Block 1 Exam Flashcards
(361 cards)
1
Q
What is the difference between the motor neurons in the somatic NS vs the ANS?
A
-Somatic innervates skeletal muscles; voluntary
-ANS: innervates smooth muscle, cardiac muscle, and glands; involuntary
2
Q
What neurotransmitter is always released by the preganglionic neurons in the ANS?
A
ACh
3
Q
What neurotransmitter is released from postganglionic neurons in the sympathetic and parasympathetic NS? What is the exception to this?
A
-Sympathetic: norepineprhine
-Parasympathetic: ACh
-Sweat glands have sympathetic input but only use ACh as a neurotransmitter
4
Q
What is another name for the sympathetic NS?
A
-“Fight or flight”
-Thoracolumbar system
5
Q
What is another name for the parasympathetic NS?
A
-“Rest and digest”
-Craniosacral system
6
Q
What is the role of the parasympathetic division?
A
-SLUD
-Salivation
-Lachrymation
-Urination
-Defecation
-BP, HR, and RR are low
-GI tract activity is high
-Pupils are constricted and lenses are accommodated for close vision
7
Q
What is the role of the sympathetic division?
A
-Mobilizes the body during activity
-Promotes adjustments during exercise or when threatened
-Blood flow is shunted to skeletal muscles and heart
-Bronchioles dilated
-Liver releases glucose
8
Q
What are the functional aspects of the parasympathetic NS?
A
-Constricts pupils
-Stimulates salivation
-Inhibits heart
-Constricts bronchi
-Stimulates GI tract
-Stimulates gallbladder
-Contracts bladder
-Relaxes rectum
9
Q
What are the functional aspects of the sympathetic NS?
A
-Dilates pupils
-Inhibits salivation
-Relaxes bronchi
-Accelerates heart
-Inhibits digestive activity
-Stimulates glucose release by liver
-Secretion of epinephrine and norepinephrine from kidney
-Relaxes bladder
-Contracts rectum
10
Q
What receptors are there in the sympathetic NS?
A
-⍺-1
-⍺-2
-β-1
-β-2
11
Q
What receptors are there in the parasympathetic NS?
A
Muscarinic
12
Q
What types of receptors do ACh bind to?
A
-Nictonic receptors
-Muscarinic receptors
13
Q
Where are nicotinic receptors found?
A
-Motor end plates of skeletal muscles
-All ganglionic neurons (sympathetic and parasympathetic)
-Hormone-producing cells of the adrenal medulla
-Effect of ACh at nicotnic receptors is always stimulatory
14
Q
Where are the muscarinic receptors found?
A
-Found on all effector cells stimulated by postganglionic cholinergic fibers
-The effect of ACh at muscarinic receptors can either be excitatory or inhibitory
15
Q
What are the two types of adrenergic receptors?
A
-Alpha
-Beta
16
Q
What is sympathetic tone?
A
-Sympathetic NS controls BP even at rest
-Keeps blood vessels in a continual state of partial constriction
-Sympathetic fibers fire more rapidly to constrict blood vessels and cause BP to rise
17
Q
What is parasympathetic tone?
A
-Parasympathetic NS dominates the heart and smooth muscle of GI tract and urinary tract organs
-Slows the HR
-Dictates normal activity levels of the digestive and urinary tracts
18
Q
What are unique roles of the sympathetic NS?
A
-The adrenal medulla, sweat glands, and blood vessels only receive sympathetic fibers
-Controls thermoregulatory responses to heat
-Release of renin from the kidneys
-Metabolic effects
19
Q
Where are β-1 receptors located that are stimulated by the sympathetic NS? What are its effects?
A
-Heart (increase HR)
-Salivary glands (increases)
-Adipose tissue (lipolysis)
-Kidney (renin secretion)
20
Q
Where are ⍺-1 receptors located that are stimulated by the sympathetic NS? What are its effects?
A
-Skin (constricts)
-Smooth muscle sphincters (contracts)
-Pupils (dilation-mydriasis)
21
Q
Where are β-2 receptors located that are stimulated by the sympathetic NS? What are its effects?
A
-Bronchioles (dilates)
-Blood vessels to skeletal muscle (dilates)
-Smooth muscle walls (relaxes)
-Bladder wall muscle (relaxes)
-Liver (gluconeogenesis, glycogenolysis)
22
Q
Where are ⍺-2 receptors located that are stimulated by the sympathetic NS? What are its effects?
A
Smooth muscle walls (relaxes)
23
Q
What are cholinergic agonists? What is another name for them?
A
-Mimic the effects of acetylcholine
-Also referred to as “parasympathomimetics”
24
Q
What are the two types of cholinergic agonists?
A
-Direct: mimic the activity of ACh at the cholinergic receptors
-Indirect: inhibit the actions of acetylcholinesterase
25
What are some examples of direct acting cholinergic agonists?
-Bethenechol
-Pilocarpine
-Methacholine
-Carbachol
26
What is the mechanism of action of bethanechol? What is its purpose?
-Targets muscarinic receptors in the GI and urinary tract
-Purpose is to increase tonicity in the destrusor muscle and stimulate gastric motility
27
What are adverse effects of bethanechol?
-Abdominal discomfort
-Urinary urgency
-Flushing of skin
-Bronchial constriction
-Asthma attacks
28
What is the mechanism of action of pilocarpine? What is its purpose?
-Targets muscarinic receptors in the lacrimal glands
-Its purpose is to decrease fluid in the eye which decreases pressure
-Used to treat glaucoma
29
What are the adverse reactions of pilocarpine?
-Blurred vision
-Decreased night vision
-Eye irritation
-Headache
-Increase sweating and salivation
30
What is methacholine used for?
To diagnose asthma
31
What is carbachol used for?
To treat glaucoma
32
What are indirect acting cholinergic agonists/cholinesterase inhibitors used for alzheimer's?
-Donepezil
-Rivastigmine
-Galantamine
33
What are indirect acting cholinergic agonists/cholinesterase inhibitors used for myasthenia gravis?
-Neostigmine
-Pyridostigmine
-Edrophonium
-Ambenonium
34
What are indirect acting cholinergic agonists/cholinesterase inhibitors used for glaucoma?
-Physostigmine
-Echothiopate
35
What is myasthenia gravis?
Weakness of the skeletal muscle and fatigue
36
What is glaucoma?
Increase in intraocular pressure which can lead to blindness
37
What are common adverse effects of cholinergic stimulants?
-GI distress
-Increased salivation
-Increased lachrymation
-Bronchoconstriction
-Bradycardia
-Difficulty in visual accommodation
38
What are common anti-cholinergic drugs?
-Atropine
-Scopolamine
-Ipratropium bromide
-Tiotropium bromide
-Oxybutynin
-Tolterodine
-Benztropine
-Tropicamide
-Dicyclomine
-Hyoscyamine
39
What are common ⍺-1 selective agonists? What is their use?
-Phenylephrine
-Pseudoephedrine
-Oxymetazoline: reduces redness of the eye
-Xylometazoline
-Decrease nasal congestion
40
What are adverse effects of ⍺-1 agonist?
-Increased BP
-Headache
-Slow HR due to reflex bradycardia
41
What are common ⍺-2 selective agonists? What is their use? What is the mechanism of action?
-Clonidine
-Methyldopa
-Antihypertensive agent
-Binds to ⍺-2 receptors on the presynaptic neuron and blocks neurotransmitter release
42
What are adverese effects of ⍺-2 agonists?
-Dizziness
-Drowsiness
-Dry mouth
43
What are common β-1 selective agonists? What is their use?
