9: Pharmacology

CHAPTER 9 Pharmacology

PHARMACOLOGICAL PRINCIPLES AND CONCEPTS

Understanding a pharmacological effect on a patient and possible interaction with other drugs is essential to safe dental care. Thorough medical history helps identify adverse effects and potential drug interactions with current prescription (Rx) drugs, dental drugs, over-the-counter (OTC) drugs. Dental settings are advised to have the current Physician’s Desk Reference (PDR) Index for reference information concerning drug information by brand and generic names, product categories, manufacturers.

image • See CD-ROM for Chapter Terms and WebLinks.
• See Chapters 6, General and Oral Pathology: disease states; 14, Pain Management: physical classification system; 8, Microbiology and Immunology: antibiotics; 10, Medical and Dental Emergencies: allergy-related emergencies in a dental setting; 11, Clinical Treatment: contraindications, xerostomia.
A. Dosage:

1. Effective dose: produces 50% of maximum response or specific response in 50% of subjects (ED50).
2. Lethal dose: kills 50% of subjects (LD50); certainly lethal dose (CLD): amount of drug likely to cause death.
3. Therapeutic index (TI): measurement of safety (= LD50/ED50); larger the number, safer the drug.
4. Maximum recommended dose (MRD): established by manufacturer (in milligrams per pound).

B. Administration: latest is time-released drug with ingredients released at predictable rate:

1. Topical: local effect applied directly where action is desired; includes eye drops and ear drops, epicutaneous, enema, vaginal.
2. Enteral: desired effect is systemic (nonlocal), given by way of the digestive tract; includes oral, by tube, sublingual, rectal administration.
3. Parenteral: desired effect is systemic, given by routes other than digestive tract; includes transdermal, intradermal, intravenous (IV), subcutaneous (SC), intramuscular (IM), intrathecal, intraperitoneal, inhalation.

C. Pharmacokinetics (“ADME” scheme):

1. Absorption: process of a substance entering the body.
2. Distribution: dispersion or dissemination of substances throughout fluids and tissues of the body.
3. Metabolism: irreversible transformation of substance and its daughter metabolites.
4. Excretion: elimination of substances from the body.

D. Indications (therapeutic uses):

1. Valid reasons to use drug (test, drug, procedure, or surgery).
2. Strictly regulated by Food and Drug Administration (FDA).

E. Reactions to drugs:

1. Potency: strength of a drug in terms of ability to achieve particular result.
2. Produces BOTH desired (therapeutic effect) and adverse effects (reaction, side effect) on the body.

a. Desired effect(s):

(1) Pharmacological effect(s): act on target organs to achieve therapeutic response.
(2) Therapeutic effect(s): dose related, predictable.

b. Adverse effect(s) (reaction[s]):

(1) Side effect(s) or unintended consequence(s) specifically arising from drug therapy; unpredictable and dose related (e.g., xerostomia [dry mouth], gingival hyperplasia).
(2) Act on nontarget organs (e.g., vomiting with antibiotic erythromycin [Robimycin, E-Mycin, E.E.S.] and topical fluoride products).

c. Interactions:

(1) Synergism: combination action of two drugs gives a greater total effect than sum of individual drug’s effects (e.g., codeine with acetaminophen for pain relief, alcohol and diazepam to cause respiratory depression).
(2) Agonist: drug that causes an effect by interacting with a receptor.
(3) Antagonist: drug that counteracts another drug’s effect on a receptor (e.g., at neuromuscular junctions).

d. Tolerance: Decreased susceptibility to effects of a drug because of repeated use (e.g., painkillers, intoxicants, or antibiotics); when occurs, MORE drug is needed to produce same pharmacological effects.

3. Toxicology:

a. Unpredictable and dose related; acts on target organs and involves extended pharmacological effect(s) (e.g., hepatotoxicity with antineoplastic methotrexate [Rheumatrex Dose Pack, Trexall]).
b. Drug allergy reaction(s): immunological response; NOT predictable or dose related; four types:

(1) Type I (immediate hypersensitivity): occurs immediately (within minutes) after exposure to previously encountered antigen (e.g., allergy to penicillins [Pen-Vee K), preservative [sodium metabisulfite] for epinephrine in local anesthetics); can be life threatening if produces anaphylaxis, must activate emergency medical services (EMS) system.
(2) Type II (cytolytic or cytotoxic): inhibits or prevents cell function; results in cell destruction; may be result of blood transfusion or drug-induced anemia.
(3) Type III (Arthus): occurs within 6 to 8 hours after exposure (SIMILAR to serum sickness); symptoms include urticaria (hives, wheals), lymphadenopathy, fever (e.g., allergy to topical benzocaine, penicillins, sulfonamides).
(4) Type IV (cell-mediated delayed hypersensitivity): occurs within 48 hours, results in an inflammatory reaction such as contact dermatitis (e.g., allergy to penicillins, poison ivy).
(5) Idiosyncratic (individual) reactions: abnormal and have genetic causes.

F. Contraindications:

1. Conditions and factors that increase risks involved in using particular drug (carrying out medical procedure or engaging in particular activity); may be absolute or relative; opposite of indication.

a. Absolute contraindication: situation that makes particular treatment or procedure inadvisable. Example: aspirin [Bayer, Ecotrin, Empirin, Bufferin] is an absolute contraindication for an infant or child because of danger that it can cause Reye’s syndrome; can substitute acetaminophen.
b. Relative contraindication: situation that makes particular treatment or procedure somewhat inadvisable but does NOT rule it out. Example: nitrous oxide sedation during pregnancy is a relative contraindication because of concerns for developing child; should not be used unless deemed absolutely necessary because it is preferable to other general anesthetics; NOT classified in Pregnancy Risk Category (PRC); need medical consult (discussed later).

