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Flashcards in Neurodegeneration Deck (17)
1

levodopa

Enhancer of DA synthesis

Precursor of DA that crosses BBB

Decreases rigidity, tremors, and other symptoms of parkinsonism

After 3-5 years patients experience decline in response to medication ("wearing off" effect)

Orally available, rapidly absorbed from small intestine

Only 1-3% of L-DOPA reaches brain, rest is metabolized peripherally by aromatic amino acid decarboxylase

Short half life (1-2hrs)

Side Effects:
- Peripheral side effects due to conversion to NE
- Nausea, vomiting, anorexia, cardiac arrthymias, orthostatic hypotension

CNS side effects:
- Visual and auditory hallucinations, abnormal involuntary movements (dyskinesia), may cause mood changes:
- Depression,
- Psychosis
- Anxiety

Drug of choice for Parkinsonism, especially late stage

2

L-DOPA+carbidopa

Increase DA synthesis

Combined therapy

Carbidopa (aromatic I-amino acid decarboxylase INHIBITOR blocks the metabolism of L-DOPA peripherally to allow availability

Allows reduction of L-DOPA by 4-5 fold to reduce the side effects of DA

3

entacapone

Enhancers of DA Synthesis

Inhibits catechol-O-methyltransferase to further decrease peripheral metabolism of Levodopa to allow availability of L-DOPA availability for the brain

4

apomorphine

Dopamine Receptor Agonist

Acute treatment for patients with ADVANCED Disease
or "Off" periods (marked bradykinesia, immobility)

Administered via subQ injection NOT IV
- IF IV may lead to thrombus formation/pulmonary embolism

SIDE EFFECTS:
- Nausea, vomiting, arrthymias, postural hypotension, hallucinations, pronounced sleepiness



5

bromocriptine

DA receptor Agonist

D2 agonist
D1 partial agonist

Effective as monotherapy early in disease or as adjunct to L-DOPA in later states of Parkinsonism

Orally active

Being with low dose:
- 1.25 mg/twice daily
- Gradually increase to reach therapeutic effect while keeping SE minimal
- Increase 2.5 mg every 2 weeks until benefit occurs
- Usual maintenance is 10-30 mg/day

Side Effects:
- Cardiovascular Effects:
- Cardiac arrthymias, postural hypotension
- Neurological effects: Depression ,hallucinations, sleepiness, impulsivity, confusion
GI problems: N/V
Contraindications: Patients with mental problems

6

pramipexole

DA receptor AGONIST

D2 Agonist
D3 Agonist

Effective monotherapy early in disease

Orally active

Begin with low doses and gradually increase until desired effect is seen

7

ropinirole

DA receptor AGONIST

D2 Agonist
D3 Agonist

Effective monotherapy early in disease

Orally active

Begin with low doses and gradually increase until desired effect is seen

8

amantadine

Mixed action Parkinson's drug therapy

Alleviates: Bradykinesia and rigidity
- Not helpful for tremors
- Useful for patients with mild to moderate disease prior to initiating L-DOPA

Mechanism:
- Moderately increase DA release
- Blocks cholinergic Muscarinic receptors
- Blocks glutamatergic NMDA receptors

Side Effects:
- Hallucinations/confusion
- Nausea
- dizziness
- Rash on low extremities
- Special caution when prescribing to patients with CHF and GLAUCOMA

Was developed as an antiviral for treatment of influenza

9

benztropine

Antagonist of Muscarinic Cholinergic Receptors

Parkinson's disease drug therapy

Used to alleviate:
- Tremor
- Rigidity
- NOT helpful in bradykinesia

Monotherapy or along with other drugs

Mechanism:
- Loss of nigrostriatal neurons from Parkinson leads to increased firing of striatal cholinergic interneurons for overstim of M receptors
- M receptor antagonist will block this effect

Side Effects:
- Typical antimuscarinic effect
- Blurred vision (loss of accomodation)
- Urinary retention
- Constipation
- Aggravation of glaucoma
- Delirium, psychosis, memory impairment

10

trihexyphenidyl

Antagonist of Muscarinic Cholinergic Receptors

Parkinson's disease drug therapy

Used to alleviate:
- Tremor
- Rigidity
- NOT helpful in bradykinesia

Monotherapy or along with other drugs

Mechanism:
- Loss of nigrostriatal neurons from Parkinson leads to increased firing of striatal cholinergic interneurons for overstim of M receptors
- M receptor antagonist will block this effect

Side Effects:
- Typical antimuscarinic effect
- Blurred vision (loss of accomodation)
- Urinary retention
- Constipation
- Aggravation of glaucoma
- Delirium, psychosis, memory impairment

11

rasagiline

MAOb inhibitor

Decrease DA catabolism

Not metabolized to amphetamine like substance

12

selegiline

MAOb inhibitor

Decrease DA catabolism

Decreases production of hydrogen peroxide, limit formation of neurotoxic free radicals

Adjunctive therapy in parkinson's patients receiving levodopa

Little benefit if taken alone

Orally active

Half life: 7-9hrs

Renal Excretion

Metabolized to methamphetamine and amphetamine

Insomnia

13

donepezil

Acetylcholinesterase Inhibitor

Treatment in Alzheimers

Block catabolism of acetyl choline to increase amount of ACh in presynaptic terminals

Produce modest improvement in some patients, may retain for several years

Good oral bioavailability

Variable pharmacokinetic and half life time

Half life: 70 hours

Metabolized by p450 enzymes:
- CYP3A4
- CYP2D6

Side effects:

- Tremors
- Bradycardia
- Nausea
- DIarrhea
- Anorexia

14

galantamine

Acetylcholinesterase Inhibitor

Treatment in Alzheimers

Block catabolism of acetyl choline to increase amount of ACh in presynaptic terminals

Produce modest improvement in some patients, may retain for several years

Good oral bioavailability

Variable pharmacokinetic and half life time

Half life: 7 hours

Metabolized by p450 enzymes:
- CYP3A4
- CYP2D6

Side effects:

- Tremors
- Bradycardia
- Nausea
- DIarrhea
- Anorexia

15

rivastigmine

Acetylcholinesterase Inhibitor

Treatment in Alzheimers

Block catabolism of acetyl choline to increase amount of ACh in presynaptic terminals

Produce modest improvement in some patients, may retain for several years

Good oral bioavailability

Variable pharmacokinetic and half life time

Half life: 1.5 hours

Metabolized by:
PLASMA CHOLINESTERASE

Side effects:

- Tremors
- Bradycardia
- Nausea
- DIarrhea
- Anorexia

16

tacrine

Acetylcholinesterase Inhibitor

Treatment in Alzheimers

Block catabolism of acetyl choline to increase amount of ACh in presynaptic terminals

Produce modest improvement in some patients, may retain for several years

Good oral bioavailability

Variable pharmacokinetic and half life time

Half life: 3 hours

Metabolized by:
- CYP3A4
- CYP2D6

Side effects:
- Hepatotoxicity

- Tremors
- Bradycardia
- Nausea
- DIarrhea
- Anorexia

17

memantine

NMDA antagonist

Treatment of Alzheimer's disease

NMDA receptor antagonist (low affinity), deriviative of AMANTADINE

Blocks NMDA receptor to protect neurons from Ca overload that can lead to neuronal death (excitotoxicity)

Improved daily acitivities and cognitive function

Benefits are additive when given DONEZEPIL

SIDE EFFECTS:
- Dizziness
- Headache
- Confusion
- Agitation
- Constipation