Term
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Definition
| MAOIs act by inhibiting the activity of monoamine oxidase preventing the breakdown of monoamine neurotransmitters and so increasing the available stores. There are two isoforms of monoamine oxidase, MAO-A and MAO-B. MAO-A preferentially deaminates serotonin, melatonin, adrenaline and noradrenaline. MAO-B preferentially deaminates phenylethylamine and trace amines. Dopamine is equally deaminated by both types. Many formulations use forms of fluoride attached to assist getting past the blood-brain barrier and is suspected as a factor in pineal gland effects. |
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Term
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Definition
Benzodiazepines produce their variety of effects by depressing the central nervous system and by modulating the GABAA receptor, the most prolific inhibitory receptor within the brain. The GABAA receptor is made up from 5 subunits out of a possible 19, and GABAA receptors made up of different combinations of subunits have different properties, different locations within the brain and importantly, different activities in regards to benzodiazepines.
In order for GABAA receptors to be sensitive to the action of benzodiazepines they need to contain an ? and a ? subunit, where the benzodiazepine binds. Once bound, the benzodiazepine locks the GABAA receptor into a conformation where the neurotransmitter GABA has much higher affinity for the GABAA receptor, increasing the frequency of opening of the associated Chloride ion channel and hyperpolarizing the membrane. This potentiates the inhibitory effect of the available GABA leading to sedatory and anxiolytic effects. |
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Term
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Definition
| SSRIs increase the extracellular level of the neurotransmitter serotonin by inhibiting its reuptake into the presynaptic cell, increasing the level of serotonin available to bind to the postsynaptic receptor. |
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Term
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Definition
| The exact mechanism of action is not well understood, however it is generally thought that tricylic antidepressants work by inhibiting the re-uptake of the neurotransmitters norepinephrine, dopamine, or serotonin by nerve cells. Tricyclics may also possess an affinity for muscarinic and histamine H1 receptors to varying degrees. Although the pharmacologic effect occurs immediately, often the patient's symptoms do not respond for 2 to 4 weeks.[1] |
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Term
| How do antiosychotics work? |
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Definition
All antipsychotic drugs tend to block the D2 receptors in the dopamine pathways in the brain, so the normal effect of dopamine release in the relevant synapses is reduced.
It is the blockade of D2 receptors in the mesolimbic pathway of the brain which is thought to produce the intended antipsychotic effect. |
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Term
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Definition
| Typical antipsychotics are not particularly selective and also block the same receptors in the mesocortical pathway, tuberoinfundibular pathway and the nigrostriatal pathway. Blocking D2 receptors in these other pathways is thought to produce some of the unwanted side effects that the typical antipsychotics can produce (see below). |
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Term
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Definition
Atypical antipsychotic drugs have a similar blocking effect on D2 receptors but seem to be a little more selective, targeting the intended pathway to a larger degree than the others. They also block or partially block serotonin receptors (particularly 5HT2A, C and 5HT1A receptors).
This combination of effects on both dopamine and serotonin receptors might be why atypical antipsychotic drugs tend to have fewer side effects than typicals and have a seemingly additional effect on the 'negative symptoms' of schizophrenia. |
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Term
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Definition
An anticholinergic agent is a member of a class of pharmaceutical compounds which serve to reduce the effects mediated by acetylcholine in the central nervous system and peripheral nervous system.
Anticholinergics are typically reversible competitive inhibitors of one of the two types of acetylcholine receptors, and are classified according to the receptors that are affected: antimuscarinic agents operate on the muscarinic acetylcholine receptors, and antinicotinic agents operate on the nicotinic acetylcholine receptors. The majority of anticholinergics are antimuscarinics. |
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Term
| How do antihistamines work |
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Definition
An antihistamine is a drug which serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions, through action at the histamine receptor. Only agents where the main therapeutic effect is mediated by negative modulation of histamine receptors are termed antihistamines - other agents may have antihistaminergic action but are not true antihistamines.
In common use, the term antihistamine refers only to H1-receptor antagonists, also known as H1-antihistamines. It has been discovered that these H1-antihistamines are actually inverse agonists at the histamine H1-receptor, rather than antagonists per se |
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Term
| what are 4 major pharma points to consider? |
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Definition
Pharmacodynamics: How does this medication work? What are its side effects? If I have to combine medications, does my plan make sense?
