Alzheimer's/Park/Hunt/ALS Rx- Dersh Flashcards
Levodopa
Mechanism?
Adverse effects?
Use?
Caution
MOA:
- Dopamine Precursor (Converted to Dopamine in Brain)
- Increases [DA] concentration in presynaptic terminals
- Given with Carbidopa (Inhibits AAAD) to prevent peripheral breakdown into DA (which can not cross BBB)
AE: (A UNH DOC)
- Arrhythmia
- Upset Stomach Vomiting
- Nausea (Stimulates CTZ)
- Hallucinations
- Dyskinesias (Choreiform, dystonia)
- Orthostatic Hypotension
- Confusion and Psychosis
AE:
-Formation of Hydrogen Peroxide (H2O2) which is neurotoxic.
Rx:
- Mild to Moderate PD
- Reduces Tremors, rigidity, bradykinesia
Note: When discontinuing the drug, slowly taper in order to prevent neuroleptic malignant syndrome.
Note: caution and tape with MAO-I to avoid hypertensive crisis.
Bromocriptine
Mechanism?
AE?
Use?
MOA:
- Ergot Derivative
- Dopa Agonist (D3, D2, & Partial D1)
AE: “PROV” it “Bro”
- Pulmonary Fibrosis
- Retroperitoneal Fibrosis
- Orthostatic Hypotension (Partial D1 agonism)
- Vasospasm (Avoid use in Lupus and Reynauds Pts)
Rx:
- Mild to Moderate PD
- To block Increased GH and Prolactin in endocrine patients. Recall Dopamine is inhibitory in this function.
Note:
- Must take Drug Holidays to prevent Pulmonary Fibrosis
- Don’t forget Ergot Poisoning Triad
- “An OLE HAG”
Pramipexole
Mechanism?
AE?
Use?
MOA:
- D3 and D2 Agonist
- D3 > D2
- Not an Ergot (so no D1 agonism)
- Longer Duration than Bromocriptine***
AE:
-Similar to Bromocriptine except: no Orthostatic Hypotension and no Fibrosis.
Rx:
-Mild to Moderate PD
What are the advantages of Dopamine Agonists over Levodopa?
Mnemonic: NSNL
- No H2O2 production
- Selective for DA receptor subtypes
- No enzyme requirement by the intact neuron to convert it.
- Longer duration of action
What is Ergot? And What is the Ergot Triad?
- Ergot is a fungus that grows on grain (especially Rye).
- Can be Poisonous (especially to an old “HAG”)
Triad of Ergot Poisoning: HAG
- Hallucinations (5HT2 agonism, Lysergic acid)
- Abortion (Direct stimulation of Uterine tissue)
- Gangrene (alpha adrenergic agonist –> Vasoconstriction, –> Necrosis)
Note: Bromocriptine derived from Ergot family.
Ropinirole
Mechanism?
AE?
MOA:
- D3 and D2 Agonist
- D3 > D2
- Not an Ergot (so no D1 agonism)
- Longer Duration than Bromocriptine***
- Ropinirol available in sustained release preparation
AE:
-Similar to Bromocriptine except: no Orthostatic Hypotension and no Fibrosis.
Rx:
-Mild to Moderate PD
Selegiline
Mechanism?
Adverse effect?
Use?
MAO: “Selective Selegiline”
- Selective Inhibitor of MAO-B (Only in CNS)
- Decreases DA metabolism
- Decreases neuronal production of H2O2.
- Active Metabolites (amphetamine and methamphetamine)
- Available in Transdermal and ODT form to avoid 1st pass metabolism and production of metabolites.
AE: (IME)
- Insomnia (active metabolites)
- May potentiate adverse motor effects of levodopa in progressed PD.
- Euphoria (active metabolites)
Rx:
- First line therapy for Early PD
- Delays the use for Levodopa (Recall that tolerance to levodopa builds quickly)
Note: Does not inhibit MAO-A found in the gut, therefore patients do not need to modify diet to avoid tyramine induced hypertensive crisis.
Rasagiline
Mechanism?
AE?
MOA:
- Selective Inhibitor of MAO-B (10x more Potent than Selegiline)
- Decreases DA metabolism
- Decreases neuronal production of H2O2.
- Metabolized into inactive compounds
AE:
- Less toxic than Selegiline
- Hypertensive Crisis if co-administered with CYP1A2 inhibitors (Ciprofloxacin, fluvoxamine).
Note: At high concentrations it loses selectivity for MAO-B.
Rx:
- Used as first line PD treatment.
- Delays use of Levodopa.
Amantadine
Mechanism?
AE?
MOA:
- NMDA Antagonist
- Muscarinic Receptor Antagonist (reduces Tremor)
AE:
- Insomnia
- Concentration difficulty
- Enxiety (anxiety)
- Seizure exacerbation
Rx:
- Used to treat Early PD (Can also be used in conjunction with other drugs in advanced PD therapy).
- Initially used to prevent Influenza A in high risk populations.
Tolcapone
Mechanism?
AE?
Use?
MOA:
- COMT Inhibitor
- Inhibit catechol-O-methyltransferase (COMT), therefore inhibits levodopa metabolism in periphery.
- Increases circulating half life of Levodopa.
- Long acting, take 2-3x per day
AE: Al Capone shoots you in the liver.
- Hepatic Necrosis (Pts must have Liver monitored regularly)
- Caution in raising Levodopa concentrations too much.
Rx:
-Used with Levodopa to treat PD
Entacapone
Mechanism?
AE?
Use?
MOA:
- COMT Inhibitor
- Inhibits COMT, therefore reduces Levodopa metabolism in the periphery.
- Increases circulating half life of Levodopa.
- Short acting, take 4-6x per day
AE:
-Caution for Increasing Levodopa concentrations too much.
Rx:
-Used with Levodopa to treat PD
Note: COMT Inhibitors are less toxic than DA agonists and Muscarinic Antagonists.
Levodopa Refractoriness
Manifests as decreased duration of effect after each dose. May lead to On/Off Phenomenon.
On/Off Phenomenon:
- Alternating periods of Severe Choreiform movement and near-total rigidity
- Short periods of functional motor ability in between.
Note: These are end-stage symptoms. More frequent Levodopa dosing and supplement with other PD drugs can help symptoms.
Inhibitors of Acetylcholinesterase
Mechanism?
AE?
Mnemonic: DR. GT (These drugs make the mind faster, GT)
MOA:
- Potentiates Cholinergic transmission by inhibiting Acetylcholinesterase.
- Results in better memory and cognitive function
AE: DNV BIN
- Cholinergic Excess Side effects:
- Diarrhea
- Nausea
- Vomiting
- Bradycardia
- Insomnia
- Nightmares
AChE Inhibitor Drugs: DRGT
- Donepezil
- Rivastigmine
- Galantamine
- Tacrine
Donepezil
Mechanism?
AE?
Use?
MOA:
- Acetylcholinesterase Inhibitor
- Available as ODT to bypass the GI effects.
AE: DNV BIN
- Cholinergic Excess (DNV)
- Bradycardia
- Insomnia
- Nightmares
Rx:
-Mild to Moderate Alzheimer’s
Rivastigmine
Mechanism?
AE?
Use?
MOA:
- Acetylcholinesterase Inhibitor
- Available as Transdermal patch
AE:
-Cholinergic Excess (DNV)
Rx:
-Mild to Moderate Alzheimer’s
