Parkinson's disease and pharmacological management, Alzheimer's disease and pharmacological management, Schizophrenia and pharmacological management, Depression and pharmacological management.
2
What is the focus of the slide?
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The focus of the slide is on the pharmacological management of various mental health conditions.
3
What are Dopaminergic Pathways?
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Dopaminergic Pathways are neural pathways in the brain that use dopamine as a neurotransmitter.
4
What diseases are associated with Dopaminergic Pathways?
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Dopaminergic Pathways are associated with neurodegenerative diseases and psychosis.
5
What is the predominant catecholamine neurotransmitter in the CNS?
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Dopamine
6
What are the enzymes that degrade dopamine?
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Monoamine oxidase (MAO) and catechol-o-methyl transferase (COMT)
7
How does dopamine cross the BBB?
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L-dopa crosses the BBB and is converted to dopamine in the brain
8
What are the main functions of D1-like dopamine receptors?
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Regulate reward system, motor activity, memory, and impulse control.
9
Which dopamine receptors are involved in renal function and renin secretion?
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D1-like dopamine receptors (D1 and D5).
10
What is the function of the Nigrostriatal pathway?
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For coordination of voluntary movement
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Which pathway regulates behavior and psychosis?
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Mesocortico/mesolimbic pathway
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What neurotransmitter is involved in the Tuberoinfundibular pathway and what does it inhibit?
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Dopamine, inhibits prolactin secretion from the anterior pituitary
13
What is the pharmacological effect of dopamine dose-dependent?
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Lower doses mainly stimulate the dopaminergic receptors, while higher doses can stimulate both dopaminergic and beta1-adrenergic receptors.
14
What are the two types of dopamine action?
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Excitatory (D1-like receptors) and inhibitory (D2-like).
15
What disorders does dopamine contribute to the pathophysiology of?
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Parkinson’s disease, schizophrenia, bipolar disorder, substance use disorders (reward system), and attention deficit hyperactivity disorder (ADHD).
16
What is the pharmacological approach to treating Parkinson's disease?
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Increase brain dopamine levels and antagonize acetylcholine action.
17
What are the movement symptoms of Parkinson's disease?
Which part of the brain is affected in Parkinson's disease?
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Degeneration of dopamine-producing neurons of the substantia nigra.
19
What is the primary mechanism of action for Dopamine precursors (Levodopa)?
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Levodopa is a precursor to dopamine, which is directly converted into dopamine in the brain.
20
What are Dopamine agonists and how do they work in the context of Parkinson's disease?
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Dopamine agonists mimic the effects of dopamine by binding to dopamine receptors in the brain, thereby treating Parkinson's disease symptoms.
21
What are MAO and COMT inhibitors and how do they contribute to the treatment of Parkinson's disease?
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MAO and COMT inhibitors inhibit the degradation of dopamine in the brain, thereby increasing dopamine levels and treating Parkinson's disease symptoms.
22
What is the mechanism of action (MOA) of Levodopa-Carbipoda?
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Levodopa acts as a dopamine precursor. It is actively transported into the CNS and converted to dopamine. Carbipoda, a dopamine decarboxylase inhibitor, inhibits the metabolism of levodopa (to dopamine) in the periphery and thus increases its availability in the CNS.
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What are the trade names for Levodopa-Carbipoda?
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Sinemet® and Duopa®.
24
What is the indication for levodopa in the management of PD?
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Management of PD
25
What are the adverse effects of levodopa?
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Orthostatic hypotension, visual and auditory hallucinations, abnormal involuntary movements, xerostomia, and taste alterations
26
What is the mechanism of action of a muscarinic antagonist?
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Overproduction of acetylcholine triggers a chain of abnormal signaling leading to impaired mobility.
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What is the example of a muscarinic antagonist mentioned in the slide?
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Benztropine (Cogentin®)
28
What are the dental-related adverse effects of muscarinic antagonists?
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Often associated with xerostomia.
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What is the mechanism of action of Entacapone?
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Entacapone inhibits COMT and reduces the peripheral metabolism of L-dopa.
30
What is the mechanism of action of Selegiline?
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Selegiline is a MAO-B inhibitor that decreases DA metabolism in the CNS, prolonging its action.
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What are the dental-related adverse effects of Entacapone?
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Entacapone can cause abnormal tastes and orthostatic hypotension.
32
What is the therapeutic goal of antipsychotic drugs in the treatment of schizophrenia?
What are the two main categories of antipsychotics?
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First-generation antipsychotics and Second-generation antipsychotics
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What are the typical side effects of first-generation antipsychotics?