Pharmacokinetics: What are the dosing strategies? What are the drug interactions? Will there be withdrawal?
Pharmacoeconomics: Is it affordable by the patient?
Psychopharmacotherapy: What does the patient think about this medication? Will they adhere to the regimen? Will the stigma of the illness affect their medication use? |
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Term
| What are 3 major classes of anxiolytics? |
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Definition
Anxiolytics:
Antidepressants;
Benzodiazepines;
Hypnotic Agents |
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Term
| What is first line for GAD? |
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Definition
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Term
| What is first line for PD? |
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Definition
|
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Term
| Which pt popuation is good for AD/SSRI? |
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Definition
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Term
| What is wrong with TCAs and MAOIs? |
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Definition
|
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Term
|
Definition
|
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Term
| What are the 2 GABA receptor sites? |
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Definition
| Benzos bind to GABA receptors at specific sites: BZ-1 (w1) and BZ-2 (w2) |
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Term
| What are the 2 respective sites associated with? |
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Definition
BZ-1 receptors: implicated in mediation of sleep
BZ-2 receptors: anxiety, cognition, memory, motor control |
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Term
| How do you characterized Benzos? |
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Definition
| duration of action, onset of action, hepatic metabolism |
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Term
|
Definition
Short Acting (3-8 hrs):
Oxazepam (Serax);
Triazolam (Halcion); Midazolam (Versed; iv only);
Alprazolam (Xanax) |
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Term
| Name intermed acting benzos |
|
Definition
Intermediate Acting (6-12 hrs):
Lorazepam (Ativan);
Estazolam (Prosom);
Temazepam (Restoril) |
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Term
|
Definition
Long Acting (12-72 hrs):
Chlordiazepoxide (Librium);
Clonazepam (Klonopin);
Chlorazepate (Tranxene);
Diazepam (Valium, Dizac);
Flurazepam (Dalmane) |
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Term
| Which are quick onset of action benzos? |
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Definition
Quickest
( 5-15 minutes to start, 1-3 hrs to peak effects):
Diazepam (3), lorazepam (2), alprazolam (1), triazolam (1), estazolam (2) |
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Term
| What are the least hepatic metabolized? |
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Definition
| Least metabolized: Oxazepam, lorazepam, temazepam |
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Term
| What are the heavily metabolized benzos? |
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Definition
| Heavily metabolized: Diazepam, chlordiazepoxide, clorazepate, flurazepam |
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Term
| Who will experience prolonged benzo duration? |
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Definition
Note that benzodiazepine duration may be markedly prolonged
in the elderly or others who have decreased hepatic metabolism. |
|
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Term
| do most people experience withdrawl with BZ? |
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Definition
| 50% of people who have stopped BZ:: Sxs : anxiety, irritability, insomnia, fatigue, HA, tremor, sweating, dizziness, trouble concentrating, depression, nausea, loss of appetite, serious sxs (paranoia, delirium, seizures) |
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Term
|
Definition
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Term
| Which BZ have the worst withdrawl? |
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Definition
| Short acting, rapid-acting BZ’s (alprazolam): worse W/D |
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Term
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Definition
Tolerance:
May develop to anxiolytic & motor effects |
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Term
| How do you OD? What is antedote? |
|
Definition
OD:
Usually OD is in combination with alcohol or other sedative
Flumazenil (Romazicon): antagonist at BZ-1 and BZ-2 sites.
