Week 3 Flashcards
(273 cards)
1
Q
What is the normal neuronal regulation?
A
- Transmission of action potential (AP) down axon 2. Release of neurotransmitter (NT) from axon
- Binding of NT to post-synaptic cell
- Post-synaptic cell changes action
2
Q
What are the ways medications can interfere with normal neuronal regulation?
A
• Alter axonal conduction
- Local anesthetics
• Alter synaptic transmission
• Receptor agonism or antagonism
3
Q
How do medications affect receptor agonism?
A
Drug causes same effect as naturally occurs => receptor activation
4
Q
How do medications affect receptor antagonism?
A
Drug reduces or causes opposite effect => receptor deactivation/blockade
5
Q
What are the steps in synaptic transmission?
A
- Neurotransmitter(NT) synthesis & storage (vesicles)
- Release of NT into cleft
• Small number of vesicles - Post-synaptic receptor
binding (reversible) - Inactivation of NT
• Reuptake
• Enzymatic degradation
• Diffusion (slow, usually does
not happen in vivo)
6
Q
What are the types of neurotransmitters?
A
Central
Peripheral
7
Q
What are the types of central neurotransmitters?
A
- Amino Acids
- Acetylcholine
- Catecholamine/Monoamine
- Peptides
8
Q
Amino acids central neurotransmitters can either be inhibitory or excitatory. What are the inhibitory amino acid central neurotransmitter?
A
- GABA
* Glycine
9
Q
Amino acids central neurotransmitters can either be inhibitory or excitatory. What are the excitatory amino acid central neurotransmitter?
A
Glutamate
10
Q
What are the catecholamine/monoamine central neurotransmitter?
A
- 5-hydroxytryptamine (Serotonin; 5HT)
- Norepinephrine (Noradrenaline; NE)
- Dopamine (DA)
11
Q
What are the peptide central neurotransmitter?
A
Opioids (enkephalins, endorphins; substance P)
12
Q
What are the types of peripheral neurotransmitter?
A
- Acetylcholine
* Catecholamine/Monoamine
13
Q
What are the catecholamine/monoamine peripheral neurotransmitter?
A
- Epinephrine (Epi)
* Norepinephrine (NE)
14
Q
Where is the primary CNS location of CNS neurotransmitter: Acetylcholine (ACh)?
A
Cerebral Cortex (many areas); basal ganglia; limbic & thalamic regions; spinal interneurons
15
Q
What is the general effect of CNS neurotransmitter: Acetylcholine (ACh)?
A
Excitation
16
Q
Where is the primary CNS location of CNS neurotransmitter: Norepinephrine (Monoamine)?
A
Neurons originating in brainstem & hypothalamus that
project throughout other areas of the brain
17
Q
What is the general effect of CNS neurotransmitter: Norepinephrine (Monoamine)?
A
Inhibition
18
Q
Where is the primary CNS location of CNS neurotransmitter: Dopamine (Monoamine)?
A
Basal Ganglia; Limbic System
19
Q
What is the general effect of CNS neurotransmitter: Norepinephrine (Monoamine)?
A
Inhibition
20
Q
Where is the primary CNS location of CNS neurotransmitter: Serotonin (Monoamine)?
A
Neurons originating in brainstem that project upward (to hypothalamus) & downward (to spinal cord)
21
Q
What is the general effect of CNS neurotransmitter: Serotonin (Monoamine)?
A
Inhibition
22
Q
Where is the primary CNS location of CNS neurotransmitter: GABA (gammaaminobutyric acid)?
A
Interneurons throughout the spinal cord, cerebellum, basal
ganglia, cerebral cortex
23
Q
What is the general effect of CNS neurotransmitter: GABA (gammaaminobutyric acid)?
A
Inhibition
24
Q
Where is the primary CNS location of CNS neurotransmitter: Glycine (Amino Acid)?
A
Interneurons in spinal cord and brainstem
25
What is the general effect of CNS neurotransmitter: Glycine (Amino Acid)?
Inhibition
26
Where is the primary CNS location of CNS neurotransmitter: Glutamate, Aspartate (Amino Acid)?
Interneurons throughout brain & spinal cord
27
What is the general effect of CNS neurotransmitter: Glutamate, Aspartate (Amino Acid)?
Excitation
28
Where is the primary CNS location of CNS neurotransmitter: Substance P (Peptide)?
Pathways in Spinal Cord
29
What is the general effect of CNS neurotransmitter: Substance P (Peptide)?
Excitation
30
Where is the primary CNS location of CNS neurotransmitter: Enkephalins (Peptide)?
Pain & suppression pathways in spinal cord & brain
31
What is the general effect of CNS neurotransmitter: Enkephalins (Peptide)?
Excitation
32
Drugs that affect the CNS can:...?
```
• Affect movement
- Limit movement
- Cause abnormal involuntary movements
• Induce sleep or arousal
• Treat anxiety, depression, and other psychiatric conditions
• Affect memory
• Increase attention and focus
```
33
What is the problem for CNS drugs?
Blood Brain Barrier (BBB)
34
What does Blood Brain Barrier (BBB) do?
• Effectively protects against passage of foreign substances into the brain
• Prevents the entry of damaging as well as therapeutic substances
• Barrier achieved by structure & function of CNS capillaries
- Tight junctions along endothelium of capillary
- Basement membrane lies between capillary endothelial cells and astrocytes -->
Impermeability
35
Compounds the cross the blood- brain barrier cross and exert effects by...?
* Passive Diffusion- diffusion gradient (non-polar, lipid soluble drugs (e.g. morphine, ETOH)
* Facilitated Diffusion (e.g. Glucose)
* Active Transport (Carrier molecules used)
36
What are the general principles for compounds crossing the blood- brain barrier?
* Large molecules do not pass easily
* Low lipid-soluble molecules do not pass, but lipid soluble pass
* Highly charged molecules do not pass easily
37
How can the blood- brain barrier be affected to allow easier entry?
