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148 Cards in this Set
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Anticholinergic drugs used in Parkinson's Disease
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1. Benztropine (Cogentin)
2. Trihexyphenidyl (Artane) Improves TREMOR Side Effects: cycloplegia, constipation, dry mouth, tachycardia, and urinary retention Older patients: memory loss, confusion, hallucinations, dysphoria, lethargy, and a frank toxic psychosis |
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What is Amantadine?
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Amantadine (Symmetrel)
antiviral drug with unknown MOA; increases synaptic levels of dopamine by increasing release of dopamine from pre-synaptic terminals; mild anticholinergic effects also has ability to block glutaminergic NMDA receptors is NOT metabolized and is excreted through the kidneys; NOT for patients with renal failure Unique adverse effect: Livedo reticularis- purplish mottling of the skin Limited duration of action- 6-9 months |
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Name the Direct Acting Dopamine Receptor Agonists
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1. Bromocriptine (Parlodel)
2. Pramipexole (Mirapex) 3. Ropinirole (Requip) 4. Apomorphine (Apokyn) 5. Rotigotine (Neupro) |
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What is Bromocriptine?
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Bromocriptine (Parlodel)
Direct-Acting Dopamine Receptor Agonist Potent D2 receptor agonist and D1 receptor antagonist Adverse effects: orthostatic hypotension, nausea, vomiting, hallucinations, peripheral edema May be combined with levodopa |
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No. 1 reason for discontinuing use of Bromocriptine?
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Hallucinations 10-30% of patients
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What is Pramipexole?
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Pramipexole (Mirapex)
Direct-Acting Dopamine Receptor Agonist non-ergot dopaminergic agonist with high affinity for D2 receptors; also activate D3 receptors Can be used with or without levodopa excreted unchanged in the urine rarely associated with orthostatic hypotension, but hallucinations are more common Sudden sleep attacks possible with all dopamine agonists |
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What is Ropinirole?
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Ropinirole (Requip)
Direct-Acting Dopamine Receptor Agonist non-ergot dopaminergic agonist with high affinity for D2 receptors; also activate D3 receptors Can be used with or without levodopa metabolized in the liver to inactive metabolites by CYP1A2 and excreted in urine Adverse effects: syncope Sudden sleep attacks possible with all dopamine agonists |
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What is Apomorphine?
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Apomorphine (Apokyn)
non-ergot dopamine agonist injected SC for hypomotility ("off episodes") in advanced PD has affinity for D1-D5 receptors take with the anti-emetic trimethobenzamide (Tigan) contraindicated with ondasteron and other 5-HT3 receptor antagonists Hypersexuality and increased erection can occur contains sodium metabisulfite and can cause allergic reactions in patients allergic to sulfites |
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Which Parkinson's drug has sodium metabisulfite and should not be given to patient with sulfite allergies?
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Apomorphine (Apokyn)
Rotigotine (Neupro) |
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What anti-emetic should be used with Apomorphine?
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trimethobenzamide (Tigan)
NO 5-HT3 antagonists (ondasteron, etc.) |
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What is Rotigotine?
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Rotigotine (Neupro)
non-ergot dopamine agonist that primarily activates D2 receptors Transdermal Patch taken off the market due to crystallization of the patch contains sodium metabisulfite; NOT okay for sulfite allergies |
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What are some advantages of DA agonists compared to L-Dopa in PD?
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1. No competition with dietary amino acids for GI uptake or BBB transfer
2. No need for CNS metabolizing pathways to activate drug 3. Increased reliability of dose-by-dose effects 4. Increased potency compared to dopamine at D2 receptors 5. Wide therapeutic windo for antiparkinsonian effects 6. Decreased risk of dyskinesias and long-term motor fluctuations 7. Metabolsim does NOT proceed via monoamine oxidase and therefore neurotoxic reactive oxygen species are less likely to be produced But they have more mental disturbances |
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What else can Dopamine agonists be used to treat besides Parkinson's Disease?
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Restless leg syndrome (RLS)
dopamine agonist inhibits the release of more DA; need to decrease DA in RLS |
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Name the reversible COMT inhibitors
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1. Tolcapone (Tasmar)
2. Entacapone (Comtan) |
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What is Tolcapone?
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Tolcapone (Tasmar)
reversible COMT inhibitor in both the periphery and CNS allows for increased levels of levodopa to be delivered centrally Explosive Diarrhea, hepatoxoicity, bright yellow discoloration of urine |
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What is Entacapone?
