Download 2 Neurotransmitters

Chapter 23
Lecture 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
Parkinsonism
Medications
• 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 Disease
Levodopa/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 Disease
Drugs
• 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 Gravis
Medications
• 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 15
Central 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/Hypnotics
Barbiturates
• 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/Hypnotics
Barbiturates
• 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/Hypnotics
Benzodiazepines
• 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/Hypnotics
Benzodiazepines
• 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