-Dobutamine: positive inotrope
-Dopamine: congestive HF
44
What are adverse effects of β-1 selective agonists?
-Chest pain
-Arrhythmias
-SOB or difficulty breathing
45
What are common β-2 selective agonists? What is their use?
-Albuterol: bronchodilator
-Salmeterol: bronchodilator
-Terbutaline: delay preterm labor (slows uterus contractions)
46
What are adverse effetcs of β-2 selective agonists?
-Nervousness
-Restlessness
-Trembling
47
What are some common non-selective adrenergic drugs? What are their uses?
-Amphetamines: treat ADHD in children, or narcolepsy
-Epinephrine: anaphylactic shock
-Norepinephrine: to treat hypotension during shock
48
What are the adverse effects of non-selective adrenergic drugs?
-CNS excitation
-Anxiety
-Arrhythmias
-Hypertension
49
What are common ⍺-1 selective antagonists? What is their use?
-Prazosin: antihypertensive
-Doxazosin: antihypertensive
-Alfuzosin: treats urinary retention
-Tamulosin: treats urinary retention
50
What is phenooxybenzamine? When is it used?
-⍺-1 selective antagonist
-Used to control BP prior to and during the removal of a pheochromocytoma (cancer of adrenal gland)
51
What are the adverse effects of ⍺-1 selective antagonists?
-Reflex tachycardia
-Orthostatic hypotension
-Dizziness
52
What are common β-1 selective antagonists? What are their uses?
-Atenolol: antihypertensice
-Bisoprolol: treats HF
-Metroprolol: treats HF
-Esmolol: treats arrhythmias
53
What are some common non-selective β blockers? What are the adverse effects of them?
-Propranolol: antihypertensive
-Timolol: treats glaucoma
-Could cause bradycardia and bronchoconstriction
54
What are the adverse effects of β-adrenergic antagonists?
-Bronchoconstriction
-Increase in airway resistance
-Bradycardia
-Dizziness
-Depression
-Lethargy
55
What are physical therapy considerations for anyone taking medications that influence the ANS?
-BP and HR may be low
-Respiratory conditions
-Dizziness and fall risk
-Endurance and fatigue: may have exercise intolerance
-Heat tolerance: anticholinergics can decrease sweating
-Cholinesterase inhibitors can cause bradycardia
-Diuretics are often prescribed with ANS agents and can cause dehydration and electrolyte imbalances
56
What are the health threats from high BP?
-Stroke
-Vision loss
-HF
-MI
-Kidney disease
-Sexual dysfunction
57
What are the two types of hypertension?
-Essential
-Secondary
58
What is essential hypertension?
Cause is not known
59
What is secondary hypertension?
-Cause is known
Can be caused by the following:
-Renal artery constriction
-Phenochromocytoma (tumor of adrenal glands)
-Primary aldosteronism
60
What is the calculation for blood pressure?
BP= CO x total peripheral resistance (TPR)
61
What is elevated BP?
SBP 120-129 and DBP less than 80
62
What is stage 1 hypertension?
SBP 130-139 or DBP 80-89
63
What is stage 2 hypertension?
SBP 140 or higher or DBP 90 or higher
64
What is a hypertensive crisis?
SBP higher than 180 and/or DBP higher than 120
65
What is the stepped approach to treatment of hypertension?
1. Lifestyle changes
2. Medication management
3. Multiple medications
66
What is non-pharmacological treatments for hypertension?
-Dietary salt restriction
-Potassium supplementation
-Weight loss
-Dietary Approaches to Stop Hypertension diet (DASH)
-Aerobic exercise
67
What are the anti-hypertensive drug categories?
-A: Angiotensin converting enzyme inhibitors
-B: Blockers of the angiotensin receptor
-C: calcium channel blockers
-D: diuretics
-Beta blockers
-Alpha blockers
-Alpha 2 agonists
-Renin inhibitors
-Vasodilators
68
What are diuretics? What are the different types?
-Acts on the kidneys to increase excretion of sodium and water
-Thiazide diuretics
-Loop diuretics
-Potassium sparing diuretics
69
What is the mechanism of action of thiazide diuretics? What are common thiazide diuretics?
-Ibhibits sodium reabsroption in the distal convoluted tubule
-Chlorothiazide
-Hydrochlorothiazide
70
What is the mechanism of action of loop diuretics? What are common loop diuretics?
-Inhibits reabsorption of sodium & chloride in the Loop of Henle
-Furosemide
-Torsemide
71
What is the mechanism of action of K+ sparing diuretics? What are common K+ sparing diuretics?
-Prevents secretion of K+
-Not as good of a diuretic but it prevents hypokalemia
-Spironolactone
-Triamterene
72
What are side effects and adverse reactions of diuretics?
-Fluid loss: can lead to orthostatic hypotension
-Electrolyte imbalance: can lead to cardiac arrhythmias
-Hypokalemia
73
How does the renin-angiotensin system work?
-Decreased BP, blood volume, or decreased sodium content
-Kidneys release renin
-Renin converts angiotensinogen (in the liver) to Angiotensin I
-Angiotensin I travels to the lungs
-Angiotensin converting enzyme (ACE) in the lungs, converts angiotensin I to angiotensin II
74
What are the effects of angiotensin II?
-Causes vasoconstriction, thereby increasing BP
-Stimulates the release of aldosterone from the adrenal cortex
-Stimulates the release of antidiuretic hormone which increases water retention and blood volume
-Induces thirst leading to increased fluid intake
75
What can occur with chronic activation of the renin-angiotensin system?
Can lead to persistent increases in blood pressure, contributing to the development of hypertension
76
What is the function of aldosterone?
It leads to sodium and water retention in the kidneys, which increases blood volume and pressure
77
What is the mechanism of action of ACE inhibitors?
-Inhibits angiotensin converting enzyme (ACE) therefore preventing angiotensin II from being made
-Inhibits aldosterone secretion as there is no angiotensin II
-Prevents remodeling of the blood vessels and heart
78
What are common ACE inhibitors?
-Benazepril
-Captopril
-Cilazapril
-Enalapril
-Fosinopril
-Lisinopril
-Quinipril
-Ramipril
79
What are side effects or adverse effects of ACE inhibitors?
-Dry cough
-Hyperkalemia
-Acute kidney damage
-Angioedema (skin & mucous membranes)
-Fetotoxi and should not be used by pregnant women!!!
80
What is the mechanism of action of angiotensin receptor blockers (ARBs)?
-Blocks the angiotensin II receptors to prevent vasoconstriction, release of aldosterone from the adrenal glands
-Same therapeutic effect as ACE inhibitors
81
What are the side effects and adverse effects of ARBs?
-Acute kidney damage
-Hyperkalemia
-Fetotoxic and should not be used by pregnant women
82
What are common ARBs?
-Candesartan
-Irbesartan
-Losartan
-Telmisartan
-Valsartan
-Olmesartan
83
What is the mechanism of action of calcium channel blockers (CCBs)?
Blocks calcium entry into the cells of the vascular smooth muscle and the heart
84
How does smooth muscle activation work in the vascular and heart smooth muscle?
-Influx of extracellular calcium releases stored calcium from the sarcoplasmic reticulum
-Intracellular calcium binds to calmodulin, which then activate myosin light chain kinase (MLCK)
-Activation of MLCK enables myosin to interact with actin to induce contraction
85
What are side effects of CCBs?
-Dizziness
-Flushing
-Headache
-Fatigue
-Peripheral edema
86
What are common CCBs?
-Verapamil
-Dilitiazem
-Amlodipine
-Felodipine
-Nifedipine
87
How do β-1 blockers effect blood pressure?
