Module 14 Flashcards
1
Q
Alzheimer’s Disease - prevalent gender
A
- Women (75%)
2
Q
Alzheimer’s Disease - symptoms (general)
A
memory loss
problems conducting routine tasks
problems with language, judgment, behaviour, intelligence)
3
Q
Alzheimer’s Disease - early symptoms
A
- confusion
- memory loss
- problems conducting routine tasks
4
Q
Alzheimer’s Disease - severe symptoms
A
= difficulty performing daily living activities (eating, bathing, speaking, controlling bowel and bladder function)
5
Q
Pathophysiology of Alzheimer’s Disease
A
- Degeneration of cholinergic neurons in hippocampus (early) then in cerebral cortex (late)
- advanced Alzheimer’s = 10% of cholinergic nerve function
6
Q
Alzheimer’s Disease - diagnosis
A
- obtained after death (when brain sample is analyzed)
- look for
- neurofibrillary tangles
- neuritic plaques
7
Q
Neurofibrillary tangles
A
- form inside neurons when microtubule arangement is disrupted
- cause = abnormal production of a protein called Tau
- can cause alzheimers
8
Q
Tau
A
- a protein responsible for forming cross-bridges between microtubules keeping their structure
- abnormal formation –> alzheimers
9
Q
Neuritic Plaques
A
- found outside of neurons –> composed of a core of protein fragments called beta amyloid
10
Q
Beta amyloid
A
- make up core of neuritic plaques
- has been shown to kill hipocampal cells + cause Alzheimer-like symptoms (when injected into monkeys)
11
Q
Etiology of Alzheimer’s Disease
A
- usually unknown
- 20% = genetic
- head injury = also a factor
12
Q
Alzheimer’s Disease - genetic predisposition (2)
A
- two copies of apoplipoprotein E4 (ApoE4) –> propotes formation of neuritic plaques by binding to beta amyloid
- Mutations in amyloid precursor gene (involved in production of beta amyloid)
13
Q
Alzheimer’s Disease - drug treatment
A
1) Cholinesterase inhibitors (inhibit breakdown of acetylcholine)
2) NMDA receptor antagonists (block NMDA mediated increases in intracellular calcium)
only minimal improvement in symptoms
14
Q
Cholinesterase inhibitors - target disease
A
- treat alzheimers disease
15
Q
Cholinesterase inhibitors - mechanism of action
A
- inhibit metabolism of acetylcholine by enzyme acetylcholinesterase
- allows more acetylcholine to remain in the synaptic cleft to exert its actions
- only able to enhance cholinergic neurotransmission in the remaining healthy neurons
16
Q
Cholinesterase inhibitors - effectiveness
A
- display minimal benefit on some measures of memorry
- only effective in 25% of patients
17
Q
Cholinesterase inhibitors - adverse effects (3)
A
- nausea and vomiting
- diarrhea
- insomnia
18
Q
NMDA receptor antagonists - target disorder
A
alzheimers
19
Q
NMDA receptor - function
A
- NDMA receptor = calcium channel blocked by magnesium at rest
- when glutamate binds to the NDMA receptor, magnesium dissociates allowing calcium to enter post-synaptic neuron (when glutamate leaves, magnesium returns)
- normal calcium influx is important in process of learning of memory
20
Q
NMDA receptor and Alzheimers
A
- Alzheimers = excess glutamate release,
- NMDA receptor remains open –>
- excess calcium enters the cell
21
Q
detriments of excess calcium influx - NMDA receptors (2)
A
1) detrimental to learning and memory (overpowers normal calcium signal)
2) causes degradation of neurons (too much calcium is toxic)
22
Q
NMDA receptor antagonists - mechanism of action
A
- NMDA receptor antagonists block calcium influx into the post-synaptic neuron
23
Q
NMDA receptor antagonists - adverse effects
A
- well tolerated
- side effects observed in clinical trials had same incidence as patients taking placebo
24
Q
Schizophrenia
A
- disorder that makes it hard to differentiate between real and unreal experiences, to think logically, to have normal emotional responses, and to behave normally in social situations
- affects 1`% of worlds population
25
Schizophrenia - age of onset
adolescence or early adulthood (16-30)
26
Symptoms of Schizophrenia (classifications)
- Positive symptoms (exaggerate or distort normal neuro function)
- Negative symptoms (where there is a loss of normal neurological function)
27
Symptoms of Schizophrenia - positive symptoms (7)
```
symptoms that exaggerate or distort normal neurological function
EX
- delusions
- Hallucinations
- agitation
- paranoia
- combativeness
- disorganized speech
- disorganized thinking
```
28
Symptoms of Schizophrenia - negative symptoms (8)
```
symptoms are those where there is a loss of normal neurological function
EX
- Social withdrawal
- poverty of speech
- poor self care
- poor insight
- poor judgment
- emotional withdrawal
- blunted affect
- lack of motivation
```
29
Etiology of Schizophrenia
largely unknown, a few factors that increase risk
- Family history