G. Excretion:

1. MOST drugs are excreted by means of renal route.
2. Extrarenal excretion routes include lungs, gastrointestinal (alimentary) tract (GIT), saliva, breast milk, sweat.
3. Lactating: many drugs are excreted into breast milk, such as tetracyclines, and can affect newborn, medical consult needed; safest drugs SHOULD be considered.

Prescription Writing

Effective prescription writing requires accurate diagnosis; proper selection of drug, dosage form and route of administration; proper size and timing of dose; precise dispensing; accurate labeling; and correct packaging. Prescription is provided by a physician, osteopath, dentist, or other approved practitioner. Note that OTC drugs do not require a prescription but must be included with drug history.

A. Prescription form and written contents:

1. Prescriber’s full name, address, telephone number, DEA number (can be preprinted); group practices may contain multiple prescribers’ names to be circled or checked.
2. Superscription: dated order includes name, address, and age of patient; with symbol ] (means prescription, capital R with a cross on diagonal) that separates superscription from inscription.
3. Inscription: body of prescription; contains name and amount and/or strength of each ingredient for prescribed drug.
4. Subscription: directions to pharmacist in short sentence.
5. Signatura (sig or signa, “write”): contains directions to patient; can be written out or abbreviations can be used (Table 9-1), with prescriber’s signature.
6. Labeling: when drug name is to be included, “label” box is checked.
7. Refills: designated by number.
8. Proprietary (brand name, trade) vs. nonproprietary (generic name): indication of desire or willingness to dispense type of drug known by chemical name (brand, generic).

B. Laws affecting prescription writing by types of drugs:

1. Restricted drugs: available without prescription but kept at pharmacy service counter because of labeling or abuse risk (e.g., drugs containing pseudoephedrine, such as Claritin-D).
2. Legend drugs: may NOT be dispensed by a pharmacist without prescription from physician, osteopath, dentist, or other approved practitioner; FDA and state drugs are legend; label carries the legend, “Caution! Federal law prohibits dispensing without a prescription.”
3. Controlled drugs: require further safeguards for storage, in addition to requiring a prescription; refills are also limited; BOTH state and federal government agencies promulgate (make public) the regulations (see Table 9-2 for Controlled Substances Act).

a. Federal agency is Drug Enforcement Administration (DEA).
b. State agency is Division of Narcotics and Dangerous Drugs (DHHR).

Table 9-1 Pharmacological abbreviations for prescription writing

Abbreviation Meaning
a.c. Before meals
b.i.d. Twice daily
h.s. At bedtime
q.d. Once per day
q.i.d. 4 times per day
q.o.d. Every other day
q6h Every 6 hours
p.c. After meals
p.o. By mouth
p.r.n. As needed
sl. Sublingual
stat Immediately
supp Suppository
t.i.d. 3 times per day
u.d. As directed

Table 9-2 Controlled substances∗

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DRUG EFFECTS ON AUTONOMIC NERVOUS SYSTEM

MANY drugs exert their effects on the autonomic nervous system (ANS). There are two ANS systems: sympathetic division (SANS) and parasymphathetic division (PANS).

• See Chapter 3, Anatomy, Biochemistry, and Physiology: ANS.
A. The SANS enables the body to function during emergencies or respond to stressful situations (engage in “fight-or-flight”):

1. By means of the release of its neurotransmitters, which include norepinephrine and epinephrine.
2. These neurotransmitters subsequently stimulate the SANS receptors, which include alpha (α)- and beta (β)-receptors:

a. Stimulation of α-receptors causes vasoconstriction of the skin and skeletal muscles.
b. Excitation of β1-receptors causes stimulation of the heart muscle and glycogenolysis.
c. Stimulation of β2-receptors causes smooth muscle relaxation, which results in bronchodilation of the lungs.

B. The PANS enables the body to maintain bodily functions during normal daily activities (engage in “stay-and-play”):

1. By means of the release of the neurotransmitter acetylcholine (ACh).
2. The ACh subsequently stimulates its receptor sites (muscarinic and nicotinic) to enhance body function.

C. Prolonged stressful situations can cause chronic SANS stimulation and depression of PANS with diarrhea, constipation, difficulty maintaining sexual arousal, depressed immune system (see Chapter 16, Special Needs Patients: mental illness).

ADRENERGICS

Adrenergics stimulate α- and β-receptors and include epinephrine, levonordefrin, isoproterenol, ephedrine, dopamine III.

• See Chapters 11, Medical and Dental Emergencies: emergency kit for the dental setting; 14, Pain Management: vasoconstrictor use.
A. Pharmacological effects:

1. Excitation of CNS.
2. Effects on cardiovascular system (CVS):

a. Hypertension (high blood pressure [HBP]), dysrhythmias, tachycardia (increased pulse rate).
b. Blood vessel vasodilation with β2-receptors, vasoconstriction with α1-receptors.

3. Hyperglycemia from β1 stimulation increases glycogenolysis, decreases release of insulin.
4. Bronchodilation, mydriasis (pupil dilation), xerostomia (dry mouth).

B. Therapeutic uses:

1. Vasoconstriction:

a. Increases duration of local anesthetic actions and decreases systemic location and toxicity.
b. Controls bleeding through hemostasis, nasal decongestants (due to α-receptors).