-Bind to β-1 receptors
-Blocks the effects of epinephrine and norepinephrine
-Decreases HR and contractility which results in reduced CO and BP
88
How do ⍺-1 blockers effect blood pressure?
Binds to ⍺-1 receptors on vascular smooth muscle to cause decrease in vascular resistance which decreases BP
89
How do ⍺-2 agonists effect blood pressure?
Stimulates ⍺-2 adrenergic receptors in the brain to reduce sympathetic outflow
90
What are common vasodilators? What are their uses?
-Hydralazine and minoxidil directly relax arteriolar smooth muscle resulting in vasodilation
-Minoxidil is a more potent vasodilator than hydralazine
-Used to treat moderate-severe hypertension
91
What is the mechanism of action of vasodilators?
-Activation of K+ channels
-Increased K+ efflux induces hyper-polarization of the smooth muscle membrane
-Calcium influx is inhibits and the arteriolar smooth muscle relaxes
92
What are side effects and adverese effects of vasodilators?
-Reflex tachycardia
-May prompt angina pectoris, MI, or cardiac failure
-Increase plasma renin concentration resulting in sodium and water retention
-Orthostatic hypotension
93
What is the mechanism of action of renin inhibitors? What is their use?
-Aliskiren
-Similar to ACE inhibitors and ARBs
-Ibhibits renin
-Monitors serum K+ and kidney function
-Must not be used during pregnancy
94
What are physical therapy considerations for anyone taking anti-hypertensives?
-BP monitoring
-Orthostatic hypotension
-Fatigue and dizziness
-Exercise intensity
-Dehydration
-Electrolyte imbalances
-Patient education
95
What are the different classes of antiarrhythmic drug classes?
-Class I: sodium-channel blocker
-Class II: beta-blocker
-Class III: potassium-channel blocker
-Class IV: calcium-channel blocker
96
What is class IA anti-arrhythmic drugs? What is their mechanism of action?
-Block fast Na+ channels
-Cause moderate phase 0 depression
-Prolong repolarization
-Increased duration of action potential
97
What are common class IA anti-arrhythmic drugs?
-Quinidine
-Procainamide
-Disopyramide
98
What are class IB anti-arrhythmic drugs? What is their mechanism of action?
-Weak phase 0 depression
-Shortened repolarization
-Decreased action potential duration
99
What are common class IB anti-arrhythmic drugs?
-Lidocaine
-Mexiletine
100
What are class I anti-arrhythmic drugs used to treat?
Ventricular arrhythmias
101
What are class IC anti-arrhythmic drugs? What is their mechanism of action?
-Strong phase 0 depression
-Little effect on repolarization
102
What are common class IC anti-arrhythmic drugs?
-Flecainide
-Propafenone
103
What are class II anti-arrhythmic drugs? What are their mechanism of actions?
-β-adrenergic blockers
-Blockade of myocardial β-adrenergic receptors
-Direct membrane stabilizing effects related to Na+ channel blockage
104
What are common class II anti-arrhythmic drugs?
-Propranolol
-Other β-adrenergic blockers
105
What are class II anti-arrhythmic drugs used to treat?
-Atrial tachycardias
-Ventricular arrhythmias
106
What are class III anti-arrhythmic drugs? What is their mechanism of action?
-K+ channel blockers
-Cause delay in repolarization
107
What are common class III anti-arrhythmic drugs?
-Amiodarone
-Dronedarone
-Ibultilide
-Dofetilide
108
What are class IV anti-arrhythmic drugs? What is their mechanism of action?
-Ca2+ channel blockers
-Slows rate of AV conduction in patients with a-fib
109
What are common class IV anti-arrhythmic drugs?
-Verapamil
-Diltiazem
-Slows SA node in tachycardia
110
What are other drugs that are used in arrhythmias?
-Adenosine: inhibits AV conduction
-Digoxin: reduces conduction through AV node
-Atropine: blocks vagal effects on the SA node to treat sinus bradycardia
111
What are physical therapy considerations for patients taking anti-arrhythmic drugs?
-Monitor vital signs
-Recognize side effects
-Pace and progression
-Consider exercise type
-Educate patients
-Be prepared
-Coordination with healthcare providers
112
What are skeletal muscle relaxants used to treat?
Used to treat conditions associated with hyper excitable skeletal muscle- specifically spasticity and muscle spasms
113
What is spasticity vs spasm?
-Spasticity: velocity dependent increase in muscle tone caused by the increased excitability of the muscle stretch reflex
-Spasms: involuntary muscle contractions
114
What are common symptoms of severe spasticity?
-Muscle stiffness
-Muscle spasms
-Rapid muscle contractions
-Fixed joints: contractures
-Exaggerated muscle jerks
-Pain or tightness around joints
115
What is the primary goal of skeletal muscle relaxants?
-Selective decrease in skeletal muscle excitability
-Decrease pain without causing a profound decrease in muscle function
116
What are common anti-spasticity drugs?
-Baclofen
-Dantrolene
-Tizanidine
-Botulinum toxin
-Gabapentin
-Diazepam (Benzodiazepines)
117
What are common spasmolytics?
-Carisoprodol (Soma)
-Cyclobenzaprine (Flexeril)
-Methocarbamol (Robaxin)
-Orphenadrine (Norflex)
118
What is the mechanism of Carisoprodol? What is a brand name of this drug?
-Its exact mechanism is unknown, but is believed to alter interneuronal activity in the spinal cord and descending reticular formation
-Polysynaptic inhibitor
-Decrease alpha motor neuron excitability
-Soma
119
What is the mechanism of Cyclobenzaprine? What is a brand name of this drug?
-Works centrally, likely by decreasing activity in the brainstem to relieve muscle spasms
-Flexeril
120
What is the mechanism of Methocarbamol? What is a brand name of this drug?
-Central muscle relaxant properties
-Robaxin
121
What is the mechanism of Orphenadrine? What is a brand name of this drug?
-Anticholinergic properties are believed to be responsible for this drugs mechanism
-Norflex
122
What are the key differences in the mechanisms for anti-spasticity drugs vs spasmolytics?
-Anti-spasticity drugs often have more specific targets
-Spasmolytics are less clear and can be diverse
123
What are the uses of polysynaptic inhibitors?
-Adjuncts to rest and PT for relief of muscle spasms associated with acute painful MSK injuries
-The same compounds sometimes incorporated into the same tablet with analgesic (Norgesic)
124
What are adverse effects of polysynaptic inhibitors?
-Drowsiness, dizziness
-Nausea, lightheadedness, vertigo, ataxia, headache
-Tolerance and physical dependence
125
What are the most common polysynaptic inhibitors?
-Carisoprodol (Soma)
-Cyclobenzaprine (Flexeril)
-Methocarbamol (Robaxin)
-Orphenadrine citrate (Norflex)
126
What is the mechanism of Diazepam (Valium)?
-Increases the inhibitory effects at CNS synapses that use GABA
-Binds to GABA A receptors: positive allosteric modulation
-Increases GABA-mediated inhibition of alpha motor neuron ------> less excitability
127
What are therapeutic uses of Diazepam?
-Treats muscle spasms associated with MSK injuries, especially low back strains
-Controls muscle spasms associated with tetanus toxin (inhibits spasms of larynx)
128
What are adverse effects of Diazepam?
-Sedation and a general reduction in psychomotor ability
-Long-term use also limited by tolerance and dependence
-Sudden withdrawal after prolonged use can cause seizures, anxiety, agitation, tachycardia, and even death
-Overdose can result in coma or death
129
What is an antidote for diazepam?
Flumazenil is antidote for Diazepam and other benzodiazepines
130
What drugs work on GABA A receptors?
