Final Exam - Section VII Flashcards
Define tremor, chorea, ballismus, athetosis, and dystonia?
- Tremor: Rhythmic movement around a joint; tremor at rest is a hallmark of Parkinsonism.
- Chorea: Muscle jerks in various areas
- Ballismus: Violent abnormal movements.
- Athetosis: Slow, writhing, twisting movements.
- Dystonia: abnormal posture
What is the relationship between the basal gangila, thalamus, and motor cortex?
Motor cortex- sends information the the muscles for movement and to the basal ganglia cells, which relay information to the thalamus.
Thalamus- sends signals to the motor cortex to slow down or enhance movement, fine tuning them.
Basal ganglia - regulates activity of the thalamus, primarily by the substantia nigra (SN). The SN releases dopamine which inhibts and excites information to the thalamus.
What is the pathology of movement related disorders?
The substantia nigra dopaminergic neurons are degraded, leading to decreased dopamine levels.
Dopamine is inhibits muscle movements.
What are the common signs of Parkinson’s disease?
TRAP
T- tremor
R - rigidity
A - akinesia; loss or impairment in power of voluntary movement
P - posture and balace instability
What is the function of synuclein?
Describe the conditions where abnormal synuclein is found?
Found in the substatia nigra that is normally diffuse within the cell. In Parkinson’s, synuclein is misfoldied and aggregated together called Lewy bodies.
Lewy Bodies are found in Parkinsons, and Alzheimers.
What is the MOA of Levodopa?
Why is it given with carbidopa?
- Levodopa is a prodrug that is converted to dopamine in the body, but only 1-3% cross into the brain
- Carbidopa increases crossing of the BBB to 10% by preventing breakdown by DOPA decarboxylase and COMT in the periphery
What are the adverse effects of levodopa and their treatments?
- Anorexia
- Dyskinesias
- Tachycardia, a fib (low incidence)
- N/V - improved with carbidopa
- Depression, anxiety, hallucinations, delusions (high incidence)
-Made worse by carbidopa
-Can be treated with Pimavanserin (Nuplazid), an antipsychotic that is an inverse agonist of the 5-HT2a receptor in the visual cortex.
What is the MOA of apomorphine?
Derivative of morphine that is a dopamine agonist
What is the “On-Off” Phenomenon?
Periods of increased mobility, followed by marked akinesia; associated with long term Levodopa use
What is the pathogenesis of Huntington’s disease?
Treatments?
- GABA is reduced in the basal ganglia
- Tetrabenazine - dopamine receptor antagonist
- Dopamine receptor blockers (Haloperidol)
- Genetic counseling, speech and physical therapy
Diagram the cell damage pathways (COX and LOX)
Describe the two different COX isoforms?
- COX-1 – Always present allows for important homeostatic functions in the GI tract, renal tract, platelet function, and macrophage differentiation. Inhibition undesirable
- COX-2 - expressed due to stimulation and leads to inflammatory response
Describe the MOA of aspirin’s irreversible inhibition?
Irreversibly blocks COX-1 by acetylation of serine 529.
This prevents arachidonic acid interacting with COX.
This prevents formation of TXA2 and platelet aggregation
What is the black box warning for NSAIDS?
Increased risk of cardiovascular events (MI, stroke) and GI bleeding
What are the benefits and drawbacks of COX-2 selective inhibitors?
Drug?
Benefits: No effect on COX-1 functions (less GI upset, no impact on platelet aggregation)
Drawbacks: Increased risk of serious CV events due to inhibition of PGI2
Celecoxib
What are the indications for diclofenac and indomethacin?
Indomethacin
* Rheumatism
* Gout
* Patent ductus arteriosus
Diclofenac
* Reduce arthritic pain
* Comes in a topical form
Why is acetaminophen not an NSAID?
It selectively inhibits COX-2 in the CNS and does not have much effect on the arachidonic acid pathway in the periphery
It has no anti-inflammatory effects
Describe the acute and chronic effects of glucocorticoids?
Acute is good, chronic is bad
Attributed to cortisol levels
What is the MOA of glucocorticoids?
- Inhibit immune response by blocking transcription/translation
- Increases Annexin-1 which suppresses phospholipase A2 and leukotriene response
- Increases secretory leukoprotease inhibitor (SLPI)
- Increases IL-10 - immunosuppressive enzyme
- Decreases NFkB which is proinflammatory
What are DMARDs?
Disease Modifying Anti-Rheumatic Drugs
Used to reduce inflammation and decrease damage to bones and joints
List the 3 biologic DMARDs and their MOA?
- Abatacept (Orencia) - Blocks T cell activation
- Rituximab (Rituxan) - Depletes B-lymphocytes
- Adalimumab (Humira) - anti TNF-alpha
Describe the 3 main fibers for sensation transmission?
- A beta fiber (myelinated) – transmits non-noxious mechanical stimuli
- A delta fiber (myelinated) - transmits noxious heat and mechanical stimuli like sharp pain. Produces initial reflex response.
- C fiber (unmyelinated) - transmits noxious heat, chemical, and mechanical stimuli (slow, burning pain).
Describe the 3 tracts in the CNS?
- Spinothalamic - (primary pain pathway) transmits signal through the thalamic nuclei to the somatosensory cortex.
- Spinoreticular - (emotional sensation) transmits signal through the reticular formation of the pons, then thalamus, then somatosensory cortex.
- Spinomesencephalic - Mu opiod receptors in the periaqueductal (PAD) grey matter of the brainstem can release endorphins to supress pain signaling.
What is the degree of tolerance for the different opiod effects?
Describe/draw the biochemical metabolism of ethanol?
- Normal pathway is alcohol dehydrogenase pathway
- Chronic users also utilize the microsomal ethanol-oxidizing system (MEOS)
What are the sedative-hypnotic barbituates and their receptor target?
- Phenobarbital, thiopental, methohexital
- GABAa receptor at level of cell wall
Explain the drug development phases?
List the purported benefits of ginseng, milk thistle, and saw palmetto
