Chapter 23Lecture 4
Neuromuscular Disorders
Parkinsonism
•Chronic neurologic disorder
•Affects extrapyramidal motor tract - posture, balance, locomotion
•Syndrome (combo. of symptoms)
- bradykinesia - slow movement & tremors
- rigidity - abnorm. muscle tone
- No facial expression
- involuntary tremors of head & neck
- pill rolling movement of hands
•usual onset between 50 & 70 yrs.
Parkinsonism
•Pathophysiology:
- Imbalance of neruotransmitters dopamine & acetylcholine
- Degeneration of neurons originating in substantia nigra of midbrain & terminate at basal ganglia of the extrapyramidal notor tract
- Cause unknown
Parkinsonism
•2 Neurotransmitters:
•Dopamine (DA)- inhibitory - from dopaminergic neurons
•Acetylcholine (ACh) - excitatory - from cholinergic neurons
- Dopamine normally controls ACh & inhibits excitatory response
•Degeneration of DA neurons (unknown) imbalance between DA & Ach
•ACh takes over excitation &
stimulation of neurons releasing gamma-aminobutyric acid (GABA) movement disorders of parkinson’s
•80% of dopamine depleted by the time symptoms appear
ParkinsonismMedications
•Drugs used to treat parkinsons are to reduce symptoms
Anticholinergics - block cholinergic receptors
Dopaminergics - stimulate dopamine receptors
•Treats symptoms of disease - does not cure
•strategy of therapy = start w/ small doses to improve symptoms
able to add more drugs & doses as disease progresses
Parkinsonism
Anticholinergics
•Benztropine mesylate (Cogentin), Trihexyphenidyl (Artane), Ethopropazine (Parsidol), Orphenadrine (Norflex)
- Used to decrease ACh levels
- Helps w/ rigidity, sweating, drooling. tremor, depression
•SE = Dry mouth & secretions, urinary retention, constipation, blurred vision
Parkinson’s Disease
•Carbidopa/Levodopa (Sinemet)
- Replaces deficient dopamine in the brain, reestablishing the dopamine/acetylcholine balance
- Drug response will diminish as disease progresses
- Synergistic mechanism of action
Parkinson DiseaseLevodopa/Carbidopa (Sinemet)
•Levodopa converted to dopamine in the brain by the enzyme dopa decarboxylase
•Carbidopa inhibits the enzyme dopa decarboxylase so more levodopa available to be converted to dopamine in the brain - lessens the amount of levodopa needed = lower dose
•SE - N & V, dystonic movement (involuntary), nd psychotic behavior
Parkinson’s DiseaseDrugs
•Selegiline HCL (Eldepryl) - MAO-B inhibitor
- Action - unknown - may selectively inhibit MAO-B (mostly in brain) & dopamine metabolism = extends action of dopamine
- Used as adjunctive therapy w/ levodopa to dec. dose
- If given early, may slow progression of disease
- Alert - Avoid Tyramine rich foods (cheese, red wine, bananas) may cause HTN crisis
- DI - severe w/ various tricyclic antidepressants (TCA) or serotonin uptake inhibitors (SSUI)
Myasthenia Gravis (MG)
•Autoimmune Disease
•Antibody response against the acetylcholine (ACh) receptor site in skeletal muscle a degradation of ACh receptors
•Lack of ACh reaching cholinergic receptors = weakness, fatigue of skeletal muscles & weak resp. muscles
•Drugs for controlling MG = AChE inhibitors or cholinesterase inhibitors & anticholinesterase that inhibit action of the enzyme more ACh activates cholinergic receptors & promotes muscle contraction (parasympathomimetics)
Myasthenia GravisMedications
•Neostigmine (Prostigmin), Pyridostigmine bromide (Mestinon), Ambenonium (Mytelase) - Used to control MG - diff. lengths of action - must be given on time to prevent muscle weakness
- Cholinergic crisis can result w/ overdosing (extreme weakness, inc. salivation, tears, sweating) - atropine sulfate should be available to counteract the OD
•Edrophonium chloride (Tensilon) - used in diagnosing MG - ptosis (droopy eyelid) gone in 1 - 5 min. & to distinguish between MG & cholinergic crisis
Chapter 15Central Nervous System (CNS)
•Brain & Spinal Cord - regulates body
functions
•Receives signals from sensory receptors - pain,
cold, smell - by way of afferent nerves
•Info. is processed & controls body response w/
signals sent via efferent nerves for cellular action