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Entacapone (Comtan)
reversible COMT inhibitor only in the periphery Adverse effects: abdominal pain and discomfort, less diarrhea and no elevation of liver function tests |
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What is the most common reason patients discontinue Tolcapone?
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explosive diarrhea
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Drugs used in PD that selectively inhibits MAO-B
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Selegiline (Eldepryl)
Rasagiline (Azilect) |
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What is Selegiline?
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Selegiline (Eldepryl)
Selective inhibitor of MAO-B which increases synaptic concentrations of dopamine selegiline is metabolized into amphetamine and methamphetamine which may produce insomnia and drug has mild mood elevation effects efficacy of selegiline lasts only months when used as monotherapy side effects more likely when combined with levodopa decreases hydroxyl radical formation and might protect dopaminergic cells from free radical destruction |
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What is Rasagiline?
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Rasagiline (Azilect)
selective MAO-B inhibitor 5 times more potent than selegiline NOT metabolized to amphetamine-like substances less likely to produce insomnia metabolized by CYPA12 may protect dopaminergic cells from free radical destruction |
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an involuntary oscillation of a body part produced by alternating or synchronous contractions of reciprocally innervated antagonistic muscles
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Tremor
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stereotypic, repetitive movements that can at least be partially suppressed by volitional control
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Tic
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rapid, flick-like movements of the limbs and facial muscles that may resemble normal restlessness or fidgeting
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Chorea
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slow, writhing movements of the fingers and hands, and sometimes the toes and feet
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Athetosis
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violent, flailing movements involving proximal parts of the limb
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Ballismus
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How to treat Postural Tremor?
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Propranolol
associated with hyperadrenergic states appears to be generated and abated by alterations of peripheral adrenergic systems |
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How to treat Essential Tremor?
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thought to be generated in the CNS
1. Metoprolol or Propranolol 2. Primidone or Topiramate 3. Ethanol 4. Alprazolam or botulinium toxin |
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What is Tardive Dyskinesia?
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drug-induced (iatrogenic) disorder that occurs in 10-20% of institutionalized patients taking anti-psychotic medication
may be due to supersensitivity (upregulation) of postsynaptic dopamine D2 receptors increase in dose suppresses disorder; anticholinergic agents will exacerbate the disorder Treatment: GABA agonists benzodiazepines sodium valproate tocopherol (Vit E) Clozapine and thioridazine are "atypical" antipsychotics that do not cause Tardive Dyskinesia |
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What are frequent signs of Tardive Dyskinesia?
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FACE: blepharospams, tremor of upper lip, pouting, puckering, smacking of lips, chewing movements, sucking movements, buccal pressing of tongue, tongue protrusion
NECK: retrocollis, spasmodic torticollis TRUNK: axial hyperkinesias, Torsion or athetotic movements EXTREMITIES: Ballistic movements, chorea of hands or toes, athetosis, rotation and flexion of ankles OTHER: grunting vocalizations, asynchronous breathing, myoclonus |
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What is Wilson's Disease?
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inherited disorder of copper accumulation; reflection of copper toxicity
biological marker is the deficiency of serum ceruloplasmin Wilson's disease patients are unable to carry out biliary excretion human chromosome 13 is defective in coding for Wilson-ATPase therefore there is a decrease in clearance of copper autosomal recessive disorder Dysarthria- speech disorder in which pronunciation is unclear (universal manifestation of the disease) Treatment: Penicillamine, Potassium, trientine, zinc acetate, and zince sulfate |
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What is Tourette's
Syndrome? |
multiple motor tics and vocalizations; coprolalia (inappropriate uttering of obscenities); echophenomena (copying behaviors, repeating words of others); and obsessive compulsive phenomena
Treatment: Haloperidol Pimozide Clonidine- best to treat tics Fluphenazine Botulinium toxin A |
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A disturbance of such magnitude that there is personality disintegration and possibly loss of reality
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Psychosis
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Disorder of emotion, feeling, or mood and are subdivided as mania, unipolar depression, and bipolar affective disorder
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Affective Disorders
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great psychomotor activity, excitement, rapid passing of ideas, and unstable attention; euphoria, irritability, accompanied by inflated self esteem
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mania
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patient that is depressed without a history of mania. accompanying feelings of sadness and low self esteem
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Unipolar depression
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depressed patient with a history of at least one manic episode
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Bipolar affective disorder
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loss of contact with the environment and a disintegration of personality
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Schizophrenia
4 Types: Simple (lack of emotion) Paranoid (delusion of persecution) Catatonic (negativeness, excitement, and stupor) Hebephrenic (hysteric symptoms) |
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A psychological or behavior disorder in which anxiety is the primary characteristic.Does NOT have gross distortions of reality or disorganization of personality
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Neurosis
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Positive vs Negative Symptoms of Schizophrenia
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Positive:
hallucinations delusions agitation, tension paranoia associational disturbances insomnia illusions delusions Negative: (absense of normal behavior) Amotivation poor social skills anhedonia (inability to experience pleasure) Alogia (limited spontaneous conversation) Poverty of speech Blunted effect Poor grooming and hygiene |
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Describe the 3 component model of schizophrenia
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1. psychotic symptoms (D1 and D2)
2. negative symptoms (D1) 3. cognitive and attentional impairment |
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area of brain most responsible for thinking; disfunction of this area may lead to negative symptoms
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prefrontal cortex
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an integrated cluster of nerve cells and their fibers, which help regulate affective behavior (feelings), memory, hormonal secretion, and other behaviors or functions relevant to schizophrenia
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limbic-midbrain system
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part of brain responsible for coordinating involuntary muscle activity
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extrapyramidal motor system
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what is the key integrative unit of the prefrontal cortex?
