder |
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Term
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Definition
• Relatively greater norepinephrine reuptake inhibition than venlfaxine but still more serotinergic than noradrenergic
• Plasma levels are more consistent than venlafaxine
• More potent effect or norepinephrine may be helpful in certain pain conditions such as fibromyalgia |
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Term
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Definition
• Serotonin and norepinephrine reuptake inhibition
• Side effect profile similar to SSRIs
• Has evidence and indication for use in depression with pain conditions |
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Term
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Definition
• Complex and unique action
• Antagonist at the central PRESYNAPTIC α 2 adrenergic autoreceptor
• Autoreceptors for neurotransmitters are located on the pre-synaptic neuron.
• The neurotransmitters in the synapse float back to these receptors, bind to them and tell the presynaptic neuron, “You’ve released enough, now stop.”
• Think about the presynaptic autoreceptor as a brake.
• When the mirtazapine blocks that autoreceptor, the neurotransmitters can’t bind and tell the neuron to stop putting out the transmitter.
• The result is increased release of neurotransmitter, the brakes are off.
• Sedating
• Antihistaminic properties dramatically increase appetite and weight gain is a serious concern.
• Rare cases of agranulocytosis but routine monitoring of CBC has not been recommended.
• Dose range is 15-45 mg
• The side effects of this antidepressant can be very helpful in medically ill individuals for whom loss of appetite and poor sleep are a problem.
• Very expensive |
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Term
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Definition
• Rarely used for the treatment of depression at this time
• Most common use is for insomnia in low doses
• Major concern is PRIAPISM
• Occurs in about 1:7000 to 1:10,000 men
• This is a very serious condition where patient education is important
• Failure to be treated in a timely manner can result in permanent erectile dysfunction (and lawsuits) |
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Term
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Definition
• Side effects are related to number of neurotransmitter systems involved
• Anticholinergic: dry mouth, urinary retention, constipation, blurred vision
• Alpha adrenergic blockade: orthostatic hypotension
• Antihistamine: sedation, increased appetite and weight gain
• TCAs cause prolongation of the QT interval and an EKG must be done prior to starting the medication and periodically during treatment.
• TCAs ARE VERY LETHAL IN OVERDOSE (2-3 GRAMS ARE LETHAL) |
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Term
| Monoamine Oxidase Inhibitors (MAOIs) |
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Definition
• Inhibits the enzyme that metabolizes norepinephrine, serotonin, dopamine, and tyramine.
• Result is increase in neurotransmitters in the synapse
• Irreversible inhibition lasts for two weeks after stopping the medication
• Used for Major Depression, particularly the atypical subtype, Anxiety Disorders, Social Phobia, Treatment Resistant Depression
• Selegiline (Emsam)
Side effect: hypertensive crisis after consuming tyramine rich foods. |
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