Pharmacology final

Recent anti-fungals

*Echinocandins* (Fungicidal) *eg. caspofungin*. Discovered following anti-fungal resistance. Rather than targeting the membrane of the fungus, they inhibit β-1,3 glucan synthase and hence they compromise cell wall integrity. Effective against candida and some filamentous species. Not many toxic effects No resistance problems due to recency The last line of Rx.!!!

Part of the brain that plays a role for the loss of control seen in drug addicts

*Frontal cortex* - the thinking center of the brain, involved in our ability to solve problems, think and plan, and make decisions.

Oral Glucose Gel

(15g) Drug class: monosaccharide/anti-hypoglycemic Alternative: orange juice ONLY if the patient is conscious. Mode of action: quickly increases blood glucose level in hypoglycemic states secondary to diabetes mellitus. Method of use: twist tip off, squeeze entire contents of tube (15 g) into mouth and swallow (place in the buccal mucosa). If no response within 15 min. repeat dosage. If no response within 30 min., call 911. Side effects: liquid or viscous oral carbohydrates should not be administered to a patient who does not have an active gag reflex or is unable to drink without assistance. Parenteral administration of anti-hypoglycemics is recommended in these situations. There are no side effects when oral carbohydrates are administered as directed. Warning: do NOT administer to any person who is unconscious or unable to swallow. Not recommended for children under 2 years of age.

Diphenhydramine

(50mg/1mL; used for allergic reactions) Drug class: non-selective anti-histamine. Mode of action: antagonizes histamine at the H-1 receptor, causes sedation and has an anticholinergic effect. Use: for non-life-threatening delayed onset allergic reactions (only involving the skin) and in definitive management of acute life-threatening allergic reactions (anaphylaxis). Method of use: 50 mg IM or IV. Side effects: include CNS depression, decreased BP, and thickening of bronchial secretions as a result of the drug's drying action. Because of this drying effect, histamine blockers are contraindicated in the management of acute asthmatic episodes.

Aspirin

(81 mg each; used for MI) Drug class: NSAID, anti-thrombotic (prevents blood clots), pain killer. Chewing and then swallowing *162 mg* aspirin (two 81 mg baby aspirin) during an acute coronary syndrome (ACS) significantly reduces mortality in heart attack victims. Presently, in individuals experiencing chest pain, it is an accepted protocol for paramedics, hospital emergency rooms, and other pre-hospital situations. According to emergency room physicians, 2-4 baby aspirins (81 mg each) or a single standard 325 mg aspirin tablet given immediately to individuals suspected of experiencing a heart attack reduces the risk of death from a myocardial infarction (MI). Mode of action: by irreversibly inhibiting cyclo-oxygenase type 1 (COX-1) within platelets, aspirin prevents the formation of thromboxane A2, thereby diminishing platelet aggregation promoted by this pathway.

Doxycycline (Tetracycline)

(Vibramycin, Vibra-Tabs) Broad spectrum: Gram +, -, anaerobes, aerobes, and spirochetes. Photosensitivity Drug interactions: anti-epileptics Side effects: GI disturbance Pregnancy category D Contraindications: pregnancy/developing dentition

Nitroglycerin

(spray 400 mcg/tablet 0.4 mg; used for angina) It comes as a sublingual tablet to take under the tongue and as a spray. Tablets are usually taken as needed, 5-10 minutes before activities that may cause attacks of angina or at the first sign of an attack. Drug class: Nitrate. Other nitrates include isosorbide dinitrate (Isordil) and isosorbide mononitrate (Imdur). Mode of action: dilates blood vessels that supply the areas of the heart where there is not enough blood flow and O2 thereby delivering O2 to the heart muscle that needs it most. In addition, blood is redistributed to the body within the widened veins, and this reduces the amount of blood returning to the heart that needs to be pumped. Therefore, the heart has less work to do and requires less blood and O2. Dilation of the arteries also lowers the pressure in the arteries against which the heart must pump. As a consequence, the heart works even less and requires less blood and O2. Method of use: spray, sub-lingual tablet Side effects: include headache, dizziness, lightheadedness, nausea, and flushing. Headache is often a sign that this medication is working. Warning: severe hypotension, esp. in upright patients, may occur with small doses this drug. Use with caution in hypotensive or those who are volume-depleted. Hypotension induced by nitroglycerin may be accompanied by paradoxical bradycardia and increased angina pectoris.

Analgesics in pregnancy

*Acetaminophen* is the analgesic of choice. NSAIDs pregnancy classification: B to D3 depending on the trimester. Do not prescribe to pregnant patients as they increase the risk of closure of the fetal ductus arteriosus and cause fetal renal damage and inhibit clotting. *If narcotics are needed, consider Codeine if approved by the Ob-Gyn*. Note: *Benzodiazepines incl. Diazepam and Midazolam* have been implicated as possible causes of craniofacial defects, such as cleft lip and palate. *Do NOT* prescribe in pregnancy!

Factors governing drug action

*Affinity and intrinsic activity* determine the effect of a drug on physiologic processes.

The antibiotic of choice for standard prophylactic regimen of antibiotic coverage for the prevention of bacterial endocarditis is:

*Amoxicillin* Standard Regimen: Adults - 2.0 g orally 30-60 minutes prior to appointment Children - 50 mg/kg (not to exceed adult dose) orally 30-60 minutes prior to appointment. Allergy to Amoxicillin - only if allergy is not of anaphylactic type. Any one of the following can be used: Clindamycin, Cephalexin, Azithromycin, and Clarithromycin. Note: *criteria for prescribing ABs to prevent infective endocarditis are the same for pregnant women as they are for all individuals*.

The main culprit in drug abuse

*Dopamine* - a neurotransmitter that helps control the brain's reward and pleasure centers, movement, and emotional responses. If deficient, Parkinson's Disease may manifest. Nearly all good feelings experienced by humans are caused by dopamine. Individuals who are dopamine deficient are at a higher risk of becoming drug addicts. Other chemicals include Serotonin, Gamma-aminobutyric acid (GABA), Norepinephrine, Endogenous opioids (endorphin and enkephalin), Acetylcholine, Glutamate, Endogenous cannabinoids (anandamide) etc.

Nitroimidazole Abx's - Metronidazole

*Bactericidal* / Anti-protozoal (Flagyl, Flagyl ER, Metrogel). Effective against *anaerobic* bacteria. It provides good anaerobic coverage. *Best used in conjunction with Penicillin in cases of infection where anaerobes are the likely cause eg. soft tissue pericoronitis from partially impacted wisdom teeth*.

Burning mouth syndrome pharmacotherapy

*Benadryl*: Diphenhydramine Elixir 12.5 mg/5 ml (alcohol-free, OTC) Instructions: rinse with 1 tsp (5 ml) for 2 minutes before each meal and swallow. Benzodiazepines and tricyclic antidepressants have been used with some success: *Diazepam* 2 mg 1-2 tables TID. *Zostrix 0.025%* (topical Capsaicin, OTC).

Why do some people become addicted to drugs while others don't?

*Biology* Genetics - gene polymorphism on protein expression and brain function. Approx. 50% of the risk for an addiction is genetic, incl. addiction to heroin, cocaine, alcohol, and nicotine. The specific genes involved in this process are not well-understood. Gender Ethnicity Mental disorders *Environment* Early exposure to drugs Family and friends General quality of life Peer pressure Physical and sexual abuse Socio-economic status Stress *Development* Environmental factors in critical developmental stages The earlier an individual uses drugs, the more likely she/he will become an addict Teenagers are prone to risky behaviors incl. trying drugs

Erythromycin is responsible for numerous drug interactions, some of which are fatal. This is because erythromycin:

*Decreases cytochrome P-450 metabolism of other drugs*. Explanation: cytochrome P-450 group of enzymes are essential for the metabolism of many medications. Expressed mainly in the liver, but also in the small intestine (reducing drug bioavailability), lungs, placenta, and kidneys. Note: interactions with warfarin, antidepressants, anti-epileptic drugs, and statins often involve the cytochrome P450 enzymes.

Pharmacological managment of Candidiasis

*Mycelex (Clotrimazole)* 10 mg troches, Sig: dissolve 1 troche orally 5 times per day (do NOT chew). *Mycostatin, Nilstat (Nystatin)* oral suspension 100,000 U/ml Disp: 240 ml Sig: rinse with 5 ml QID for 3 minutes and expectorate (if swallowed, < 5% is absorbed systemically, OK in controlled diabetics). Continue use for 7 days after signs of infection disappear. Children tolerate this medication well. For denture wearers: instruct to add a few drops of oral Nystatin suspension added to water and soak denture. Systemic antifungals used for muco-cutaneous and oropharyngeal candidosis: *Ketoconazole (Nizoral) and Fluconazole (Diflucan)*: inhibitors of cytochrome P-450. Prescribed by a physician as liver function tests (LFT's) need to be monitored.

Angular cheilitis pharmacological management

*Mycolog II, Nytrex Cream/Ointment (nystatin triamcinolone acetonide)*, dispense (15) fifteen grams, apply to corners of mouth QID. Instruct patient to wash hands before and after use. Clean and dry the affected area then apply a small amount of medication in a thin layer on the skin and rub in gently BID.

EpiPen (Epinephrine)

*Non-selective alpha and beta-adrenergic receptor agonist*. *A vasoconstrictor*. Indications: in the emergency treatment of Type I allergic reactions including anaphylaxis caused by allergens or unknown triggers involving the respiratory or cardiovascular function. For the management of individuals who are at increased risk for Type I allergic reactions, ACLS protocols, and acute bronchospasm. Pregnancy classification C: Used in pregnancy if the potential benefit justifies the potential risk to the fetus (fetal anoxia, spontaneous abortion, or both). Lactation safety: Since many drugs are excreted into human milk, it is best to assume that Epi is also excreted. Use with caution with nursing mothers.

Which drug is the most preferable antibiotic for the treatment of non-penicillinase-producing G + staph. infections?

*Penicillin VK* Explanation: always use an Abx with a *narrow spectrum* of activity and one that is *bactericidal* in order to minimize bacterial resistance. Penicillin VK has these properties.

Dentoalveolar abscess

*Poly-microbial infection* Facultative anaerobes include Strep. viridans and Strep. anginosus groups. Strict anaerobes include Prevotella and Fusobacterium. Anaerobic cocci can be predominant. Treatment: Surgical procedures such as incision and drainage of pus eliminate the source of infection. Abx's assist this process of elimination by limiting the spread of infections.

Antifungal Agents in Clinical Use

*Polyenes (Fungicidal)* Mode of action: they act directly on the membrane by binding directly to ergosterol (hence their toxicity), the major sterol in plasma membrane, and cause leakage. The 2 major ones in clinical use are: Amphotericin B [AMB] (systemic administration): not very water-soluble, used for systemic infections; AMB toxicity is a problem. Nystatin (topical application): more soluble than AMB; troche or oral suspension; it enhances anti-coagulant activity of warfarin. *Azoles (Fungistatic)* - Most widely used class. They are less toxic vs polyenes. Disadvantage: Rx. is usually long-term, weeks or even months thus anti-fungal resistance. Mode of action: they interfere with the synthesis of the membrane by interfering with the chemical pathway that results in the synthesis of ergosterol. Inhibition of P-450 cytochrome lanosterol -14α demethylase interferes with ergosterol biosynthesis, and accumulates toxic sterols. Compromises membrane integrity and function. Binds to heme-binding pocket in heme-containing proteins. Acquired resistance is the major problem with systemic azoles; less so with topical azoles. Azoles contain 2 major classes: Imidazoles (2 nitrogens) - Miconazole, Clotrimazole (topical) and Ketoconazole. Miconazole can be fungicidal at high conc. Triazoles (3 nitrogens) - Fluconazole (most widely used)

Examples of Schedule III/IIIN drugs:

*Products containing no more than 90 mg of codeine per dosage unit* (Tylenol with Codeine), and Buprenorphine (Suboxone). Ketamine and anabolic steroids.

