Pharm - 28: Drugs Used In Parkinsonism & Other Movement Disorders

Front 1

What are the 5 main classes of drugs used for Parkinson's disease

Back 1

Dopamine Precursor
Dopamine Agonists
MAO Inhibitors
COMT Inhibitors
Muscarinic antagonists

Front 2

Parkinson's involves degeneration of what part of the brain?

Back 2

Substantia nigra pars compacta dopaminergic neurons

Front 3

What are the main symptoms of parkinson's?

Back 3

RAFT (plus more)

Rigidity
Akinesia/Bradykinesia
Flat Facies
Tremor at REST

Front 4

Why does Parkinson's cause decreased movement, and not increased movement?

Back 4

The dopaminergic neurons from the substantia nigra pars compacta are degenerated, and no longer stimulate the direct pathway or inhibit the indirect pathway.

Front 5

Where does ACh come into play with the direct and indirect pathways?

Back 5

ACh stimulates the Inhibition of GPe on Subthalamic nucleus

Front 6

What 2 antipsychotic drugs cause a reversible parkinson-like syndrome? How?

Back 6

Butyrophenone
Phenothiazine

*Block brain Dopamine receptors*

Front 7

How does reserpine cause parkinson-like syndrome?

Back 7

By depleting brain stores of dopamine

Front 8

What chemical causes irreversible parkinsonism through destruction of dopaminergic neurons in the nigrostriatal tract

Back 8

MPTP

Front 9

Which dopamine receptors normally promote the direct pathway?

Back 9

D2

Front 10

Which dopamine receptors normally inhibit the indirect pathway?

Back 10

D1

Front 11

Can dopamine, levodopa, and carbidopa cross the blood brain barrier?

Back 11

Dopamine, and Carbidopa do NOT cross the BBB

Levodopa does cross BBB

Front 12

How does Levodopa enter the brain?

Back 12

via an L-amino acid transporter

Front 13

How is levodopa converted to dopamine?

Back 13

via Aromatic L-amino acid decarboxylase (DOPA Decarboxylase)

Front 14

What is the function of Carbidopa?

Back 14

*Inhibits DOPA decarboxylase in peripheral tissues*

Doesn't cross BBB, so prevents Levodopa from being decarboxylated to dopamine and being used up in the periphery. Doesn't affect the brain's levodopa levels.

Decreases the peripheral side effects of levodopa.

Front 15

Which parkinson's symptom does levodopa treatment ameliorate the most?

Back 15

Bradykinesia

Front 16

How do COMT inhibitors help with the use of levodopa?

Back 16

Improve the fluctuations in responses to levodopa

Front 17

What are the main adverse effects of levodopa?

Back 17

Anorexia, Nausea, vomiting
Postural hypotension
Tachycardia, asystole, arrhythmias
Behavioral problems: Anxiety, depression, confusion, agitation, delusions, hallucinations

Front 18

Which patients are Levodopa and bromocriptine contraindicated in?

Back 18

Pt's with a history of Psychosis

Front 19

What are 2 ergot alkaloid dopamin agonists used for parkinson's?

Back 19

Bromocriptine

Pergolide (discontinued)

Front 20

What is the action of Bromocriptine?

Back 20

Partial agonist at the D2 receptor in the brain.

Increases the functional activity of dopamine neurotransmitter pathway

Front 21

What are the main adverse effects of Bromocriptine?

Back 21

Anorexia, nausea, vomiting
Postural hypotension
Arrhythmias
Dyskinesias
Behavioral: confusion, hallucination, delusions
Ergot-related effects: Pulmonary infiltrates, erythromelalgia

Front 22

What are some nonergot dopamin receptor agonists?

Back 22

Pramipexole

Ropinirole

Front 23

What receptors do pramipexole and ropinirole act on?

Back 23

Ropinirole = pure D2 agonist

Pramipexole = increased D3 affinity

Front 24

Adverse effects of pramipexole and ropinirole

Back 24

Anrexia, nausea, vomiting (min. by taking w/ meals)

Dyskinesias, postural hypotension, lassitude, sleepiness.

Front 25

Which drug has a neuroprotective role on the brain by scavenging for hydrogen peroxide?

Back 25

Pramipexole

Front 26

In which patients should the dose of pramipexole be reduced?

Back 26

pts. with Renal dysfxn

Front 27

How is ropinirole metabolized?

Back 27

Liver: CYP1A2

Also metabolizes Caffeine and WARFARIN

Front 28

What drug is used for "off" periods in off-on phenomenon, pt's using dopaminergic therapy?

Back 28

Apomorphine

Temporary relief (1-2h)

Front 29

What should you pretreat pt's with before giving apomorphine?

Back 29

Trimethobenzamine

Front 30

Action of amantadine

Back 30

Enhances dopaminergic neurotransmission

Muscarinic blocking action too

Front 31

Which drug causes livedo reticularis?

Back 31

Amantadine

Front 32

Mechanism of action of selegiline and Rasagiline

Back 32

Inhibit MAO Type B

Both inhibit MAO type A at high doses

Front 33

What is MAO type B?

Back 33

It metabolizes dopamine in preference to norepinephrine and serotonin, os decreases dopamine levels. Inhibiting MAO type B may increase brain dopamine levels

Front 34

Selegiline combined with what drug can cause death?

