Antipsychotics/Neuroleptics

Mechanism of typical antipsychotics

Antipsychotics/Neuroleptics

4 Clinical Indications for use

1. Schizophrenia (primarily treats positive symptoms)

2. psychosis

3. acute mania

4. Tourette's syndrome

Antipsychotics/Neuroleptics

Four aspects of its toxicity/side effects

1. Highly lipid soluble, stored in body fat, so its very slow to be removed from the body

2. Extrapyramidal system (EPS) side effects

3. Endocrine side effects (hyperprolectinemia -> galactorrhea)

4. Side effects from blocking receptors...

muscarinic (dry mouth, constipation)

alpha adrenergic (hypotension)

histamine (sedation)

2 serious and/or long-term toxicities assoc w/ neuroleptics

(there's a mnemonic for one of them)

Tardive dyskinesia - sterotypic oral-facial movements due to long-term antipsychotic use; Often irreversible

Neuroleptic malignant syndrome (NMS) - clinical tetrad:

1. rigidity

2. myoglobinuria

3. autonomic instability

4. hyperpyrexia

Treat with dantrolene, agonists (eg bromocryptine)

For NMS, think FEVER:

Fever

Encephalopathy

Vitals Unstable

Elevated Enzymes

Rigidity of Muscles

Antipsychotics/Neuroleptics

Name 3 high-potency examples, and side effects

Haloperidol

Trifluoperazine

Fluphenazine

Neurologic side effects

Non-neurologic side effects

Chloropromizine -> Corneal deposits

Thioridazine -> reTinal deposits

Atypical Antipsychotics

Give 6 specific drug examples

(theres a mnemonic to remember them)

It's atypical for OLd CLOSets to QUIETly RISPER from A to Z

Olanzapine

Clozapine

Quetiapine

Risperidone

Aripiprazole

Ziprasidone

They block

5HT-2,

alpha,

H1,

and dopamine receptors

Schizophrenia - treats positive AND negative symptoms!

Olanzapine can also be used to treat:

OCD

anxiety disorder

depression

mania

Tourette's syndrome

The atypicals have fewer extrapyramidal and anticholinergic side effects than traditional antipsychotics

Olanzapine and clozapine can cause significant weight gain

Clozapine can cause agranulocytosis, requires weekly WBC monitoring

Depression

Major Depressive Episode:

Definition

Characterized by at least 5 of these 9 symptoms for 2 weeks (symptoms must include patient-reported depressed mood or anhedonia):

1. Sleep Disturbance

2. Loss of Interest (Anhedonia)

3. Guilt or feelings of worthlessness

4. Loss of Energy

5. loss of Concentration

6. Appetite/weight changes

7. Psychomotor retardation or agitation

8. Suicidal ideations

(9) Depressed mood

SIG E CAPS!

Depression 

Recurrent major depressive disorder: 

Depression

Dysthymia:

Depression

Seasonal affective disorder:

assoc w/ winter

improves in response to full-spectrum light exposure

Depression

6 changes in sleep stages typically experienced by patients with depression

1. decreased slow wave sleep

2. decreased REM latency

3. increased REM early in sleep cycle

4. Increased total REM sleep

5. Repeated nighttime awakenings

6. Early morning awakening (important screening question)

Depression

Atypical Depression

3 defining characteristics

2 associated symptoms

T/F: Its the most common subtype of depression

2 Treatment options

(Differs from classical forms of depression)

Characterized by:

Hypersomnia

Overeating

Mood reactivity (= ability to experience improved mood in response to positive events, as opposed to unrelenting sadness)

Associated w/:

Weight Gain

Sensitivity to rejection

True!

Treatment: MAOI's, SSRI's

Depression

Electroconvulsive Therapy (ECT)

What is it used to treat?

How does it work?

What are 2 major adverse effects, and how can you minimize these?

Used to treat major depressive disorder that is refractory to other treatments

Works by producing a painless seizure in an anesthetized patient

Major adverse affects:

disorientation

anterograde or retrograde amnesia -- can be minimized when ECT is performed unilaterally

Bipolar Disorder

Definition 

How are the patient's mood and functioning between episodes?

How do BPD patients respond to antidepressants?

Characteristic behavior?

What is their suicide risk compared to other psychiatric patients?

