Download ADVERSE REACTIONS - Dentalelle Tutoring

Pharmacology
DENTALELLE TUTORING
WHAT ARE AUTACOIDS?
OCCUR NATURALLY IN THE
BODY
PRODUCED IN ONE ORGAN AND ARE
TRANSPORTED VIA THE LYMPH SYSTEM
ALL OCCUR (MADE) NATURALLY IN THE
BODY.
•
•
Terms & Definitions
 Autacoids - Examples:
 Prostaglandins – lipids that are synthesized
locally by inflammatory stimuli –↑↑ PAIN
receptors
 Thromboxanes (a vasoconstrictor and a potent hypertensive
agent, and facilitates platelet aggregation [clotting]).
 Leukotrienes (Inflammatory molecules; precursor of
prostaglandins)
 “-kinins” - messengers
IS PAIN DIFFERENT FOR
EVERYONE?
YES
WHAT ARE PLACEBOS?
‘’FAKE’ DRUGS
FOR SOME PEOPLE, PAIN CAN ALSO BE
EFFECTIVELY TREATED WITH INACTIVE
PILLS (PLACEBOS)
WHAT ARE ANTIPYRETICS
ALSO CALLED?
NON-OPIODS
NON OPIOID ANALGESICS ARE ALSO CALLED:
NONNARCOTIC, PERIPHERAL, MILD, AND
ANTIPYRETIC (AGENTS THAT REDUCE
FEVER)
OPIOID ANALGESICS ARE ALSO CALLED:
NARCOTIC,
CENTRAL, OR
STRONG ANALGESICS.
Classification of Analgesic Agents
1. Nonopioids (nonnarcotics)
 Act primarily at the:
peripheral nerve endings
Difference is in
their site of action
 Inhibit prostaglandin
synthesis (regulating the
contraction and relaxation of
smooth muscle tissue)
 Not effective for severe pain
 3 subgroups:
• Salicylates (aspirin-like group)
• NSAIDs
• Acetaminophen
Difference in their
mode of action
2. Opioids (narcotics)
Act primarily within the:
central nervous
system
Depress the central
nervous system
Effective
for severe pain
Examples:
Morphine,
Codeine, Agents in cough
suppressants
We
will discuss this area
more in the next chapter
WHAT CATEGORY IS ASPIRIN
UNDER?
SALICYLATES
ASPIRIN IS THE MOST USEFUL AND COMMON
SALICYLATE TO REDUCE PAIN (ANALGESIC
ACTION)
ACETYL SALICYLIC ACID (ASA) – THE
CHEMICAL NAME FOR ASPIRIN
WHAT DOES NSAIDS STAND
FOR AND WHAT DOES IT
MEEAN?
NONSTEROIDAL ANTIINFLAMMATORY DRUGS
Salicylates
• Aspirin belongs to a class of medications called
nonsteroidal antiinflammatory drugs (NSAIDs).
– Aspirin and other NSAIDs, for example,
ibuprofen (eg. Motrin, Advil) and naproxen (eg.
Aleve), are widely used to treat fever
(antipyretic action), pain (analgesic action), and
inflammatory (anti-inflammatory action)
conditions such as arthritis
– Aspirin is also known for its anti-platelet action
Salicylates:
ASA
• Aspirin have:
Whereas,
Acetaminophen
– anti-inflammatory,
drugs have only
– antipyretic,
antipyretic &
analgesic
– analgesic, and
actions.
– antiplatelet actions.
• These actions are related to the ability to
inhibit prostaglandin synthesis
Salicylates:
ASA
• Aspirin inhibits cyclo-oxy-genase (COX)
to block production of prostaglandins
• Prostaglandins can sensitize pain
receptors to substances such as
BRADYKININ (SEE NOTE)
– A reduction in prostaglandins results
in a reduction in pain
HOW LONG BEFORE
ASPIRINS PEAK EFFECT?
30 MINUTES
REMEMBER NOT TO APPLY TOPICALLY TO
ORAL MUCOSA!!!!
Salicylates:
ASA
3. Reye’s Syndrome
• Associated with use of aspirin in children &
adolescents who took it when they had the
chickenpox or influenza
•
Fatal disease that causes numerous detrimental effects to many organs,
especially the brain and liver.
