Drugs for Neurologic Disorders Flashcards
PARKINSON’S DISEASE
Low dopamine
degeneration of dopaminergic neurons in brain
Reason is unknown
PARKINSON’S DISEASE
information
Chronic degenerative neurologic disorder of the extrapyramidal motor tract
movement disorder: resting tremor rigidity/freezing bradykinesia posture changes shuffling gait lack of facial expression pill-rolling motion of fingers
PARKINSON’S DISEASE
TERMS
dopaminergic neurons:
release dopamine
Dopamine: inhibitory neurotransmitter in the CNS
ACh: excitatory neurotransmitter in the CNS
extrapyramidal motor tract: originate in the brainstem, carrying motor fibers to the spinal cord; they are responsible for the involuntary (automatic) control of all musculature, such as muscle tone, balance, posture and locomotion
PARKINSONISM TREATMENT
Pharmacologic measures
Can not halt the progression of PD
Can improve quality of life,
ability to performs ADLs (symptom mgmt.)
PARKINSONISM TREATMENT
Dopaminergic
Delivering dopamine across BBB
Dopamine agonist
Improve dopamine action
Anticholinergic centrally acting
Block cholinergic receptors in CNS
Dystonia: involuntary abnormal posture stiffness, contraction, twisting, distortions, spasms
Dyskinesia: involuntary abnormal movements
- DOPAMINERGIC
carbidopa-levodopa
carbidopa-levodopa
MOA
dopamine replacement
Gradual lower effectiveness after about five years of treatment
carbidopa-levodopa
COMBINATION REASONING
When levodopa is used alone, only 1% reaches the brain
99% converts to dopamine while in the PNS
hence mixed with carbidopa
carbidopa inhibits conversion of levodopa to dopamine in the periphery
more levodopa would cross the BBB and reach the brain
carbidopa-levodopa
DURATION
Short duration (4-5 hrs; t1/2 50min) => must take frequent doses
“Wearing off” or “off” episodes may happen at any time lasting minutes to hours (even at high dose)
DOPAMINERGIC SIDE EFFECTS AND NURSING
carbidopa-levodopa
Dystonia
involuntary abnormal posture stiffness, contraction, twisting, distortions, spasms
Dyskinesia
involuntary abnormal movements (head bobbing, tics, grimacing)
Akathisia motor restlessness
the compulsive urge to move constantly
Psychosis:
hallucinations, nightmares, paranoia, severe depression, suicidal ideation
avoid:
CNS depressants,
dopamine-blockers
- e.g. antipsychotics haloperidol (Haldol)
Peripheral nervous system effects:
1. Anticholinergic effects (see code phrases)
- Do not abruptly discontinue
- Warn of harmless brown discoloration of urine & sweat
- N/V: may activate vomiting center in the brain, warn, report
- Avoid pyridoxine (B6 reduces drug effects)
- fortified cereals &
- meat/poultry/fish/soybean (protein foods are high in B6) - Monitor skin for malignant melanoma
- Monitor blood cell counts
- Leukocytopenia, thrombocytopenia
DOPAMINERGIC SIDE EFFECTS AND NURSING
carbidopa-levodopa
NOTES
Dystonia: involuntary abnormal posture stiffness, contraction, twisting, distortions, spasms
Dyskinesia: involuntary abnormal movements
tardive dyskinesia: dyskinesia
Malignant melanoma: skin cancer
Leukocytopenia: low white blood cells (WBC)
Agranulocytosis: sever leukopenia
Thrombocytopenia: low platelets
Dopamine-antagonist (GI effects) => ↑ GI motility: promethazine (Phenergan), metoclopramide (Reglan), prochlorperazine (Compazine)
- DOPAMINE AGONISTS
amantadine
amantadine
MOA
Also antiviral drug for influenza A
improve dopamine action
amantadine
TOLERANCE
Drug tolerance develops
only temporary improvement of symptoms
Do not discontinue abruptly
amantadine
SIDE EFFECTS
livedo reticularis
- temporary skin discoloration while on amantadine