* At birth-not fully formed
* Post-radiation
* Infectious agents present
* Trauma, ischemia & inflammation
38
What are the pharmacological means to reduce the risk of a Transient Ischemic Attack (TIA)?
Antiplatelet agents = aspirin
(ASA) monotherapy; combo of
aspirin & extended release
dipyridamole; clopidogrel (Plavix®) monotherapy
39
What is the action of the anti-platelet agents used to reduce the risk of a TIA?
ASA irreversibly acetylates COX-1 to prevent synthesis of TXA2, key to platelet aggregation
40
What is the pharmacological means to treat a post-stroke: thrombolysis?
Tissue Plasminogen Activators (tPA)
41
What is the criteria for treating post-stroke: thrombolysis?
Time, Age, med hx, including BP, DWI-PWI MRI
42
What is the most common drug used to treat post-stroke: thrombolysis?
tPA-alteplase (Activase®)
43
What is the action used to treat post-stroke: thrombolysis?
Clot buster
44
What are the side effects of tPA-alteplase used to treat post-stroke: thrombolysis?
• Hemorrhage, usually into
region
• Mild systemic bleeding
- Internal bleeding: GI or GU
45
What are the things to monitor for a patient that takes a tPA-alteplase used to treat post-stroke: thrombolysis?
• VS & neuro checks q 15 min for 2 hrs, then q 30 min for 6 hrs, then q hr until 24 hrs
• No other anticoagulants for
24 hrs
46
What is the MOA of tPA-alteplase (Activase®) used to treat post-stroke: thrombolysis?
1. tPA (Activase®) binds to fibrin in thrombus
2. Converts entrapped plasminogen to plasmin
that
3. Initiates local fibrinolysis (clot breakdown)
47
What are the ways to avoid an ischemic stroke?
Blood Pressure Control
• Blood pressure recommendations: < 185/110 mm Hg
- Preserve cerebral perfusion AND minimize risk of bleed
48
What are the ways BP is controlled with IV medications?
• Labetalol- Trandate® 10-20 mg IV over 1-2 minutes (a- & b-blocker; blocks Epinephrine)
• Hydralazine- Apresoline® 10-20 mg IV over 1-2 minutes (direct smooth muscle relaxation)
• Metoprolol 5-15 mg IV over 1-2 minutes (b-blocker)
• Sodium nitroprusside- Nipride® 0.5-10 mcg/kg/min (max 10 mcg/kg/min)
(direct smooth muscle relaxation)
• Nicardipine drip- Cardene ® 5 mg/hr (max 15 mg/hr)(Ca++ channel blocker)
49
What are the different ways a person can have spasticity?
* Imbalance between excitatory and inhibitory input to a motor neuron
* Motor unit changes: collateral sprouting, silent synapse activation, denervation super sensitivity
* Mechanical properties of mm change post-stroke; sarcomere shorter and stiffer
50
What are the complications seen with spasticity?
* Positioning
* Hygiene
* Activities of Daily Living (ADLs)
* Sitting or Standing Balance
* Contractures
51
What are the treatment goals of a patient with spasticity?
* Improvements in position
* Ease of care are possible
* Mobility
* Contracture prevention
52
What are the indications for spasticity management options?
Patients with CVA, MS, TBI, SCI, CP
53
What are the spasticity management options?
* Therapeutic modalities (ice)
* Oral Medications
* Nerve blocks & Chemical neurolysis
* Surgery: Orthopedic procedures
* Intrathecal Medications
* Medical Marijuana
54
What are the effects of muscle relaxants as a way to treat spasticity?
* Decrease somatic motor activity
| * Reduce muscle tone
55
What are the side effects of muscle relaxants as a way to treat spasticity?
• CNS depression
• Sedation
• Anticholinergic side effects
-- Especially in elderly
56
How is BOTOX® (Botulinum Toxin Type A): A Focal Therapeutic used to treat spasticity?
Injected directly into overactive muscles
57
What are the effects of botox as a means used to treat spasticity?
Reduces contractions, relaxes muscles
58
What are the advantages of local injection (max dose is
| < 500 units/visit) used to treat spasticity?
− Targeted to specific muscles that are causing symptoms
− When used at recommended doses, avoids systemic, overt distant clinical effects
− A nerve impulse ''blocker'’; prevents release of ACh at neuromuscular junction
− Expected to last 3-3.5 months
− Takes effect <2 weeks post-injection
59
What are the main methods for muscle identification and injection used to treat spasticity?
• Exam and anatomic atlas
• EMG assistance and
guidance
• Electronic stimulation
60
What are the side effects of the use if botox to treat spasticity?
• Localized
- Hematoma and bruising are seen regardless of the site injected
- Muscle weakness near injection site
• Low risk: Botulinum toxin contained in Botox can
spread to other body areas beyond where it was injected & this could cause serious life-threatening side effects, even when used for cosmetic purposes.
61
When should 911 be called for a person that uses botox?
If trouble breathing, talking, swallowing, or total body weakness
62
What is the onset of action of the use of intrathecal baclofen drug infusion pump to treat spasticity?
Onset of action is ½ hr-1 hr after intrathecal
| bolus.
63
When is the peak effect of the use of intrathecal baclofen drug infusion pump to treat spasticity?
Approx 4 hours after dose;
| effects may last 4 – 8 hrs.
64
What are the characteristics of intrathecal baclofen drug infusion pump to treat spasticity?
* Fewer side effects, better relief of spasticity
* Usually more effective for spasticity in lower extremities
* Requires committed patient and family, pump must be refilled every 3 months.
65
What are the main active ingredients of cannabis?
• Tetrahydrocannabinol (THC)
• Cannabinoids (chemicals related to THC)
• Resemble endogenous NT: anandamide (AEA). Anandamide
"turns on" CNS nerve receptors that effect motor functioning,
nausea, and other functions
66
____ may alleviate pain, blocks
| psychotropic effects of THC
*Cannabidiol (CBD)* may alleviate pain, blocks
| psychotropic effects of THC
67
What are the characteristics of cannabis as a treatment method to treat spasticity?