•Stimulation of the CNS may either increase nerve
cell (neuron) activity, or block nerve cell activity
CNS
•Blood Brain Barrier - BBB
- Impedes entry of drugs into the brain d/t the cells composing the walls of the capillaries surrounding the brain being tight
1. lipid soluble agents can cross - Chloromycetin
2. Drugs w/ specific “transport systems” can cross - Claforan, Rocephin, Mefoxin
(+) - Protects the brain from invasion of potentially toxic
substances
(-) - Significant obstical in treatment of CNS infections
CNS
•CNS neurotransmitters - Unlike PNS
- There are a lot of them
- Exact functional role not clear
- Complexity makes it difficult to know exactly how CNS drugs work
•CNS has ability to alter effects of drugs when taken chronically. Adaptive changes occur in brain w/ prolonged use
Can produce alterations in theraputic & side effects
•Tolerance & physical dependence can occur
Tolerance = dec. response with prolonged use (Parkinson’s)
Dependence = Abrupt withdrawl = withdrawl syndrome (illegals)
CNS Stimulants
•Major stimulants =
- Amphetamines & caffeine - stimulate cerebral cortex of brain
- analeptics & caffeine - act on brain stem & medulla to stimulate respirations
- anorexiants - act on cerebral cortex & hypothalamus to suppress appetite
•Uses - narcolepsy, attention deficit disorder (ADD), appetite suppressants, stimulate respirations, & migraine headaches
Chapter 16
Central Nervous System Depressants:
Sedative-Hypnotics
Sedative - Hypnotics
•Problem State - Insomnia
•Adequate sleep important for maintainance of body functions. 4 stages:
1. I & II = light sleep - easy arousal
2. III = transition from light to deeper
3. IV = Deep sleep - dreamless, restful Bp & resp
4. Rapid Eye Movement (REM) - Dreaming phase. Reestablishes psyhic equilibrium
Sedative - Hypnotics
•Insomnia = Most common sleep disorder
- Symptom of physical or emotional distress
•Desired Drug Action = calm client, little or no daytime sedation or drowsiness, fall asleep quickly, awaken refreshed without any drug hangover
•Problem caused by - difficulty falling asleep, staying asleep, early morning awakenings
•One of the most frequently prescribed drugs d/t high incidence of sleep disorders
Sedative/Hypnotics
•Drugs used in conjunction with altered patterns of sleep:
- Hypnotic - drug that produces “natural sleep”
- Sedative - diminishes physical & mental responses, but doesn’t affect consciosness. Quiets the client. Used mostly during the daytime.
- dose of drug may induce sleep
•Sedative/hypnotics are sometimes the same drug, but certain drugs used more often for hypnotic effect
Sedative/HypnoticsBarbiturates
•Not as commonly used for sleep/sedation d/t side effects & potential for abuse
- benzodiazepines more frequently used today
•Long, intermediate, short & ultrashort - acting
•Elderly should not take - CNS depression
•Restict use (2 weeks or less) d/t side effects & drug tolerance
•Class II
Sedative/HypnoticsBarbiturates
•Pentobarbital (Nembutal) - short-acting, long t1/2
* rapid onset, short duration of action
* Primarily used to induce sleep & for sedation needs
* many drug interactions
Alert - Don’t confuse with Phenobarbital
•Phenobarbital - long acting
* Used to control seizures in epilepsy
* Used for pre-op sedation
Sedatives/HypnoticsBenzodiazepines
•Considered safer than barbiturates - short-acting
•Closer to ideal/desired action
•Effective for sleep disorders for several weeks longer than other sedative-hypnotics
•Should not be used for longer than 3 - 4 weeks as a hypnotic to prevent REM rebound
•Small doses may be used for clients with renal or hepatic dysfuction
Sedative/HypnoticsBenzodiazepines
•Flurazepam (Dalmane) - intermediate to long acting, long t1/2, highly protein bound
* Used to treat insomnia by inducing & sustaining sleep
* Rapid onset of action
•Triazolam (Halcion) - short-acting hypnotic
* Used to treat insomnia
* May cause memory loss with prolonged use
•Temazepam (Restoril) - hypnotic
* Used for insomnia & to dec. nocturnal awakenings