Anticholinergic effects: (see code phrases)
3- ANTICHOLINERGICS
Centrally acting anticholinergic
benztropine
benztropine
MOA
inhibit the release of acetylcholine in CNS
benztropine
SIDE EFFECTS
may affect PNS =>
anticholinergic side effects (see code phrases)
Dystonia
- involuntary abnormal posture
- stiffness,
- contraction,
- twisting,
- distortions,
- spasms
benztropine
CONTRAINDICATION
history of Alzheimer or MG
benztropine
NOTES
Antihistamine: diphenhydramine (Benadryl)
ALZHEIMER’S DISEASE
Pathophysiology
Chronic,
progressive,
degenerative condition of the cholinergic neurons in the brain
low Acetylcholine
cognitive dysfunction
Incurable dementia illness
compare & contrast:
Low ACh neurotransmitter (CNS) in AD
Low ACh receptor sites (nicotinic receptors) in MG
ALZHEIMER’S DRUGSCHOLINESTERASE INHIBITORS (AChE-I)
donepezil
memantine
donepezil
memantine
MOA
Prevents the breakdown of ACh => more ACh in neuron synapses
improve cognitive function
done memory
donepezil
memantine
SIDE EFFECTS
Dizziness, insomnia, HA, anorexia, muscle cramps
MYASTHENIA GRAVIS (MG)
Acquired chronic autoimmune disorder
Destruction of ACh receptor sites by
- antibodies
Lack of nerve impulses
& muscle responses
at myoneural junction
Chronic fluctuating muscle weakness
and fatigue
(mostly voluntary muscle)
compare & contrast:
Low ACh neurotransmitter (CNS) in AD
Low ACh receptor sites (nicotinic receptors) in MG
CHOLINESTERASE INHIBITORSAChE Inhibitor
edrophonium
ultra short-acting for diagnosing myasthenia crisis vs. cholinergic crisis
neostigmine
short-acting for treatment of acute myasthenic crisis
Reversal of nondepolarizing paralytic agents
pyridostigmine
intermediate-acting for maintenance therapy of MG
edrophonium
neostigmine
pyridostigmine
MOA
preventing destruction of ACh =>
better transmission of neuromuscular impulses
edrophonium
neostigmine
pyridostigmine
SIDE EFFECTS
cholinergic effects on the peripheral autonomic nervous system
See code phrases
Fasciculation: muscle twitching
Lacrimation: tear production
edrophonium
ultra short-acting for diagnosing
neostigmine
crisis
Reversal of nondepolarizing paralytic agentsshort-acting
- for treatment of acute myasthenic
pyridostigmine
intermediate-acting for maintenance therapy of MG
MUSCLE SPASM
localized involuntary muscle contractions (increased tone) with pain
When do we need muscle paralysis without the presence of muscle spasm?
(see neuromuscular blockers in anesthesia slides)
Neuromuscular blockers
succinylcholine
vecuronium, pancuronium
cyclobenzaprine, carisoprodol
vecuronium, pancuronium
Centrally acting muscle relaxants (used as antispasmodic)
- PARALYTIC AGENTS
INDICATIONS
adjunct to general anesthesia
short procedures that require flaccidity (such as intubation)
during mechanical ventilation
during electroconvulsive therapy (ECT)
- PARALYTIC AGENTS
EFFECTS
Do not cross BBB => no CNS effects
No unconsciousness, amnesia, analgesia
- PARALYTIC AGENTS
DRUGS
A. depolarizing (succinylcholine)
B. non-depolarizing (vecuronium)
neostigmine (Prostigmin) short-acting AChE-I, used for treatment of acute myasthenic crisis & reversal for nondepolarizing neuromuscular blockers
- PARALYTIC AGENTS
a. depolarizing
succinylcholine
succinylcholine
MOA
ACh agonist,
binds to nicotinic receptor at the neuromuscular junction
ACh at nicotinic receptors is an stimulant
Not metabolized by AChE but metabolized by plasma pseudocholinesterase hence short acting (so with short term airway support and ventilation succinylcholine will be metabolized)
succinylcholine
CAUSES
Causes sustained depolarization of the muscle => muscle paralysis!!!
