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corness blk 4

The attempted focus of antipsychotic treatment is to treat psychosis while (2): a) not exacerbating or b) actually alleviating concomitant mood disorders
Postive sxms of Schizophrenia (4) 1.Hallucinations 2.Delusions 3.Disorganised speech/thought 4.Disorganized motor behaviour or catatonic behaviour
What sxms of Schizophrenia are caused by to much D2 Hallucinations Delusions Disorganised speech/thought
what are the negative symptoms of schizophrenia (5) 1.Loss of interest/ detachment from pleasure (Anhedonia) 2.Blunted emotions (Blunted Affect) 3.Limited communication (Alogia) 4.Dysfunctional motivation (Alvolition) 5.Dysfunction of socialization/interaction (Asociality)
What sxms of schizophrenia are caused by to little D1 (mainly in the prefrontal cortex)? 1.Loss of interest/ detachment from pleasure (Anhedonia) 2.Blunted emotions (Blunted Affect) 3.Limited communication (Alogia) 4.Dysfunctional motivation (Alvolition) 5.Dysfunction of socialization/interaction (Asociality) 6.disorganized motor/cata
Pychosis is caused by over activity or dopamine where in the brain? nucleus accumbens
All known antipsychotics have had significant affinity to D__ 2
drug induced psychosis is caused by degeneration of neurons from ______________ to the dorsal rache nuclues and VTA Habenula
D1 and D2 receptors what tract in the substantia nigra innervates what part of the brain and cause what function? Nigrostriatal, Caudate & Putamen; Extra pyramidal motor control
D2 receptors what tract in the VTA innervates what part of the brain and cause what function? Mesolimbic; nucleus accumbens; arousal, memory, motivation
D1 receptors what tract in the VTA innervates what part of the brain and cause what function? Mesocortical; Frontal and prefrontal cortex; cognition, communications, emotions,
D2 receptors what tract in the hypothalamus innervates what part of the brain and cause what function? Tubero-infundibular; pituitary; inhibits prolactin secretion
What part of he brain should neurleptics increase dopamine? Prefrontal cortex in the mesocortical tract
Side effects of typical antipsychotics (4 1.Extrapyramidal and Parkinsons-like symptoms 2.)Tardive dyskinesia 3.Endocrine dysfunction 4.Dysphoria
what endocrine dysfunctions occur with the side effects of typical antipsychotics 1.Increased prolactin levels 2.Neuroleptic malignant syndrome (NMS) 3.SIADH (excess ADH and hyponatremia)
what tardive dyskinesia occur with the side effects of typical antipsychotics 1.Involuntary excessive movement 2.Can be long-lasting or permanent
what extrapyramidal and parkinsons-like sxms occur with the side effects of typical antipsychotics 1.Dystonia 2.Muscle rigidity, bradykinesia and tremor 3.Akathisia (restlessness)
What two drugs have sedation(H1 block), Hypotension (alpha blockade), Anti –muscarinic effects* Chlorpromazine; Thioridazine
What 2 drugs help EPS (Parkinsonism) via D1 and D2 block Fluphenazine; Haloperidol
Antipsychotics are lipophilic, orally effective However, ___________ and ____________ are available as IM long acting preparations (2-4 weeks); hence rapid initiation of treatment and maintenance is possible in noncompliant patients Haloperidol; Fluphenazine
What are the acute EPS adverse effects of typical antipsychotics and there timelines 3.Acute muscular dystonia – 4 hours 2.Akinesia - 4 days – can not initiate movements -Pseudo-parkinsonism symptoms- 1-4 weeks (rigidity, tremor, hypokinesia, mask like face, shuffling gait) - pill-rolling 3.Akathisia- 4 weeks
what is the timeline for chronic tardive diskinesia? 4 months
what causes chronic tardive dyskinesia? supersensitivity of DA receptors due to chronic blockade (months or years) of DA receptors in caudate, putamen
How do you treat neuroleptic malignant syndrome? stop offending antipsychotic drug and start bromocriptine (DA receptor agonist) /Amantadine/Dantrolene and Diazepam, along with symptomatic management
what causes life-threatening condition , extreme muscle rigidity, hyperthermia, autonomic dysfunction. Altered level of consciousness, associated with 20% mortality rate. Occurs due to rapid and excessive blockade of postsynaptic DA receptors Neuroleptic malignant syndrome (NMS)
