Physio & Pharma Flashcards
Dopamine
Dopaminergic Pathways
- both excitatory and inhibitory
- movement, personality, mood, sleep
- Parkinson’s disease (low dopamine in substantia nigra), Tourette’s (excessive dopamine in caudate nucleus), Schizophrenia (dopamine hypothesis, high dopamine levels)
Dopaminergic Pathways: - mesolimbic pathway: reward circuit, ventral tegmental area to ventral striatum (nucleus accumbens)
- mesocortical pathway: motivation, emotion, EF; ventral tegmental area area to PFC
- tuberoinfundibular pathway: hormone regulation (prolactic); hypothalamus to pituitary gland
- Nigrostriatal pathway: purposeful movement; substantia nigra to dorsal striatum (caudate nucleus, putamen)
Acetylcholine (ACh)
- both excitatory and inhibitory
- movement, arousal, attention, memory
- Alzheimer’s memory loss assoc with low ACh in entorhinal cortex & hippocampus
- causes muscles to contract, myasthenia gravis destroys ACh receptors at neuromuscular junctions
Glutamate
- excitatory
- movement, emotions, learning, memory
- Gluatamate induced excitotoxicity –> cell death in diseases like stroke, seizures, Huntington’s, Alzheimer’s
Norepinephrine
- excitatory
- arousal, attention, learning, memory, stress, mood
- Chatecholamine hypothesis: depression caused by low norepinephrine, mania by excess norepinephrine
Serotonin (5-HT)
- inhibitory
- arousal, sleep, sexual activity, mood, apetite, pain
- Low serotonin assoc with depression, suicide, bulimia, OCD, migraine
- Anorexia (high serotonin–> anxiety –> lowered by restricting)
- ASD- high blood level serotonin
Gamma Aminobutyric Acid (GABA)
- pimary inhibitory
- mood, memory, arousal, sleep, motor control
- Low GABA-> insomnia, seizures, anxiety; benzos increase GABA
- Low GABA and ACh in basal ganglia assoc with Huntington’s motor x’s
Reticular formation
- neuron network from medulla to midbrain
- regulates muscle tone, controls eye movement, controls pain
- reticular activating system (RAS): consciousness/arousal, sleep/wake cycle, alerts cortex to incoming sensory stimuli. RAS lesions cause coma, electrical stimulation of RAS can wake you up.
Substantia Nigra
- reward-seeking, drug addition, motor control (with basal ganglia connections, nigrostriatal dopamine pathway)
- dopamine degeneration in substantia nigra –> Parkinson’s motor x’s (tremor, slow movement, rigidity)
Hypothalamus & substructures
Hypothalamus
* maintains homeostasis, regulates survival fx’s (body temp, BP, HR, sex, respiration, hunger/thirst, stress response)
* sends hormones to pituitary glad (GnRH for secondary sex dev, oxytocin and vasopressin for social bonding, sex, social recog, etc.)
* HPA axis- mediates stress response
* emotions- bilateral damage can cause aggression/rage, electrical stimulation can cause other emotions (pleasure, fear)
Substructures
* mammillary bodies- memory
* suprachiasmatic nucleus- biological clock; circadian rhythms and sleep/wake cycle
oxytocin has positive emo recog effects for ASD & Schizo. but negative for healthy controls (oversensitive to facial exp)
Thalamus
Korsakoff syndrome
Thalamus- relay station to cortex of all senses except smell, language/speech, declarative memory, coordinates sensory & motor functioning.
Korsakoff syndrome- thiamine deficiency (usually due to alcoholism) damages neurons in thalamus & mammillary bodies, x’s include anterograde & retrograde amnesia, confabulation.
Basal ganglia
- striatum (caudate nucleus, putamen, nucleus accumbens) receives input from cortex, and globus pallidus sends info to thalamus
- motor initiation & control, procedural memory, attention & decision-making, emotions
- Linked to mood, Huntington’s & Parkinson’s, schizophrenia, ADHD, OCD, Tourette’s.