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Pyramidal neuron
impaired functioning leads to negative symptoms of schizophrenia PFC regulates limbic structure; therefore, affecting the positive symptoms of schizophrenia |
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What type of Dopamine recepters dominate in the PFC?
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D1 receptors outnumber D2 receptors by a ratio of 10:1
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What does D1 receptor activation in the PFC do?
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D1 receptor activation seems to suppress the response to weak, temporally incoherent excitatory inputs, while augmenting the response to maintained, synchronized inputs.
Treatment which increases activation of D1 receptors in the PFC, will likewise improve the integrative capacity of surviving PFC pyramidal neurons, and theoretically, would be effective in alleviating the symptoms of schizophrenia *Modulatory effect* |
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The higher the affinity of an antipsychotic for D2-like receptors, the more POTENT the agent is in controlling the __________ symptoms of schizophrenia
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Positive symptoms
conventional antipsychotics have little effect on PFC pyramidal neurons because of the small number of D2 receptors in this region. hence their actions are primarily limited to their D2 like receptor blocking actions in the mesolimbic system.... thus effective in treating positive symptoms but poor in alleviating negative symptoms |
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What causes positive symptoms of schizophrenia vs negative symptoms of schizophrenia?
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Positive- disinhibition of the mesolimbic system
Negative- loss of brain mass |
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What is the glutamate hypothesis of schizophrenia?
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Theory that focusses on a critical glutamate receptor subtype- NMDA receptor
release of glutamate and the activation of NMDA receptor are required for normal development of the CNS DA, NE, and 5-HT are all known to modulate glutamingergic neurotransmission |
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What drugs can produce a psychotic state in humans which resembles both positive and negative symptoms of schizophrenia
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Phencyclidine (PCP, angel dust)
Ketamine (Special K) |
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What is the limbic structure that has been the focus of intensive investigation with regards to the positive symptoms of schizophrenia
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Nucleus accumbens (NAc)
blockade of D2 receptors in the NAc is primarily responsible for controlling positive symptoms |
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Describe the reentrant circuit involving the dorsal striatum
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Cortex
Caudate putamen (dorsal striatum) dorsal pallidum thalamus back to motor cortex |
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Describe the reentrant circuit involving the ventral striatum
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PREFRONTAL CORTEX
nucleus accumbens (ventral striatum) ventral pallidum thalamus (mediodorsal nucleus) back to prefrontal cortex |
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Conventional vs Atypical Antipsychotics
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Conventional- approved before 1975 and act primarily by antagonizing D2 like dopamine receptors
Atypical- 1990 and after; action on5-HT2 receptors as well as D2 like receptors |
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Name the Conventional Antipsychotics
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Phenothiazines:
Chlorpromazine (Thorazine) Thioridazine (Mellaril) Thiothixene (Navane) Trifluoroperazine (Stelazine) Fluphenazine (Prolixin) Perphenazine (Trilafon) Mesoridazine (Serentil) Haloperidol (Haldol) Loxapine (Loxitane) Molindone (Moban) |
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Name the Atypical Antipsychotics
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Clozapine (clozaril)
Risperidone (Risperdal) Olanzapine (Zyprexa) Quetiapine (Seroquel) Ziprasidone (Geodon) Aripiprazole (Abilify) Paliperidone (Invega) Iloperidone (Fanapt) Asenapine (Saphris) Lurasidone (Latuda) |
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Describe Phenothiazines
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3 types of substitutions on phenothiazine ring structure:
1. Aliphaitc 2. Piperidine 3. Piperazine (most potent) potent antagonists as D2, D3, and D4 dopamine receptors |
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What is chlorpromazine?