What antipyschotic ADR do you treat with beta blockers? Akathisia
What pathway (direct/indirect) does D1 (stimulate/inhibit)? What about D2? What pathway facilitates motion and what pathway involves tonic inhibition? D1:direct; stimulate; motion D2: indirect; inhibit; tonic
If D2 is blocked or lost, this inhibition is more sensitive. ____________ block is needed when D2 stimulation is down Muscarinic M1
DAergic that stimulates DA release and inhibits reuptake and manages L-dopa off periods Amantadine
DAergic that is a D2 agonist and weak partial D1 agonist and manages L-dopa off periods Bromocriptine
Ca release inhibition that is a ryanodine receptor type 1 (RYR-1) and is a muscle relaxant Dantrolene
antiAch is a muscarinic antagonist for Parkinson’s Disease Biperiden
antiACh is a M1/H1 antagonist for second line Parkinson's disease Benztropine
antiAch is a M/H1 antagonist which is a antihistamine Diphen-hydramine
Benzo that facilitates GABA-induced Cl influx that is a anxiolytic muscle relaxant Diazepam
-generation anti-psychotics target D2 as antagonists, and also manage to reduce or eliminate extrapyramidal symptoms (EPS). __________
Most atypical neuroleptics now show a narrow range of ___-___% D2 receptor occupancy at the optimal therapeutic dose. 60-65; Higher affinity for D2 = greater occupancy by the neuroleptic = greater EPS
High or Low 5HT2A/D2 ratio means most likely chance of EPS. high
Clozapine is a better anti-psychotic than its binding affinity to D2 would suggest for two reasons? 1.Clozapine shows rapid dissociation from D2 binding sites 2.Clozapine in an atypical neuroleptic and atypicals tend to antagonizes more than just D2.
Serotonin acting through 5HT2A has an inhibitory effect on DA release in which two brain areas? dorsal striatum and prefrontal cortex
Blocking 5HT2A increases DA release in dorsal striatum and prefrontal cortex improves what? EPS and mood and cognitive symptoms (negative symptoms).
_________ receptor activation by serotonin in the NAc would normally stimulate DA release but _________ receptor blockade achieved by atypical neuroleptics allows the same neuroleptic dose to occupy a greater number of D2 receptors. 5HT2A
antipsychotic antagonism of what receptors causes appitite stimulation (3)? 1.Histamine H1 2.5HT2A 3.5HT2C
what is a main feature of atypical neuroleptics and is related to their binding profile? show clinical efficacy at dosing levels which do not show extensive EPS
What side effect is respiradone known for? hyperprolactinemia and EPS side effec
what side effects are , olanzapine and clozapine known for? weight gain, hyperglycemia and sedation
What 4 Atypical Neuroleptics features that affect EPS 1.They target D2 (little or no affinity to D1) 2.They all have very low affinity to D2 3.They almost all have affinity to 5HT2A (antagonists) 4.Atypicals with anti-muscarinic actions show added benefits against EPS
what 3 Atypical Neuroleptics features affect negative symptoms? D2 (little affinity to D1) 2.They all appear to have affinity to 5HT2A *3.Atypicals with partial 5HT1A agonist actions show added benefits against negative symptoms
name 2 D2 recpetor blockade side effects EPS; prolactin elevation
name 3 H1 receptor blockage side effects weight gain, dizziness, sedation
name a 5-HT2C receptor blockage side effects satiety blockade (leads to weightgain)
which Antipyschotic drug has a prolonged QT interval side effect? thioridazine*, rispiradone, ziprasidone, clozapine, quetiapine, haloperidol,
which antipyschotic drug has agranulocytosis side effect? clozapine
what is the Poikilothermic effect temperature (body temp varies with environment) ie chlorpromazine)
Primarily a sodium channel blocker that may also increase GABA transmission used in the treatment of Bipolar disorder Valproate / Valproic acid
drug that may modulate glutamate and GABA transmission. Interferes with IP3 turnover (affecting M1, M3, alpha1, 5HT1A. Used to treat Bipolar Disorder Lithium
dry mouth, increased thirst or urination; diabetes insipidus diarrhea are side effects of what bipolar drug? Lithium