Which of the following antibiotics has been implicated in the vast majority of cases of oral contraceptive failure during antibiotic use?

*Rifampicin* Explanation: it (used for TB) reduces the effectiveness of hormonal contraception by affecting liver enzymes which speed up the removal of chemicals incl. estrogen and progestin (found in oral contraceptives). Ampicillin has also been found to decrease the effectiveness of oral contraceptives (suppression of GI flora involved in the recycling of active steroids from bile conjugates, leading to more rapid excretion of the steroids from the body). However, certain articles concluded that "antibiotics cause contraceptive failure in a very small percentage of patients". Therefore, warn patients about a possible interaction, recommend extra precautions and DOCUMENT the discussion in patients' charts.

Naloxone (Narcan)

*Short-acting narcotic antagonist*; reverses heroin and prescription opioid overdoses. Competitively blocks CNS opioid receptors. Higher affinity for mu receptors. Also available as an injection. Indication: Reversal of narcotic respiratory depression and coma. Safety: Naloxone is as non-toxic as water and has no potential for addiction. It has no effect on a person who has not used opioids. Not a controlled substance (no abuse potential) but requires prescription. The half-life of Narcan is approx. 30-60 mins which is shorter than the half-life of common narcotics (but not that of heroin which is a few minutes). Pregnancy class B Lactation safety - unknown.

Buprenorphine

*Sub-lingual tablets, they are opioid partial agonist*. There is a formula with Naloxone. Like opioids, it produces euphoria or respiratory depression. However, these effects are weaker than those of full drugs such as heroin and methadone. Lowers the potential for misuse. *Produces diminished effects of physical dependency to opioids, such as withdrawal symptoms and cravings. Dosing is usually every other day* Safer in cases of overdose Has a ceiling effect: its opioid effects increase with each dose until at moderate doses they level off, even with further dose increases. This effect lowers the risk of misuse, dependency, and side effects.

Drug interaction resulting in serious adverse CVS effects, including death, might occur between erythromycin and which of the following anti-histamine?

*Terfenadine (Seldane)* Explanation: the interaction between Erythromycin and Terfenadine resulted in abnormalities of the electrical impulse that stimulates the heart to contract causing QT interval prolongation and ventricular arrhythmia.

Pain management - combination therapy

- 400 mg ibuprofen/1000 mg acetaminophen was more efficacious than placebo, acetaminophen/codeine, and ibuprofen/codeine. - 200 mg ibuprofen/500 mg acetaminophen was superior to acetaminophen/codeine and non-inferior to ibuprofen/codeine combination. - *400 mg ibuprofen/1000 mg acetaminophen* was more efficacious than 200 mg ibuprofen/500 mg acetaminophen. - Ibuprofen/codeine combination was more efficacious than acetaminophen/codeine combinations, and both were more efficacious than placebo. - *Conclusion*: "dental surgery post-op pain is treated more effectively with *Ibuprofen-Acetaminophen combination* than medications containing narcotics".

5 Key indicators the Maine PMP achieved:

- Mandatory Prescriber Education - Opioid Prescribing Guidelines - Prescription Drug Monitoring Programs - Increased Access to Naloxone - Availability of Opioid Use Disorder Treatment

What determines the intensity of drug activity?

- The concentration at the site of the receptor - The density of receptors on the cell surface - The mechanism by which a signal is transmitted into the cell, such as by: 1. second messengers, and 2. regulatory factors that control gene translation and protein production may influence drug effect.

Pain management in pregnancy

-Acetaminophen (aka Paracetamol) -Codeine, hydrocodone and oxycodone: virtually any drug in a pregnant patient can cross the placenta and enter the fetal circulation; drug use in pregnant patients is a source of special concern; therefore consult with the patient's Ob/Gyn prior to prescribing and document the consult.

Narcotic prescriptions are contra-indicated in:

-Biliary obstruction -COPD -MAO inhibitors for depression - they inhibit the activity of the monoamine oxidase enzyme family. -Urinary retention *Combination therapy is indicated

How do medical conditions change the PD of a drug?

-By changing receptor binding -Altering the level of binding proteins -Decreasing receptor sensitivity

Absolute N2O Contraindications

-Cancer therapy using Bleomycin sulfate -Chronic obstructive pulmonary disease (COPD) -Current or recovering drug use/addiction -Current psychotropic drug use (EtOH, meth, weed, etc.) -Cystic fibrosis -First trimester of pregnancy -Inability to understand or unwilling to consent to procedure

Pain management in dentistry

-Consider non-opioid analgesics as first line agents for post-op pain management. -Consider combining NSAID's with acetaminophen to provide a greater analgesic effect than the single agent alone.

Relative N2O Contraindications

-Current upper respiratory tract infection. -Middle ear disturbance/surgery eg. grafting. -Recent eye surgery using perfluoropropane or sulfur hexafluoride.

Naloxone (Narcan) side effects and clinical effects

-In opioid-dependent patients, Naloxone may result in severe opioid withdrawal which includes: body aches, diarrhea, tachycardia, fever, runny nose, sneezing, goose bumps (piloerection), sweating, yawning, nervousness, nausea and vomiting, restlessness or irritability, shivering, abdominal cramps, weakness and hypertension. -Re-sedation may occur, because the duration of effect of the opiate may exceed that of Naloxone. In the event of re-sedation, repeat doses may be administered. Patients need to be monitored for vitals and alertness until they their baseline level of consciousness. In case of overdose, the toxicity may return in 30-90 min. following the use of Narcan. *Clinic staff must call 911 following an initial dose of Narcan* as additional doses and monitoring will be/may be required.

Major components of the candida cell envelope:

-Manno-protein (the outer fuzzy layer): permeability barrier, attachment, branched mannose polymers attached to protein core (more developed when compared to that of humans) -**Glucan (the next layer, chicken wire-like): structural integrity of cell, β-1,6 and β-1,3 glucose polymers, porous -Chitin: structural scaffold for growing bud, polymer of N- acetylglucosamine -**Plasma membrane: ergosterol as the major sterol **targets of 2 major classes of antifungal drugs.

What criteria(s) should you consider when selecting an analgesic agent for a patient?

-Pregnancy and age of patient -Type of pain and patient's medical conditions -Concurrent medication and their chronic pain drugs

Hypo-salivation promotes Oro-pharyngeal Candidiasis through:

-Saliva washes away microbes, debris, and dead organisms. A decreased flushing action increases oral retention of C. albicans; denture stomatitis. -pH changes:candida is extremely tolerant to pH changes; reduction in pH such as in a high carb./sugar diet, enhances candida adhesion -Some salivary components inhibit/reduce fungi such as histatins; therefore a reduction in anti-fungal components in saliva permits more vigorous candida growth. -A detrimental effect on epithelial integrity/function leads to tissue invasion.

fMRI (coronal sections) and drug abuse

-Show areas of brain activation and deactivation during cocaine intoxication compared with those after saline administration. -During intoxication, a complex pattern of activation and/or deactivation is seen - it includes the ventral tegmental area (VTA) and the substantia nigra (SN), where dopamine cells are located, as well as brain areas involved with *reward*; nucleus accumbens (NAc), basal forebrain (BF), globus pallidus (GP); with *memory* (amygdala); and with *motivation*; subcallosal cortex (SCC).

PET Scans (axial sections) and drug abuse

-Show the effects of chronic drug exposure on proteins involved in dopamine (DA) neurotransmission and on brain function (assessed by brain glucose metabolism). -Methamphetamine abusers show a decrease in DA transporters in the striatum (possibly the result of neurotoxicity to DA terminals). -Cigarette smokers show a decrease in brain monoamine oxidase B (aka MAO B), the enzyme involved in DA metabolism.

What determines the affinity of a drug for its receptor and its intrinsic activity?

-The chemical structure of the drug -As a result, minor modifications in a drug molecule is likely to result in major changes in its pharmacological properties

Drug addiction pathophysiology

-Upon initial consumption, a drug of abuse such as heroin or MDMA enters the brain. -The drug then binds to its initial protein target. -This protein binding results in disturbances in the synaptic transmission at certain neural synapses in the brain. -This in turn disrupts neuro-transmission, the process of communication between brain cells. -Such disruption produces acute behavioral effects - euphoria, sedation, ill-behavior etc. -The development of drug addiction requires *a number of adaptations* (molecular and cellular changes that alter the way neural circuits function) to repeated drug consumption, which result in behavioral abnormalities. -Neurons are particularly affected. -These adaptations are a result of *neural plasticity*. -Neural plasticity is the process by which our brain regulates the learning processes and helps us to adapt to our surroundings. -Once exposed to a drug of addiction, changes or adaptations in the *Ventral Tegmental Area* (VTA) and *Nucleus accumbens* (Nac) increase or decrease the user's sensitivity to the rewarding effects. These changes result in withdrawal symptoms upon ceasing the drug. -Alterations in the amygdala and hippocampus mediate drug craving and relapses usually triggered by cues or memories of past drug use incl. specific location where the drug was consumed, certain events that took place during consumption etc.

Doxycycline (Tetracycline) dosing

100mg qd-bid x 7-14 days (no pediatric dose) Capsules: (50mg, 100mg) Tablets: (100mg)

The average time for the onset of drug effect after subcutaneous administration is:

15 minutes. -Oral route: approx. 30 minutes following administration . -Intramuscular injection: approx. 5 minutes due to high blood flow through the muscles. -Inhalation: gases eg. N2O is absorbed rapidly though the lungs; it gains access to the general circulation within 5 minutes. -Patch delivery: approx. 15 minutes and similar to subcutaneous injection. Drug is released into the blood stream over a 12-24 hour period.

Salivary hypofunction

25% of adults complain of xerostomia. It is important to distinguish between xerostomia and salivary hypofunction: one can have xerostomia without salivary hypofunction. Most people (non-medicated) are capable of producing saliva well into their 70's or 80's. As we get older we get fat tissue taking over our glands so we lose spare K+ but the saliva produced is still enough to function. Xerostomia is associated with a 50% reduction in whole resting flow rate. The quality and content of the saliva is currently being studied - still in its infancy. Salivary glands are like muscles: you have to use them in order for them to work adequately If you cut the nerve supply, the muscle will atrophy with time eg. people on liquid diet complain of xerostomia due to lack of glandular stimulation. Approx. 600 drugs have the potential to cause xerostomia. Of the 200 most frequently prescribed drugs in the US, about 2/3 are associated with xerostomia. Consumption of xerogenic drugs and therefore xerostomia have a female predilection. The longer a patient takes xerogenic drugs, the more likely it is that a long-term drop in saliva will occur: still unknown whether this is due to a neural complication or glandular atrophy.

Tetracyclines

30S subunit protein synthesis inhibitor. Bacteriostatic Not well-absorbed with food Multiple resistant strains present Not very useful in odontogenic infections Useful for: peri-implantitis; periodontal infections; and possibly topical 3rd molar application.

Pregnancy and hypertension

6-8% of pregnant patients will have a hypertensive disorder. There are 4 categories of "hypertension in pregnancy": Chronic hypertension Gestational hypertension Preeclampsia Preeclampsia superimposed on chronic hypertension A maternal BP measurement of *≥140/90 mm Hg on two occasions before 20 weeks of gestation* indicates chronic hypertension. *Severely elevated BP is 150-180 / 100-110 mmHg*: likely to cause maternal end-organ damage. If not well-controlled, severe hypertension increases. Bleeding risk during surgical and dental procedures Consult with the Ob-Gyn as needed.

