Term
| Three Classes of Symptoms of Psychosis and Schizophrenia: |
|
Definition
(1) Positive Symptoms
- Delusions
- Hallucinations
(2) Negative Symptoms
- Affective flattening
- Anhedonia – no pleasure
- Avolition - no motivation
(3) Disorganized speech and behavior, and poor attention |
|
|
Term
| Delusioins in psychosis and schizophrenia are Most often are _______ |
|
Definition
| auditory -> usually threatening voices |
|
|
Term
| ____ is the onset of schizophrenia & increases in frequency in ____ |
|
Definition
|
|
Term
| The initial antipsychotic drug (_____) was discovered in the mid-1950’s while developing _____. Unlike other ____, it was effective against ______. Mechanism of action studies focused subsequent research on brain ___ |
|
Definition
chlorpromazine
anti-histamines.
anti-histamines
schizophrenia
dopamine |
|
|
Term
| All Antipsychotics Block _____ Receptors |
|
Definition
|
|
Term
| 2 Major Families of antipsychotics (___ family and ___ family). |
|
Definition
|
|
Term
| Cell bodies of dopamine neurons in the ____ give rise to release of dopamine in the ____ system, including the ___ and the ___ . This system likely mediates: (3) |
|
Definition
ventral tegmental area (VTA)
mesolimbic
nucleus accumbens
prefrontal cortex
Natural reinforcers
Euphoria from drugs of abuse
Psychosis |
|
|
Term
| Excess dopamine in the mesolimbic system is a likely site accounting for _____ symptoms in schizophrenia |
|
Definition
|
|
Term
| Dopamine Hypothesis of Schizophrenia: |
|
Definition
There is an imbalance in the brain that leads to over stimulation of postsynaptic dopamine receptors
Receptor over-stimulation can be attenuated by dopamine receptor antagonists.
Key piece of evidence: all antipsychotics block DA (D2) receptors |
|
|
Term
Evidence in favor of the dopamine hypothesis:
older antipsychotics (typical antipsychotics) act at the ___ receptor |
|
Definition
|
|
Term
Evidence in favor of the dopamine hypothesis:
Data concerning amphetamines are particularly compelling. Clinical studies have shown that high-dose amphetamines, which release ___, cause a temporary psychosis in _____ individuals. The psychosis can include _____, a symptom that is seldom found in any disorder other than schizophrenia |
|
Definition
DA
normal
auditory hallucinations |
|
|
Term
Evidence Against the Dopamine Hypothesis:
Therapeutic effects on delusional thought requires time (__-__ weeks) before antipsychotics are effective, whereas binding to DA receptors occurs ______. |
|
Definition
immediately
3-6
"When block D2 receptor, they quit having + hallucinations, but delusions only slowly improve." |
|
|
Term
Evidence Against the Dopamine Hypothesis:
Many schizophrenics get no help from antipsychotics. Implies a _____ of illness. |
|
Definition
|
|
Term
Evidence Against the Dopamine Hypothesis:
The psychosis seen with amphetamine is invariably ___ in type. Lacks the diversity of signs and symptoms of schizophrenia. |
|
Definition
|
|
Term
Evidence Against the Dopamine Hypothesis:
Several laboratories have studied the expression of ___ receptors in normal and schizophrenic individuals. The reports are conflicting as to whether there are differences in the expression of ___ or ___ receptors in these populations. |
|
Definition
|
|
Term
Evidence Against the Dopamine Hypothesis:
Emerging role for ____ receptors. Newer (and much better) antipsychotic drugs are only modest D-2 antagonists, but all of these newer agents also block ___ receptors. |
|
Definition
|
|
Term
| Newer, atyptical antipsychotic drugs bind to ___ and ____ receptor sites. They have a ____ onset but still 1-3 weeks for _____ to improve |
|
Definition
|
|
Term
| Data is less convincing about role of DA receptors in ____ symptoms |
|
Definition
|
|
Term
| Newer antipsychotics (“atypicals”) have somewhat better actions against ____ symptoms. These drugs are antagonists at both ____ and ____ sites. |