Has a half-life of 7-15 minutes |
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Term
| Where do hypnotic agents act? |
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Definition
| act on BZ-1 sites pref. (SLEEP!) |
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Term
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Definition
| Rare side effect: can cause hallucinations! |
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Term
| What are examples of hypnotics? |
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Definition
Zolpidem (Ambien) - half life 4 hrs
Zaleplon (Sonata) - half-life 2 hrs
Eszopiclone (Lunesta) – half-life 6 hrs; occassional odd tastes
New medication with a novel mechanism:
Ramelteon (Rozerem) high affinity melatonin receptor agonist (MT1/MT2) |
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Term
| What are + symptoms of schiz? |
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Definition
| Positive Sxs: (6 months): hallucinations &/or delusions |
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Term
| What are negative symptoms of Schiz? |
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Definition
Negative Sxs: (4 A’s): Autism, affect, association, ambivalence
Although the positive sxs are more flamboyant, the cognitive and social impairments can be more devastating for the patient. |
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Term
| What neurotransmitters are disturbed in schiz? |
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Definition
| May involve disturbances in: Dopamine, Serotonin, Glutamate, or Others |
|
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Term
| what are 4 pathways involved in regulating dopamine? |
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Definition
Tuberoinfundibular::
Prolactin Inhibition ; Mesocortical (VTA-PFC)::
Processing,
negative/positive sxs
May degrade in schizophrenia ; Nigrostriatal::
Motor movement
Parkinson's; EPS ; Mesolimbic (VTA-NA)::
Attention, pleasure
may be overactive in
schizophrenia |
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Term
| What SE associated with D2 Blockade? |
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Definition
D2 Blockade::
EPS, flattened affect,
slowed cognition,
increased prolactin |
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Term
| What are characteristics of High potency TA? |
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Definition
High potency agents: D2 antagonists;
also block a1 receptors |
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Term
| WHat are characteristics of mid potency AT? |
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Definition
Mid potency agents: less potent D2 antagonists;
also block a1, H1, and muscarinic receptors |
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Term
| What are characteristics of low potency ATs? |
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Definition
Low potency agents: least potent D2 antagonist,
have a higher potency for muscarinic receptors |
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Term
| For HP ATs, what are classic D2 SE? |
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Definition
Classic D2 side effects:
Extrapyramidal symptoms [EPS]; tardive dyskinesia; akathisia; gynecomastia, menstrual irregularities; neuroleptic malignant syndrome [NMS] |
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Term
| For HP ATs, what are classic alpha-1 SE? |
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Definition
Classic a1 side effects:
orthostatic hypotension, sedation |
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Term
| For HP ATs, what are other worrisome SE? |
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Definition
Other worrisome side effects:
Reduced seizure threshold, thermodysregulation, esophogeal dysmotility;
cardiac arrhythmias
Very little anticholinergic side effects |
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Term
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Definition
| Use anticholinergic agents (i.e., benztropine) or antihistaminergics for EPS |
|
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Term
| What do you use for Akathisia? |
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Definition
| Use benzodiazepines or beta-adrenergic blockers (i.e., propranolol) for akathisia |
|
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Term
| WHat is a classic ex of a high pot TA? |
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Definition
| haloperidol (Haldol): also available in long-acting decanoate |
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Term
| What is main diff btwn mid and high potency tA |
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Definition
More anticholinergic and antihistaminergic than high potency agents:
more sedation; dry mouth, blurred vision, Nausea & Vomiting, urinary retention;
Less EPS (compared to high potency agents) |
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Term
| What is a good example of a MID TA? |
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Definition
loxapine (Loxitane)
molindone (Moban)
perphenazine (Trilafon) |
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Term
| What are 4 systems associated with AcH? |
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Definition
Lateral Tegmental
Arousal, Other Functions ; Striatal Interneurons
Motor function;
oppose effects of DA
; Nucleus Basalis
of Meynert
Learning, memory,
problem solving, Alzheimer's ; Peripheral:
Cardiac, GI, salivary gland,
Eye,bladder, etc. |
|
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Term
| what are side effects of anticholinergics? |
|
Definition
Anticholinergic (M):
Blurred vision;
Dry mouth;
Constipation;
Difficulty urinating |
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Term
| What is notable about LOW TA? |
|
Definition
Most anticholinergic effects
Lowest levels of EPS of the typical antipsychotics;
most sedation; agranulocytosis [1:500,000]; liver disease [1:1000]; dermatitis; ophthalmologic effects |
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Term
| What is classic example of LOW TA? |
|
Definition
chlorpromazine (Thorazine)
thioridazine (Mellaril)
mesoridazine (Serentil) |
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Term
|
Definition
Neuroleptic Malignant Syndrome : Features:
Thermal dysregulation (temps up to 46C/106F)
Muscle rigidity (can lead to CK elevations > 300 U/mL)
Autonomic instability
Altered level of consciousness
Fatal in 5-20% of untreated cases |
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Term
| What kind of disorder is NMS? |
|
Definition
|
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Term
|
Definition
Treatment:
Stop the neuroleptic (may restart after 2 weeks, if needed);
Supportive treatment of symptoms (i.e., cooling, IVF, respiratory support, cardiac telemetry, etc);
Pharmacologic:
Muscle Relaxants (dantrolene);
DA agonists (bromocriptine, amantadine);
Anticholinergics (benztropine, trihexyphenidyl)
Benzodiazepines |
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Term
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Definition
| an adverse rxn to neuroleptics/antipsychotic |
|
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Term
| Name expected symptom improvement for TA? |
|
Definition
Typical Antipsychotics
Efficacy for treatment of positive symptoms (hallucinations, delusions, etc)
May worsen negative symptoms (cognition, mood, affect, social function)
Risk of TD (up to 20% of patients chronically treated with typical agents!) |
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Term
| Name symptom improvement for AA? |
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Definition
Atypical antipsychotics
May improve both positive and negative symptoms.