Substance abuse

A diagnosis requires the recurrent use of a substance over the past 12 months with subsequent adverse consequences. Pertains to repeated and prioritized use of drugs or substances with an overwhelming desire to consume more of psychoactive substance in order to experience euphoria and a perceived emotional or physical pain relief. This kind of disorder is part of the human condition, and touch as many as one in four American families. Genetic component - results in genetic expression through biochemical changes in the brain. These changes only occur with exposure to mood-altering chemicals over a significant period of time. These chemicals include: alcohol, opiates, sedatives, tranquillizers, stimulants, cannabinoids, etc.

Agonist

A drug that binds to physiological receptors and mimics the regulatory effects of the endogenous signaling compounds. Example: GABAergic neurons are inhibitory, so GABA agonists usually inhibit neural activity and behavior.

Antagonist

A drug that binds to receptors without regulatory effect, but this binding blocks the binding of the endogenous agonist. May still produce useful effects by inhibiting the action of the agonist (eg. by competing for agonist binding sites).

Minimum Bactericidal Concentration (MBC)

A higher antibiotic concentration that *will kill the organisms*.

Glucagon

A hormone secreted by pancreatic alpha-cells. Plays a critical role in the regulation of glycemia. Is closely related to insulin-secreting beta cells. Is crucial for keeping the body's blood glucose levels stable.

Therapeutic index (TI)

A measure of drug safety, *the larger it is, the safer the drug*. A ratio of the blood level at which a drug becomes toxic and to that at which the drug is effective.

Cevimeline (Evoxac) - Sialogogue

A para-sympathomimetic and muscarinic agonist (more M3 selective). Approved for use in Sjogren's Syndrome, off label use for post-radiation xerostomia. Longer duration of action/half-life compared to Pilocarpine (use Pilocarpine first). Metabolized by CYP450. Dose: *30 mg PO TID*.

Pilocarpine (Salagen) - Sialogogue

A para-sympathomimetic/muscarinic agonist alkaloid obtained from the leaves of tropical American shrubs from the genus Pilocarpus. Non-selective muscarinic receptor agonist in the parasympathetic nervous system, which acts therapeutically at the muscarinic acetylcholine receptor M3 due to its topical application eg. in glaucoma. Approved for use in radiation-induced salivary hypofunction and Sjögren's Syndrome. *Initial dose is 5 mg TID*. Typical side effects: sweating, nausea, flushing, GI distress, and accommodation?

What can we do as clinicians to minimize the development of life-threatening situations in the dental chair?

A pre-treatment physical evaluation of each patient: medical and medication history, an accurate dental history, and PCP consult for medically-compromised patients. Physical examination: BP, pulse etc. Possible modifications in dental care to minimize medical risks eg. local anesthetic modification, reduce appointment times, etc. A well-prepared and written down plan for emergencies: all clinic staff to be familiar with this plan. Ensure that all practice staff are at least BLS-certified (and up-to-date). Ensure that the drugs in the emergency kit are in date: a system needs to be in place to ensure this. Certain companies provide this service for a yearly fee. Mock codes.

Baclofen

A selective GABA beta agonist, it enhances the release of GABA and is used clinically as a muscle relaxant.

Sialogogue

A substance that stimulates the flow rate of saliva.

Secretagogue

A substance that stimulates the secretion of a substance.

The gram (G) stain

A test which classifies bacteria according to *blue staining*. It is accurate for early diagnosis and treatment, a guide to antibiotic therapy, but not performed in private practice (performed in a hospital environment). Possible results of this test: G+ bacteria retain the blue stain G-bacteria lose the blue stain upon intermediate acetone treatment and will stain red

Angular Cheilitis / Cheilosis

A.k.a Angular Stomatitis, Cheilosis Etiology and Predisposing Factors: Dribble of saliva causing a form of contact irritant dermatitis/perlèche known as eczematous cheilitis Condition is worsened by licking one's lips May last a few days or be persistent

Herpes Simplex Virus (HSV) recurrent herpes labialis

A.k.a Cold Sores, Fever Blisters. Etiology: 90% of oral herpes cases are caused by HSV- 1 (genital herpes cases are for the most part caused by HSV-2). 10% are thought to be caused by HSV-2. Extremely common disease Clinical Description: characterized by an eruption of small and painful blisters on the skin of the lips, mouth, gingiva, or the skin around the mouth.

Aphthous stomatitis

A.k.a canker sores, mouth ulcers. Etiology: Common oral condition esp. in young adults. Familial tendency. Etiologic factors are not completely clear but include stress, physical or chemical trauma, food sensitivity and infection. Clinical Description: lesions may be single or multiple. Size: ranges from less than 1mm to 2 cm. Patients with benign aphthous ulcers should have no other findings such as fever, adenopathy, gastrointestinal symptoms or other skin or mucous-membrane symptoms. Most ulcers heal spontaneously at 10-14 days.

Ammonia Inhalants

A.k.a. "Aromatic Ammonia" or "Smelling Salts". Drug class: ammonia 15% Mode of action: they release ammonia (NH3) gas that irritates the membranes of the nose and lungs, and thereby triggers an inhalation reflex (works by increasing the body's urge to breathe). This reflex alters the pattern of breathing, resulting in improved respiratory flow rates and possibly alertness. Use: used to treat syncope (to arouse consciousness). Syncope may follow an unpleasant or stressful event, or by a serious medical problem, such as heart disease. Fainting in an older person is often more serious than fainting in a younger person. Older people and people with a history of heart problems should seek medical attention as soon as possible after fainting. Method of use: hold inhalant away from face and crush between thumb and forefinger. Carefully approach crushed inhalant to nostrils of affected person. Side effects: coughing or watery eyes may occur. Warning: keep away from the eyes.

Albuterol inhaler

A.k.a. "Salbutamol", (equivalent to 90 mcg per actuation; used for asthma) Drug class: beta-2 adrenergic agonist. Mode of action: mimics the action of naturally occurring catecholamines incl. norepinephrine, epinephrine and dopamine. Use: acts mainly on the smooth muscle of the vasculature, bronchial tree, intestines and uterus. Also acts on the liver stimulating glycogenolysis and release of glucose from the liver and muscle (particularly if used in high doses). Used to prevent and treat difficulty breathing, wheezing, SOB, coughing, and chest tightness caused by lung diseases such as asthma and chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways). When given in large doses or after intentional overdose, albuterol can cause liver injury. Method of use: shake well, give to the patient (they usually know how to use it - they will press the inhalant approx. twice), and ensure that the mouthpiece is firmly attached to the patient's mouth before use.

Organ transplant patients in dentistry

Active infections incl. oral infections have been associated with severe clinical complications following organ transplant surgery. A study by the School and the National Institute of Transplantation, stated that "kidney transplant patients affected by gum disease are at risk for viral replication within the gum tissues despite antiviral therapy prior to and after transplantation". Good oral health is important for successful organ transplantation: many surgeons will request a *dental clearance* prior to performing transplant surgery.

Steady state [SS] of a drug

Absorption and removal drugs take place concurrently. Following repeated doses of a drug, plasma concentration builds up to eventually reach SS. At SS, *the amount of a drug in the plasma has built up to a concentration level that is therapeutically effective*. Regular administration of a drug will "balance" the amount of the drug being cleared: this will ensure that the drug continues to be active.

Which drug(s) would you prescribe to a patient with a history of gastric ulcers?

Acetaminophen/Paracetamol Remember - the following analgesics should be avoided in patients with renal disease: aspirin, acetaminophen, NSAIDs, meperidine and morphine. Consult with the patient's PCP if need be.

Glucagon action on cells

Action is dominant is fasting state. Prevents hypoglycemia by increasing glucose production by cells. In order to maintain blood glucose levels, the liver is the primary target.

Reversal of anti-coagulants

Activated PCC (aPCC) - replaces coagulation factors reduced by warfarin. Idarucizumab - antibody, neutralizes the effects of Dabigatran only. Protamine - negates the effects of heparin. Partially reverses the effects of LMWH. Vitamin K - results in the production of functional coagulation factors II, VII, IX and X. Works on warfarin. No effect of other anticoagulants.

Action of glucagon

Acts on the liver to cause glycogenolysis, which results in the release of glucose into the bloodstream, inhibiting glycolysis. Maintains blood glucose levels during fasting by inceasing gluconeogenesis (glucose production from amino acids), and increasing lipolysis, to free fatty acids for metabolic use. Prevents hypoglycemia and increases with exercise independent of blood glucose.

Which term is a compulsive, uncontrollable dependence on a substance, habit, practice to such degree that cessation causes severe emotional, mental or physiological reactions?

Addiction

Addiction vs Dependence (of Morphine)

Addiction to morphine follows the brain's reward pathway. Dependence to morphine develops in the *thalamus and brainstem*. It is possible to be dependent on morphine, without being addicted to morphine eg. cancer patients may be dependent on morphine without being compulsive users of it.

Burning mouth syndrome treatment rationale

Address etiologic factors in order to reduce discomfort: remove any irritating factors eg. sharp teeth/restorations; examine RPD's and ensure a good fit; recommend more fluids, saliva replacement etc. (for xerostomia, if it's a side effect to current medication, discuss with the patient's PCP). For thrush: prescribe antifungals Eliminate mouthwash esp. if alcoholic Eliminate a reaction to toothpaste Eliminate factors such as chewing gum, tobacco and acidic drinks such as fruit juices, coffee and soft drinks and reassess. If symptoms do not resolve after the elimination process described above, refer for further investigation.

Intra-nasal dosage and administration of Narcan (Naloxone)

Administer a single spray to adults or pediatric patients intra-nasally into one nostril. Seek emergency medical care immediately after use. Administer additional doses, using a new nasal spray with each dose. If the patient does not respond or responds and then relapses into respiratory depression, additional doses may be given every 2-3 minutes until emergency medical assistance arrives.

Penicillin V dosing

Adults: *500 mg QID every 6-8 hours* Children: 25-50 mg/kg/day in divided doses (max. 3g per day) every 6-8 hours. Note: to be taken on an empty stomach - it is degraded by acid and enzyme activity in the stomach associated with ingestion of food. Use cautiously in patients with: renal impairment and history of seizures (it has been reported to exacerbate renal impairment and induce seizures).

Amoxicillin

Adults: *500 mg TID or 875mg BID* Dosage form: capsules of tablets Children: 50 mg/kg/day in children in 3 divided doses. Max. daily dose is 90 mg/kg. Dosage form: 125 and 250 mg/5 ml suspension; 250 and 500 mg capsules and 125 and 250 mg chewable tablets. Dose interval: every 8 hours.

Amoxicillin / Clavulanic acid (Augmentin) dosing

Adults: *500-875 mg BID for 5 days*. Children: 40 mg/kg per day, in 2-3 divided doses for 5 days. Dose Forms: Tablets (250/125mg, 500/125mg, 875/125mg, XR 1000/62.5mg). Chewable tablets (125/31.25mg, 200/28.5mg). Oral suspension (125/31.25mg, 200/28.5mg, 250/62.5mg, 400/57mg, 600/42.9mg per 5ml). Most common side effects: stomach cramps and diarrhea.

Cefaclor dosing

Adults: 250-500mg TID Children: 20-40mg per kg /day (max. 1g)

Azithromycin dose

Adults: 500 mg 1st day, then 250 mg/day for days 2-5 (long half-life of 11-14 hours). Children: 10-12 mg/kg on day one then 5 mg/kg for days 2-5.