|
Definition
|
|
Term
| What does “Burnt out schizophrenics” mean? |
|
Definition
These patients often display primarily negative symptoms
so the atypicals are good for them |
|
|
Term
| Antipsychotics as a term refers to both the entire class of these drugs as well as to an older set of drugs that should now be seen as a subclass (a class sometimes described as _____ or _____). At one time this subclass comprised scores of drugs. This subclass is rapidly being supplanted by a new subclass, the so-called _____. |
|
Definition
Neuroleptics
Typical Antipsychotics
Atypical Antipsychotics |
|
|
Term
| Haloperidol is what type of drug? |
|
Definition
|
|
Term
| ______= typical antipsychotic against which all other drugs are judged |
|
Definition
|
|
Term
| What drug is the purest D2 blocker? |
|
Definition
|
|
Term
| Olanzapine is what type of drug? |
|
Definition
|
|
Term
| Clozapine is what type of drug? |
|
Definition
|
|
Term
| Aripiprazole is what type of drug? |
|
Definition
|
|
Term
| _____ was the first atypical on the market. Strong bind to ____ & weak bind to ___ |
|
Definition
|
|
Term
Mechanism of Action of Antipsychotics:
All block __ receptors, particularly the __ receptor. Their clinical efficacy against ___ symptoms is relatively well correlated with this action. Many of their side-effects are well correlated with this action. |
|
Definition
|
|
Term
General Effects of ALL Antipsychotics:
Control bizarre behavior and calm ____. Cause psychomotor ____, decrease agitation, aggression and impulsivity. Produce emotional ____. If the dose is high enough, they do these things in ___.
Which property makes them first-choice for controlling disruptive behavior? |
|
Definition
agitation
slowing
quieting
everyone
psychomotor slowing |
|
|
Term
Effects of Antipsychotics in SCHIZOPHRENICS:
They improve the _______ disorders in about 50-70% of schizophrenics. |
|
Definition
|
|
Term
Effects of Antipsychotics in SCHIZOPHRENICS:
Those with ____ symptoms are particularly resistant to pharmacotherapy (atypical antipsychotics are said to be better against _____ symptoms – evidence for this is not impressive) |
|
Definition
|
|
Term
| Other Uses of Antipsychotics (3) |
|
Definition
(1) Tourette’s Syndrome
(2) Hiccups
- Brainstem (D2 receptors)
(3) Nausea
- Chemoreceptor trigger zone in the floor of the
fourth ventricle
- D2 receptors are greatly involved in N/V
- This is significant in chomotherapy & migrain headaches so
these drugs can be used to decrease N/V |
|
|
Term
Two broad classes of Typical Antipsychotics:
Name the drug in each class: |
|
Definition
Phenothiazines -> Chlorpromazine
Butyrophenones -> Haloperidol |
|
|
Term
| Typical Antipsychotics are ____ affinity ___ receptor antagonists. Clinical potency is highly correlated with affinity for __ receptors. |
|
Definition
|
|
Term
| Typical Antipsychotics: Most of these drugs are very messy in their pharmacology. They are Antagonists at (4) receptors. |
|
Definition
dopamine
alpha1
muscarinic
histamine |
|
|
Term
| ____: standard against which older and newer drugs are judged |
|
Definition
|
|
Term
Haloperidol is a Relatively clean D2 antagonist
Highly effective against _____ symptoms; some effect against _____ symptoms |
|
Definition
|
|
Term
| Haloperidol: Greater potential for _____ side-effects than many ____(and all ____) antipsychotics |
|
Definition
neurologic (extrapyramidal) motor
typical
atypical |
|
|
Term
| Rapidly Occurring Neurologic Side-Effects of antipsychotics are the Direct Result of Blocking ___ Receptors in the ____ |
|
Definition
|
|
Term
| The extrapyramidal effects of antipsychotics are mediated by the _______, while the antipsychotic effects are mediated by the _____ and _____ systems. |
|
Definition
basal ganglia (caudate/putamen)
