Lecture 14b Flashcards
CNS drugs part II (93 cards)
1
Q
What is epilepsy?
A
neurological disorder (not disease) that produces brief disturbances in the normal electrical activity in the brain - characterized by sudden, brief seizures (recurrent and spontaneous)
2
Q
What is a seizure?
A
a sudden alteration of behaviour that is caused by CNS dysfunction
are sudden and transient
3
Q
What are epileptic seizures?
A
seizure caused by primary CNS dysfunction due to excess depolarization (firing of action potentials) and hyper synchronization of neurons
4
Q
What are non-epileptic seizures?
A
seizure-like episode that is not the result of abnormal electrical activity in the brain
5
Q
What is status epilepticus?
A
a single unremitting epileptic seizure of duration longer than 30 min or frequent seizures without recovery of awareness in between
- is an emergency
6
Q
What are the 3 main types of epileptic seizures?
A
- focal/partial seizure
- generalized seizure
- secondary generalized seizures
7
Q
What can focal/partial seizures be further broken down into?
A
- simple partial seizure
2. complex partial seizure
8
Q
What can generalized seizures be further broken down into?
A
- absence seizures
- tonic/clonic seizure
- myoclonic seizure
- tonic seizure
- atonic seizure
9
Q
What are focal/partial seizures?
A
- arise in one area of the brain
10
Q
What are simple partial seizures?
A
- involve no loss of consciousness
- symptoms depend on where the seizures activity is arising from
11
Q
What are complex partial seizures?
A
- involves loss of consciousness
- may appear to be awake but are not aware of surroundings
- symptoms depend on where seizure activity is taking place
12
Q
What are generalized seizures?
A
- bilateral, diffuse onset arising from all areas of the brain AT ONCE
13
Q
What are absence seizures?
A
- also: “petit-mal”
- loss of consciousness, behavioural arrest and staring
- usually brief, may occur in clusters or recur multiple times a day
- RARELY: automatisms (unusual purposeless movements)
- more common as childhood (often mistaken for staring off into space)
14
Q
what are tonic/clonic seizures?
A
- also: “grand-mal”
- abrupt loss of consciousness
- tonic period (muscles rigid)
- clonic period (involuntary muscle contraction)
- may be incontinent; tongue biting
- post-ictal phase: drowsiness, confusion, headache
15
Q
What are myoclonic seizures?
A
- sudden, brief muscle contractions (any muscle group)
- no loss of consciousness
- associated with a later development of generalized tonic-clonic seizures
16
Q
What are tonic seizures?
A
- sudden muscle stiffening (rigidity)
- impaired consciouness
17
Q
What are atonic seizures?
A
- sudden loss of muscle tone
- brief
- “drop seizures”
- potential falling injuries
18
Q
What are secondary generalized seizures?
A
- beings in one area of the brain (like focal) and then spreads throughout
- preliminary focal phase referred to as an “aura” (helps patients predict more serious symptoms are coming)
19
Q
How can the location of a focal seizure be determined?
A
- by evaluating the patients symptoms
20
Q
What would indicate a focal seizure in the frontal lobe?
A
- simple repetitive motor movements involving a localized muscle (seizure activity in contralateral primary motor cortex)
- tonic posturing affecting entire side of body (seizure activity in the contralateral supplemental motor area)
- complex behavioural automatisms involving bilateral movement (swimming, bike riding) = activity in higher areas of frontal cortex (can also include vocalizations, laughter or crying)
21
Q
what would indicate a focal seizure in the temporal lobe?
A
- emotions such as anger, fear, euphoria and psychic symptoms
- auditory hallucinations (buzzing, talking), olfactory and gustatory hallucinations
- visual distortions, paresthesias (numbness) and autonomic disturbances
22
Q
What would indicate a focal seizure in the parietal lobe?
A
- localized paresthesias = activity in contralateral somatosensory cortex
- complex and widespread paresthesias = activity in somatosensory association cortex
- complex multi-sensory hallucinations and illusions = activity in higher order sensory association areas (can be hard to distinguish from the more common temporal lobe activity)
23
Q
What would indicate a focal seizure in the occipital lobe?
