Pathopharmacology & Pathophysiology

Exam 1 Mobility
Readings:
Aschenbrenner Ch. 13: 164-167, 184 (Carbidopa-Levodopa)
Aschenbrenner Ch. 14: 197-199, 216 (Antiparkinsons agents)
Aschenbrenner Ch. 20: 342-353 (Muscle relaxants)
Aschenbrenner Ch. 21: 360-371
Giddens Ch. 23
Lewis: 1432-1436, 1506-1509
Perry: 1716, 1571-1576 (Cerebral Palsy)

MOBILITY: purposeful movement gross movements, fine movements, and

coordination
Immobility = an inability to move
Impaired physical mobility = state in which a person has a limitation in physical
movement, but is not immobile
Impaired bed mobility = inability to change positions in bed independently
Deconditioned = a loss of physical fitness
Mobility Involves:
o Musculoskeletal System: bone, joints, muscles
o Nervous System: cognition
Mobility issues: brain, spinal cord, peripheral nerves &&
neurotransmitters
o Cardiovascular System: perfusion
Need oxygen and nutrients to tissues
o Respiratory System: LUNGS = oxygenation
Mobility issues: gas exchange problems; Asthma and COPD [Chronic
Obstructive Pulmonary Disease]; Vasoconstriction of lungs; Always
short of breath
Populations at Risk for Mobility Problems:
o Elderly muscles weaken, weak bones (arthritis, osteoporosis)
o Persons with acute of chronic diseases rheumatoid arthritis (chronic)
o Persons with respiratory diseases
o Persons with cardiovascular diseases
o Chronic pain
o Trauma spinal cord injuries, broken bones
o Congenital abnormalities
Preventing Mobility Problems
o Primary = KEY
Physical activity
Healthy weight/height
Proper nutrition
o Secondary
Osteoporosis screening
Fall risk assessment will do this for every pt in hospital

 Implementing precautions
Pharmacotherapies
o Anti-inflammatory agents: non-steroidal (ibuprofen, aspirin, naproxen) or
steroids
o Analgesic and muscle relaxants: pain killers, acetaminophen, narcotis
o Supplements: herbal (glucosamine)
o Medications to treat neurological disorders
Interrelated Concepts
o Gas exchange
o Intracranial regulation
o Nutrition not eating, needs fluids, proteins, nutrients to heal
o Pain
o Perfusion respiratory system (not expanding lungs, pneumonia)
o Tissue integrity pressure sores, clottingpulmonary embolism
o Elimination incontinence, constipation
Nervous System
Central Nervous System (CNS) = brain and spinal cord
Peripheral Nervous System (PNS) = all neurons found in the rest of the body
o Afferent Branch
o Efferent Branch
Somatic
Autonomic (ANS)
Sympathetic (SNS)
o Adrenergic
o Fight-or-flight
Parasympathetic
o Cholinergic
o Rest and digest
Neurotransmitters = the connection between neurons and organs or tissues
using synaptic transmission
o Neurotransmitters of the Autonomic Nervous System (ANS):
Acetylcholine (ACh): preganglionic neurotransmitter in the SNS; pre
& postganglionic neurotransmitter in the PSNS
Released in response to an action potential, and then binds to
cholinergic receptors on the target organs or tissues.
Norepinephrine (NE): postganglionic neurotransmitter in the SNS
Adrenergic receptor to various organs
Responds to action potential; released and floods the synaptic
cleft. NE can then bind to postsynaptic receptors, which are
alpha-1, beta-1, and beta-2.
Epinephrine (Epi): hormone that is converted enzymatically from NE
in the adrenal medulla, in the SNS to various organs
Dopamine (precursor to NE): Somatic Nervous System = motor
neuron neuromuscular junction
Capable of stimulating all adrenergic receptors (alpha-1, alpha-2,
beta-1, beta-2) as well as specific dopamine receptors
Muscle Spasms & Spasticity

Muscle Spasms: a sudden, violent involuntary contraction of a muscle or group of

muscles
o Common in athletes
o Related to a localized skeletal muscle injury or an imbalance in electrolytes
o Tonic Spasm = characterized by an unusually prolonged and strong
muscular contraction
o Not associated with spinal cord injury
Spasticity: condition in which certain muscles are continuously contracted
o Contraction causes stiffness or tightness of the muscles
o May be associated with spinal cord injury