Limbic system
Amygdala
Kluver-Bucy Syndrome
- emotions (especially fear), emotion recognition in facial exprations, evaluating emotional significance of events, emotions linked to memories (flashbulb memories)
- PTSD- hyperactivity of amygdala and hypoactivity of vmPFC (which regulates the amygdala)
- Kluver Bucy Syndrome- bilateral amygdala lesions cause hyperorality, hyperphagia, hypersexuality, reduced fear, visual agnosia.
Limbic system
Cingulate Cortex
- includes cingulate gyrus & sulcus
- emotional reaction to pain, motivation, memory
- Abnormalities linked to depression and bipolar disorder
Limbic system
Hippocampus
- more memory than emotion; transfers declarative memory from STM into LTM, spatial memory
- Damage to hippocampus –> episodic memory & spatial deficits in Alzheimer’s
- Chronic cortisol increases in hippocampus impairs retrieval
- PTSD- severity of trauma and x’s linked to (smaller) size of hippocampus
Broca’s aphasia
slow & labored paraphrase speech (verbs & nouns only), anomia and impaired repetition, intact comprehension (written and spoken)
Role of the dorsolateral prefrontal cortex (dlPFC)?
EF.
Damage causes concrete thinking, impaired judgment/insight, impairments in planning & WM, apathy/disinterest, perseverative responses.
Don’t care (apathy), don’t know (judgment), don’t know how (planning)
Role of the orbitofrontal cortex (OFC)?
Response inhibition, emotion regulation, social behaviors.
Damage causes impulsivity, inappropriate social behaviors, lack of concern for others, aggression, antisocial behaviors, affective lability, distractibility.
AAA, crystal orb (unpredictable)
What is the role of the ventromedial prefrontal cortex (vmPFC)?
Social cognition, decision making, memory, emotion regulation.
Damage causes impaired social cognition (empathy, emotion recognition), lack of insight, impaired decision-making & moral judgment, emotional blunting.
Social cognition, can’t make a decision, blunted emotion.
Supplementary motor cortex vs premotor cortex
Supplementary motor cortex plans & coordinates self-initiated movements.
Premotor cortex plans & coordinates movements in response to external stimuli.
Wernicke’s aphasia
impaired comprehension (spoken & written), impaired repetition, anomia. Speech is fluent but meaningless and with errors/susbtitutions.
Anosognosia vs asomatognosia
Anosognosia- unaware of own illness
Asomatognosia- lack of interest/recognition of own body part
Hemispatial neglect
Caused by damage to right parietal lobe, neglect left side body & stimuli.
Ideomotor apraxia vs ideational apraxia
Ideomotor apraxia- cannot carry out motor action on verbal command (“pretend to brush your hair”)
Ideational apraxia- inability to plan/execute a task with sequential steps
Both usually due to left (dominant) parietal damage
Gerstmann’s Syndrome
Acalculia, agraphia, right-left confusion, finger agnosia. Due to left (dominant) parietal damage.
What is cortical blindness?
What is blindsight?
What is affective blindsight?
Cortical blindness: eyes and optic nerves intact but occipital lobe is damaged, resulting in visual deficits.
Blindsight: Pts with cortical blindness do not consciously see stimulus but respond appropriately to it (ex, reach for object they claim they cannot see).
Affective blindsight: do not consciously see emotional sitmuli but respond appropriately (ex, cannot see picture of angry/happy face but correctly guess what was shown to them)
What causes prosopagnosia?
Bilateral damage to occipitotemporal junction
Types of colorblindness
Red/green colorblindness: genetic (X-linked) or injury/disease (MS, diabetes). Most common.
Blue/yellow colorblindness: rare; autosomal dominant.
Theories of color vision
Trichromatic theory- we have cones for red, blue, and green in retina.
Opponent-process theory- three types of opponent process cells (blue/yellow, red/green, white/black). Accounts for afterimages and types of colorblindness.
Depth perception cues
Binocular cues- retinal disparity, convergence
Monocular cues: relative size, texture changes, linear perspective, motion parallax
Psychophysics
Weber’s law
Fechner’s law
Steven’s power law
Psychophysics: studies the relationship between magnitude of stimuli & psychological sensation
Weber’s law: just noticeable difference (JND) is a cosntant proportion (e.g., 2% for weight)
Fechner’s law: JND grows to a greater degree wit each increment in intensity (aka logarithmic relationship)
Steven’s power law: exponential relationship between magnitude and sensation, exponent varies by stimulus. Most accurate.