Clarithromycin (Biaxin, Biaxin XL) dose

Adults: 500 mg BID. Children: 7.5 mg per kg/day. Tablets (250mg, 500mg, XR 500mg) Oral suspension (125mg, 250mg per 5ml)

Erythromycin dosage

Adults: 500 mg QID Children: 40 mg per kg/day

Cephalexin dosing

Adults: 500mg QID Children: 25-50 mg per kg/day

Missed Abx doses

Advise to: take dose as soon as she/he remembers, skip dose if too close to the next dose, and never double on medication.

pc (post cibum)

After meals

Chapped / cracked lips risk factors

Alcoholism due to susceptibility to malnutrition and vitamin deficiency. Dehydration and malnutrition Medications including vitamin A, retinoids (Retin-A), lithium for bipolar and certain chemotherapy agents. Older adults Chelitis - a severe form, characterized by cracked skin at the corners of the lips. Frequent sun exposure in the summer worsens the condition.

Factors influencing hepatic drug metabolism include which of the following?

All of the following: Microsomal enzyme inhibition, Microsomal enzyme induction, Plasma protein binding, Genetic factors, and Liver disease.

The Controlled Substance Act [CSA] of 1970 uses which criteria for inclusion of a drug into one of the 5 schedules?

All of the following: Potential for abuse, Medical usefulness, Degree to which it produces physiological dependence, and Degree to which it produces physical dependence.

Examples of Schedule IV drugs:

Alprazolam (Xanax) Carisoprodol (Soma) Clonazepam (Klonopin) Clorazepate (Tranxene) Diazepam (Valium) Lorazepam (Ativan) Midazolam (Versed) Temazepam (Restoril) Triazolam (Halcion)

Anti-cholinergics

Also referred to as anti-muscarinics. They block the activity of the neurotransmitter acetylcholine, which stimulates the part of the brain that triggers nausea and vomiting, as well as involuntary muscle movement in the lungs, and the GI and urinary tracts. Belladonna Alkaloids: Atropine, Belladonna, Hyoscyamine, Scopolamine. Belladonna alkaloid combinations and phenobarbital are used to relieve cramping pains in conditions such as IBS and spastic colon.

The 4 most potent anti-depressants in terms of anti-muscarinic action:

Amitriptyline Butriptyline Dothiepin Protriptyline

Phentolamine

An *alpha adrenergic blocker*. Recall that alpha 1-adrenoceptor antagonists are used in treating primary HTN. *Used IV during surgery to control blood pressure*.

Partial agonist

An agent that is only partly effective as an agonist relative to a full agonist. Example: Buprenorphine binds to μ opioid receptors and causes them to produce analgesic and euphoric effects, but to a lesser extent than full agonists. Increasing the dosage of a partial agonist produces a small increase in the production of endorphins.

Glycopyrollate in dentistry

An anti-cholinergic historically used in dentistry instead of a rubber dam in heavy saliva secreters; gives a couple of hours of dryness so the operator can work in a dry field. An anti-sialogogue not used as often today in dentistry.

Flumazenil (Romazicon)

An imidazo-benzodiazepine derivative. A *benzodiazepine receptor antagonist* which prevents benzodiazepines from binding to their receptor; it does not affect the GABA alpha receptor. For this reason, it can be used in the treatment of a benzodiazepine overdose. Indictations: Complete or partial reversal of the effects of benzodiazepines used as general anesthetics, or during diagnostic or therapeutic procedures. For management of benzodiazepine overdose. Dosing: For Reversal of Conscious Sedation or General Anesthesia - *IV (Adults): 0.2 mg*. Additional doses may be given at 1-min intervals until desired results are obtained, up to a total dose of 1 mg. If re-sedation occurs, regimen may be repeated at 20-min intervals, not to exceed 3mg/hr. Contraindications: Hypersensitivity to Flumazenil or benzodiazepines, and Benzodiazepine dependence. Pregnancy class C Lactation safety: not established

Pseudomembranous Colitis [PC]

An inflammation of the colon which occurs in certain individuals following antibiotic treatment. A.k.a antibiotic- associated colitis or Clostridium difficile (C. diff.) colitis. Is almost always associated with an overgrowth of C. diff. Severe pseudomembranous colitis can be life-threatening. However, treatment is usually successful. Signs and Symptoms include: diarrhea that can be watery and sometimes bloody, abdominal cramps and pain, fever, pus or mucus in the stool, nausea, and dehydration.

Medications prescribed by dentists

Analgesics (eg. acetaminophen/paracetamol) Antimicrobials (eg. antibiotics, antifungals and antivirals) Anxiolytics/sedatives Corticosteroids: in oral surgery and the ER NSAID's (eg. Ibuprofen)

Angular Cheilitis / Cheilosis susceptible population

Anemic patients, patients with general poor health - inflammatory bowel disease such as ulcerative colitis and Crohn's disease, patients with overhang of upper lip resulting in deep furrows (marionette lines), patients with ill-fitting dentures, and patients who have lost VDO. Immunosuppression: diabetics, immune-suppressed, long -term antibiotic therapy, patients with long-term oral infections incl. oral thrush. Poor nutrition: coeliac disease, iron, and riboflavin deficiency Down's syndrome patients Patients using oral retinoid medication eg. Sotretinoin for acne and Acitretin for psoriasis.

Drugs allowed during pregnancy

Antibiotics: (all FDA category B) Penicillins Cephalosporins Clindamycin *Metroidazole (avoid in 1st trimester)* Azithromycin Antifungals: Fluconazole (C) Nystatin (B/C) Antivirals: Acyclovir (C) Famciclovir (B) Valacyclovir (B) Non-narcotic analgesics: Acetaminophen (B) Narcotic analgesics: All 4 drugs - use with caution, low dose, short duration, and consult with Ob-Gyn. Codeine (C/D3) Hydrocodone (C/D3) Oxycodone (C/D3) Propoxyphene (C) Local anesthetics: Lidocaine Prilocaine Use these with caution, consult OB/Gyn - Articaine, Bupivacaine, and Mepivacaine. Sedatives / Hypnotics: Nitrous oxide - Not rated. Use is controversial. Can use at 30% when local anesthetic is not sufficient. Sedation is achieved with a lower level of N2O in pregnancy. Consult Ob-Gyn; if OK in 2nd and 3rd trimester, use for less than 30 minutes. Sialagogues: avoid all. Other: CHX (B)

Drugs with anti-muscarinic action as an adverse effect

Antihistamines Orphenadrine (Norflex, Norgesic) Promethazine (Phenergan, Mepergan) Chlorpheniramine (Atrohist, Tuss, Donatussin) Benadryl Pseudoephedrine Antidepressants: typically tricyclics *Amitriptyline (Elavil, Etrafon, Limbitrol)*: #1 salivary drying agent! Imipramine (Tofranil) Desipramine (Norpramin)

EpiPen side effects and warnings

Anxiety, Apprehensiveness, Restlessness, Tremor, Weakness, Dizziness, Sweating, Palpitations, Pallor, Nausea and Vomiting, Headache, and Respiratory difficulties. Do not inject IV, into buttock, or into digits, hands, or feet. Each device is a single-use injection.

Dental management of drug addicts

Anxious patients: very often, drug abusers have dental anxiety. Prior to initiating anxiolytic medications, consult with the patient's PCP as to which is the most suitable choice. Consider nitrous oxide and oxygen. Analgesics: avoid narcotics. Use NSAID's whenever possible. If narcotics are required, consult with the patient's PCP. Anesthetics: *avoid epinephrine for 24 hours post the last dose of cocaine and methamphetamine as it can potentiate their effect* (inadvertent intravascular injection would potentiate the vasoconstriction of cocaine and produce a hypertensive crisis). Blood-borne diseases. Liver disease: avoid acetaminophen-based products. Suggest to the PCP to switch from methadone to a sub- lingual buprenorphine tablet [Subutex and Suboxone] (a semi-synthetic opioid used as a substitute for methadone) or sugar-free methadone [Methadose], or Methadone tablets if suitable. Meechan JG reported evidence that substance misusers have a low pain tolerance. They have increased incidence of dental anxiety and mental health issues. Perform complex dental procedures only when the patient is stable. Bleeding issues: this is esp. a concern in alcohol abusers which may have liver problems. Consult with the patient's PCP regarding lab tests. CVS: Hypertension is a potential problem with all drug users and alcohol abusers. Ensure that vitals are measured prior to surgical procedures. Emergency equipment to be checked. It is vital when treating a drug abuser, to be in communication with the patient's PCP, Pharmacist, Psychologist, RN, etc. Consider referring to a dietitian. If you recognize drug abuse, refer the patient to their PCP.

Acamprosate (Campral)

Approved by the FDA in 2004 and in Europe since 1989. Alcohol inhibits the activity of receptors called N-Methy- D-aspartate receptors (NMDARs), causing the brain to create more NMDARs. The absence of alcohol, or no inhibition of NMDARs receptors, causes them to be overly active which results in symptoms such as delirium tremens. *Reduces glutamate surges that excite NMDARs*. *Useful in treating the withdrawal symptoms in alcoholics who have achieved abstinence and want to maintain it*. Is a neuro-protectant: protects neurons from damage caused by alcohol withdrawal.

Naltrexone (Revia or Vivitrol)

Approved for use in the treatment of alcoholism in April of 2006. Recommended for patients aiming to cut down alcohol *Synthetic opioid antagonist* Reverses the effects of opioids and produces complete blockade of the euphoric effects of opioids (mechanism is not clear). Used in the management of: alcohol and opioid dependence. Reduces the craving for alcohol Can be administered in a *50 mg or IM injection* Side effects include nausea Can be effective for up to 30 days Drug-drug interactions are not very significant except for Naltrexone's interaction with opioid analgesics. Cannot be used in patients who have severe liver disease or need opioids.

Penicillin allergy in the dental practice

Approx. 10% of the general population is allergic to it. Cross allergy from one penicillin to another. Skin rash (a delayed reaction) is the most prevalent allergic manifestation. Life-threatening anaphylaxis can occur, but is very rare esp. with oral dosing. Symptoms seen during allergic reactions to vary according to the severity and they include: Bronchoconstriction (severe) Cardiovascular collapse (severe) Dermatitis (more common) Stomatitis (more common)

Recommended Maximum doses of LAs with a Vasoconstrictor:

Articaine - 7 carpules Prilocaine - 8 Bupivacaine - 10 Mepivacaine - 11 (7 if plain) Lidocaine - 13

Tobacco and Drug abuse

As a result of a lifestyle which is likely to involve smoking, drinking and a poor diet, drug abusers are likely to be at a higher risk of oral cancer. Degendardt L. and Hall W. reported a strong association between substance misuse and tobacco use. Olsen J. et al reported that the effect of combined exposure to alcohol and tobacco on cancer of the hypopharynx seemed to be multiplicative rather than additive. These results are similar to Rothman and Keller's results found for oral cancer. Franceschi et al reported the risk of OSCC to be 80 times greater in patients who smoke and drink heavily. Other oral complications include: delayed gingival healing delayed as a result of vasoconstriction by nicotine use, and increased risk of alveolar osteitis following extractions.