- Drug abuse
- Low birth weight
- Low IQ
30
Etiology of Schizophrenia - family history
- 10% of schizophrenics have a parent with the disease
| - both parents with schizophrenia --> 25% chance their children will have it
31
Etiology of Schizophrenia - drug abuse
- methamphetaine (crystal meth), phencyclidine (PCP, angel dust) and lysergic acid diethylamid (LSD)
32
Etiology of Schizophrenia - low birth weight
babies born at less than 5.5 pounds have increased risk of developing schizophrenia
33
Etiology of Schizophrenia - low IQ
lower IQ = greater risk of developing schizophrenia
34
Brain regions affected by Schizophrenia (6)
- Basal ganglia
- Frontal lobe
- Limbic system
- Auditory system
- occipital lobe
- hippocampus
35
Brain regions affected by Schizophrenia - basal ganglia
- normal = movement and emotions
| - abnormal = abnormal activity --> paranoia and hallucinations
36
Brain regions affected by Schizophrenia - frontal lobe
- normal = problem solving and insight
| - Abnormal - associated with difficulty planning actions and organizing thoughts
37
Brain regions affected by Schizophrenia - Limbic System
- normal = emotions
| - Schizophrenia = contributes to agitation
38
Brain regions affected by Schizophrenia - Auditory system
- overactivity --> hallucinations
39
Brain regions affected by Schizophrenia - occipital lobe
- normal = processes visual info
| - Abnormal = involved with interpreting images, reading emotion on other;s faces and recognizing motion
40
Brain regions affected by Schizophrenia - hippocampus
- normal = mediates learning and memory
| - abnormal = learning and memory hindered
41
Pathophysiology of Schizophrenia (3)
- increased dopaminergic nerve transmission (opposite side of Parkinson's spectrum) = increased domaminergic neurotransmision and increased binding of dopamine to D2 receptors
- 5-HT (seretonin) imbalance... decreased number of 5HT 2A receptors, increase in 5-HT 1A receptors --> impact symptoms
- Glutamate - patients with schizophrenia have a decreased number of NMDA receptors in some regions of their brain --> symptoms of schizophrenia
- PCP (angel dust) = antagonist of NMDA receptor
42
Schizophrenia - how is it diagnosed?
- no definitive test
| - diagnosis made by psychiatrist after interviewing patient and family
43
Schizophrenia - diagnostic criteria (5)
1) changes in function from before illness
2) developmental bacground
3) family history'
4) response to meds
5) brain scans (enlarged ventricles, decreased frontal lobe brain activity)
44
Drug treatment of Schizophrenia
- blocking dopamine and/or serotonin neurotransmission in the brain
45
Drug treatment of schizophrenia - classification (2)
- conventional antipsychotics
| - atypical antipsychotics
46
Conventional antipsychotics - mechanism of action
- work primarily by blocking dopamine 2 (D2) receptors primarily in the mesolimbic area of the brain
- lesser degree - also block receptors for acetylcholine, histamine, norepinephrine
47
Conventional antipsychotics - potency
directly proportional to thier ability to inhibit D2 receptors
48
Conventional antipsychotics - efficacy
- mostly efficient at treating positive symptoms of schizophrenia than the negative symptoms
- initial effects seen in 1-2 days, substantial improvement takes 2-4 weeks
49
Conventional antipsychotics - adverse effects (6)
1) extrapyramidal symptoms
2) sudden high fever
3) anticholinergic effects
4) orthostatic hypotension
5) sedation
6) skin reactions
50
Extrapyramidal symptoms (what, pathophysiology, 4 types)
- movement disorders that resemble the symptoms of parkinson's disorder
- due to blockade of D2 receptors
- 4 types = acute dystonia, parkinsonism, akathesia, tardive dyskinesia
51
Acute Dystonia
- an extrapyramidal symptoms
| - involuntary spasm of the muscles in the face tongue, neck or back. typically occurs early in therapy
52
Parkinsonism (what,, symptoms (4), treatment)
- a type of extrapyramidal symptoms (EPS)
- bradykinesia, mask-like face, rigitity, stooped posture
- treated with anticholinergic drug (avoid L-DOPA)
53
Akathesia
- an extrapyramidal symptom
- pacing, squirming, desire to continually be in motion
- typically occurs early in treatment
54
Tardive Dyskinesia
- an extrapyramidal symtom
- occurs in 20% of patients on longterm therapy
- irreversible (early detection is essential)
- involuntary twisting and writhing of the face and tonuge, lip smacking
- switch medications immediately
55
Atypical antipsychotics - mechanism of action
- block both dopamine D2 receptors and 5-HT-2A receptors
| - can block D2 receptors, but affinity is very low.... Therapeutic action is due to blockade of 5-HT receptors
56
Which is better - conventional antipsychotics or atypical antipsychotics
atypical psychotics...