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Chlorpromazine (CPZ, Thorazine)
Phenothiazine with Aliphatic substitution potent blockade of alpha 1 and H1 receptors (orthostasis and sedation) moderate EPS Used for: agitated schizophrenics |
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What is thioridazine?
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thioridazine (Mellaril)
Phenothiazine with N incorporation into a piperidine ring used parenterally blocks alpha1 and H1 (orthostasis and sedation) potent antimuscarinic (Most anticholinergic) Least amount of EPS amonst typical antipsychotics |
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What is mesoridazine?
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mesoridazine (Serentil)
Phenothiazine with N incorporation into a piperidine ring used parenterally blocks alpha1 and H1 (orthostasis and sedation) potent antimuscarinic (Most anticholinergic) Least amount of EPS amonst typical antipsychotics |
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What is fluphenazine
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fluphenazine (Prolixin)
Phenothiazine with N incorporation into a piperazine ring insignificant sedative effects; less orthostasis and cholinergic effects Used for: depressed or withdrawn schizophrenics HIGH incidence of EPS best anti-emetic activity Potency: fluphenazine> thiothixene> trifluoroperazine> perphenazine |
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What is thiothixene
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thiothixene
Phenothiazine with N incorporation into a piperazine ring insignificant sedative effects; less orthostasis and cholinergic effects Used for: depressed or withdrawn schizophrenics HIGH incidence of EPS best anti-emetic activity Potency: fluphenazine> thiothixene> trifluoroperazine> perphenazine |
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What is trifluoroperazine
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Trifluoroperazine (Stelazine)
Phenothiazine with N incorporation into a piperazine ring insignificant sedative effects; less orthostasis and cholinergic effects Used for: depressed or withdrawn schizophrenics HIGH incidence of EPS best anti-emetic activity Potency: fluphenazine> thiothixene> trifluoroperazine> perphenazine |
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What is perphenazine
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perphenazine (Trilafon)
Phenothiazine with N incorporation into a piperazine ring insignificant sedative effects; less orthostasis and cholinergic effects Used for: depressed or withdrawn schizophrenics HIGH incidence of EPS best anti-emetic activity Potency: fluphenazine> thiothixene> trifluoroperazine> perphenazine |
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What is the MOA of Phenothiazines/Thioxanthenes and the Other Conventional Antipsychotics?
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They increase dopamine turnover in the CNS via their ability to block autoreceptors on dopaminergic neurons
takes several weeks to develop full antipsychotic effects because it takes time for the disinhibited presynaptic dopaminergic neurons lose their ability to fire because they become "exhausted" depolarization block D2 receptors remain blocked projections from VTA do not undergo depolarization block which means dopaminergic neurotransmission to the PFC is preserved D1 activation in the PFC is beneficial in treating schizophrenia |
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What causes the high incidence of EPS with Phenothiazines?
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depolarization block of the dopaminergic neurons of the substantia nigra decreases the dopamine content in the caudate-putamen (striatum)
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What is akathisia?
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motor restlessness, muscular quivering, and the inability to remain in a sitting position
side effect of Conventional antipsychotics |
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Which antipsychotic is the most cardiotoxic and can cause ventricular fibrillation?
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Thioridizine
prolongs QT interval (conventional antipsychotic) |
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What is the maximum dose of Thioridazine?
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800mg/day dose limit with thioridazine or blindness may occur due to toxic pigment deposits in the retina (irreversible)
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Which conventional antipsychotic has the least weight gain?
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Molindone
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Which antipsychotics lower seizure threshold?
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Aliphatic and Piperidine compounds are most likely to have this effect
Clozapine is the agent most likely to cause seizures |
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How to treat Pseudo-parkinsonism
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Pseudo-parkinsonism- akinesia, tremor, rigidity
oral anticholinergic drugs: benzotropine trihexylphenidyl diphenhydramine or amantadine |
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How to treat Dystonia
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Dystonia- spasms involving the head, neck, trunk, and extremities
Parenteral anticholinergics: benztropine trihexylphenidyl diphenhydramine or diazepam |
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How to treat Akathisia
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Akathisea- state of extreme motor restlessness and drive to move
propranolol benzodiazepines amantadine |
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How to treat Perioral tremor
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Perioral Tremor- rabbit syndrome, late-appearing form of pseudo-parkinsonism
Anticholinergic agents: benztropine trihexylphenidyl diphenhydramine |
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How to treat Tardive Dyskinesia?
