Motor Dysfunction Disease

Pharmacology 000 with Johnson at University of California - Riverside

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By: Tung Tran
Created: 2011-01-29
Size: 21 flashcards
Views: 28

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What is Parkinson?

Caused by progressive degeneration of dopamine containing neurons in the substantia nigra pars compacta; however, there are also the degeneration of other neurotransmitter systems (i.e. cholinergic, adrenergic, sertonergic)

Mechanism of Action of Levodopa

MA: Remember that dopamine do not pass through the BBB and thus have no therapeutic effects in parkinsonism. Levodopa can pass through the BBB and convert into Dopamine by L-Dopa Decarboxylase

Dose Dependent Peripheral Actions of Dopamine

Low Concentration: activates DA receptor (D1) in renal, mesentery, coronary, and intracerebral vascular beds --> vasodilitation
Moderate concentration: causes release of NE and EPI (has sympathomimetic effects) --> increase rate and force contraction of heart and increase systolic BP but decrease in mean BP
High Concentration: activates alpha and beta1 receptor directly --> renal and mesentery vasoconstriction causing increase in BP and increase rate and force of contraction of heart

DA pathway and Receptor location

Mesolimbic pathway: important for memory and motivation and may play a role in schizophrenia (addicting drugs increase DA in this area)
Mesocortical pathway: mlafunction can result in symptoms of schizphrenia (hallucination and disordered thinking, antipsychotics block D2)
Nigrostriatal system: Degeneration associated with Parkinson's disease
Tuberoinfundibular DA pathway: influence secretion of prolactin (decrease)
DA receptor in CTZ: antiemetic effect

Adverse Effects of Levodopa

nausea or vomiting through activation of CTZ
mental changes (paranoid ideation and psychotic episode)
Adventitious movement (choreiform and/or dystonia)
Postural hypotension due to DA receptors
worsening peptic ulcers
Sweating
wearing off period (motor fluctuation)
Neuroleptic Malignant Syndrome (associated with abrupt withdrawal of levodopa)

Major Drug interactions with Levodopa

DA antagonist: Phenothiazines and other antipsychotics
Parasympathomimetic/cholinomimetics: i.e. pilocarpine, physostigmine
Non-selective MAO inhibitors: can result in hypertensive crisis and hyperpyrexia (must wait 14 days following discontinuation of MAOI before starting on DA agonist). Example: phenelzine and tranylcypromine

Interaction of Levodopa with Vitamins

Vitamin B6 (pyridoxine B6) are important cofactors needed for the conversion of Levodopa into dopamine by Levodopa decarboxylase

Larobec

A multiple vitamin without Vitamin B6 can be used in Levodopa overdose

Carbidopa

Allow the use of 20x less levodopa --> decrease levodopa toxicity and for more to enter into the brain

It does so by inhibiting the actions of Levodopa Decarboxylase

What is the drug with the trade name Sinemet

Levodopa + carbidopa

Centrally Active Dopamine Agonist

1st generation agonists

bromocriptine
apomorphine

2nd generation agonist

Ropinirole
pramipexole

Efficacy of Centrally Active Dopamine Agonists

Less effective than levodopa
less likely to cause dyskinesias and motor fluctuation

Adverse Effects of Centrally Active Dopamine Agonists

Nausea or vomiting
Neuropsychiatric side effects
Postural hypotension
Vasospasm
Ankle swelling
Retroperitonela fibrosis-accumulation of cell sin the back of the abdomen which may block ureters (rare and associated with ergots)

COMT inhibitors

Ex: Tolcapone and Entacapone
Use as an adjuvant with Sinemet
MA: Slow break down of dopamine
Reduce motor fluctuation and dyskinesias

Selegiline

Class: Selective MAO-B inhibitor
MA: recall that MAO-B are the predominant form found in the striatum and is responsible for the oxidative metabolism of DA. At low therapeutic concentrations, it acts to only irreversibly inhibit MAO-B. No effects on the peripheral, so no interactions with Tyramine. However, not its amphetamine like metabolites can cause cognitive side effect
Used as neuroprotectant and low efficacy agent
Rarely interacts with SSRI, TCA, and opiates

Anticholinergics

Class: Trihexyphenidyl, Benztropine, Diphenhydramine
Weak efficacy: used esp. for tremor and drooling
Adverse effects:

neuropsychiatric (hallucination, poor concentration/memory, confuse state)
Blurred near vision due to mydriasis and cycloplegia
aggravation of glaucoma
Anticholinergic effects: dry mouth, constipation, urinary retention in males with prostate enlargement
Abrupt withdrawal can exacerbate these symptoms

T/F diphenhydramine also are H1 blockers

true

Amantidine

Class: Antiviral agent
Used for mild parkinson. Used early as a monotherapy and then with the more efficacious sinemet when needed later
MA: unknown but is thought to stimulate the release of DA, block reuptake, and/or have antimuscurinic activity, and NMDA receptor antagonist
Good for short term use, but may take 2 weeks to work and must be withdrawn slowly

Baclofen

Class: analog of GABA
MA: A GABA_B agonist thought to work on spinal cord by activating K channel
Used to treat spasticity and Acute Muscle Spasm

Diazepam

Class: Benzodiazepine
MA: enhance GABA_A receptor (leads to increase chloride ion conductance)
Used to treat Spasticity and Acute muscle spasm

Dantrolene

MA: peripherally acts as a skeletal muscle relaxant by inhibiting calcium release within sarcoplasmic reticulum
Used to treat spasticity and muscle spasm

About this deck

By: Tung Tran
Created: 2011-01-29
Size: 21 flashcards
Views: 28

About StudyBlue

“I have been getting MUCH better grades on all my tests for school. Flash cards, notes, and quizzes are great on here. Thanks!”
Kathy