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Block 8: Psych > Week 1 (Mood Disorders and Addiction) > Flashcards

Week 1 (Mood Disorders and Addiction) Flashcards

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1
Q

Dopamine neurons effect on both motor function and behavior

A

1) Dopamine neurons from substantia nigra to caudate and putamen are important for motor function
2) Dopamine neurons from ventral tegmental area (VTA) to frontal cortex, striatum (nucleus accumbens, caudate, putamen), limbic cortex (temporal lobe) and amygdala, hippocampus are important for behavior

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2
Q

Basal ganglia circuit loops influenced by dopamine

A

1) Motor cortex
2) Frontal cortex (dorsolateral prefrontal cortex)
3) Limbic cortex

Note: dopamine acts at putamen and anterior caudate

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3
Q

Major depressive disorder (MDD)

A

Unipolar, “clinical” depression

10% of the population

17% will have MDD at some point

Leading cause of disability for age 15-44

Females more than males

Onset in 20s/30s, another peak in perimenopausal women, another peak >65yo

Diagnosis made by presence of critical number of symptoms

Heterogeneous disease

Several pathophysiologic models, not one etiology for all

Treatment works, but not one-size-fits-all

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4
Q

How is treatment for MDD?

A

Many not treated at all, some treated pooly

Treatment rates vary by ethnic group (whites treated best and mexicans treated worst)

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5
Q

Diagnosis of MDD

A

Clinical syndrome

Symptoms present for >/= 2 weeks

Must have major impact on person

Must not be explained by something else (substance abuse, medication side effects, other illness)

No diagnostic biomarker, must use diagnostic interview (“structured interview”)

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6
Q

Major depression symptoms

A

Depressed mood

Diminished interest or pleasure in most activities

Significant weight loss or gain (>5%) or appetite change

Insomnia or hypersomnia

Psychomotor agitation or slowing

Fatigue or loss of energy

Worthlessness or guilt

Impairments in attention or decisiveness

Recurrent thoughts of death

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7
Q

Comorbidities with depression

A

Diabetes: poor metabolic control, poorer adherence to medication and diet regimens, lower quality of life, higher medical expenditures

Cardiovascular disease: 1/5 with CVD have MDD also, and another 1/5 have minor depression; 1/3 get depression 1 year after MI and then have higher mortality than non-MDD; MDD predicts development of CVD also

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8
Q

Mechanisms of MDD

A

Behavioral: diet, exercise, meds

Autonomic: heart rate variability less in people with MDD (bad!)

Inflammatory signaling: cytokines increased by 3x in MDD

Molecular mechanical: platelet adhesion increased (serotonin in serum sticks to platelets and increases adhesion –> can cause clot or MI)

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9
Q

Screening for suicidality

A

Highest rate of completed suicide are older, unmarried, white males

First ask about suicidal ideation (have you ever felt that life is not worth living?), then follow up on nature, frequency, extend, timing of suicidal thoughts, especially the context (job loss, death of loved one)

See if there is a plan (details, lethality, practicing, firearms in the home)

Degree of intent (motivation, extent of aim to die, associated behapiors or planning for suicide)

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10
Q

Neurobiology of MDD

A

Catecholamine hypothesis: monoamine, biogenic amine, abnormal signaling with 5HT, NE, DA

Neurotrophin hypothesis: deficits in neurotrophins (BDNF) lead to withered neurons, reduced plasticity and neurotransmission impairments

Vascular hypothesis: microvascular disease in white matter disrupts circuits leading to symptoms

Inflammatory hypothesis: cytokines and cortisol disrupt neuronal function

Psychological: cognitive, behavioral, psychosomatic, social, personality, psychosomatic; mind not tied to physical brain?

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11
Q

Candidate gene x environment interactions (cGxEs)

A

Are not as robust as they appear because of publication bias

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12
Q

Effective treatments for MDD

A

Antidepressant medications

Psychotherapy

Brain stimulation: electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS)

No one treatment works for everyone

May take several weeks for benefits to emerge

Side effects occur first but fade with time (reason for patients stopping tx before it starts to work!)

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13
Q

How to assess treatment success in MDD

A

Remission (symptom resolution) instead of response (>50% improvement) leads to less disability and less risk of relapse

Simple rating scale (“measurement based care”) can give reliable benchmark (don’t just ask how’s your hypertension, you measure it)

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14
Q

Failure of treatment

A

Less than 1/3 of patients remit with initial treatment (so treatment fails in more than 2/3)

Can be because of biological factors, patient couldn’t tolerate getting to appropriate dose, patient didn’t see benefits so stopped taking med, misconceptions or stigma derailed treatment

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15
Q

Next step treatments for MDD

A

Combined medications: SSRI plus bupropion; antidepressant plus T3 or lithium; antidepressant plus aripiprazole

Medication plus therapy

TMS

ECT

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16
Q

Complementary and alternative medicine for MDD

A

Folate and 5-methyltetrahydrofolate (MTHF) (Deplin)

Vitamin B12

Omega-3 fatty acids

S-adenosyl-L-methionine (SAMe)

St John’s Wort

Yoga

Tai Chi

Acupuncture

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17
Q

DSM

A

Diagnostic and Statistical Manual of Mental Disorders

Collection of diagnostic criteria used as a standard for communication, billing, and research into psychiatric disorders

Organized by major symptoms (not etiology) and is primarily descriptive

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18
Q

Disorders we will study that are in the DSM

A

Mood disorders: major depressive disorder, dysthymic disorder, bipolar I disorder, bipolar II disorder

Substance related disorders: dependence, abuse, intoxication

Anxiety disorders

Somatic distress disorders

Sleep disorders

Personality disorders

Adjustment disorders

Schizophreniform disorder

Schizoaffective disorder

Delirium

Dementia

Other cognitive disorders

Disorders usually first diagnosed in infancy, childhood or adolescence: autism, learning disorders, communication disorders, ADD, disruptive disorders, mental retardation)

Eating disorders: anorexia nervosa, bulimia nervosa

Sexual and gender identity disorders

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19
Q

Factors necessary for diagnosis

A

Meet specific criteria (or number of symptoms from a list)

Meet duration or age of onset requirements

Have clinically significant distress or impairment in social, occupational or other important areas of functioning

Not have exclusionary disorders

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20
Q

Etiology is important in which disorders?

