2nd module - a bit more neuro (stroke, MS, park, vestibular) Flashcards
Cerebrum
cerebral cortex; motor, sensory, conscious function
basal ganglia
control of motor activities
diencephalon
thalamus and hypothalamus
mescencephalon and brain stem
vital function
cerebellum
coordination
limbic system
emotional and behavior
spinal cord
spinal cord
blood brain barrier
CNS capillaries lack the gaps that are seen in peripheral capillaries and instead hold tight junctions that prevent many substances from entering the brain and spinal cord.
Drugs attempting to exert their effects on the CNS must be able to pass from bloodstream into the brain and SC.
nonpolar, lipid soluble drugs able to cross by passive diffusion
polar and lipophobic copaounds are usually unable to enter.
other drugs may be able to enter by active transport or by endocytosis.
active transport systems exist that are responsible for removing drugs and toxins from the brain. This makes it difficult for drugs to ahve therapeutic levels.
Review of presynaptic neuro and postsynaptic neuron
action potential, synthesis, storage, release, reuptake, degradation, postsynaptic receptor, presynaptic “auto receptor”, membrane (drugs can affect all these areas)
ACH
acetyloholine, in cerebral cortex (many areas), basal ganglia, limbic and thalamic regions, spinal interactions, for excitation
ACH locations
cerebral cortex (many areas), basal ganglia, limbic and thalamic regions, spinal interactions
ACH general effects
EXCITATION
Norepinepherine
CNS location: neurons originating in brainstem and hypothalamus that project throughout other areas of brain
General effects: inhibition
Dopamine
CNS location: basal ganglia, limbic system
General effects: inhibition
neurotransmitter serotonin
CNS location: neurons originating in brain stem that project upward (to hypothalamus) and downward (to spinal cord)
General effects: inhibition
Neurotransmitter GABA (gamma-aminobutyric acid)
CNS location: interneurons throughout the spinal cord, cerebellum, basal ganglia, cerebral cortex
General effects: inhibition
neurotransmitter glycine
CNS location : interneurons in spinal cord and brainstem
General effects: inhibition
glutamate, aspartame neurotransmitter
CNS location: interneurons throughout brain and spinal cord
General effects: excitation
Substance P neurotransmitter
CNS location : pathways in spinal cord and brain that mediate painful stimuli
General effects: excitation
enkephalins neurotransmitter
CNS location : pain suppression pathways in spinal cord and brain
General effects: excitation
Stroke Drugs list
Thrombolytics
Anticoagulants
Antiplatelet Therapy
Antihypertensive agents
Angiotensin II receptor antagonists
anticholesterol agents/statins
antispasmodics/spasmolytics
antispastics
anticonvulsants
GABA receptor antagonists
Neurotoxins
Antidepressants
Ischemic stroke: blood clot
Drugs used
Thrombolytic Drugs
Tissue plasminogen Activator(T-PA) <> IV Alteplase
Converts plasminogen to plasmin -> degrades clot bound fibrin.
Clinical Indications/Implications:
Recognize signs of stroke: “BE FAST”
Determine ischemic or hemorrhagic
Ischemic: 3 -4.5 hours since onset
used for lysis of thrombi in arteries, pulmonary emboli, thrombi in stroke
Clinical Implications
Risk of hemorrhaging; look for signs of bleeding
Monitor vital signs, especially with aerobic exercise
Use of compression stocking, compression pumps
Drug <> Drug interactions
Antiplatelet therapy: Aspirin
recommended within 24 - 48 hours of AIS. delayed 24 hours if TPA was administered
Flaccid
complete a sense of resistance to elongation
hypotonia
decreased resistance to elongation
spastic hypertonia
increased resistance to elongation that increases with FASTER stretch (VELOCITY DEPENDENT), usually more predominant in muscle on one side of affected joints in stroke/TBI (or in both agonists and antagonists in affected areas following SCI) and more obvious toward the end of the range when the muscle is on maximal stretch
Rigid hypertonia
increased resistance to elongation that does not increase with faster stretch (present even at slow speeds) often present in muscles on both sides of the joint and present through the range (though it may show a “cog - wheel pattern)
Spastic hypertonia is ________ dependent
velocity
Baclofen (Tone drug?)
MOA: acts as a GABA agonist, inhibits transmission at SC: inhhibitory effect on excitatory neurons that synapse with the alpha motor neuron (presynaptic inhibition)
Adverse reactions: dizziness, fatigue, weakness, drowsiness
Clinical Implications:
monitor changes in spasticity, strength, or mood/behavior
blood pressure
Drug <> Drug: CNS depression with other CNS depressants
Dantrolene Sodium/Dantrium (Tone drug?)
MOA: Ca 2+ release is inhibited when dantrium binds to ryanodine type 1 receptor on the calcium channels in SKELETAL muscle SR
Adverse reactions: drowsiness, weakness, diarrhea, hepatotoxicity
Clinical Implications: monitor signs of hepatotoxicity, spasticity, dizziness,
Drug <> Drug: CNS depression with other CNS depressants, hepatotoxicity, risk of arrhythmia. Use cautiously with cardiac, pulmonary or previous liver disease
Diazepam/Valium
Classification: anti anxiety, anticonvulsants, muscle relaxant sedative
MOA: depresses the CNS, potentiating GABA. Skeletal muscle relaxation by inhibiting spinal polysynaptic afferent pathways.