2. Treatment of cardiac arrest by epinephrine (because of β1-stimulation).
3. Bronchodilation (because of β2-receptors) for treatment of asthma and emphysema.
4. Stimulation of central nervous system (CNS) by methylphenidate (Ritalin) or pemoline (Cylert) for treating attention deficit–hyperactivity disorder (ADHD).

C. Adverse reactions:

1. CNS stimulation, resulting in anxiety and tremors.
2. Heart palpitations and dysrhythmias.
3. HBP (if drug affects α-receptors).

D. Drug interactions:

1. Decreased pressor effect with haloperidol, phenothiazines, thioxanthenes, diuretics.
2. Cardiac dysrhythmias with halogenated general anesthetics, cardiac glycosides, tricyclic antidepressants (TCAs).
3. HBP with β-blockers from blocking β-adrenergic effects of epinephrine.

E. Contraindications:

1. Narrow-angle glaucoma from an increase in intraocular pressure.
2. Cardiac dysrhythmias.

ADRENERGIC BLOCKERS

Adrenergic blockers inhibit α- and β-receptors, including (1) α-adrenergic blockers such as tolazoline (Priscoline) and phentolamine (Regitine); (2) β-adrenergic blockers, including nonspecific blockers such as propranolol (Inderal) and nadolol (Corgard) and specific blockers such as metoprolol (Lopressor) and atenolol (Tenormin); (3) α- and β-adrenergic blockers such as labetalol (Normodyne, Trandate). See later discussion of patient with CVD.

A. Pharmacological effects:

1. α-Blockers inhibit vasoconstriction in blood vessels (α-receptor effects).
2. β-Blockers competitively block the effects of adrenergics on β-receptors and may inhibit specific β-receptors or be nonspecific receptor site inhibitor.

B. Therapeutic uses:

1. α-Blockers:

a. Peripheral vascular disease (PAD) or Raynaud’s syndrome.
b. Pheochromocytoma, catecholamine-secreting tumor of adrenal medulla.

2. β-Blockers and α1-selective blockers:

a. HBP, angina pectoris, dysrhythmias, migraine headaches, alcohol withdrawal, myocardial infarction (MI, heart attack) prophylaxis, anxiety syndromes.

C. Adverse reactions:

1. Few occur because receptor effects are MORE site specific.
2. Xerostomia, nausea, vomiting.
3. Hypotension (low blood pressure).

D. Drug interactions (see also antiadrenergics under antihypertensives):

1. Effects of β-blockers:

a. Decreased by sympathomimetics, nonsteroidal antiinflammatory drugs (NSAIAs/NSAIDS), rifampin (Rifadin, Rimactane).
b. Increased by calcium channel blockers.

E. Contraindications:

1. Hypersensitivity, asthma.
2. Congestive heart failure (CHF).

CHOLINERGICS

Cholinergics stimulate body functions by direct action (choline esters) or indirect action (inhibition of acetylcholinesterase). Include pilocarpine (Salagen) and bethanechol (Urecholine).

A. Pharmacological effects:

1. Effects on the CVS:

a. Bradycardia (slow pulse rate), hypotension (direct effect on heart), tachycardia (rapid pulse rate).
b. HBP (indirect effect on blood vessels).

2. Nausea, diarrhea, dyspepsia (indigestion).
3. Miosis (pupil constriction), decreased intraocular pressure.

B. Therapeutic uses:

1. Xerostomia.
2. Glaucoma by decreasing intraocular pressure.
3. Urinary retention after surgery by increasing secretions and activity of GIT.
4. Myasthenia gravis (MG) by decreasing muscle weakness.

C. Adverse reactions: increased salivation, lacrimation, urination, defecation.
D. Drug interactions:

1. Reduced effects with anticholinergics.
2. Enhanced effects with cholinergics.

E. Contraindications:

1. Severe cardiovascular disease (CVD) from its CVS effects.
2. Peptic ulcer, asthma, obstruction of GIT or urinary tract by increasing secretions.
3. Uncontrolled hyperthyroidism, with impaired drug metabolism.
4. Patients with MG taking cholinesterase inhibitors (neostigmine [Prostigmin]).

ANTICHOLINERGICS

Anticholinergics (parasympathomimetics) inhibit body functions by blocking muscarinic cholinergic receptors. Include atropine (oral, Sal-Tropine; ophthalmic, Atropair) and propantheline bromide (Pro-Banthine).

A. Pharmacological effects:

1. The CNS effects are dose dependent:

a. High doses result in stimulation.
b. Therapeutic doses result in depression.

2. The CVS effects are dose dependent:

a. High doses result in tachycardia (vagal blockade).
b. Small doses result in bradycardia.

3. Smooth muscle relaxation results in bronchodilation and constipation.
4. Exocrine gland by reducing secretions in the respiratory tract, genitourinary tract, GIT.
5. Include mydriasis and cycloplegia (blurred vision).

B. Therapeutic uses:

1. Preoperative drug to inhibit salivary and bronchial secretions, producing dry field.
2. Eye examinations with relaxation of the lens and mydriasis.
3. Blocking of vagal slowing of the heart in response to general anesthetics.
4. Parkinson-like tremors caused by smooth muscle relaxation from antipsychotics.
5. Motion sickness; also sleep aid with depression of CNS.
6. GIT disorders with decreasing secretions and hypermotility (e.g., gastric ulcers).

C. Adverse reactions:

1. Xerostomia, photophobia (light sensitivity), cycloplegia (paralysis of the lens).
2. Signs of CNS stimulation, tachycardia, hyperpyrexia (high fever).
3. Urinary and GIT stasis.