A

PTSD requires a specific event

Adjustment disorders are a response to an event

Mental disorders due to specific general medical condition

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21
Q

Biopsychosocial model for coding

A

Axis I: clinical disorders and other conditions which may be a focus of clinical attention; typically require immediate attention from a clinician (usually we have medications for these disorders)

Axis II: personality disorders/mental retardation;maynot require immediate carebut cancomplicatetreatment so should be taken into account by the clinician

Axis III: general medical conditions (diabetes, CVD, etc)

Axis IV: psychosocial and environmental problems (poverty, dysfunctional families, other factors in patient’s environment that might have impact on person’s ability to function)

Axis V: global assessment of functioning (overall rating of person’s ability to cope with normal life in school, work, social settings; 10 is persistent danger of severely hurting self or others and 100 is superior functioning)

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22
Q

Cerebral cortex receives brainstem projections of which biogenic amines?

A

Dopamine (from substantia nigra and VTA)

Norepinephrine (from locus coeruleus)

Serotonin (from raphae)

These regulate many aspects of behavior including mood

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23
Q

Fast acting amino acid neurotransmitters

A

Glutamate (excitatory)

GABA (inhibitory)

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24
Q

Glutamate signaling

A

Excitatory, fast acting

Important in long distance, point to point connections

Receptors are AMPA (ion channel), NMDA (ion channel), metabotropic (second messenger)

Mechanism for synaptic plasticity via LTP

Basis for excitotoxicity (mechanism for neuronal death in CNS trauma, ischemia and neurodegenerative disease)

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25
Q

Memantine

A

Glutamate antagonist

Drug for Alzheimer’s disease

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26
Q

GABA

A

Inhibitory, fast acting

Important in local interneuron connections

Important in many behavioral syndromes (anxiety, etc)

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27
Q

Drugs that act on GABA receptor

A

Benzodiazepine

Barbiturates

Alcohol

This can be additive so don’t drink while taking benzos/barbiturates!

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28
Q

Biogenic amines

A

Neuromodulators with effects on many behaviors and mood disorders

Catecholamines: DA, NE, E

Indoleamine: 5HT

Imidazoleamine: histamine

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29
Q

Amine inputs to the cerebral cortex

A

Diffuse (NT released from varicosities), and target ALL cortical layers

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30
Q

Where else (other than synapses) do aminergic neurons release NTs from?

A

Aminergic neurons release NTs from varicosities along the axon fibers in a paracrine fashion (act on target molecules on neurons (?) nearby, but not at a synapse)

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31
Q

Receptor subtypes for aminergic neuromodulators

A

Multiple receptor subtypes are generated from different genes or RNA splice variants

Different receptor subtypes can mediate different effects and can be selectively targeted by pharmacological agents

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32
Q

How do many aminergic receptors work?

A

Many are metabotropic receptors that activate G-proteins, which then modulate ion channels or trigger intracellular second messenger systems

NE –> beta adrenergic receptor –> G-protein –> adenylyl cyclase –> cAMP –> PKA –> increase protein phosphorylation

DA –> dopamine D2 receptor –> G-protein –> adenylyl cyclase –> cAMP –> PKA –> decrease protein phosphorylation

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33
Q

Conventional anti-psychotic therapeutic drugs

A

Blockers of D2 receptors (have Parkinsonian motor side effects!)

Have other actions as well (Chlorpromazine, Haloperidol)

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34
Q

Dopamine synthesis

A

Tyrosine turned to DOPA by tyrosine hydroxylase (rate limiting enzyme in both DA and NE synthesis!)

DOPA durned to dopamine by DOPA decarboxylase

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35
Q

Homovanillic acid (HVA)

A

Major metabolite of dopamine

Can be measured in urine, plasma and CSF

HVA is increased in psychosis (DA) and pheochromocytoma (NE)

HVA is decreased in depression, Parkinson’s (DA), when taking anti-psychotics

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36
Q

Where are DA neurons located?

A

In the midbrain:

Substantia nigra

Ventral tegmental area (VTA)

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37
Q

Dopamine terminal fields

A

Caudate, putamen (nigro –> striatal) for motor

Nucleus accumbens (ventral striatum) important in reward (VTA) (meso –> limbic)

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38
Q

How does DA influence behavior?

A

Dopaminergic projections to frontal cortex, limbic cortex, amygdala, hippocampus

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39
Q

How are biogenic amines cleared?

A

Reuptake

Note: this can be target of psychoactive agents and drugs

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40
Q

Transporters that regulate levels of DA release and re-uptake

A

Vesicular monoamine transporter (VMAT)

Dopamine transporter (DAT)

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41
Q

Which drugs target DAT (dopamine transporter)

A

Ritalin (methylphenidate): stimulant

Bupropion: antidepressant

Cocaine

These all block reuptake and increase dopamine concentrations at synapses

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42
Q

NE synthesis

A

Tyrosine turned to DOPA by tyrosine hydroxylase (rate limiting enzyme in both DA and NE synthesis!)

DOPA durned to dopamine by DOPA decarboxylase

Dopamine turned to NE by dopamine-beta-hydroxylase

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43
Q

Vanillylmandelic acid (VMA)

A

Major metabolite of NE

Can be measured in urine, plasma, CSF

VMA is increased in pheochromocytoma

VMA is decreased in depression

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44
Q

Where are NE neurons?

A

Locus coerulus of the brainstem (pons)

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45
Q

Where do NE pathways project?

A

All neocortical areas (frontal, etc)

Limbic cortex (temporal lobe)

Amygdala

Hippocampus

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46
Q

Transporters that regulate levels of NE release and re-uptake

A

Vesicular monoamine transporter (VMAT)

Norepinephrine transporter (NET)

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47
Q

Drugs that target norepinephrine transporter (NET)

A

Ritalin (methylphenidate): stimulant

Tricyclic antidepressants: imipramine, nortriptyline, desipramine

These block reuptake

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48
Q

Epinephrine synthesis

A

NE turned into Epi by phenylethanolamine N-methyltransferase

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49
Q

Targets of epi pathways

A

More restricted projections to subcortical regions

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50
Q

Serotonin (5HT) synthesis

A

Tryptophan turned to 5-hydroxytryptophan by tryptophan-5-hydroxylase

5-hydroxytryptophan turned to serotonin (5HT) by aromatic L-amino acid decarboxylase

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51
Q

5-hydroxyindoleacid (5-HIAA)

A

Major metabolite of serotonin

Can be measured in urine, plasma and CSF

5-HIAA increased in autism

5-HIAA decreased in depression, suicide, aggression and violence

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52
Q

Where are serotoninergic neurons located?