Adverse reactions: dizziness, drowsiness, lethargy
Clinical Implications:
assess spasms, pain, ROM, dizziness, drowsiness, BP
can acuse physical dependence
Drug <> Drug: CNS depression with other CNS depressants/antihistamines/opioids, fluoxetine/metoprolol/propoxyphene/propranolol/valproic acid may decrease metabolsimf of diazepam. may decrease the efficacy of levodopa
Gabapentin
Classification: analgesic adjunct, anticonvulsant
MOA: debatable. Gaba agonist, allowing Cl- into cell vs inhibiting specific calcium channels in presynaptic terminal -> decreases release of glutamate and other (+) NT.
Adverse reactions: confusion, depression, drowsiness, ataxia
Clinical Implications: monitor signs of drowsiness, confusion, dizziness, monitor pain, paresthesias, may increase risk of suicidal ideation,
Drug <> Drug: antacids may decrease absorption, risk of CNS depression, morphine increases gabapentin levels -> risk of toxicity
Tizanidine
Classification: anti spasticity (pharm: adrenergic)
MOA: debatable. alpha-adrenergic agonist, reduces spasticity by increasing presynaptic inhibition of motor neurons.
Adverse reactions: anxiety, depression, dizziness, sedation, weakness, hypotension, abdominal pain, skin ulcers, back pain, paresthesia. May slow recovery in acute phase of stroke or TBI
Clinical Implications: monitor signs of spasticity, back pain, paresthesias, dizziness, depression, hallucinations, BP. Has been used for chronic pain as well.
Drug <> Drug: risk of hypotension with other alpha adrenergic antihypertensives, CNS depression,
Botox
Normal Phys: Protein receptors direct vesicles to fuse with the surface and allow AcH to be released.
MOA: inhibits the release of acetylcholine which decreases local muscle activity. Used to inhibit contraction of intrafusal muscle fibers in the skeletal muscle, some literature in effects on CNS.
Adverse reactions: headache, nausea, local muscle weakness, allergic reactions
Clinical Implications: education, effects last 2-3 months, to maximize effects engage in serial casting/ROM etc to maintain muscle range.
Parkinson’s disease
Neurodegenerative condition that progresses as a slow degeneration of dopamine-secreting neurons in the basal ganglia.
Issues with medical management
Dopamine does not cross the blood brain barrier
Which drug does not cross the blood brain barrier, relative to parkinsons?
dopamine
Parkinson’s disease
Usual drug that treats this
Primary Drug: Carbidopa-Levodopa (sinemet)
Levodopa - precursor to dopamine, able to cross BBB.
Carbidopa: decarboxylase inhibitor, prevents premature levodopa breakdown.
Adverse Reactions: Gi issues: nausea/vomiting, arrhythmias, dyskinesias: chorea, athetosis, ballismus, dystonia, behavioral changes, diminished response, on/off phenomenon
Parkinsons disease
Other drugs that treat it
Dopamine Agonists: Bromocriptine, ropinirole (table 10-2), apomorphine: use in advanced PD,
Clinical implications: sometimes used alone in early Parkinsonism, used alongside sinemet can produce optimal results with smaller dosage,
Adverse reactions: GI issues, confusion, hallucinations
Anticholinergic Drugs: deficiency in striatal dopamine is associated with increased activity in cholinergic pathways in the BG.
Clinical implications: drugs that limit AcH transmission can help with symptoms of tremor and rigidity.
Adverse reactions: AcH agents are nonselective which may result in CNS side effects, cardiac irregularities, dry mouth, and urinary retention.
Amantadine: useful in reducing dyskinesias and motor complications with levodopa and advanced PD.
MOA: effects likely from blocking NMDA receptor in brain -> inhibiting glutamate. More research underway
Monoamine Oxidase B Inhibitors: selegiline, rasagiline
MOA: inhibit the MAO-B enzyme which is responsible for breaking down dopamine. Inhibiting the enzyme prolongs the local effects of dopamine at the synapse.
Catechol-o-methyltransferase inhibitors: entacapone, tolcapone
MOA: inhibit the enzyme catechol-o-methyltransferase (COMT) which converts levodopa to an inactive metabolite. Prevent levodopa conversion in peripheral tissues.
Clinical implications: may prolong “on” times.
Adverse reactions: dyskinesias
Multiple sclerosis
autoimmune disease - inflammation, selective demyelination of the CNS
guillain barre syndrome definition
autoimmune disease - inflammation, selective demyelination of the PNS
MS management
Corticosteroids: used to treat acute relapses because of their anti-inflammartory and immunosuppressive effects.
Plasmapharesis: Remove harmful antibodies in the blood. Mainly used for RRMS.
Disease-modifying therapeutic agents: Prevent future progression of disease but do not return function.
Includes interferons which slow down the immune system byblocking activated T cells from crossing blood brain barrier
Ocrevus: monoclonal antibody that binds to a molecule on the surface of B cells and depletes them from circulation
Vestibular and inner ear disorder treatment drug
Meclizine: Antivert
Classification: Antiemetic, antihistamine
MOA: central anticholinergic, CNS depressant and antihistaminic properties. Decreases excitability and conduction between the middle ear and cerebellar pathways.
Clinical implications: Long term use can limit vestibular recovery.