1) same efficacy versus positive symptoms of schizophrenia
2) much greater efficacy versus negative symptoms of schizophrenia
3) much lower risk of developing extrapyramidal symptoms
57
Atypical antipsychotics - adverse effects (5)
- sedation
- orthostatic hypotension
- weight gain (sometimes severe)
- risk of developing type II diabetes
- anticholinergic effects
58
Epilepsy
- neurological disorder that produces brief disturbances in the normal electrical activity in the brain
- Characterized by sudden, brief seizures (vary from person to person)
59
Seizure
a sudden alteration of behaviour caused by CNS dysfunction
| - transient and sudden
60
Epileptic seizure
- a seizure caused by primary CNS dysfunction
| - due to excess depolarization and hypersynchronization of neurons
61
Non-epileptic seizure
- a seizure-like episode that is not the result of abnormal electrical activity in the brain
62
Epilepsy (definition)
- a tendency for recurrent spontaneous epileptic seizures
63
Status epilepticus
- a single unremitting epileptic seizure of duration longer than 30 minute OR
- frequent seizure without recovery of awareness in between
EMERGENCY
64
Categories of seizures (2)
- epileptic
| - non-epileptic
65
Categories of Epileptic seizures (3)
- focal/partial seizure
- generalized seizure
- secondary generalized seizure
66
categories of focal/partial seizure (2)
- complex
| - simple
67
Categories of generalized seizure (5)
- abscence seizure
- tonic/clonic seizure
- myoclonic seizure
- tonic seizure
- atonic seizure
68
Focal/partial seizure
- arise in one area of the brain
- 2 types
- simple partial seizure
- complex partial seizure
69
Simple partial seizure
- no loss of consciousness
- symptoms depend on where the seizure activity is arising from
- EX - L motor strip oglidendroglioma --> clonic movement of right arm, then right face, then right leg. No impairment of consciousness, lasts 45 seconds`
70
Complex partial seizure
- loss of consciousness (patient may appear to be awake but are not aware of surroundings)
- symptoms depend on where seizure is taking place
- EX - right temporal lobe epilepsy --> whistling, bicicling movements in left leg, rising epigastric sensation with nausea, normal ictal speech, no memory of events post ictally (after seizure), lasting 30-45 seconds
71
Generalized seizures
- bilateral diffuse onset, seeming to arise form all areas of the brain at once
- 5 types
- abscence seizure
- tonic/clonic seizures
- myoclonic seizures
- tonic seizures
- atonic seizures
72
Absence seizures - symtoms
- loss of consciousness, behavioural arrest, staring
| - rarely associated with automatisms (unusual purposless movements)
73
Absence seizure - frequency and timing
- usually brief
| - may occur multiple times in a day
74
Absence seizures - population
more common in childhood
75
Tonic/Clonic seizures - symptoms
- abrupt loss of consiousness
- a tonic period (muscles become rigid) lasting 1 minute)
- a clonic period (involuntary muscle contractions) lasting 2-3 minutes
- patient may become incontinent and have tongue biting
- post-ictal --> drowsy, confusion, frequently complaining of headaches
76
Tonic - definition
muscles become rigid
77
Clonic - definition
involuntary muscle contractions
78
Myoclonic seizures
- sudden, brief muscle contractions that can involve any muscle group
- usually no loss of consciousness
- sometimes associated with a later developemnt of generalized tonic/clonic seizures
79
Tonic seizures
- sudden msucle stiffening (rigidity)
| - often involve impaired consiousness
80
Atonic seizures
- sudden loss of muscle tone
- brief (15 seconds)
- aka drop seizures (patients drop to the grund)
- risk for falling injuries
81
Secondary generalized seizure
- a seizure that begins in one area of the brain (like a focal seizure) then spread throughout the brain
82
an "aura"
- preliminary focal phase of a secondary seizure
83
Localizing focal seizures
evaluating the patients symptoms vs what we know about vaious regions of the brain
84
Focal seizures - frontal lobe (3)
- simple repetitive motor movements involving a localized muscle group --> seizure activity in the contralateral primary motor cortex
- tonic posturing affecting entire side of the body --> seizure in contralateral Supplemental Motor Area (SMA) + other higher level motor structures
- Very complex behaiour automatisms involving bilateral movment (swimming, bicycle riding movements) = seizure in higher areas of frontal cortex, may involve vocalizations (laughter, crying)
85
Where is the seizure? - simple repetitive motor movements involving a localized muscle group
- frontal lobe (primary motor cortex)
86
Where is the seizure? = tonic posturing affecting entire side of the body
Frontal lobe (Contralateral Supplemental motor area/ other higher level motor structures)
87
Where is the seizure - Very complex behavioural automatisms involving bilateral moment (swimming, bicycle riding movements), may involve vocalizations (laughter, crying)
Frontal lobe (higher areas of the frontal cortex)
88
Focal Seizures - Temporal Lobe
- typically associated with auditory hallucinations (buzzing, voices talking), olfactory (smell), gustatory (taste) hallucinations
- more ocmplex sensory phenomena (visual distortions, paresthesias (numbness) and autonomic disturbances
89
Where is the seizure? - auditory, olfactory, gustatory hallucinations
temporal lobe
90
Where is the seizure? - paresthesias, autonomic disturbanes
temporal lobe
91
Focal Seizures - Parietal Lobe (3)
- localized paresthesias = numbness, "pins and needles" = somatosensory cortex
- complex/widespread paresthesias = somatosensory association cortex