A

Raphe nuclei along midline of brainstem (medulla, pons and midbrain)

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53
Q

Major targets of serotinergic pathways

A

All neocortical areas (frontal, etc)

Limbic cortex (temporal lobe)

Amygdala

Hippocampus

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54
Q

SERT

A

Serotonin transporters (SERT) regulate levels of 5HT reuptake

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55
Q

Drugs that target SERT (serotonin reuptake transporter)

A

SRI (serotonin reuptake inhibitors) antidepressants: fluoxetine (Prozac), peroxatine

Tricyclic antidepressants: imipramine, nortriptyline, desipramine

MDMA (ecstasy)

These block reuptake and increase serotonin concentrations at synapses

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56
Q

Monoamine oxidases (MAO) and MAO inhibitors

A

MAOs enzymatically degrade catecholamines

MAO inhibitors block catecholamine breakdown (so increase concentrations) and are used as antidepressants and in anxiety disorders (Phenelzine, Selegeline)

Two forms of monoamine oxidase have different specificities: MAO-A (5HT, NE, DA), MAO-B (DA)

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57
Q

Histamine synthesis

A

Histidine turned to histamine by histidine decarboxylase

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58
Q

Major targets of histamine pathways

A

All neocortical areas (frontal etc)

Limbic cortex (temporal lobe)

Amygdala

Hippocampus

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59
Q

What does histamine influence?

A

Sleep and wakefulness

Appetite

Drugs that increase histamine (increase release or receptor agonist) promote wakefulness and reduce appetite: modafinil (promotes histamine release)

Drugs that decrease histamine (decrease release or block H1 receptors) promote drowsiness and sleep (anti-histamines) and promote appetite: diphenhydramine (Benadryl which is anti-histamine, H1 blocker)

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60
Q

What are the targets of Ach pathway?

A

Basal nucleus (forebrain) cholinergic system sends projections to all cortical regions including hippocampus and amygdala

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61
Q

Which neuron terminals are lost in Alzheimer’s?

A

ACh terminals in the hippocampus and cerebral cortex

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62
Q

Cholinomimetic drugs

A

Promote memory and attention

Approved treatment for Alzheimer’s disease

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63
Q

Neuromodulatory peptides that have effects on behavior

A

Enkephalins: endogenous opiates; pain modulation; reward

Leptin: appetite regulation

Oxytocin and vasopressin: social bonding

CRH: stress response

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64
Q

Demographics of Bipolar Disorder

A

1-2% lifetime prevalence (up to 5% if broader definitions)

Onset of clear episodes in 20s but some report teen/childhood onset

25% attempt suicide and 15% complete

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65
Q

Diagnosis of bipolar disorders

A

Family of clinical diagnoses defined by presence of symptoms of these states: depressed, manic, hypomanic, mixed

Have major impact on the person (impairment)

Not explained by something else

No diagnostic biomarker; diagnostic interview is gold standard

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66
Q

Symptoms of a manic episode

A

Elevated, expansive or irritable mood for at least one week (or any duration if hospitalized) along with >/= 3 of:

Inflated self-esteem or grandiosity

Decreased need for sleep

More talkative than usual (pressured speech)

Racing thoughts or flight of ideas (thoughts only tangentially related to each other)

Distractibility

Increase in goal-directed activity

Excessive involvement in high risk activities

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67
Q

Symptoms of a hypomanic episode

A

Elevated, expansive or irritable mood for at least 4 days, clearly different from a person’s usual mood, and >/= 3 other symptoms of mania (>/= 4 if only irritable)

Non-subtle change in functioning (ex: sufficiently more productive in a way noticeable to others)

Not severe enough to cause serious impairment in social or occupational functioning, or to necessitate hospitalization and there are no psychotic features

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68
Q

Symptoms of a mixed episode

A

“Black Mania”

Meet criteria for both manic and depressed episodes, except duration of depression need only be one week

Severe, causing marked impairment

Rule out substance induced, general medical condition, etc

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69
Q

DSM-IV-TR classification of Bipolar Diagnoses

A

Bipolar I Disorder: at least one lifetime episode of mania or mixed state; although not required for diagnosis, one lifetime episode of major depression occurs in the majority

Bipolar II Disorder: at least one lifetime episode of hypomania; at least one lifetime episode of major depression

Bipolar NOS: not otherwise specified

Bipolar disorder with “rapid cycling”: meets criteria for bipolar I or bipolar II; 4 or more episodes of major depression, (hypo)mania, or mixed state in any one year

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70
Q

Possible triggers for depression and (hypo)mania

A

Depression triggers: stressful event, poor social support, negative cognitions, poor nutrition, sedentary lifestyle, medication effects, alcohol/substance misuse

(Hypo)mania triggers: poor/reduced sleep pattern, stressful life event, severe emotional stress, drug misuse or abuse, “switching” from medication, natural rhythmicity of the disorder

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71
Q

Co-morbidities with bipolar disorder

A

Psychiatric co-morbidities: 77% have some disorder; 44% have >/= 3; 63% anxiety disorder (50% panic); 37% substance disorder (34% alcoholic); 45% behavioral disorder (20% ADHD)

Medical co-morbidities: cardiovascular (HTN, hyperlipidemia), endocrine/metabolic (obesity, thyroid, T2DM)–can occur within first decade of illness

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72
Q

Course of bipolar disorder

A

37% relapse within one year

73% relapse within 5 years despite treatment

Question is not whether or not they’ll have another episode, but when

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73
Q

Pathophysiology of bipolar disorder

A

Neuroimaging studies show key regions of the brain that differ in volume and/or activity (ex: medial prefrontal cortex, putamen, amygdala more active when processing emotionally expressive faces)

Signaling cascades are affected by drugs (lithium, etc), so these may be involved in pathophysiology

Family pedigree and GWAS studies duggest specific genes, but replication is problematic

Gene x Environment interaction is likely

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74
Q

What can lead to dysregulation of mood in the brain?

A

Diminished prefrontal modulation of subcortical and medial temporal elements (amygdala, anterior striatum, thalamus)

75
Q

What signaling pathways/molecules are targeted by mood stabilizers (lithium and divalproate) for treating bipolar disorder?

