Pharmacology of Dentistry of Action Local anaesthetics bind to site on Na+ channel Inhibits the...

Pharmacology in DentistryNiagara Peninsula Dental Association

Dr. Peter [email protected] 1

Pharmacology in DentistryDr. Peter Nkansah

Niagara Peninsula Dental Association

January 12, 2018

Pharmacokinetics & pharmacodynamics

Review of local anaesthetics

Review of analgesics

Review of anti-infectives

Anti-thrombotics

Conscious sedation drugs

Bisphosphonates

Herbal supplements

Overview



Editorial by Dr. J. Goodman in Oral Health (March 2013)

Notes that adverse drug reactions are the 4th leading cause of death in the US

90% of the drugs are metabolized by the liver

Most by the CYP450 enzymes

Notes several Internet resources to help with familiarization of the drugs, their metabolism and interactions

“Pharmacology Made Easier”



Accidental deaths rank 5th as a cause of death in the US

This includes drug-induced deaths

More than 40,000 people in the US in 2010

Heart disease and cancer are #1 and #2

Reverse order in Canada

Death By Drugs

Recent issue of Dispatch noted the reprimand of a colleague for:

The prescription of 5800 tablets of Oxycontin (80 mg) to one patient over a 2-year period

The prescription of 560 tablets of Percocet (5 mg) to one patient over a 2-year period

The prescription of 60 Oxycontin tablets to a patient on one date for the treatment of post-op pain from the placement of 2 implants

Prescriptions for Trouble



Pharmacokinetics & Pharmacodynamics

What the body does to drugs

Absorption

Distribution

Metabolism

Elimination

Pharmacokinetics



What drugs do to the body

Includes duration and magnitude of responses

Dose-response considerations

Pharmacodynamics

Local Anaesthetics



History of Local Anaesthetics

Local anaesthetics have been isolated since the 1860s (cocaine)

Sensory nerve blockade was first described by Halsted in 1884

“Novocaine” (procaine) was the first commonly used local anaesthetic in dentistry

Lidocaine is the original amide LA Commercially available in 1948

Articaine is the newest popular LA Released in Canada in 1982 (US in 2000)

Common LA Preparations

Articaine

Bupivacaine

Lidocaine

Mepivacaine

Prilocaine



To stop the generation and conduction of nerve impulses

To abort impulses from stimuli, like tooth extraction

E.g. To stop the patient from feeling pain

Purpose of LA



Mechanism of Action

Local anaesthetics bind to site on Na+ channel

Inhibits the permeability to Na+

Block propagation of action potential

Structure

3 common features:

Lipophilic (aromatic) group

Intermediate chain with amide or ester linkage

Hydrophilic (tertiary amine) group



By themselves, LA solutions are weakly basic, poorly soluble in water and unstable

Used as salt solutions (usually HCl) which are water-soluble and stable

With the addition of vasopressors, the solutions become acidic

LA Solutions

Amide LAs are primarily biotransformed in the liver

Cytochrome P450 CYP3A4

Medical history concerns:

Severe liver dysfunction

Pseudocholinesterase deficiency (for esters)

Biotransformation & Elimination



Proximity to target site

Concentration

Lipid solubility

Nerve morphology

pH of the tissue

pKa

Onset determinants

pH at which amount of base = amount of cation

All LA’s have pKa > 7.4

pKa = potency

Dissociation Constant (pKa)



pKa of Local Anaesthetics

pKa % base at pH 7.4

Time to onset (min)

Mepivacaine 7.6 40 2-4

Articaine 7.8 29 2-4

Lidocaine 7.9 25 2-4

Prilocaine 7.9 25 2-4

Bupivacaine 8.1 18 5-8

Procaine 9.1 2 14-18

Henderson-Hasselbalch Equation

pKa – pH = log 10Ionized (BH+)Unionized (B)



Example: Lidocaine

pKa – pH = log [ionized/un-ionized]

7.9 – 7.4 = log [ionized/un-ionized]

100.5 = ionized / un-ionized

~3 / 1 = ionized / un-ionized

Drug Ionization

Example: Procaine



101.5 = ionized / un-ionized

~32 / 1 = ionized / un-ionized

Drug Ionization



Example: Lidocaine in site of infection



103 = ionized / un-ionized

1,000 / 1 = ionized / un-ionized

Drug Ionization

Lipid solubility

Protein binding

Concentration/dose

Redistribution from site

Duration Determinants



Maxillary Paraperiosteal (min) IAN Block (min)

Preparation Pulp Soft Tissue Pulp Soft Tissue

Lidocaine w epi 60 150 75 180-300

Articaine w epi 60 120-360 75 120-360

Prilocaine w epi 40 120 75 180

Prilocaine plain 15 60-90 60 150

Mepivacaine w levo 50 180-300 75 180-300

Mepivacaine plain 20 120-180 40 120-180

Bupivacaine w epi 60 240-540 180 240-540

Duration of Action

LA maximum doses

Drug Max (mg/kg)

Max (mg) Max

(mg w/o epi)

# cart. (for 70 kg adult)

lidocaine 7 500 300 13

articaine 7 500 300 7

prilocaine 8 600 400 8

bupivacaine 2 200 75 10

mepivacaine 7 450 300 8



Expressing a % solution

in mg/ml

Example: 2% lidocaine

2% = 20 mg/ml

1 cartridge has 1.8 ml of fluid

= 36 mg of drug/cartridge

LA Dosage



Local Anaesthetic ToxicitySigns and Symptoms

Mild (excitatory)

Confused

Talkative

Tremors

Muscle twitch

BP, HR and RR

Severe (depressive)

Tonic-clonic seizures

Drowsiness

Loss of consciousness

Respiratory depression

BP, HR

CV collapse

Intralipid® 20% is a 20% intravenous fat emulsion

Its primary indication for use is as a source of calories and essential fatty acids for patients requiring TPN for extended periods of time

LipidRescue™ is indicated for the treatment of local anaesthetic-induced cardiac arrest that is unresponsive to standard therapy

Intralipid Rescue



Epinephrine or levonordefrin are added to LA solutions to increase duration and depth of anaesthesia

Use their alpha-agonist interaction with adrenoceptors

Short-lasting drugs by themselves

Vasoconstrictors

Vasoconstrictors

Epinephrine

1:50,000

1:100,000

1:200,000

Levonordefrin

1:20,000



Epinephrine

Rapid onset

Exogenous epinephrine is metabolized by COMT

Short duration of action

5 to 10 minutes if intravenous injection

10 to 20 minutes if intraoral injection

Maximum single appointment dose for a healthy adult = 0.2 mg (200 mcg)