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Tardive Dyskinesia- stereotyped, repetitive, involuntary movements of the mouth, lips, tongue, and choreiform movements of the limbs and body
AVOID anticholinergic drugs switch to clozapine, switch to atypical, benzodiazepines, calcium channel blockers Tardive Dyskinesia is a major problem with the use of conventional anti-psychotic drugs |
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How to treat Neuroleptic malignant syndrome?
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Neuroleptic malignant syndrome- catatonia, stupor, fever, unstable blood pressure, myoglobinemia, can be fatal
stop neuroleptic immediately; dantrolene or bromocriptine may help; antiparkinsonian agents not effective |
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Which medication is most likely and least likely to cause Tardive Dyskinesia?
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Haloperidol= most likely
Thioridazine= least likely |
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This is the Extrapyramidal Effect Description of what?
akinesia, muscle rigidity, shuffling gait, drooling, mask-like face, tremor of extremities |
Parkinsonian symptoms
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This is the Extrapyramidal Effect Description of what?
Oculogyrics crisis (fixed upward stare), Torticollis (unilateral spasm of neck muscles), Opisthotonus (arched back), Trismus, larngospasm (spasm of muscles in jaw,throat) |
Dystonic Reactions
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This is the Extrapyramidal Effect Description of what?
Motor restlessness, inability to sit or stand still, rocking and shifting of weight while standing |
Akathisia
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This is the Extrapyramidal Effect Description of what?
Rhythmic clonic musculature contractions such as spasms, tics, involuntary muscle movements |
Dyskinesias
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This is the Extrapyramidal Effect Description of what?
Rhythmical, involuntary movement of tongue, lips, or jaw, choreiform movements of extremities, athetoid movements of extremities (writhing, worm-like movements) |
Tardive Dyskinesia
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Which conventional anti-psychotic is the most potent?
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Haloperidol (Haldol)
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Name the Conventional Butyrophenones
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Butyrophenones:
1. Haloperidol (Haldol) 2. Droperidol |
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What is Haloperidol?
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Haloperidol (Haldol)
Butyrophenone Class of Conventional Antipsychotic extrapyramidal effects are common; very potent D2 dopamine receptor antagonist also has alpha 1 blocking activity therefore can cause orthostatic hypertension alleged to have anti-agitation properties and has been used in emergency situations to calm violent or highly agitated patients |
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What is Droperidol?
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Droperidol
butyrophenone derivative used mainly as a preanesthetic medication Droperidol + fentanyl= INNOVAR |
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What is Pimozide?
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Pimozide
Diphenylbutyropiperdine (typical antipsychotic) less sedation than haloperidol orphan drug to treat Tourette's Syndrome (biggest use) |
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What is Loxapine?
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Loxapine (Loxitane)
Typical Antipsychotic Chemical type: Dibenzoxepine High incidence of EPS; about 10 times more potent than CPZ |
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Which Typical agents also have 5HT-2A blocking activity?
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Chlorpromazine (CPZ)
Loxapine (Loxitane) |
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What is Molindone?
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Molindone (Moban)
Dihydroindolone class of typical agents high incidence of EPS with perhaps higher incidence of akithisia than other antipsychotics little or no weight gain does NOT lower seizure threshold (seizure is less likely) |
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What are the advantages and disadvantages of Atypical antipsychotics?
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Advantages:
treats both positive and negative symptoms produces less EPS improves cognitive effects more effectively less elevation of serum prolactin Disadvantages: Hyperglycemia Hyperlipidemia |
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Which Atypical antipsychotics are most likely to cause hyperglycemia and hyperlipidemia?
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Olanzepine
Clozapine |
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What is the effect of 5-HT-2A activation on heteroceptors?
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inhibits DA release
blocking 5HT-2A heteroceptors increases DA release |
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What is Ritanserin?
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pure 5HT-2A antagonist that combined with conventional antipsychotic agents to improve negative symptoms
NOT effective when used alone |
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What is Clozapine?