D. Drug interactions:

1. Increased anticholinergic effects with TCAs, antihistamines, antidepressants, opioids, antipsychotics.
2. Decreased absorption of ketoconazole (Nizoral).

E. Contraindications:

1. Prostatic hypertrophy or intestinal or urinary obstruction or retention because drug increases urinary retention.
2. For CVD because of tachycardia, vagal blockade.
3. Glaucoma (narrow-angle) from an increase in intraocular pressure.

ANXIETY AND PAIN MANAGEMENT

Management of pain and anxiety during dental treatment uses antianxiety drugs, analgesics, anesthetics, sedatives.

Antianxiety Drugs

Main purpose of antianxiety (tranquilizer) drugs is to decrease anxiety through depression of the CNS. Drugs are also noted with therapeutic uses.

A. Benzodiazepines (BZDs) (suffixes “-lam,” “-pam”):

1. Pharmacological effects:

a. Antianxiety and anticonvulsant effects and muscle relaxation.
b. Anterograde amnesia (temporary memory impairment).
c. Wide therapeutic index makes overdose poisoning rare (compared with barbiturates).

2. Therapeutic uses:

a. Anxiety associated with depression and panic attacks with diazepam (Valium), alprazolam (Xanax), temazepam (Restoril), triazolam (Halcion).
b. Insomnia by means of CNS depression with flurazepam (Dalmane).
c. Alcohol withdrawal (agitation, tremors [delirium tremens, DTs]) with chlordiazepoxide (Librium), lorazepam (Ativan), oxazepam (Serax).
d. Epileptic seizures with clonazepam (Klonopin), diazepam (Valium).
e. Antianxiety premedication in dentistry with diazepam (Valium) or alprazolam (Xanax); also memory loss of stressful dental procedures.

3. Adverse reactions:

a. Xerostomia.
b. Depression of CNS, which results in sedation and fatigue.
c. Thrombophlebitis, if given IV.
d. Possible physical and psychological addiction; occurs less often than with barbiturates.
e. Possible teratogenicity, especially during first trimester.

4. Drug interactions:

a. Increased effects with alcohol and CNS depressants.
b. Decreased effects with smoking.
c. Avoid with antifungals.
d. Increases effects of digoxin (Lanoxin) and phenytoin (Dilantin) (particularly with clonazepam [Klonopin]).

5. Contraindications:

a. Drug addiction, narrow-angle glaucoma, hypersensitivity, pregnancy.
b. Psychosis (experience CNS stimulation), chronic pain (because of possible abuse and addiction).

B. Barbiturates (among first antianxiety drugs):

1. Classified (by length of action):

a. Ultrashort acting: methohexital (Brevital) and thiopental sodium (Pentothal).
b. Short acting: pentobarbital (Nembutal) and secobarbital (Seconal).
c. Intermediate acting: amobarbital (Amytal) and butabarbital (Butisol).
d. Long acting: phenobarbital (Luminal).

2. Pharmacological effects:

a. Depression of CNS, which results in sedation.

(1) Higher doses result in greater CNS depression, including respiratory and CVS depression.

b. Anticonvulsant effect.
c. Stimulate microsomal liver enzymes to stimulate metabolism of other drugs metabolized by liver.

3. Therapeutic uses (by duration of action):

a. Ultrashort-acting barbiturates: short-term general anesthesia.
b. Short-acting and intermediate-acting barbiturates: replaced by benzodiazepines for antianxiety and insomnia.
c. Long-acting barbiturates: treatment of seizures with epilepsy.

4. Adverse reactions:

a. Like alcohol, barbiturates are intoxicating:

(1) Mild: slurred speech, loss of coordination, stumbling, staggering, shallow breathing, fatigue, frequent yawning, irritability.
(2) High: unpredictable emotional reactions and mental confusion, severely impaired judgment, mood swings.

b. Mental effects depend on amount and strength; person falls asleep but drug remains in system for long time.

5. Drug interactions:

a. Decreased effects of acetaminophen (Tylenol), β-blockers, oral contraceptives, doxycycline (Vibramycin), phenytoin (Dilantin), steroids, TCAs, warfarin (Coumadin).
b. Increased effects with disulfiram, monoamine oxidase inhibitors (MAOIs), propoxyphene (Darvon).
c. Increased CNS depression with alcohol and other CNS depressants.

6. Contraindications:

a. Hypersensitivity.
b. Porphyria (excess amount of porphyrins); can stimulate and increase the production of porphyrins.
c. Chronic pain and drug addiction (because of risk of further abuse and addiction).

C. Chloral hydrate (orally): sedation of children.
D. Meprobamate: dental anxiety disorders and as muscle relaxant for acute temporomandibular disorders (TMD) with muscle spasms.
E. Zolpidem (Ambien): nonbenzodiazepine sedative hypnotic that is used as short-term sleep aid for insomnia: SAME adverse effects and drug interactions as other sedatives.

CLINICAL STUDY

Age 45 YRS SCENARIO
Sex image Male image Female The patient is scheduled for an oral prophylaxis today. He has generalized dental biofilm and slight calculus deposits throughout, with only slight to moderate gingivitis.
B/P 105/57
Chief Complaint “I hate being here but I know that I have to keep up my mouth.”
Medical History
Myasthenia gravis (MG)
Rheumatoid arthritis (RA)

Current Medications
prednisone (Deltasone) 20 mg qod
neostigmine (Prostigmin) 5 mg qd
diazepam (Valium) 10 mg before dental appointments

Social History Science fiction writer

1. What types of drugs are prednisone (Deltasone) and neostigmine (Prostigmin), and why is he taking them?
2. What type of drug is diazepam (Valium)? Identify its common uses.
3. What are the oral signs of MG that are possible for him?
4. Why does the patient especially need to avoid stress that a dental appointment might bring on, as well as avoid any dental infections?

