Parkinson's disease (Test 1) Flashcards
Chronically progressive neurodegenerative disease
PARKINSON’S DISEASE
PARKINSON’S DISEASE Results from loss of dopaminergic neurons in the __________pars compacta region of the basal ganglia
substantia nigra
The presence of _______ is also a consistent feature of parkinson’s disease
Lewy bodies
Dopamine does not readily cross the blood brain barrier (bbb). Approaches to therapy have involved _________(precursor of dopamine) or drugs that mimic the actin of dopamine
Levodopa
Levodopa Crosses the bbb and is converted to dopamine by __________________
L-amino-acid decarboxylase (dopa decarboxylase enzyme)
Levodopa usually administered with a _______________.
peripheral decarboxylase inhibitor (carbidopa or benserazide)
Abrupt d/c of levodopa may result in a precipitous return of symptoms of Parkinson’s disease and associated with __________________-like syndrome.
Thus levodopa should be continued through the perioperative period
neuroleptic malignant-like syndrome
Inhibition of the peripheral activity of the _________ enzyme greatly increases the fraction of administered levodopa that remains intact to cross the bbb.
decarboxylase
Metabolism of Levodopa
metabolized in liver excreted by kidney
Most common SE (in first few weeks) with levodopa and dopamine agonists is __________ and ________.
nausea and hypotension
What color urine is normal with levodopa?
red or black
Levodopa may cause a _____ _____ tests: Test for antibodies in blood stream determining if the immune system is destroying the patient’s own blood cells causing anemia
Positive Coomb’s
Drug Interactions Levodopa:
Antipsychotic Drugs:
Butyrophenones and phenothiazines can antagonize effects of dopamine and should not be given to Parkinson’s patients (known or suspected).
Droperidol: causing severe skeletal muscle rigidity and pulmonary edema (may be d/t sudden antagonism of dopamine)
Droperidol as been know to produce a Parkinson’s disease-like syndrome in otherwise healthy patients
Metoclopramide may also interfere with dopamine activity
Monoamine Oxidase Inhibitors:
Can exaggerate PNS and CNS effects of levodopa. Hypertension and hyperthermia are side effects with concurrent administrations
Anticholinergic Drugs: Act synergistically with levodopa to improve certain symptoms of Parkinson’s disease especially tremor
Large doses of anticholinergics can slow gastric emptying such that absorption of levodopa from the GI tract is decreased
Pyridoxine (Vitamin B): in doses as a low as 5 mg can abolish the therapeutic efficacy of levodopa by enhancing the activity of pyridoxine-dependent dopa decarboxylase and thus increasing the metabolism of levodopa in the circulation before it can enter CNS
Peripheral Decarboxylase Inhibitors
Allows more levodopa to escape metabolism into dopamine in the peripheral circulation and thus is more available to enter CNS
N/V and cardiac dysrhythmias are diminished or absent
Does not treat abnormal involuntary movements and psychiatric disturbances.
Carbidopa and Benserazide:
levodopa and carbidopa in a 10:1 or 4:1
Sinemet
levodopa and benserazide in a 4:1 ratio
Madopar:
SYNTHETIC DOPAMINE AGONISTS
Do not require transformation or facilitated transport across the bbb.
Bromocriptine and Pergolide (tetracyclic ergot alkaloids)
Pramiperxole, ropinirole, and rotigotine (non ergot alkaloids)
Bromocriptine metabolized in _____, excreted in _____.
liver, bile
Bromocriptine side effects
Visual and auditory hallucinations
Hypotension
Dyskinesia
These occur more using bromocriptine than levodopa
Asymptomatic increases of serum transaminase and alkaline phosphatase
Doxapram moa
Centrally acting analeptic that also acts peripherally on chemoreceptors augmenting breathing efforts.
Doxapram use
Used as a temporary measure to maintain ventilation during administration of supplemental O2 to patients with chronic obstructive airway disease who would otherwise rely on hypoxic drive to maintain
Post-operatively has been used to prevent ventilatory depression produced by opioids without altering analgesia
Been shown to be useful in stopping post-op shivering
Baclofen moa
Acts as an agonist at GABAB receptors in the dorsal horn of the spinal cord and is often administered for treatment of spastic hypertonia of cerebral and spinal cord origin.
Relieves spasticity by activating G protein-linked presynaptic GABAB receptors that hyperpolarize muscle spindle afferent neurons, thereby decreasing the number and amplitude of excitatory postsynaptic potentials along the dendrites of motor neurons.
Baclofen treatment
Flexor spams
Skeletal muscle rigidity associated with spinal cord injury or MS
Baclofen:
Therapeutic plasma concentrations _____mg/mL
80-400
Baclofen Side Effects:
Sedation
Skeletal muscle weakness
Confusion
Baclofen sudden d/c may result in:
Multiple organ system failure
Tachy
Auditory and visual hallucinations
A known case of cardiac arrest has been reported
Vocal cord spasm following abrupt d/c of intrathecal infusion
Coma, depression of ventilation and seizures with overdose
Threshold for initiation of seizures may be lowered in pts with epilepsy
Mild hypotension in awake pts
Bradycardia, hypotension and delayed awakening when general anesthesia is used
Dantrolene moa
Exerts antispasmodic effect by decreasing calcium release from sarcoplasmic reticulum
Dantrolene Dose
DOSE: 2.5 MG/KG TO MAX 10 MG/KG GIVEN EVERY 5 MINUTES UNTIL EPISODE HAS STOPPED
Dantrolene half life
6hrs
Dantrolene AFTER EPISODE IS CONTROLLED dose
1 MG/KG IV Q 6 HOURS FOR 24 - 48 HOURS TO PREVENT RELAPSE (MH CAN RECUR WITHIN 24 HOURS AFTER INITIAL EPISODE)
Dantrolene side effects
MOST SERIOUS COMPLICATION OF USE: GENERALIZED MUSCLE WEAKNESS THAT MAY RESULT IN RESPIRATORY INSUFFICIENCY OR ASPIRATION PNEUMONIA
