PD and AD Medications Flashcards
Pathophysiology of AD
AD and dementias are NOT normal aging
AD = Alzheimer’s Disease
Cortical Atrophy and loss of neurons
- in parietal and temporal lobes
- ventricualr enlargement = hydrocephalus
Microscopic Changes
- Neurofibrillary tangles
- amyloid plaques
Neurochemical cahnges
- decreased choline acetyltransferase :
in sum
- many pathways destroyed: loss of cholenerigc neurons is prominent (hence why we avoid anticholnerigcs at all costs)
- lost nicotinic receptors in hippocampus and cortex = whywe get the symptoms of memory lossand eventuall langugae
symptoms/signs of dementia
- memory loss (first)
- poor judgement
- dimished driving
- disorientation and inability to adapt
- insomina & sundowing (agitation)
- wandering and falling
- aggresivemenss
- personality cahnges
- communication issues
- emotional liability
- gait distubances
Medications that can aggrevated dementia and delirum
- opioids
- ANTICHOLENERGICs: avoid avoid avoid
- anticonvuslants (phenobarb)
- TCAS
- benzos
- cardio drugs (Digoxin, reserpine, methlydopa)
- ranitidine (H2)
- antipsychotics and lithium
Treatment Approach to Dementia
avoid anticholenergics
Treatment goals = increasd Ach in the cleft or decreased degradation of Ach OR decreased glutamate (the excitatory neruon)
cholinesterase inhibitors: block breakdown of acetylcholine by inhibiting cholinesterase enzyme
NDMA antagonists
Acetylcholinesterase Inhibitors
names
MOA
MOA
- block the breakdown of Ach in the cleft by inhibiting the acetylcholinesterase enzyme from wroking: increasing ACH
Names
- Donepezil : MC
- Rivastigmine
- Galantamine
Dosing = 5-10 mg with titrating up
Cholinesterase Inhibtiors
Side Effects
Drug Interactions
Side Effects
- cholenergic effects: SLUD
- salivation
- lacrimation
- urination
- DIARRHEA
- Nightmares donepezil: dont give at bedtime
- bradycardia (since cholenergic: parasymp)
- anorexia/WL
Drug Interactions
- anticholenerigcs: obv. will decrease effectivenss
- beta blockers, nondihydro CCB: will only increase the bradycardia
Memantine (NMDA antagonist)
indications
MOA
ADR
INdications
- moderate to severe AD try achinhibitiors first then these as disease progresses
MOA
- prevent excitatory toxicity (block glutamate receptors- the NMDA receptor)
- titrate dosing
ADR
- CNS: nervousness, agitation, vertigo, fatigue and dizziness
- Dirrhea and constipation: big big side effect here
namzaric is a combo med: memantine and donepizil
Anti-Amyloid Monoclonoal ab.
names
MOA
Aducanumab
Lecanemab
MOA
- monoclonoal ab. that target amyloid beta to reduce plaques
lots of adr and possible brain edema/ hemorrhage so not loved
Use of Antipsychotics in those with AD?
Indications
preferred meds
there is a BBW of increased death in dementia pt. if using these
Indications
- for the behavioral disturbances
Preferred Meds
- first line = you want to control with non-pharm
- rispridone
- ariprprazole
- olanzapine
Parkinson’s Disease
patho & Risk factors
Parkinson’s Disease
- onset in 60s
- rural living, well water and heavy metal exposure
Pathology
- destruction of the nirostriatal pathway: depletion of dopamine into the putamen (basal ganglia)
- the dopamine depletion is depleted in relation to teh amount of Ach in the body (so less DA relative to Ach)
- thus targets: decreased Ach or increase DA
Clinical Features
- bradykinesia: slow movements, freezing, masked facies +1 of…..
- limb/muscle rigidity
- resting tremor
- postural instability
Monoamine Oxidase INhibitors (MAO) -B
parkinsons treatment
MOA
who gets this
Selegiline speicifcs
Rasagiling Specifics
Safinamide specifics
MOA-B inhibitors
MOA: they inhibit MAO-B which degrades DA
who gets this
- younger pts. with no significantimpairment yet: give them rasagiline
Selegiline
- ADR: Nausea, dizzy, orthostatis hypotension, hallucinations
- active metabolite (ampheatmine: stimulation)
- no tyramine interactions
Rasagiline
- lots and lots of D-D interactions so this is for pt. who are younger with minimal medications
- ADR: N/V, dyskinesias, falls, postural hypotension, dry mouth
- tyramine interaction: hyertensive crisis possible; avoid cheeses, metas, red wine and soY
Safinamide
- can only be adjunct treatment: added onto carbadopa/levadopa
- need to titrate on/off
- watch with tyramined
- ADR: dyskinesia ,HTN, orthostatic hypotension/falls
- lots of D-D interactions
Anticholenergics for PD
MOA
Benefits
ADRs
Anticholenergics: Benztropine, Trihexphendiyl
MOA: block the cholenergic recptor: reduce Ach therefor restore the balane of DA to Ach
Benefits
- reduce tremor
- reduce sialorrhea
ADR
- dry mouth
- blurry vision
- constipation
- urinary retention
- sedation
- cognitive impairment!!!
Amatadine
MOA
indications
ADRs
Amatadine
MOA:
- blocks Da reuptake
- increased DA release
Indications
- mild PD
- add-on to help with levadopa-induced dyskinesias
- helpful to reduce tremor, bradykinesias and rigidity
ADR
- confusion
- sedation
- vivid dreams & hallucinations
- dry mouth
Carbidopa/Levodopa
MOA
INdications
ADR
the cornerstone for PD treatment
MOA
L-dopa: the active med
- thise works as the precursor to dopamine
- passes the BBB and converted in DA in the brain
Carbidopa: no effect alone
- inhibits the ability of L-dopa to be converted in the peripheral –> thus you have less periphearl conversion; localized to brain
- need approx. 75g/day
Side Effects
- N/V (carba decreases this)
- postural hypotension
- psychosis
- motor complications
Dosing of Carbadopa/Levodopa
- meal time consierations
- wearing-off effects
Dosing
- ER or IR can be given
- IR: can be good for first AM dose or to reduce freezing episodes faster
Meal Time
- the absorbtion can be decreased with the intake of a high protein meal!!
Motor Complications
- the longer the pt. on the med, the smaller the therapeduic window will be
- this occurs due to decreased neuronal storage of DA: need more doses to get same effect
- at overactive dosing: get dyskinesias
- at underactive: get stiffness, brdaykinesias
- thus a wearing on-off phenomenon