Dental management of previous drug addicts

As previously mentioned, previous drug addicts are at risk of relapse. Dentists should hence avoid prescribing sedatives, narcotics, and psychoactive drugs. Consult with the patient's PCP if a drug from the above categories is required.

hs or qhs

At bedtime (each night)

Anti-cholinergic drugs

Atropine (Lomotil): used for diarrhea. Scopolamine (Transderm-Scop, skin patch): used for Parkinson's, nausea and vomiting, motion sickness and recovery from anesthesia and surgery. Both: in large doses, block the cardiac slowing effect of the vagus nerve. Should be used with caution in patients with cardiovascular disease. Are contra-indicated in patients with glaucoma, prostate hypertrophy and intestinal obstruction. It also produce dilation (mydriasis) and paralysis of accommodation for distance vision and light (cycloplegia). Their side effects are: blurred vision, tachycardia, urinary retention, constipation, decreased salivation, sweating, and dry skin. Oxybutynin (Oxytrol): used for urinary dysfunction. Glycopyrrolate (Cuvposa, Glycate, Robinul, Robinul Forte): a quaternary analog of atropine used as a pre-op medication to reduce salivary and respiratory secretions, and in combination with neostigmine to reverse the effects of non-depolarizing skeletal muscle relaxants eg. pancuronium, at the end of surgery. It decreases acid secretion in the stomach and so may be used for treating stomach ulcers, in combination with other medications. Its use in treating asthma and COPD has been described. It has been used topically and orally to treat hyperhidrosis (excessive sweating for no apparent reason).

Alternatives to Penicillin

Azithromycin (Zithromax) Good choice in cases of: Penicillin allergy, unwillingness to follow a 10-day regimen, and failure of Penicillin treatment. Clindamycin (Cleocin) Use clindamycin in patients with: Penicillin/amoxicillin allergy and common oral-facial infections caused by aerobic G+ cocci and susceptible anaerobes. Misuse can cause pseudomembranous colitis.

Erythromycin (EES 200; EES 400; Eryc)

Bacteriostatic used in penicillin allergy and mild infections. High incidence of GI irritation, bacterial resistance, and drug interactions. Risk of causing torsade de pointes.

ac (ante cibum)

Before meals

Can drug addiction be cured?

Being a chronic disease, treatment for drug addiction is, in general, NOT a cure! Successful treatment modalities are usually tailored to each patient's needs and they incorporate a mental, occupational and social approach. Recovering addicts are likely to be at risk of relapse for their whole lives. Relapse rates are compared to those suffering from diabetes, HTN, and asthma - relapse is similar and common across these illnesses. Recovery from drug addiction can happen in certain cases esp. when pharmacotherapy is combined with behavioral therapy (CBT). Recovery requires complete abstinence. The "recovered" brain may acquire some of its former functions, but not completely.

EpiPen mechanism of action

Being a direct-acting sympathomimetic, it acts as an agonist at alpha and beta-adrenergic receptors. Results in vasoconstriction which counteracts the vasodilation and resulting hypotension associated with anaphylaxis. CVS effects: increased HR and contractility. Pulmonary effects: *Epi relieves bronchoconstriction due to its broncho-dilatory effects and its ability to reduce mucosal edema (reduced secretions) which is turn improves respiratory effort*. Epi down-regulates the release of inflammatory mediators from *mast cells* and *basophils* incl. *histamine* and *tryptase*: this improves respiratory function and reduce pruritus, urticaria, angioedema, and GI symptoms following exposure to an allergen.

Pregnancy and radiography

Benefits of radiographs should outweigh risks. *2nd trimester is considered the safest to use radiography: recent evidence shows no harm in all 3 trimesters*. Control panel settings must be at optimum level to obtain diagnostic quality radiographs. Only address areas of concern. Periapicals and bitewings are preferred due to small exposure. No Panoramic or CBCT unless indicated in rare cases: if a panoramic is needed, ensure that the long side of the lead apron covers the back as this is where the primary beam area is located. Limit the exposure: use the ALARA principles Ensure the following: the thyroid shield covers the thyroid gland. The shield must fit around the neck properly and the collar should not hang loosely. The fetus is covered by the lead apron. No primary radiation aimed at the fetus. Following delivery: usual precautions and ALARA.

Aphthous Ulcers Differential Diagnoses

Benign aphthae tend to be smaller, are more often self- limited vs more serious conditions. Major lesions may be associated with HIV infection: consider referral for HIV testing if lesions are large and slow to heal. Viral Treponemal (syphilis) Fungal (histoplasma) Autoimmune: Behcet's syndrome, Reiter's syndrome, IBS, Lupus, Pemphigus, Pemphigoid Hematologic: cyclic neutropenia Neoplastic: SCC

Inverse agonist

Binds to *benzodiazepine receptors*, stabilizes them and exerts the opposite effect to that of conventional agonist (reduces the activity). Example: carboline carboxylate ethyl ester (CEE), binds to benzodiazepine receptors and produces signs of increased anxiety and convulsions.

Flumazenil (Romazicon) mechanism of action

Binds to CNS benzodiazepine receptors and competitively blocks benzodiazepine activation of inhibitory GABAergic synapses (CNS effects of benzodiazepines).

The neurological control of salivary gland secretions

Both branches of the ANS, parasympathetic (cholinergic) and the sympathetic (adrenergic) innervate the salivary glands. Typically, stimulation on the parasympathetic side comes down and goes through a ganglion; then the post- ganglionic neuron releases endogenous neurotransmitters in the salivary gland. The flow rate (watery secretion) is more or less a function of the parasympathetic stimulation. Parasympathetic stimulation evokes a copious flow of saliva. Sympathetic stimulation produces either a small flow, which is rich in protein, or no flow at all. Sympathetic stimulation of salivary glands is referred to as a weak stimulation.

Lincosamide (clindamycin)

Broad spectrum *Bacteriostatic* (and bactericidal in high concentrations) against: aerobic, anaerobic, and beta-lactamase producing G+. Adverse Reactions: GI - diarrhea, C. difficile associated diarrhea Skin - rash, anaphylaxis, Stevens-Johnson syndrome Cardiovascular - hypotension Pregnancy Risk Factor: C

Azithromycin / Clarithromycin

Broader spectrum vs other Abx's. Bacteriostatic but bactericidal in higher doses. Resistance: most oral strep. and staph, oral anaerobes and B. fragilis. Drug interactions: Cytochrome P-450 (fewer drug/drug interactions). Pregnancy category B.

The 4 least potent anti-depressants in terms of anti-muscarinic action:

Bupropion (Wellbutrin or Zyban - relatively weak inhibitor of the neuronal reuptake of norepinephrine and dopamine). Nomifensine (norepinephrine-dopamine reuptake inhibitor). Trazodone (Oleptro, 5-HT2) antagonist and reuptake inhibitor). Viloxazine (Vivalan ICI, a selective norepinephrine reuptake inhibitor).

What is the effect of aging on the PD of a drug?

By affecting pharmacodynamic responses through changes/alterations in receptor binding or in post-receptor response sensitivity.

How can First Pass Effect (FPE) be bypassed?

By giving the drug via *sublingual or buccal routes*. The mucosa has a rich blood supply and it is relatively permeable. In the buccal route, the drug is placed between the teeth and the mucous membrane of the cheek (eg. Fentanyl).

Burning mouth syndrome lab testing

CBC; Fasting glucose; Ferritin; Folic acid and vitamin B12; and Thyroid profile.

Pathophysiology of Aphthous Ulcers

Mononuclear infiltrate with a fibrin coating are found in the lesion. Recurrent cases show alteration of local cell-mediated immunity and systemic T-and B-cell responses have been reported as altered.

Aphthous Ulcers Pharmacological Management

Can be divided into 5 categories: antibiotic, anti- inflammatory, immune modulatory, symptomatic and alternative. Rx: Tetracycline 250 mg capsule, take 1 capsule dissolved in 180 mL of water; rinse with this suspension four times daily for 4 to 5 days. Rx: Tetracycline 250 mg/5 mL syrup, take 5 mL "swish and spit" QID for 4-5 days Rx: Minocycline 100 mg tablet, take 1 tablet dissolved in 180 mL of water; rinse with this suspension BID for 4-5 days. Research Evidence: use is supported by RCT studies. Rx: (Kenalog in Orabase) Triamcinolone 0.1% in Orabase, apply to dried ulcer 2-4 times daily until healed. Rx: Dexamethasone elixir, 0.5 mg per 5 mL, rinse with 5 ml for 2 minutes QID and spit out. Discontinue when lesions become asymptomatic. Research Evidence: RCT studies show decreased pain. Symptomatic management: Viscous lidocaine, 2%, apply to ulcer PRN. Research Evidence: for brief local pain relief only. Alternative management: Zinc lozenges (OTC), 1 lozenge 4-6 times daily. Research Evidence - no scientific studies available. Vitamin C, 500 mg (OTC), 1 tablet QID. Vitamin B complex (OTC), 1 tablet QID L-Lysine, 500 mg (OTC), 1 tablet, 1-3 times daily Research Evidence - no scientific studies to support use.

Antifungals - On a CHROMagar Candida plate, the following are the observed color changes:

Candida albicans - green Candida tropicalis - blue Candida parapsilosis - white Candida glabrata - pink

Microbial factors of Candida

Candida has a wide pH tolerance (1.5 -10). Adhesion of candida is critical role for cell wall. Candida grows as a biofilm -this poses the following challenges: The biofilm can become too big to be "eaten" by phagocytes The biofilm can become resistant to immune attack by humoral and cellular factors The biofilm can become resistant to anti-fungal compounds.

With the exception of __________, almost all of the fungal infections come from the _______________.

Candida; Environment.

Odontogenic infections

Caused by 300-700 species. 50% or more of those species cannot be cultured. Infections are: mixed aerobic and anaerobic: 60%; aerobic only: 7%; and anaerobic only: 33%.

Supine Hypotension Syndrome (SHS)

Caused by a *decrease* in BP and Heart Rate (HR) when the patient is in the supine position. Reason: compression of the inferior vena cava by the gravid uterus. This compression results in a decrease in Cardiac Output of up to 14%. Clinical manifestations of SHS: transient initial increase in HR and BP followed by hypotension, bradycardia, pallor, sweating, nausea, dizziness, and syncopy. SHS resolves when the patient is turned on her side.

Clinical revelance of the steady state of a drug

Certain drugs require to be initially given as "loading dose" in order to reach SS and hence a therapeutic stage.

Dental bleeding and infections in organ transplant patients

Certain patients may be at risk of bleeding as a result of: organ dysfunction, medications eg. anticoagulants, and a decreased platelet count. End-stage liver disease patients do not produce sufficient amounts of clotting factors. Obtain lab results from the patient's physician prior to commencing any treatment. If infections such as purulent infections, abscessed teeth, etc. are present at the first appointment, discuss the issue with the patient's MD and prescribe the appropriate antibiotic.

Primary mechanisms of saliva stimulation

Chewing: pressure receptors in the periodontium are activated; their activation stimulates salivary centers located in the salivary nuclei; parasympathetic and sympathetic fibers are then stimulated, resulting in stimulation of salivary secretions. Saliva production due to stimulation takes place only on the working side. The amount of saliva produced is related to the amount being chewed. Tasting: taste signals transmitted to the brain activate efferent neural pathways which result in the stimulation of salivary secretions.

Types of antibiotic resistance transformations

Chromosome-mediated Plasmid-mediated conjugation Transposon transduction and transformation

Clinical relevance of drug clearance

Comparison of drug CL values with glomerular filtration rate (GFR), renal blood flow, or liver blood flow may give a clue to mechanisms of drug removal: Drugs eliminated entirely by glomerular filtration will have a max. CL of *120 mL/min*, ie. GFR. Drugs with tubular secretion have a CL of 120 mL/min. Drugs with tubular reabsorption, CL may be 120 mL/min *The max. drug CL from blood by metabolism is equal to the liver blood flow (1500 mL/min)*. Total body CL is the sum of all CL processes: CL (total) = CL (renal) + CL (liver) + CL (other).

Drug receptors

Components of an organism with which a chemical agent (drug) is presumed to interact. *Proteins* form the most important class of drug receptors. When activated, receptors regulate cellular biochemical processes, including protein phosphorylation, enzymatic activity, ion conductance, DNA transcription etc.

