UNIT 9: ANALGESICS

(Analgesic) (Pain) (subjective) (nociceptive or neuropathic pain)

(_____________)

• Management of pain is one of clinical medicine’s greatest

challenges.

• (_________) → pain reliever; given in order to manage pain

• (______) → is defined as an unpleasant sensation that can

be either acute or chronic and is a consequence of

complex neurochemical processes in the peripheral and

central nervous systems (CNS).

• It is (______), and the clinician must rely on the

patient’s perception and description of pain.

• Alleviation of pain depends on the specific type of pain,

(_______/______).

(Nociceptive pain) (Nociceptive pain)

(_________) → is a medical term used to describe

the pain from physical damage or potential damage to the

body.

• Examples might be the pain felt from

a sports injury, a dental procedure,

or arthritis.

• (_________) is the most

common type of pain people

experience.

• It develops when the nociceptive

nerve fibers are triggered by

inflammation, chemicals, or physical

events, such as stubbing a toe on furniture.

(NEUROPATHIC PAIN) (neuropathic pain)

(o Alcoholism

o Shingles

o Unmanaged diabetes

o Stroke

o Multiple sclerosis

o Or even cancer treatments)

(__________) → is used to describe the pain that

develops when the nervous system is damaged or not

working properly due to disease or injury.

• It is different from nociceptive pain

because it does not develop in

response to any specific

circumstance or outside stimulus.

• In fact, people can suffer from

(1) (__________) even when the

aching or injured body part is not

actually there.

• (1) (_________) is also referred to

as nerve pain and is usually chronic.

• Neuropathy can result from may different conditions such

as:

o

o

o

o

o

o

(nociceptive pain), nonopioid analgesics) (nonsteroidal anti-inflammatory agents (NSAIDs)) (opioids)

• For example, with mild to moderate arthritic pain

(_________, _________) such as

(_______________________) are

often effective.

• Neuropathic pain can be treated with opioids (some

situations require higher doses) but responds best to

anticonvulsants, tricyclic antidepressants, or

serotonin/norepinephrine reuptake inhibitors.

• However, for severe or chronic malignant or

nonmalignant pain, (_______) are considered part of the

treatment plan in select patients.

(Opioids) (natural opioid analgesics)

(_________) are natural, semisynthetic, or synthetic

compounds that produce morphine-like effects.

o Eg. (___________________) can be produced from

somniferum papaver

• These agents are divided into chemical classes based on

their chemical structure.

(• Morphine

• Codeine)

(• Hydromorphone

• Hydrocodone

• Oxycodone

• Oxymorphone)

(• Fentanyl

• Meperidine

• Methadone

• Tapentadol

• Tramadol)

SUMMARY OF CHEMICAL CLASSES OF OPIOID

AGONISTS

NATURAL	SEMISYNTHETIC	SYNTHETIC

(peptide neurotransmitters) (analgesic effect) (Endorphins, enkephalins, and dynorphin)

• All opioids act by binding to specific opioid receptors

in the CNS to produce effects that mimic the action of

endogenous (______________) (for example,

endorphins, enkephalins, and dynorphins)

• Our bodies produce these neurotransmitters in order to

produce (__________).

• Unfortunately, widespread availability of opioids has led

to abuse of those agents with euphoric properties (which

is why morphine is a controlled substance).

• Note: (_______, _________, _______) are

powerful peptide or polypeptide analgesics.

(μ (mu) (Endorphins > Enkephalins > Dynorphins) (δ (delta))

(Enkephalins > Endorphins and Dynorphins) (κ (kappa))

(Dynorphins > > Endorphins and enkephalins) ()

OPIOID RECEPTOR SUBTYPES, THEIR FUNCTIONS,

AND THEIR ENDOGENOUS PEPTIDE AFFINITIES

RECEPTOR SUBTYPE	FUNCTIONS	ENDOGENOUS OPIOID PEPTIDE AFFINITY
(________)	Supraspinal and spinal analgesia; sedation; inhibition of respiration; slowed gastrointestinal transit; modulation of hormone and neurotransmitter	(__________)
(_________)	Supraspinal and spinal analgesia; modulation of hormone and neurotransmitter release	(__________)

(_________)	Supraspinal and spinal analgesia; psychotomimetic effects; slowed gastrointestinal transit	(_______)

(• Morphine

• Methadone

• Fentanyl) (fentanyl, morphine) (morphine only) (methadone only)

SUMMARY: OPIOIDS, OPIOID SUBSTITUTES, AND OPIOID ANTAGONISTS

SUBCLASS, DRUG	MECHANISM OF ACTION	EFFECTS
	• Strong μ- receptor agonists • Variable affinity for δ and κ receptors	• Analgesia • Relief of anxiety • Sedation • Slowed gastrointestinal transit
	• Less efficacious than morphine • Can antagonize strong agonists	• Like strong agonists • Weaker effects