- complex multi-sensory hallucinations and illusions = higher order sensory association (difficult to distinguish from the more common temporal lobe seizure)
92
Where is the seizure? - numbness, "pins and needles"
parietal lobe (somatosensory cortex)
93
Where is the seizure? - complex/widespread parenthesis
Parietal lobe (somatosensory association cortex)
94
Where is the seizure - complex multi-sensory hallucinations and illusions
Parietal lobe (higher order sensory association areas)/temporal lobe
95
Focal seizures - occipital lobe
- Visual hallucinations (flashing.repeated pattern in the environment, rather than organized objects such as people or faces)
- Temporary blindness/decreased vision, sensation of eye movement, nystagmus (involuntary eye movement)
- can be mistaken for migraine headaches
96
Where is the seizure? - Visual hallucinations (flashing.repeated pattern in the environment
occipital lobe
97
Where is the seizure? - Temporary blindness/decreased vision, sensation of eye movement, nystagmus (involuntary eye movement)
Occipital lobe
98
Epileptogenesis (3)
1) symptomatic epilepsy
2) idiopathic epilepsy
3) cryptogenic epilepsy
99
Symptomatic epilepsy
epilepsy arising from an identified physical cause (ex brain tumour, stroke, infection, other injury)
100
Idiopathic epilepsy
epilepsy that does not have identifiable cause; often there is a family history of seizures, genetics likely play a role
101
Cryptogenic epilepsy
epilepsy that is likely to have an underlying cause that has not been identified
102
The seizure threshold (2)
- thought of as the balance between excitable and inhibitory forces in the brain
- everybody has a seizure threshold --> affects how susceptible a patient is to having a seizure
103
The Seizure threshold - contributing factors (~7)
- Determining factors - anything that causes changes in electrical activity/affects firing of action potentials
- EX: stroke, head injury, drug/alcohol withdrawal, infection, tumour, severe fever, visual stimuli (flashing lights)
104
Anti-epileptic drugs - categories
1) blocking sodium channels
2) blocking voltage-gated calcium channels
3) glutamate antagonists
4) potentiating the actions of GABA
105
Anti-epileptic drugs - blocking sodium channels - mechanism of action
- recall - sodium influx contributes to generation of action potential
- NORMAL - after sodium enters the cell, sodium channel enters inactive
state where sodium entry to cell is prevented...return to normal active state
very quickly
- Sodium channel blocker AEDs prolong inactivation state of sodium channel = don't allow to fire at high frequency
106
Phenytoin - function
- most widely used anti-epileptic drug
107
Phenytoin - mechanism of action
blocks sodium channels
108
Phenytoin - indications for use
useful in the treatment of all types of epileptic seizures except absence seizures
109
Phenytoin - metabolism and effect
- metabolism of the liver is limited --> non-linear kinetics
- small increase in dose = large increase in plasma concentration
- narrow therapeutic range --> drug monitoring
110
Phenytoin - adverse effects
- sedation
- gingival hyperplasia
- skin rash
- teratogenic
111
Anti-epileptic drugs - blocking voltage dependent calcium channels
- NORMAL - influx of calcium through VG calcium channels promotes neurotransmitter release from pre-synaptic nerve terminal
- inhibition of calcium suppresses neurotransmitter release
112
Glutamate antagonists - mechanism of action (2)
- Glutamate = an excitatory CNS neurotransmitter
- block glutamate in two places --> dereased CNS excitation
- NMDA receptor blockage
- AMPA receptors blockage
113
GABA receptor (what, mechanism of action, result)
- inhibitory CNS neurotransmitter
- binding of GABA to its receptor causes negatively charged chloride ions to rush into the cell
- result = makes it more difficult for threshold to be reached + difficult to have an action potential
114
Potentiating the actions of GABA - anti-epileptic drug
- potentiate actions of GABA --> increase inhibitory stimuli --> suppress seizure activity
115
Potentiating the actions of GABA - anti-epileptic drug - 4 ways to mediate
1) enhancing binding of GABA to its receptor
2) stimulating GABA release
3) Inhibiting GABA re-uptake
4) inhibiting GABA metabolism
116
Anti-epileptic dug - classififications (2)
- Traditional = phenytoin, valpoic acid
| - Newer = lamotrigine
117
Classifications of anti-epileptic drugs - differences
1) effectiveness is similar
| 2) newer AEDs have decreased side effects + decreased propensity to induce hepatic drug metabolizing enzymes
118
Depression
- when symptoms of depression are prolonged and interfere with everyday life
- 1/3 people will experience depression at some time in their life
- current estimate = 3% currently have depression
119
Diagnosis of depression (9)
5 of the following symptoms
- depressed mood most of the day, nearly everyday
- loss of interest or pleasure in all or almost all activities
- significant weight loss (no diet) or weight gain
- insomnia or hypersomnia
- psychomotor agitation or retardation
- fatigue and energy loss
- feelings of worthlessness or excessive guilt
- decreased ability to think, concentrate, excessive indecisiveness
- recurrent thoughts of death or suicidal ideations`
120
Types of depression (2)
2 main types =
- exogenous
- endogenous
121
Exogenous depression
- triggered by external stimuli
122
endogenous depression
may or may not be related to external events
123
Exogenous depression - classifications (2)
- pathological grief
| - adjustment disorder
124
Pathological grief (what, treatment)
- prolonged grieving coupled with excessive guilt.
