Type of solubility that passes BBB - Answers Lipid soluble
Low weight passes BBB easier
Parkinson's disease - Answers Neuro degenerative disease
Destruction of dopaminergic neurons in the substantia negra (black substance)
Causes a progressive reduction in dopamine action in the basal ganglia leading to motor control
function
Parkinsonian pharmacology goal - Answers To restore dopamine in the basal ganglia & antagonizing
the excitatory effect of acetylcholine at the muscarinic receptors
Reinstates balance of dopamine/acetylcholine
Does not stop or reverse neuronal degeneration
Glutamate Antagonist (Amantadine) - Answers Enhances dopaminergic neurotransmission &
muscarinic blocking
Used for minor symptoms
Caution in patients with seizures & CHF
Anticholinergic (antimuscarinic) agents - Answers Decreases the excitatory actions of cholinergic
neurons on cells in the striatum by blocking muscarinic receptors
Improves tremor & rigidity but not bradykinesia
Benxtropine (Cogentin) - Answers Antimuscarinic
Can cause narrow angle glaucoma
Caution in elderly, BPH, urinary retention, liver, renal or GI disease
Dopamine Receptor Agonists - Answers Pramipexole (mirapex) & ropinerole (requip)
Treatment for mild Parkinson's
Used in restless leg syndrome
Use in combo with levadopa
Monamine Oxidase B Inhibitors (MAO-B) - Answers Selegiline (eldepryl) & rasagiline (azilect)
Used in early disease & as adjunct RX with levadopa
Do not combine with fluoxetine or meperidine due to additive effects
Dopamine Precursors - Answers Levadopa & carbidopa (sinemet)
Enhances synthesis of dopamine in surviving neurons of the substantia nigra conversion of levodopa
to dopamine
Overtime the number of available neurons decreases so drug does not work forever
Works to decrease symptoms only while drug is present in the body
Levodopa - Answers Attempts to replace dopamine
Crosses BBB
short half life- "on off phenomenon" due to unstable levels
Taken on empty stomach
Levodopa ADE - Answers NV and anorexia
Tachycardia, PVCs, postural hypotension
, Mydriasis
CNS effects- hallucinations, abnormal involuntary movements, dyskinesias, mood changes
C/I in hx of psychosis
Levodopa Carbidopa Combination - Answers Potent & effective
Carbidopa enhances the effect of levodopa by allowing more availability to cross into the CNS
significantly reduces severity of symptoms
Typical decline in response in 3rd to 5th year of treatment
COMT Inhibitors - Answers Entacapone (comtan)
Increases uptake of levadopa resulting in increased concentration of dopamine in CNS
Adjunct therapy with Levodopa carbidopa
Frequent dosing
Don't use MAO & COMT together (both metabolize catecholamines)
Alzheimer's Disease - Answers Progressive memory impairment, dementia, & cognitive dysfunction
Alzheimer's Disease Pharmacologic Therapy - Answers Goal is to improve cholinergic transmission in
the CNS & prevent excitotoxic actions resulting from overstimulation of NMDA glutamate receptors
Palliative & modest short term benefit
Cholinesterase Inhibitors - Answers Mild to moderate Alzheimer's
Can be initiated by PCPs
Block enzymes that degrade acetylcholine leaving more acetylCh at the synaptic cleft
Only helps slow progression of symptoms, not the disease
1/3 rule
NMDA receptor antagonist - Answers Namenda
Moderate to severe
Often given together with cholinesterase inhibitors
100% bioavailability with or without food
Neuroprotective
Dose reduction in renal impairment
GABA Analog - Answers Gabapentin used for tonic clonic, partial & generalized seizures
Pregabalin used for partial seizures
Decrease excitatory transmission
Not metabolized, elderly well tolerate
Fosphenytoin & Phenytoin - Answers first line for generalized convulsant and seizure disorders and
status epilepticus
zero order pharmacokinetics
Fosphenytoin & Phenytoin ADE - Answers gingival hyperplasia, folic acid deficiency
multiple drug interactions