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Clozapine (Clozaril)
dibenzodiazepine antipsychotic drug which blocks D2 receptors in the mesolimbic-mesocortical system while having less D2 blocking activity in the extrapyramidal system minimal EPS and lack of tardive dyskinesia also has high affinity for D4 dopamine receptors found in the PFC, potent anticholingergic, and alpha 1 blocking agent because of toxicity, only recommended for patients who have not responded adequately to standard antipsychotic drugs Adverse Effects: Agranylocytis (requires weekly blood count monitoring) Seizures Sedation Black Box Warning: Myocarditis |
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What is Resperidone?
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Risperidone (Risperdal)
Qualitatively atypic antipsychotic agent low incidence of EPS; treats positive and negative symptoms *Most widely used single antipsychotic drug blocks D2, 5-HT2, and alpha-1 adrenergic receptors adverse effects: insomnia, agitation, anxiety, sedation, weight gain, sexual dysfunction, and difficulty concentrating; orthostatic hypotension and reflex tachycardia can occur in the elderly Most likely to produce elevated prolactin Does NOT produce agranulocytosis, cardiac effects, or seizure induction can cause neuroleptic malignant syndrome |
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What is Paliperidone?
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Paliperidone (Invega)
active metabolite of risperidone; first extended release antipsychotic to be marketed 60% renally eliminated can cause elevated prolactin longer half life, less side effects high dose= EPS |
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What is Olanzapine?
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Olanzapine (Zyprexa)
clozapine analogue; low EPS; treats both positive and negative symptoms blocks D2, 5-HT2, D1, D4, 5-HT3, alpha 1, and H1 Significant weight gain! Highest propensity to produce hyperglycemia and hyperlipidemia amonst atypical agents once a day administration |
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What is Quetiapine?
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Quetiapine (Seroquel)
Clozapine analogue; low potency antipsychotic binds to 5-HT2a, D1, D2, alpha-1 receptors; low affinity for muscarinic receptors less beneficial effects on negative symptoms than other atypicals transcient prolactin elevations requires multiple doses per day Used as sleep inducer "expensive benedryl" monotreatment of depressive phase of Bipolar |
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What is Ziprasidone?
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Ziprasidone (Geodon)
atypical antipsychotic agent antagonist at both D2 and 5HT2a/2c receptors; also agonist at 5HT1a receptors and antagonist at 5HT1b/1d; antagonizes H1 Potent inhibitor of NE and 5-HT reuptake Side effects: transient prolactin elevation, less EPS, more nausea and vomiting, less weight gain, and prolongation of QTc interval some orthostasis and minor sedation |
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What is Aripiprazole?
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Aripiprazole (Abilify)
newest of the atypical antipsychotics "dopamine system stabilizer" (DSS) partial agonist at D2 and 5-HT1A receptors, antagonist at 5-HT2A receptors Partial D2 receptor agonists serve as functional postsynaptic antagonists in the presence of excessive amounts of dopamine (only dopamine has full D2 agonist) thus they reduce dopaminergic neurotramission when dopamine is excessive in the limbic system metabolized by CYP3A4 and CYP2D6 Side effects: nausea and vomiting due to partial agonism of D2 in CTZ) Does NOT cause hyperprolactemia, hyperlipidemia, hyperglycemia, or weight gain Does NOT increase the QT interval |
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What is the Receptor Binding profile for the atypical antipsychotic Clozapine?
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muscarinic= H1> alpha 1> 5HT2a> D4> D2> D1
most anticholinergic antipyschotic significant weight gain, dose-related seizures, agranulocytosis, high sedation, sialorrhea (drooling), Myocarditis Most effective agent in therapy of treatment-resistant schizophrenia |
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What is the Receptor Binding profile for the atypical antipsychotic Risperidone?
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5HT2a> alpha 1> D2> D4>>D1
no antimuscarinic activity; very potent 5HT-2A receptor blockade doses above 6-10 mg/day may produce EPS has more prolactin elevations than any other atypical agent |
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What is the Receptor Binding profile for the atypical antipsychotic Olanzapine?
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5HT2a> muscarinic> H1> D2> D4>D1= alpha 1
sedation, significant weight gain, greatest incidence of hyperglycemia and hyperlipidemia |
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What is the Receptor Binding profile for the atypical antipsychotic Quetiapine?
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H1> alpha 1> muscarinic> D2 = 5HT2a> D1> D4
weight gain requires BID dosing |
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What is the Receptor Binding profile for the atypical antipsychotic Ziprasidone?
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5HT2a> 5HT1d= 5HT1a> D2>alpha 1> D4> D1
no muscarinic activity; very potent 5-HT2a and D2 blockade potent reuptake inhibitor of NE and 5-HT contraindicated in combination with other agent that prolongs the QT interval less weight gain |
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What is the Receptor Binding profile for the atypical antipsychotic Aripiprazole?