Lower risks for EPS and TD. |
|
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Term
| What 2 neurtransmitters pathways overlap? |
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Definition
|
|
Term
| Which DA areas are there lots of 5HT? |
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Definition
| There are more 5HT2 receptors on some areas: nigrostriatal, mesocortical, and tuberoinfundibular, Then on others: mesolimbic |
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Term
| Why are atypicals possibly better? |
|
Definition
(A) Activation of 5HT-2A receptors on DA cell bodies and nerve terminals ? DECREASE in DA release;
(B) Blockade of 5HT-2A receptors ? INCREASE in DA release.
Atypical Antipsychotics: The higher level of dopamine (released from 5HT2A effect) may compete with the D2 antagonist
Cortex (enhanced cognition, improvement in negative symptoms),
Striatum (improvement in EPS)
Pituitary (less prolactin release) (THIS IS ALL B)
Atypical Antipsychotics: maintain D2 block in
Limbic System (improvement in positive symptoms) (THIS IS ALL A) |
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Term
| With What does level of EPS correlate? |
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Definition
| Level of EPS correlates with how tightly an antagonist binds to the D2 receptor. |
|
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Term
| What is a rapid Koff rate? |
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Definition
Some atypical antipsychotic have rapid Koff rates (“loose” binding).
These agents cause less EPS.
They never fully block the D2 receptors.
Can be considered as “partial antagonists” |
|
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Term
| What is classical atypical? |
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Definition
|
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Term
| What are 2 major risks associated? |
|
Definition
| agranulocytosis (not dose dependent), and seizure risk (dose dep) |
|
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Term
| What are 5 other major AA? |
|
Definition
Risperidone (Risperdal) -
EPS, hyperprolactinemia, wt gain
Palliperidone (Invega)-
Risperidone metabolite; NEW on the market (2007)
Olanzapine (Zyprexa) -
wt gain, sedation, elevated transaminases;
Quetiapine (Seroquel) ::
sedating, wt gain, cataracts
; Ziprasidone (Geodon)
QTc elevations (10-20 ms); EPS
weight neutral;;
Aripiprazole (Abilify)::
Akathisia, Insomnia
Generally weight neutral (but may cause weight gain at higher doses)
D2 & 5HT1A partial agonist; antagonist of 5HT2 |
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Term
| What iatrogenic illness is associated with AA? |
|
Definition
Diabetes and risk of hyperglycemia;
CVA risk when used off-label for elderly with dementia-related psychosis
Metabolic Syndrome:
Central Obesity,
Hyperglycemia,
Dyslipidemia (elevated cholesterol, triglycerides) |
|
|
Term
| Which is more expensive: AA or TA? |
|
Definition
|
|
Term
| Which system is disturbed in BAD? |
|
Definition
| May involve disturbance in second messenger systems |
|
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Term
|
Definition
Lithium;
Antiepileptic Drugs;
Valproate (Depakote, Depakene)
Carbamazepine (Tegretol)
Lamotrigine (Lamictal)
Others ? (gabapentin, topiramate, zonisamide, etc)
Atypical Antipsychotics;
Combinations are the norm (3-4 meds are average) |
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Term