A

BDNF pathway

Extracellular signal-regulated kinase pathway

Glycogen synthase kinase-3-mediated pathway

Bcl-2

76
Q

Genetic factors important in bipolar disorder

A

Not yet known, but being investigated by GWAS (genomewide association studies)

77
Q

Challenges to treating bipolar disorder

A

Manic episodes are more responsive to treatment than depressive, but people LIKE their manias

Depressive episodes account for much of the disability

Loss of insight interferes with receiving effective treatment

Psychotherapeutic interventions improve outcomes but require willing participation

78
Q

Treatments for mania or mixed episodes

A

Lithium

Anticonvulsant agents: valproate, lamotrigine, carbamazepine

Antipsychotic agents: olanzapine, risperidone, quetiapine, ziprasidone, aripirazole

Adjunctive benzodiazepines commonly used

ECT or clozapine for refractory cases

If psychotic symptoms, include antipsychotic

Psychoeducation

79
Q

Treatments for depressive episodes

A

Lithium and lamotrigine are first-line

Antidepressants remain controversial: olanzapine-fluoxetine combo has FDA approval (Zyprexa plus Prozac = Symbax)

Quetiapine has FDA approval

Psychotherapy (cognitive behavioral therapy, interpersonal therapy, social rhythm therapy)

ECT for refractory situations

Be watchful for potential “switch” into mania

If psychotic symptoms, include an antipsychotic

80
Q

Maintenance treatment for bipolar disorder

A

Lithium (dose once per day to give renal cells a chance to regenerate)

Valproate

Lamotrigine

Aripiprazole

Quetiapine, Ziprasidone as adjunct to lithium or valproate (FDA approved)

Need to monitor for long-term toxicities (thyroid, renal, hepatic impact) and side effects (diabetes, dyslipidemias)

81
Q

Complementary and alternative medicine for bipolar disorder

A

Omega-3 fatty acids

BCAA (branched chain amino acids)

N-acetylcysteine

Folic acid

Magnesium

Inositol

Acupuncture

82
Q

Harmless use

A

Use patterns that do not predispose to harm or risk of harm

Perceptions of harm vary according to cultural norms (alcohol normal in US but opiates normal in Middle East)

83
Q

At-risk use

A

Elevated risk for substance-related problems (exceeding recommended limits, non-medical use, illicitly obtaining drug)

No long-lasting harm

84
Q

Substance abuse

A

Maladaptive use –> impairment

>/= 1 within 12 months and recurrent: failure to fulfill obligations, use in hazardous situations, legal problems, social problems

Criteria for dependence not met

85
Q

Substance dependence

A

Maladaptive use –> impairment

>/= 3 within 12 months:

Tolerance

Withdrawal

Larger amounts or period than intended

Unable to decrease use

Excessive time spent

Decrease important activities

Use despite physical or psychological problems

86
Q

What is addiction?

A

Chronic, relapsing brain disease characterized by compulsive use despite harmful consequences

87
Q

How does neurobiology affect diagnosis/treatment of addiction?

A

Addiction is a brain disease so we need to give therapy

Engage personal responsibility for disease management

Biopsychosocial model in practice

Combination of pharmacotherapy plus behavioral therapy and social support is recommended as the standard of care

88
Q

Clinical course of addiction

A

Volitional at first

Chronic

Relapsing (loss of control)

Never “cured” but controllable

Same condition, different targets

Natural recovery possible

89
Q

How many people have dependence on drugs, alcohol or nicotine?

A

3% drugs

8% alcohol

21% nicotine

90
Q

Biological risk factors for addiction

A

40-60% of vulnerability is genetic (metabolism, reinforcing effects, responses to the environment)

Neurochemicals

Neurocircuits

91
Q

NTs involved in addiction

A

DA: in nucleus accumbens and substantia nigra; role in motivation and pleasure

5HT: in dorse raphe; role in mood, pain, impulsivity

Opioid: everywhere; role in pain and pleasure

Glutamate (+): in hippocampus; role in learning and memory

GABA (-): everywhere; role in alertness

92
Q

Psychological risk factors

A

Risk-taking

Sensation-seeking

Impulsive

Unhealthy coping skills

Psychiatric conditions

Self-esteem issues

93
Q

Environmental risks

A

Drug availability

Cultural values

Lack of parental support/family dysfunction

Drug-using peers

Life stressors

Lack of structure

Poorly developed social skills

94
Q

NTs and alcohol

A

Alcohol increases DA –> pleasure, reward, craving

Alcohol decreases serotonin –> impulsivity, disinhibition

Alcohol increases opiates –> euphoria

Alcohol increases GABA –> sedation, hypnotic

Alcohol inhibits glutamate –> amnesia, learning impairments

95
Q

Alcohol intoxication depending on BAC

A

0-100 mg/dl: euphoria disinhibition

100-200: slurred speech, incoordination

200-300: confusion

300-400: stupor

400-500: coma

>500: death

96
Q

Maximum drinking limits

A

Men: 2 drinks per day and 14 per week

Women: 1 drink per day and 7 per week

One episode of heavy drinking past 1 month (>5 for men; >4 for women)

97
Q

Methamphetamine

A

Synthetic

High lasts 8-24 hours

Half life 12 hours

Causes DA release

Limited medical uses

Neurotoxic

98
Q

Cocaine

A

Plant-derived

High lasts 20-30 minutes

Half life 1 hour

Blocks DA reuptake (?)

Used medically

Not directly neurotoxic

99
Q

Methamphetamine intoxication

A

Rush (5 to 30 minutes): adrenal gland release of epi, rapid release of DA, intensely euphoric, tachycardia, BP spike, heart rhythm abnormalities

High (4 to 6 hours): continuation of the physical and mental hyperactivity

Binge (3 to 15 days): larger doses required to achieve same intensity, little or no rush or high felt, physical and mental hyperactivity

100
Q

Methamphetamine withdrawal

A

“Crash” (1 to 3 days): follows a binge, tired, lifeless, and sleepy, feelings of emptiness and dysphoria, often repeat use of this drug or alcohol/other drugs to self-medicate withdrawal symptoms

Withdrawal (several days to weeks): depressive symptoms, lethargy, cravings, and suicidal thoughts

101
Q

Long term effects of methamphetamine use

A

Addiction

Psychosis (paranoia, delusions, hallucinations, repetitive motor activity)

Changes in brain structure and function

Memory loss

Aggressive or violent behavior

Anxiety and mood disturbances

Fatigue

Dental problems

High BP, tachycardia, tachypnea

MI, stroke

Skin lesions

Dehydration, weight loss

Death

102
Q

Marijuana

A

THC (delta-9-tetrahydrocannabinol)

Euphoria, attention/short term memory, impulsiveness, time distortions, conjunctival injection, impaired coordination

Association with psychosis with frequent users

103
Q

Medical marijuana

A

Compassionate Use Act 1996

SB 420 (2003) establishes ID card, county level “regulation”

Explosion (2007-2010; 439 in LA)

Legalization in 2013?