• ACETAMINOPHEN and NSAIDs are now used for
fever (antipyretic action) or pain (analgesic
action) in pediatric and adolescents to reduce
the chances of Reye’s Syndrome
WHAT DRUG SHOULD YOU
NOT TAKE WITH ASPIRIN?
WARFARIN
A DRUG INTERACTION BETWEEN ASPIRIN
AND WARFARIN CAN RESULT IN
SIGNIFICANT BLEEDING
NSAIDs
• A rapidly growing group with important
application in dentistry
– Mechanism of action and many of their
pharmacologic effects and adverse reactions
resemble aspirin
• Many authors agree that the NSAIDs are
the most useful drug group for the
treatment of dental pain.
– Most are available without a prescription.
WHEN IS THE PEAK PERIOD
FOR MOST NSAIDS?
1-2 hours
NSAIDs
• Most NSAIDs peak in about 1-2 hours
– Well absorbed orally and food reduces
the rate but not the extent of
absorption
• Metabolized in liver, excreted in kidneys
NSAIDs
• have a significant anti-inflammatory
effect
• Similar as aspirin:
– analgesic
– antipyretic
– anti-inflammatory
• They inhibit prostaglandin synthesis
ARE NSAIDS ADDICTING?
NO!
NSAIDS ARE NOT ADDICTING, TOLERANCE
DOES NOT DEVELOP, AND NO WITHDRAWAL
SYNDROME CAN BE INDUCED.
NSAIDs
7. Pregnancy and Nursing
• Contraindicated in pregnancy;
• Like aspirin, NSAIDs given late in pregnancy
can prolong gestation
• IBUPROFEN is drug of choice for nursing
DENTAL PAIN IS BEST
MANAGED BY HOW MUCH MG
OF IBUPROFEN?
400MG
IN USUAL PRESCRIPTION DOSES, NSAIDS
CAN BE SHOWN TO BE STATISTICALLY
SIGNIFICANTLY BETTER THAN CODEINE
ALONE, ASPIRIN, ACETAMINOPHEN, OR
PLACEBO.
NSAIDs
• NSAIDs should be used with caution in
patients with:
Contraindicated in
1. asthma
pregnancy
2. cardiovascular disease
3. Renal diseases with fluid retention
4. coagulation problems
5. peptic ulcer disease
6. ulcerative colitis
WHAT IS THE MOST
COMMONLY USED NSAID?
IBUPROFEN
WHAT HAS NO ANTIINFLAMMATORY EFFECT?
ACETAMINOPHEN
Acetaminophen
• Used as an analgesic and antipyretic
in children and adults when aspirin is
contraindicated
• Has no anti-inflammatory action
Acetaminophen
• Rapidly and completely absorbed from the GI
tract
• Peak plasma level in 1 – 3 hours
• Half life of 1 to 4 hours
• Metabolized by the liver
• Excreted by the kidneys in 24 hours
• When large doses are ingested, an intermediate
metabolite is produced that is thought to be
hepatotoxic and possibly nephrotoxic.
AN ACUTE OVERDOSE OF
ACETAMINOPHEN CAN CAUSE
WHAT?
LIVER DAMAGE
Acetaminophen
• Acetaminophen is used as an:
–Analgesic agent (↓ pain)
–Antipyretic agent (↓ fever)
Acetaminophen
• Used when hypersensitivity to aspirin or for
patients experiencing aspirin-gastric
induced irritation.
• Used as an antipyretic instead of aspirin for
young children; due to aspirin’s association
with Reye’s syndrome.
• Can be used in all stages of pregnancy
(always ask doctor)
WHAT DRUGS ARE USED TO
TREAT GOUT?
Allopurinol AND Probenecid
Drugs Used to Treat
Gout
Allopurinol (Zyloprim)
• used in PREVENTION of a gout attack.
– Inhibits the synthesis of uric acid
– Also used in patients receiving either
chemotherapy or irradiation
– If a pruritic rash should occur, the drug
should be promptly discontinued
Probenecid (Benemid)
• used in PREVENTION of a gout attack.
– Is an uricosuric drug that increases uric acid
excretion in the urine
CHAPTER 6
WHAT ARE OPIODS USED TO
TREAT?