| - psychotherapy is usually more effective than drugs
125
Adjustment disorder (what)
prolonged depression following failure or rejection (i.e. losing your job, failing out of school
126
Adjustment disorder (common symptoms)
hypersomnia (excess sleep), hyperphagia (overeating)
127
Adjustment disorder (treatment)
- psychotherapy is often more effective than drug therapy
128
Endogenous depression - categories (7)
- major depression
- severe depression
- atypical depression
- dysthymia
- seasonal affective disorder (SAD)
- postpartum depression
- bipolar disorder
129
Major depression (symptoms) 3
- loss of interest and lack of response to positive stimuli
- symptoms usually worse in the morning
- insomnia and weight loss are typical
130
Severe depression (symptoms) (~6)
- similar symptoms to major depression (- loss of interest and lack of response to positive stimuli; symptoms usually worse in the morning; insomnia and weight loss are typical)
- severe suicidal ideation
- psychoses
131
Atypical depression
- similar to symptoms of major depression (loss of interest and lack of response to positive stimuli; symptoms usually worse in the morning)
- BUT atypical symptoms of hypersomnia and hyperphagia
- often patients with atypical depression are obese
132
Dysthymia (symptoms, treatment)
- patient's mood is regularly low but symptoms are not as severe as major depression
- symptoms are more noticeable to family members/close friends than they are to the patient
- usually responds better to psychotherapy than drugs
133
Seasonal affective disorder
- mild or moderate symptoms of depression related to the lack of sunlight
- usually affects people only in the winter months
134
Postpartum depression
- moderate to severe depression in women after they give birth
- usually occurs within 3 months of delivery but may occur up to a year after birth
135
Bipolar disorder (depression)
- alternating periods of elevated or irritable mood and periods of depression
136
The monoamine hypothesis
- depression - exact cause and pathophysiology is unknown
| - THEORY = altered monoamine release, receptor sensitivity, post-synaptic function lead to symptoms of depression
137
Antidepressants - function
- act to increase synaptic levels of one or more monoamine neurotransmitters
138
Antidepressants - efficacy
- difficult to assess since it often take months for effects to occur
- results from placebo-controlled clinical trials = 40% effects observed may be attributed to the placebo effect
139
Antidepressants - mechanisms of action
- act to increase synaptic levels of one or more monoamine neurotransmitters
1) inhibiting monoamine reuptake
2) inhibiting monoamine metabolism
140
Classes of antidepressant drugs (4)
1) tricyclic antidepressants
2) selective serotonin reuptake inhibitors (SSRIs)
3) selective serotonin/norepinephrine reuptake inhibitors
4) monoamine oxidase inhibitors (MAOIs)
141
Tricyclic antidepressants (mechanism of action)
- inhibit reuptake of both serotonin and norepinephrine
142
Tricyclic antidepressants - target population
effective in treatment of major depression
143
Tricyclic antidepressants - adverse effects (7)
- anticholinergic effects
- sedation
- orthostatic hypotension
- decreased seizure threshold
- cardiac toxicity (rare but potentially serious)
- weight gain
- sexual dysfunction
144
Selective serotonin reuptake inhibitors (SSRIs) - mechanism of action
- block serotonin reuptake
145
Selective serotonin reuptake inhibitors (SSRIs) - when used
- most commonly used
- similar efficacy to Tryciclic antidepressants, but incidence of side effects are lower
- most commonly used in major depression
146
Selective serotonin reuptake inhibitors (SSRIs) - adverse effects (4)
- weight gain
- sexual dysfunction
- insomnia
- Serotonin syndrome (agitation, confusion, anxiety, hallucinations, incoordination occurring within 3 days of initial therapy disappearing when drug is stopped)
147
Selective Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs) - mechanism of action
- block re-uptake of both norepinephrine and serotonin (similar mechanism to TCAs)
148
Selective Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs) - onset of action
- FASTER (huge advantage)
149
Selective Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs) vs Tryciclic antidepressants
- TCAs have three-ringed structure
| - SNRIs do not and have faster onset
150
Selective Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs) - adverse effects
- nausea
- diastolic hypertension
- sexual dysfunction
151
Monoamine Oxidase
- an enzyme that inactivate monoamine neurotransmitters
152
Monoamine Oxidase - 2 types, what they (M)
- MAO-A: metabolizes serotonin and norepinephrine
| - MAO-B: metabolizes dopamine
153
Monoamine Oxidase Inhibitors (MAOIs) - mechanism of action
- inactivates MAO, which are enzymes that inactivate monoamine neurotransmitters
- non-selective = inhibit both MAO-A and MAO-B
- RESULT = inhibits metabolism of monoamines in the pre-synaptic neuron
154
Monoamine Oxidase Inhibitors (MAOIs) - population to treat