CYCLOBENZAPRINE (Flexeril): Centrally Acting Muscle Relaxant

Pharmacotherapeutics: manages muscle spasms associated with back sprain or
muscle injury
Pharmacokinetics
o A: GI tract; oral
o D: systemic
o E: urine & bile
o M: liver, first-pass effect
o Dur: takes 1-2 days for full effect
Pharmacodynamics: unknown relieves muscle spasm through central action...
possibly due to sedative effect
o No action at neuromuscular junction = Would not be effective on someone
who has had spinal cord injury
Contraindications/Precautions: pt on MAOI (monoamine oxidase inhibitor)
Adverse Effects: drowsiness, dizziness (sedation), hypotension, CNS
depression, Constipation
Interactions: MAOIs, herbal remedies (St. Johns Wort)
Labs to be Monitored: Liver function tests and kidney function test
o Impaired liver function = higher amt of drug in system = toxicity
Patient Teaching: dont drive until you know effects of drug, increase fluids, avoid
alcohol, long-term use may result in independence, orthostatic hypertension, fall
risk
Lifespan Issues: elderly (50yo) patient teaching = higher risk for falls; college
student patient teaching = higher risk for injury (and other interactions [alcohol,
other drugs])

Cerebral Palsy (CP)

A group of permanent disorders of the development of movement and postures,
causing activity limitations that are attributed to non-progressive disturbances that
occurred in the developing fetal or infant brain
o Most common permanent physical disability in childhood can occur before
child is born
o Some cases also have cognitive/developmental problems but not all!!!
Some just mobility
Characterized by: abnormal muscle tone and coordination

Incidence 1.5-3 per 1000 live births

o 15-60% of these children will have epilepsy
Etiology of CP:
o Prenatal brain abnormalities
80% caused by unknown brain abnormalities
Intrauterine exposure to chorioamnionitis
Inflammation of fetal membranes due to bacterial infection
12% of infants born prior to 36 weeks
Periventricular leukomalacia
Death of white matter due to softening of brain caused by lack of
oxygen
Result of shaken baby syndrome
Types of CP
o Spastic: most common, represents an upper motor neuron muscular
weakness
Child has very hypertonic muscles (stiff) with poor control of
posture/balance/coordinated motion, degree of some neuromuscular
impairment,
Characteristic physical signs: increased stretch reflexes, increased
muscle tone, and (often) weakness.
o Dyskinetic: lack of oxygen, hypoxia, or brain injury
Abnormal movements (face, tongue)
o Ataxic: less common
Repetitive movements, wider gait
Possible Motor Signs of CP
o Poor head control after age 3 months
o Stiff or rigid limbs
o Arching back/pushing away
o Floppy tone dependent on type of CP (not spastic)
o Unable to sit without support at age 8 months
o Clenched fists after age 3 months
Pharmacotherapy
o Baclofen (sometimes through intrathecal pump)
o Antiepileptic drugs
Carbamazine (Tegretol)
Divalproex (valproate sodium & valproic acid)
Gabapentin (in adults)
BACLOFEN: Central Acting Spasmolytics
Pharmacotherapeutics: relieve some components of spinal spasticity; multiple
sclerosis, CP
Pharmacokinetics
o A: GI system; oral, intrathecal
o D: systemic; crosses BBB, placenta, breastmilk
o E: kidneys
o M: liver, first-pass effect
Pharmacodynamics: : oral - derivative of GABA, acts at end of spinal cord.

Inhibits transmission of impulses to cause hyperpolarization. As result of this,

reduces excessive reflex activity and allows muscle relaxation
Contraindications/Precautions: spinal cord injuries
Adverse Effects: CNS depression, dizziness, drowsiness (sedation);
constipation, hypotension
Interactions: MAOIs (monoamine oxidase inhibitor), antidepressants (bc they
work on same neurotransmitters)
Labs to be Monitored: Liver, kidney function, blood glucose levels (drug
increases levels), ROM/pain before and after drug, respiratory status
Patient Teaching: dont drive until they know how drug effects them (sedation),
alcohol; abrupt discontinuation should be avoided = severe side effects
Lifespan Issues: not recommended for children under 12 (only kids with severe
spastic CP but with heavy monitoring); not recommended for elderly either

Parkinsons Disease
A chronic progressive neurodegenerative disease characterized by slowness in the
initiation and execution of movement, increased muscle tone, tremor risk, and gait
disturbances
Idiopathic or Parkinsonism
Autosomal dominant and recessive genes have been linked to familial PD
o Genetic predisposition with environmental exposure
Cause is thought to be a combinations of genes and genetic factors
Disease of basal ganglia characterized by:
o Slowing down in the initiation and execution of movement
o Increased muscle tone
o Tremor at rest (slight hand tremor is one of first symptoms)
o Gait disturbances
o ***Diagnosis when pt has two s/s
DIAGNOSIS: increases with age, with peak onset in seventh decade
More common in men, ratio of 3:2
Pathologic process of PD involves degeneration of dopamine-producing neurons in
substantia nigra of the midbrain
o Imbalance of dopamine-acetylcholine in basal ganglia (due to
decrease in dopamine)
Signs/Symptoms
o Gradual and insidious
o Gradual progression and prolonged course
Classic signs include (triad): need 2/3 to positively diagnose
Tremor
o Often 1st sign
Rigidity
o 2nd sign
o Increased resistance to passive motion
o Caused by sustained muscle contraction
Bradykinesia = abnormal slowness of movement
o Loss of autonomic movements
o Stooped posture

