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62 Cards in this Set
- Front
- Back
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What are the clinical features of Parkinson's Disease? (4)
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1. Tremor (at rest)
2. Rigidity 3. Bradykinesia = extreme slowness in movement 4. Mask-like expression |
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What can Parkinson's Disease be a complication of?
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1. Influenza epidemic of 1918
2. certain medications 3. MPTP toxicity 4. other neurologic disorders -Progressive Supranuclear Palsy -Shy-Drager Syndrome -Creutzfeld-Jacob Disease |
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What is the pathophysiology of Parkinson's Disease?
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Loss of Nigrostriatal Dopamine neurons = pale Substantia Nigra
Loss of Dopaminergic innervation of the Basal Ganglia |
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What are the 2 families of Dopamine receptors?
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D1-like = D1 & D5
D2-like = D2, D3, & D4 |
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What is important for the greatest efficacy in therapeutic strategy for Parkinson's treatment?
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balance between D1 & D2
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What is the Primary Strategy in Parkinson's treatment? Secondary?
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Primary = replace Dopamine
Secondary -Dopamine agonists -block Dopamine catabolism -Anticholinergics -Antivirals |
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Since Dopamine does not cross the BBB, what is given to replace it?
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L-DOPA
"The Lazy Dog Naps Easily" |
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What are the pharmacological effects of L-DOPA?
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Motor = reversal of rigidity, tremor, & bradykinesia
Psychic -improved mental function -sense of well-being |
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What are the Early Side Effects of Levodopa (L-DOPA)?
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GI = N/V = due to stimulation of the Chemoreceptor Trigger Zone (CTZ) (very common)
Cardiovascular -Postural Hypotension (very common) = due to stimulation of D1 Dopamine receptors in Kidney & Vasculature -HTN, esp. w/ Sympathomimetics -Arrhythmia -Tachycardia Neuroendocrine -decreased Prolactin secretion = due to stimulation of D2 receptors in Pituitary |
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What are the long-term Motor side effects of L-DOPA?
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1. fluctuations in efficacy
2. "on-off" - symptoms reappear periodically 3. "wearing off" - effects don't last as long |
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What are the long-term Neurological side effects of L-DOPA?
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Abnormal movements
-Dystonia -Dyskinesias -Chorea **this is very common |
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What are the long-term Psychic effects of L-DOPA?
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Hallucinations, Paranoia, Mania, Anxiety, Depression
-due to stimulation of dopamine receptors in targers of the Mesolimbic & Mesocortical pathways -can lower dose or treat with newer Antipsychotics that do not tend to produce EPS |
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What are the long-term Neuroendocrine side effects of Levodopa?
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Renewed Sexual interest & behavior
Hypersexuality |
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L-DOPA Pharmacokinetics:
1. Route of Administration 2. Absorption 3. Peak Levels 4. t1/2 5. Metabolism & excretion |
1. Oral
2. dependent on GI transit time 3. 1/2 to 2 hrs after administration 4. 1-3 hours 5. >95% decarboxylated in periphery & excreted in urine |
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What is L-DOPA virtually always administered with? Why?
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Carbidopa
-Increases Levodopa to the brain -can used decreased doses -decrease side effects, esp. GI |
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Non-ergot D2/D3 Dopamine agonists
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1. Pramipexole
2. Ropinerole "Ropin some Prami's" with D2/D3 |
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2 Ergot Dopamine Agonists
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Bromocriptine
Pergolide |
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D1/D2 Dopamine agonist
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Apomorphine
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What is the mechanism of action of the Dopamine agonists?
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Agonist at D2 & other Dopamine receptors
Activity at D3 receptor may confer greater efficacy & may mediate neuroprotective effects |
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Which Dopamine agonists may be used as Monotherapy or with L-DOPA?
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D2/D3 agonists = Pramipexole & Ropinerole
**others are used with L-DOPA in pts with "on-off" or whose symptoms are not controlled by L-DOPA |
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What are the side effects of the Dopamine Agonists?
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N/V
Postural Hypotension Hallucinations |
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Selective MAO-B inhibitor that blocks that catabolism of Dopamine
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Selegeline
"Select a Gel Line" that inhibits sweating "My Ass Off" (MAO-B) |
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What is the use of Selegeline?
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Adjunct to L-DOPA
-increases efficacy -decrease L-DOPA dose -decreases "on-off" effect |
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2 COMT inhibitors that block catabolism of Dopamine
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Tol-capone
Enta-capone "Al CAPONE watched the COuntry Music Television Inhibitor" |
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What are the uses of COMT inhibitors?
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Adjunct to L-DOPA
-increases efficacy -decrease L-DOPA dose -decreases "on-off" effect |
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What side effect can MAO inhibitors cause?
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Hypertensive Crisis
-esp. MAO-A inhibitors |
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What drugs can decrease GI motility and result in decreased absorption of L-DOPA?
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Anticholinergics
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What drug can increase L-DOPA metabolism?
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Pyridoxine = vitamin B6
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What are 2 Anticholinergics used to treat Parkinson's Disease? Why are they used?
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TRIHEXYPHENYDYL & BENZTROPINE
Block the actions of Striatal Interneurons = curb the excess Cholinergic activity |
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What are the side effects of Trihexyphenydyl & Benztropine?
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1. Constipation
2. Urinary Hesitance, retention 3. Mental confusion 4. Hallucinations |
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What antiviral is used to treat Parkinson's disease? What is a proposed mechanism?