• Anecdotal reports that cannabis helps with excessive
muscle tone and pain
• Studies in MS (2013) have shown cannabis ↓ tone
measured by Ashworth (avg change of 2.7 points),
but did affect cognition in pts with MS (2014).
68
Drugs can cause ___ or __ effect on neurotransmitters in CNS
Drugs can cause *excitation or inhibition* effect on
| neurotransmitters in CNS
69
What is the progression of parkinsons?
Unilateral -> Bilateral -> Balance Issues -> restricted to walking cane or bed
70
What is the etiology of parkinsons associated with?
With consequences of ↓ DA levels produced by substantia nigra (SN) neuron loss.
71
Where do the neurons produced by the substantia nigra supply?
Neurons from SN supply DA to the corpus striatum (caudate,
| putamen & globus pallidus )
72
What is the function of the corpus striatum?
Initiates movement and self-expression
73
What are the non motor effects of parkinsons?
* Cognitive: verbal fluency, abstract reasoning, executive function & memory
* Behavioral: anxiety, apathy, depression
* Dementia
* Disturbance of autonomic nervous system (difficulty in urinating)
74
What are the characteristics of parkinsons?
* Tremor @ rest
* Rigidity
* Akinesia, bradykinesia
* Postural instability
75
What is the pathophysiology of parkinsons?
* Degradation of DA-secreting neurons in basal ganglia
| * Decreased DA input in corpus striatum allows Acetylcholine (ACh) to dominate: imbalance of DA and ACh
76
___ is the most effective single drug for PD
*Levodopa* is the most effective single drug for PD
77
What is the dose adjustments of levodopa based on?
Symptoms
78
What are the side effects of levodopa?
```
• GI
• CV
• Psych
• Hypotension.
• Dyskinesia & neuropathy
after prolonged use
```
79
When can a person have a reduced response to levodopa?
After prolonged use 2°
| tolerance or disease progression
80
A decreased response to levodopa can be aided by..?
1) Controlled release formulation
| 2) Adding additional medications to regimen
81
What are the kinetics of levodopa?
* Well absorbed, delayed by high protein meals
| * Most levodopa metabolized in periphery, small amount crosses BBB, leads to nausea
82
What are the adverse effects of levodopa?
```
• Nausea and vomiting
- Food will dec nausea but will delay absorption
• Dyskinesias (80%) later in treatment
• CV: postural hypotension
• Psychotic symptoms (20%)
- Hallucinations, agitation, etc.
```
83
How is levodopa usually administered?
With carbidopa in a formulation
| called Sinemet
84
What causes most of the nausea that occurs as a result of levodopa?
By conversion of levodopa to DA in the periphery
85
What should be done to prevent the conversion of levodopa to DA in the periphery?
Administer with carbidopa
86
What are the side effects of Carbidopa/Levodopa (Sinemet)?
```
• GI upset; N&V
• Cardiovascular problems
– orthostatic hypotension
• Dyskinesias
– Choreoathetoid movements
– Ballismus
– Dystonia
```
87
How is Carbidopa/Levodopa (Sinemet) dosed?
Until symptom relief or side effects seen
• Available dose combinations: 10/100mg ,
25/100mg , 25/250 mg
88
What are the characteristics of Carbidopa/Levodopa (Sinemet)?
```
• Sustained release product:
25/100mg, 50/200mg
• High protein foods ↓
absorption. Can take before
meals or light carbohydrate
snack
```
89
What is the effect of carbidopa on levodopa absorption?
Without carbidopa, most L- dopa is converted to DA in
periphery
• Unable to cross BBB
• Causing severe nausea
90
How does carbidopa impact its effect on levodopa absorption?
• Carbidopa inhibitsperipheral decarboxylase (D-C ase) enzyme so that levodopa can cross the
BBB intact.
• Carbidopa does not cross
BBB allowing conversion of levodopa in the CNS
91
What are the diminished responses of Carbidopa/Levodopa (Sinemet)?
* Tolerance may build over time and disease will continue to progress
* Controversy: when to begin Sinemet vs other meds
* Drug holiday from all anti-parkinson meds for 3 days to 3 weeks – resume at lower doses (does not work in all patients)
92
What are the characteristics of when happens when the end-of-dose of Carbidopa/Levodopa (Sinemet) is wearing off?
* Effectiveness wears off before next dose given, symptoms reappear
* Doses given more frequently to cover “offs”
* Sustained release products can be used
* Catechol-O-methyltransferase (COMT) inhibitors
93
What is the function of COMT Inhibitors?
Inhibits action of enzyme that degrades NTs (L-dopa) to increase its availability
• Extends half-life of levodopa from 1.5 to 2.5 hrs
94
What is the place in therapy of COMT Inhibitors?
2nd line agent- used only in combination with levodopa/carbidopa
95
What is the effect of COMT Inhibitors?
Decreases “wearing off,”
| on-off times, and motor fluctuations
96
What are the two common COMT Inhibitor medications?
Entacapone® (200 mg); Tolcapone® (100 mg tid)
97
Why is tolcapone rarely used?
Due to liver toxicity
98
What are the adverse effects of COMT Inhibitors?
* Nausea, vomiting, diarrhea, abdominal pain
| * Dyskinesias
99
What are dopamine agonists used for?
Used in the early stages of PD to reduce symptoms
100
What do dopamine agonists do?
Delays need for levodopa and delays motor fluctuations that
| occur with prolonged levodopa use (dyskinesias)
101
What are the common dopamine agonists medications?
* Bromocriptine (Parlodel®)- PD & Restless Leg Syndrome (RLS)
* Pramipexole (Mirapex®) - PD and RLS
* Ropinirole (Requip®) - PD and RLS
* Cabergoline (Dostinex®) – RLS (not indicated for PD)
102
What is the MOA of dopamine agonists?
* Stimulates DA receptors in the absence of DA.
| * May prolong or ↓ need for levodopa
103
When may dopamine agonists be the 1st line therapy or may be added to levodopa/carbidopa in later stages of PD?