What Bipolar drugs are C.I.'s during pregnancy? which drug should be used instead? Valproate and Lithium; Quetiapine is considered safer during pregnancy
What drug(s) can only use in patients with normal cardiac and renal function? and which drug(s) ADRs include hepatotoxicity and pancreatitis Valproate; Valproate
Drugs for absence siezures (petit mal) (2) Valproate, ethosuxemide
drugs for myoclonic siezures (2) Valproate clonazepam
drugs for tonic-clonic (grand mal) (3) Valproate, phenytoin, carbamazepine --> (pediatric)
drugs for partial (focal) seizures Carbamazepine, phenytoin, valproate
what drugs ↓axonal conduction by preventing Na+ influx through fast Na+ channels-? (6) 1.phenytoin 2.carbamazepine 3.valproate 4.topiramate 5.lamotrigine 6.zonisamide
what drugs ↑inhibitory tone by facilitation of GABA-mediated hyperpolarization? (2) 1.) Benzo's 2.) Barbiturates
what anti-epileptic drugs ↓ excitatory effects of glutamic acid? (2) 1. topiramate (block AMPA receptor) 2.felbamate (blocks NMDA receptors)
what drugs↓ presynaptic Ca2+ influx through type-T channels in thalamic neurons? (2) ethosuximide and valproic acid
what is the mechanism for valproate? and what enzyme does it inhibit? 1.Prolongs inactivation of Na+ channel (similar to phenytoin and carbamazepine)- hence blocks sustained high-frequency repetitive firing of neurons 2.Blocks T-type Ca2+ channels 3.)inhibits Cyp450-2C9
what is Divalproex sodium? 1.a combination of sodium valproate and valproic acid 2.reduced to valproate when it reaches GIT 3.better GI tolerance hence preferred by patients
What is the mechanism for Phenytoin blocks axonal Na+ channels in their inactivated state (prolongs the inactivated state) and slows its rate of recovery ---> prevents seizure propagation
which drug needs plasma monitoring (Therapeutic range - 10-20μg/mL) b/c Small increases in a daily dose can produce large increases in the plasma concentration, resulting in drug-induced toxicity Phenytoin
toxicity from what drug causes Gingival hyperplasia (Gum hypertrophy) and Hirsutism, Megaloblastic anemia, Aplastic anemia, Osteomalacia (interferes with Vit. D, Inhibition of ADH release Phentoin
is a prodrug of Phenytoin, rapidly converted to phenytoin in plasma. Intravenous _____________ can be used as a substitute for Phenytoin AND neurosurgery and status epilepticus. fosphenytoin
DoC for Trigeminal neuralgia Carbamazepine
The following ADR's are associated with what drug? 1.Dilutional hyponatremia (↑ADH secretion/sensitivity) 2.may cause an increase in seizures 3.Exfoliative dermatitis 4.Fetal malformations Carbamazepine
A prodrug with improved toxicity profile than carbamazepine does not produce the epoxide metabolite, which is largely responsible for the ADR of carbamazepine Oxcarbazepine
Drug? blocks Na+ channels, high voltage-dependent Ca2+ channels effective in a variety of seizure disorders: partial seizures, generalized seizures, absence seizures,Lennox-Gastaut syndrome (as adjunct). approved for bipolar (maintenance) LAMOTRIGINE
broad-spectrum anticonvulsant  delays the recovery of the inactivated Na+ channels enhance GABA activity by binding to the GABA receptor blocks the activation of AMPA receptors add on therapy for Partial seizures prophylaxis for migraine TOPIRAMATE
What is the consensus mechanistic goal of the antipsychotic agents to treat the positive symptoms of schizophrenia Decrease DA in NAc
What advantage do the atypical neuroleptics have over the typical neuroleptics and how do they achieve this? Treat – sxm’s and EPS
What Drug can be used for bipolar maintenance, acute bi-polar mania, and bi-polar depression? Quetiapine
What neuroepileptic can be used in children and adolescence (4) Aripriprazole; Lurasidone; Olanzapine; Quetiapine
what's the difference between sedatives and hypnotics Sedatives: decrease activity, moderate excitement and calm the recipient. Hypnotics: Produce drowsiness and facilitate the onset and maintenance of a state of sleep that resembles natural sleep and from which the recipient can be easily aroused.
Created by: moore420
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