Benzodiazepines (Valium/diazepam)
131
What drugs work on GABA B receptors?
Baclofen
132
What drugs work on alpha 2 receptors in the spinal cord?
Tizanidine
133
What drugs work directly on the skeletal muscle?
Dantrolene
134
What is the chemical name of Baclofen (Lioresal)? What is the mechanism?
-Chemical name: beta-(p-choloro-phenyl)-GABA
-Derivative of the central inhibitory GABA
-Binds to GABA B receptors in spinal cord
-Inhibits transmission within the spinal cord at specific synapses causing an inhibitory effect on alpha motor neurons within spinal cord
135
What are common uses of Baclofen?
-Administered orally to treat spasticity with spinal cord lesions (paraplegia, quadriplegia, SC demyelination)
-Drug of choice with MS because of fewer side effects
-Does not cause as much generalized muscle weakness as direct-acting relaxants such as Dantrolene
136
What are the adverse effects of Baclofen?
-Transient drowsiness which usually disappears within a few days
-Sometimes confusion and hallucinations in patients with CVA or in elderly
-Nausea, muscle weakness
-Headache
137
What are intrathecal injections? What are they used for? What is the benefit?
-Spinal injections
-Used in severe spasticity (Baclofen)
-Catheter and "pump" deliver drug to subarachnoid space
-May decrease spasticity with less drug, fewer systemic side effects
138
What is an itrathecal baclofen pump?
-Smaller catheter usually implanted surgically
-Open end of the catheter is attached to some type of programmable pump
-Pump is implanted subcutaneously in the abdominal wall
-Adjusted to deliver drug at slow, continuous rate
-Rate of infusion titrated over time to achieve best clinical reduction in spasticity
139
What are adverse effects of intrathecal baclofen?
-Disruption in delivery system
-Pump malfunction
-Increased drug delivery can cause overdose
-Abrupt stoppage of drug secondary to pump dysfunction can cause withdrawal syndrome (fever, confusion, delirium, seizures)
-Tolerance with long-term use
140
What is the mechanism of adrenergic alpha-2 receptor agonists? What is the primary agent?
-Primary agent: Tizanidine (Zanaflex)
-Stimulate alpha-2 receptors located on spinal interneurons
-Cause inhibition of interneurons which decreases excitatory input onto alpha motor neuron
-Tizanidine decreases excitability by both pre and post synaptic inhibition
-Efficacy similar to Baclofen but with less generalized muscle weakness
141
What are the uses of alpha-2 agonists?
-Control spasticity from spinal lesions and central lesions
-As effective in decreasing spasticity as oral baclofen or diazepam
-Milder side effects and less generalized muscle weakness
-Tizanidine is better than Clonidine because it has less cardiovascular side effects and hypotension
142
What are the adverse effects of alpha-2 agonists?
Sedation, dizziness, dry mouth
143
What is the mechanism of Gabapentin (Neurontin)?
-Calcium channel blocker
-Developed originally as anti-seizure drug
-Enhances GABA effect in spinal cord (exact mechanism unclear)
144
What are the uses of Gabapentin (Neurontin)?
-Decrease spasticity associated with SCI and MS
-Best use may be in combination with other anti-spasticity agents (Gabapentin + Baclofen)
-May help in reducing certain types of chronic pain
145
What are adverse effects of Gabapentin?
-Sedation and fatigue
-Dizziness
-Ataxia
146
What is the mechanism of Dantrolene (Dantrium)?
-Only direct acting muscle relaxant
-Inhibits release of calcium from skeletal muscle sarcoplasmic reticulum
147
What are the uses of Dantrolene?
-Effective in treating severe spasticity
-Not prescribed to treat muscle spasms caused by MSK injury
148
What are adverse effects of Dantrolene?
-Generalized muscle weakness most common
-Use of Dantrolene therefore can be counterproductive because increased motor function with decreased spasticity is offset by muscle weakness
-Severe hepatotoxicity and fatal hepatitis
149
What is the mechanism of Botulinum Toxin?
-Injected locally for severe spasms such as torticollis, laryngospasms
-Increased use in spasticity
-Inhibits release of acetylcholine at neuro-muscular junction
150
Where is Botulinum injected into? How long does it last? How does it help with spasticity?
-Injected into skeletal muscle
-Relaxation/paralysis occur within 3-7 days and lasts 2-3 months
-Remove spastic dominance in certain patients
-Volitional motor function can be facilitated
-Improved gait and other functional activities in patients with cerebral palsy or TBI
-Helps to stretch muscle and prevent joint contractures
-Enables patients to wear orthotic devices
151
What are the problems and limitations with Botulinum Toxin?
-Local irritation at injection site
-Only a limited number of muscles can be injected during a given treatment
-Must limit total dose (300-400 units of Type A, 2500-5000 units Type B)
-Exceeding recommended dosage can cause immune response which will create antibodies against toxin making subsequent treatments less effective
152
How do effects of Botulinum Toxin wear off?
-New presynaptic terminal sprouts from axon that originally effected by toxin
-New motor end plate with new source of acetylcholine
-Another injection needed to block sprout
153
What is the duration of action of carisoprodol (Soma)?
4-6 hours
154
What is the duration of action of chlorzoxazone?
3-4 hours
155
What is the duration of action of cyclobenzaprine (Flexeril)?
12-24 hours
156
What is the duration of action of Diazepam (Valium)?
Up to 24 hours
157
What is the duration of action of Metaxalone?
4-6 hours
158
What is the duration of action of Methocarbamol (Robaxin)?
Unknown
159
What is the duration of action of Orphenadrine citrate (Antiflex, Norflex)?
12 hours
160
What are alternatives to skeletal muscle relaxants?
-Physical therapy
-Ibuprofen/NSAIDS
-Tramadol
-Opioids
161
What are special concerns for rehab patients who use skeletal muscle relaxants?
-Meds are used to compliment PT interventions
-Long term use is not recommended: addiction
-PT can reduce the need for meds
-Possible drastic change in muscle tone over short period of time
-Pt's sometimes rely on muscle spasms or spasticity for functioning
162
What effects of anti-spastic and spasmolytic drugs can interfere with rehabilitation?
-Motor control problems
-Functional decline for daily activities
-Decreased alertness
-Weakness
-Tolerance and physical dependence
163
What are possible PT solutions to effects of anti-spastic and spasmolytic drugs?
-Schedule PT for time of day when sedative effects are less marked
-Discuss with pt's PCP
-In pt's with spasticity due to neurological injury, use intensive PT to return pt to normal physiologic motor control
-Use intensive therapy for acute MSK injuries
-Improve muscle strength, posture, and flexibility which can decrease need for medications
164
What is allodynia?
Pain due to a stimulus that does not normally provoke pain
165
What is hyperalgesia?
Increased pain from a stimulus that normally provokes pain
166
What is hypoalgesia?
Diminished pain in response to a normally painful stimulus
167
What is neuralgia?
Pain in the distribution of a nerve or nerves
168
What is neuritis?
Inflammation of a nerve or nerves
169
What is nociception?
The neural process of encoding noxious stimuli
170
What is a nociceptor?
A high threshold sensory receptor of the peripheral somatosensory nervous system that is capable of transducing and encoding noxious stimuli
171
What is nociceptive pain?
Pain that arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors
172
What is neuropathic pain?
Pain caused by a lesion or damage or disease of the neurons or somatosensory nervous system
173
What is the WHO analgesic ladder?
-Step 1: Mild pain
-Step 2: Moderate pain
-Step 3: Severe pain
-Step 4: Acute, chronic, and palliative
174
What medications or treatment is used for step 1 on the WHO analgesic ladder?