mesocortical
prefrontal cortex |
|
|
Term
| Extrapyramidal effects include: (3) |
|
Definition
1. Dystonias (body twisting) -> muscle spams, twisting of the head torticollis is a major one.
2. Parkinsonism -> indicates that the dose is too high
3. Neuroleptic Malignant Syndrome |
|
|
Term
| Parkinson’s disease is also caused by antipsychotics blocking ____ receptors in the ____. |
|
Definition
|
|
Term
Symptoms of Parkinsons-Like Syndrome Include:
Rigidity or tremor (___ per second) at rest
Facial “____” – muscles become immobilized, leaving them with blank expressions
_______ - slow movements
_______ - muscles are so rigid – cogwheel rigidity
Parkinson’s-like Syndrome |
|
Definition
3
mask
bradykinesia
akinesia |
|
|
Term
| Neuroleptic Malignant Syndrome will occur in ___-___% of patients. |
|
Definition
|
|
Term
| Neuroleptic Malignant Syndrome is a toxicity of ______ antipsychotics. |
|
Definition
|
|
Term
| Neuroleptic Malignant Syndrome Resembles a severe form of Parkinsonism with _____, _____ and instability of the ____ ( i.e. alterations in blood pressure and pulse rate). |
|
Definition
catatonia
tremors
autonomic system ANS |
|
|
Term
| In severe cases of Neuroleptic Malignant Syndrome, impairment of _____ and ____ can ensue with a 10% mortality rate. |
|
Definition
|
|
Term
| Treatment for Neuroleptic Malignant Syndrome? |
|
Definition
| Treated by cooling (ice bath) and using a dopamine agonist |
|
|
Term
| Dysphoria is a side effect of antipsychotics. It was once said that no one likes to take these drugs. But aversion to them is less with the ______ agents. |
|
Definition
|
|
Term
Endocrine Abnormalities = side effect of antipsychotics
Increased secretion of _____ which is caused by block of dopamine receptors in the _____. (Release of ____ is under negative regulation by dopamine secreted from cells in the tuber-infundibular system of the ______)
With Females -> ______
With Males -> ________ |
|
Definition
prolactin (hyperprolactinemia)
pituitary
prolactin
hypothalamus
Galactorrhea -- excessive/spontaneous production of milk
Gynecomastia – enlargement of breasts |
|
|
Term
| Weight gain = side effect of antipsychotics - particularly with some of the _____ antipsychotics |
|
Definition
|
|
Term
Long Term Neurologic Side Effects of antipsychotics:
________ is the major long-term side effect of chronic treatment with _____ antipsychotics (especially ______). |
|
Definition
Tardive dyskinesia
typical
haloperidol |
|
|
Term
| The ____ the D2 blocker and the ____ the pt. has been on it and the ____ the dose = you are much more likely to see tardive diskinesia |
|
Definition
|
|
Term
tardive = _____
dyskinesia = ______ |
|
Definition
belated or delayed
impairment of voluntary movement |
|
|
Term
| Tardive Diskenesia is ____ appearing |
|
Definition
|
|
Term
| Tardive Diskinesia occurs after chronic treatment with _____ antipsychotics (usually > ___ years) |
|
Definition
|
|
Term
| ___-___% of institutionalized patients on typical antipsychotics will develop Tardive Diskinesia |
|
Definition
|
|
Term
| Tardive Diskinesia is more prevalent in ____ patients |
|
Definition
|
|
Term
| Tardive Diskinesia Appears to be due to _____ DA receptors |
|
Definition
|
|
Term
Why is Tardive Diskinesia a permanent syndrome?
How do you deal with it? |
|
Definition
Permanent b/c it is a spread of supersensitive DA receptors. So if you see TD and withdraw the drug, it gets much worse. If you increase the drug, then it goes away but will never get back to normal. But then the receptors return w/ a vengence and it is worse when trying to withdraw the drug.