What are 2 categories of pharmacological treatment agents for BPD, and give 3 specific examples

BDP is defined by the presence of at least 1 manic (Bipolar I) or hypomanic (Bipolar II) episode, with depressive symptoms at some point.

Patient's mood and functioning usually return to normal between episodes

Use of antidepressants in BPD patients can lead to increased mania

Also, repeated loss of efficacy of anti-depressant is displayed in BPD patients after initial response

Tend to engage in pleasurable activity that have potentially painful consequences

Suicide risk is high

Treatment:

Mood stabilizers, such as lithium, valproic acid, and carbamazepine

Atypical antipsychotics

BPD

Manic Episode:

Def

What is required for Dx of manic episode?

Manic episode = distinct period of abnormally and persistently elevated, expansive, or irritable mood lasting at least 1 week. (or any duration if hospitalization is necessary)

Dx requires 3 or more of the following during mood disturbance (4 if mood is only 'irritable'):

1. Distractability

2. Irresponsibility/Impulsive Behavior - seeks pleasure w/o regard to consequences; hedonistic

3. Grandiosity - inflated self-esteem

4. Flight of ideas - racing thoughts

5. Increase in goal-directed Activity/psychomotor Agitation

6. Decreased need for Sleep

7. Talkativeness or pressured speech

maniacs DIG FAST

Assoc. w/ marked impairment in functioning

Symptoms can NOT be due to:

a. the effect of a substance (SSRI's, coke, meth, PCP)

b. a general medical condition

Individual w/ DIG FAST characteristics, like manic episode, except mood distrubance is not severe enought to cause marked impairment in social and/or occupational functioning or to necessitate hospitalization. (and appears for only 4 days instead of the minimum of 6)

NO psychotic features.

Antidepressants

Name 4 different classes, and on what component of what neuron that each acts

(give specific drug eg's where appropriate)

1. MAOI's, act on pre-synaptic mono-amine oxidases of noradrenergic and serotonergic neurons

2. Tricyclics (maprotiline) - NE reuptake inhibitors

3. SSRI's (trazodone) - Selective Serotonin Reuptake Inhibitor

4. Mirtazapine - alpha2 adrenergic receptor inhibitor (a2-R normally has inhibitory effects in the CNS)

Tricyclic Antidepressants

Give 7 specific tricyclic drugs

Mech of action?

4 Indications for use? (Give specific assoc drugs where appropriate)

Imipramine, amitriptyline, desipramine, nortiptyline, clomipramine, doxepin, amoxapine (in step 1 book, not in notes)

Mech:  Block reuptake of NE and serotonin

Indications:

Major depression

Bedwetting, aka Enuresis (imipramine) --- due to its anticholinergic side effects

OCD (clomipramine)

Fibromyalgia

(Other indications from lecture: Pain disorder, including migraine and chronic pain, urticaria (hives), pruritis (itch)

Tricyclic Antidepressants

Side effects? (3) How do primary/secondary/tertiary TCA's compare in their side effect profiles?

Symptoms associated w/ toxicity? (6)

Any treatment(s) for these effects?

Side effects:

1. Sedation

2. alpha-blocking effects

3. Atropine-like anticholinergic effects (eg tachycardia, urinary retention)

Cause sexual dysfunction - ED and delayed ejaculation in men, anorgasmia in women

Antidepressants cause Mania in BPD patients

• Tertiary TCA's (amitriptyline) have more anticholinergic effects than the Secondary TCA's (nortriptyline)
• Desipramine is the least sedating and has lower seizure threshold

Toxicity:

Tri-C's - Convulsions, Coma, Cardiotoxicity (arrhythmias)

Respiratory Depression

Hyperpyrexia (way high temp)

Confusions and hallucinations in elderly due to anticholinergic side effects (use nortriptyline to avoid this)

Use NaHCO3 to treat CV toxicity

SSRI's

List 4 specific SSRI drugs

Clinical Indications? (4)

How long after administration does it take for SSRI's to have antidepressant effect?