-PT
-OT
-Non-opioid analgesics
-NSAIDs
-Adjuvant pain medications
175
What medications or treatment is used for step 2 on the WHO analgesic ladder?
-PT/OT
-Weak opioids
-Psychology, behavioral therapy, etc.
176
What medications or treatment is used for step 3 on the WHO analgesic ladder?
-Strong opioids
-PT/OT
-Psychology, behavioral therapy, etc.
177
What medications or treatment is used for step 4 on the WHO analgesic ladder?
-PT
-OT
178
What treatments can be used at every step on the WHO analgesic ladder?
-NSAIDs
-PT/OT
-Acupuncture
-Massage
-TENS
179
What is adjuvant pain medications?
Medications that are not typically used for pain but may be helpful for its management
180
What are some examples of adjuvant pain medications?
-Anti-depressants
-Anti-seizure medications
-Muscle relaxants
-Sedatives
-Anti-anxiety medications
-Botulinum toxin
181
What are medications that help to alter the perception of pain in the brain?
-Opioids
-TCAs
-SSRI
-SNRIs
-⍺-2 agonists
182
What are medications that help to modulate the ascending/descending pain pathway?
-TCAs
-SSRIs
-SNRIs
183
What are medications that limit the transmission of pain in the peripheral nerves?
-LAs (ask Dr. Pattipatti what this is)
-Opioids
-⍺-2 agonists
184
What are medications that limit the transduction of peripheral nociceptors?
-LAs
-Capsaicin
-Anticonvulsants
-NSAIDs
-ASA (what is this?)
-Acetaminophen
-Nitrate
185
What are examples of TCAs and SSRIs?
-Amitriptyline
-Noritryptiline
-Duloxetine
186
What are examples of topical agents?
-Capsaicin
-Lidocaine patch
187
What are examples of opioids?
-Tramadol
-Tapentadol
-Hydrocodone
-Oxycodone
-Methadone
188
What are examples of NMDA inhibitors?
-Ketamine
-Amantidine
-Memantine
189
What are examples of anticonvulsant agents?
-Pregabalin
-Gabapentin
-Carbamazepine
190
Where does opioids come from? What is the history of its use?
-Exudate from the opium poppy
-Has been used for 2,000-6,000 years
-Known to relieve pain, diarrhea, and produce euphoria
-Serturner isolated and puriphied morphine in 1803
-Semisynthetic compounds (Heroin- 1874)
-Fully synthetic opioids (Meperidine- 1939)
-Medicinal and recreational uses firmly established
191
Where are endogenous opioids derived from?
Peptides
192
Where are endorphins derived from? What types of endorphins are there? What receptors do they work on?
-Derived from proopiomelanocortin (POMC)
-2 types of β-endorphins: β-endorphin-1 and β-endorphin-2
-Primarily µ agonist and also has 𝛿 action
193
Where are enkephalins derived from? What types are there? What receptors do they work on?
-Derived from proenkephalin
-Met-ENK
-Leu-ENK
-Met-ENK: µ and 𝛿 agonist
-Leu-ENK: 𝛿 agonist
194
Where are dynorphins derived from? What types are there? What receptors do they work on?
-Derived from prodynorphine
-DYN-A
-DYN-B
-Potent 𝜿 agonist and also have µ and 𝛿 action
195
What are the 3 opioid receptors? What therapeutic effects does agonists of these receptors create?
-Mu (µ)
-Kappa (𝜿)
-Delta (𝛿)
-Creates spinal and supraspinal analgesia
196
What are other effects of µ agonists?
-Sedation
-Respiratory depression ***this is why opioid overdose can cause death***
-Constipation
-Inhibits neurotransmitter release (ACh, dopamine)
-Increases hormonal release (prolactin, growth hormone)
197
What are other effects of 𝜿 agonists?
-Sedation
-Constipation
-Psychotic effects
198
What are other effects of 𝛿 agonists?
-Increases hormonal release (growth hormone)
-Inhibits neurotransmitter release (dopamine)
199
What are opioid receptor agonists?
Activate one or more opioid receptors
200
What are opioid receptor antagonists?
Occupy receptors and prevent agonist binding (e.g. Naloxone)
201
What are opioid mixed receptor agonist-antagonists?
Agonist activity at one type of receptor and antagonist activity at another type of receptor (e.g. Buprenorphine)
202
What is the difference between and opioid and an opiate?
-Opioid: any naturally occurring, semi-synthetic, or fully synthetic compound that binds to opioid receptors and share the properties of one or more of the naturally occurring endogenous opioids
-Opiate: any naturally occurring opioid derived from opium
203
What are examples of strong opioid receptor agonists? What receptor do they primarily interact with?
-Strong agonists are used to treat severe pain
-Interact primarily with µ receptors
-Fetanyl (Duragesic, Sublimaze)
-Morphine (MS Contin)
-Hydromorphone (Dilaudid)
-Oxymorphone (Numorphan)
-Meperidine (Demerol)
-Methadone (Dolophine)
-Oxycodone (Oxycontin)
204
What are examples of mild to moderate opioid receptor agonists?
-These are used for mild to moderate pain
-Codein
-Hydrocodone (Hycodan)
205
What are examples of mixed opioid receptor agonist-antagonist?
-Some of these bind to 𝜿 receptors while block or partially block µ receptors making them µ receptor antagonists or partial agonists
-Buprenorphine (Buprenex)
-Nalbuphine (Nubain)
206
What are examples of opioid receptor antagonists?
-Particular affinity for µ
-Naloxone (Narcan)
-Naltrexone (ReVia, Vivitrol)
207
What are other uses of Naltrexone?
-Can be used in conjunction with behavioral therapy to maintain an opioid-free state for recovering opioid addicts
-Can be used in treating alcohol dependence
208
What is the mechanism of action of opioids?
-Bind to opioid receptors
-Two well established direct G-protein coupled actions
-They close voltage gated Ca2+ channels on presynaptic nerve terminals which reduces neurotransmitter release (glutamate and substance P)
-They open K+ channels on postsynaptic neurons and hyperpolarize them and inhibit postsynaptic neurons
209
What are the sites of putative action of opioid analgesics?
-Primary afferent nociceptor terminals
-Dorsal horn
-Ventral posterolateral nucleus (VPL) of the thalamus
-Possibly in the amygdala as well
210
What are the key pharmacological actions of morphine and other opioid agents?
-Analgesia
-Respiratory depression
-Spasm of smooth muscle of the gastrointestinal (GI) and genitourinary (GU) tracts, including the biliary tract (bile ducts)
-Pinpoint pupils (miosis)
211
What is a way to determine if someone if overdosing from opioids or another drug?
If someone's pupils are constricted/has pinpoint pupils, they are overdosing from opioids
212
What are the CNS effects of opioids?
-Analgesia
-Euphoria
-Sedation
-Respiratory depression
-Cough suppression
-Miosis
-Truncal rigidity
-Nausea and vomiting
-Body temperature
-Sleep disturbances
213
What are the effects of opioids on the cardiovascular system?
-Typically no significant effects
If there are effects:
-Bradycardia
-Hypotension
-Increased cerebral blood flow
-Increased intracranial pressure (opioids contraindicated in brain injury patients)
214
What are the effects of opioids on the gastrointestinal system?
Constipation
215
What are the effects of opioids on the biliary tract?
Biliary colic (blockage of bile ducts- contraction of biliary smooth muscles)
216
What are the effects of opioids on the renal system?
-Decreased renal function
-Anti-diuretic effect
-Urinary retention
217
What are the effects of opioids on the endocrine system?
