Advanced Pharmacology Exam 2
Neurology Part 1
Alzheimer’s Disease (Ach Deficiency)
- Progressive degenerative disease ultimately resulting in cerebral atrophy
- Signs and Symptoms: Difficulty performing tasks, difficulty reading and writing, loss of memory and delusions, depression and ag...
advanced pharmacology exam 2 neurology part 1 alzheimer’s disease ach deficiency progressive degenerative disease ultimately resulting in cerebral atrophy signs and symptoms difficulty perfor
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Advanced Pharmacology Exam 2
Neurology Part 1
Alzheimer’s Disease (Ach Deficiency)
- Progressive degenerative disease ultimately resulting in
cerebral atrophy
- Signs and Symptoms: Difficulty performing tasks, difficulty reading
and writing, loss of memory and delusions, depression and
agitation.
Medications used in the treatment of Alzheimer’s Disease:
Cholinesterase Inhibitors:
- Donepezil (Aricept) = May cause Insomnia
- Rivastigmine (Exelon) = Hepatoxicity
- Galantamine (Razadyne) = Weight Gain
o Mechanism of Action: Selectively inhibit cholinesterase [enzyme
that hydrolyzes (inactivates) Ach] in the CNS
▪ (Increase Ach concentrations in the cerebral cortex)
o May slow deterioration of cognitive function
▪ Preserves memory, learning and attention.
o Side Effects (ALL): Diarrhea, Urination, Miosis,
Bronchospasm, Emesis, Lacrimation, Salvation (SLOWLY
TITRATE)
o Drug Interactions: Anticholinergic Drugs, Donepezil is a minor
substrate of CYP 3A4
o Cholinergic Crisis S/Sxs: Salivation, Lacrimation,
Urination, Defecation, Gastric Upset, Emesis
NMDA receptor antagonist
, - Memantine (Namenda)
o Mechanism of Action: NMDA (glutamate receptor) antagonist
▪ Attenuates excitotoxic effects of
glutamate (neuroprotective)
o No CYP 450 drug interactions
o Indicated for moderate to severe disease
▪ Often used in combination with cholinesterase inhibitors
o Adverse Effects:
▪ Constipation
▪ Headache, confusion, dizziness, hallucinations
▪ Hypertension
o Available in combination with donepezil (Namzaric)
o Both formulations given via oral route
- Combination
o Donepezil + Memantine (Namzaric)
Parkinson’s Disease (Lack of Dopamine)
- Degenerative disease of the basal ganglia, resulting in gradual decline in
motor, autonomic and cognitive functioning.
- Severe loss (about 80%) of dopaminergic neurons of the substantia nigra
o Presence of Lewy Bodies (intracellular inclusions)
o Creates imbalance of acetylcholine and dopamine
- No treatment = progresses to an akinetic state (5-10 years) Mortality due
to immobility (aspiration pneumonia, clotting disorders)
- DA receptors (5 totals, grouped into D1 and 2)
o D1 – stimulate synthesis of cyclic AMP (excitatory)
2
, o D2 – Inhibit cyclic AMP synthesis, suppress CA currents, activate
K currents (inhibitory)
Medications used in the Treatment of Parkinson’s Disease:
Dopaminergic Agents:
- Levodopa
o Biosynthetic precursor of dopamine
▪ Increased the concentration of dopamine in the brain
o Metabolized in the peripheral tissue Decarboxylase and Catechol-O-
methyl transferase (COMT)
o Less than 1% of administered drug reaches the brain if given as
monotherapy (always need decarboxylase inhibitor and often
also need COMT-inhibitor)
o Adverse Effects:
▪ N/V (Antacid may help 30-60 minutes before dose)
▪ Orthostatic hypotension, sedation
▪ Depression, delirium, paranoia, delusions, hallucinations (CNS
effects associated with long-term use)
▪ Motor fluctuations (end of dose wearing off; peak-
dose dyskinesia)
o ALWAYS given in combination with Carbidopa.
Decarboxylase Inhibitor:
- Carbidopa
o Mechanism of Action: Inhibits conversion of levodopa to dopamine
in peripheral tissues
▪ Increase amount of levodopa that enters the brain
▪ Decreases GI and cardiovascular adverse effects due to
less conversion in peripheral tissue
o Wearing off phenomenon
3
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