o Masked face
o Drooling of saliva
o Shuffling gait = risk for falls
Complications
o Motor symptoms:
Dyskinesia = difficulty in performing voluntary movements
Weakness
Akinesia = loss of voluntary movement
Neurological problems
Neuropsychiatric
Dysphagia = difficulty swallowing
o Other issues:
Pneumonia
UTI
Skin breakdown
Orthostatic hypotension
Loss of postural reflexes
Sleep disorders or decline in cognition as ell
Course of Disease
o Motor Signs
Onset = symptoms unilateral, mild tremor, slight limp, or decreased
arm swing
Later = shuffling, propulsive gait with arms flexed and loss of postural
reflexes
o Non-Motor Signs
Depression
Anxiety
Apathy
Fatigue
Pain
Constipation
Impotence
Short term memory impairment
Pharmacotherapy
o Carbidopa-Levodopa (Sinemet)
Dopaminergic = increases dopamine levels
o Bromocriptine (Parlodel)
Dopamine agonist = stimulates dopamine receptors
o Benztropine
Anticholinergics = prevent activation of cholinergic receptors
Treat other disorders but in Parkinsons, they help to manage
symptoms
Block access of acetylcholine
Treats tremors and rigidity
o Antihistamine = manage tremors
o Beta-blockers = prevent tremors

CARBIDOPA-LEVODOPA: Dopaminergic
Dopaminergic = increases dopamine levels
Pharmacotherapeutics: treats Parkinsons disease (can take up to 6months for
full effect)
Pharmacokinetics
o A: GI; oral
o D: BBB (levodopa); crosses placenta, breast milk
o E: kidneys (as dopamine metabolites)
o M: into dopamine in periphery
o Dur: some may see effects in 1-2months, can take up to 6 months for full
effect
Pharmacodynamics: combination drug, we want this to cross BBB and turn into
dopamine. We dont have a lot of meds making it to brain, so we combine
levodopa with Carbidopa (doesnt cross BBB) but helps the levodopa cross through
o Without Carbidopa, only 2% crosses BBB. With, 10% crosses BBB
o Carbidopa prevents levodopa from being metabolized in periphery
Contraindications/Precautions: pregnant women, cardiac disease
Adverse Effects: BP (orthostatic hypotension), GI upset, pt displays abnormal
mvmts, cardiac arrhythmias
Interactions: tricyclic antidepressants, MAOIs
Labs to be Monitored: Kidney: BUN, Creatinine (could be lowered); Vitals: BP
Patient Teaching: Cannot be given with protein/food, best to give on empty
stomach [must space out giving pt protein], timing of medications want the
drug to peak around mealtimes so that the patient doesnt have trouble
swallowing/aspirate. Causes GI upset so give non-protein snack about 30
minutes before administration of drug
o Patient usually takes awhile to eat, so space out meals
o Keep pt close to nursing station mobility problems
o On/Off Syndrome, Freezing
Lifespan Issues: not safe for pregnant/breast-feeding mothers, cardiac disease;
less effective in Chinese/Philippian pt

BROMOCRIPTINE: Dopamine Agonist

Dopamine Agonist = stimulate dopamine receptors
Pharmacotherapeutics: treatment of Parkinsons disease; sometimes used in pt
with pituitary tumors, infertility
Pharmacokinetics
o A: stomach; oral
o D:
o E: kidneys
o M: liver, first-pass
Pharmacodynamics: Dopamine agonist essentially stimulates dopamine 2

receptor sites (mechanism of action)

Contraindications/Precautions:
Adverse Effects: has more side effects= causes peripheral vasodilation
hypotension, GI upset, psychiatric disturbances (these disturbances increase
with drug dosage), dizziness, drowsiness
Interactions:
Labs to be Monitored: Liver: AST, ALT; Kidney: BUN, Creatinine
Patient Teaching: can give with food, encourage pt to drink lots of fluids
o On/Off Syndrome, Freezing
Pregnancy Category: C; benefits need to outweigh risk

BENZTROPINE: Anticholinergic
Anticholinergic = prevents activation of cholinergic receptors, helps manage
Parkinsons tremors and rigidity; blocks access of acetylcholine
Pharmacotherapeutics: helps manage Parkinsons tremors and rigidity
Pharmacodynamics: Decrease ACh to balance... Use when dopaminergic or
dopamine agonist arent working = On/Off Syndrome