MODERATE TO SEVERE PAIN
AT FIRST REFERRED TO DRUGS THAT ARE
DERIVATIVES OF OPIUM POPPY
OPIOID OR NARCOTIC ANALGESICS ARE
USED TO MANAGE DENTAL PAIN IN PATIENTS
IN WHOM NSAIDS ARE CONTRAINDICATED
CLASSIFICATION
-THREE GROUPS1.
Mechanism of action at the receptor site:
GROUP
 OPIOID
AGONISTS
 MIXED
OPIOIDS
SUBGROUP
EXAMPLE
morphine,
codeine
pentazocine
 AGONISTANTAGONISTS
 PARTIAL
buprenorphine
AGONIST
 ANTAGONISTS
Naloxone
53
CLASSIFICATION:
CHEMICAL STRUCTURE
BOX 6-1 OPIOD ANALGESIC AGENTS BY STRUCTURE GROUP
•
•
•
•
hydromorphone (Dilaudid) agonist
hydrocodone (in Vicodin) agonist
dihydrocodeine (in Synalgos-DC)
oxycodone (in Percodan, Percocet, Tylox) agonist
METHADONE
•
•
methadone (Dolophine) agonist
propoxyphene (Darvon) agonist
MORPHINAN
•
•
butorphanol (Stadol) agonist-antagonist
pentazocine (in Talwin-NX) agonist-antagonist
MEPERIDINE
•
•
•
meperidine (Demerol) agonist
fentanyl (Sublimaze) agonist
diphenoxylate (in Lomotil)
OTHER
•
buprenorphine (Buprenex, Subutex) partial agonist
MORPHINE AND
CODEINE
(Largest Group)
Do not give any of these
drugs if the patient has an
allergy to morphine or
codeine
54
WHAT ARE WEAKER FORMS
OF OPIODS?
Codeine (in Tylenol#3) and
Hydrocodone (in Vicodin) are
some of the weakest
DRUG NAME (SOME
EXAMPLES)
COMMENTS
SCHEDULE
FOR
CONTROLLED
SUBSTANCE
STRONGEST
MORPHINE
MERPERIDENE
(Demerol)
Standard agent;
prototype
II
Abused by
professionals
II
INTERMEDIATE
OXYCODONE
(in Percocet)
Popular with addicts
‘shopping’ for opioids
II
WEAKEST
HYDROCODONE
(in Vicodin)
CODEINE
(in Tylenol#3)
57
III
#2=15mg; #3-30mg;
#4=60mg
III
WHERE DO NONOPIODS
ACT?
PERIPHERAL NERVE
ENDINGS
OPIOIDS BIND TO RECEPTORS IN BOTH THE
CENTRAL NERVOUS SYSTEM (CNS) AND THE
SPINAL CORD, PRODUCING AN ALTERED
PERCEPTION OF REACTION TO PAIN
WHAT ARE NATURAL
OPIODS?
RELIEVE PAIN AND
RELAXATION
NATURAL OPIOIDS (ALSO CALLED ENDOGENOUS
OPIOIDS), INCLUDE:
ENKEPHALINS
ENDORPHINS
DYNORPHINS
THESE ARE THE CHEMICALS THAT MAKE SURE
WE CAN FUNCTION DURING ACCIDENTS, LIKE
AFTER BREAKING OUR LEG…
MECHANISM OF ACTION
The Discovery of 3 Groups of
Endogenous Substances
Enkephalins
stimulates delta()
receptor
2.
Endorphins
reduces pain & positively
affects mood.
3.
Dynorphins
stimulates the kappa ()receptor
1.
All
62
Probably function
as
neurotransmitters,
although their
exact function has
not been
elucidated.
3 have opioid-like action and are found in the body.
They are naturally occurring peptides that possess
analgesic action and addiction potential
WHEN DO OPIODS START
WORKING?
WITHIN 1 HOUR
THE DOSING INTERVALS OF MOST OPIOIDS
ARE BETWEEN 4-6 HOURS; THE USUAL DOSE
DEPENDS ON THE DRUG.
DURATION – NECESSITATES DOSING EVERY
4-6 HOURS
WHAT IS THE FIRST PASS
EFFECT?
REDUCES THE
BIOAVAILABILITY
UNDERGOES FIRST PASS METABOLISM IN
THE LIVER AND INTESTINE, REDUCING ITS
BIOAVAILABILITY.