104
Q

Screening for nicotine dependence

A

How long from the time you wake up is your first cigarette?

< 5 min = severe nicotine dependence

< 60 min = moderate nicotine dependence

> 3 hours = mild nicotine dependence

105
Q

Opioid intoxication

A

Initial euphoria followed by apathy, sedation, retardation, impaired function

Pupillary constriction

Drowsiness, slurred speech, inattention, memory impairments

106
Q

Opioid withdrawal

A

Dysphoria

N/V

Myalgias

Lacrimation

Yawning

Insomnia

Diarrhea

Craving and anxieties

107
Q

Highest risk for problem/pathological gambling

A

AA, disabled, unemployed

108
Q

Physical health issues of pathological gamblers

A

Heart disease, liver disease, HTN, stress-related physical problems (migraines, tension headache, IBS, ulcers, insomnia and sexual dysfunction)

More likely to have had a physical injury

More likely to have needed ER visit

3.5x more likely to have sleep problem, poorer sleep quality and increased daytime sleepiness

109
Q

What does problematic sleep cause?

A

Impaired self-control and decision-making

Increases impulsivity

Attenuate responses to losses and increase expectations of gains

Degrade cognition in executive functioning tasks

SO we need to become aware whether client is also suffering sleep problems and include that in management!

110
Q

Psychotropic (psychoactive) drug

A

Crosses BBB and acts primarily on CNS

Affects brain function, resulting in alterations in perception, mood, consciousness, cognition and behavior

111
Q

Catecholamine Hypothesis of affective disorders (mood)

A

Dysfunction in NE and/or 5HT systems

Depression is deficiency in NT activity (alterations in receptor sensitivity/function?)

Mania is excessive NT activity

112
Q

Do people usually respond to antidepressant drugs?

A

Response in 50-60% of adults with major depression

Remission in 30%

80% of patients will eventually respond to drug therapy

113
Q

Tricyclic antidepressants (TCAs)

A

Inhibit reuptake of biogenic amines (NE, 5HT): inhibition of reuptake occurs immediately but takes 2-3 weeks to see antidepressant activity and 8-10 weeks for maximal effect

Block muscarinic cholinergic receptors (are antimuscarinic)

Block alpha-1 adrenergic receptors

Block H1 histamine receptors

Note: muscarinic, alpha1 and H1 actions not wanted–just because of structure of drug

114
Q

Binding affinities of TCAs

A

TCAs have high binding affinity for NET and SERT (not as much DAT)

Also may have high affinity for unwanted receptors (like 5HT2A which is responsible for psychosis?!)

115
Q

Pharmacologic effects of TCAs

A

CNS effects

Sedation: can be used to induce sleep; contraindicated in combination with other CNS depressants (ethanol, sedating antihistamines)

Normal subjects do not show mood elevation, and may feel unpleasant or dysphoric

Can produce seizures at high doses

Weight gain

Withdrawal if stopped abruptly (nausea, dizziness, headache, increased perspiration, salivation)

Patients should be slowly tapered off drug

ANS: anticholinergic (antimuscarinic) activity causes dry mouth, blurred vision, constipation, urinary retention

CV: tachycardia and arrhythmias due to increased NE in cardiac tissue and antimuscarinic activity; orthostatic hypotension due to alpha-adrenergic block; bundle branch block and signs of impaired conduction due to local anesthetic activity

116
Q

What do you do if you OD on antidepressants?

A

OD can be fatal!

Treat by controlling arrhythmias w/lidocaine and propanolol

Control seizures with diazepam or lorazepam

Reduce CNS antimuscarinic effects with physostigmine

117
Q

Clinical uses for antidepressant drugs

A

Depression

Enuresis = bed-wetting (imipramine is most commonly used)

Chronic pain (amitriptyline is most commonly used)

118
Q

Drug interactions of antidepressants

A

Potentiate effects of other CNS depressants

Potentiate hypertensive effects of sympathomimetic amines

Additive effects with other antimuscarinic drugs

Cause severe reaction when administered with MAOIs

119
Q

Mirtazapine (Remeron)

A

Second generation antidepressant

Blocks 5HT2 and alpha2 adrenergic receptors

Does not inhibit reuptake; very sedative and associated with weight gain

120
Q

Bupropion (Wellbutrin/Zyban)

A

Second generation antidepressant

Inhibits reuptake of NE, DA; nAChR antagonist

Does not cause weight gain or sexual dysfunction

Also used for smoking cessation

121
Q

Trazodone (Desyrel)

A

Second generation antidepressant

Inhibits 5HT reuptake and blocks 5HT2 receptors; little antimuscarinic and autonomic activity

Very sedative; frequently used to promote sleep nondepressed patients (?)

122
Q

St. Johns Wort

A

Herbal treatment (Hypericum perforatum) for depression

Induces CYP450 (so decreases concentrations of other drugs!)

123
Q

Examples of selective serotonin reuptake inhibitors (SSRIs)

A

Fluoxetine (Prozac): long half life (2-3 days) and active metabolite norfluoxetine has 7-9 day half life

Paroxetine (Paxil)

Fluvoxamine (Luvox)

Sertraline (Zoloft)

Citalopram (Celexa)

Escitalopram (Lexapro)

Note: no evidence that any SSRI is superior to any other, but some patients who fail to respond to one SSRI will respond to another because of differences in tolerability

124
Q

SSRIs

A

Little effect on NE reuptake

Produce few CV and antimuscarinic side effects

Metabolism: fluoxetine and paroxetine metabolized by CYP2D6, and paroxetine by CYP3A4 also

Adverse effects: nausea, diarrhea, headache, insomnia, jitteriness, fatigue and sexual dysfunction, hyponatremia (SIADH especially in elderly)

125
Q

Serotonin Syndrome

A

Triad of mental status changes, autonomic hyperactivity, neuromuscular abnormalities

Signs: tremor, hyperreflexia, muscular rigidity, ocular clonus, hyperthermia, agitation

Drugs that cause excess serotonin: MAOIs, TCAs, SSRIs, opiate analgesics, OTC cough medicine, antibiotics, weight-reduction agents, antiemetics, antimigraine agents, drugs of abuse, herbal products

Management: removal of precipitating drugs, provision of supportive care, control of agitation, administration of 5HT2a antagonists, control of autonomic instability, control of hyperthermia

126
Q

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

A

Duloxetine (Cymbalta): blocks both 5HT and NE reuptake

Venlafaxine (Effexor): primarily blocks 5HT reuptake at lower doses, and both 5HT and NE reuptake at higher doses; may cause more restlessness and insomnia than the SSRIs