-Decreased testosterone with chronic use
-Decreased libido, energy, and mood
-Dysmenorrhea or amenorrhea in women
218
What are the effects of opioids on the skin?
-Pruritis (itchy feeling of the skin)
-Produce flushing and warming of the skin accompanied sometimes by sweating, urticaria (itchy red bumps), and itching
-Peripheral histamine release
219
What is the duration of action of fentanyl?
1 hour
220
What is the duration of action of methadone?
8 hours
221
What is the duration of action of morphine?
4 hours
222
What is the duration of action of oxycodone?
4 hours
223
What is the duration of action of codeine?
4 hours
224
What is the duration of action of hydrocodone?
4 hours
225
What is the duration of action of tramadol?
4 hours
226
What is the duration of action of buprenorphine?
5 hours
227
What is the duration of action of naloxone?
2 hours
228
What is the duration of action of naltrexone?
24 hours
229
What are the clinical used for opioids?
-Analgesia
-Acute pulmonary edema
-Cough
-Diarrhea
-Anesthesia
230
What are the signs & symptoms of opioid overdose?
-Euphoria
-Unconsciousness
-Respiratory depression
-Miosis
-Pulmonary edema
-Seizures
-Hypothermia
-Death
231
What is the opiate toxicity triad?
-CNS depression (coma)
-Respiratory depression (cyanosis)
-Pupillary miosis
232
What are adverse effects with chronic opioid use?
-Hypogonadism
-Immunosuppression
-Increased feeding
-Increased growth hormone secretion
-Withdrawal effects
-Tolerance, dependence
-Abuse, addiction
-Hyperalgesia
-Impairment while driving
233
What does a person develop tolerance for on opioids?
-Analgesic effect
-Sedating effect
-Respiratory depressant effects
-Antidiuretic, emetic, and hypotensive effects
234
What tolerance does not develop on opioids?
-Mitotic effect
-Convulsant effect
-Constipating effect
235
What is physical dependence of opioid use?
An invariable accompaniment of tolerance to repeated administration pf an opioid of the µ type
236
What are symptoms of withdrawal to opioids?
-Rhinorrhea
-Lacrimation
-Yawning
-Chills
-Gooseflesh
-Hyperventilation
-Hyperthermia
-Mydriasis
-Muscular aches
-Vomiting
-Diarrhea
-Anxiety
-Hostility
237
What is psychological dependence of opioids or other drugs?
Addiction
238
What are benefits of patient controlled anesthesia?
-May allow better pain control with fewer side effects
-Requires patient awareness and cognitive ability
-Increases patient satisfaction
239
What are special concerns for rehab with opioids?
-Schedule therapy when drugs reach peak
-Consider respiratory depression
-Constipation: pts may be uncomfortable
-Withdrawal symptoms or addiction
240
What are non-opioid analgesics?
-Non-steroidal anti-inflammatory drugs (NSAIDs)
-Acetaminophen (Tylenol)
241
What are the primary therapeutic effects of NSAIDs?
-Analgesic
-Anti-inflammatory
-Antipyretic (reduces body temp.)
-Anticoagulant
-Anticancer (colorectal cancer)
242
What are prostaglandins (PGs)?
-Small lipid compounds produced in almost all cells
-Cells begin to synthesize PGs in response to damage
243
What are the function of PGs?
-In the hypothalamus: thermoregulation
-Responsible for coagulation
-PGs can exaggerate pain
-Promote inflammation
-Abnormal coagulation
244
How are PGs synthesized?
Prostaglandings are made by an enzymatic reaction where cyclooxygenase (COX-1, COX-2) converts arachidonic acid into prostaglandins
245
What is the mechanism of action of NSAIDs?
NSAIDs inhibit cyclooxygenase (COX-1, COX-2) from converting arachidonic acid to prostaglandins
246
What are non-selective NSAIDs? What are examples of them?
-Inhibit COX-1 and COX-2
-Diclofenac
-Ibuprofen
-Naproxen
247
What are COX-2 selective NSAIDs? What are examples of them?
-Specifically inhibit COX-2
-Celecoxib (Celebrex)
-Rofecoxib
248
Why if Rofecoxib banned?
Due to cardiovascular side effects
249
What are the functions of the prostaglandins that COX-1 produces?
-PGs that mediate homeostatic functions
-Constitutively expressed
-Homeostatic protection of gastric mucosa
-Platelet activation
-Renal functions
-Macrophage differentiation
250
What are the functions of the prostaglandins that COX-2 produces?
-PGs that mediate inflammation, pain, and fever
-Induced mainly in sites of acute inflammation by cytokines
-Pathologic inflammation
-Pain
-Fever
-Dysregulated proliferation
251
What are common NSAIDs?
-Aspirin
-Ibuprofen
-Naproxen
-Indomethacin
-Meloxicam
-Diclofenac
-Celecoxib
252
What are common side effects of NSAIDs?
-Nausea and vomiting
-Diarrhea
-Constipation
-Decreased appetite
-Rash
-Dizziness
-Headache
-Drowsiness
253
What are side effects associated with chronic use of NSAIDs?
-Kidney failure
-Liver failure
-Ulcers
254
What are uncommon side effects of NSAIDs?
-Prolonged bleeding after injury or surgery
-Fluid retention/edema
255
What is the benefit of selective COX-2 NSAIDs vs non-selective NSAIDs?
-May decrease pain & inflammation with less toxicity (less gastritis)
-Better for long term use
256
What are the benefits of acetaminophen?
-Analgesic and antipyretic effects
-No gastric irritation
-No anticoagulant effects
-No anti-inflammatory effects
257
What are side effects of acetaminophen if taken in high doses?
Liver toxicity
258
What are indications for acetaminophen?
-Frequently 1st drug used to control pain in early stages of OA and other MSK conditions that do not have an inflammatory
-Children and teenagers
259
What is a contraindication for acetaminophen?
-Reyes syndrome
-This syndrome is a rare but serious condition that causes confusion, swelling in the brain, and liver damage
260
What is the mechanism of action of acetaminophen?
-Not fully understood
-Inhibits cyclooxygenase (COX)
-Unclear why it does not exert anticoagulant & anti-inflammatory effects: thought to preferentially inhibit CNS PG production vs peripheral
261
Why can high doses of acetaminophen cause liver toxicity?
-Acetaminophen metabolizes into a toxic intermediate
-It is quickly detoxified and eliminated via the urine
-High doses can result in accumulation of the toxic intermediate with subsequent toxicity to liver proteins
262
What are common acetaminophen + opioid combinations?
-Lortab, Lorcet: hydrocodone + acetaminophen
-Darvocet: propoxyphene + acetaminophen
-Percocet: oxycodone + acetaminophen
263
What are physical therapy considerations for patients on NSAIDs or acetaminophen?
-Pain masking
-GI effects
-Cardiovascular risks
-Renal effects
-Hepatotoxicity
-Therapy timing
-Patient education
-Monitoring side effects
264
What are steroidal anti-inflammatory drugs (SAIDs)?
-Glucocorticoids
-Derived from cholesterol
265
What three 1° adrenal steroids does the adrenal cortex produce?
-Glucocorticoids (cortisol, corticosterone)
-Mineralocorticoids (aldosterone)
-Sex hormones
266
What are the physiological functions of glucocorticoids?
-Control glucose metabolism
-Controls the body's ability to deal with stress
-Decrease inflammation
-Suppress the immune system
267
What is the precursor to steroids?
Cholesterol
268
What is the mechanism of action of glucocorticoids?