Trade name = Neocobefrin

1:20,000 = 90 μg per cartridge

Similar concerns to those when using epinephrine

Consider the maximum dose of 0.2 mg

Levonordefrin



Beware of interactions with:

Non-selective β-blockers

Tricyclic antidepressants

Cocaine or amphetamine use

COMT inhibitors (e.g. Comtan™ for Parkinson’s disease)

Not an issue with MAOI

Vasoconstrictors



A non-selective α-adrenergic antagonist

Blocks the effects of vasoconstrictors in LA preparations

Increases the redistribution of LA away from injection site

Phentolamine Mesylate

Reduces duration of anaesthesia by 50%

Non-toxic and well-tolerated < age 6 years

Only observed adverse effect is a minor increase in postoperative pain shortly after return to normal sensation

Phentolamine Mesylate



Injectable Bupivacaine Liposome Suspension

Trade name: Exparel® (Pacira Pharmaceuticals Inc.)

Marketed as an opioid-free way to manage post-surgical pain

Consists of multivesicular liposomes (DepoFoam®) that release doses of bupivacaine as the chambers break down

Injected into the surgical site

Not used for nerve blocks

Ref.: https://www.exparel.com



Exparel®

A 1.33% bupivacaine suspension

Maximum recommended dose for adults = 266 mg

Not based on patient weight

Can be mixed with non-liposomal bupivacaine for faster onset

Maximum HCl:Exparel ratio of 1:2

Should not be mixed with other local anaesthetics

Placebo vs. Pharmacology?

If pharmacology works, then topicals must be placed on dried mucosa for 1-2 minutes

NB: Most topical anaesthetics are esters

Some new research into gels containing KNO3 and sprays using ethyl chloride

Topical Anaesthetics



Topical Anaesthetics

Effective only on surface tissues (2 to 3 mm)

Benzocaine and lidocaine base are insoluble in water

However, they are soluble in alcohol, propylene glycol, polyethylene glycol, and other vehicles suitable for surface application

Adverse reactions to LAToxicity of LA or vasoconstrictor

Psychogenic reactions

Allergic reactions to LA or to metabisulfite

Methemoglobinemia

Paraesthesia



Toxicity of LA or vasoconstrictor

Adverse reactions

Psychogenic reactions

Syncope is the most common medical emergency

Occurs most often at the time of injection

Changes in heart rate +/- blood pressure

Hyperventilation

Nausea and vomiting

Adverse reactions



Allergic reactions

The component ingredients in a cartridge are:

Local anaesthetic

Vasoconstrictor

Metabisulfite

Adverse reactions

Adverse reactions

Methemoglobinemia

Condition in which cyanosis develops in the absence of cardiac or respiratory abnormalities

May be congenital or acquired through drugs or chemicals

Prilocaine or large doses of benzocaine

MetHb is normally <1%

Cyanosis and respiratory distress may occur with MetHb>10%



Methemoglobinemia

Delayed in its onset

Unresponsive to O2

Pulse oximeter readings are abnormal (~85%)

Blood is chocolate brown

Treated by 1% methylene blue IV

Avoid prilocaine or benzocaine in patients with congenital methemoglobinemia

Adverse reactions

Paraesthesia



There are numerous reports regarding the association between 4% solutions and a higher-than-expected incidence of paraesthesias

Note the risk:benefit equation

Overall paraesthesia incidence is 1:800,000 injections

There has been an RCDSO advisory regarding 4% solutions used for blocks

Paraesthesias

Paraesthesia

Broad term for prolonged anaesthesia or altered sensation, beyond expected duration of action of local anaesthetic

Adverse reactions



Paraesthesia

Most are transient, usually resolving within 8 weeks

If not, prognosis is very poor

Precise cause not known with certainty

Hemorrhage into nerve sheath

Scar formation

Alcohol or sterilizing solution

Neurotoxicity - controversial

Adverse reactions

A 21-YEAR RETROSPECTIVE STUDY OF REPORTS OF PARESTHESIA FOLLOWING LOCAL ANESTHETIC ADMINISTRATION

Haas and Lennon, JCDA, 1995, 61:319-330

Adverse reactions



The overall incidence of paraesthesia following local anesthetic administration for non-surgical procedures in dentistry is very low 1:785,000

If, however, paresthesia does occur, the results suggest that it is more likely if either articaine or prilocaine is used

Reasons are speculative only

Adverse reactions

Results (1973-1993)

0

10

20

30

40

50

60

Articaine Bupivacaine Lidocaine Mepivacaine Prilocaine



Nerve injury caused by mandibular block analgesia

Hillerup and Jensen, Int J Oral Maxillofac Surg, 2006, 35: 437-443

Prospective study in Denmark

Results: Neurologic evidence of neurotoxicity, not mechanical injury

Articaine had > 20-fold in paraesthesia compared to all other locals combined

Adverse reactions

Fink and Kish, Anesthesiology, 1976 Barsa et al, Anesthesia Analgesia, 1982 Rigler et al, Anesthesia Analgesia, 1991 Lambert and Hurley, Anesthesia Analgesia, 1991 Kalichman et al, Journal of Neuropathology, 1993 Selander, Regional Anesthesia, 1993 Lambert et al, Anesthesiology, 1994 Kanai et al, Anesthesia and Analgesia, 1998 Cornelius et al, Journal Cranio-maxillofacial Surgery, 2000 Johnson et al, Anesthesiology, 2002

Studies of Dose-Dependent Neurotoxicity



Practice Alert: Paraesthesia Following Local Anaesthetic Injection

“Until more research is done, it is the College’s view that prudent practitioners may wish to consider the scientific literature before determining whether to use 4% local anaesthetic solutions for mandibular block injections.”