Desvenlafaxine (Pristiq): desmethyl version of venlafaxine

127
Q

Adverse effects of SSRIs and SNRIs in children

A

Similar to those in adults but increases in motor acivity more common

Long-term safety of these drugs (effects on growth, personality development and behavior) is unknown

Greater risk of suicidal thoughts or behaviors (but not actually suicide) when children or adolescents take SSRIs and SNRIs –> black-box warnings on all antidepressant drug labels

128
Q

CYP450 metabolism of SSRIs, TCAs

A

Metabolite of parent compound is active, with pharmacology similar (but not identical) to parent compound

Duration of clinical activity associated with AUC of parent compound and active metabolite (not just plasma half life of drug) defined by total time above threshold plasma levels assumed for efficacy

Long half-life of metabolites provides drug-generated “tapering” effect contrasts with drugs with shorter half lives and inactive metabolites that require continued drug administration with increasingly lower dosages (both strategies minimize drug withdrawal symptoms that can be observed if the parent drug is discontinued abruptly)

129
Q

Examples of Monoamine Oxidase Inhibitors (MAOIs)

A

Isocarboxazid (Marplan): hydrazide; non-selective MAOI; irreversible or slowly reversible; no tyramine-containing food

Phenelzine (Nardil): hydrazide; non-selective MAOI; irreversible or slowly reversible; no tyramine-containing food

Tranylcypromine (Parnate): non-hydrazide structurally similar to d-AMPH; non-selective MAOI; irreversible or slowly reversible; no tyramine-containing food

Selegiline (Deprenyl): selective irreversible MAO-B inhibitor; used for Parkinson’s disease

130
Q

MAOIs

A

Can inhibit both MAO-A and MAO-B or just one

MAO is enzyme responsible for intracellular oxidative deamination of catecholamines and 5HT

Metabolism: hydrazides metabolized by acetylation; rate of metabolism variable

Since new enzyme must be synthesized to overcome inhibition, it lasts days after drugs gone from plasma

131
Q

Lithium as a mood stabilizer

A

Mechanism not yet known but may change electrolyte conductance, may be due to interference with phosphatidylinositol signaling cascade in brain

Pharmacologic effects: CNS effects are small in normal people but calms manics and dampens mood swings in bipolar patients; no peripheral autonomic blocking activity

Absorbed rapidly and well

Not metabolized

Renal excretion (clearance reduced by diuretics so must decrease lithium dose if taking diuretics)

Adverse reactions: low TI (adverse effects at therapeutic levels, must monitor), fine tremor (treat w/propanolol), N/V/D, polyuria and polydipsia (Li+ blocks action of ADH on distal tubule), decreases thryoid function, cardiac arrhythmias, weight gain, fluid retention

132
Q

Mood stabilizers (other than lithium)

A

Valproic acid: monitor liver function

Carbamazepine: do CBC

Lamotrigine

Some atypical antipsychotic drugs: olanzapine, aripiprazole, ziprsaidone, risperidone, quetiapine

133
Q

Choice of drug for major depression

A

SSRI is initial treatment: citalopram or sertraline in adults, fluoxetine for children or adults

SNRI or bupropion or mirtazapine can also be first-line

Secondary treatment after 2-4 weeks of SSRI with only partial response (use a different antidepressant or 2 different classes like SSRI and bupropion)

134
Q

When people abuse drugs or are addicted to gambling, what is happening in their brains?

A

DA released from VTA into nucleus accumbens (in ventral striatum)

Then, leads to changes in homeostasis of DA regulation

135
Q

Which two systems converge on medium spiny neurons in the nucleus accumens?

A

Cortical (glutamatergic)

VTA (dopaminergic)

Coincident activity in these two pathways lead to “reward” sensation

When DA present, accumbens medium spiny neurons become more responsive to glutamate inputs from amygdala, frontal cortex, cingulate cortex and other limbic areas

136
Q

Endogenous neural transmitters and their receptors that are involved with VTA-accumbens circuitry (reward circuitry)

A

VTA using dopamine on D1 and D2 receptors

Cortex using glutamate on AMPA and NMDA receptors

Interneurons using GABA on GABA-A receptors

Raphe using 5HT on 5HT receptors

Interneurons using ACh on nicotinic receptors

Interneurons using enkephalins on mu and delta opioid receptors

Interneurons using anandamide on cannabinoid (CB1) receptors

137
Q

What other neurons affect DA neurons that lie in the VTA?

A

GABA neurons (stim by enkephalins)

Cortex neurons (which have glutamate inputs)

138
Q

What other neurons affect GABA neurons that lie in the nucleus accumbens?

A

Cortex neurons (with glutamate inputs)

139
Q

Hedonistic substances and their NTs and receptors

A

Cocaine, amphetamine, ritalin –> DA –> DA reuptake inhibitor

Alcohol –> GABA –> GABA-A agonist (increase DA in accumbens)

Alcohol –> glutamate –> NMDA antagonist (increase DA in accumbens)

Nicotine –> ACh –> nicotinic agonist (increase DA in accumbens)

Opiates –> enkephalins –> mu and delta opioid agonist (inhibit GABA in VTA to activate DA neurons of VTA)

Ketamine/PCP –> glutamate –> NMDA antagonist (disrupt signaling at NMDA receptors on medium spiny neurons)

Benzodiazepines/barbiturates –> GABA –> GABA-A agonist

Marijuana –> anandamide (2-AG) –> cannabinoid (CB1) agonist (trigger DA release in accumbens and have direct effects on medium spiny neurons)

Hallucinogens (LSD, etc) –> 5HT –> 5HT2A agonist

140
Q

Nicotinic ACh receptor

A

Ligand gated ion channel (Na+) with multiple potential combinations of different types of subunits

Alpha 4 beta 2: post-syn, DA release from nucleus accumbens, primary target of nicotine

141
Q

3 stages of progression to addiction

A

1) Intoxication stage: pleasure from substance of behavior, involves normal circuitry
2) Negative affect stage: gradual dysphoria, negative emotional state, stress–gradual changes and adaptations in circuitry, tolerance, involvement in stress systems and amygdala
3) Craving stage: preoccupation with addiction–substantial cellular and molecular adaptations in circuitry

142
Q

What happens in the reward circuit when you’re addicted?