Glucagen Hypokit Emergency Kit

Consider Glucagon *if BGL is less than 40mg/dL* and the patient is unable to eat or drink safely due to confusion or disorientation, unconscious, or convulsing.

Dental management following organ transplant surgery

Consider the following before treating post-op: immunosuppressive medications are usually given at high doses in the early post-transplant period. Risk for rejecting the transplanted organ is high in the first 3 months post-op. The risk for serious complications is high. Consider extracting teeth that could be sources of infection incl. partially erupted 3rd molars and teeth with potential pericoronitis. Adrenal insufficiency: patients require increased steroid doses for oral surgery/extensive dental procedures to avoid adrenal insufficiency syndrome. Recommend alcohol-free antimicrobial and fluoride oral rinses and saliva substitutes. Treat only emergent cases/needs pre-transplant. Treat all infections aggressively Avoid treatment for 3 months min. following organ transplantation. 3-6 months post-op, the organ is likely stabilized: treat then with the proper precautions. Consider more frequent regular checkups. Treatment plans should include pre and post surgery phases.

Oraverse

Contains Phentolamine Mesylate (0.4mg/1.7ml). Produces a *short alpha-adrenergic block*. Results in vasodilatation when applied to vascular smooth muscle. Is indicated for patients ages 3 and above. *Max of 2 carpules for adults*. When injected after an intraoral injection of lidocaine 2% with 1:100K epi. (same location, infiltration or block), it causes the local blood vessels to expand, thereby increasing blood flow. It reverses soft tissue anesthesia. Also reverses functions associated with soft tissue anesthesia

Angular cheilitis lab testing

Culture of swabs taken from the corners of the mouth may reveal: C. albicans; Staph. aureus; and Herpes simplex. Skin biopsy is not usually necessary.

Example of Schedule V drugs:

Cough preparations containing *not more than 200 milligrams of codeine per 100 milliliters or per 100 grams* (Robitussin AC, Phenergan with Codeine), and Ezogabine.

Schedule II/IIN controlled substances

Dangerous drugs with high potential for abuse, which may lead to *severe psychological or physical dependence*. *Combination products with less than 15 mg of hydrocodone per dosage unit (Vicodin)*

Overuse of antibiotics

Dentistry accounts for 6.7-11.3% all abx prescription, with a concerning trend of increased use. The overuse of abx's in dental medicine is well-documented. Abx's s are used as "drugs of fear" by many clinicians. Prevention of claims of negligence is the basis for use by certain clinicians. In the hospital setting, Abx's are used: empirically, prophylactically, and with culture and sensitivity. ADA's Council on Scientific Affairs stated that: "Any perceived potential benefit of antibiotic prophylaxis must be weighed against the development, selection and transmission of microbial resistance". They are used commercially in agriculture.

Role of the pancreas

Digestion: secretion of digestive enzymes Metabolism: regulates carbohydrates, lipids, and proteins. Produces primary messengers (hormones): alpha cells produce glucagon, beta cells produce insulin, and gamma cells produce somatostatin.

Nitrous oxide in pregnancy - principles to follow

Do NOT use during the 1st trimester (time for organogenesis). Consider when anesthetics alone are "insufficient". Consider using in non-complicated pregnancies. Use following approval/clearance from Ob-Gyn. Use with caution: use for less than 30 minutes with at least 50% O2. Use only if your office is well-equipped to handle medical emergencies (ACLS cart). Use if you are trained on handling complications in pregnant patients (ACLS-trained) incl. hypoxia which is to be avoided at any costs.

The "learning process" of drug addiction

Drug addiction develops as result of complex interplay of psycho-social and neurobiological factors. The "learning process" eventuates when an individual consumes a psychoactive substance regularly, which he/she enjoys the effects of. In other words, *drug addiction is the use of a drug, despite its negative or dangerous effects*.

What happens to the brain when a person takes drugs?

Drugs of abuse affect the brain's "reward circuit" by flooding it with DA. The reward circuit controls the body's ability to feel pleasure and motivates a person to repeat pleasurable behaviors. An over-stimulated reward circuit results in the intense "high" which in turn leads to repeat drug consumption. Repeated drug use causes the brain to adjust to the excess DA by making less of it and/or reducing the ability of cells in the reward circuit to respond to it. This in turn reduces the "high" that the person feels compared to the high experienced upon initial consumption (this is tolerance). Tolerance is the reason for further consumption in an attempt at achieving the same DA high. This "high" is the reason a drug addict may lose interest in other pleasurable activities incl. food, socializing etc.

Reversal agents

Drugs that reverse the effects of other drugs such as benzodiazepines, opioids, anesthetics, toxic agents etc. They can be: Naloxone (Narcan) Flumazenil (Romazicon) Epinephrine (EpiPen) Glucagon (Glucagen) Phentolamine Mesylate (Oraverse)

Pharmacotherapy in drug addiction

Drugs used in treating alcoholism usually aim at creating adverse reaction to imbibing alcohol. Medications used in the treatment of alcohol abuse and drug addiction include: Disulfiram Naltrexone Acamprosate Methadone Buprenorphine Benzodiazepine

Half life and Steady State correlate

Drugs with short t½ reach a SS relatively quickly. Conversely, *drugs with long t½ take a long time to reach SS*. *The shorter the t½ the more dosing is required*. It takes approx. 4-5 t½ for a medication to reach SS. Drugs with a long t½ incl. Digoxin take longer to reach a SS than drugs with a shorter t½ and has a narrow TW.

Duration of antibiotic prescriptions

Due to the nature of oro-dental infections, we prescribe AB to reduce the spread of infection. The following is recommended: Beta-Lactams: 7-10 days Clindamycin: 5 days Metronidazole: 7 days (esp. if given with Pen.) Azithromycin: (Z-Pak): 1 course of 5 days In general, 5-10 days until all taken. However, new research challenges the need for a full course of Abx's (currently controversial).

Cardiovascular changes in pregnancy

During second trimester, Cardiac Output increases. This increase can be associated with a systolic heart murmur, heard in up to 90% of pregnant patients During second and third trimesters: "Supine Hypotension Syndrome" (SHS).

Which erythromycin is both enteric coated and long acting?

ERYC

Is there a link between Candida and Dental Caries? Does candida contribute to the formation of dental caries?

Early childhood caries patients have a high incidence of oral candida colonization. A prevalence of candida in dental plaque. Contributor or "accidental tourist"? Further epidemiological studies are needed. If we take a saliva sample from individuals with ECC and plate it on a medium (SAB/CHL agar), we will see growth of a mixed candida species. However, if we take a plaque sample from individuals with ECC and plate it on a medium (SAB/CHL agar), we will see growth of C. albicans ONLY.

Drug Enforcement Administration (DEA) tasks:

Enforces the "Controlled Substances Act" and combats drug smuggling and use within the U.S.

Candidiasis supportive measures

Ensure appropriate salivation as a low salivary flow predisposes patients at risk. Prescribe sugar-free gum and alcohol-free mouth rinses. Consider sialogogues: *pilocarpine* (cholinergic alkaloid, para-sympathomimetic, muscarinic agonist) or *cevimeline* (para-sympathomimetic and muscarinic agonist, M3 selective)

Managing Organ Transplant/Recipient Patients

Ensure that the medical and dental histories are up-to- date and accurate and perform a non-invasive initial examination *without periodontal probing*. Ensure to have a discussion with the patient's PCP to become familiar with your patient's: current health status; immune system; extent of organ dysfunction; need for pre -medication; transplant scheduling and timing of treatment; and tendency for excessive bleeding. Organ recipients are prescribed anti-rejection drugs incl. *Cyclosporine, Prednisone, and Azathioprine*. These drugs: suppress the formation of saliva and result in xerostomia, compromise the immune systems and increase susceptibility to infections, incl. thrush, herpes, and various aggressive bacteria.

Which of the following is NOT acceptable for the prevention of infective endocarditis?

Erythromycin

The rank order of arrhythmogenicity potential in Abx's:

Erythromycin > Clarithromycin > Azithromycin

DEA number

Essentially a precaution by the DEA to ensure that controlled substances are being prescribed by only qualified professionals. Assigned to licensed prescribers and dispensers by the DEA. It is an authorization number in order to prescribe narcotics (scheduled drugs). First letter - the registrant type (A, B, F, or M) Second letter - the first letter of the registrant's last name

Photodynamic therapy (PDT)

Established as a treatment in the oncology literature. Effective against drug resistant strains as no acquired resistance is documented. Emerging treatment for infectious diseases where infected cells are treated with photosensitizing agent which preferentially attaches to the microorganisms. Light exposure follows treatment with the agent; this exposure activates the photosensitizing agent to convert O2 to singlet oxygen (1O2): oxidation of macromolecules then causes cell death.

Primary Herpetic Gingivostomatitis

Etiology: A transmissible infection with herpes simplex virus type I. Less commonly HSV type II Clinical Description: Usually affects children younger than 5 years of age Multiple, painful extra and intra oral ulcers preceded by clear later yellowish vesicles Skin lesions may be present Gingivae often are red, enlarged, and painful Possible systemic signs include regional lymphadenitis, fever, and malaise Significance of the Condition: Self-limiting 10-14 days is usual healing period Reactivation of latent virus results in secondary infections Circulating antibodies provide only partial immunity

Cephalexin

First generation cephalosporin. Effective for oral Strep., Staph. and some oral anaerobes Resistant: Enteric flora and B. fragilis Increased risk of cross-reactivity in penicillin allergic patients in comparison with other cephalosporins.

On which embryonic period is the risk for teratogenicity the highest?

First trimester, because fetal organogenesis takes place during this trimester (first 12 weeks).

Hematologic changes in pregnancy:

Fluid retention results in a 40% increase in intravascular blood volume by the end of pregnancy. Blood cell mass remains unchanged: hemodilution. This results in a physiologic anemia with an average hematocrit of 30-35%; iron deficiency; and increased production of clotting factors (this puts pregnant patients at a greater risk of thromboembolism).

Pharmacokinetic Factors Determining Ideal Therapeutics

For "immediate" effect, an LD is needed to achieve a desired Cp of the drug. LD is determined by the volume of distribution (Vd). Maintaining a certain Cp requires a Maintenance Dose [MD] regimen. The MD rate is determined by CL (drug clearance). The t½ determines the fluctuations within a dosing interval.

Macrolides and Cardiology (QT intervals)

For Clarithromycin: causes prolongation of the QT interval (cardiac arrhythmia, a.k.a *torsade de pointes*) Azithromycin: The FDA has stated that "patients at risk for this azithromycin-induced arrhythmia include those who already have a prolonged QT interval, low blood levels of potassium or magnesium, and an abnormally slow heart rate, or who take drugs to treat arrhythmias. Elderly patients and patients with cardiac disease also may be more susceptible to the arrhythmogenic effects of the antibiotic". *QT interval may lead to fainting and sudden death due to ventricular fibrillation*.

Flumazenil (Romazicon) dosage and administration

For Reversal of Conscious Sedation or General Anesthesia - *IV (Adults): 0.2 mg*. Additional doses may be given at 1-min intervals until desired results are obtained, *up to a total dose of 1 mg*. If re-sedation occurs, regimen may be repeated at 20-min intervals, not to exceed 3mg/hr. IV (Children): 0.01 mg/kg (up to 0.2 mg); if the desired level of consciousness is not obtained after waiting an additional 45 sec, further injections of 0.01 mg/kg (up to 0.2 mg) can be administered and repeated at 60-sec intervals when necessary (up to a maximum of 4 additional times) to a maximum total dose of 0.05 mg/kg or 1mg, whichever is lower. The dose should be individualized based on the patient's response. For Suspected Benzodiazepine Overdose- IV (Adults): 0.2 mg. Additional 0.3 mg may be given 30 sec later. Further doses of 0.5 mg may be given at 1-min intervals, if necessary, to a total dose of 3 mg. Usual dose required is 1-3 mg. If re-sedation occurs, additional doses of 0.5 mg/min for 2 min may be given at 20-min intervals (given no more than 1 mg at a time, not to exceed 3mg/hour). IV (Children): Unlabeled—0.01 mg/kg (maximum dose 0.2 mg) with repeat doses every minute up to a cumulative dose of 1 mg. As an alternative to repeat doses, continuous infusions of 0.005-0.01 mg/kg/hour have been used.