Signal detection theory
- Perception = sensation + decision-making
- sensitivity= ability to distinguish between stimulus and noise
- Decision criterion (aka decision bias) = tendency to say stimulus is there in ambiguous situations
- d’ = estimate of sensitivity in STD experiment
- ROC curve = how often false alarms/hits occur for different levels of sensitivity and how decision criterion affects this
Brain areas involved in memory
- Hippocampus- consolidation of ST declarative memory into LT, spatial WM (HM case)
- Basal ganglia, cerebellum, supplementary motor area- procedural memory, implicit memory
- Amygdala- attaching emotions to memories
- PFC- WM, prospective memroy
- Thalamus & mammillary bodies- damage causes anterograde amnesia
Long-term potentiation (LTP)
STM involves changes in neurotransmitters, LTM involves changes in neuron structure and new synapses. Synaptic changes associated with LTM depend on RNA synthesis.
Stages of sleep
- low frequency high-amplitude alpha waves (drowsiness), then low frequency-low amplitude theta waves
- Theta waves continue, interrupted by sleep spindles and K complexes
- Begins after 20 minutes of sleep; low frequency/high amplitude delta waves slow-wave deep sleep
- Delta waves continue (with higher amplitude) slow-wave deep sleep
- REM sleep; begins after 80-90 minutes of sleep, similar to stage 1, paradoxical sleep(active brain paralyzed body), most dreams occur here and are vivid, bizarre & detailed.
After 10 minutes of REM sleep, cycle repeats with longer REM and shorter deep sleep as the night goes on.
What are the first-generation antipsychotics?
How do they work?
What are the side effects?
Pharma: Antipsychotics & Antidepressants
- haloperidol (Haldol)
- chlorpromazine (Thorazine)
- thioridazine (Mellaril)
- fluphenazine (Prolixin)
They work by blocking D2 dopamine receptors, more effective for treating positive symptoms.
Side effects:
- anticholinergic effects (dry mouth, blurred vision, tachychardia, urinary retention, constipation)
- extrapyramidal effects (parkinsonism, dystonia, akathysia, tardive dyskenisia)
- neuroleptic malignant syndrome (muscle rigidity, high fever, autonomic dysfunction, altered MS)
What are the second-generation antipsychotics?
How do they work?
What are the side effects?
Pharma: Antipsychotics & Antidepressants
- Clozapine (Clozaril)
- Risperidone (Risperidal)
- Olanzapine (Zyprexa)
- Quetiapine (Seroquel)
- Aripriprazole (Abilify)
Work by blocking D3 and D4 dopamine receptors as well as serotonin receptors, help with positive and negative x’s.
Side effects:
- anticholinergic effects
- neuroleptic malignant syndrome
- metabolic syndrome (weight gain, high BP, insulin resistance, hyperglycemia, risk of diatebetes)
- agranulocytocis (low WBC count), moslty with clozapine
What are the SSRIs?
What do they treat?
What are the side effects?
Pharma: Antipsychotics & Antidepressants
- fluoxetine (Prozac)
- citalopram (Celexa)
- escitalopram (Lexapro)
- fluvoxamine (Luvox)
- paroxetine (Paxil)
- sertraline (Zoloft)
They treat: depression, persistent depressive disorder, premenstrual dysphoric disorder, OCD, panic, GAD, PTSD, bulimia, premature ejaculation.
Side effects:
- GI symptoms
- insomnia, anxiety
- sexual dysfunction
- discontinuation syndrome (labile mood, impaired concentration, flu-like x’s)
- serotonin syndrome (agitation, autonomic instability, tremor, seizures, delirium, potentially fatal) if taken with MAOI or other serotonergic drug
- tachyphylaxis (antidepressant poop-out; apathy, fatigue, low cognitivie fx)
What are the SNRIs?
What do they treat?
What are the side effects?
Pharma: Antipsychotics & Antidepressants
- Venlafaxine (Effexor)
- duloxetine (Cymbalta)
- desvenlafaxine (Pristiq)
Treat depression (esp. severe depression), social anxiety, neuropathic pain/pain disorders.