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Higher incidence of extrapyramidal symptoms (EPS)
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What are the examples of first-generation antipsychotics?
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Chlorpromazine (Thorazine®), Fluphenazine, and Haloperidol (Haldol®)
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What is the mechanism of action of first-generation antipsychotics?
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Competitive blocker of D2 receptors in the mesolimbic pathway
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What are the side effects of first-generation antipsychotics?
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Can block receptors in other DA pathways causing extrapyramidal syndrome (EPS), especially haloperidol. Haloperidol can also cause tardive dyskinesia & trismus.
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What are second-generation antipsychotics also known as?
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Atypical antipsychotics
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What are the examples of second-generation antipsychotics?
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Clozapine (Clozaril®) and risperidone (Risperdal®)
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What is the indication for clozapine?
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First-line therapy for schizophrenia, management of manic episodes, and adjunct treatment for refractory depression
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What is the Extrapyramidal syndrome?
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A group of motor symptoms including Parkinson-like movements, muscle rigidity, and spasms of the neck and facial muscles.
46
What are the autonomic effects of the drug?
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Xerostomia and orthostatic hypotension.
47
What is the sedative effect of the drug?
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Due to anti-histaminic action.
48
What is tardive dyskinesia?
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A rare but potentially irreversible motor disorder characterized by involuntary facial jaw movements, sticking-out the tongue, lip smacking, and 'fly-catching' motions of the tongue, as well as uncontrollable movements in the arm, leg, and torso.
49
List the symptoms of tardive dyskinesia.
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Protrusion and rolling of the tongue, sucking and smacking movements of the lips, chewing motion, facial dyskinesia, and involuntary movements of the body and extremities.
50
What is xerostomia?
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Dry mouth
51
What are the side effects of antipsychotics?
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CNS depressant effects
52
What oral health issues might patients with schizophrenia face?
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Poor oral hygiene and self-harming behaviors such as tongue, lip, and/or cheek biting
53
What is the therapeutic goal of drugs for dementia disorders?
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The therapeutic goal is mostly palliative to help with decreasing symptoms or stabilizing patient condition.
54
What are the main mechanisms of action for drugs targeting Alzheimer's disease?
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Increasing acetylcholine availability or blocking glutamate or decreasing amyloid plaques.
55
What are Acetyl cholinesterase inhibitors and provide examples?
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Acetyl cholinesterase inhibitors are drugs that increase the levels of acetylcholine in the brain. Examples include Donepezil (Articept) and Rivastigmine (Exelon).
56
What is an NMDA receptor antagonist and how is it used in the treatment of Alzheimer's Disease?
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An NMDA receptor antagonist is a drug that blocks glutamate receptors. It is used in combination with Acetyl cholinesterase inhibitors to treat Alzheimer's Disease.
57
What is Aducanumab and when was it approved for use in Alzheimer's Disease?
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Aducanumab is an Amyloid beta-directed monoclonal antibody. It was approved for use in Alzheimer's Disease in 2021.
58
What is the mechanism of action (MOA) of acetylcholinesterase inhibitors?
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Reversibly inhibit centrally active acetylcholinesterase (AChE; enzyme responsible for ACh hydrolysis)
59
What are the FDA-approved uses of Donepezil?
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Dementia associated with Alzheimer's disease (AD)
60
What are the adverse effects of acetylcholinesterase inhibitors?
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Nausea, diarrhea, sleep disturbances, bradycardia, and hypotension due to enhanced vagal tone
61
What is the mechanism of action of Memantine?
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Memantine is an NMDA receptor antagonist that limits calcium influx into neurons to prevent excitotoxicity.
62
What is the purpose of Aducanumab?
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Aducanumab is an amyloid beta-directed monoclonal antibody that aims to reduce amyloid beta plaques and delay Alzheimer's disease progression.
63
What is the primary characteristic of Amyotrophic Lateral Sclerosis (ALS)?
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Degeneration of motor neurons leading to the inability to control muscle movement.
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What is the mechanism of action (MOA) of Riluzole (Exservalan®) in managing ALS?
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Inhibits glutamate release and inactivates sodium channels.
65
What are the adverse effects of Riluzole (Exservalan®) in managing ALS?
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Nausea and oral hypoesthesia.
66
What is serotoninergic neurotransmission?
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The process by which serotonin, a neurotransmitter, is released, transmitted, and then reabsorbed or degraded in the synaptic cleft.
67
What are the key steps in serotoninergic neurotransmission?
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Synthesis of serotonin in the presynaptic neuron, storage in synaptic vesicles, release into the synaptic cleft, binding to receptors on the postsynaptic neuron, and reuptake or degradation of serotonin.