1. Prednisone (Deltasone) is a corticosteroid, antiinflammatory drug. It treats various diseases of allergic, inflammatory, autoimmune origin. Patient takes prednisone to treat RA, an inflammatory joint disease. Neostigmine (Prostigmin) is an anticholinesterase muscle stimulant that markedly improves muscle strength by improving muscle contraction; he takes it to treat MG, disease of muscular weakness.
2. Diazepam (Valium) is a benzodiazepine (BZD), antianxiety, anticonvulsive drug. He takes it as an antianxiety premedication to help cope with dental anxiety.
3. MG affects facial and cervical musculature, leading to loss of control of facial muscles and resulting in difficulty with smiling, eating, swallowing, speaking, vision; when severe, can cause respiratory distress.
4. Crisis can occur as result of infection (oral included), emotional stress (such as dental care), and surgery. It could involve a myasthenic crisis, which includes loss of swallowing and speaking ability and difficulty breathing and seeing; caused by undermedication, underlying illness, risk factors, or worsening of disease. Or it could involve a cholinergic crisis: related to overmedication with anticholinesterase, occurs within hour of drug use, causes increased muscle weakness, gastrointestinal upset, respiratory difficulties. Both crises require the dental office to provide basic life support and activate EMS system.

Analgesics

Analgesics inhibit perception of pain. Nonopioids reduce pain perception by inhibiting prostaglandin synthesis; MORE effective if they are taken before onset of pain. Opioids depress pain perception in CNS by binding with opioid receptors (Tables 9-3, 9-4, and 9-5).

• See Chapter 11, Medical and Dental Emergencies: emergency kit (aspirin).
A. Nonopioids:

1. Salicylates: aspirin (Bayer, Ecotrin, Empirin, Bufferin) and long-acting diflunisal (Dolobid).

a. Pharmacological effects:

(1) Analgesia for mild-to-moderate pain relief; antipyretic effect (reduces fever).
(2) Antiinflammatory effect (from inhibition of prostaglandin synthesis), decreases vasodilation and swelling.
(3) Antiplatelet effect (from reduction of platelet aggregation), results in reduced clotting.
(4) Uricosuric effect; high doses (MORE than 5 g/24 hours) cause increase in uric acid secretion in urine.

b. Therapeutic uses:

(1) Analgesia for mild-to-moderate pain.
(2) Reduction of fever (antipyretic effect).
(3) Reduction of pain and swelling (antiinflammatory effect); also treats inflammatory conditions such as arthritis.
(4) Prevention of post–myocardial infarction (MI, heart attack) (because of antiplatelet effect) at low-dose (LD) levels.

c. Adverse reactions:

(1) GIT irritation, MOST common (caused by direct irritation of stomach mucosa).
(2) Bleeding levels monitored by international normalized ratio (INR); INRs ≤2.5 are safe for invasive dental work; older test is prothrombin time (PT).
(3) Asthmatics; use acetaminophen (FIRST choice) as substitute for its analgesic and antipyretic effects to avoid aspirin-induced attack.

d. Drug interactions:

(1) Increased risk of bleeding with anticoagulants.
(2) Increased risk of GIT complaints with NSAIAs, corticosteroids, alcohol.
(3) Increased risk of hypoglycemia with oral antidiabetics.
(4) Decreased effects of gout drugs such as probenecid (Benemid, Probalan) and sulfinpyrazone (Anturan).
(5) Increased risk of toxicity with methotrexate (Rheumatrex Dose Pack, Trexall), lithium (Lithobid, Eskalith), zidovudine (AZT; Retrovir).

e. Contraindications:

(1) Hypersensitivity.
(2) GIT bleeding and bleeding disorders (because of GIT irritation and antiplatelet effect); peptic ulcers (because of GIT irritation).
(3) Children with flulike symptoms (Reye’s syndrome [abnormal accumulations of fat begin to develop in the liver and other organs of the body, along with a severe increase of pressure in the brain] can occur during some viral infections).
(4) Can be toxic if larger doses taken, especially if expired (will smell like vinegar).

2. NSAIAs (NSAIDs): naproxen (Naprosyn; OTC: Aleve, Anaprox), ibuprofen (OTC: Advil, Motrin, Pamprin), etodolac (Lodine), ketorolac (Toradol), indomethacin (Indocin), celecoxib (Celebrex).

a. Pharmacological effects:

(1) Analgesic, antipyretic, antiinflammatory effects SIMILAR to aspirin (Bayer, Ecotrin, Empirin, Bufferin).

b. Therapeutic uses: control of mild to moderate pain, fever, inflammatory conditions such as RA.
c. Adverse reactions:

(1) Stomach mucosa irritation SIMILAR to aspirin’s effect on GIT; xerostomia.
(2) Inhibition of platelets; occur ONLY for drug’s duration.
(3) Depression of the CNS, including sedation, dizziness, depression.
(4) Teratogenicity (can interfere with closure of ductus of fetal heart [ductus arteriosus]).

d. Drug interactions:

(1) Decreased effects of antihypertensives.
(2) Increased effects of oral anticoagulants, lithium (Lithobid, Eskalith), digoxin (Lanoxin), phenytoin (Dilantin), sympathomimetics.
(3) Increased risk of toxicity with methotrexate (Rheumatrex Dose Pack, Trexall) and cyclosporine.
(4) Raises serum concentration of hypoglycemic agents.
(5) May cause GIT ulcers with corticosteroids.

e. Contraindications:

(1) Hypersensitivity to ANY antiinflammatory drugs.
(2) Blood clotting problems (because of antiplatelet effect).
(3) Renal disease (caused by higher risk of adverse renal reactions); GIT disorders, such as peptic ulcer; asthma.
(4) Celecoxib (Celebrex) is a COX II inhibitor: increased risk of MI/CVA (cardiovascular accident, stroke) but can be taken with low-dose aspirin (Bayer, Ecotrin, Empirin, Bufferin).

3. Acetaminophen (N-acetyl-para-amino-phenol [NAPP]; OTC: Tylenol).

a. Pharmacological effects:

(1) Analgesic and antipyretic effects SIMILAR to aspirin (Bayer, Ecotrin, Empirin, Bufferin) and NSAIAs.
(2) Little or NO antiinflammatory effect occurs (UNLIKE other NSAIAs).

b. Therapeutic uses: reduction of mild to moderate pain and fever; as substitute for its analgesic and antipyretic effects to avoid aspirin-induced attack in asthmatics.
c. Adverse reactions:

(1) Hepatotoxicity and nephrotoxicity (associated with long-term use, excessively high doses).

(a) Minimum toxic dose is 10 g (140 mg/kg), but liver damage occurs with one 5.85-g dose.
(b) Chronic excessive use (MORE than 4 g/day) can cause transient hepatotoxicity.
(c) Safe dose for chronic alcoholics should NOT exceed 4 g/day; should be 2 g/day or less if hepatotoxicity has occurred (occurs in some chronic alcoholics who take the therapeutic dose).

d. Drug interactions: rare at therapeutic doses.
e. Contraindications:

(1) Hypersensitivity.
(2) Hepatic and renal disease.

B. Opioids: morphine (MS Contin), hydromorphone (Dilaudid), meperidine (Demerol), propoxyphene (Darvon), codeine (various cough preparations), oxycodone (OxyContin; with acetaminophen [Percocet], with aspirin [Percodan]) (Table 9-4).

1. Pharmacological effects:

a. Analgesic effect for relief of moderate to severe pain; sedative effect for relief of mild anxiety.
b. Antitussive effect (cough suppression); antidiarrheal effect (caused by increase in smooth muscle tone in GIT); constipating.
c. Depress CNS by interacting with opioid receptors.

2. Therapeutic uses: analgesia for moderate to severe pain, cough suppression, sedation, anxiety relief.
3. Adverse reactions are related to the drug’s potency (greater potency, greater risk of adverse reactions):

a. Addicting; can be abused.
b. Drowsiness, sedation, and (occasionally) stimulation; decreased rate and depth of respiration (causing death with overdose).
c. Increased intracranial pressure (because of cranial vasodilation); bradycardia and orthostatic hypotension.
d. Nausea, emesis (vomiting), constipation; urinary retention.
e. Miosis (pupil constriction); may be used to determine abuse or overdose.

4. Drug interactions: increased sedation and respiratory depression with other CNS depressants such as MAOIs, TCAs, alcohol.
5. Contraindications:

a. Hypersensitivity.
b. Respiratory problems, including asthma and emphysema (because of respiratory center depression).
c. Chronic pain (abuse and addiction may occur).
d. Head injury (caused by increase in intracranial pressure).

C. Semisynthetic opioids: hydrocodone (Vicodin, Lorcet):

1. Derived from two of the naturally occurring opiates, codeine or thebaine.
2. Combined with paracetamol (acetaminophen, Tylenol), aspirin (Bayer, Ecotrin, Empirin, Bufferin), ibuprofen (Advil, Motrin, Pamprin), homatropine methylbromide (hydrocodone compounds).
3. Purpose of the noncontrolled drugs in combination:

a. Provide increased analgesia because of synergy.
b. Limit intake by causing unpleasant and often unsafe side effects at higher than prescribed doses.

4. Pharmacological effects and therapeutic uses: narcotic analgesic and antitussive.
5. Adverse so reactions, drug interactions, contraindications: SAME as opioids.

a. Addicting, so can be abused.
b. Liver problems caused by larger amounts of acetaminophen (Tylenol).

D. Opioid antagonists:

1. Short-acting naloxone (Narcan): used to reverse respiratory depression caused by opioids.
2. Long-acting naltrexone (ReVia, Trexan): used for opioid addiction after detoxification.

Table 9-3 Drug interactions with commonly used analgesics

Drug Interactions
NSAIA
Decrease antihypertensive effects of ACE inhibitors (captopril), beta blockers, loop diuretics, and thiazide diuretics
Increase effects of anticoagulants
Increase effects of digoxin
Increase effects of phenytoin
Increase effects of lithium
Increase methotrexate toxicity
Increase effects of sympathomimetics
Nephrotoxicity with cyclosporine
Probenecid increases NSAIA concentrations
Salicylates decrease NSAIA concentrations

Salicylates (aspirin [Bayer, Ecotrin, Empirin, Bufferin])
Alcohol increases gastrointestinal ulceration and bleeding time
Corticosteroids decrease salicylate concentrations
Decrease antihypertensive effects of ACE inhibitors (captopril), beta blockers, loop diuretics, and thiazide diuretics
Decrease NSAIA concentrations
Decrease uricosuric effect of probenecid and sulfinpyrazone
Increase effects of anticoagulants
Increase effect of sulfonylureas and exogenous insulin, thereby increasing hypoglycemic effect
Dose >2 g per day displaces VA from binding site, thereby increasing VA effect
Nizatidine increases salicylate concentrations
Acetaminophen (Tylenol)
Alcohol increases hepatotoxicity
Beta blocker (propranolol) increases effects of acetaminophen
Oral contraceptives decrease half-life

ACE, Angiotensin converting enzyme; NSAIA, nonsteroidal antiinflammatory agent; VA, valproic acid.