succinylcholine
NO REVERSAL AGENT: BUT..
reversal agent: none
intubate/ventilate the patient until the drug is metabolized
succinylcholine
CONTRAINDICATION
pregnancy,
MG
succinylcholine
SIDE EFFECTS
hyperkalemia (see code phrases)
succinylcholine
ADVERSE EFFECTS
respiratory depression,
apnea (support airway and ventilation)
malignant hyperthermia (muscle rigidity, high temp (109℉))
Stop the drug,
dantrolene
IVP & gtt, O2, cooling measures (cooling blanket, iced IVF)
- PARALYTIC AGENTSb. nondepolarizing
vecuronium
pancuronium
vecuronium
pancuronium
MOA
Competitive antagonist
binds to ACh receptors without inducing the effect of ACh
vecuronium
pancuronium
EFFECTS
paralysis
vecuronium
pancuronium
SIDE EFFECTS
histamine release => rash, hives, angioedema, bronchospasm, low BP, tachycardia
vecuronium
pancuronium
NURSING
Prepare antihistamine to treat the side effects
Must use reversal agent
neostigmine
vecuronium
pancuronium
REVERSAL AGENT
neostigmine
Nondepolarizing: act as competitive antagonist (bind to receptor (competing with ACh) but not induce the effect of ACh which is to open Na+ channels (antagonist) AChE inhibitors (used for MG e.g., neostigmine (Prostigmin)) are the reversal agent for nondepolarizing blockers (pancuronium)!!! Do not get confused (-ium) is shared between these drugs and AChE-inhibitors used for MG
- SPASMCENTRALLY ACTING MUSCLE RELAXANTS
CNS sedation => depress spasticity of muscles
cyclobenzaprine
carisoprodol
cyclobenzaprine
carisoprodol
SIDE EFFECTS
Sleepiness,
lightheadedness,
fatigue,
fall
Physical dependence:
Short term use,
taper the dose,
avoid stopping abruptly
cyclobenzaprine
carisoprodol
EDUCATION
Educate safety,
avoid CNS stimulants/depressants,
driving
MULTIPLE SCLEROSIS (MS) Pathophysiology
Neuromuscular autoimmune disorder
Progressive loss of myelin sheath of nerve fibers in CNS
No cure (mgmt. symptoms, reduce frequency of exacerbations)
No specific diagnostic test
MULTIPLE SCLEROSIS (MS) Characteristics
Early onset 20s-40s
Slow progression,
remissions and exacerbations
MULTIPLE SCLEROSIS (MS)
CHARACTERISTICS
SENSORY
diplopia, blurred vision, paresthesia, vertigo, tinnitus
MULTIPLE SCLEROSIS (MS)
CHARACTERISTICS
MOTOR
weakness/spasticity/paralysis,
fall
MULTIPLE SCLEROSIS (MS)
CHARACTERISTICS
EMOTIONAL
depression
MULTIPLE SCLEROSIS (MS)
CHARACTERISTICS
CEREBELLAR
nystagmus,
ataxia,
dysarthria,
dysphagia
MULTIPLE SCLEROSIS (MS)
CHARACTERISTICS
NEUROLOGIC
neuropathic pain
MS DRUGS
Immunomodulators
reduce the frequency of flare-ups (prevent relapses)
MS DRUGS
interferon beta 1a
IM/SubQ injection
interferon beta 1b
SubQ injection
interferon beta 1a
IM/SubQ injection
interferon beta 1b
SubQ injection
SIDE-EFFECTS
Flu-like symptoms (body-ache, fever/chills, fatigue/malaise)
myalgia, arthralgia, muscle spasm
depression, suicidal ideation, dizziness, fatigue
Mgmt. of MS exacerbation:
Corticosteroids prednisone (Deltasone)
MS DRUGS
NOTES
Interferon are a group of glycoproteins produced by the body to:
fight viral infections and other foreign matter
help control immune system activities
inhibit inflammation that can cause MS flare-ups
Don’t confuse with interferon alpha (discussed in cancer non-cytotoxic, Biologic Response Modifiers)
CP: chest pain