RCDSO Dispatch (2005)

Retrospective Review of Voluntary Reports of Non-Surgical Paresthesia in Dentistry Gaffen and Haas, 2009, Journal of the Canadian Dental

Association, 75(8): 579

OBJECTIVES: To analyze cases of paresthesia associated with local

anesthetic injection that were reported to the province of Ontario’s Professional Liability Program (PLP) from 1999 to 2008 inclusive

To update previous study (1995)

Adverse reactions



Results: Distribution of paresthesias

0

10

20

30

40

50

60

70

articaine bupivacaine lidocaine mepivacaine prilocaine

Percentage

These data suggest that post-injection paresthesia following a mandibular block is more likely if a 4% solution (articaine or prilocaine) has been administered

These data are consistent with and support previously published findings (Haas and Lennon, 1995)

Conclusions



JADA (July 2010)

JADA (July 2010)



Incidence is very low

Yet data are strongly suggestive of an association

No proof of cause-effect

It is not the drug per se

Higher concentrations may simply predispose to greater effect

Conclusions

Analgesics



Eliminate the source of pain

Consider adjusting regimens according to the patient’s needs and response

Maximize NSAID/acetaminophen doses before adding opioids

Patients who do not respond to one NSAID may respond to another

Avoid chronic use

General guidelines



AA

lipoxygenase

Leukotrienes

Bronchospasm

Inflammation

COX-1

PG’s

GI protection

Uterine cont.

Renal function

TXA’s

Platelets

COX-2

PG’s

Pain

Inflammation

Arachidonic Acid Cascade

Analgesic (mg) NNT

Ibuprofen 600/800 1.7

Ketorolac 20 1.8

Diclofenac 100 1.8

Acetaminophen 1000 + Codeine 60 2.2

Acetaminophen 500 + Oxycodone 5 2.2

Ibuprofen 400 2.5

Diclofenac 25 2.6

Ketorolac 10 2.6

Naproxen 400/440 2.7

Diclofenac 50 2.7

Ibuprofen 200 2.7

Acetaminophen 1000 3.7

Codeine 60 16.7

Oxford League Table



Non-steroidal anti-inflammatory agents are central to pain control in dentistry

They inhibit COX-2 +/- COX-1 enzymes

Tissue damage activates COX-2

NSAID

Analgesic

Anti-inflammatory

Anti-pyretic

Anti-dysmenorrheal

NSAID Therapeutic Effects



NSAID Dosages for Post-Operative Pain

Drug Adult Dose (mg) Frequency Daily Max

ASA 325-1000 q 4-6 h 4,000

Ibuprofen 400 q 4-6 h 3,200*

Diflunisal 1000, then 500 q 12 h 1,500

Naproxen 500, then 250 q 6-8 h 1,375

Ketorolac 10 q 4-6 h 40 (5 days)

Diclofenac 50-100, then 50 q 6-8 h 225

Celecoxib 200 q 12 h 400

Acetylsalicylic Acid

Salicylate-based medicines date back to the Egyptian pharoahs in the 2nd century BC

ASA introduced to modern medicine in 1899 by Dreser

Sold by Bayer as Aspirin

Initially popular as a less-irritating salicylate-based medicine

Now back in favour because of its antiplatelet effect



Ibuprofen

Patented in 1961 by Dr. A. Dunlop, Dr. S. Adams and their team at the Boots Group

Propionic acid derivative

The target was treatment of rheumatoid arthritis

Sold first in the UK in 1969

An effective and very popular NSAID

Sold as Advil, Motrin, and Nuprin in Canada

Ibuprofen

Effective doses are 200-400 mg every 4-6 hours

Maximum daily dose = 3200* mg

Loading doses are effective

Elimination t½ = 2 hours

Solubilized liquigels and ibuprofen lysine have faster onset and better peak analgesia than conventional tablets



Naproxen

Developed in 1976 by Syntex Corp. (now Roche Bioscience)

First sold as Naprosyn

Propionic acid derivative

Brand names = Naprosyn, Aleve

Indicated for mild-moderate pain, osteoarthritis, rheumatoid arthritis, psoriatic arthritis, tendonitis, ankylosing spondylitis, gout and dysmenorrhea

Naproxen

Effective dose = 500 mg first, then 250 mg every 6-8 hours

Analgesia of 220 mg naproxen ≈ 200 mg ibuprofen

Peak levels in 2-4 hours

Naproxen sodium peaks in 1-2 hours

Elimination t½ = 12-15 hours

More GI irritation than ibuprofen



Ketorolac

Developed in by Syntex Corp. (now Roche Bioscience) in 1989

A pyrrole derivative

First marketed as Toradol®

The first injectable NSAID

Tablets are most effective after IM administration

Approved for IV use in the US

Available as a nasal spray in the US (Sprix®)

Ketorolac

Indicated for moderate-severe pain

Effective dose is 30-60 mg IM first, then 15-30 mg every 6 hours

Oral dose = 10 mg every 4-6 hours

As effective as 400 mg ibuprofen

Suggested limit of 5 days of administration because of GI bleed concerns

Ref.: Strom et al., JAMA, 1996



Diclofenac

A phenylacetic acid derivative that has a two- to threefold preference for COX-2

Sold as Voltaren

Indicated for inflammatory conditions and dysmenorrhea

Associated with greater hepatotoxicity than other NSAIDs

A formulation with misoprostol is available

Misoprostol is abortifacient

Diflunisal

Developed in 1971 by Merck Sharp & Dohme

Salicylate derivative

Brand name = Dolobid

Distinct among the NSAIDs because of its long half-life


Needs a loading dose, then can be taken only twice a day



Diflunisal

Main indication for use is for treatment of mild-moderate pain and for osteoarthritis and rheumatoid arthritis

Dosage of 1000 mg first, then 500 mg bid

Relatively slow onset of action

2-3 hours for peak blood levels

Provides better analgesia than acetaminophen

Comparable to combinations with opioids

COX-2 Inhibitors

Vioxx® and Celebrex® are the famous examples

The benefits are:

Less GI bleeding

Fewer gastroduodenal ulcers

Is there a predisposition to myocardial infarction?

Vioxx® voluntarily withdrawn from the market in 2004

GI concerns not a big issue in dentistry because of the short-term post-operative use



Celecoxib

Brand name = Celebrex®

Indicated for:

Osteoarthritis

Rheumatoid arthritis

Dysmenorrhea

Familial adenomatous polyposis (?)

Mental illness (?)

