OHIA AD and PD Flashcards
TorF: Carbidopa is an inhibitor of AADC
True
Carbidopa effectively prevents the conversion of levodopa to
DA in the __________ and __________ leading to an increased availability of this drug in the CNS.
Carbidopa effectively prevents the conversion of levodopa to
DA in the GASTROINTESTINAL TRACT and PERIPHERAL TISSUES leading to
an increased availability of this drug in the CNS.
What is the MOA of DA precursors?
-Restores dopaminergic transmission in the striatum by enhancing the synthesis of DA in the surviving neurons of the substantia nigra
pars compacta
-Decreases the rigidity, tremors and other symptoms of PD
Levodopa/carbidopa can be used in the tx of:
motor fluctuations in advanced Parkinson’s disease
These compounds enhance dopaminergic neurotransmission by
activating postsynaptic DA receptors:
Drugs in this class includes ropinirole and pramipexol.
TorF: DA receptor agonists have a shorter half life compared to LDOPA
False. They have longer durations of action than levodopa (8-24 h v. 6-8h)
and therefore, have been effective in patients exhibiting fluctuations
in their response to levodopa.
TorF: DA receptor agonists are peptide molecules that compete with LDOPA to cross the BBB
False. These drugs are non-peptide molecules, they do not compete with levodopa for transport across the blood-brain barrier.
TorF: DARA require enzymatic conversion by AADC and, therefore, can be effective late in the course of PD.
False: These drugs do not require enzymatic conversion by AADC
and, therefore, can be effective late in the course of PD.
TorF: DARA is associated with less risk of developing dyskinesia and motor fluctuations when compared
to patients started with levodopa therapy.
True
DARA can be used in the tx of:
Idiopathic PD and Restless Legs Syndrome.
this class include selegiline, rasagiline
INHIBITORS OF DA METABOLISM
TorF: Rasagiline is metabolized to methamphetamine and
amphetamine
False. Selegiline is metabolized to methamphetamine and
amphetamine. Rasagiline does not form such toxic metabolites.
TorF: Both selegiline and rasagiline can improve motor function in PD when used alone and both can potentiate the effectiveness of levodopa therapy
True
Selegiline and rasagiline are used:
as adjunct to levodopa/carbidopa in Parkinsonism.
Tolcapone and Entacapone ________ the peripheral metabolism of levodopa, thereby increasing central uptake and brain concentrations of DA.
They DECREASE METABOLISM of levodopa, thereby
INCREASING UPTAKE and brain concentrations of DA.
_____________ can cross the blood-brain barrier and inhibit COMT in the
brain
Tolcapone can cross the blood-brain barrier and inhibit COMT in the
brain
TorF: Entacapone is only distributed into peripheral tissues.
True
TOLCAPONE and ENTACAPONE is used in the tx of:
Adjunct to levodopa/carbidopa in idiopathic Parkinsonism
especially in patients who have symptom fluctuations
ANTIMUSCARINIC AGENTS incl
Drugs in this class includes BENZTROPINE and TRIHEXIPHENIDYL.
BENZTROPINE and TRIHEXIPHENIDYL block __________ receptors and reduce cholinergic tone in the CNS.
BLOCK MUSCARINIC RECEPTORS and REDUCE CHOLINERGIC TONE in the CNS.
These drugs are presumed to act by modifying the activity of striatal cholinergic interneurons that regulate the interactions of neurons of the direct and indirect pathways.
TorF: BENZTROPINE and TRIHEXIPHENIDYL reduce tremor more than bradykinesia.
True
How are benzotrpine and trihexiphenidyl used?
Adjunct in Parkinsonism
Drug-induced extrapyramidal disorders.
An antiviral agent used in the prophylaxis and treatment of influenza.
Has an anti-Parkinson’s disease action.
AMANTADINE
What are the effects of AMANTADINE on neurotransmitters?
- Increases the release of DA
- Blocks cholinergic receptors
-Blocks NMDA glutamate receptors (major pathway involved in
PD)
TorF: Amantadine has little or no effect on tremor but is effective against
rigidity and bradykinesia
True
Alzheimer’s disease (AD) refers to dementia that does
not have antecedent causes such as stroke, brain trauma
or alcohol.
Typically, dementia begins after age 60 with prevalence:
- doubling approximately every 5 years thereafter
- in persons aged 85 or older, around 50% have this disease.