A
- visual hallucinations (flashing, repeated pattern, not usually of organized objects)
- temporary blindness or decreased vision, sensation of eye movement
- reflex nystagmus (involuntary eye movement)
- can be mistaken for migraines
24
Q
What are the 3 main classifications for the etiology for epilepsy?
A
- symptomatic epilepsy
- idiopathic epilepsy
- cryptogenic epilepsy
25
What is symptomatic epilepsy?
epilepsy arising from an identified physical cause like brain tumor, stroke, infection, or other injury
26
What is idiopathic epilepsy?
- no identifiable cause (often family history)
27
What is cryptogenic epilepsy?
- likely to have an underlying cause that has not been identified yet
28
What is the seizure threshold?
- balance between excitable and inhibitory forces in the brain
- affects how susceptible a patient is to having a seizure
29
What are some factors that affect the seizure threshold?
- stroke
- head injury
- drug/alcohol withdrawal
- infection
- tumour
- severe fever
- visual stimuli (flashing lights)
30
What are the 4 mechanisms by which anti-epileptic drugs work?
1. blocking sodium channels
2. blocking voltage-dependent calcium channels
3. glutamate antagonists
4. potentiating the actions of Gaba
31
How does blocking sodium channels stop epilepsy?
- after sodium enters cells it becomes inactive during which further sodium entry to the cell is prevented
- normally it would return b quickly to active state allowing more sodium to enter
- these act to prolong the inactivation state of the sodium channel = neurons cant fire at a high frequency
32
What is the most common sodium channel blocker?
Phenytoin
- useful in all types except absence seizures
- metabolic capacity of liver to break it down = limited = non-linear kinetics (small increase in dose produce large increase in plasma conc)
- has narrow therapeutic range
33
What are the adverse effects of phenytoin?
- sedation
- gingival hyperplasia
- skin rash
- teratogenic
34
How does blocking voltage dependent calcium channels work?
- influx of calcium through voltage-dependent calcium channels promotes neurotransmitter release from the pre-synaptic nerve terminal
- inhibition of calcium channels suppresses neurotransmitter release
35
How do glutamate antagonists work?
- glutamate = excitatory CNS neurotransmitter
- blocking glutamate decreases CNS excitation
- glutamate can bind either the NMDA or AMPA receptors so antagonists usually block binding to these preventing CNS excitation
36
What is GABA and the GABA receptor?
- GABA: inhibitory CNS neurotransmitter
- binding of GABA to receptor = Cl- ions rush into cell = increased negativity inside cell and more difficulty having an action potential
37
What do drugs that potentiate the actions of GABA do?
- increase inhibitory stimuli in the CNS and suppress seizure activity
38
What are the 4 different ways that drugs that potentiate GABA mediate their effects?
1. enhancing binding of GABA to receptor
2. stimulating GABA release
3. Inhibiting GABA reuptake
4. Inhibiting GABA metabolism
39
What is the benefit of newer AED's (lamotrigine) vs traditional (phenytoin, valproic acid) ?
- effectiveness of the two is similar
| - newer = decreased side effects; decreased propensity to induce hepatic drug metabolizing enzymes
40
What is depression?
prolonged symptoms of grief and sadness that interfere with everyday life
41
For a diagnosis of depression, you need at least 5 out of the following symptoms to occur for at least two weeks:
- depressed mood most of the day, nearly everyday
- loss of interest or pleasure in all or almost all activities
- significant weight loss (without dieting) or weight gain
- insomnia or hypersomnia
- psychomotor agitation or retardation
- fatigue or energy loss
- feelings of worthlessness or excessive guilt
- decreased ability to think, concentrate, or excessive indecisiveness
- recurrent thoughts of death or suicidal ideations
42
What are the two major types of depression?
1. exogenous: triggered by external stimuli
| 2. endogenous: may or may not be related to external events
43
What are the two types of exogenous depression?
- pathological grief
| - adjustment disorder
44
What is pathological grief?
- prolonged grieving coupled with excessive guilt
| - psychotherapy usually more effective than drugs
45
What is adjustment disorder?