* Levodopa no longer adequately controls symptoms
* ↑ dose to control sxs would cause excessive side effects.
* Severe motor fluctuations
104
What are the side effects of dopamine agonists?
* N/V
* Orthostatic hypotension*
* Drowsiness
* Dizziness*
* Hallucinations
* Confusion
* Unsteadiness*
* Dyskinesias,
* Hypersexuality
* Compulsive gambling
105
What type of drug is Apomorphine (Apokyn®)?
Dopamine Agonist
106
What is Apomorphine (Apokyn®) used for?
For akinetic “off” episode
• Patient is “stuck”
• Must be administered under medical supervision initially
• Administered with nausea agent, causes SEVERE nausea
• Used in advanced disease
107
What kind of drug is Amantadine?
Dopamine agonist, also anti-viral affects
108
How often is Amantadine usually taken?
Usually taken twice daily (BID)
109
What is the MOA of Amantadine?
DA agonist; glutamate antagonist
110
What are the symptomatic benefits of Amantadine?
Tremor, rigidity & bradykinesia (200-300 mg/day)
111
What is Amantadine effective for?
Levodopa induced dyskinesias
112
What are the pharmacokinetics of Amantadine?
Well absorbed, long half-life, excreted unchanged by the kidney
113
What are the side effects of Amantadine?
* Blurred vision
* Dizziness
* Trouble sleeping
* Depression/anxiety
* Swelling feet/hands
* SOB
* Difficulty urinating.
114
How long is the duration of benefit of Amantadine?
< 1 yr
115
What is the place of Selegiline /Eldepryl® in therapy?
1st line in patients with mild disease to slow progression and delay need for L-dopa
116
What is the action of Selegiline /Eldepryl®?
A selective irreversible MAO-B inhibitor to ↓ breakdown of DA;
in larger doses loses specificity and will ↓ breakdown of serotonin, dopamine AND tyramine
117
What can high doses of MAO-B inhibitor lead to?
Hypertensive crisis if taken with tyramine containing foods (fermented, pickled foods)
118
How can Selegiline /Eldepryl have possible neuroprotective effects?
By reducing oxidative metabolism of dopamine
119
What does Selegiline /Eldepryl do as adjunct therapy for parkinsons?
As adjunctive therapy (5-10 mg/day) increases “on” time; decreases amount of levodopa needed to reduce side effects of levodopa
120
What is the usual dose of Selegiline /Eldepryl?
5 mg BID (Q AM and Q Noon)
121
What are the adverse effects of Selegiline /Eldepryl?
* Confusion, hallucinations
* Nausea
* Orthostatic hypotension, tachycardia
* Dry mouth
* SOB
122
What are the risk factors of dementia?
* Aging
* Family hx
* Environmental
123
What is the pathophysiology of dementia?
* Neuronal degeneration
| * Reduced Cholinergic (Ach) Transmission
124
What is the characteristic morphology of dementia?
* Amyloid plaques
* Neurofibrillary tangles
* Apo E4, ER-assoc binding protein, homocysteine
125
What is dementia characterized by?
By a loss of cognition and loss of at least one of the following abilities:
• to speak coherently and understand language
• to recognize or identify objects
• to execute motor activities
• to think abstractly, make sound judgment, and plan and
carry out complex tasks; personality changes
126
What are the pharmacological treatments of Alzheimer Disease (AD)?
• Cholinesterase inhibitors are helpful for ~ 1/3 of patients
- Will slow progression of disease, but NOT cure
• Psychiatric drugs (e.g., antidepressants, antipsychotics) are used to manage some of the psychological disturbances
• Experimental treatments include:
- vitamins E and C (antioxidants)
- ginkgo biloba (antioxidant & vasodilator)
127
What are the characteristics of Cholinesterase inhibitors (AChE-I) in Alzheimer Disease (AD)?
* In AD, ACh transmission in brain is 90% < non-AD, age-matched.
* ACh essential for forming memories
* AChE-I help mild-moderate patients
128
What are the Cholinesterase inhibitors (AChE-I) meds approved by the FDA?
* Donezepil (Aricept®)
* Rivastigmine (Exelon®)
* Galantamine (Razadyne®)
129
What is the the MOA of Cholinesterase inhibitors (AChEI)?
Inhibits AChE breakdown, which leads to↑level & duration of ACh
130
What is the function of Cholinesterase inhibitors (AChE-I) as a treatment for Alzheimer?
Slows progression of symptoms, but does not reverse loss of neurons
131
What are the effects of Cholinesterase inhibitors (AChE-I) as a treatment for Alzheimer?
May produce small improvements in memory and general ability to function
132
What are the side effects of Cholinesterase inhibitors (AChEI)?
* Indigestion
* N&V
* Diarrhea
* Loss of appetite -> wt loss
* Dizziness
* Slowed HR
133
What is the most common medication form of Cholinesterase inhibitors (AChEI)?
Rivastigmine- applied thru skin patch (↓side effects)
134
What are the characteristics of the dosage of Cholinesterase inhibitors (AChEI)?
Dosage requires titration over weeks (up to 4)
135
____, the most effective treatment for parkinsonism, impacts dopamine function either alone or in combo with other drugs.
*Levodopa*, the most effective treatment for parkinsonism, impacts dopamine function either alone or in combo with other drugs.
136
Other dopamine agonists have been developed 2nd line
| treatments to ___ and ___
Other dopamine agonists have been developed 2nd line
| treatments to *reduce side effects and prolong function.*
137
Although there is no cure for Alzheimer's, 1/3 can
experience improved psychological function with
____
Although there is no cure for Alzheimer's, 1/3 can
experience improved psychological function with
*Cholinesterase inhibitors.*
138
____ may block effects of plaque production and
| minimize memory loss.
*Memantine* may block effects of plaque production and
| minimize memory loss.