Table 9-4 Nonopioids: comparison of analgesic efficacy

image

Table 9-5 Analgesic drug combinations and uses

image

Anesthetics and Sedatives

Anesthetic, local (with or without vasoconstrictors) and systemic, as well as sedatives to control pain.

• See Chapter 14, Pain Management: local anesthetics, vasoconstrictors, drug for reversal of local anesthesia, nitrous oxide sedation.
A. Local anesthetics:

1. Pharmacological effects:

a. Reversibly blocked peripheral nerve conduction.
b. Depressed cardiac conduction and excitability that results in hypotension.

2. Therapeutic uses:

a. Topical: 20% benzocaine (preinjection or surgical gel, liquid, or spray, Americaine, Lanacaine, Hurricane; oral gel, Anbesol, Orajel) and 5% lidocaine (preinjection or surgical gel, Topicaine; patch, Lidoderm; preinjection or anesthetic cream 2.5% with prilocaine 2.5%, EMLA):

(1) Esters can result in topical allergies (from PABA) (see earlier discussion).
(2) Overall, can increase plasma levels with overuse and lead to toxicity.

b. Periodontal gel: 2.5% lidocaine, 2.5% prilocaine (Oraqix) for site-specific soft tissue anesthesia; see state regulation if can be used by dental hygienist:

(1) LOW levels in plasma, NO allergenic potential; MRD 5 cartridges or 8.5 mg, with 1 cartridge usually used per quadrant.
(2) Used with caution in patients with severe impairment of renal or hepatic function; NOT used with pregnant woman or under age 18.
(3) Indications: nonsurgical periodontal therapy, substitution for injection when injection is contraindicated.
(4) Technique:

(a) Apply on gingival margin around selected teeth using blunt-tipped applicator; wait 30 seconds and fill periodontal pockets until becomes visible.
(b) Wait another 30 seconds before starting treatment.

c. Lidocaine transoral delivery system (DentiPatch): 46.1 mg of lidocaine for site-specific soft tissue anesthesia.

(1) Onset of action is 5 to 10 minutes; duration of action is ∼45 minutes.
(2) Indications: preinjection anesthesia (especially in palatal areas), nonsurgical perio-dontal therapy, substitution for injection when injection is contraindicated.
(3) Technique:

(a) Remove plastic backing.
(b) Isolate and dry targeted area for 30 seconds.
(c) Apply with pressure for 30 seconds.

d. Injected for soft and hard tissue anesthesia:

(1) Esters:

(a) Procaine (Novocaine) and propoxycaine.
(b) Withdrawn from market (because of increased allergenic potential).

(2) Amides:

(a) Shorter-acting injectables: 2% lidocaine (Xylocaine, Anestacaine), 2% and 3% mepivacaine (Carbocaine), 4% prilocaine (Citanest), 4% articaine (Septocaine, Zorcaine).
(b) Longer-acting injectables: 2% bupivacaine (Marcaine), 1.5% etidocaine (Duranest).

3. Adverse reactions:

a. Talkativeness, apprehension, tremors, seizures (sometimes followed by CNS depression, respiratory and CVS depression, coma).
b. Hematoma at site of injection (especially if piercing pterygoid plexus of veins, maxillary artery).
c. Allergy, ranging from a rash to anaphylaxis; allergic reactions to esters occur MORE often than those to amides; if there is an allergy to BOTH esters and amides, first-generation antihistamine diphenhydramine (Benadryl) can be used for a local anesthetic effect.
d. Metabolism of amides occurs primarily in liver; esters hydrolyzed by pseudocholinesterase, a plasma enzyme.
e. BOTH amides and esters are excreted by kidneys.

4. Drug interactions: additive effect with CNS depressants.
5. Contraindications:

a. Hypersensitivity; sulfite compounds in articaine (Septocaine, Zorcaine).
b. May cause allergic reactions in asthmatics and/or sensitivity to sulfites.

B. Vasoconstrictors (inclusion in some local anesthetics): epinephrine, levonordefrin (Neo-Cobefrin).

1. Pharmacological effects:

a. Cardiac stimulation and lipolysis in response to β1-receptor stimulation.
b. Bronchodilation in response to β2-receptor stimulation.
c. Epinephrine causes vasoconstriction of blood vessels in response to α1 receptor stimulation.

2. Adverse reactions: tremors, anxiety, palpitations, HBP.
3. Therapeutic effects:

a. Epinephrine is available with ALL amides EXCEPT mepivacaine, which is available ONLY with levonordefrin (Carbocaine with Neo-Cobefrin).

(1) Available at 1:20,000 (with levonordefrin), 1:50,000, 1:100,000, 1:200,000 (with epinephrine).
(2) An MRD of 0.2 mg per appointment for healthy patients.
(3) Used MAINLY at 1:100,000 for nerve blocks and 1:50,000 for infiltrations; higher levels do NOT increase effectiveness, only hemorrhage control.

b. Increased duration of local anesthetics because of decreased absorption into CVS.
c. Decreased absorption of local anesthetics into CVS because of blood vessel constriction.
d. Epinephrine has hemostatic properties (stoppage of bleeding) by blood vessel constriction.