Clinical uses for VD

For determining the *LD necessary* for a desired blood concentration of a drug, and for estimating a blood concentration in the treatment of overdose.

Treatment of the breast feeding patient

For most drugs, the infant is exposed to a much higher dose in utero than during lactation. Medications used during lactation have a safer therapeutic index (TI= LD50/ED50, a measure of drug safety: *the larger the TI, the safer the drug*). Always assume that any medication you prescribe will be excreted to a certain extent in breast milk. *Advise patients to separate the dose from breastfeeding by 4-6 hours and to express milk prior to taking the medication*.

Dental treatment principles in managing organ transplant patients

For patients undergoing hemodialysis, perform dental procedures on their days off hemodialysis. A number of patients are likely to be anxious and their pain tolerance may be low. Morning appointments are preferred. Local anesthetics, with or without vasoconstrictors, may be safely used with the following precautions: select the appropriate local anesthetic for the procedure; use the minimum amount; aspirate; slow injection - max. of one minute per carpule is recommended. Monitor patients during and after the injection for any reactions to local anesthesia. Following consultations with the medical team and the transplant coordinator, treat all active oral disease prior to transplantation: this is due to the fact that post-op immunosuppression reduces that patient's ability to fight oral and systemic infections. Extract non-restorable teeth, grossly carious teeth and those periodontally involved. Consider using temporary material such as RMGI to avoid extensive removal of tooth structure. Patients receiving Cyclosporine post-op will develop gingival hyperplasia; consider removing orthodontic bands (improves oral hygiene) and adjusting dental prostheses. Hyperplasia is minimized with good oral hygiene. Use *aggressive suctioning techniques* to control excessive bleeding for surgical and invasive procedures to prevent patients swallowing blood as this will likely increase the risk of hepatic coma in patients with advanced liver disease. Discuss vitamin K and fresh frozen plasma with the MD to control bleeding. Extensive treatment to be performed *3-6 months* following organ transplant surgery.

EpiPen dosage and administration

For patients ≥ 30 kg (66 lbs), use EpiPen *0.3 mg*. For patients 15-30 kg (33-66 lbs), use EpiPen Jr 0.15 mg. Inject EpiPen and EpiPen Jr IM or Sub-cutaneous into the anterolateral aspect of the thigh. Through clothing if necessary.

Cocaine and drug abuse

Friedlander AH et al reported bruxism and TMD to be common in cocaine users. TMD can result in flattening of occlusal surfaces and tenderness of the muscles of mastication. Driscoll reported a higher incidence of caries incidence in cocaine users, likely due to sugar in pure cocaine. Directly applied to the gingiva, cocaine can result in non -healing defects and localized bone loss and necrosis. Thrombocytopenia as a result of cocaine. Burday reported spontaneous gingival bleeding in cocaine users. Recall that cocaine acts as an anesthetic; care with anesthetic use.

Patients on methadone treatment

Gallagher et al suggested that caries is potentiated by the xerostomic effects of methadone. Others suggest that the high acid and sugar content of methadone increases the risk for tooth erosion. Advise patients NOT to brush teeth immediately following methadone dosing in order to reduce chemical erosion. Use of a straw for ingestion of methadone should be encouraged to minimize contact with enamel. Use of high fluoride prescription toothpaste such as PreviDent 5000.

Intra-lesional corticosteroids

Generally not recommended in general practice. Reserved for the management of severe oral mucosal lesions and disease. Agents in aqueous suspension, such as triamcinolone acetonide and methylprednisolone acetate, can be placed as superficial injections in small volume.

The urinary elimination of drugs is controlled by all of the following except one. Which one is the exception?

Glomerular filtration *Microsomal enzyme induction* Renal tubular reabsorption Active transport through renal tubular cells

Other factors regulating Glucose Homeostasis

Glucocorticoids (cortisol): stimulate gluconeogenesis and lipolysis, and increase breakdown of proteins. Epinephrine/norepinephrine: stimulates glycogenolysis and lipolysis. Growth hormone: stimulates glycogenolysis and lipolysis.

Risk Factors of Pathogenesis of Oro-Pharyngeal Candidiasis [OPC] are an interplay of:

Host Factors: a diet rich in carbohydrates is a risk factor in developing candidiasis. The wall of the fungus is very rich in carbohydrates.

Medications most commonly linked to overdose deaths

Hydrocodone (Vicodin) > Oxycodone (Percocet) > Alprazolam (Xanax) > Methadone (stays in the body longer than other painkillers) > Morphine > Diazepam (Valium) > Citalopram (Celexa) > Quetiapine (Seroquel) > Carisoprodol > Clonazepam (Klonopin).

Examples of Schedule II/IIN drugs:

Hydromorphone (Dilaudid) Methadone (Dolophine) Meperidine (Demerol) Oxycodone (OxyContin, Percocet) Fentanyl (Sublimaze, Duragesic) Morphine, Opium, Codeine, and Hydrocodone Amphetamine (Dexedrine, Adderall) Methamphetamine (Desoxyn) Methylphenidate (Ritalin)

Oraverse contra-indications, safety, and adverse effects

Hypersensitivity to phentolamine or to the inactive ingredients in the formulation. Well-tolerated in clinical trials No reported contraindications or drug interactions Pregnancy category C: has not been tested in pregnant women or nursing mothers. Adverse rxns: post-procedural pain, injection site pain, tachycardia, headache, and bradycardia.

Angular cheilitis treatment rationale

Identification of predisposing factors Elimination of primary and secondary infections Eradiation of inflammation Certain cases are self-limiting, no treatment is needed Depending on the specific cause, the following treatments may be useful: lip balm or thick emollient ointment, applied frequently; topical antiseptics; or topical or oral anti-staphylococcal antibiotic. Also: topical anti-fungal cream; oral anti-fungal medication; topical steroid ointment; nutritional supplements; and filler injections or implants to build up the oral commissures.

Prescribing to lactating patients

If drug elimination takes approx. 4 half-lives, when you prescribe drugs to a lactating mother, advise the following: pump breast milk prior to drug administration and store it in the fridge; amount pumped should last a few feeds; following drug administration, pump and discard all breast milk: most mothers are reluctant to do this!!!; and supplement feeding with formula

Severities of Penicillin allergy

If non-anaphylactic, symptoms include: Erythema - red skin Pruritis - itchy skin Raised skin or hives If anaphylactic: symptoms are immediate, 5-60 min. They include - swelling of mucosal membranes resulting in tightness of throat and chest, hives, hypotension and possible organ compromise. Instruct patients to: cease AB, take antihistamine (diphenhydramine), call prescriber, and ensure allergy is documented upon return to healthcare providers. If severe: cease Abx, call 911, take *antihistamine diphenhydramine* and document dose time and amount as this will help the EMT with giving Epi-Pen, and ensure allergy is documented upon return to healthcare providers.

Importance of glucose regulation

If too little - brain fuel deprivation, resulting in functional brain failure. If profound, hypoglycemia causes brain death that is not the result of fuel deprivation per se. If too much - cellular and systemic osmotic water loss blood vessel damage.

Vulnerability to drug addiction

Imaging studies show that differences in reward circuits underlie the variability in responsiveness to drugs of abuse, which in turn influence vulnerability. In those studies, the variability in the number of dopamine (DA) D2 receptors in non-drug abusing subjects affected their sensitivity to stimulant drugs (variability in the expression of DA D2 receptors). Individuals with *low* numbers of DA D2 receptors tended to describe the effects of the stimulant drug methylphenidate as *pleasant*. Individuals with high numbers of DA D2 receptors tended to describe it as unpleasant (which may limit its abuse). The numbers of DA D2 receptors predicted how much subjects liked the effects of methylphenidate. The association between drug "enjoyment" and DA D2 receptors can be described as "*causal*": a study showed that inserting a DA D2 receptor gene (via a viral vector) to increase DA D2 receptor expression in mice previously lab -trained to self administer alcohol resulted in marked reductions in alcohol intake. As the number of DA D2 receptors returned to baseline levels, alcohol intake decreased.

Treatment rationale for Candidiasis

Improve oral hygiene Re-establish normal balance of oral flora Arrest the infection Prevent spread of infection Remove pathogens from dentures: clean/disinfect removable oral prostheses with antifungal denture-soaking solutions Treatment period: 10 days following the disappearance of symptoms in order to minimize recurrence Laboratory testing done in certain cases - hospitalized patients.

The Most Common Medical Emergencies in the Dental Office

In a combined survey, 96.6% respondents answered positively to the following question: "In the past ten years, has a medical emergency occurred in your dental office?" Syncope > mild allergic rxn > angina pectoris > postural hypotension > seizures > asthma attack (bronchospasm) > hyperventilation > epinephrine rxn > hypoglycemia > cardiac arrest > anaphylactic rxn

Pharmacodynamics (PD)

In brief: "what a drug does to the body". Pertains to the relationship between drug concentration at the site of action and the resulting effect, including the time course and intensity of therapeutic and adverse effects.

Disulfiram (Antabuse)

In healthy patients, alcohol is broken down by alcohol dehydrogenase into acetaldehyde, then into acetic acid by acetaldehyde dehydrogenase. Disulfiram *blocks the oxidation of alcohol through its irreversible inactivation of aldehyde dehydrogenase*, which acts in the second step of ethanol utilization. This *causes an accumulation of acetaldehyde in the blood* producing highly unpleasant symptoms. The drug competitively binds and inhibits the peripheral benzodiazepine receptor. It is slowly excreted from the body and it is hence effective 5-7 days from the last dose. Shows effects as a dopamine breakdown inhibitor. Can be court mandated *Does not show tolerance* *No longer considered first-line treatment due to difficulties with adherence and toxicity*. It is being investigated as a treatment for cocaine addiction. Symptoms/Effects: nausea, vomiting, headaches, chest pain.

Pseudomembranous Colitis [PC] - special precautions with Clindamycin

Its use is restricted by its adverse effects, mainly severe diarrhea and PC, both of which are caused by the overgrowth of C. diff. Cases of colitis have been reported during, or even 2 or 3 weeks following treatment with Clindamycin. Inform the patient to discontinue taking Clindamycin as soon as marked diarrhea is experienced.

When do we culture bacteria?

In serious/life-threatening infections Persistent infections following repeated AB therapy Immunocompromised patients Cases with osteomyelitis Cases with suspected actinomycosis - rare subacute to chronic infection caused by Actinomyces species (anaerobic, G+, filamentous bacteria usually found in oral cavity, digestive and genital tracts). Usually suppurative and results in discharge of sulfur granules. Seen in face/neck (eg. lumpy jaw), thoracic, pelvic and GI areas).

Heroin and drug abuse

In their studies, Ma H. et al, and Picozzi et al, reported heroin users to show poor oral health as a result of a high rate of caries and periodontal diseases. Madinier reported that regardless of their oral hygiene, heroin injectors suffer from progressive dental caries. Lowenthal reported caries in heroin users to be darker and usually limited to buccal and labial surfaces. French researchers, Madinier I. et al, conducted a case-control study on the impact of illicit drugs on oral health and the use of drugs for toothache. They reported that: 52% of IV heroin users and 21% of other illicit drug abusers admitted using drugs as pain-killers.