Side effects:
- similar to SSRIs (discontinuation syndrome, serotonin syndrome)
- elevated BP
What are the NDRIs?
What do they treat?
What are the side effects?
Pharma: Antipsychotics & Antidepressants
- bupropion (Wellbutrin, Zyban)
- Used to treat depression and smoking cessation
- Side effects: insomnia, agitation, lower apetite/weight loss, seizures.
- Do not cause: sexual dysfunction, anticholinergic effects, cardiotoxicity
What are the TCAs?
What do they treat?
What are the side effects?
Pharma: Antipsychotics & Antidepressants
Tertiary
- amitriptyline (Elavil)
- imipramine (Tofranil)
- clomipramine (Anafranil)
- doxepin (Sinequan)
Secondary
- nortriptyline (Pamelor)
- desipramine (Norpramin)
Prescribed for: depression, panic, OCD, neuropathic pain.
Side effects:
- cardiovascular
- anticholinergic
- sedation
- weight gain
- sexual dysfunction
- cardiotoxic in overdose
*secondary amines have fewer side effects
What are the MAOIs?
How do they work?
What do they treat?
What are the side effects?
Pharma: Antipsychotics & Antidepressants
- phenelzine (Nardil)
- isocarboxazid (Marplan)
- tranylcypromine (Parnate)
Work by increasing norepinephrine, serotonin, dopamine.
Prescribed for: treatment resistant depression, atypical depression (reverse vegetative x’s).
Side effects:
- anticholinergic
- orthostatic hypotension
- sedation
- sexual dysfunction
- hypertensive crisis if combined with certain drugs or foods
What are the benzodiazepines?
What do they treat & how?
What are the side effects?
Pharma: Other
- diazepam (Valium)
- alprazolam (Xanax)
- lorazepam (Ativan)
They treat anxiety, insomnia, seizures & alcohol withdrawal by increasing GABA.
Side effects:
- drowsiness/sedation
- weakness/unsteadiness
- memory & concentration impairments
- anticholinergic effects
- sexual dysfunction
- disorientation/confusion (in older adults)
- paradoxical effects (increased anxiety)
- lethal if combined with alcohol
- can drop BP too much if combined with high BP meds
- can cause tolerance, dependence, withdrawal
What are the barbiturates?
What do they treat & how?
What are the side effects?
Pharma: Other
- thiopental (Pentothal)
- amobarbital (Amytal)
- secobarbital (Seconal)
They treat anxiety, insomnia and seizures by increasing GABA. Also used as general anesthetics.
Side effects:
- drowsiness
- dizinness
- confusion
- ataxia
- cognitive impairment
- paradoxical excitement
- lethal if combined with alcohol
- can lead to tolerance, dependence, withdrawal
- sudden withdrawal -> seizures, delirium, death
What are azapirones?
What do they treat?
What are the side effects?
Pharma: Other
-buspirone (BuSpar)
-used to treat GAD and other anxiety disorders
Side effects:
- do not cause tolerance, dependence, withdrawal
- headache, nausea, sweating, dry mouth, diziness
What are the naroctic-analgesics (opioids)?
What are the side effects/overdose symptoms/withdrawal symptoms?
Pharma: Other
- natural opioids: opium, heroin, morphine, codeine
- synthetic opioids: oxycodone, methadone, hydrocodone, fentanyl
- side effects: dry mouth, nausea/constipation, diziness/drowsiness, pupil constriction, postural hypotension, respiratory depression
- Overdose symptoms: convulsions, coma, death
- Withdrawal symtpoms: flu-like at first, then insomnia, abdominal cramps, diarrhea, increased HR/BP. Methadone used for heroin detox
What do beta-blockers do and what do they treat?
What is a beta blocker we should know about and what are the side effects?
Pharma: Other
-propanolol
- beta blockers reduce sympathetic nervous sytem activity
- they are used generally to treat hypertension, arhythmia, tremor & migraines
- propanolol (Inderal) used to treat anxiety, particularly somatic x’s.
- Side effects include hypotension, decreased sex drive, insomnia, GI. Sudden discontinuation can cause rebound effects (hypertension, headache, arhythmia)
What are the types of mood stabilizers used for bipolar? When is each used? What are the side effects of each?