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Aripiprazole
D2> 5HT2a> alpha a>> D4> D1 partial agonist at D2 receptors which essentially acts as a functional antagonist at D2 receptors partial agonism of D2 in striatum produces less EPS antagonism at 5HTsa receptors contributes to decreased incidence of EPS and treats negative symptoms NO weight gain, hyperglycemia, hyperlipidemia, nor hyperprolactemia |
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What atypical antipsychotics are most likely to cause weight gain and/or diabetes?
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1. Clozapine
2. Olanzapine |
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What atypical antipsychotics are most likely to cause EPS and elevated prolactin?
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1. Paliperidone
2. Rsperidone |
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Which atypical antipsychotic may cause QTc prolongation?
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Ziprasidone (Geodon)
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Which atypical antipsychotics are most likely to decrease weight gain?
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1. Aripiprazole
2. Ziprasidone |
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What is Iloperidone?
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Iloperidone (Fanapt)
atypical antipsychotic agent chemically related to risperidone combines D2 and 5-HT2A antagonism; also has alpha 1 blocking activity may prolong QTc interval |
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What is Asenapine?
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Asenapine (Saphris)
sublingual Atypical antipsychotic for acute treatment of schizophrenia and manic or mixed episodes associated with bipolar disorder antagonist at D2 and 5-HT2a and partial agonist at D1 and 5-HT1a receptors also has high affinity for other dopamine and serotonin receptors as well as alpha and histamine receptors low affinity for muscarinic receptors may increase QTc interval |
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What is Lurasidone?
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Lurasidone (Latuda)
atypical antipsychotic approved in 2010 D2 and 5HT2A receptor antagonist metabolized by CYP3A4 80mg is max dose |
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Treatment of acute manic phase of bipolar disorder
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Haloperidol
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Relief of panic reactions and psychosis associated with illicit drug use
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Haloperidol
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Treatment of acute manic phase of bipolar disorder
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Haloperidol
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Antiemetic therapy
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Phenothiazines
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Treatment of acute manic phase of bipolar disorder
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Haloperidol
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Relief of panic reactions and psychosis associated with illicit drug use
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Haloperidol
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Treatment of Tourette's disorder
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Haloperidol
or pimpozide |
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Antiemetic therapy
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Phenothiazines
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Relief of panic reactions and psychosis associated with illicit drug use
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Haloperidol
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Antiemetic therapy
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Phenothiazines
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Treatment of Tourette's disorder
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Haloperidol
or pimpozide |
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Treatment of intractable hiccups
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Perphenazine
or Chlorpromazine |
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Treatment of Tourette's disorder
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Haloperidol
or pimpozide |
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Treatment of intractable hiccups
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Perphenazine
or Chlorpromazine |
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Treatment of intractable hiccups
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Perphenazine
or Chlorpromazine |
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What are the cardinal symptoms of Mania?
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1. Psychomotor excitement
2. Euphoria 3. Flight of ideas 4. Delusions/Hallucinations |
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What are signs of depressive episode in Bipolar Disease?
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1. Change in appetite and weight
2. Lethargy 3. Increased feeling of fear and guilt 4. Concentration difficulties and constant feeling of danger 5. Sad, often lonely feeling 6. Thoughts of death and suicide |
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What is a Hypomanic episode and its signs?
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feeling of irritability and inflated self-esteem lasting over 4 days. similar to manic episode but there are less severe symptoms and no delusions or hallucinations. Does not usually affect a person's daily routine
1. Decrease need for sleep 2. Easily distracted 3. seeks exposure to highly pleasurable activities that have high risks 4. no sign of fatigue 5. moderate levels of euphoria and confidence |
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What are the signs of a manic episode?
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period of heightened and irritable mood level lasting for as least 1 week
1. Difficulty concentrating 2. delusions, and in the most severe instances, hallucinations 3. Excessive self-confidence 4. Aggressive behavior and poor judgment 5. Changes in speech patterns |
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What are symptoms of Mixed Episode?
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1. Suicidal thoughts
2. Extreme euphoric highs and feelings of despair 3. increased aggression 4. prolonged periods without sleep |
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Type 1 vs. Type 2 Bipolar Diagnosis Types
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Type 1:
one or more manic episodes, major depressive episodes, episodes not due to medical condition or prior substance abuse, 90% recurrence in episodes, suicidal rate as high as 20% Type 2: one or more depressive episodes, no extremely heightened mood levels or emotions evident, often induced by substance abuse and prior medical conditions |
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What are indications for Lithium use?
