Analgesics & Muscle

Relaxants:
Primum non nocere
Kenneth McCall, BSPharm, PharmD
Associate Professor
UNE College of Pharmacy

Objectives
Classify opioids based upon agonist, partial

agonist, or antagonist receptor effects.

Classify benzodiazepines based upon their
half-life and duration of action.
Classify NSAIDs according to their
cyclooxygenase selectivity.
Identify the DEA schedule for a given drug.
Recognize the pharmacologic effects of
opioids, benzodiazepines, non-benzo muscle
relaxants, and NSAIDs.

Outline: The Duality of Analgesics

Opioids
Benzodiazepines
Non-benzo Muscle Relaxants
NSAIDs

Opioids in Nature
Opium Poppy
Endorphins
Decrease appetite
Decrease stress
Reduce pain
Make you happy

Classification of Opioids
Agonists
Morphine, codeine, hydrocodone , methadone,
meperidine, fentanyl, oxycodone
Partial agonists
Buprenorphine (reach a plateu), pentazocine
Antagonists
Naloxone (reverse overdose from an opioids),
naltrexone

Pharmacology

Agonist = drugs that occupy a receptor and activate them

Antagonist = drugs that occupy a receptor and block receptor
activation.

Agonist alone

FULL ACTIVATION

Agonist + Antagonist
Antagonist alone
Stimulates and blocks
- Creates a plateu in
the pharmalogic effect

LESS activation

No activation

Before Opioid Receptor Activation

After Opioid Receptor Activation

After Opioid Receptor Activation

Opioid Pharmacologic
Effects
Mu-1 and Mu-2 Receptor Mediated
Analgesia
Sedation- can develop a tolerance to if on for a
while
Euphoria
Respiratory depression
Cough suppression
Miosis
Nausea & vomiting
Constipation
Tolerance, physical dependence, and withdrawal

Pharmacodynamics
Dose-Response Curve

Opioid Indications
Acute and chronic pain
Malignant and nonmalignant pain
Scientific evidence for malignant pain (cancer)
No evidence for long term opioid use for
nonmalignant pain
Neuropathic and muskuloskeletal pain

DEA Classification

Schedule I
High potential for abuse and no currently accepted
medical use in the US (heroin, MDMA, marijuana)
Schedule II
High potential for abuse and currently accepted medical

use in the United States (pure opiates, amphetamines,

barbiturates, hydrocodone).

Schedule III
Potential for abuse less than the drugs in schedules I
and II (codeine mixed with NSAID or APAP,
buprenorphine).
Schedule IV
Low potential for abuse relative to the drugs in schedule

III (benzodiazepines, z-drugs zolpidem, tramadol).

Which of the following is an opioid

antagonist?
1.
2.
3.
4.

Morphine
Hydrocodone
Fentanyl
Naloxone

Which of the following is a partial

agonist?
1.
2.
3.
4.

Oxycodone
Buprenorphine
Naloxone
Hydrocodone

Which of the following is NOT a

pharmacologic effect of an opioid agonist?

1.
2.
3.
4.

Sedation
Mydriasis
Respiratory depression
Euphoria

Categorize hydrocodone/APAP
according to the DEA Classification.
1.
2.
3.
4.

Schedule
Schedule
Schedule
Schedule

I
II
III
IV

Benzodiazepine Mechanism of
Action
Benzodiazepines enhance the effect of the
neurotransmitter gamma-aminobutyric acid
(GABA). (inhibitory)

http://pharmacologycorner.com/animation-benzodiazepines-diazepam-lorazepam-alprazolam
/

Classification of Benzos
Short acting
midazolam, triazolam
Intermediate acting
alprazolam, lorazepam, temazepam
Long acting
Diazepam (valeum), chlordiazepoxide,
flurazepam

Benzo Pharmacologic
Effects*
Sedation
Hypnotic
Anxiolytic
Anticonvulsant
Muscle relaxant
Amnesia
Tolerance, physical dependence, and

withdrawal

*Z drugs (zolpidem etc) only cause sedation and do not

have anxiolytic, anticonvulsant and muscle relaxant effects

Benzodiazepine
Indications
Insomnia short term use
Anxiety
Seizure disorders
Muscle spasm
Pre-surgical retrograde amnesia

2012 Beers Criteria Benzos

Recommendation: Avoid benzodiazepines of

any type for treatment of insomnia, agitation,

or delirium.
Rationale: Older adults have increased
sensitivity to benzos and slower metabolism
of long-acting agents. In general, all benzos
increase risk of cognitive impairment,
delirium, falls, fractures, and motor vehicle
accidents.
J Am Geriatr Soc 2012.

2012 Beers Criteria Z

drugs
Recommendation: Avoid chronic use (>90

days)
Rationale: Benzodiazepine receptor agonists
have adverse events similar to those of
benzodiazepines in older adults (delirium,
falls, fractures).

J Am Geriatr Soc 2012.

Benzodiazepines are classified based on

their half-life. Which of the following is
long acting?
1.
2.
3.
4.

Midazolam
Alprazolam
Diazepam
Lorazepam

Compare the pharmacological effects of alprazolam

and zolpidem. Which of the following is true for both?

1.
2.
3.
4.

Sedation
Anxiolytic
Anticonvulsant
Muscle relaxant

Non-Benzodiazepine Muscle
Relaxants
metaxalone (Skelaxin)
cyclobenzaprine (Flexeril)
carisoprodol (Soma)
methocarbamol (Robaxin)

Centrally Acting Muscle Relaxants

Mechanism of Action
Decrease muscle tone and alleviate muscle

spasm, pain and hyper-reflexia.