139
____ may cause excess influx of Ca++ into neurons
*Amyloid plaques* may cause excess influx of Ca++ into neurons
140
Overexcitation of NMDA receptors by glutamate may play a role in ____ memory & learning
Overexcitation of NMDA receptors by glutamate may play a role in *decreasing* memory & learning
141
What happens when there is too much glutamate exciting NMDA receptors?
Allows Ca++ into nerve which leads to cell death
142
What is used to partially block NMDA receptors in moderate to severe AD?
NMDA receptor Antagonist
| Memantine (Namenda®)
143
What are the pharmacological parameters of NMDA receptor Antagonist Memantine (Namenda®)?
5-10 mg tablet bid; Half life 3-7 hrs; food does not affect absorption
144
What are the side effects of NMDA receptor Antagonist
| Memantine (Namenda®)?
* HA
* Dizziness
* Constipation
* Confusion
*Not recommended for
pts with renal impairment
145
What are the characteristics of Multiple Sclerosis?
• Unpredictable, progressive,
degenerative of CNS myelin
• (exacerbation & remission)
• Onset: 20-50 yrs; Caucasians more common
• Autoimmune disorder; antibodies attack myelin
146
What are the parameters of Multiple Sclerosis?
* Lesions in time & space-CNS
* Myelin loss ->↓ nerve conduction of AP & ↓ function
* May have normal lifespan
147
How is Multiple Sclerosis diagnosed?
* MRI (plaques)
* CSF analysis (↑ protein & slight ↑ WBCs)
* Evoked potentials (extent of damage)
148
The symptoms of Multiple Sclerosis is related to?
Location of plaque (lesion) formation
149
What are the symptoms of Multiple Sclerosis?
* Motor control- spasticity
* Difficulty walking
* Fatigue
* Vision problems
* Numbness
* Depression
* Emotional changes
* Vertigo & dizziness
* Changes in sexual function
* Coordination problems
* Balance problems
* Pain
* Changes in cognitive function
* Bowel/bladder dysfunction
150
What are the Pharmacological Goals/Treatment of Multiple Sclerosis?
• MS disease-specific medications (Primary Symptom
Treatment)
- Modify course of MS - Prevent relapse and MS
progression
- Control symptoms and prevent complications
• Secondary Symptoms
- Caused by primary symptoms
- Example: Urinary tract infection due to urinary
retention
• Tertiary Symptoms
- Psychological symptoms
151
Interferons are medications used for Multiple Sclerosis. What is it?
Family of naturally-occurring proteins secreted by
| immune system cells
152
What is the action of Interferons?
Modulate immune system response
153
What are the side effects of Interferons?
* Mild to severe flu-like symptoms in 50% of patients following each injection
* Managed with analgesics (acetaminophen) and antihistamines (Benadryl)
* Depression
154
What are the characteristics of the medications for MS?
* ALL MS medications for designed to modulate the immune system
* Reducing exacerbations
* Ultimately reducing damage that leads to further symptoms
155
What are the symptom management meds for MS?
* Baclofen > Dantrium: for spasticity
* Antidepressants: Prozac, Zoloft, etc.
* Beta blockers for tremors EX: Inderal
* Antiseizure: for neuropathic pain. EX: Tegretol, Topamax, etc.
* Anticholinergics: for bladder dysfunction. EX: Ditropan, Vesicare, etc.
* Corticosteroids (methylprednisone), used to treat acute exacerbations (vision loss, pins, needles, etc.)
156
What kind of drug is Methylprednisolone (Solu-Medrol®, Medrol®)?
Corticosteroid, glucocorticoid, anti-inflammatory
157
What is the action of methylprednisolone?
Anti-inflammatory & immunosuppressive properties. Alters the bodies immune response to a variety of stimuli
158
What are the contraindications of methylprednisolone?
Suspected fungal infections, known sensitivity
159
What are the side effects of methylprednisolone?
* Edema
* Hypokalemia
* Hypo- /hyper-tension
* Hyperglycemia
* CHF
More common when used frequently
160
What are the dosage parameters of methylprednisolone?
Methylprednisolone IV 50-100 mg daily for 3 to 7 days.
161
What are the characteristics of Seizures/ Epilepsy?
* Seizures are neuronal activity, firing in the brain
| * The seizure may stop in one part of the brain or spread throughout the brain
162
What are the classifications of Seizures/ Epilepsy?
* Partial Seizures
| * Generalized Seizures
163
What is a partial seizure?
Localized to one hemisphere of the brain
164
What is a generalized seizure?
Spread to the opposite hemisphere of the brain after initiation of seizure
165
What is the duration of a simple partial seizure/ epilepsy?
90 seconds
166
What are the clinical features of a simple partial seizure/ epilepsy?
* Consciousness not impaired
| * Motor, somatosensory, autonomic, or psychic symptoms
167
What is the duration of a complex partial seizure/ epilepsy?
1-2 minutes
168
What are the clinical features of a complex partial seizure/ epilepsy?
* Consciousness impaired
* May have aura
* Motor, somatosensory, autonomic, or psychic symptoms
* Automatisms
169
What is the duration of a generalized absence seizure/ epilepsy?
2-15 seconds
170
What are the clinical features of a generalized absence seizure/ epilepsy?
* Rapid seizure onset, period of unresponsiveness, rapid recovery
* Stare
* Eyes fluttering
* Automatisms if prolonged
171
What is the duration of a generalized tonic-clonic seizure/ epilepsy?
1-2 minutes
172
What are the clinical features of a generalized tonic-clonic seizure/ epilepsy?
* Loss of consciousness without warning or preceded by myoclonic jerks
* Cry, fall
* Tonicity, clonicity
* May have cyanosis
173
What are the stages of a seizure?
```
• Aura
• Seizure=ictus
• Post-ictal
- Confusion
- Disorientation
- Weakness
- Hypoglycemia
• Status Epilepticus: seizure that lasts >30 minutes
```
174
What are the rationale for Anti-Epileptic Drugs (AEDs)?
* Prevention
* Seizures are generally self-limiting
* Minimize cell and muscular damage
* Improve quality of life
175
What is the general mechanism of Anti-Epileptic Drugs (AEDs)?
