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