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1. treatment of acute manic episodes, or unipolar depressive states
2. prophylaxis of both manic and depressive episodes 3. treatment of alcoholism where depression is a major component of the disorder 4. management of violence and aggression, explosive personalities, and emotionally unstable character disorders requires 4-10 days to exert its therapeutic effect no sedation or tranquilization |
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Lithium vs neuroleptics
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Lithium:
more specific antimanic effect objective monitoring parameters (blood levels) lack of adverse effects lacks dysphoric sedative or tranquillized effect also prophylactic greater patient acceptance Disadvantages of Lithium: narrower therapeutic-toxic index overdose harder to manage requires more consistent patient compliance slower onset |
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Which antipsychotics are used to treat manic episodes?
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Aripiprazole
Olanzapine |
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MOA for Lithium?
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inhibits the depolarization-evoked and Ca2+ dependent release of DA and NE, but NOT 5-HT from nerve terminals; infact Lithium enhances 5-HT release
prevents the supersensitivity of D2 receptors that occurs with chronic antipsychotic administration to animals Lithium inhibits removal of the phosphate group from monophosphoinositol to generate inositol; inositol is usually recycled and regenerates PIP2 which yeilds IP3 and DAG these PIP2 depleting effects are limited to the CNS |
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What are the Toxicyt and Side Effects associated with Lithium?
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Narrow therapeutic index
Side effects when <1.5mEq/L: gastrointestinal distress polyuria and polydipsia fine hand tremor slight muscle weakness Levels between 1.5-2.5 mEq/L: Coars hand tremor muscle hyperirritability slurred speech confusion or somnolence profuse diarrhea Levels >2.5 mEq/L: deep tendon reflexes irregular pulse hypotension epileptic seizure stupor or coma Renal, aggravtion of psoriasis and acne, weight gain, non-toxic goiter and /or hypothyroidism; leukocytosis monitor blood levels of lithium every 1-2 months |
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What effects Lithim Levels in the body?
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Na and diuretics
Lithium competes with sodium for reabsorption in the renal tubules; therefore, low na= high lithium and high Na= low Li levels Lithium is NOT reabsorbed in the distal limb of the loop of Henle or beyond; therefore, thiazides do not directly affect lithium clearance Thiazide diuretics can reduce lithium excretion by as much as 50%; reduce lithium dose if given with thiazides Therapy with Loop Diuretics does not present this concern because of teh increased reabsorption of lithium in the proximal tubule is counteracted by increased excretion in the loop of henle Co-administration of NSAIDS can increase lithium toxicity by inhibiting its excretion should monitor lithium blood levels every 1-2 months |
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Name other drugs besides Lithium used to treat Bipolar Disorder
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1. Valproate
2. Carbamazepine 3. Lamotrigine 4. Gabapentin 5. Topiramate |
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What is Divalproex sodium?
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Divalproex sodium (Depakote/ Valproate)
treats manic episodes associated with Bipolar Dissorder increases presynaptic concentrations of GABA, the principal inhibitory neurotransmitter in the brain better tolerated than Lithium used to calm agitation or impulsive aggression in psychiatric patients |
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What is Carbamazepine?
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Carbamazepine (Tegretol)
used to treat mania and may be helpful in patients intolerant or nonresponsive to lithium or valproate less effective at treatment of bipolar disorder compared to lithium used to treat post-traumatic stress disorder, withdrawal from substance abuse, borderline personality disorder, and explosive behavior associated with head injury or developmental disability |
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What is Lamotrigine?
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Lamotrigine (Lamictal)
used for treatment of bipolar depressive phase effective in treatment of refractory mood episode in rapid and non rapid cycling patients adverse effects: dizziness, ataxia, somnolence, blurred vision, and nystagmus; also severe life-threatening rashes including Stevens-Johnson syndrome and toxic epidermal necrolysis can occur |
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What is Gapapentin?
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Gabapentin (Neurontin)
Bipolar Treatment less effective than lamotrigine on refractory mood disorders; promising results reported for patients with anxiety, social phobia, panic disorder, aggressive behavior and withdrawal from substance abuse suitable as an add-on treatment |
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What is Topiramate?
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Topiramate (Topamax)
has been used as a mood stabilizer and for treatment of binge-eating; it does not cause weight gain and may cause weight loss; cognitive impairment can occur |