PHARMACOKINETICS
Distribution:
Oral
bioavailability of opioids is
primarily limited by first pass metabolism.
Undergoes
first pass metabolism in the liver
and intestine, reducing its bioavailability.
Degree of first pass differs among individuals.
May cause respiratory depression in fetus
when mother is given opioids near term.
67
PHARMACOKINETICS
A.D.M.E
Excretion:
Most
opioids are excreted through the kidneys,
but this action does not selectively affect their
availability after oral administration.
Metabolized opioids and the unchanged
drug are excreted in the urine.
68
severity of side effects is
proportional to the efficacy
(strength)?
TRUE OR FALSE?
TRUE
A PHARMACOLOGIC EFFECT MAY ALSO BE AN
ADVERSE REACTION, DEPENDING ON THE
CLINICAL USE OF THE AGENT.
IS MORPHINE THE STRONGEST
OR WEAKEST OPIOD?
THE STRONGEST
•
MORPHINE IS THE OPIOID AGONIST BY
WHICH ALL OTHERS ARE MEASURED.
STRONGEST CAN RELIEVE SEVERE PAIN
WHILE WEAKER AGENTS MIXED WITH NONOPIOIDS ARE EQUIVALENT TO NSAIDS.
•
PHARMACOLOGIC
EFFECTS
Analgesia
What do aspirin, acetaminophen, ibuprofen,
and codeine have in common?
Aspirin
73
(ASA) and ibuprofen (NSAID) are
analgesic, antipyretic, and
antiinflammatory, and they inhibit platelet
aggregation.
 Acetaminophen is analgesic and
antipyretic.
Codeine is analgesic.
WHAT IS AN ANTITUSSIVE?
SUPRESSES A COUGH
DEXTROMETHORPHAN
PHARMACOLOGIC
EFFECTS
Gastrointestinal Effects
Opioid
analgesics ↑ smooth muscle tone and
↓ propulsive contractions and motility (some
opioids have constipation as a side effect).
Useful
for treating diarrhea.
Opioids are not used for depression,
infections, or hypertension
Example: diphenoxylate (in Lomotil)
76
ADVERSE REACTIONS
TRUE or FALSE
Combining an opioid with a nonopioid
analgesic produces an additive analgesic
effect with fewer adverse reactions.
TRUE
These agents work at two different levels on pain
and produce an additive analgesic effect. In
combination products, lower doses of each analgesic
may be used, and a potential exists for a reduction in
adverse reactions.
77
DO OPIODS INCREASE OR
DEPRESS THE RESPIRATORY
CENTRE?
DEPRESS THE RESPIRATORY
CENTER IN A DOSE RELATED
MANNER
THE RATE AND DEPTH OF BREATHING ARE
REDUCED.
THE DEPRESSION IS RELATED TO A
DECREASE IN THE SENSITIVITY OF THE
BRAINSTEM TO CARBON DIOXIDE.
ADVERSE
REACTIONS
Respiratory Depression
(RP)
Not a problem
with usual doses
in normal
patients
80
RP is usually
the cause of
death with an
overdose
ADVERSE
REACTIONS
Nausea and Emesis
Analgesic
doses of opioids often produce
nausea and vomiting.
Result
of their direct stimulation of the
chemoreceptor trigger zone (CTZ) located in
the medulla.
Repeated administration of regular doses
can prevent vomiting at the vomiting center
(VC).
81
WHAT IS A VERY COMMON
SIDE EFFECT OF OPIOD USE?
CONSTIPATION
THEIR DURATION OUTLASTS THEIR
ANALGESIC EFFECT
WHAT IS A SIGN IN
RECOGNIZING AN OPIOD
ADDICT?
MIOSIS – ‘PINPOINT PUPILS’.
RESPIRATORY DEPRESSION
HOW DO YOU TREAT AN
OVERDOSE TO OPIODS?
AN ANTAGONIST
AN ANTAGONIST
SUCH AS NALOXONE (IN NARCAN)
ADVERSE
REACTIONS
Biliary Tract
Constriction
Opioids
may constrict the biliary duct,
causing biliary colic (bile duct
obstruction leading to gall stones).
Importance
in patients passing gallstones
who are being treated with opioids.
88
A MOTHER ON OPIODS – WHAT
CAN HAPPEN TO THE BABY?