-Act on inflammatory cells
-Drug binds to glucocorticoid receptors in cytoplasm
-Drug-receptor complex travels to nucleus of the cell and alters gene expression
-Decreases expression of inflammatory proteins
-Increases expression of anti-inflammatory proteins
269
What is the clinical use of glucocorticoids?
-Endocrine conditions: normalize adrenal cortical hypofunction
-Nonendocrine conditions: RA, tenosynovitis, myositis, collagen disease
270
How are glucocorticoids for nonendocrine conditions such as RA or tenosynovitis administered?
Injections into specific tissues to help localize effects
271
What are some common glucocorticoids?
-Cortisone
-Dexamethasone
-Prednisone
-Hydrocortisone
272
What glucocorticoid is typically used for anaphylaxis?
Dexamethasone
273
What are methods of administering glucocorticoids?
-Oral: systemic
-Injections: local
-Dose packs: provide large dose but tapers off over 4-5 day period
274
What are adverse effects of glucocorticoids?
-Adrenocortical suppression
-Peptic ulcers
-Drug induced Cushing Syndrome
-Adrenal crisis/shock
-Breakdown of supporting tissues
-Decreases body's ability to absorb calcium and can lead to osteoporosis
275
What are side effects of glucocorticoids?
-Headache
-Irregular heartbeat
-Sweating
-Dizziness
-Irritability
276
How does breakdown of supporting tissues occur from glucocorticoid use?
-Bone, ligaments, tendons, and skin are subject to a wasting effect from prolonged use
-Inhibits the genes responsible for production of collagen and other tissue components by increasing the expression of substances that promote breakdown of bone, muscle, etc.
-Interferes with muscle protein synthesis
-Can cause skeletal muscle atrophy
277
What are the signs & symptoms of drug induced Cushing Syndrome?
-Roundness and puffiness in the face
-Fat deposition and obesity in the trunk
-Muscle wasting in extremities
-Hypertension
-Osteoporosis
-Increased body hair
-Glucose intolerance
278
What are signs & symptoms of adrenal crisis/shock?
-Vasodilation of the organs
-Vascular collapse
-Severe hypotension
-Pain in legs, low back, abdomen
-Low BP, syncope
-Vomiting and diarrhea
-Hyperkalemia
-Hyponatremia
279
How can glucocorticoids lead to osteoporosis?
-Shifts the balance of bone metabolism leading to increased breakdown
-Stimulates osteoclast-induced bone resorption
-Inhibits osteoblast-induced bone formation
280
What are other side effects of glucocorticoids?
-Salt/water retention
-Increased infection
-Gastric ulcers due to decreased good PGs in stomach
-Glucose intolerance
-Glaucoma-effect vitreous humor drainage
-Adrenal suppression
281
What are PT considerations for glucocorticoid use?
-Increased risk of fractures, falls, and infection
-Strengthening exercises to maintain muscle mass
-Encourage weight bearing activities such as walking
-Inspection for skin breakdown
-Monitor blood pressure
282
What is arthritis?
-A general term that refers to a group of more than 100 disorders affecting the joints
-Inflammation, pain, and stiffness in the joint
283
What are different types of arthritis?
-Osteoarthritis
-Rheumatoid arthritis
-Psoriatic arthritis
-Gout
-Ankylosing spondylitis
284
What is rheumatoid arthritis?
-Autoimmune disorder
-The body's immune system attacks the joints
285
What are signs and symptoms of rheumatoid arthritis?
-Often affects joints symmetrically
-Commonly affects wrists, fingers, knees, feet, and ankles
-Usually starts at middle age
-Joints may be swollen, warm, and puffy
-Morning stiffness > 30 minutes
-Systemic inflammation
-Pain worse after periods of inactivity
-May be accompanied by fever, fatigue, and weight loss
286
What drugs can be used to treat RA?
-Disease modifying antirheumatic drugs (DMARDS)
-NSAIDs
-Corticosteroids
-Biologic agents
287
What is osteoarthritis?
-Degenerative disorder
-Wear and tear of the joint cartilage
288
What are the signs and symptoms of osteoarthritis?
-Usually affects weight bearing joints (hips, knees, spine)
-Usually starts at middle age or older adults
-Morning stiffness < 30 minutes
-Reduced ROM
-Inflammation localized to affected joint
-No systemic symptoms
289
What drugs can be used to treat osteoarthritis?
-Acetaminophen
-NSAIDs
-PT
-Weight management
-Joint injections
-Surgery
290
What is typically the first-line treatment for pain relief in osteoarthritis?
Acetaminophen
291
What is the most significant concern with high doses of acetaminophen?
Liver toxicity
292
What are common side effects from acetaminophen?
-Nausea or vomiting
-Loss of appetite
-Allergic reactions like skin rash, itching, or hives
293
What is the maximum recommended daily dose of acetaminophen?
4,000mg for adults but lower limits are often recommended
294
What are the most common NSAIDs used for osteoarthritis?
-Ibuprofen
-Naproxen sodium
-Celecoxib
-Diclofenac
-Meloxicam
295
What is the mechanism of action of hyaluronic acid injections for osteoarthritis?
-Hyaluronic acid is a polysaccharide similar to the natural joint fluid that lubricates the joint
-When injected into the joint, it acts as a lubricant and shock absorber
-Helps to reduce pain and friction in the joint
296
What are the side effects of hyaluronic acid injections?
-Pain at the injection site
-Joint stiffness
-Headache
297
What is the mechanism of action of chondroitin sulfate for osteoarthritis?
-Chondroitin sulfate is one of the building blocks of cartilage
-It is believed to help prevent the breakdown of cartilage and stimulate its repair mechanism
-Also thought to have anti-inflammatory properties and improve the consistency of synovial fluid
298
What are side effects of chondroitin sulfate?
-Stomach pain
-Nausea
-Diarrhea
-Constipation
-Headache
-Swelling of the eyelids or legs
299
What are physical therapy considerations when working with patients with osteoarthritis that are taking medication?
-Medication schedule
-Monitor for overuse
-Educate on medication limits
-Check for side effects
-Patient feedback
300
What is the prevalence of rheumatoid arthritis?
1% of the population and is more common in women
301
What is the pathogenesis of RA?
-Antigen presenting cells process and present antigens to T cells, which may stimulate B cells to produce antibodies and osteoclasts to destroy and remove bone
-Macrophages stimulated by immune response can stimulate T cells and osteoclasts to promote inflammation
-Activated T cells and macrophages release factors that promote tissue destruction, increase blood flow, and result in cellular invasion of synovial tissue and fluid
302
What are the main pro-inflammatory cytokines that are involved in the pathogenesis of RA?
-Interleukin-1 (IL-1)
-Tumor necrosis factor-⍺ (TNF-⍺)
303
What is the difference between traditional Disease Modifying Anti-Rheumatic Drugs (DMARDs) and targeted DMARDs?
-Traditional DMARDs restrict your immune system broadly
-Targeted DMARDs block precise pathways inside immune cells
304
How are biologic drugs produced? How do they work?
-Produced by living cells
-Work on individual immune proteins called cytokines
305
What is the general strategy of biologic drugs for RA?
-Inhibit autoimmune response underlying RA
-Inhibition of cytokines
-Inhibit cellular activation
306
What is the mechanism of action of Methotrexate for RA?
Inhibits dihydrofolate reductase enzyme, which reduces nucleotide synthesis
307
What are the adverse effects of Methotrexate?
-Hepatic fibrosis
-Rash
-Thrombocytopenia
-Leukopenia
308
What is the mechanism of action of hydroxychloroquine for RA? What are the adverse effects?
-Not well understood
-Thought to be an immunomodulator
-Retinal damage
-Rash
309
What is the mechanism of action of Leflunomide for RA? What are the adverse effects?