So how do deal with it? Don’t use pure D2 for a long time. For anyone on anti-psychotic drug, ask someone to open mouth on physical exam & can see tongue making small movements. Use the atypicals that are less likely to have TD |
|
|
Term
| Tardive Diskinesia is Motostereotypical, repetitive, involuntary movements. It involves ____ jaw movements, _____, and Twisting and protrusion of the ____. In early stages of the disorder, can see this on physical exam by asking the patient to open their mouth. It will subsequently become obtrusive and obvious. It is Purposeless movements of the extremities dysfunction. |
|
Definition
Lateral
Lip smacking
tongue |
|
|
Term
| risperidone (Risperdal) is what type of drug? |
|
Definition
|
|
Term
| quetiapine (Seroquel) is what type of drug? |
|
Definition
|
|
Term
| What atypical antipsychotic is Somewhat more likely to cause extrapyramidal effects than other atypical drugs -> more likely to have TD? |
|
Definition
|
|
Term
| What atypical antipsychotic Is more sedative than the other atypical agents? |
|
Definition
|
|
Term
| Since atypical antipsychotics risperidone (Risperdal)and quetiapine (Seroquel) have more negative side effects, which atypical antipsychotics would you rather use? (3) |
|
Definition
olanzapine (Zyprexa)
clozapine (ClozariL)
aripiprazole (Abilify) |
|
|
Term
The claim: all atypical antipsychotics are better than typical antipsychotics in terms of
(1) greater efficacy against ____ symptoms
(2) less likely to cause _____
Remember that in addition to blocking D2 receptors, they block ____ receptors which likely accounts for both phenomena |
|
Definition
negative
tardive dyskinesia
5-HT2 |
|
|
Term
| The evidence: Claim for less likelihood of atypical antipsychotics producing tardive’s is well substantiated. The less ___ blockade, the less likely tardive’s. Hence, of the atypicals, _____, which has the greatest D2 affinity, has the worst profile for producing tardive’s. |
|
Definition
|
|
Term
FYI
Claim for better efficacy of atypicals against negative symptoms has come under fire.
Initial trials were extremely positive
But small sample size
Mean reversion effect
Funded by vested interest
More recent data says there is very little difference between typical and atypical antipsychotics in terms of efficacy against negative symptoms |
|
Definition
|
|
Term
| ______ Rapidly becoming the standard against which both typical and atypical antipsychotics are judged |
|
Definition
|
|
Term
| Olanzapine (Zyprexa): With the exception of ____ and ____, the side-effect profile is much more acceptable with this drug. |
|
Definition
|
|
Term
| Recent controversy concerning Olanzapine (Zyprexa) (and, all atypical antipsychotics) causes ______. Perhaps because of this, and perhaps because of remarkable efficacy against both schizophrenia and depression, ____ is an interesting alternative. |
|
Definition
type 2 diabetes.