Back 34

Meperidine

Front 35

Which Parkinson's drug is involved in serotonin syndrome?

Back 35

Selegiline

Front 36

What is COMT?

Back 36

Catechol-O-Methyltransferase

Converts levodopa to 3-O-methyldopa (3OMD)

Front 37

Why are COMT inhibitors used in parkinson's patients?

Back 37

Increased levels of 3-O-methyldopa are associated with poor response to levodopa, b/c 3OMD competes with levodopa for active transport into the CNS.

Front 38

COMT Inhibitors are used with levodopa-carbidopa therapy, and prolong ______

Back 38

"on-time"

Front 39

What are COMT inhibitors what are used?

Back 39

Entacapone

Tolcapone

Front 40

Adverse effects of COMT inhibitors

Back 40

Orange urine
+
Same as related to Increased leveles of Levodopa

Front 41

Adverse effects of Tolcapone

Back 41

Acute Liver failure

should moniter LFT's

Front 42

Anticholinergic drugs used in parkinson's

Back 42

Benztropine

Trihexyphenidyl

Front 43

Which parkinson's symptons are improved by Anticholinergics?

Back 43

Tremor and rigidity

Little effect on bradykinesia

Front 44

Adverse effects of Anticholinergics

Back 44

Atropine-like effects

Front 45

What drugs can be used for Essential and physiological tremor?

Back 45

Propranolol (Beta blocker)

Metoprolol (Beta-1 selective)

Primidone (Antiepileptic)

Front 46

When should you watch out when giving Propranolol to pt's with tremor?

Back 46

Pt's with CHF
Asthma
Diabetes
Hypoglycemia

Front 47

Which drug can you for Tremor in pt's with co-existing Pulmonary disease?

Back 47

Metoprolol

Front 48

Huntington's diasease involves an imbalance between which two systems of the Basal Ganglia?

Back 48

Diminished GABA functions

Enhanced Dopaminergic functions

Cholinergic deficit

Front 49

How are Choline acetyltransferase levels affected by Huntington's disease?

Back 49

Decreased

Front 50

Drug therapy used for Huntington's

Back 50

Amine-depleting drugs: Reserpine, tetrabenazine

Dopamine receptor antagonists: haloperidol

Front 51

Drug therapy for Tourette's

Back 51

Haloperidol

D2 receptor blockers: Pimozide

Carbamazepine, clonazepam, clonidine

Front 52

What drugs induce Parkinson-like syndrome

Back 52

Antipsychotics

Front 53

What causes Tardive dyskinesia?

Back 53

older antipsychotics

Cant be reversed, or treated with other dugs.

Front 54

What is Wilson's Disease?

Back 54

Recessive disorder in Copper metabolism, yielding copper deposits in Liver and brain and damage.

Front 55

How do you treat Wilson's disease?

Back 55

Penicillamine

a copper chelating agent

Front 56

What is the preferred treatment for Restless Leg syndrome?

Back 56

Ropinirole

Dopaminergic therapy

Front 57

* Irreversible condition resulting form the use of antipsychotics, reserpine at high doses, and MPTP (byproduct of illicit meperidine analog)

Back 57

Drug-induced Parkinsonism

Front 58

*Agent used in drug therapy of Parkinson's instead of Dopamine which has low bioavailability and does not cross BBB

Back 58

L-dopa

Front 59

* This is combined with L-Dopa, inhibits DOPA decarboxylase (active only peripherally) which allows lower effective doses of L-dopa and allows for fewer SE's (GI distress, postural Hypotension, & Dyskinesias)

Back 59

Carbidopa

Front 60

Clinical response that may fluctuate in tx of Parkinson's disease

Back 60

"on-off phenomenon"

Front 61

Anti-parkinson's drug that increases intraocular pressure and is contraindicated in closed angle glaucoma

Back 61

Levodopa

Front 62

Ergot alkaloid that is a parial agonist at D2 receptor in the brain, used for pt's who are refractory or cannot tolerate levodopa, causes erythromelalgia.

Back 62

Bromocriptine

Front 63

Non ergot agents used as first-line therapy in the initial management of Parkinson's

Back 63

Pramipexole and ropinirole

Front 64

Enhances dopaminergic neurotransmission SE's including CNS excitation, Acute toxic psychosis and livedo reticularis

Back 64

Amantadine

Front 65

Inhibitor of MAO type B which metabolizes dopamine, used adjunct to levodopa or as sole agent in newly diagnosed pts.

Back 65

Selegiline

Front 66

Inhibitors of catechol-O-methyltransferase (COMT), used as adjuncts in Parkinson's dz and cause acute hepatic failure (need to monitor LFT's)

Back 66

Entacapone & Tolcapone

Front 67

Agent decreases the excitatory actions of cholinergic neurons. May improve tremor and rigidity but have LITTLE effect on bradykinesia. Atropine-like side effects

Back 67

Benztropine

Front 68

Agent effective in physiological and essential tremor

Back 68

Propranolol

Front 69

Agest used in Huntington's disease

Back 69

Tetrabenazine (Amine depleting)

Haloperidol (antipsychotic)

Front 70

Agents used in Tourette's disease

Back 70

Haloperidol or Pimozide

Front 71

Chelating agent used in Wilson's disease

Back 71

Penicillamine