Two microscopic features are characteristic of AD:
-EXTRACELLULAR AMYLOID PLAQUES, consisting of amorphous extracellular
deposits of β-amyloid protein (known as Aβ).
-INTRANEURONAL NEUROFIBRILLARY TANGLES, comprising filaments of a
phosphorylated form of a microtubule-associated protein (Tau).
Aβ accumulation is an upstream event that triggers tau pathology resulting in:
Aβ accumulation is an upstream event that triggers tau pathology resulting in impaired neuronal function and cell loss.
The most prominent feature of AD is:
deficiency of acetylcholine
Anatomical basis of ACh deficit is due to:
-Atrophy and degeneration of subcortical cholinergic neurons
especially those in the nucleus basalis of Meynert NBM).
-NBM is a pivotal cholinergic relay system projecting widespread innervation to the cortex and medial temporal lobe structures.
TorF: donepezil is an irreversible inhibitor of acetylcholinesterase (AChE) with preference for the enzyme located in the brain.
False. It Is a REVERSIBLE inhibitor of acetylcholinesterase (AChE) with
preference for the enzyme located in the brain.
Donepezil drug intx:
Antagonizes anticholinergics.
May potentiate succinylcholine-type muscle relaxants, cholinergic agonists.
Concomitant NSAIDs may increase risk of GI bleeds.
Rivastigamine inhibits:
reversible inhibitor of AChE.
Also inhibits butyrylcholinesterase (serum and hepatic
cholinesterase that is upregulated in AD brain).
Active orally or transdermally.
Rivastigamine intx:
Antagonizes anticholinergics
May potentiate succinylcholine-type muscle relaxants
Concomitant metoclopramide, beta-blockers not recommended
Rivastigamine uses:
Mild to moderate dementia for AD
Mild to moderate dementia associated with Parkinsonism
What class of medication is Galantamine apart of:
CHOLINESTERASE INHIBITORS
Galantamine intx:
Potentiates neuromuscular blockers, cholinesterase inhibitors, cholinergic agonists.
Antagonizes anticholinergics
May be potentiated by substrates for CYPs (ketoconazole, paroxetine, cimetidine.)
Memantine drug class:
NMDA RECEPTOR ANTAGONIST
TorF: memantine is a competitive NMDA-type glutamate receptor antagonist
False. a noncompetitive of the NMDA-type glutamate receptor.
Memantine interacts with the _______ binding site of the channel to prevent its excessive activation
Interacts with the Mg2+ binding site of the channel to prevent its
excessive activation.
Memantine MOA:
noncompetitive of the NMDA-type glutamate receptor.
Interacts with the Mg2+ binding site of the channel to prevent its
excessive activation.
Reduces the rate of clinical deterioration in patients with moderate
to severe AD.
TorF: Urinary disorders is a SE of memantine
True
Memantine drug intx:
Drug Interactions:
Caution with other NMDA antagonists (e.g., amantadine,
ketamine)
May affect renally-excreted drugs (e.g., triamterene, cimetidine,
metformin, nicotine, ranitidine)
Plasma levels may be increased by urinary alkalinizers.
Parkinson’s disease (PD) is a progressive neurological disorder of muscle movement characterized by
Bradykinesia (slowness and poverty of movement)
Muscular rigidity
Resting tremor (which usually abates during voluntary movement)
An impairment of postural balance leading to disturbances of gait and to falling.
Nonmotor manifestation of PD include:
depression,anxiety, psychosis, cognitive changes, fatigue, sleep disorders and autonomic disorders.
TorF: Dementia or mild cognitive impairment will eventually develop in most patients.
True
PD has been correlated with the destruction of ______ neurons in the ___________ that provides innervation to the striatum (caudate and putamen)
PD has been correlated with the destruction of DA neurons in the
SUBSTANTIA NIGRA PARS COMPACTA that provides innervation to the
striatum (caudate and putamen), parts of the basal ganglia
system involved in motor control.
Indirect pathway:
PUTAMEN—>GPe—>STN—>GPi—>THALAMUS—>cortex
The net effect of stimulating the indirect pathway at the level of the
striatum is to reduce the excitatory outflow from the thalamus to the cerebral cortex.
Direct pathway:
Signals from putamen to GPi to thalamus and then to cortex
The net effect of stimulation of the direct pathway at the level of the
striatum is to increase the excitatory outflow from the thalamus to
the cortex.