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Amantidine
May release Dopamine and/or have anticholinergic properties **used as adjunt to L-DOPA |
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What are the side effects of Amantidine?
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Similar to Dopamine agonists
May produce Livedo reticularis, Peripheral Edema, & Headache |
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What is the cause of Drug-induced Parkinsonism?
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Blockade of Striatal Dopamine receptors
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What drugs most commonly produces Drug-induced Parkinsonism? What is the treatment?
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Antidopaminergic, antipsychotic drugs such as HALOPERIDOL
Tx = Trihexyphenidyl & Bentropine |
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What are the clinical features of Huntington's Disease?
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1. Progressive Chorea = abnormal involuntary movements
2. Progressive Dementia |
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What is the pathology of Huntington's Disease?
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Functional overactivity of Dopaminergic Nigrostriatal pathways due to loss of Striatal GABAergic neurons projecting to the Globus Pallidus
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What is the treatment for Huntington's Disease?
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Haloperidol
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What are the clinical features of Tourrette's Syndrome?
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Tics
Involuntary movements or outbursts |
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What is the pathology of Tourette's Syndrome?
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Unknown, but involves increased activity of Striatal neurons
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What is the treatment of Tourrette's Syndrome?
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Haloperidol
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What are Physiologic Postural Tremors? What receptors does it involve?
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Normal phenomenon enhanced by anxiety, fatigue, thyrotoxicosis, or administration of Sympathomimetics
Beta-1 & Beta-2 receptors |
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What are Essential Tremors? What receptors are primarily involved?
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Essential Tremor = neurological disorder characterized by shaking of hands (and sometimes other parts of the body including the head), evoked by intentional movements
Beta-1 receptors |
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What is the treatment for Tremors?
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Physiologic & Essential = Propranolol (Beta-1 & 2 blocker)
Essential = Metoprolol (Beta-1 selective) |
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What is "Spasticity"?
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Violent, painful, involuntary muscle contractions resulting from dysfunction or descending motor input
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What can cause Spasticity?
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Trauma, inflammation, or diseases such as Multiple Sclerosis & Cerebral Palsy
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What is the site of action of Diazepam as an Antispastic drug? What is its mechanism?
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Spinal & Supraspinal
Enhances GABAergic transmission at GABA-A receptors |
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What are the principal uses of Diazepam as an Antispastic drug?
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All types of Spasticity associated with Spinal Cord lesions
Cerebral Palsy |
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Diazepam as an Antispastic:
1. Administration 2. Duration of action |
1. Oral or IM
2. >24 hrs due to active metabolites |
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What is the site of action of Baclofen as an Antispastic drug? What is the mechanism?
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Gamma motor neurons in the Spinal Cord
GABA-B agonist = inhibits release of excitatory transmitters & increases threshold for excitation thus decreasing mono- & polysynaptic spinal reflexes |
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What are the side effects of Baclofen?
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1. Drowsiness
2. Insomnia 3. Weakness 4. Dizziness 5. Confusion **side effects can be decreased with Intrathecal administration |
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What are the principal uses of Baclofen?
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Spinal Cord injuries & Multiple Sclerosis
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Baclofen pharmacokinetics:
1. Administration 2. Half-life 3. Excretion? |
1. rapidly absorbed after oral administration
2. 3-4 hours 3. unchanged in urine |
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What is Dantrolene's site of action? What is its mechanism?
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Muscle
reduces muscle contraction by decreasing Ca++ release from Sarcoplasmic Reticulum |
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What are Dantrolene's side effects?
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Generalized Muscle Weakness
Hepatotoxicity *"Dan the Lean" man has muscle weakness & Liver problems |
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What are the principal uses of Dantrolene? What is another use?
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Paralysis & Hemiparalysis
Cerebral Palsy Multiple Sclerosis Malignant Hyperthermia = hereditary condition in which certain anesthetics (e.g., halothane) cause high body temperatures and muscle rigidity |
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Dantrolene pharmacokinetics:
1. Administration 2. Plasma half-life 3. Metabolism & excretion |
1. Orally
2. 9 hours 3. Hepatic metabolism & urine excretion "Dan the Lean" man gets oral for 9 hours |
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What is Botox's site of action as an Antispastic drug? What is it's mechanism?
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Muscle
Acts on Cholinergic vesicles to inhibit ACh release |
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What are the principal uses of Botox?
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Local muscle spasm & more generalized spastic disorders such as Cerebral Palsy
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Botox pharmacokinetics:
1. Administration 2. Duration of action? |
1. injected into muscle
2. weeks-months after a single injection |
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What 2 drugs are used for the treatment of acute muscle spasm cause by acute trauma or strain? What is their mechanism of action?
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Cyclobenzaprine & Carisoprodol
Act as either a sedative &/or at the level of the brain stem or spinal cord "Clarissa-Pro-Doll drives her Circle-Benz-aprine so much she gets sleepy (sedatives) & doesn't have muscle spasms" |
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What is Cyclobenzaprine structurally relted to? What is it not effective against?
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Tricyclic Antidepressants
Spasms due to Cerebral Palsy or Spinal Cord injury |
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What is Carisoprodol metabolized into? What is the significance of this?
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Meprobamate = sedative-hypnotic with abuse potential
"Clarissa the Pro Doll" has a daughter named "Me Probe a Mate" who is sedated all the time, with whom she is addicted to |