68
What is the main storage location for serotonin?
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Enterochromaffin cells of the small intestine
69
What enzyme degrades serotonin?
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Monoamine oxidase (MAO)
70
How is serotonin transported to storage vesicles?
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Via vesicular monoamine transporter
71
What are serotonin receptors and how many families are there?
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Serotonin receptors are a group of receptors that bind to serotonin, and there are seven families of serotonin receptors.
72
What are the coupling mechanisms of 5-HT1 receptors and what tissues do they affect?
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5-HT1 receptors are Gi coupled and affect brain and smooth muscle tissues.
73
What are the coupling mechanisms of 5-HT2 receptors and what effects do they mediate?
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5-HT2 receptors are Gq coupled and mediate hallucinogenic effects and platelet aggregation.
74
What are the pharmacological effects of serotonin in the CNS?
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Serotonin affects mood, appetite, body temperature regulation, and sleep cycle.
75
What therapeutic implications does modulating serotonergic transmission have?
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It can be useful in treating anxiety, psychosis, major depression, posttraumatic stress disorder, and migraines.
76
What is the prevalence of depression in females compared to males?
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Females have a higher prevalence at 16% compared to males at 10.1%
77
What percentage of patients receiving therapy or counseling are estimated to have depression?
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Around 30%-40%
78
What is the monoamine hypothesis of depression?
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It states that depression is caused by the lack of monoamine transmitters in the brain, particularly serotonin and norepinephrine.
79
What role does dopamine deficiency play in depression?
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Dopamine deficiency plays an important role in the lack of interest (anhedonia) symptom commonly seen in depression.
80
What is the time frame for the clinical response to antidepressant drugs?
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Weeks
81
What neurotransmitters are not consistently decreased in postmortem studies of depressed brains?
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Norepinephrine and serotonin
82
What is brain-derived neurotrophic factor and its role in depression?
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A protein necessary for neurogenesis and neural survival, downregulated in depressed brains
83
What is the Neuroplasticity Hypothesis?
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It suggests that lowered levels of brain-derived neurotrophic factor (BDNF) or dysfunction of its receptor, TrkB, plays a significant role in depression development.
84
What are the key components of the Neuroplasticity Hypothesis?
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Lowered levels of brain-derived neurotrophic factor (BDNF) and dysfunction of its receptor, TrkB.
85
What does MAOIs stand for?
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Monoamine Oxidase Inhibitors
86
What are the abbreviations for the different types of antidepressants mentioned?
What are Tricyclic Antidepressants (TCAs) and what are some examples?
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TCAs are a class of antidepressants that inhibit the reuptake of norepinephrine and serotonin, leading to an increase in their neurotransmitter action. Examples include Amitriptyline (Elavil®) and Clomipramine (Anafranil®).
88
What is the mechanism of action (MOA) of TCAs?
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TCAs inhibit the reuptake transporters of norepinephrine (NET) and serotonin (SERT), thereby potentiating the action of these neurotransmitters.
89
What is Clomipramine used to treat?
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Obsessive-compulsive disorder (OCD)
90
What are some adverse effects of Clomipramine?
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Antimuscarinic effects (xerostomia), alpha-adrenergic effects (orthostatic hypotension, dizziness), histaminic side effects (sedation), and sympathomimetic effects (tachycardia, agitation, sweating)
91
How do TCAs interact with local anesthesia in dentistry?
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TCAs may potentiate the sympathetic action of epinephrine in local anesthesia
92
What are Monoamine Oxidase Inhibitors (MAOIs)?
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MAOIs are a class of drugs that bind and inactivate the MAO enzyme, leading to increased monoamine neurotransmitter concentrations.
93
What is the mechanism of action (MOA) of MAOIs?
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MAOIs bind and inactivate the MAO enzyme, which is responsible for the metabolism of neurotransmitters, thereby increasing monoamine neurotransmitter concentrations.
94
What are the adverse effects of MAOIs?
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The adverse effects of MAOIs include drowsiness, orthostatic hypotension, xerostomia, and constipation.
95
What is the 'tyramine pressor response'?
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A sudden increase in blood pressure and hypertensive crisis due to the accumulation of tyramine in the diet of individuals taking MAO inhibitors.
96
How should patients taking MAO inhibitors be monitored when receiving local anesthetics with epinephrine?
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Carefully monitored due to the potentiation of the action of sympathomimetics by MAO inhibitors.
97
What are Selective Serotonin Reuptake Inhibitors (SSRIs)?
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SSRIs are a class of antidepressants that selectively inhibit the reuptake of serotonin into the presynaptic neuron, thereby increasing serotonin levels in the synaptic cleft.