A

“Opponens” compensatory adaptations in VA-accumbens circuitry

Decreased basal glutamate and basal DA

Increased stimulated (phasic) glutamate and increased stimulated DA

Substances are required to balance opponens processes and achieve “normalcy”

143
Q

Phases of addiction (dependence) behavior

A

1) Compulsion to seek substance
2) Loss of control in limiting intake
3) Emergence of a negative state (dysphoria, anxiety, irritability)

144
Q

Caffeine

A

Antagonist at adenosine receptors (A1, A2)

Adenosine receptors implicated in regulating sleep and arousal

Certain adenosine receptors coupled to, and inhibit, D2 receptors

Caffeine promotes activity at those D2 receptors!

145
Q

NIDA treatment principles for treatment of addiction

A

No single treatment appropriate for everyone

Remaining in treatment for adequate period of time important

Counseling and other behavioral therapies commonly used

Medications may be important especially when combined with counseling

Treatment must be assessed continually and modified

Treatment does not need to be voluntary

146
Q

Treatment approaches for addictive disorders

A

1) Medications (Bio)
2) Therapy (Psycho)
3) Lifestyle changes (Social)

147
Q

Medications for treatment of addiction

A

Manage detox, target urges/cravings, increase likelihood of abstinence, reduce harm from addictive behavior, lay the groundwork to do recovery

For alcohol: Antabuse (disulfiram), Vivitrol (IM naltrexone), Revia (naltrexone), Campral (acamprosate)

For opiate addiction: Suboxone (buprenorphine + valoxone), Subutex (buprenorphine), methadone, Revia (naltrexone), Vivitrol (IM naltrexone)

For nicotine addiction: nicotine replacement therapies (patch, lozenge, inhaler, gum), Chantix (varenicline), Zyban (bupropion)

148
Q

Disulfiram (Antabuse)

A

Mechanism: inhibits aldehyde dehydrogenase, increasing acetaldehyde (causes flushing, tachycardia, etc?)

Most likely to benefit highly motivated and directly observed patients

Side effects: nausea, metallic taste, dysphoria, fatigue, hepatitis, psychosis (DA)

Effects can last 72 hours after last dose

Second/third line treatment for alcoholism, won’t see many patients on this

149
Q

Naltrexone (Revia)

A

Opiate antagonist

Decreases positive reinforcing effects, increases negative aspects, decreases craving from first dose (prime), decrease craving from cues

Side effects: dysphoria, nausea, increased LFTs, expensive

Only shows modest effect: decreased time to relapse, # of drinks, cravings

“Curbs your enthusiasm for alcohol”

150
Q

IM Naltrexone (Vivitrol)

A

Opiate antagonist

Injection once per month (so internal med or family med doctors do this, not psychiatrists!)

No oral lead-in

Decreases drinking days and decreases heavy drinking days

151
Q

Acamprosate (Campral)

A

Mechanism: made from taurine; restores NMDA receptor tone in the glutamate system; GABA properties

Targets “negative reinforcement”

Higher abstinence, higher % of days abstinent and increased time to first drink

Side effects: diarrhea, rash

Start once detox is complete

152
Q

How does medical treatment for opiate addiction (using subtex or suboxone) work?

A

Office-based

Sublingual administration

Manages withdrawal

Used as maintenance therapy

Limited abuse potential

Great because meant people didn’t have to go to methadone clinics every day at 5am!

153
Q

Naltrexone for opiate addiction

A

Supposedly reduces pleasure from opiates

Doesn’t seem to reduce cravings in opiate dependents

Some evidence for “highly motivated” patients or directly observed

OD risk increased after discontinuation

154
Q

Nicotine patch

A

Slow onset, continuous delivery

24-16 hour dosing

Easy compliance

With or without taper

OTC

155
Q

Nicotine gum

A

Use every 1 hour

Bite and “park”

Slow, buccal absorption

Acidic foods decrease absorption

OTC

156
Q

Bupropion SR (Zyban/Lobutrin?)

A

Nicotinic receptor antagonist

Nonsedating/activating

Affects NE and DA

Side effects: headache, insomnia

Contraindicated in seizures/eating disorders

Start 10-14 days prior to quit date

300mg dose has least weight gain

Note: “side effect” of antidepressant trial was that people smoked less

157
Q

Varenicline (Chantix)

A

Partial nicotinic agonist of receptors JUST in nucleus accumbens limbic system (mimics and blocks receptors)

Attenuates withdrawal

Decreases craving

40 continuous abstinence at 12 weeks

Starter Pak then Continuing Pak

Side effects: nausea, H/A, insomnia, psych

158
Q

Are there medications for cocaine, methamphetamine, MJ, gambling or sexual addictions?

A

None that are FDA approved

For marijuana: Rimonabant (cannabinoid antagonist, but increased suicidal ideation); Marinol + Lofexidine (synthetic THC plus adrenergic modulator)

Considered for cocaine: modafinil, disulfiram, propanolol (WD), GVG (vigabatrin), topiramate, DHEA, TA-CD vaccine, buprenorphine, N-acetylcystine, d-amphetamine

Considered for meth: bupropion, mirtazapine, naltrexone, d-amphetamine, methylphenidate

159
Q

Psychosocial treatments

A

Residential treatment programs (30 day)

Intensive outpatient programs

Family treatment

Individual counseling

12-step support (not treatment because not a physician!)

160
Q

Evidence-based treatments

A

Motivational interviewing

Relapse prevention therapy

Cognitive-behavioral therapy

Contingency manageent

12-step facilitated groups

161
Q

Typical treatment plan for addiction

A

Bio: medication for SUD and psychiatric disorder, address medical consequences

Psycho: begin individual therapy; educate and motivate

Social: attend 12-step; make lifestyle changes

Supervise and monitor: urine drug screen, recovery check-ups

162
Q

Therapeutic indications for CNS depressants

A

Produce sedation

Reduce anxiety

Promote sleep

Induce anesthesia

Treat seizure disorders

163
Q

GABA receptors

A

GABA-A: ligand-gated Cl- channel; activation of GABA-A causes Cl- influx then hyperpolarization of postsyn membrane then neuronal inhibition

GABA-B: G-protein coupled receptor increases K+ conductance and decreases Ca2+ conductance (increases firing of GABA neurons?)