Central nervous system relaxation is achieved
in general by mimicking or enhancing the
effects of substances such as GABA.

Centrally Acting Muscle Relaxants

Pharmacologic Effects
Sedation
Impaired motor coordination
Dependence
Dry mouth, constipation, blurred vision

2012 Beers Criteria Muscle

Relaxants
Recommendation: Avoid.
Rationale: Most muscle relaxants are poorly

tolerated by older adults because of

anticholinergic adverse events, sedation, and
risk of fractures.

J Am Geriatr Soc 2012.

Avoid Anticholinergics

Arch Intern Med. 2008;168(5):508-513

Avoid Anticholinergics
Highest Risk:
Amitriptyline, atropine, benztropine, carisoprodol,
chlorpheniramine, cyproheptadine, dicyclomine,
diphenhydramine (Benadryl), fluphenazine,
hydroxyzine, hyoscyamine, imipramine, meclizine,
oxybutynin, perphenzazine, promethazine,
thioridazine, thiothixene, tizanidine, trifluoperazine
High Risk:
Amantadine, baclofen, cetirizine, cimetidine,

clozapine, cyclobenzaprine, desipramine,

loperamide, loratadine, nortriptyline, olanzapine,
prochlorperazine, pseudoephedrine, tolterodine
Arch Intern Med. 2008;168(5):508-513

Avoid Anticholinergics
Medium Risk:
Carbidopa-levodopa, entacapone, haloperidol,
methocarbamol, metoclopramide,
mirtazapine, paroxetine, pramipexole,
quetiapine, ranitidine, risperidone, selegiline,
trazodone, ziprasidone

Arch Intern Med. 2008;168(5):508-513

Which of the following drugs

contains anticholinergic properties?
1.
2.
3.
4.

Codeine
Cyclobenzaprine
Lorazepam
Lunesta

Non-steroidal Anti-inflammatory
Drugs

NSAIDs Mechanism of
Action
Reduce prostaglandin production by inhibiting

cyclo-oxygenase (COX-1, COX-2) enzymes.

Decreased prostaglandin production
Analgesia
Antipyresis (reduce fever)
Anti-inflammation

NSAIDs Mechanism of
Action
Cell membrane phospholipids
Endolipase corticosteroids
Arachidonic acid
Cyclooxygenase NSAIDs
Thromboxane
Prostaglandins
Prostacyclin

COX-1 vs. COX-2

Cyclooxygenase 1
Platelet activation and aggregation
Afferent arteriole dilation and increased
glomerular filtration
Increased GI mucous production
Cyclooxygenase 2
Analgesia and inflammatory response

NSAID Classification vs
APAP
Non-selective
Ibuprofen, naproxen, ketoprofen, indomethacin, aspirin,

etodolac, piroxicam, ketorolac

Risk of GI, Renal side effects and elevated Blood Pressure

Selective COX-2 Inhibitors

Celecoxib, valdecoxib, rofecoxib
Less GI risk
Same renal risk and elevated blood pressure as non-selective
Acetaminophen
Analgesia, but no anti-inflammatory properties
Less GI, blood pressure and renal risks
Liver toxicity avoid daily doses > 3 grams in adults
#1 cause of hepatic injury due to overdose

2012 Beers Criteria NSAIDs, nonselective

Recommendation: Avoid chronic use unless

other alternatives are not effective and

patient can take gastroprotective agent (PPI
omeprazole)
Rationale: Increases risk of GI bleeding and
peptic ulcer disease in high-risk groups
including those >75, taking oral
corticosteroids, anticoagulants, or antiplatelet
agents. Indomethacin and ketorolac have
highest rate of adverse effects.
J Am Geriatr Soc 2012.

Which of the following agents has

anti-inflammatory properties?
1.
2.
3.
4.

Oxycodone
Ibuprofen
Acetaminophen
Diazepam

Which of the following agents has muscle

relaxant properties, but not anticholinergic.

1.
2.
3.
4.

Lorazepam
Carisoprodol
Naproxen
Acetaminophen

Compare the adverse effects of NSAIDs and

Acetaminophen. Which analgesic is safest for
a patient with high blood pressure and
chronic renal disease?

1.
2.
3.
4.

Indomethacin
Ibuprofen
Acetaminophen
Celebrex

CASE Discussion
45 year-old man. Three years ago,

symptomatic beginning of lumbar painwhen

the patient, spending a lot of time seated in
his office, complained of pain in his back when
standing up from the chair.
The ordered lumbar MRI at that time showed
spondylosis and degenerative disc disease
mostly in the L3-4 and L4-5 segments with
right L4-5 disc herniation.
Medical Opinion Medical Case Studies

CASE Continued
The pain was persisting on and off until four

weeks ago, when the axial low back pain

increased with lower extremities radiation,
parasthesias andtingling.
The pain is constant, fluctuating at a 18/10VAS level. The pain increases with
prolonged sitting and getting up from the
chair. It improves insupine positionand
resolves with an injection of Voltaren.

CASE Continued
The lumbar MRI, that was repeated,

was consistent with spondylosis and

degenerative disc disease.
Worsening disc herniation both at
L3-4 with left side herniation and L45 with right disc herniation.

CASE Continued
What physical therapy and pharmacologic

plan do you recommend?

Questions???
Ask your pharmacist.