Serotonin-specific reuptake inhibitors

Fluoxetine, paroxetine, sertraline, citalopram

Indications:

1. Depression

2. OCD

3. Bulimia

4. Social Phobias

(additional indications from Lecture: GAD, Panic disorder, PTSD, PMDD, Premature ejaculation, Pain syndromes)

Takres 2-3 weeks for SSRI's to have an effect

SSRI's

Toxicities? (3 major ones)

1. GI distress

2. Sexual dysfunction (anorgasmia)

3. Serotonin Syndrome - can occur w/ any drug that increases serotonin (so MAOI's may cause same effect):

• hyperpyrexia
• muscle rigidity
• cardiovascular collapse
• flushing/sweating
• diarrhea/abdominal pain
• seizures

SNRIs

2 specific SNRI drugs

What are they? (Mech)

Clinical Indications (3; indicate specific drugs where appropriate)

Do either of the drugs affect NE or 5HT more?

Toxicity due to SNRI (main one and 3 less common ones)?

Inhibit serotonin and NE reuptake (try to increase therapeutic NE effects w/o all the original side effecs of TCA's)

Indications:

Depression

Venlafaxine is also used in generalized anxiety disorder GAD, Panic Disorder

Duloxetine also indicated for diabetic peripheral neuropathy

Dual acting effects is thought to have moved more people into full remission

Duloxetine has a greater effect on NE

Toxicity:

Serotonin mediated:  Nausea, stimulation/activation effects; sexual dysfunction (same as SSRI's)

NE-mediated: Increase BP; tremor, agitation

(Tolerability is nearly the same SSRI's)

MAOI's

4 Specific MAOI's; any selectivity?

3 Clinical Indications

2 Toxicity Effects

Containdicated w/ any other meds (3)?

Phenelzine

trancylcypromine

isocarboxazide

selegiline (selective MAO-B inhibitor)

Indications:

Atypical depression (sleeping too little, eating too much)

anxiety

Hypochondriasis

(Also in lecture: Major Depression, Dysthymia, Panic Disorder, Bulimia, Treatment Resistant Depression, OCD, GAD, Headache)

Toxicity/Contraindications:

• Hypertensive crisis w/ tyramine ingestion
• CNS Stimulation
• Hypertensive crisis also occurs w/ beta-agonists
• SSRI's and meperidine w/ MAOI's can both cause serotonin syndrome

BUT MAOI's have little to no anticholinergic side effects

(From lecture: orthostatic hypOtension, weight gain, sexual dysfunction, and insomnia)

also should avoid sympathomimetic agents and other antidepressants when on MAOI's to prevent Hypertensive crisis

meperidine is a narcotic analgesic, pain reliever similar to morphine

Atypical Antidepressants

Name 4

Bupropion (Wellbutrin)

Mirtazapine

Maprotiline

Trazodone

Atypical Antidepressants

Bupropion:

How does it affect the CNS?

Other uses?

List 4 toxicity side effects

aka Wellbutrin

Increases NE and DA via unknown mech

Toxicity:

1 & 2. stimulant effects (tachycardia, insomnia)

3. headache

4. seizure in bulimic patients

No sexual side effects

Atypical Antidepressants

Mirtazapine:

How does it act on the CNS?

4 Toxicity/side effects

alpha 2 antagonist (halts CNS inhibition and increases the realease of NE and serotonin)

Its also a potent 5HT2 and 5HT3 receptor antagonist

Toxicity:

sedation

increased appetite

weight gain

dry mouth

Atypical antidepressants

Maprotiline

Mech?

2 toxicities?

NE reuptake inhibitor

Toxicity:  Sedation,

orthostatic hypotension

Atypical Antidepressants

Trazodone

Mech in the CNS?

Clinical indication(s)?

4 associated toxicity side effects?

Primarily inhibits serotonin reuptake

Used for insomnia, as high doses are needed for antidepressant effects

Tox:  

Sedation

nausea

priapism (erection lasting 4+ hours) - trazoBONE

postural hypotension

Mood Stabilizers

Lithium:

Mech of action?

Indications?

7 Toxicities? (how can you remember these?)

Narrow/Wide therapeutic window?

