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

ParkinsonismAnticholinergics

• 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