- prolonged depression following failure or rejection
- common symptoms include hypersomnia (excess sleep) and hyperphagia (over eating)
- psychotherapy often more effective
46
What are the 7 major types of endogenous depression?
- major depression
- severe depression
- atypical depression
- dysthymia
- seasonal affective disorder (SAD)
- postpartum depression
- bipolar disorder
47
What is major depression?
- common symptoms = loss of interest and lack of response to positive stimuli
- symptoms usually worse in the morning
- insomnia and weight loss also typical
48
What is severe depression?
- similar symptoms to major depression
| - addition of severe suicidal ideation and psychoses
49
What is atypical depression?
- similar to major depression
- experience hypersomnia and hyperphagia
- are often obese
50
What is dysthymia?
- mood is regularly low but symptoms not as severe as major depression
- symptoms usually more noticeable to family members/close friends
- psychotherapy > drugs
51
What is SAD?
- mild or moderate symptoms of depression related to lack of sunlight
- usually in winter months
52
What is postpartum depression?
- moderate to severe depression in women after they give birth
- occurs within 3 months of delivery up to 1 year
53
What is bipolar disorder?
- alternating periods of elevated or irritable mood and periods of depression (mania and depression)
54
What is the monoamine hypothesis?
- altered monamine release, receptor sensitivity, or post-synaptic function lead to symptoms of depression
55
What do antidepressant drugs do?
- act to increase the synaptic levels of one or more monamine neurotransmitters
- efficacy difficult to assess since it takes months for effects to occur
56
What are the two major mechanisms by which antidepressant drugs mediate their effects?
1. inhibiting monamine reuptake
| 2. inhibiting monamine metabolism
57
What are the 4 major classes of drugs used to treat depression?
1. tricyclic antidepressants
2. selective serotonin reuptake inhibitor (SSRIs)
3. selective serotonin/norepinephrine reuptake inhibitors (SNRIs)
4. Monamine oxidase inhibitors (MAOIs)
58
What are tricyclic antidepressants?
- name stems from chemical structure (has 3 rings)
- act by inhibiting the reuptake of both serotonin and norepinephrine to increase their effects
- effective for major depression
59
What are the adverse effects of tricyclic antidepressants?
- anticholinergic effects
- sedation
- orthostatic hypotension
- decreased seizure threshold
- cardiac toxicity - rare but potentially serious
- weight gain
- sexual dysfunction
60
What are selective serotonin reuptake inhibitors (SSRIs)
- similar to TCAs but only block serotonin uptake
- similar efficacy to TCAs but less side effects
- most commonly used in major depression
61
What are the adverse effects of SSRIs?
- weight gain
- sexual dysfunction
- serotonin syndrome (agitation, confusion, anxiety, hallucinations, incoordination; symptoms appear within 3 days of initial therapy)
62
What are selective serotonin/norepinephrine reuptake inhibitors (SNRIs)?
- block re-uptake of both norepinephrine and serotonin and are effective treatments of major depression
- have faster onset of action
- mechanism similar to TCAs but structure is different
63
What are the adverse effects of SNRIs?
- nausea
- diastolic hypertension
- sexual dysfunction
64
What are monoamine oxidase inhibitors (MAOIs)?
- MAO (MAO A: metabolizes serotonin and norepinephrine; MAO B: metabolizes dopamine) inactivates monoamine neurotransmitters
- MAOI's are non-selective and therefore inhibit both MAO-A and MAO-B
- inhibit the metabolism of MAOs in the pre-synaptic neuron
- useful for atypical depression and dysthymia
65
What are the adverse effects of MAOIs?
- CNS excitation (anxiety, insomnia, agitation)
- orthostatic hypotension
- hypertensive crisis if taken with tyramine containing foods
66
When do symptoms of bipolar disorder usually begin?
- in adolescence or early adulthood
67
What are the symptoms of manic phase?
- irritation
- inflated self-esteem
- little need for sleep
- poor control of temper
- reckless behaviour (binge eating, drinking, drug use)
- easily distracted
68
What are the 3 major groups of drugs used to treat bipolar disorder?
1. mood stabilizers
2. antipsychotics
3. antidepressants
69
what are mood stabilizers used for?