THE INFANT MAY HAVE
DEPRESSED RESPIRATION AND
WITHDRAWL SYMPTOMS
NOT TERATOGENIC, BUT MAY PROLONG
LABOR OR DEPRESS FETAL RESPIRATION IF
GIVEN NEAR TERM.
.
NOT USUALLY A PROBLEM WITH MOTHER’S
MILK WITH THERAPEUTIC DOSES.
Use of opioids is
NOT
contraindicated
in hypertensive
patients.
ADVERSE REACTIONS
Addiction
The
degree of addiction potential is
proportional to analgesic strength.
An
addict will develop tolerance to the
effects of opioids, EXCEPT for miosis and
constipation.
92
ADVERSE
REACTIONS
Addiction
Since
the duration of use in dentistry is
usually short – addiction for dentistry does
not pose a problem
NSAIDs should be used to control dental
pain in the addict.
AN ADVANTAGE OF NSAIDs OVER OPIOIDS:
NSAIDs are not addictive, tolerance does not
develop, and no withdrawal syndrome can be
induced.
93
IF A CLIENT CLAIMS ALLERGIES
TO NSAIDS, WHAT COULD THIS
MEAN?
OPIOD ADDICT
TERMED ‘SHOPPERS’ THE CLIENT IS
LOOKING FOR A SPECIFIC OPIOD.
KEEP IN MIND – THIS ISNT ALWAYS THE
CASE…LOOK FOR OTHER SIGNS NOT JUST
ONE
ADVERSE
REACTIONS
The
Addiction:
Identification of an Addict
“shoppers” - What to look for:
 Asks
for the opioid analgesic by name and says that this is the only drug that
works for them.
 Claims allergies to NSAIDs .
 Cancels dental appointment but still requests the opioid analgesic even
though they will be “out of town on business”.
 Experiences pain for days after scaling and root planing
 Moves from office to office because “others don’t understand”.
 Claims a “low pain threshold”.
 Needs refills several days after a procedure without complications.
 Calls with a request for an opioid analgesic just as the office is closing or after
hours.
96
WHAT IS METHADONE?
USED TO TREAT OPIOD
ADDICTION AND WITHDRAWL
MAINTAINING PATIENTS ON HIGH DOSES OF
METHADONE (METHADONE MAINTENANCE).
ADVERSE
REACTIONS
Addiction:
4 Treatment Options
Addiction,
overdose, and withdrawal can be
treated with opioid antagonists
1.
2.
3.
4.
99
Substituting addict with oral opioid (methadone).
Going cold turkey and using medication such as
phenothiazines, clonidine or benzodiazepines (to alleviate
symptoms of withdrawal).
Maintaining patients on high doses of methadone (methadone
maintenance).
Administering an orally effective, long-acting antagonist
Naltrexone (Trexan).
ADVERSE REACTIONS
Addiction: Treatment Options
Example: The Heroin Addict
The
following drugs can be used to treat heroin addiction
METHADONE, is used by substituting
methadone for heroin and then tapering
off or maintaining the addict on oral
methadone.
NALTREXONE, a long-acting opioid
antagonist, is used to block the action of
usual doses of opioid administered illegally
100
IS TRUE OPIOD ALLERGY
COMMON?
NO
MOST COMMON TYPES OF TRUE ALLERGIC
REACTIONS TO OPIOIDS IS DERMATOLOGIC
IN NATURE.
DUE TO THE HISTAMINE-RELEASING
PROPERTIES OF OPIOID ANALGESICS.
INCLUDES SKIN RASHES AND URTICARIA.
GI SIDE EFFECTS ARE OFTEN REPORTED.
This includes:




oxycodone
hydromorphone,
hydrocodone, and
dihydrocodone
Because they are all
members of the same
morphine and codeine
group.
103
WHAT IS THE PROTOTYPE
OPIOD AGONIST WHICH OTHER
OPIODS ARE MEASURED?
MORPHINE
SPECIFIC OPIODS
The
prototype opioid agonist which other
opioids are measured
Parenterally:
used to control
postoperative pain
Orally:
107
used primarily in the
treatment of cancer
SPECIFIC OPIODS
Used
alone or combined with aspirin (in
Percodan) or acetaminophen (in Percocet,
Tylox) with fewer adverse reactions.