- atypical depression and dysthymia
155
Monoamine Oxidase Inhibitors (MAOIs) - adverse effects (3)
- CNS excitation - anxiety, insomnia, agitation
- orthostatic hypotension
- hypertensive crisis if taken with tyramine containing foods
156
Bipolar disorder
- severe illness - recurrent fluctuations between episodes of mania and depression
157
Bipolar disorder - onset
- symptoms begin in adolescence or early adulhood
158
Bipolar disorder - mania (6)
- irritation
- inflated self-esteem (delusions of grandeur)
- little need for sleep
- poor control of temper
- reckless behaviour (binge eating, drinking, drug use)
- easily distracted
159
Patterns of mood episodes - bipolar
- cycles vary (some experience repeat mania with occasional depression, others repeated depression with occasional mania)
- Average = 2 episodes every 5 years
160
Drug treatment of bipolar disorder (3)
1) mood stabilizers
2) antipsychotics
3) antidepressants
161
Mood stabilizers - function
1) relieve symptoms during manic or depressive episodes
2) prevent recurrence of manic or depressive episodes
3) do not worsen symptoms of mania or depression and do not alter rate of cycling
162
Mood stabilizers - bipolar disorder (2)
- lithium
| - valproic acid (anti-epileptic drug)
163
Lithium - mechanism of action
- unclear
| - alters uptake and release of glutamate and blocking binding of serotonin
164
dangers of lithium (2)
1) narrow therapeutic range
2) plasma concentrations may be altered by sodium
- agents that increase sodium loss from body (diuretics) increase lithium concentrations and may produce toxicity
165
Symptoms of lithium toxicity
- GI upset
- tremor
- sedation
- hypotension
166
Antipsychotics - use for bipolar
- acute = control mania symptoms, longterm to stabilize mood
- benefit patients even if they don't have psychotic symptoms
- preference for atypical antipsychotics (lower risk of extrapyramidal symptoms)
167
Antidepressants and bipolar disorder
- used in bipolar disease to treat depressive episodes
- always combined with a mood stabilizer (used alone, they may preciptate mania)
- no good evidence for which one works best
168
Anxiety
- normal physiological response to stress
- normal before an exam or before a first date
- turns into a disorder when symptoms create functional impairment in a patients daily living
- linked with depression
169
Types of anxiety (7)
- generalized anxiety disorder
- panic disorder
- agoraphobia
- obsessive-compulsive disorder
- social anxiety disorder
- post-traumatic stress disorder
- simple phobia
170
Generalized anxiety disorder
- patient is overwhelmed with uncontrollable worrying
| - unrealistic or excessive worry about several activities lasting 6 months or longer
171
Panic disorder
- patients have a sense of impending doom that is unrelated to stressors
- panic attacks (sudden onset of heart palpiltations, chest pain, shortness of breath, dizziness [mimic heart attack])
172
Agoraphobia
- anxiety where the patient feels judged or a situational anxiety where escaping would be difficult or embarrassing
173
Obsessive-compulsive disorder
- persistent obsession and compulsions that interfere with daily life (hand-washing, checking locks, etc)
174
Social anxiety disorder
- anxiety in social situations
| - patients may not be able to talk (or stop talking), eat in front of others or use public washrooms
175
Post-traumatic stress disorder
- anxiety occurring after experiencing a traumatic event
| - symptoms = re-experiencing the event and severe insomnia
176
Simple phobia
symtoms related to a specific fear (spiders, elevators)
177
Drug treatment for anxiety (3)
- benzodiazepines (BDZs)
- buspirone
- antidepressants
178
Benzodiazepines (target disorder)
- first line of therapy for anxiety
179
Benzodiazepines - mechanism of action
- work by potentiating the actions of GABA at GABA receptor
- note: NOT GABA agonists....bind to a different site on the GABA receptor and cause increased binding of GABA to the receptor
- GABA binds to the receptor, opening a channel, so chloride ions move into the cell -->CNS depression
- note: BZD amplify endogenous GABA there is a limit to the CNS depression they may produce making them much safer than Barbituates
180
Therapeutic uses for benzodiazepines (5)
1) anxiety
2) seizures
3) insomnia
4) alcohol withdrawal
5) muscle spasm
181
Dosing a benzodiazepine
- different dose = different effects
| - EX - higher dose of BD is used to treat insomnia than anxiety
182
Benzodiazepines - target disorders
- treat generalized anxiety and social anxiety disorders
183
Benzodiazepines - adverse effects (6)
- CNS depression - drowsiness, difficulty concentrating,
- Anterogade amnesia - impaired memory of events that occur following dosing
- respiratory depression (rare, but more common if combined with alcohol)
- teratogenic
- tolerance
- withdrawal (should be tapered slowly
184
Buspirone - mechanism of action
- not a CNS depressant
| - mechanism UNCLEAR --> modulation of serotonergic and/or dopaminergic neurotransmission
185