Pharma: Other
Lithium (Eskalith, Lithobid)
* used for classic bipolar (mania without rapid cycling)
* side effects include GI x’s, increased thirst, weight gain, impaired concentration, hand tremor.
* Toxicity leads to seizures, coma, death
AEDs: valproic acid (Depakote) and carbamazepine (Tegretol)
* used to treat bipolar with mixed episodes
* side effects include ataxia, tremor, impaired concentration, lethargy, visual disturbances.
* can lead to liver failure, agranulocytosis, and aplastic anemia
What drugs are used to treat Alzheimer’s disease?
Pharma: Other
Cholinesterase inhibitors delay breakdown of acetycholine
* acrine (Cognex), donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne)
NMDA receptor antagonist regulates glutamate acitivity
* memantine (Namenda)
What are the stimulants for ADHD and how do they work?
What are the side effects?
Pharma: Other
- methylphenidate (Ritalin, Concerta)
- pemolin (Cylert)
- amphetamine-dextroamphetamine (Adderall)
They work by increasing dopamine & norepinephrine activity in the PFC. Do not increase academic performance on youth without ADHD and may even have negative effects on WM.
Side effects
- decreased apetite, weight loss
- insomnia
- nervousness
- abdominal pain
- stunted growth
What are non-stimulant drugs for ADHD and how do they work?
Pharma: Other
- atomoxetine (strattera) is a norepinephrine reuptake inhibitor, more effective for ADHD with comorbidities
- guanfacine (Intuniv) and clonidine (Kapvay) are alpha-2-adrenergic agonists and usually prescribed for ADHD + tic disorder
- some antidepressants are third line treatmetns and increase norepinephrine and dopamine (bupropion, desipramine)
How does tetrahydrocannabinol (THC) work and what is it prescribed for?
Pharma: Other
- increases dopamine in ventral striatum (specifically nucleus accumbens)
- prescribed for anorexia, AIDS and chemo patients
What drugs are used to treat alcohol use disorder and how do they work?
Pharma: Other
- disulfiram causes unpleasant symptoms when taken with alcohol
- naltrexone and topiramate reduce pleasurable effects and cravings
- acamprosate reduces cravings
Drugs used for tobacco use disorder
Pharma: Other
- nicotine replacement therapy prevents withdrawal symptoms
- bupropion (Wellbutrin) reduces cravings and withdrawal
- varenicline reduces cravings and maybe pleasurable effects
What is a drug half life?
What is drug tolerance and cross tolerance?
What is therapeutic index and how is it calculated in humans?
Pharma: Other
- half-life: time it takes for peak blood level of the drug to reach 50%. If drug has a short half-life, interval between doses is short. some drugs may have a longer half-life for older adults so start low and go slow.
- tolerance: repeated use leads to reduction in drug’s effects
- cross-tolerance: tolerance to one drug produces tolerance to other drugs in the same class
- Therapeutic index: measure of drug’s safety. measured by TD50/ED50. If therapeutic index is is 1 or less, it has a narrow therapeutic window (not very safe). If TI is >1 it has a wide therapeutic window (safe).
James-Lange Theory of Emotions
Emotions & Stress
“we are afraid because we run”
1) physiological arousal & behavior, 2) emotional experience.
facial feedback hypothesis- facial expression leads to physiological changes associated with an emotion. ex) smiling makes us feel happy.
JUMP LATER THE EMOTION
Cannon-Bard Theory of Emotions
Thalamus causes simultaneous physiological arousal (via SNS) and emotional reactions (via cortex) to stimuli.
All emotions have similar phsyiological arousal.
CO-OCCUR BOTH THALAMUS
Schacter & Singer Two-Factor Theory
AKA cognitive arousal theory
1) physiological arousal –> 2) cognitive attribution for arousal –> emotional experience
Physiological arousal similar for all emotions, only cognitive attributions change.
Epinephrine studies- participants experiencing unexplained arousal (epinephrine) determined their emotion by looking to confederate. Later ‘misattribution of arousal’.
Zillman’s excitation transfer theory
arousal by one event can be transferred to and intensify arousal for a later event.