Inhibit firing of specific neurons
• ↑ inhibitory effects of GABA
• ↓ effects of excitatory glutamate
• Blocking action potentials (e.g. sodium influx)
176
What is the US FDA approved 1st line agent for partial seizures?
Carbamazepine
177
What are the other pharmacological agents for partial seizures?
* Phenytoin
* Oxcarbazepine
* Valproic acid
178
What is the US FDA approved 1st line agent for generalized seizures?
Valproic acid
179
What are the other pharmacological agents for generalized seizures?
* Lamotrigine
| * Topiramate
180
What is the US FDA approved 1st line agent for absence seizures?
Valproic acid
181
What are the other pharmacological agents for absence seizures?
Ethosuximide
182
What are the side effects of Anti-Epileptic Drugs: Carbamazepine?
* Aplastic anemia
| * Liver toxicity
183
What are the side effects of Anti-Epileptic Drugs: Phenytoin?
* Cardiac
* Confusion
* Dizziness
* Vitamin D deficiency
* Hepatotoxic
* Gingival hyperplasia
184
What are the side effects of Anti-Epileptic Drugs: Valproic Acid?
* Pancreatitis
* Liver toxicity
* Alopecia
* Tremor
* Stomach upset
185
What are the side effects of Anti-Epileptic Drugs: Lamotrigine?
Rash with highly escalated dosing
186
What are the most common mechanisms of anti-seizure drugs?
• Modification of ion conductance
- Prolongation of Na+ channel inactivation
- Inhibition of Ca++ current in thalamus
• Increase inhibitory (GABAergic) transmission: Cl- channels open
• Glutamate receptor antagonist (ex: NMDA)
187
What are the common side effects of anti-seizure drugs?
* Dizziness
* CNS depression
* Drowsiness
* Lethargy
* Mental slowing
* Weight gain
* Glaucoma
* Skin rash
* Hepatotoxicity
* Dyskinesias
188
What is the presentation of anti-seizure drugs toxicity?
* Ataxia/slurred speech
* Diplopia/nystagmus
* Hypotension
* Pupils fixed/coma
189
What are the most common causes of a TBI?
* MVC
* Falls
* Sports
* Violence
190
What is the difference between a Coup vs Contrecoup TBI?
Coup TBI is when you have a direct impact on your head and a countercoup is when you jostle your head and your brain moves
191
What are examples of focal brain injuries?
Contusions, epidural hemorrhage, subdural qhematoma
192
What class of drug is Mannitol (Osmitrol®)?
Electrolytic & water balance, diuretic
193
What is the action of Mannitol (Osmitrol®)?
Hyperosmolar agent draws fluid into vascular space. Fluid is filtered by kidneys to dec Na+ reuptake and inc water loss. Onset of action 15min to dec ICP
194
What are the indications for Mannitol (Osmitrol®)?
Acute brain injury with evidence of ICP
195
What are the side effects of Mannitol (Osmitrol®)?
* Hypotension
* Dehydration
* Acidosis
* Alectrolyte imbalances.
* If patient has poor renal function, edema, HTN, HA, N&V
196
What is the usual adult dosage of Mannitol (Osmitrol®)?
For ICP 1.5-2.0g/kg IV over 30-60min
197
What is the usual pediatrics dosage of Mannitol (Osmitrol®)?
Not given for ICP
198
What is the usual supplied dosage of Mannitol (Osmitrol®)?
20% vials containing 200g
199
What are the contraindications of Mannitol (Osmitrol®)?
* Hypotension in trauma pt
* Severe dehydration
* Acute pulmonary edema,
200
_____ does not have a cure, but drugs such as interferons can modulate immunoresponse
*Multiple sclerosis* does not have a cure, but drugs such
| as interferons can modulate immunoresponse
201
Drugs used with MS can be categorized as _____
Drugs used with MS can be categorized as *disease specific, secondary effects & tertiary effects*
202
____ has many types and causes which leads to a
large number of medications used to try manage
symptoms/reduce frequency
*Epilepsy* has many types and causes which leads to a
large number of medications used to try manage
symptoms/reduce frequency
203
What are the characteristics of Sedative-Hypnotics & Anxiety Drugs?
```
• Among most commonly used
drugs worldwide
• CNS Depressants
• High use in PT/OT patient
populations
```
204
What are the different classes of Sedative-Hypnotic Drugs?
* Relaxation
* Sleep
* Anesthesia
205
What is the pharmacology of sedative- hypnotics?
* An effective sedative (anxiolytic) agent should reduce anxiety and exert a calming effect with little or no effect on motor or mental functions
* A hypnotic drug should produce drowsiness and encourage the onset and maintenance of a state of sleep that as far as possible resembles the natural sleep state
206
What are the characteristics of Benzodiazepines?
```
• Includes anti-anxiety drugs
• Regarded as safer
• Block GABA
- Similar to AEDs
- Not used in seizures due to
potential for tolerance
- May lead to breakthrough
seizures
• Decreases arousal
```
207
What are the characteristics of non-benzodiazepines?
```
• Barbiturates
• Smaller therapeutic Index
• Quickly approach lethal
doses
• Abuse potential
• Used more in past
• Also potentiate GABA
effects
- Phenobarb for seizures
```
208
What are the characteristics of newer non-benzodiazepines “Z-Drugs”?
* Promote sleep as effectively as benzodiazepines
* No effect on anxiety or seizure prevention
* Bind preferentially to subunit on GABA receptor
209
What are the common newer non-benzodiazepines “Z-Drugs"?
* Zolpidem (Ambien®)
* Eszopiclone (Lunesta®)
* Zaleplon (Sonata®)
210
What are the pharmacokinetics for sedative drugs?
* Highly lipid soluble– makes crossing BBB easy
* Oral Administration usually
* Absorbed in GI track
* Uniform Distribution
* Metabolized in Liver
* Excretion: Susceptible to Re-absorption *Hangover Effect
* Risk for Dependence
211
What are the characteristics of anti-anxiety drugs: Benzodiazepines?