For
It
moderate to severe pain.
is located in the middle of the chart for
strength value.
108
SPECIFIC OPIODS
Weak
opioid analgesic with fewer adverse
reactions.
 Less potential for abuse.
 Combination of Hydrocodone (5mg) with
acetaminophen (500mg) is recommended for
the majority of dental patients with pain
In
Vicodin, it has been reported as
being safe to use when breastfeeding
109
WHAT IS THE MOST COMMON
OPIOD IN DENTISTRY?
CODEINE
MOST COMMONLY USED OPIOID IN
DENTISTRY AND IS OFTEN COMBINED WITH
ACETAMINOPHEN (TYLENOL #3) FOR ORAL
ADMINISTRATION
SPECIFIC OPIODS
Favorite
drug of abuse for medical personnel;
100mg meperidine=10mg morphine.
For
acute management of moderate to severe
pain.
Poor choice for oral use because it has a high
first pass effect; short duration of action.
Less constipating, and without miosis or
cough suppression.
EXAMPLE:
112
meperidine HCl (Demerol)
WHAT IS HYDROMORPHINE
USED FOR?
MANAGEMENT OF SEVERE
PAIN, MORE POTENT THEN
MORPHINE
SPECIFIC OPIODS
An
orally effective opioid, reserved for
management of severe pain.
More potent than morphine
Similar adverse reactions to morphine.
Favourite of the addicts because of its high
strength; requires careful monitoring.
EXAMPLE: Dilaudid
115
SPECIFIC OPIODS
Slower onset and longer duration of
action.
Similar to morphine.
EXAMPLE: Dolophine
Used primarily to
treat any opioid
addicts
(eg. Heroin addicts)
116
Methadone is used
either to withdraw the
patient gradually or for
methadone
maintenance. Because
it has a longer duration
of action, withdrawal
from methadone is
easier than from
heroin. Because it is an
opioid analgesic,
however, the risk for
dependence still exists.
SPECIFIC OPIODS
Naloxone
will block the therapeutic and
toxic actions of opioids
 Methadone
is an opioid used in treatment of addiction, but will exacerbate
symptoms of an opioid overdose.
An
pure opioid antagonist that is active
parenterally.
Drug of choice for treating
agonist or mixed opioid
overdoses.
117
WHAT IS TRAMADOL?
(ULTRAM)
AN ORALLY ADMINISTERED NON-OPIOID
WITH WEAK ANALGESIC ACTIVITY
SPECIFIC OPIODS
Tramadol (Ultram)
Few
studies have confirmed its efficacy:
 Binds
with mu (μ) opioid receptors; inhibits reuptake of serotonin and norepinephrine,
and modifies ascending pain pathways.
Its
analgesic efficacy is equivalent to that of codeine.
Side effects can include: miosis and CNS effects, such as
dizziness, headache and stimulation and GI tract effects
include nausea, diarrhea, constipation and vomiting.
Is moving up the top 200 most prescribed drugs.
120
DENTAL USE OF OPIODS
Most
dental pain can be managed with
NSAIDs.
If NSAIDs are contraindicated - the DDS has a
wide variety of opioids to choose from.
Eg.
Beginning with codeine or hydrocodone
combinations, and progressing to oxycodone
combinations.
Only
in rare cases and for short periods of
time (approx. 1-2 days) should stronger
opioids be prescribed for outpatient dental
pain.
121
ARE OPIODS USED FOR
CHRONIC OR ACUTE PAIN?
ACUTE IS PREFERRED* BUT
CAN BE USED FOR CHRONIC
PAIN
REVIEW: USE OF OPIODS
Opioids are considered first-line therapy
Pain associated with procedures (bone marrow biopsy)
Pain due to trauma or cancer (burns)
Visceral pain (appendicitis)
Majority
for:
used to relieve acute or chronic pain.
Few, such as fentanyl (Sublimaze, Duragesic),
alfentanil (Alfenta), and sufentanil (Sufenta), are
primarily indicated for preoperative sedation to
reduce patient apprehension.
Also used to suppress cough and treat diarrhea
124
Some of the Opioids found in the
TOP 200
#1.
Hydrocodone
#32. Tramadol
#105. Oxycodone
#133. OxyContin
#156. Fentanyl transdermal
#175. Methadone HCl noninjectable
125