aripiprazole |
|
|
Term
| Ziprasidone is what type of drug? |
|
Definition
|
|
Term
| Risperidone is more likely to cause does-related ____ side effects as well as have a greater propensity to produce ____ with long-term use. Otherwise, there is very little to chose from these agents (atypicals) over olanzapine. |
|
Definition
|
|
Term
| FDA requires a warning for all atypical antipsychotics concerning their propensity to cause ____ and ____ |
|
Definition
hyperglycemia
diabetes
"Label states: hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics." |
|
|
Term
_____:The original atypical antipsychotic. Appears to be more efficacious than other antipsychotics, particularly against _____ symptoms -> has gotten them up and moving
Essentially devoid of _____ motor side-effects |
|
Definition
Clozapine (Clozaril)
negative
extrapyramidal |
|
|
Term
| ________: causes blood dyscrasias (agranulocytosis) in about 2% of patients. So need to Monitor blood, particularly between 6th and 18th week. Can only be prescribed under a blood-monitoring program. Other side effects are strong _____, anticholinergic effects (____), and ____effects |
|
Definition
Clozapine
sedation
urinary retention
hypotensive |
|
|
Term
| ______: A partial dopamine agonist. Also a Partial 5-HT1A agonist (like buspirone) and partial 5-HT2 agonist |
|
Definition
|
|
Term
| Aripiprazole: efficacy against both schizophrenia (as a weak ____ it blocks the full agonist, ____) and depression (efficacy as a _____ is enough to provide therapeutic efficacy – think of the mechanism of bupropion). |
|
Definition
partial-agonist
dopamine
partial agonist |
|
|
Term
| Aripiprazole: Efficacious against ____ symptoms as well as ___ |
|
Definition
positive and negative
depression |
|
|
Term
| Aripiprazole: Remarkably low incidence of side-effects, including no ____, and less ___ than olanzapine |
|
Definition
tardive dyskinesia
weight gain |
|
|
Term
| Which atypical antipsychotic has a Lesser incidence of Type 2 diabetes? |
|
Definition
|
|
Term
| Epileptic seizures are ____ and ____ episodes of motor, sensory, autonomic or psychic disturbance triggered by abnormal neuronal changes in the brain. Epileptic seizures result from abnormal discharge of ____ neurons. |
|
Definition
sudden
transient
cerebral |
|
|
Term
| Causes of Epileptic Seizures: (5) |
|
Definition
(1) Structural damage in the brain: Trauma, tumors, cerebrovascular disease or hemorrhage
(2) Imbalance of excitatory and inhibitory neurotransmission
(3) Disruption of the ion channels
(4) Metabolic disorders: Hypoglycemia, alcohol abuse
(5) Genetic causes
|
|
|
Term
| Partial (focal) seizures (3) |
|
Definition
Simple partial seizures
Complex partial seizures
Secondary generalized seizures |
|
|
Term
|
Definition
Clonic, tonic, or tonic-clonic
Myoclonic
Absence
Atonic |
|
|
Term
Neurotransmitter and epilepsy:
Seizures probably arise from local imbalance between excitatory neurotransmission, principally mediated by ____, and inhibitory neurotransmission mediated by ____ which leads to a focus of neuronal instability |
|
Definition
|
|
Term
| Firt Line Drugs for Partial Seizures: (4) |
|
Definition
Carbamazepine
Phenytoin
Valporate
Lamotrigine |
|
|
Term
| Second-line Drugs for partial seizures: (5) |
|
Definition
Phenobarbital/primidon
Clonazepam/clobazam
Gabapentin(as adjunct)
Vigabatrin (as adjunct)
Topiramate (as adjunct) |
|
|
Term
| First-line drugs for Tonic-clonic (Grand mal) seizures: (4) |
|
Definition
Vaproate
Carbamazepine
Phenytoin
Lamotrigine |
|
|
Term
| Second-line drugs for Tonic-clonic (Grand mal) seizures: (2) |
|
Definition
Phenobarbital/primidone
Vigabatrim (as adjunct) |
|
|
Term
| First-line drugs for myoclonic seizures: (1) |
|
Definition
|
|
Term
| Second line drugs for myoclonic seizures: (2) |
|
Definition
|
|
Term
| first-line drugs for absence seizures: (2) |
|
Definition
|
|
Term
| second-line drugs for absence seizures: (2) |
|
Definition
|
|
Term
| first line drugs for atonic seizures: (1) |
|
Definition
|
|
Term
| second-line drugs for atonic seizures (5) |
|
Definition
Phenytoin
Lamotrigine
Clonazepam
Ethosuximide
Phenobarbital |
|
|
Term
Carbamazepine and oxcarbazepine
Indications: |
|
Definition
| Most types of epilepsy and absences |
|
|
Term
| Carbamazepine and oxcarbazepine Contraindication: |
|
Definition
|
|
Term
Carbamazepine and oxcarbazepine
Route of administration: |
|
Definition
| Administered orally. Absorption of Carbamazepine is slow and incomplete. However Oxcarbazepine absorption is well and rapid |
|
|
Term
Carbamazepine and oxcarbazepine
Metabolism: |
|
Definition
|
|
Term
Carbamazepine and oxcarbazepine
Half-life: |
|
Definition
| Carbamazepine-Prolong and Oxcarbazepine-Intermediate |
|
|
Term
Carbamazepine and oxcarbazepine:
Mechanisms of Action: Incompletely Understood.