98
What are some examples of SSRIs?
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Examples include Fluoxetine (Prozac®), Sertraline (Zoloft®), Citalopram (Celexa®), and Escitalopram (Lexapro®).
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What is the mechanism of action (MOA) of SSRIs?
Show answer
SSRIs selectively inhibit the serotonin reuptake transporter (SERT) to increase serotonin concentration in the synaptic cleft.
100
What are the adverse effects of SSRIs mentioned in the slide?
Show answer
Gastrointestinal irritation (nausea, diarrhea), sexual dysfunction, weight gain, and teeth grinding or bruxism.
101
What is serotonin syndrome and what are its symptoms?
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Serotonin syndrome is the accumulation of serotonin in the body, which can lead to fatal complications due to cardiovascular collapse. Symptoms include anxiety, disorientation, tachycardia, hyperthermia, high blood pressure, and neuromuscular abnormalities (tremors, muscle rigidity).
102
What is the risk associated with simultaneously prescribing NSAIDs and SSRIs?
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The risk of gastrointestinal bleeding significantly increases.
103
Which two SSRIs inhibit CYP2D6?
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Fluoxetine and paroxetine.
104
What is the consequence of simultaneously using SSRIs and supplements that increase serotonin levels?
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Patients are at risk of serotonin syndrome.
105
What are Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)?
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SNRIs are a class of antidepressants that selectively inhibit the reuptake transporters of serotonin and norepinephrine.
106
What are some examples of SNRIs?
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Venlafaxine (Effexor®) and duloxetine (Cymbalta®) are examples of SNRIs.
107
What is the main indication for SNRIs?
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SNRIs are primarily used for the treatment of depression and other psychiatric disorders.
108
What are the gastrointestinal adverse effects of certain medications?
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Nausea and diarrhea
109
What is bruxism?
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Grinding of teeth
110
What are the noradrenergic-related adverse effects?
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Increased blood pressure and heart rate, insomnia, and anxiety
111
What is the mechanism of action (MOA) of rapid-acting antidepressants like Ketamine?
Show answer
Enhance glutamate release and block NMDA receptors
112
What are the adverse effects of rapid-acting antidepressants like Ketamine?
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Increase in blood pressure, tolerance and dependence, dizziness, sialorrhea, altered sense of taste
113
What are serotonin receptor antagonists and what are their effects?
Show answer
Serotonin receptor antagonists are drugs that block selective serotonin receptors (5-HT2a) with minor effects on other receptors. They are used in some depression patients, particularly females, and can cause sedative effects and xerostomia.
114
What is a dopamine-norepinephrine reuptake inhibitor and what is an example of one?
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A dopamine-norepinephrine reuptake inhibitor is a drug that increases the levels of dopamine and norepinephrine in the synaptic cleft. An example is bupropion, which is also used for tobacco cessation.
115
What is the active ingredient in St. John's Wort?
Show answer
Hyperforin
116
How does St. John's Wort interact with CYP 450 enzymes?
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It induces CYP 450 enzymes, specifically CYP3A4 and CYP2C9.
117
What is the therapeutic index of lithium salts?
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Narrow therapeutic index (low safety margin)
118
What is the indication for lithium salts?
Show answer
Managing bipolar disorders
119
What are some adverse effects of lithium salts?
Show answer
Xerostomia, metallic taste, sedation, polyuria, polydipsia, hand tremors
120
What is the primary route of excretion for lithium?
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Kidney
121
What are the drug interactions that can increase the plasma levels of lithium?
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NSAIDs, certain antibiotics like doxycycline and metronidazole
122
How does chronic lithium treatment affect the duration of local anesthetics?
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It may prolong the duration of local anesthetics
123
What are the adverse effects of Valporic acid?
Show answer
Teratogen (spina bifida) & thrombocytopenia (increases risk for bleeding)
124
What are the adverse effects of Carbamazepine?
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Teratogen (cleft palate), bone marrow suppression (risk of infection?)
125
What are the implications of depression on dental caries risk?
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Depression increases the patient risk for dental caries and other oral health issues due to lack of self-care, reduced salivary flow, and preference for carbohydrates.
126
What is xerostomia and how can it be caused?
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Xerostomia is a condition characterized by dry mouth, and it can be caused by many antidepressants.
127
What are mental disorders?
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Chronic diseases requiring long-term control through pharmacological and/or psychological means.
128
What are some self-harming behaviors associated with mental illness?
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Tongue, lip, and/or cheek biting.
129
What therapeutic options are available for treating depression, bipolar disorder, and psychoses?