| What is theraputic Blood levels for Li? |
|
Definition
Therapeutic blood level of 0.6-1.1 mEq/L
Toxic: > 1.5
Coma: >1.8 |
|
|
Term
| What is recommended for pts on Li? |
|
Definition
| Drink Fluids! If toxic, can use IV fluids, dialysis |
|
|
Term
| What are common side effects of Li? |
|
Definition
Common Side Effects: GI, sedation, tremor, wt gain, acne, psoriasis, polyuria, polydipsia, Worrisome side effects:
slurred speech, muscle twitching, memory problems, edema, seizure, coma, death
Also worrisome:
thyroid inhibition, arrhythmia, renal dysfunction,
teratogenicity (low probability for Epstein’s Anomaly). |
|
|
Term
| what should you test for with Li? |
|
Definition
Check:
Pregnancy test; CBC, EKG, Electrolytes, Renal fxn, Thyroid fxn
Routinely monitor: TSH, Cr, Bun, Lithium level |
|
|
Term
| What drug-drug interactions increase Li Level? |
|
Definition
Some drugs increase lithium level
NSAIDS, ACE Inhibitors, loop & potassium sparing diuretics, phenytoin, tetracyclines |
|
|
Term
| What d-d interactions decrease Li? |
|
Definition
Some drugs decrease lithium level
Caffeine, carbonic anhydrase inhibitors, calcium channel blockers, osmotic diuretics, theophyllines |
|
|
Term
| Which D-D interactions increase risk of serotonin syndrome? |
|
Definition
Some drugs increase risk of serotonin syndrome (
Sibutramine, SSRI’s, SNRI’s, TCA’s, tramadol) |
|
|
Term
| What drugs with LI combine CNS side-effects/neurtox? |
|
Definition
Some drugs combine CNS side-effects/neurotoxicity:
Carbamazepine, haloperidol, meperidine, promethazine, phenothiazines, phenytoin, tetracyclines |
|
|
Term
|
Definition
Common Side Effects: tremor, dizziness, sedation, N/V, GI, HA, elevated LFT, rash; also hair loss, wt gain
Worrisome Side Effects: thrombocytopenia, prolonged coagulation time, pancreatitis, teratogenic (think folate); ?PCOS |
|
|
Term
| What is VPA metabolized by? |
|
Definition
| Valproate is metabolized by P450 enzymes, and it inhibits P450 enzymes. |
|
|
Term
|
Definition
Many drug-drug interactions (more than VPA).
Induces P450 3A4
(reduces levels of neuroleptics, OCP, carbamazepine, others)
CBZ level increased by inhibitors of P450-3A4
(H2 blockers, nefazodone, erythromycin, isoniazid, VPA, Ca channel blockers) |
|
|
Term
|
Definition
Lots of potential side effects
dizziness, sedation, unsteady gait, cognitive problems, blurred vision, alopecia, GI, elevated LFT, aplastic anemia, agranulocytosis, thrombocytopenia, rash (including Stevens-Johnson), hyponatremia, thyroid, arrhythmia, SLE, teratogen. |
|
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Term
|
Definition
Used frequently for bipolar depression
though not FDA approved for this indication
Rash (any type) is common – up to 10%
Stevens Johnson Syndrome or other serious rash is rare – up to 0.3%
Risk factors for serious rash:
pediatrics, rapid tapers |
|
|
Term
| Which antipsychotics have been approved for BP mania? |
|
Definition
Several Antipsychotics have been approved for bipolar mania:
Olanzapine -Risperidone - Quetiapine
- Aripiprazole - Ziprasidone
- Chlorpromazine |
|
|
Term
| What antipsychotics have been indicated for BP depression? |
|
Definition
For Bipolar Depression:
Olanzapine-Fluoxetine Combination (Symbyax)
Quetiapine (Seroquel)
Other drugs that may be beneficial for bipolar depression:
pramipexole (Mirapex), a D3 agonist and
lamotrigine (Lamictal), an antiepileptic drug
Other atypical antipsychotics as monotherapy? |
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