Inhibition of repetitive neuronal firing by use-dependent blockade of___channels
Attenuation of the action of ____ at NMDA receptors, and reduced ____ release |
|
Definition
|
|
Term
Carbamazepine and oxcarbazepine
Adverse effects:
GI Tract:
Skin:
CNS:
Blood:
Hyponatraemia: |
|
Definition
GI Tract: Nausea and vomiting, constipation, diarrhea and anorexia
Skin: Rashes, erythema
CNS: Toxicity leads to double vision (diplopia), dizziness, drowsiness, or confusion, ataxia in high doses
Blood: Leukopenia, bone marrow depression
Hyponatraemia: |
|
|
Term
Phenytoin and Fosphenytoin
Indications: ____
Contraindication: _____ |
|
Definition
All types of epilepsy except absence
Pregnancy |
|
|
Term
| Phenytoin and Fosphenytoin are effective against ____ seizures and makes ____ seizures worse! |
|
Definition
|
|
Term
Phenytoin and Fosphenytoin:
Mechanisms of Action:
Inhibition of repetitive neuronal firing by use-dependent blockade of ____ channels
Blockade of voltage activated L-type ___ channels
Potentiation of the action of ____ at ____ receptors |
|
Definition
|
|
Term
| Phenytoin and Fosphenytoin: widely used because there is Little clouding of ____ |
|
Definition
|
|
Term
Phenytoin and Fosphenytoin
GI Tract:
CNS:
Connective Tissue:
Skin:
Blood:
Teratogenic Effects: |
|
Definition
GI Tract: Nausea and vomiting
CNS: Signs of overdose: confusion, dizziness, tremor, nervousness, insomnia, nystagmus, blurred vision (diplopia), ataxia
Connective Tissue: *Gum hyperplasia*
Skin: Rashes;*hirsutism-> growth of hair in women
Blood: Megaloblastic Anemia
Teratogenic Effects: Facial and digital malformation
*do not prescribe to women in child bearing years |
|
|
Term
Phenytoin:
Unusual pharmacokinetics
___-order in the low to mid-therapeutic range
___-order at high therapeutic range and above
Excess dose is compounded by the ___-order elimination. |
|
Definition
|
|
Term
______, along With valproate are primary drugs for absence seizures
Adverse effects typically are related to the g.i. tract: ___ |
|
Definition
Ethosuximide
pain, nausea and vomiting |
|
|
Term
| _____: Effective against all seizure types and has Little clouding of ____ |
|
Definition
|
|
Term
Valproated Adverse Effects:
___:(frequent, and troubling) "tears your stomach apart"
____damage: (monitor liver enzymes when starting the drug)
Makes it less popular a drug
Teratogenic – doubles the probability of ___ |
|
Definition
|
|
Term
| _____, Like valproate, can be used in a broad type of seizures |
|
Definition
|
|
Term
Lamotrigine Side effects: relatively benign compared to other anit-seizure agents. ___-_ is much more likely than with valproate. _____ rxs (Steven’s Johnson syndrome) are much more likely when the dose is being increased quickly.
Initial use of the drug (go ____)
Discontinuation of the drug followed by resumption of dosing (go ____!) |
|
Definition
Hypersensitivity
Hypersensitive
slow
slow |
|
|
Term
| What benzodiazepine is used in special circumstances to terminate status epilepticus? |
|
Definition
|
|
Term
| Why is Lorazepam not used long term? |
|
Definition
|
|