1. relieve symptoms during maniac or depressive episodes
2. prevent reoccurrence of manic or depressive episodes
3. do not worsen symptoms of mania or depression and do not alter the rate of cycling
70
What are the two main mood stabilizers?
- lithium and the anti-epileptic drug valproic acid
71
How does lithium work?
- mechanism of action is not clear, but thought to work by altering the uptake and release of glutamate and blocking the binding of serotonin
- has a narrow therapeutic range
- plasma concentrations can be altered by sodium
- agents that increase sodium loss from the body increase lithium concentrations and may produce toxicity (GI upset, tremor, sedation and hypotension)
72
What are antipsychotics?
- used to control symptoms during manic episodes and long term to help stabilize mood
- benefit patients with BPD even if they dont have psychotic symptoms
- atypical antipsychotics > conventional antipsychotics bc lower risk of EPS
73
how are antidepressants used in BPD?
- used in BPD to treat depressive episodes
- always combined with a mood stabilizer
- if used alone may trigger manic episode
74
What is anxiety vs anxiety disorder?
- normal physiological response to stress
- anxiety disorder: symptoms of anxiety create a functional impairment in a patients daily living; closely linked to depression
75
What are the 7 general categories of anxiety?
1. general anxiety disorder
2. panic disorder
3. agoraphobia
4. obsessive-compulsive disorder
5. social anxiety disorder
6. post- traumatic stress disorder
7. simple phobia
76
What is general anxiety disorder?
- overwhelmed with incontrollable worrying
- unrealistic or excessive worry
- lasting 6 mo or longer
77
What is panic disorder?
- sense of impending doom that is unrelated to stressors
- panic attacks (sudden in onset; heart palpitations; chest pains; shortness of breath; dizziness; often confused for a heart attack)
78
What is agoraphobia?
- patient feels judged or a situational anxiety where escaping would be difficult or embarassing
79
What is OCD?
- persistent obsession and compulsions that interfere with daily life
80
What is social anxiety disorder?
- anxiety in social situations
| - may not be able to talk, eat or use public washrooms
81
What is PTSD?
- occurs after experiencing a traumatic event
| - symptoms include re-experiencing the event and sever insomnia
82
What is simple phobia?
- symptoms related to a specific fear (i.e spider, elevators etc)
83
What are the 3 major classes of drugs?
1. benzodiazepines (BDZs)
2. buspirone
3. antidepressants
84
What are BDZs?
- first line therapy for anxiety
- act by potentiating the actions of GABA at the GABA receptor
- BDZs are not GABA agonists they bind to a different site on the GABA receptor and cause increased binding of GABA to the receptor
- it opens a channel and chloride ions move into the cell = CNS depression
- limit to how much CNS depression produced bc not GABA agonists, they just amplify the actions of endogenous GABA = much safer this way
85
What are the therapeutic uses of BDZs?
1. anxiety
2. seizures
3. insomnia
4. alcohol withdrawal
5. muscle spasm
- different dosages treat different things
86
What are the adverse effects of BDZs?
- CNS depression
- anterograde amnesia
- respiratory depression
- teratogenic
- tolerance
- withdrawal
87
What is buspirone?
- not a CNS depressant but useful in treating anxiety in those who use alcohol
- involves modulation of serotonergic and/or dopaminergic neurotransmission
- treats generalized anxiety disorder but ineffective treating other
- no sign of tolerance or dependence
- effects develop slowly
- well tolerated and non-sedating
88
What are the common adverse effects associated with buspirone?
- dizziness
- lightheadedness
- excitement
89
Which antidepressants can be used for generalized anxiety disorder?
SSRIs and SNRIs effective but slow to generate effect
90
what antidepressants can be used for panic disorder /agoraphobia?
- SSRIs, TCAs, and MOA inhibitors
| - effects take 6-12 weeks to appear
91
Which antidepressants can be used for OCD?
- SSRIs first line therapy
| - also behavioural therapy
92
Which antidepressants can be used for Social anxiety disorder?
- SSRIs first line therapy but BDZ can also be used
93
Which antidepressants can be used for PTSD?
none