Based on the assumptions that: physiological arousal decreases slowly, residual arousal can intensify future arousal, people are bad at knowing the cause of their arousal.
Lazarus’ Cognitive Appraisal Theory
1) Cognitive appraisal (of an event) –> 2) different physiological arousals and emotional reactions.
Primary appraisal- is it irrelevant, benign, or stressful?
Secondary appraisal- if stressful, how will I cope?
Reappraisal- changes primary/secondary appraisal.
Ledoux’s Two-System Theory of Emotion
Originally developed for fear; two separate systems mediate fear:
* subcortical system- aka survival system, generates automatic physiological and defensive behavioral responses to threatening stimuli
* cortical system- aka conscious emotional system, uses subcortical system, senses, and memories to generate conscious feeling of fear when it determines there is a threat.
Selye’s general adaptation syndrome
Body’s response to stress is the same and always involves three stages
1. alarm reaction stage- SNS gives energy for fight/flight
2. Resistance stage- if stressor continues, some functions return to baseline, cortisol remains high to maintain high energy
3. exhaustion stage- if stressor continues, physiological processes break down
not fully supported by research showing type of stress, genetic factors, and previous experiences affect body’s response to stress
Allostatic load model
Allostasis = maintaining stability during times of stress. Allostatic state can be maintained for a time.
An extended allostatic state (caused by chronic stress or repeated acute stress) leads to allostatic load, and then allostatic overload (which involves negative phsyical and mental effects).
Symptoms of stroke in:
middle cerebral artery
anterior cerebral artery
posterior cerebral artery
- middle cerebral artery: contralateral sensory loss, contralateral hemiparesis/hemiplegia, contralateral homonymous hemianopsia, dysarthria, aphasia (if dominant hemisphere) OR apraxia & hemineglect (if nondominant hemisphere)
- anterior cerebral artery: contralateral sensory loss & hemiparesis, apathy, confusion, mutism, impaired insight/judgment, urinary incontinence.
- posterior cerebral artery: contralateral sensory loss & hemiparesis, contralateral homonymous hemianopsia or other visual impairment, dysarthria, nausea and vomiting, and memory loss
Huntington’s Disease
- autosomal dominant, onset around 30-50 years, mood x’s precede cognitive & motor symtpoms
- Cognitive x’s: impaired STM, attention, judgment
- Motor x’s: chorea (involuntary, rapid & jerky), athetosis (nonrhythmic, slow & writhing), clumsinness, fidgeting, facial grimacing
- basal ganglia abnormalities, GABA & glutamate abnormalities
may meet criteria for neurocognitive disorder eventually
Parkinson’s disease
- genetic & environmental risk factors
- loss of dopamine cells in substantia nigra & basal ganglia (motor x’s), excessive glutamate in basal ganglia (disease progression), loss of norepinephrine in locus coreuleus (non-motor x’s)
- motor x’s: tremor, balance/coordination, rigidity, bradykenisia (slowed movement)
- depression in 50% of cases
- x’s temporarily managed with l-dopa (levodopa) and deep brain stimulation
Focal seizure types
- focal aware (aka simple partial seizure) vs focal impaired awareness (complex partial seizure)
- temporal lobe seizures: most common focal type, aura, autonomic x’s, automatisms, impaired speech/comprehension, can be triggered by stress.
- frontal lobe seizures: often during sleep and <30 secs, x’s include kicking/repetitive movements, posturing, laughter/screaming, impaired speech (intact comprehension)
- parietal lobe seizures: abnormal sensations (tingling, pain, numb), feelings of movement, body distortions
- occipital lobe seizures: rapid blinking/eye movements, visual abnormalities, visual hallucinations, visual impairments.
Hyperthyroidism vs hypothyroidism
Hyperthyroidism- hypersecretion of thyroid hormones, x’s include increased metabolism, high body temp, insomnia, emotional lability, short attention span
Hypothyroidism- hyposecretion of thyroid hormones, x’s mimic depression, slow metabolism, confusion, impaired concentration & memory
Diffuse tensor imaging (DTI)
Detects abnormalities in white matter. Used for seizures, neurocognitive disorder, etc.
Reward center of the brain
Nucleus accumbens (ventral striatum)