-Inhibits pyrimidine synthesis
-Hepatitis
310
What is the mechanism of action of Sulfasalazine for RA? What are the adverse effects?
-Not well understood
-Rash
-Photosensitivity
311
What are common TNF-⍺ blockers used for RA?
-Etanercept
-Infliximab
-Adalimumab
-Certolizumab
-Golimumab
312
What are adverse effects of TNF-⍺ blockers?
-Local injection site reactions
-Infection
-Immune reactions
-Malignancy
313
What are common non-TNF-⍺ biologics that are used to treat RA?
-Rituximab
-Abatacept
-Tocilizumab
-Baricitinib
-Anakinra
314
What are physical therapy considerations for patients on medications for RA?
-DMARDs can cause fatigue or reduced tolerance to exercise
-Injection site
-Steroids can increase risk of fx
-Pain masking: monitor for signs of overuse
-Understanding interactions of medications and PT
315
What is osteoporosis?
A bone disease characterized by a decrease in bone density and an increases risk of fractures
316
What is the prevalence of osteoporosis?
-10 million diagnosed with osteoporosis
-34 million with low bone density
-1.5 million fractures annually
317
What are risk factors for osteoporosis?
-Postmenopausal women
-Old age
-Medications
-Endocrine disorders
-Inflammatory arthropathy
-Hematopoietic disorders
-Nutrition disorders
318
What is used to diagnose osteoporosis and measure bone density?
Dual X-ray absorptiometry (DEXA)
319
What are the different bone cell types?
-Osteogenic cell: bone stem cell
-Osteoblast: bone forming cell
-Osteoclast: bone resorption
-Osteocyte: maintains bone tissue
320
How does parathyroid hormone effect bone density?
-In low and intermittent doses, it increases bone formation
-In excess doses, it increases bone resorption
321
What stimulates the release of parathyroid hormone? What does this cause?
-Low Ca2+ levels in the blood trigger the release of PTH which increases bone resorption to release calcium from bone tissue
-PTH release increases renal reabsorption of Ca2+
322
How does vitamin D effect bone formation?
It stimulates intestinal absorption of Ca2+ and phosphate
323
How does calcitonin effect bone tissue?
Lowers blood levels of Ca2+ and phosphate by inhibiting osteoclast activity
324
What is involved in normal bone homeostatis?
-PTH binds to receptors on osteoblasts
-Osteoblasts secrete RANKL and OPG (decoy receptor for RANKL)
-Osteoclasts are activated by RANKL
-There is a balance between osteoblast activity and osteoclast activity
325
What is involved in osteoporsis bone formation and resorption physiology?
-Osteocytes upregulates RANKL and down regulates OPG synthesis
-RANKL binds to osteoclasts and increases osteoclast proliferation
-Activated osteoclasts cause significant resorption
326
What are some common drugs that are used to treat osteoporosis?
-Bisphosphonates
-Selective estrogen receptor modulators (SERMs)
-Calcitonin
-RANKL inhibitors
-Parathyroid hormone (low doses)
-Calcium and vitamin D supplements
327
What is the mechanism of action of bisphosphonates?
-Binds to osteoclasts and promotes apoptosis
-Binds to hydroxyapatite and prevents osteoclast activity
328
What are common bisphosphonates used to treat osteoporosis?
-Alendronate
-Risedronate
-Ibandronate
-Zoledronic acid
329
What are side effects of bisphosphonates?
-GI disturbances: acid reflux
-Osteonecrosis of the jaw
-Atypical femur fractures
330
What are special instructions for patients taking bisphosphonates? Why?
-Swallow whole with water 30 minutes before breakfast
-Sit or stand upright for 30 minutes after taking the tablet
-To avoid gastric reflux
331
What is the mechanism of action of selective estrogen receptor modulators (SERMs)?
Mimic estrogen in bone, reducing bone resorption without stimulating breast or uterine tissue
332
What are common side effects of SERMs?
-Hot flashes
-Leg cramps
-Increased risk of venous thromboembolism
333
What is a common SERM used to treat osteoporosis?
Raloxifene
334
What is the mechanism of action of calcitonin?
Inhibits osteoclast activity
335
What are common side effects of calcitonin?
-Nasal irritation (with nasal spray)
-Hot flashes
336
What is a common calcitonin used to treat osteoporosis?
-Miacalcin
-Salmon calcitonin
337
What is the mechanism of action of parathyroid hormone analogs?
Stimulates osteoblast activity
338
What are common side effects of parathyroid hormone analogs?
-Leg cramps
-Dizziness
-Nausea
339
What are common parathyroid hormone analogs used to treat osteoporosis?
-Teriparatide
-Abaloparatide
340
What is the mechanism of action of monoclonal antibodies for osteoporosis?
Binds and inhibits RANKL, reducing osteoclast activity
341
What are some common side effects of monoclonal antibodies used to treat osteoporosis?
-Skin reaction at the injection site
-Osteonecrosis of the jaw
-Hypocalcemia
342
What is a common monoclonal antibody that is used to treat osteoporosis?
Denosumab (Prolia, Xgeva)
343
How does low levels of vitamin D effect PTH?
Low levels of vitamin D can stimulate the parathyroid gland to produce more PTH (secondary hyperparathyroidism)
344
What is the role of calcium in bone?
It forms hydroxyapatite crystals, which gives bone its hardness
345
What are PT considerations for patients taking bisphosphonates?
-Be aware of GI issues
-Have pt take medication at least 1 hour prior to session
-Rare risk of atypical femur fracture or osteonecrosis of the jaw
346
What are PT considerations for patients taking SERMs?
-Hot flashes or leg cramps
-Watch for signs of venous thromboembolism
347
What are PT considerations for patients taking calcitonin?
Monitor for nasal irritation side effects
348
What are PT considerations for patients taking parathyroid hormone analogs?
Monitor for leg cramps and dizziness
349
What are PT considerations for patients taking monoclonal antibodies?
-Monitor for joint pain: back and/or arm or leg pain
-Pts may have low calcium levels
350
What are schedule I drugs?
-Drugs or substances that have no currently accepted medical use and a high potential for abuse
-Ex: heroin, LSD, marijuana, MDMA
351
What are schedule II drugs?
-Drugs or substances with a high potential for abuse but has accepted medical use
-Ex: fetanyl, cocaine, oxycodone, morphine, etc.
352
What are schedule III drugs?
-Drugs with moderate or lower abuse potential compared to schedule II
-Ex: anabolic steroids, testosterone, codeine, ketamine, etc.
353
What are schedule IV drugs?
-Drugs with lower abuse potential compared to schedule III
-Ex: diazepam, lorazepam, tramadol, etc.
354
What are schedule V drugs?
-Drugs with the lowest abuse potential
-Ex: low dose opioids in cough medicine, pregabalin, lamotil, etc.
355
What is pharmacokinetics?
What the body does to the drug
356
What is pharmacodynamics?
What the drug does to the body
357
What are the principles of pharmacokinetics?
-Absorption (stomach/intestines)
-Distribution
-Metabolism (liver)
-Excretion (kidney)
358
What is the median effective dose (ED50)?
Dose at which 50% of the population responds to the drug in a specific manner (positively)
359
What is the median toxic dose (T50)?
Dose at which 50% of the population experiences adverse effects
360
What is the median lethal dose (L50)?
Dose that causes death in 50% of the population
361
What is the therapeutic index (TI)?
-Indicator of the drugs safety
-Median toxic dose (TD50) divided by median effective dose (ED50)
-TI= TD50/ED50
-The greater the TI, the safer the drug