164
Q

Barbiturates mechanism

A

Barbiturates bind to specific site on GABA-A receptor to increase GABA-mediated neuronal inhibition

Absorption in small intestine

Distribution: all highly lipid soluble and the more lipid soluble it is, the faster it gets into the CNS

Metabolism: slow (18-96hr half life); inducers so increase metabolism of other drugs that are metabolized by hepatic enzymes; induces aminolevulinic acid (ALA) synthetase (motor disturbances and peripheral neuropathic disturbances)

165
Q

Examples of barbiturates

A

Thiopental, thiamylal: ultrashort-acting (consequence of its initial distribution to brain followed by subsequent redistribution to other tissues)

Secobarbital, pentobarbital: short-intermediate

Phenobarbital: long-acting

166
Q

Pharmacologic effects of barbiturates

A

Cause CNS dose-dependent depression (from slight sedation to coma and death); low TI

Dependence: psychological and physical dependence, and serious withdrawal symdrome (restlessness, anxiety, insomnia, weakness, orthostatic hypotension, convulsions, death)

167
Q

Clinical uses of barbiturates

A

Anxiety

Insomnia

Anticonvulsant (phenobarbital)

Anesthesia: thiopental, thiamylal used for induction

Adverse reactions: death from OD due to respiratory depression, CV collapse, pulmonary edema, pneumonia

Drug interactions: additive effects and cross-tolerance with other CNS depressants; induction of hepatic microsomal enzymes (accelerates metabolism and decreases conc of other drugs)

168
Q

Ethanol absorption, distribution, etc

A

Absorption: from GI tract, and food in stomach will delay absorption

Distribution: distributed throughout body and can cross placenta

Metabolism: two enzyme systems; primarily by liver so metabolism decreased in liver disease

169
Q

Metabolism of ethanol

A

This is the PRIMARY pathway of alcohol metabolism

Ethanol turned to acetaldehyde by alcohol dehydrogenase (ADH)

Acetaldehyde turned to acetic acid by aldehyde dehydrogenase (ALDH)

In each step, NAD+ turned to NADH

ADH has multiple isoforms, one of which has HIGH activity and is found in asians

ALDH has 2 forms, and Aisans have type II which has LOW activity (thus Asians build up acetaldehyde and get red!)

170
Q

Secondary pathway for metabolism of ethanol

A

Microsomal ethanol oxidizing system (MEOS) metabolizes some alcohol under high alcohol conditions and is due to CYP2E1

Ethanol turned to acetaldehyde by MEOS in this pathway, and then like normal acetaldehyde turned to acetic acid by ALDH

After chronic ethanol consumption, activity of MEOS increases, associated with rise of CYP2E1

171
Q

Zero order kinetics

A

When substrate concentration is much higher than Km

V = Vmax

Vmax is independent of substrate concentration

172
Q

Buprenorphine

A

Partial opioid agonist

In Suboxone an Subutex

173
Q

Is alcohol metabolism first order or zero order kinetics?

A

At doses we drink, it is zero order (pharmacologic concentration range greater than 200 mg/L)

Note: ethanol metabolism is ~10g/hr (1 drink per hour) and any dose frequency that exceeds this causes alcohol accumulation and effects of alcohol

174
Q

Pharmacologic effects of ethanol

A

CNS: depression; GABA-mediated neuronal inhibition (but apparent stimulatory effects if decrease inhibitory control mechanism)

CV: vasodilation, depress myocardial contractility

GI effects: stimulate gastric secretions, inhibit intestinal brush border enzymes involved in absorption of nutrients

Endocrine: decrease testosterone, inhibit ADH (diuresis), sexual dysfunction

175
Q

Chonic adverse effects of alcohol

A

Nervous system: peripheral neuropathy (paresthesias, tingling), cerebellar cortical degeneration, motor dysfunction, mammillary body atrophy

Sleep disturbances

Amnesia for recent events (alcoholic blackouts)

Wernicke-Korsakoff syndrome: ivolve thiamine (vitamin B1) deficiency; confusion, oculomotor dysfunction, ataxia, polyneuropathy (Wernicke part); learning and memory problems (Korsakoff part)

176
Q

Alcohol effects of CYP2E1

A

Acute: alcohol sits on CYP2E1 so decreases rate of metabolism of other drugs (enzyme competition)

Chronic: increases rate of drug metabolism because alcohol induces CYP2E1 (enzyme induction)

177
Q

NADH/NAD+ ratio in alcoholism

A

Increased NADH/NAD+ in alcoholics

Reduces gluconeogenesis, causes hypoglycemia and ketoacidosis

Fatty acid synthesis requires NADH so get fatty liver

178
Q

Liver and pancreatic effects of alcohol

A

Can get cirrhosis which causes liver damage that slows metabolism of other drugs

Pancreatitis

179
Q

Acetominophen metabolism in the liver

A

Major pathway: phase II metabolism to produce inactive metabolites (nontoxic glucoronide, nontoxic sulfate)

When phase II pathway saturated, or when CYP450 induction, use CYP450 system (CYP2E1) which creates toxic intermediate, which can still be metabolized by GSH (yay!)

However, alcoholics are depleted in GSH so cannot metabolize toxic intermediate and instead get buildup of toxic intermediate which reacts with liver proteins and causes hepatotoxicity and acute renal failure

180
Q

Alcohol withdrawal

A

Begins right after you stop drinking

Anxiety, insomnia, tremor, palpitations, nausea, anorexia

Withdrawal seizures

Alcoholic hallucinations

Delirium tremens (tachycardia, hypertension, low-grade fever, tremor, diaphoresis, delirium, agitation)

Note: detoxwithbenzodiazepines because work on GABA channel also

181
Q

Treatment of alcohol withdrawal/detoxification

A

Adjunctive to behavioral modification

Disulfiram: aldehyde dehydrogenase inhibitor; build-up of acetaldehyde causes headache, nausea, vomiting –> acts as negative reinforces

Naltrexone: opioid receptor antagonist –> associated with reinforcement and craving

Acamprosate: NMDA receptor antagonist; GABA agonist; increases abstinence; may restore balance between excitation and neuronal inhibition altered by chronic alcohol

182
Q

Methanol

A

Metabolized to formaldehyde and formic acid by the same enzyme systems that metabolize ethanol

Poisoning due to metabolites (formaldehyde cross-links protein)

Causes severe acidosis, optic nerve damage and blindness

Treatment: sodium bicarb for acidosis; use ethanol as competitive substrate inhibitor; fomepizole is alcohol dehydrogenase inhibitor to prevent methanol metabolism to formaldehyde

183
Q

Ethylene glycol

A

Colorless, sweet tasting solvent used in antifreeze solutions

Metabolism by alcohol dehydrogenase too, then generates oxalates which are very insoluble, especially w/Ca2+ (calcium oxalate salts) so can cause renal stones and renal failure

184
Q
A

Block 8: Psych (5 decks)

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