Buspirone - target population
- useful in patients who use alcohol
| - generalized anxiety disorder (ineffective for other types such as panic disorder or OCD)
186
Buspirone - advantages (4)
- not a CNS depressant = can be used in patients who use alcohol
- no signs of tolerance or physical dependence
- few adverse effects
- non-sedating
187
Buspirone - disadvantage
- anxiolytic effects develop slowly = ineffective at treating symptoms that require immediate relief
188
Buspirone - adverse effects (3)
- well tolerated, non-sedating
- dizziness
- lightheadedness
- excitement
189
Antidepressants - anxiety
useful in certain types of anxiety
190
Antidepressants + generalized anxiety disorder (which types x3)
- SSRIs and SNRIs effective
| - buspirone slow to enact their effect
191
Antidepressants + panic disorder/agoraphobia (which ones (3) work, which one is prefered)
- SSRIs, TCAs, MAOI are useful but effects take 6-12 weeks to appear
- SSRIs preferred (better tolerated)
192
Antidepressants + OCD
- SSRIs = first line of therapy
| - used in conjunction with behavioural therapy
193
Antidepressants + social anxiety disorder
- SSRI = first line of therapy, BDZ can also be used
BDZ = immediate relief, SSRIs = LT
194
Neuropharmacology
study of how drugs affect the function of the central nervous system
195
What is the brain composed of
millions of neurons
196
neurons
- excitable cells that transmit information by electrical and chemical signalling
197
How is information transmitted in neurons
```
Dendrite of neuron recieves signal from other neuron
Action potential (electric signal) propagates along axon of the neuron
AP reaches pre-symaptic nerve terminal, causes release of neurotransmitters (chemical signalling)
```
198
Action potentials
A depolarization, positive charged Na+ ions enter cell through VG Na+ channels = membrane changes from -70mV to +35 mV
Na+ channels then close and potassium channels open allowing Na+ to leave cell during repolarization
overshoot (-70 mV)
199
Synapse - transmitting the AP
send neurotransmitters
- once AP reaches pre-synaptic neuron, Ca2+ influx
- cause vesicles with Neurotransmitters to release into the synaptic cleft
200
Neurotransmitters in the CNS that are monoamines (4)
- norepinephrine
- epinephrine
- dopamine
- seretonin
201
Norepinephrine - associated disorders
depression and anxiety
202
Epinephrine - associated disorders
anxiety
203
Dopamine - associated disorders
parkinson's + schizophrenia
204
Norepinephrine - classification
monoamine
205
Epinephrine - classification
monoamine
206
dopamine - classification
monoamine
207
Serotonin - classification
monoamine
208
Neurotransmitters in the CNS - classifications (3)
- Monoamines
- Amino acids
- other
209
Neurotransmitters - amino acids - classification
- Excitatory
| - Inhibitory
210
Neurotransmitters - excitatory amino acids - classification (2)v
- Glutamate
| - asparate
211
Neurotransmitters - inhibitory amino acids - classification
- GABA
| - Glycine
212
Glutamate - associated disorder
- alzheimer's
213
Glutamate - classification
amino acid neurotransmitter
214
Aspartate - associated disorder
Alzheimer's
215
Aspartate - classification
Amino Acid neurotransmitter
216
GABA - associated disorder
Anxiety
217
GABA - classification
amino acid neurotransmitter
218
Glycine - associated disorder
- anxiety
219
Glycine - classification
amino acid neurotransmitter
220
Acetylcholine - associated disease
Alzheimer's and Parkinson's
221
Basic Mechanisms of CNS Drug action (5)
1) Replacement (what is low in disease)
2) agonists/antagonist (drug directly binds to receptors)
3) inhibiting neurotransmitter breakdown (inhibit metabolism)
4) blocking reuptake
5) nerve stimulation
222
Parkinson's Disease - pathology
Progressive loss of dopaminergic neurons in substantia nigra of the brain (70-80%)
progresses in 5-10 years to state where patients cant care for themselves
223
Symptoms of Parkinson's Disease (6)
1) Tremor (extremities = hands, arms, legs, jaw, face)
2) Rigidity
3) bradykinesia (slowness of movement/slow to initiate movement
4) masklike face (cant show expression + difficult blinking, swallow)
5) postural instability
6) dementia (later in disease)
224
Parkinson's disease - pathophysiology (3)
- imbalance between acetylcholine and dopamine in the brain
- dopamine release is decreased (not enough present to inhibit GABA
release)
- relative excess of acetylcholine compared to dopamine, resulting in
increased GABA release
- excess GABA causes movement disorders
225
Etiology of parkinson's disorder
largely unknown
226
Parkinson's Disorder - Risk factors (5)
- Drugs (by product of street drug synthesis produces MPTP. MPTP causes irreversible death of dopaminergic neurons
- Genetics - mutation in 4 genes (alpha sunuclein, parkin, UCHL1, DJ-1)
- Environmental Toxins - pesticides --> PD
- Brain trauma (from injury)
- oxidative stress (reactive oxygen species...diabetes induced oxidative damage --> PD)
227
Drug treatment of parkinson's disease
reverse degeneration of dopaminergic neurons (ideal)
but. ....