Mech:  not established, maybe related to inhibtion of phosphoinositol cascade

Used as a mood stabilizer for BPD

Also used for SIADH (syndrome of inappropriate ADH hypersecretion)

Toxicities:

1. Tremor

2. Sedation  (including cognitive dulling, decreased creativity, decreased memory and concentration)

3. Edema

4. Heart Block

5. Hypothyroidism

6. Polyuria (its an ADH antagonist, causes nephrogenic diabetes insipidus)

7. Teratogenesis

LMNOP = 

Lithium side effects:

Movement (tremor)

Nephrogenic diabetes insipidus

HypOthyroidism

Pregnancy problems

Narrow therapeutic window, requires close monitoring of serum levels

(other adverse affects listed in lecture: GI effects, weight gain, and dermatologic effects like psoriasis/acne, and benign leukocytosis)

1. BPD***

2. Depression Augmentation

3. Schizoaffective disorder

4. Refractory (treatment-resistant) schizophrenia

5. PTSD

6. Borderline Personality Disorder

7. Intermittent Explosive Disorder

8. Neuropathic Pain

9. Alcohol Detox 

Panic Disorder 

Definition

4 Treatment Options? (3 are drugs)

Defined by the presence of recurrent periods of intense fear and discomfort peaking in 10 minutes w/ at least 4 of the following:

Parasthesias

Abnormal distress

Nausea

Intense fear of dying or losing control

lIght-headedness

Chest Pain

Chills

Choking

disConnectedness

Sweating

Shaking

Shortness of breath

remember it as PANICS

Associated with persistent fear of having another attack

Treatment Options:

1. Cognitive Behavioral Therapy

2. SSRI's

3. TCAs

4. Benzodiazepines

Specific Phobia

Def

What is patient's opinion of their phobia?

Treatment?

Fear that is excessive or unreasonable and interferes w/ normal function

Cued by presence or anticipation of a specific object/situation

Patient recognizes their fear as excessive

Rx: systematic desensitization

What other neurological disorder is OCD assoc. w/?

Rx?

PTSD

Def:

How does it change the individual's behavior?

Persistent reexperiencing of a previous traumatic event; may involve nightmares or flashbacks, intense fear, helplessness, or horror

Leads to avoidance of stimuli assoc w/ the trauma, and persistently increased arounsal

Can cause impaired functioning

PTSD

Typical time of onset?  How long must the disturbance last to be considered PTSD?

Rx? (One pharmacologic and one non-pharmacologic)

Onset typically greater than 1 month after the event;

Disturbance lasts greater than 1 month in true PTSD; disturbances lasing between 2 days and 1 month are referred to as acute stress disorders

Rx:  psychotherapy, SSRI's

Benzodiazepines

Mech of action?

Most have short/long half lives and active/inactive metabolites?

Facilitates action of GABA-A by increasing frequency of Cl channel opening

(frenzodiazepines!)

Like barbituates, GABA itself is still required to open the Cl channel

Most benzodiazepines have long half lives and active metabolites

Benzodiazepines

6 Clinical Indications:

1. Anxiety

2. Spasticity

3. Status epilepticus (anticonvulsant effects) 

4. Alcohol Detox

5. Insomnia, night terrors, sleepwalking, 

6. General anesthetic (for amnesia and muscle relaxation)

Its mode of treatment is sedation

(can be used as adjunctive treatment in acute mania, because it works instantly)

How do Benzodiazepines compare with Barbiturates in their toxicities/adverse effects?

How do you treat a benzo overdose?

Potential for withdrawl?

Benzo:

1. tolerance, dependence, abuse potential 

2. Additive CNS depression effects w/ EtOH

(3. Cognitive effects (anterograde amnesia)

4. Paradoxical effect - just like some people are angry beligerant drunks even tho alcohol is a depressant

5. Sedation, ataxia (for ppl using heavy machinery, or increases fall risk in the elderly)

Notice these are many of the same symptoms of alcohol withdrawl; Hereditary vulnerability to alcoholism may extend to risk for benzo dependence/abuse

*However, LESS risk of resp depression and coma than what is seen in barbiturates

Treat a benzo overdose w/ flumazenil (a competetive antagonist at GABA benzo receptor)

Yes, withdrawl can happen, must slowly taper off the meds for 6 weeks to 6 months, depending on the dose

Name 3 Short-Acting Benzodiazepams (how can you remember these?)

Do these have a higher or lower addiction potential than other benzo's?

Short acting, thing TOM thumb:

Triazolam

Oxazepam

Midazolam

These have the highest addiction potential!