• Usually front-line management, short term
• Mechanism same as described previously
• Also increases inhibition in spinal cord -> muscle relaxation
• Potential for overdose with EtOH (respiratory depression)
• Diazepam (Valium®), lorazepam (Ativan®), clonazepam (Klonopin®),
alprazolam (Xanax®)
212
What class drug is buspirone?
Azapirone Class
213
What is the mechanism of Buspirone?
Inc effects of serotonin (5-HT). AKA: Serotonin Agonist
214
What are the characteristics of Buspirone?
* Not as sedating as benzodiazepines
* No abuse potential
* Only used for generalized anxiety, onset 2-4 weeks
215
Sedatives & Tranquilizers are prescribed for ___
Sedatives & Tranquilizers are prescribed for *acute anxiety, tension, sleep disorders*
216
What is the action of sedatives & tranquilizers?
Slow brain function
217
What are the short-term effects of sedatives & tranquilizers?
• Sleepy
• Uncoordinated initially, but
diminish
• High doses -> impairs memory, judgment & coordination, paranoid & suicidal ideation.
218
What are the short-term paradoxical reactions of sedatives & tranquilizers?
* Agitation
* Aggression
More common in elderly and pediatrics
219
What are the precautions of sedatives & tranquilizers?
Use of sedatives and tranquilizers with ETOH ->
| slow breathing and/or slow HR.
220
What are the long term effects of sedatives & tranquilizers?
• Physical dependence; when stopped abruptly -> withdrawal sxs: seizures
221
What are the effects of CNS depression?
* Slowing of heart rate and breathing (ANS)
| * Can affect other brain functions, resulting in problems with thinking, perception, movement, and speech
222
What are the characteristics of when CNS depression occurs secondary to CNS dx (stroke, MS, etc)?
• Thought to result from deficiency of norepinephrine (NE) or serotonin (5HT)
• Antidepressants ↑ availability of one of both of NTs in the
CNS synapse by inhibiting their re-uptake by pre-synaptic
neuron
223
What are the characteristics of when CNS depression is caused by drugs (CNS depressants)?
Include barbiturates, alcohol and benzodiazepines.
224
What are the complications seen when CNS depression is caused by drugs (CNS depressants)?
Fatal coma, most commonly occurs when 2 or more CNS depressants are used in combination
225
What are the characteristics of major depression as defined by the American Psychiatric Associations Diagnostic and Statistical Manual Disorders?
• Depressed Mood or loss of interest in activities that usually
produce pleasure (anhedonia)
• Loss of energy, fatigue
• Indecisiveness
• Difficulty, thinking and concentrating
• Inappropriate feelings of guilt and worthlessness
• Loss or appetite or excess eating
• Sleep disorders (hypersomnia or insomnia)
• Obsession with death, thoughts of suicide
226
___ are indicated for patients with a major depressive disorder
*Antidepressant Medications*
| are indicated for patients with a major depressive disorder
227
What are the first line (more tolerable than tricyclics) antidepressant medications?
Selective serotonin reuptake inhibitors (SSRI)-Fluoxetine (Prozac), Sertraline (Zoloft), citalopram (Celexa)
228
Which antidepressant medications are very anticholinergic, and are an OD potential?
Tricyclic Antidepressants “ine”– • Imipramine (Tofranil)
• Clomipramine (Anafranil)
• Amitriptyline (Elavil)
• Nortriptyline (Pamelor)
229
What are the Monoamine oxidase inhibitors (MAOIs) used as an antidepressant medications?
* Isocarboxazid (Marplan), tranylcypramine (Parnate)
| * Restricted diet, anticholinergic, lots of drug-drug interactions
230
What is the mechanism of action Tricyclic Anti-Depressant (TCA)?
```
• Block reuptake of amine NT at
presynaptic terminal ->
• Prolonged stimulation decreases receptor sensitivity
->
• Depression decreases
```
231
What are the side effects of Tricyclic Anti-Depressant (TCA)?
(include) Muscle Weakness, Sedation, highest OD risk
232
What is an example of Tricyclic Anti-Depressant (TCA)?
Amitriptyline
233
What are the characteristics of Anti-Depressant Drugs: MAO Inhibitors?
* Not usually front-line treatment
| * 2 forms or types of MAO inhibitors (A,B)
234
What are the side effects of Anti-Depressant Drugs: MAO Inhibitors?
* Restlessness
* Irritability
* Increased BP
* Food interactions
235
What is an example of Anti-Depressant Drugs: MAO Inhibitors?
Isocarboxazid
236
What is the MOA of Tricyclic Anti-Depressant (TCA)?
• Drug inhibits MAO enzymes
that break down neurotransmitters located at amine synapses ->
• More neurotransmitter
remains in synaptic cleft ->
• Neurotransmitters have more time to exert effects: depression
decreases
237
What are the characteristics of a tricyclic antidepressants overdose?
Lethal—70 to 80% die before reaching the hospital
• CNS and cardiovascular systems are mainly affected
• Death results from seizures or dysrhythmias
238
What are the ways to manage a tricyclic antidepressants overdose?
* Decrease drug absorption with activated charcoal
* Speed elimination by alkalinizing urine
* Manage seizures and dysrhythmias
* Basic life support
239
How long does it take for the symptoms of MAOIs Overdose to appear?
12 hours after ingestion
240
What are the symptoms of MAOIs Overdose?
* Tachycardia
* Circulatory collapse
* Seizures
* Coma
241
What is the treatment of MAOIs Overdose?
Protect brain and heart, eliminate toxin
• Gastric lavage
• Urine acidification
• Hemodialysis
242
What are the PT concerns for antidepressant drugs?
• Patient perception of the rehabilitation process
being positively influenced by medications
• Active cooperation and continuity of treatment session may be compromised due to side effects
• Fall prevention
• HTN crisis
• Suicidal tendencies
243
What are the types of medicines that include pain and antidepressants?