1) Increase dopamine
2) decrease acetylcholine
228
Drugs that increase Dopamine Neurotransmission
1) dopamine replacement
2) dopamine agonist
3) dopamine releaser
4) catecholamine-O-Methyltransferase inhibitor
5) Monoamine oxidase-B (MAO-B) inhibitor
229
Dopamine replacement - main drug name
Levodopa (L-Dopa)
230
L-Dopa - use
- treats Parkinson's disease
- most effective drug
- use decreases with time
231
Levodopa (L-DOpa) - transportation to site
- crosses blood brain barrier by an active transport protein
232
Levodopa (L-DOpa) - mechanism of action
- inactive on its own, converted to dopamine in dopaminergic nerve terminals
- reaction mediated by decarboxylase enzymes in the brain
- cofactor pyridoxine (vit B6) speeds up this reaction
233
Levodopa (L-DOpa) - why not just give dopamine
- Dopamine does not cross blood brain barrier
| - dopamine has a very short half-life in blood
234
Levodopa (L-DOpa) - adverse effects (5)
- nausea and vomiting (dopamine trigger chemoreceptor in medula of brain)
- dyskinesias (abnormal involuntary movements)
- cardiac dysrhythmias (dopamine in periphery can activate cardiac beta 1 receptors)
- orthostatic hypotension
- psychosis (20% of patients)
235
Levodopa (L-DOpa) - peripheral metabolism (solution, impact)
only 1% of L-Dopa reaches brain, rest is metabolized in peripheral tissue
- solution = give with carbidopa
236
Carbidopa (what, function, effect)
carbidopa (decarboxylase inhibitor)
inhibits peripheral metabolism of L-DOPA
= 10% of L-DOPA reaches brain, less cardiac dysrhythmia, decreased N+V
237
Levodopa (L-DOpa) - types of loss of effect (2)
1) wearing off - gradual loss
| 2) on-off - abrupt loss of effect
238
Wearing off (L-DOPA)
a gradual loss of effect
usually occurs at the end of the dosing interval and indicates that drug levels might be low
239
Wearing off (L-DOPA) - solutions
- shorten dosing interval
- give drug that inhibits L-DOPA metabolism (ie a COMT inhibitor)
- add a dopamine agonist to the therapy
240
On-off (L-DOPA) - what/when it occurs
- abrupt loss of effect
| - can occur even when drug levels are high
241
On-off (L-DOPA) - solutions
- divide med into 3-6 doses per dya
- use a controlled release formulation
- moving protein-containing meals to the evening
242
Dopamine Agonist - mechanism of action
- produce effects by directly activating dopamine receptors on the post-synaptic cell membrane
243
Dopamine Agonist - indications for use-
- not as effective as L-DOPA
| - first line of treatment for patients with midler symptoms
244
Dopamine Agonist - adverse effects (3)
- hallucinations
- daytime drowsiness
- orthostatic hypotension
245
Dopamine Releaser - mechanism of action (3)
- stimulate release of dopamine from dopaminergic neurons
- blocks dopamine reuptake into pre-synaptic nerve terminals
- blocks NMDA receptors (decrease dyskinesia side effect of L-Dopa)
246
Dopamine Releaser - indications for use
- not as effective as L-dopa, used in combo with L-DOpa or alone in mild PD
247
Dopamine Releaser - adverse effects (5)
- dizziness,
- nausea,
- vomiting,
- lethargy,
- anticholinergic side effects
248
Catecholamine-O-Methyltransferase Inhibitor (COMT) - mechanism of action
- Inhibits COMT (enzyme that adds methyl group to dopamine and L-DOPA, rendering them inactive)
- results in a greater fraction of Dopamine and L-Dopa that can be converted to dopamine
249
Catecholamine-O-Methyltransferase Inhibitor (COMT) - indications for use
- moderately effective in treating symptoms ---> combine with L-DOPA
250
Catecholamine-O-Methyltransferase Inhibitor (COMT) - adverse effects (4)
- nausea
- orthostatic hypotension
- vivid dreams
- hallucinations
251
Monoamine oxidase-B (MAO-B) inhibitor - mechanism of action
- inhibits MAO-B facilitated oxidation (metabolism) of dopamine and L-Dopa
- Result = more L-DOPA conversion to dopamine, more dopamine in nerve terminals
252
Monoamine oxidase-B (MAO-B) inhibitor - indications for use
- moderately effective on their own at treating symptoms --> combine with L-DOPA
253
Monoamine oxidase-B (MAO-B) inhibitor - adverse effects (3)
- insomnia
- orthostatic hypotension
- dizziness
- does not inhibit MAO-A in liver = dont cause hypertensive crisis in patients eating tyramine-containing fod
254
Excess acetylcholine symptoms (3)
- diaphoresis (excess sweat)
- salivation
- urinary incontinence
255
Anticholinergic drugs - mechanism of action
- block binding of acetylcholine to its receptor
| - also called cholinergic antagonists
256
Anticholinergic drugs - indications for use
- may increase effectiveness of L-Dopa
- may decrease incidence of diaphoresis, salivation, incontinence
- NOT for elderly (more likely to experience severe CNS side effects)
257
Anticholinergic drugs - adverse effects (6)
- dry mouth
- blurred vision
- urinary retention
- constipation
- tachycardia
Elderly CNS effects = confusion, hallucination, deliriumm