Celecoxib

Dosage is 200 mg bid


Equal efficacy to 650 mg ASA in dental pain studies

Less effective than ibuprofen or naproxen

No specific advantage in dentistry



Increased bleeding*

Gastric mucosal damage

Dyspepsia

Renotoxicity

Anaphylactoid reactions

NSAID Adverse Effects

Gastric ulcers

Bleeding dyscrasias or concerns

Significant renal disease

asa (or other NSAID) hypersensitivity

Combination of severe asthma, nasal polyps and multiple allergies

Can lead to ARDS

NSAID Contraindications



Pregnancy

Especially in the 3rd trimester

Children

asa only

Elderly

Concurrent use of certain other drugs

NSAID Contraindications

Acetaminophen (Paracetamol)

Actual generic name is N-acetyl-p-aminophenol (APAP)

Synthesized in 1878

First used clinically in 1887

Largely discarded in favour of phenacetin, which was believed to be less toxic

Ref.: Bertolini et al., CNS Drug Reviews, 2006



Acetaminophen (Paracetamol)

Launched in North America and the UK from 1955-57

Phenacetin became “condemned” because of its nephrotoxicity, methemoglobinemia and carcinogenicity

Popularity took off in the 1970s

By 1979, Tylenol was the best-selling health and beauty aid product, passing Crest toothpaste

Ref.: Bertolini et al., CNS Drug Reviews, 2006

Acetaminophen

Analgesic of (popular) choice in dentistry

Effective anti-pyretic and analgesic

Not anti-inflammatory

No NSAID side effects (e.g. anti-platelet, GI)

No respiratory depression

Very safe at normal doses

Category B for use during pregnancy

Hepatotoxic at high doses



Acetaminophen

Pharmacology

Mechanism of action not entirely understood

Not a COX inhibitor peripherally, but does inhibit the synthesis of prostaglandins peripherally

May inhibit prostaglandin synthesis in the CNS

Potentiates the cannabinoid/vanilloid tone in the brain and in dorsal root ganglia

Marijuana’s THC is a cannabinoid

There are CB1 receptors in the periphery also

Acetaminophen

Use with caution in the following patients:

Liver disease

Fasting

Chronic alcoholism

Poor nutrition

The metabolite, NAPQI, is potentially toxic if not adequately conjugated



Acetaminophen

Dosages

Adult dose is 500-1,000 mg every 4-6 hours to a maximum of 4 grams per day

Paediatric dose is 10-15 mg/kg every 4-6 hours to a maximum of 80 mg/kg

Toxic at 140 mg/kg

Acetaminophen

Dosages

Now available (here) in an IV formulation

650-1000 mg every 4-6 hours if > 50 kg

12.5-15 mg/kg up to 75 mg/kg/24 h if < 50 kg

Avoids the first-pass hepatic exposure and metabolism

Therefore may be less hepatotoxic



Two different mechanisms of action for analgesia

Potentially synergistic in the short-term

Potentially renotoxic in the long-term

NSAID & Acetaminophen

Opioids



Terminology

Opioid

All drugs with opium-like activity

Opiate

Naturally-occurring alkaloids

Narcotics

A “controlled substance”

Most specifically a legal term

Refers to natural, semi-synthetic & synthetic compounds

Opioid History & Context

The first documented descriptions of Papaversomniferum appeared around 1550 BC in ancient Egypt

Morphine was not isolated or named until 1806 by Sertürner




Mechanism of action

Opioids act at specific CNS and peripheral sites to relieve pain

Act at the descending pain inhibitory system and in the brain (changing signal interpretation)

The significant effects are mediated through the μ and κreceptors

μ receptors may have an unlimited dose response

κ-agonist/μ-antagonist (e.g. nalbuphine) have ceiling effects


Mechanism of action

Possible peripheral analgesic action

Elsharrawy and Elbaghdady (2007) compared supplemental PDL injections with fentanyl vs. mepivacaine with epinephrine for endodontic treatment

Found fentanyl to be more satisfactory than mepivacaine



Opioids

In dentistry, they are indicated for use in the treatment of moderate to severe pain

Other opioid effects:

Antitussive

Constipation

Sedation

Mood alteration (euphoria)


Nausea and vomiting


Current commonly used opioids:

Morphine & codeine

Hydrocodone & oxycodone

Meperidine, fentanyl, & methadone



Opioids

2 broad categories of patients:

Opioid-naïve

No opioids for the past 7 days

Opioid-tolerant

Ref.: VCU Massey Cancer Centre, July 2010

Mechanism of action

Analgesia site of action is the CNS

Possible peripheral anti-inflammatory action

One study compared supplemental PDL injections with fentanyl vs. mepivacaine with epi

Ref.: Elsharrawy and Elbaghdady, Journal of Pain and Symptom Management, 33(2), 2007

Opioids



Addiction is a real possibility

The public (and the government) are currently on high alert about the use of opioids in healthcare

Opioids

Equipotent Opioid Doses

Drug Oral dose (mg) IM dose (mg)

Morphine 30 10

Codeine 200 120

Oxycodone 25 10

Meperidine 300 75



Opioids

Recommended oral doses

Codeine = 60 mg

Oxycodone = 5-10 mg

Meperidine = 100 mg

Opioid Combinations

They have the advantage of convenience

They do not have sensible formulations

Drug Acetaminophen(mg)

Codeine (mg)

Tylenol #1 300 8

Tylenol #2 300 15

Tylenol #3 300 30

Tylenol #4 300 60



Opioid Combinations

Name Nonopioid Opioid

Percocet 325 mg acetaminophen 5 mg oxycodone

Percocet 325 mg acetaminophen 5 mg oxycodone

Percodan 325 mg ASA 5 mg oxycodone

Opioid Combinations

Name Nonopioid Opioid

OxyContin 5-80 None 5-80 mg oxycodone

OxyNeo 10-80 None 10-80 mg oxycodone



Codeine for Kids?

As of June 2013, Health Canada no longer recommends codeine for children younger than 12 years

Codeine, as a prodrug, can be metabolized/activated at different rates

Can lead to a morphine overdose

Ref.: Wong, Oral Health, Feb. 2014

Codeine for Kids?

WHO analgesic ladder for paediatric pain:

Mild Pain

•Acetaminophen

•NSAID

Moderate to Severe Pain

•NSAID

•+/- Acetaminophen

•+ Morphine



Codeine for Kids?Drug Pediatric Dose Maximum Availability

Acetaminophen 15 mg/kg q4-6h PO 90 mg/kg/day

(Not to exceed adult

max: 4 g per 24 hr)

Oral:

32 mg/mL

80 mg/mL

Rectal:

40 mg/kg loading dose,

then 20 mg/kg q6h

Rectal:

120 mg, 325 mg, 650 mg

suppository

Ibuprofen 10 mg/kg q6h PO 40 mg/kg/day

(Not to exceed adult

max: 2.4 g per 24 hr)

Oral:

20 mg/mL

40 mg/mL

100 mg chewable tablet

Morphine

(immediate release)

0.2-0.5 mg/kg q4h PO WHO recommends 5 mg

as a guideline.