* Duloxetine (Cymbalta)
| * TCAs
244
What are the parameters of pain and antidepressant: Duloxetine (Cymbalta)?
* Used for diabetic neuropathy and fibromyalgia
| * Serotonin-norepinephrine reuptake inhibitor
245
What is the most common medication that is considered a TCA for pain and antidepressant?
Amitriptyline (Elavil)
246
What is pain and antidepressant amitriptyline (Elavil) used for?
Used for neuropathy and migraine prevention
247
What are the uses of second-gen antidepressants?
• Used for depression—very few serious side effects
• Obesity
• Eating disorders
• Obsessive-compulsive disorder
• Panic disorder, Generalized Anxiety
• Myoclonus
• Treatment of various substance abuse problems
(bupropion [Zyban] is used for smoking cessation treatment)
248
What are the CNS side effects of Second-Generation
| Antidepressants?
* Headache
* Dizziness
* Tremor
* Nervousness
* Insomnia
* Fatigue
249
What are the GI side effects of Second-Generation
| Antidepressants?
* Nausea
* Diarrhea
* Constipation
* Dry mouth
250
What are the other side effects of Second-Generation
| Antidepressants?
* Sweating
| * Sexual dysfunction
251
What is the indications of CNS stimulants for anorexiants?
Stimulates the hypothalamus to release NE, thus reducing appetite
252
What is the indications of CNS stimulants for ADHD?
Stimulate the areas in the brain responsible for mental alertness and attentiveness by blocking the re-uptake of DA and NE
253
What is the indications of CNS stimulants for Narcolepsy?
Increase mental alertness
254
What is the indications of CNS stimulants for Narcolepsy?
Caffeine, co-administered with other drugs, used to treat
| headaches. Vasoconstriction minimizes migraine pain
255
What are the parameters for the side effects of CNS stimulants?
* Wide range, dose related
| * Tend to “speed up” body systems
256
What are the common adverse effects of CNS stimulants?
* Palpitations
* Tachycardia
* Hypertension
* Angina
* Dysrhythmias
* Nervousness
* Restlessness
* Anxiety
* Insomnia
* Nausea
* Vomiting
* Diarrhea
* Increased urinary frequency
257
What is the MOA for amphetamine?
Block the reuptake of norepinephrine and dopamine into the presynaptic neuron and
increase the release of these monoamines into the extraneuronal space.
258
What is the clinical use for amphetamine?
* Narcolepsy
| * Attention-deficit hyperactivity disorder
259
What are the adverse effects of amphetamine?
* Cardiovascular: Hypertension (7% to 22%, pediatric )
* Endocrine metabolic: Weight loss (4% to 9%, pediatric; 11%, adults)
* Gastrointestinal: Abdominal pain (11% to 14%, pediatrics ), Loss of appetite (22% to 36%), Xerostomia (35% )
* Neurologic: Headache (26% ), Insomnia (12% to 17%, pediatric; 27%, adults )
* Psychiatric: Feeling nervous (6% )
260
What are the contraindications of CNS Stimulants: Amphetamines?
* Glaucoma
* Hyperthyroid
* CV disease
* Drug abuse history
* Agitation
* Anxiety
* Tourette’s syndrome
261
What are the considerations of CNS Stimulants: Amphetamines?
* Empty stomach
* 1st dose wakening
* Last dose 6 hrs before bed
* ADHD benefits in 3-4 wks
* Avoid caffeine, colas, chocolate, tea, ETOH
* No abrupt discontinuation
* Withdrawal: HA, N/V, myalgia, depression, fatigue, hunger
262
What are the side effects of CNS Stimulants: Amphetamines?
```
– Restlessness, insomnia,
hyperactivity, talkative
– Palpitations, arrhythmias
– Tachycardia
– CV collapse
– Dry mouth
– N&V
– Impotence
– Libido change
– Growth suppression
– Dependence & abuse
– Dyskinesia
```
263
What are the common CNS Stimulants: Amphetamines?
* Amphetamine (Adderall®)
* Dexroamphetamine (Dexadrine®)
* Dexmethylphenidate (Focalin®)
* Methylphenidate (Ritalin®; Concerta®; Metadate®; Methylin®)
264
What are the characteristics of CNS Stimulants: Amphetamines?
• For ADHD; narcolepsy
• Inhibits catecholamine reuptake; blocks DA & NE transporter -> ↑ concentration
of DA and NE in cleft
• Improves attention, in prefrontal cortex maintain alertness, increases wakefulness; enhances performance
265
What are CNS stimulants?
Drug that tends to ↑ behavioral activity when administered
266
What are the disorders treated with CNS stimulants?
• Obesity
• Narcolepsy
• Attention Deficit Hyperactivity Disorder (ADHD)/ Attention
Deficit Disorder (ADD)
267
CNS stimulants act by facilitating...?
* Initiation and
| * Transmission of Action Potentials (AP) to excite other neurons.
268
New CNS stimulants act selectively to do what?
To inhibit reuptake or norepinephrine (NE) in the nervous system
269
What are the contraindications for CNS Stimulants: Anorexiants
(appetite suppressant)?
* Narrow Angle glaucoma
* Hyperthyroid
* CV disease
* Drug abuse history
* < 12yrs old
* Agitation
* Anxiety
* Tourette’s syndrome
270
What are the considerations for CNS Stimulants: Anorexiants
| (appetite suppressant)?
* Give on empty stomach
* Take 6 hrs before bed
* No OTCs - can lead to a fatal reaction
271
What are the effects of Diethylpropion (Tenuate®) stimulants?
1. Elevate Mood
2. Increase Motor Activity
3. Increase Alertness
4. Decrease need for Sleep
272
What can does the overdose of Diethylpropion (Tenuate®) lead to?
Convulsion & death
273
What are the side effects of Diethylpropion (Tenuate®) stimulant?
```
• Restlessness, insomnia
• Palpitations
• Dysmenorrhea
• Tachycardia
• Reverse HTN treatment
• Decrease seizure
threshold
• Dependence and abuse
```