4. Drug interactions:

a. HBP, when used in conjunction with nonselective β-blockers.
b. Vasoconstriction is enhanced with TCAs when epinephrine is given IV.
c. Increase in blood glucose with oral antidiabetics.

5. Contraindications:

a. Absolute: hypersensitivity to sulfite compounds that serve as preservative antioxidants may cause allergic reactions in asthmatics and/or sensitivity to sulfites (red wine, aged cheese).
b. Relative: CVD patient who undergoes elective dental treatment should:

(1) Receive a local anesthetic with a vasoconstrictor to increase pain control and its duration, which lowers patient stress level (decreasing endogenous epinephrine).
(2) Receive an MRD of 0.04 mg of vasoconstrictor per appointment (equal to one cartridge of 1:50,000, two cartridges of 1:100,000, or 4 cartridges of 1:200,000).

C. General anesthetics:

1. Pharmacological effects: depress CNS.

a. Guedel’s stages:

(1) Stage I: analgesia (reduced pain sensation).
(2) Stage II: delirium and excitement (unconsciousness and involuntary movement).
(3) Stage III: surgical anesthesia.
(4) Stage IV: respiratory and medullary paralysis (death occurs if NOT reversed).

b. Flagg’s phases (better description of anesthesia levels):

(1) Induction phase: occurs before surgery.
(2) Maintenance phase: begins when depth of anesthesia necessary for operation is achieved; continues until procedure is completed.
(3) Recovery phase: occurs at end of operation, continues through postoperative period until patient is fully responsive.

2. Adverse reactions:

a. Dysrhythmias, cardiac arrest, HBP, hypotension.
b. Respiratory depression and arrest.
c. Teratogenicity, with chronic exposure.
d. Hepatotoxicity, with chronic exposure.

D. General anesthetics:

1. Nitrous oxide, inhalation gas (relatively odorless, colorless).

a. Pharmacological effects:

(1) Analgesia and amnesia, affecting the CNS, with NO significant effect on the respiratory system.
(2) Used instead in MOST cases for mild to moderate (conscious) sedation and NOT at usual general anesthetic levels (less than 50%, standard of care) during nonsurgical dental treatment.

b. Adverse reactions:

(1) Peripheral vasodilation.
(2) Nausea and vomiting, especially if patient consumes large meal before.
(3) Diffusion hypoxia may result in headache or other adverse reactions if patient does NOT receive 5 minutes of 100% oxygen when sedation is terminated.
(4) Neuropathy and paresthesia result with abuse; symptoms include numbness of hands and legs, as well as liver and kidney problems.
(5) Inhalation volatile liquids.

c. Absolute contraindications:

(1) Recent ophthalmic surgery during which gas was administered (C3F8, perfluoropropane or SF6, sulfur hexafluoride).

(a) Gas bubble in the eye is associated with perfluoropropane use within the past 8 weeks or with sulfur hexafluoride use within the past 14 days.
(b) Can disrupt the bubble and cause blindness.

(2) Cystic fibrosis.
(3) Lack of patient cooperation or existence of communication barrier (such as differing language).
(4) Patients with head trauma or shock.
(5) Patients who fear nitrous oxide or those who must ALWAYS be in control (NEVER talk anyone into use).

d. Relative contraindications:

(1) Respiratory obstruction and congested airway (NO exchange of gas possible through nasal passages).
(2) Chronic obstructive pulmonary disease (COPD) (CANNOT tolerate receiving additional oxygen).
(3) Emotional instability, mental illness (altered sense or euphoria may occur); poor patient communication.
(4) Pregnancy because of concerns for developing fetus unless it is absolutely necessary because other general anesthetics cannot be used; NOT classified in Pregnancy Risk Category (PRC); chronic exposure reduces fertility in women; spontaneous abortion or miscarriage may occur.
(5) Contagious disease (e.g., tuberculosis, hepatitis) if nonautoclavable tubes are used.

2. Benzodiazepines (BZDs): diazepam (Valium), midazolam (Versed):

a. Pharmacological effects: used IV for conscious sedation, short-duration sedation; often used for oral surgery; also used as adjunctive drug in balanced anesthesia technique or for antianxiety premedication before appointment.
b. Adverse reactions: thrombophlebitis with diazepam (Valium); using water-soluble midazolam (Versed) reduces risk.

3. Halogenated ether, enflurane (Ethrane).

a. Pharmacological effects: produces greater skeletal muscle relaxation than halothane.
b. Adverse reactions:

(1) Respiratory depression, hypotension, myocardial contractility depression.
(2) Dysrhythmias (occur less often than with halothane).
(3) Depressed renal function.
(4) Possible seizure activity.

4. Halogenated hydrocarbon, halothane (Fluothane).

a. Pharmacological effects:

(1) Fruity odor; is nonflammable, nonexplosive.
(2) Safe for asthmatics because d/>

Related posts:

  1. 10: Medical and Dental Emergencies
  2. 8: Microbiology and Immunology
  3. 15: Dental Biomaterials
  4. 14: Pain Management
  5. 6: General and Oral Pathology
  6. 3: Anatomy, Biochemistry, and Physiology

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Jan 1, 2015 | Posted by in Dental Hygiene | Comments Off on 9: Pharmacology

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