Otherwise, there is no

fixed maximum dosage.

Oral:

1 mg/mL

5 mg/mL

10 mg tablet

Morphine for Adults?

Indication is moderate-to-severe pain

1 mg IV = 3 mg po

Dosing:

5-15 mg of immediate release morphine every 3 hours

If inadequate, the dosage can be increased by 50%

Ref.: VCU Massey Cancer Centre, July 2010



Analgesic Strategies

Analgesic Sites of Action

Central (mostly)

Opioids

Acetaminophen

Peripheral (mostly)

NSAIDs



Strategies

Maximize NSAID (or acetaminophen) before adding opioid

Optimize dosing regimen before switching

If the patient does not respond to one NSAID, they may respond to another

Strategies

Consider:

Pre-operative dosing

Loading doses

Giving the first dose before local anaesthetic wears off

4-hour interval instead of prn for the first day



Mild to moderate pain

Acetaminophen

(up to 1000 mg)

NSAID

Add codeine to NSAID or acetaminophen

Add oxycodone w/ acetaminophen

Add codeine or oxycodone

Analgesic Algorithm

Antibiotics



Use only when there is an indication

Choose the narrowest spectrum drug that will be effective

Consider the risk/benefit equation

Prescribe an adequate dose

Adequate frequency

Adequate duration

Prescribing Principles

Wrong drug or dose

Bacterial resistance

Host defences depressed

Poor compliance

Reasons for Failure



Antibiotic Actions

Bactericidal

Penicillins

Metronidazole

Cephalosporins

Aminoglycosides*

Vancomycin*

Bacteriostatic

Clindamycin

Erythromycin

Tetracyclines

Oral penicillins are penicillin V and amoxicillin

Pen V is narrow-spectrum against gram-positive Strepand others

Drug of choice for orofacial infections

Dose = 300-500 mg qid

Amoxicillin is broad-spectrum and better absorbed orally

Dose = 250-500 mg q8h

Penicillins



Adverse reactions

Allergy

Diarrhea (2-10% incidence)

Nausea and vomiting

Pseudomembranous colitis

Candidiasis

Penicillins

Allergy rate is 1-10% of the population

Penicillins responsible for 75% of anaphylaxis deaths

400-800 deaths per year in the US

Mild anaphylaxis occurs 1:200 courses

Severe anaphylaxis occurs 1:2,000 courses

Penicillins



An alternative for penicillin-allergic or penicillin-resistant patients

Active against gram-positive and gram-negative anaerobes and facultative/aerobic bacteria

Dose = 150-300 mg q6h

Clindamycin

Also known as antibiotic-associated diarrhea (AAD)

Occurs in as many as 30% of patients

Broad-spectrum antibiotic use alters the composition of gut bacteria This allows the overgrowth of other bacteria

Clostridium difficile (C. difficile) is the beneficiary of interest here The presence of C. difficile and its toxins cause

pseudomembranous colitis

Characterized by diarrhea, fever and abdominal pain




Risk factors

Drugs include:

Penicillins (esp. ampicillin)

Cephalosporins

Clindamycin

Erythromycin

Advanced age

Females with genitourinary disease

Uremic patients (e.g. kidney dialysis patients)


Treatment Stop all antibiotics

Keep the patient hydrated

Refer to a physician

Prescribe:

Vancomycin 500 mg po qid for 2 days (if severe)

Vancomycin 125 mg po qid for 10-14 days

Metronidazole 500 mg po tid for 7-14 days

Metronidazole IV

Probiotic therapy (Saccharomyces boulardii) has been tried adjunctively




Group includes erythromycin, clarithromycin and azithromycin

Erythromycin was the former drug of choice for penicillin-allergic/penicillin-resistant patients

Numerous GI adverse effects

Active against gram-positive aerobic/facultative staph and strep and gram-negative anaerobes

Not particularly good against dental infections

Macrolides

Trade name is Flagyl™

Active against obligate, gram-negative anaerobes only

Used in combination with penicillin

Avoid concurrent use of alcohol or warfarin

Dose = 250-500 mg tid

Metronidazole



Group includes tetracycline, doxycycline (Vibramycin, Periostat) and minocycline (Minocin)

Broad-spectrum, bacteriostatic

Useful in treatment of periodontal disease

Widespread resistance

Host of adverse effects including: tooth staining, photosensitivity, blood dyscrasias, GI effects

Tetracyclines

CYP3A4 is a major metabolizing enzyme

Part of the cytochrome P450 enzyme system

Clarithromycin, erythromycin and the azole antifungals (e.g. ketoconazole, fluconazole) are potent inhibitors of CYP3A4

Single-dose regimens, as in antibiotic prophylaxis are not of major concern

Antibiotic Drug Interactions



Anecdotally reported

Scientific evidence implies rifampin (Rifadin®, Rofact™) only

Virtually untestable

Rationale is that antibiotics reduce enterohepaticrecycling of estrogen → subtherapeutic blood levels that allow ovulation

Antibiotics and Oral Contraceptives

From Resnick and Misch (2008):

Overall incidence is 6-7%

Possible reactions include:

GI tract complications

Colonization of resistant or fungal strains

Cross reactions with other medications


Development of resistant bacteria and superinfection

Little concern about short-term use

Antibiotic Adverse Reactions



Sometimes recommended to combat antibiotic-associated diarrhea (AAD)

May be useful for frail patients or patients who have had this before

Lactobacillus and bifidobacterium are the preferred probiotics

Fermented foods with “friendly” bacteria may also help

E.g. kefir, yogourt, kimchi, miso, sauerkraut, or kombuchatea

Probiotics

Review by Hempel et al. 2012 reviewed and evaluated 82 RCTs for evidence regarding probiotic use in the prevention of AAD

The principal finding was that probiotics did reduce the risk of AAD

NNT=13

The findings did not clearly indicate which probiotics were best

Lactobacillus genus was the most tested, either alone or with other genera (e.g. Bifidobacterium)

Probiotics

JAMA, vol. 307(18), pp. 1959-1969



Antibiotic prophylaxis

Indicated for patients with: Prosthetic heart valves

History of infective endocarditis

Cardiac transplant with subsequent heart valve problem

Some congenital heart conditions Unrepaired cyanotic disease (incl. shunts and conduits)

Repaired defect (<6 months) with prosthetic material or device

Repaired defect with residual defect at or adjacent to the site of repair

Antibiotic Prophylaxis



Coverage is not indicated for patients with:

Surgically constructed systemic pulmonary shunts

Isolated secundum atrial septal defect

Previous coronary artery bypass graft surgery

Physiologic (functional, innocent) heart murmurs

Pacemakers and implanted defibrillators


Indicated for the following procedures: Implant placement

Extractions

Periodontal procedures

Reimplantation of avulsed teeth

Endodontics beyond the apex of the tooth

Intraligamentary injections

Subgingival placement of fibres or strips

Placement of orthodontic bands

Polishing of teeth or implants where bleeding is expected




Drug Adult Dose Paedo Dose

Amoxicillin 2 g 50 mg/kg

Clindamycin 600 mg po/IV 20 mg/kg po/IV

Azithromycin 500 mg 15 mg/kg

Clarithromycin 500 mg 15 mg/kg

Ampicillin 2 g IM/IV 50 mg/kg IM/IV


Patients already taking an antibiotic used for prophylaxis should:

Be prescribed an antibiotic from a different class

Be scheduled at least 9 days after the completion of the current prescription




May be indicated for patients at increased risk including:

< 2 years post-surgery

Inflammatory joint disease

Immunosuppression (incl. drug-induced, radiation-induced, HIV)

Previous joint infections

Type I diabetes mellitus

Total Joint Prosthesis

Prophylaxis may be indicated for patients at increased risk including: < 2 years post-surgery

Inflammatory joint disease (e.g. rheumatoid arthritis, lupus)

Immunosuppression (incl. drug-induced, radiation-induced, HIV)

Previous joint infections

Type I diabetes mellitus

Hemophilia

Malignancy

The literature is unclear

Prophylaxis for Total Joint Prostheses



Regimens:

Amoxicillin or cephalexin 2 g po, 1 hour pre-op

Clindamycin 600 mg po/IV, 1 hour pre-op

Total Joint Prostheses

Literature Review 2003 Total Joint Advisory Statement from the ADA and AAOS

(the American Academy of Orthopedic Surgeons)

Recommended prophylaxis for 2 years for specific dental procedures

AAOS issued a new statement in 2009 that consolidated dental and medical procedures

“Given the potential adverse outcomes and cost of treating an infected joint replacement, the AAOS recommends that clinicians consider antibiotic prophylaxis for all total joint replacement patients prior to any invasive procedure that may cause bacteremia.”




Literature Review

Statement from ADA and AAOS in 2012

1. “The practitioner might consider discontinuing…routinely prescribing prophylactic antibiotics…”

This is a limited recommendation meaning that the quality of the supporting evidence is unconvincing


Literature Review


2. “We are unable to recommend for or against the use of topical oral antimicrobials in patients…”

This is inconclusive recommendation meaning that there is an unclear balance between benefits and potential harm

Patient preference should be a major guiding factor




Literature Review


3. “In the absence of reliable evidence linking poor health to prosthetic joint infection, it is the opinion of the work group that patients with prosthetic joint implants or other orthopaedic implants maintain appropriate oral hygiene.”

A consensus opinion stands because of experts agreeing as opposed to the review of empirical evidence

Practitioners can be flexible about whether or not to follow consensus opinions

Patient preference is important again


Clinical Practice Guideline from the ADA, January 2015

Q: For patients with prosthetic joints, is there an association between dental procedures and PJI [prosthetic joint infections]

“…the 2014 Panel judged with moderate certainty that there is no association between dental procedures and the occurrence of PJIs”

The Panel consisted of experts from the ADA only

Total Joint Prosthesis



The concept of using antibiotics to enhance the outcome of implant surgery is not new

Adel et al. (1981) used Penicillin V for 10 days

Adel (1985) used 2 g Penicillin V for 10 days

Buser et al. (1990) used short-term amoxicillin or erythromycin

Antibiotics & Implant Surgery

Cochrane Review by Esposito et al. (2008) investigated the use of antibiotics to prevent complications in implants

Two randomized controlled studies were subjected to meta-analysis

Showed a statistically significant higher number of implant failures in the group that did not receive antibiotics

“It might be recommendable to suggest the use of one dose of prophylactic antibiotics prior to dental implant placement

2 g of amoxicillin preoperatively?

Antibiotics & Implant Surgery



Clavulin® = amoxicillin and clavulanic acid

Dose = 875/125 mg bid for 7 days

Chlorhexidine 0.12% rinse

Start both medications 1 day pre-operatively

Sinus Lift Pre-/Perioperative Medication

Possible complications that may require medications are:

Site infection

Chlorhexidine 0.12% mouthrinse bid for 2 weeks

Nasal congestion

Pseudoephedrine (Sudafed®) 120 mg q12h

Phenylephrine (Sudafed PE®) 10 mg q4h

Oxymetazoline 0.05% (Claritin® Nasal Pump, Drixoral®) 2 sprays in each nostril q12h

Afrin® in the US

NB: other formulations of Claritin® are loratidine, an antihistamine

Sinus Lift Postoperative Considerations



Bisphosphonates

They inhibit bone resorption by inhibiting osteoclasts and impairing angiogenesis

Indicated in the treatment of:

Osteoporosis

Paget’s Disease

Prolonged glucocorticoid therapy

Metastatic cancers (e.g. breast, lung, prostate and renal)

Osseous lesions associated with multiple myeloma

Bisphosphonates



Associated with osteonecrosis of the jaws

Other bones rarely affected

Oral vs. intravenous

Consider as 2 distinct risk groups

Oral formulations include alendronate (Fosamax™), risedronate (Actonel™), ibandronate (Boniva™) and etidronate (Didrocal™)

Bisphosphonates

Bisphosphonate-associated osteonecrosis (BON) incidence estimates:

~0.8%-20% of patients in cancer therapy

0.01%-0.04% of patients taking oral formulations

0.09%-0.34% in cases of dental extractions

30 million prescriptions in the US in 2006

< 10% of BON cases associated with oral bisphosphonates

Ref.: ADA, JADA 139(12): 1674-1677, 2008

Osteonecrosis Incidence



General dentistry

Areas of bony infection should be treated immediately

No change in routine care

Periodontal disease

Try to use non-surgical therapies with re-evaluation in 4-6 weeks

Use bone grafting and guided tissue regeneration judiciously

ADA Recommendations

Oral and maxillofacial surgery

Discuss risks (though small) and alternate treatments (e.g. RCT, FPD’s, RPD’s)

Post-operative prophylactic antibiotic use should be for risk of infection vs. use of bisphosphonates