MIXED OPIOID AGONIST-ANTAGONISTS
	• Partial μ agonist • κ antagonist	• Like strong agonists but can antagonize their effects • Also reduces craving for alcohol
	• κ agonist • μ antagonist	• Similar to buprenorphine

CLINICAL APPLICATIONS	PHARMACOKINETICS,
• Severe pain • Adjunct in anesthesia (______, _____) • Pulmonary edema (________) • Maintenance in rehabilitation programs (___________)	• First-pass effect • Duration 1-4 h except methadone, 4-6 h • Toxicity: respiratory depression, • Severe constipation, • Addiction liability, • Convulsions
• Mild-moderate pain • Cough (codeine)	• Like strong agonists, toxicity dependent on genetic variation of metabolism

• Moderate pain • Some maintenance rehabilitation programs	• Long duration of action 4-8 h • May precipitate abstinence syndrome
• Moderate pain	• Like buprenorphine

NON-OPIOID ANALGESICS

• In terms of effect, they can remove pain but they do not

produce the effects of morphine or narcotic effects.

• Generally safer; most of them can be bought OTC.

(prostaglandins) ()

• The NSAIDs act by inhibiting the synthesis of

(___________).

• (__________) → created from arachidonic acid

(a 20-carbon fatty acid in the body) that is converted by

cyclooxygenase enzyme; the major mediator of pain and

causes inflammation

(BAYER, BUFFERIN, ECOTRIN) (CELEBREX)

(CATAFLAM, FLECTOR, PENNSAID, VOLTAREN) (DOLOBID) (NALFON) (ANSAID) (ADVIL, MOTRIN) (INDOCIN) (ACULAR, ACUVAIL, TORADOL) (PONSTEL) (MOBIC) (WINTERGREEN OIL)

(ALEVE, ANAPROX, NAPROSYN) (DAYPRO) (FELDENE) (CLINORIL) (TOLMETIN SODIUM)

NSAIDs

Aspirin	(___, ___, ___)
Celecoxib	(____)
Diclofenac	(__, ___, ____, ____)

Diflunisal	(_______)
Etodolac
Fenoprofen	(________)

Flurbiprofen	(________)
Ibuprofen	(____, ___)
Indomethacin	(________)

Ketorolac	(___, ___, __)
Ketoprofen
Meclofenamate

Mefenamic acid	(_______)
Meloxicam	(________)
Methyl salicylate	(________)

Nabumetone
Naproxen	(____, _____, ____)
Oxaprozin	(________)

Piroxicam	(______)
Salsalate
Sulindac	(_______)

Tolmetin	(________)

(Arachidonic acid) (Cyclooxygenase

Reaction) (Prostaglandin G2) (Peroxidase

reaction) (Prostaglandin H2)

(_______)

↓

(___________)

↓

(__________)

↓

(____________)

↓

(______________)

↓

Prostaglandins

Prostacyclin

Thromboxanes

• Mucosa

protection

• Platelet

aggregation

• Renal blood

flow)

(- Inflammation,

Pain

• Fever

• Ischemia

(CNS)

• Morbus

Alzheimer

• Cancer)

• Kidney:

renin

secretion

• Wound/ulcer

healing

• Female

reproductive

functions

• Bone

metabolism

• Vascular

protection)

COX-1

Homeostasis

COX-2

Pathophys- iology	Adaptation

(Upper Gl disturbance are common) (Low cost; long history) (No antipyretic e-ec t) (Less Gl irritation than aspirin) (Very potent; should be used only after less toxic agents have proven ine ec tive Long half-life permits dally or twice-daily dosing CNS disturbances are common, Upper Gl disturbance are common) (Long half-life permits dally or twice-daily dosing) (Lower toxicity and better acceptance in some patients. Naproxen is considered by some experts as one of the safest NSAIDS) (Long half-life permits dally or twice-daily dosing) (Potential for increasing myocardial infarctions and strokes) (Less Gl irritation than aspirin)

Salicylates:

Therapeutic disadvantage of selected NSAID		Therapeutic disadvantage of selected NSAID
(______)	Aspirin	(_______)
	Salicylate salt

(________)	Diflunisal	(_______)

Acetic acids:

(________)	Indomethacin	(_______)
	Sulindac	(_______)
	Tolmetin

Propionic acids:

	Ibuprofen Fenoprofen Flurbiprofen Ketoprofen Naproxen Oxaprozin	(__________)

Oxicams:

	Piroxicam Meloxicam	()

Fenamates:

	Mefenamic acid
	Meclofenamlc acid

COX-2 inhibitors:

	Celecoxib

(Acetaminophen) (Acetaminophen) (cyclooxygenase) (peripheral tissues)

(____________) (N-acetyl-p-aminophenol or APAP or

paracetamol in the PH) inhibits prostaglandin synthesis in

the CNS.

• This explains its antipyretic and analgesic properties.

• (___________) has less effect on (___________) in

(____________) (due to peripheral inactivation), which

accounts for its weak anti-inflammatory activity.

• It is inactivated in our periphery.