Implants

Placement of implants may pose increased risk

Peri-implantitis should be approached non-surgically first

ADA Recommendations



A twice-yearly injection that also prevents osteoclast activity by affecting precursor cells

Branded as Prolia™

Association with MRONJ largely untested to date

Important to ask about injections along with “pills or puffers”

Denosumab

Paper expands BRONJ to MRONJ because of denosumab and antiangiogenic therapies

The risk of MRONJ to osteoporosis patients ranges from 0.017%-0.04% which approximates the placebo risks (0%-0.02%)

Risk appears to increase over time, plateauing after 4 years

Staging and treatment strategies outlined

AAOMS MRONJ Position Paper

Web ref.: https://www.aaoms.org/docs/position_papers/mronj_position_paper.pdf?pdf=MRONJ-

Position-Paper



Antithrombotics



3 categories:

1. Antiplatelet drugs

Inhibit platelet aggregation

2. Anticoagulants

Inhibit the formation of fibrin strands

3. Fibrinolytics

Dissolve existing clots

Excellent review by Dr. D. Becker in AnesthesiaProgress, vol. 60, pp. 72-80, 2013

Antithrombotic Overview

Thrombus Formation



Used to prevent the formation of thrombi in the arteries

The most popular antiplatelet drug is asa (aspirin)

Prescribed for the prevention of MI and ischemic stroke

Used in the treatment of AMI

Mechanism of action is the permanent inhibition of TXA2

synthesis

Antiplatelet Drugs

Clopidogrel (Plavix®) and Prasugrel (Effient®) work by permanently blocking ADP receptors on platelet cell membranes

This means that the platelets do not bind fibrinogen

Both are prodrugs

Clopidogrel has 15% activation

Prasugrel has ≈ 100% activation

Both complicate the approach to control bleeding incidents

Antiplatelet Drugs



Clopidogrel (Plavix®)

Indicated for secondary prevention in cases of stroke, post-MI, or stent placement

Less spontaneous bleeding than with aspirin

Plasma half-life = 20-50 hours

6 days needed for normalization after discontinuation

~ 4 half-lives

Antiplatelet Drugs

Prasugrel (Effient®)

Same indications as clopidogrel

Plasma half-life = 7 hours

1½-2 days needed for normalization

Antiplatelet Drugs



Patient assessment

INR does not work for patients on antiplatelet therapy

A platelet function test would be necessary

Ref.: D Mylotte, Cardiovascular & Hematological Agents in Medicinal Chemistry, 9: 14-24, 2011

Antiplatelet Drugs

Dental implications

Ibuprofen and naproxen are competitive inhibitors of asa on platelet cyclooxygenase

The clinical relevance of this fact is insignificant

Problem is avoided by having asa at least 1 hour before the other NSAID

Antiplatelet Drugs



Dental implications

Low-dose asa and regular-dose clopidogrel do not pose a bleeding risk in minor surgeries

For extensive surgeries, bleeding times return to normal after 4-5 days of withholding the antiplatelet drug

Antiplatelet Drugs

Patients with coronary stents

According to the American College of Chest Physicians, delay elective surguries

6 weeks following bare-metal stent placement

6 months following drug-eluting stent placement

Antiplatelet Drugs



Used primarily to prevent thromboembolic events

E.g. DVT, post-pulmonary embolus, atrial fibrillation, prosthetic mitral or aortic valve

Can be used in combination with antiplatelet drugs in high-risk patients

The common drugs are warfarin (Coumadin), heparin and dabigatran (Pradexa)

Anticoagulant Drugs

Warfarin (Coumadin) competes with vitamin K in the liver to inhibit the production of a number of clotting factors

This mechanism of action is fairly imprecise

Takes several days for full effect (or full offset)


Effects measured by PT (or INR)

Can do work with INR < 3-3.5

Contraindicated in pregnancy

Anticoagulant Drugs



Heparin is injectable (SC or IM) only

Mechanism of action is the potentiation of antithrombinin the plasma

Again, the effects are fairly imprecise

Effects measured by aPTT


Anticoagulant Drugs

Low-molecular-weight-heparins (LMWH) are as effective as heparin but act more selectively and for longer times

E.g. enoxaparin (Lovenox®), dalteparin (Fragmin®)


Anticoagulant Drugs



NEW: Dabigatran (Pradaxa, Pradax) is an orally-administered direct thrombin inhibitor

Blocks conversion of fibrinogen fibrin

Used to prevent stroke in people with atrial fibrillation

Advantages include a broad therapeutic window, short half-life, fixed dosing, no interaction with cytochrome P450

Effects are difficult to assess

Inconsistent effects on aPTT, and PT largely unaffected

No standardized reversal procedure

Post-operative bleeding effects slightly less than with heparin

Anticoagulant Drugs

Dabigatran

Administered as a prodrug

Dose = 75-150 mg bid

Onset of action = 1 hour


Best effect assessment by ecarin clotting test (ECT; rare)

Anticoagulant Drugs



Dabigatran

Dental treatment modifications

Avoid aspirin and NSAIDs

If needed, skip 1-2 doses

Anticoagulant Drugs

NEW: Oral Factor Xa Inhibitors

Rivaroxaban (Xarelto®) and apixiban (Eliquis®) inhibit the conversion of prothrombin thrombin

Anticoagulant Drugs



Rivaroxaban (Xarelto®)

Indicated for VTE after knee or hip replacement, prevention of stroke, DVT or PE, treatment of DVT or PE

10-20 mg given once per day


Normal Xa activity returns after ~24 hours

Anticoagulant Drugs

Apixiban (Eliquis®)

Indicated for stroke or VTE prevention

Dose = 5 mg bid


Status can be monitored via PT (INR)

Discontinue drug for 24-48 hours before elective surgery or invasive procedures

Anticoagulant Drugs



Dental implications Risk of postoperative bleeding Minor surgery is OK if the INR is less than 3.5

Vitamin K reversal works for warfarin, not dabigatran

Extensive surgical procedures may need bridge therapy where injectable anticoagulants replace warfarin

CYP2C9 interactions between warfarin and metronidazole, macrolide antibiotics and azole antifungals

Watch out for NSAIDs because of GI bleed risks

Anticoagulant Drugs

“Clot busters” work by converting plasminogen to plasmin

Inactivates fibrinogen and lyses fibrin strands

Recombinant tissue plasminogen activator (rTPA) is the most commonly used agent

Not an issue for outpatient dentistry

Fibrinolytic Drugs



Sedative Agents

Conscious Sedation(minimal and moderate*)

Deep Sedation

General Anaesthesia

Spectrum of Anaesthesia



Conscious Sedation

Ref.: RCDSO, 2012

“…a minimally to moderately depressed level of consciousness that retains the patient’s ability to independently and continuously maintain an airway and respond appropriately to physical stimulation and verbal command.”

The RCDSO is more concerned about the intent of sedation than the endpoint achieved

Warning:

Any method of sedation and any choice of drug can lead to any level of

consciousness



Nitrous Oxide

Benzodiazepines

Antihistamines

Useful Conscious Sedation Drugs

The Good:

Fast onset, fast offset

Easy to administer

No lasting effects

0.004% metabolized

Very safe

Has some analgesic properties

Nitrous Oxide and Oxygen



The Bad:

Difficult for claustrophobic patients

May not be strong enough

Requires active dentist participation

Nitrous Oxide and Oxygen

The Good: Familiar, noninvasive route of administration

No special office equipment is needed*

The Bad: Not titratable or recoverable Benzodiazepines are reversible but not orally

Beware of DOCS* protocols

Slow onset

Patients must be accompanied home

Ref.: Donaldson et al., Anesthesia Progress, 54:118, 2007

Oral Medications



An anxiolytic-specific category of drugs

Act on GABAA receptors in the CNS to hyperpolarize cells

Lowers brain activity

Little effect on the respiratory and central nervous systems

Metabolized by the CYP450 3A4 enzyme system

Watch out for inducers or other system occupiers

Benzodiazepines

Effects are sedation, anterograde amnesia and anxiolysis

Popular choices are midazolam, triazolam, diazepam, lorazepam and temazepam

Peak of action in about 1 hour, except for midazolam

Be careful with multiple doses or alternate routes of administration (e.g. sublingual)

Benzodiazepines



Agents include:

Zolpidem (Ambien)

Fast onset, short duration, no active metabolites

Zopiclone (Imovane)

Similar pharmacologic profile to zolpidem

Ramelteon (Rozerem)

A melatonin receptor agonist

Non-BZD GABA Agonists

Sedation is a side effect

Agents include hydroxyzine (Atarax), diphenhydramine (Benadryl) and promethazine (Phenergan)

Very safe

Antihistamines



Warnings:

1. Oversedation = medical emergency

2. Incremental dosing of oral sedatives is now discouraged in Ontario*

Adverse Events During Paediatric Dental Anaesthesia

Article by Chicka et al. in Pediatric Dentistry, 2012; 34: 231-238

Analyzed 17 closed malpractice insurance claims in the US from 1993-2007

1 GA, 3 LA, 13 sedation & LA

9 outcomes of “major” severity (i.e. death or brain damage)

8 outcomes of “minor” severity (i.e no permanent morbidity)




Article by Chicka et al. in Pediatric Dentistry, 2012; 34: 231-238

82% of the claims involved children < 6 years

Most sedated children are < 6 years (78%)

Average age of “major” outcomes = 3.6 years

There is an inverse relationship between patient age and sedation risk

47% of the outcomes were “minor”

Good management vs. self-limiting events


Article by Chicka et al. in Pediatric Dentistry, 2012; 34: 231-238 No single sedative agent was most frequently associated with

“major” outcomes

Drug dose more important than drug choice

41% of the claims involved an overdose of LA

LA toxicity may be masked by concomitant BZD use

Most claims involved events at the dental office

The dentist is likely to be the first responder Important for the dentist and the team to be ready



Drug Therapy in the Elderly

Pharmacokinetic changes

Pharmacodynamic changes

Systemic disease

Polypharmacy

Factors to consider



Absorption

Increased gastric pH

Decreased gastric emptying

Impaired gastric motility

Overall minor effect

Pharmacokinetics

CNS drugs have magnified effects (e.g. benzodiazepines)

Can result in

Excessive sedation

Mental confusion

Delirium


Pharmacodynamics



Systemic disease

Some examples of diseases that affect pharmacologic effects include:

Disease Effect

Renal disease ↑ serum half-life and concentration

Congestive heart disease ↑ serum half-life and concentration

Benign prostatic hypertrophy ↑ urinary retention with anticholinergics

Dementia ↓ ability to comply with prescriptions

Use of prescription medications, OTC medications, natural medicines and alternative medicines is very widespread in Canada

Concerns for adverse drug reactions and drug interactions

According to a 2009 report from Ramage-Morin (Statistics Canada)

In 2005, pharmacists dispensed an average of 35 prescriptions per person aged 60 to 79 74 prescriptions per person aged 80 or older

Compared with an overall average of 14 prescriptions per Canadian

Math, co-morbidities and physiologic changes put seniors at risk

Polypharmacy



53.1% of institutionalized seniors and 12.8% of seniors in private households reported polypharmacy (taking 5 medications or more in the past 2 days)

97% of institutionalized seniors reported taking some medication in the past 2 days

76% of seniors living in private households

Ramage-Morin (2009)

Local anaesthetics

No change in administration

Consider reducing maximum dose if the patient has congestive heart disease

Limit vasoconstrictor dose to 40 μg per appointment

Specific Considerations



Acetaminophen

Analgesic of choice

Dosage of 325-1000 mg q4h to a daily maximum of 4 g

Reduce the daily maximum if there is alcoholism or significant liver disease


NSAIDs

Note the possibilities for bleeding, ulceration or perforation

Increased risk of GI toxicity

Increased risk of renal toxicity

Increased risk of hepatic toxicity

Consider celecoxib (Celebrex®) as your NSAID




Opioids

Level of effect increased

Duration of effect prolonged

Increased likelihood of adverse reactions

Consider using a reduced dose or avoid opioids


Antibiotics

Increased risk of pseudomembranous colitis

No need to alter regimens solely because of age




Nitrous oxide & oxygen First choice for conscious sedation

Advantages Titratability

Rapid onset and offset

Disadvantages Patient acceptance

Limited effectiveness

Equipment costs

Not useful for Alzheimer’s/dementia patients


Oral sedation Advantages

Easy to administer

No equipment costs*

Disadvantages

Dosage is a guess

Onset is delayed and unreliable

Effects are prolonged

Limited efficacy

Many side effects

May not be suitable/effective for dementia patients




Goals

Review the patient’s current drug list

Simplify the treatment regimens

Reduce the number of drugs and the dosing frequency

Monitor the patient after providing a prescription

Pharmacotherapy for the Elderly Patient

Herbal Supplements



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