Regulation of glucagon release

Increased blood glucose levels inhibit glucagon release. Amino acids *stimulate* glucagon release (high protein, low carbohydrate meal). Stress: epinephrine acts on beta adrenergic receptors on alpha cells, increasing glucagon release (increases availability of glucose for energy). Insulin *inhibits* glucagon secretion.

Who is likely to become a drug addict?

Individuals with a history of drug addiction who use pain medication. Individuals with an established diagnosis of depression, schizophrenia, anxiety and bipolar disorders, etc. Individuals with easy access to drugs including medical, dental, nursing and pharmacy personnel. Individuals with low self-esteem, or problems with personal and family relationships. Individuals with stressful lifestyles, those in economic hardship and those with emotional problems. Individuals living in cultures with a high social acceptance of drug use.

The site of opportunistic infection depends on which defects?

Low CD4+ helper T lymphocyte count (eg. AIDS) - muco-cutaneous, oropharyngeal involvement. Low neutrophil count (eg. radiotherapy patients, immunosuppressive therapy patients) - systemic involvement; the kidney is a sensitive target organ Wet skin, weakened stratum corneum, diaper rash, and bedsores.

Signs and symptoms of angular cheilitis

Inflammation of the corners of the mouth (oral commissures). Fissures at the corner of the oral cavity result from a mixed Candida albicans, staph. and strep. infection. Painful cracks/fissures Blisters/erosions/ooze/crusting Redness Bleeding

Bacteriostatic Abx's

Inhibit or delay bacterial growth and replication. Examples: tetracycline; clindamycin; timethoprim.

Progression of odontogenic infections

Initiation is by way of *aerobic organisms*: -Gaining entrance to soft tissue -Eventually resulting in cellulitis -Hypoxia and acidosis follow -Result: a favorable environment for anaerobic organisms is created. Anaerobic organisms follow: -Tissue destruction takes places -This leads to pus Eventually: the symbiotic activity between the different organisms leads to serious oral infections.

Schedule IV controlled substances

Low potential for abuse relative to Schedule III substances.

Drug addiction and blood borne diseases

Intravenous Drug Use or Injection Drug Use aka IDU, is common among drug addicts. It usually follows oral drug abuse. IDU is a major cause of blood-borne infections such as HIV and viral hepatitis.

Types of interactions when a drug binds to a receptor

Ionic Covalent Hydrophobic Van der Waals Hydrogen bonding

Consequences of long term drug use from drug abuse and addiction:

It alters brain biochemical systems and circuits, negatively impacting important functions such as: Behavior Decision-making Judgment Learning Memory Stress

Respiratory system changes in pregnancy

It increases O2 consumption by 15-20%, which results in a reduced O2 reserve. Hyperventilation is experienced in the 1st trimester; it persists throughout pregnancy. Consider pregnant patients to have a baseline respiratory alkalosis (elevated arterial pH, acid/base levels of CO2, and O2 in the blood are not balanced). The diaphragm is displaced by up to 4 cm (due to the gravid uterus): this results in a 15-20% decrease of Functional Residual Capacity (FRC). Capillary enlargement results in upper airway edema: this leads to an increased risk of supraglottic obstruction.

Drug addiction diagnosis

It is made when drug tolerance, dependence, and withdrawal are observed. It is related to the effects of the drug on specific areas of the brain that increase an individual's motivation to use the drug.

Our role in preventing prescription opioid abuse

It is reported that 5-23% of all prescription opioid doses dispensed are misused. Immediate Release [IR] opioid preparations such as hydrocodone [Vicodin-hydrocodone + acet.] and oxycodone [Oxycontin] are the most frequently abused opioids (*12% of IR opioids are prescribed by dentists* and 15% by physicians)

Drug withdrawal

It manifests as a group of unpleasant symptoms when a drug is ceased abruptly. For example, ceasing benzodiazepines abruptly such as Diazepam (Valium), may precipitate seizures.

Schedule V drugs

Low potential for abuse relative to Schedule IV substances. Consist primarily of preparations containing limited quantities of certain narcotics.

Bactericidal Abx's

Kill target organisms. Examples: penicillins; cephalosporins; aminoglycosides (gentamicin).

Immune system changes in pregnancy

Leukocytes increase by 5,000-10,000 cells. This is a secondary result to: an increased circulation of catecholamines; an increased circulation of cortisol; and demargination of leukocytes from the endothelial lining of the vasculature. Gestational diabetes occurs in 2-5% of pregnant patients, usually diagnosed after 24 weeks of gestation - this has dental implications.

Chapped / cracked lips treatment

Lip balm and SPF sunscreen to minimize further drying effects; for PABA-allergic patients, prescribe non-PABA sunscreens. Also Vaseline, Lanolin and Cocoa butter. The following can be used multiple times during the day: Oral Balance Moisturizing Gel (OTC) (contains glycerin, water, sorbitol, xylitol, carbomer, hydroxyethyl cellulose and sodium hydroxide).

Which factors can increase the t½ of a drug, which in turn *increase* the effect of the drug?

Liver disease Decreased renal blood flow Drug-drug interactions incl. addition of a second drug that displaces the first from plasma proteins. Decreased metabolism: as a result of liver disease or in the presence of other drugs

The most important enzyme systems for the biotransformation of drug molecules are found where?

Liver. Explanation: Hepatic metabolism of drugs occurs in Phase I reactions catalyzed by a microsomal mixed-function oxidase system (aka the P-450 system) and in Phase II reactions known as conjugation reactions.

Indication for systemic antibiotics

Local: Minor vestibular abscess Chronic localized abscess Periodontal treatment (advanced cases): short-term, local or oral RCT: possibly in flare-ups? Mild pericoronitis Systemic: Medical history dictates Abx use Immuno-suppression Fever > 100 degrees F Cellulitis, abscessed teeth, spreading infection Malaise Lymphadenopathy Trismus

Supportive care of common oral lesions in the immuno-compromised

Management of common oral lesions should focus on: local control of the disease process, adequate patient hydration and nutrition, and good oral hygiene. Pain control: suggest *2% viscous lidocaine hydrochloride* for adults and topical anesthetic applied with a cotton swab for children. Prevent secondary infection. Referral of severe and recurring cases to PCP/oral medicine. Oral Hygiene: bacterial plaque on mucosal lesions results in secondary infection, thus oral hygiene should be meticulous. Encourage the use of a soft toothbrush soaked in warm water for 1-2 minutes (softens the bristles). Tartar control toothpastes that contain *calcium pyrophosphate* should be avoided because of their caustic nature and reported association with circum-oral dermatitis. SRP under local anesthesia to be performed.

Receptor interaction

Many drugs that act on physiological receptors mimic the effects of the endogenous signaling compounds. Hence the following nomenclature: Agonist Antagonist Partial agonist Inverse agonist

Oraverse dosing

Max doses: for adults and adolescents 12 years of age and older - 2 cartridges. For patients 6-11 years of age and over 66 lbs - 1 cartridge. For children 6-11 years of age weighing 33-66 lbs - 1/2 cartridge.

Macrolides Abx's

Mechanism of Action: bind reversibly to 50s ribosomal subunit. Inhibits bacterial protein synthesis. *Result*- slower cell growth. Bacteriostatic, but bactericidal in high concentration. Examples: Azithromycin, Clarithromycin and Erythromycin, all of which can cause prolongation of the QT interval!

Fresh Frozen Plasma [FFP]

Mechanism: replaces coagulation factors lowered by warfarin. It contains all coagulant factors in diluted inactive form, incl. factors II, VII, IX, and X. Kinetics: onset is approx. 1-4 hours depending on dose and magnitude of anticoagulation. Duration of effect: ≤ 6 hours. Rebound of anticoagulant effect after reversal: 4-6 hours. Reversal of warfarin effect is partial. Does not affect INR values after 12 hours when combined with Vitamin K vs Vitamin K alone. *Example of use in dental medicine*: patients with FXIII deficiency, vWF, or other bleeding disorders can be managed successfully for routine dental care and surgical treatment following infusion of FFP.

Nitroimidazole side effects and warnings

Metallic taste, urine discoloration (dark brown), dry mouth and dysuria (painful or difficult urination). Also convulsive seizures and peripheral neuropathy. Topical: skin irritation, pruritis, and burning. Do not use in pregnancy (category B but do not use in 1st trimester) Not to Drink Alcohol: Disulfiram/Antabuse reaction. Reaction between EtOH and MTZ. Severe nausea, vomiting and abdominal cramping. No alcohol following 2-3 of treatment. No alcohol-based mouthwash. No cough medicine with EtOH.

Types of Aphthous Ulcers

Minor lesions: are < 0.5 cm, usually located on the buccal or labial mucosa, soft palate and floor of the mouth. Major lesions: (aka Sutton's disease) are > 0.5 cm, involve deeper ulceration, likely to scar with healing. Herpetiform: pinpoint, vesicular in morphology.

Ligands

Molecules (eg. neurotransmitters, drugs, hormones etc.) that bind to a receptor.

Oral cavity organisms

More than 700 species, they include aerobic and anaerobic organisms (anaerobic more common), spirochetes, candida, and viruses.

Antibiotics in pregnancy

Most antibiotics commonly used for oral infections are classified as pregnancy category B incl. *Penicillin, Amoxicillin, Cephalexin and Clindamycin*. Do not use Tetracycline and its derivatives as they are classified as pregnancy category D and they are contraindicated throughout pregnancy. Due to increased maternal blood volume, *conventional doses of antibiotics may prove ineffective in pregnancy*. Monitor infections closely. Persistent infections with a poor response to antibiotics should be referred to an OMFS.

Most Abx's and their side effects

Most disrupt normal GI and vaginal flora, resulting in these 4 major side effects: nausea and vomiting, diarrhea, and yeast infection incl. oral candidiasis. Therefore: take Abx's with food if possible, eat anti-diarrheal foods incl. cheese and peanut butter, and eat yogurt for probiotics.

Brain circuits involved in drug abuse and addiction

Motivation/Drive Circuit in Addiction Learning/Memory Circuit in Addiction Control Circuit in Addiction: the *prefrontal cortex* is involved in decision making and in inhibitory control. Its disruption leads to inadequate decisions that favor immediate rewards over delayed but more favorable responses.

Continuous/Prolonged use of topical steroids for > 2 weeks is likely to cause:

Mucosal atrophy, secondary candidiasis, and potential systemic absorption. Topical steroid therapy for conditions such as lichen planus should be tapered to alternate day therapy or treatment given less often once the condition has improved: the decision is case-based (tendency to recur).

The effect of insulin on tissues

Muscle: uptake of glucose and immediate use during exercise or storage as glycogen (exercising muscles can take up glucose without insulin). Liver: uptake of glucose and storage as glycogen - inhibits glycogen phosphorylase, activates glycogen synthase, inhibits glucose synthesis, and promotes excess glucose conversion to fatty acids. Adipose Tissue: promotes glucose uptake and conversion to glycerol for fat production.

Nitrous oxide in pregnancy

N2O affects vitamin B12 metabolism, which in turn inactivates methionine synthase, an enzyme which is necessary for the production of DNA. Use in pregnancy is controversial as long-term exposure to N2O may be associated with spontaneous abortion and birth defects. In an ADA survey, wives of dentists who were exposed to N2O were found to be at higher risk for spontaneous abortions relatively to the control group (unexposed dentists' wives).

Drugs contra-indicated in pregnancy

NSAID's: may cause premature closure of the ductus arteriosus and prolong labor and delivery.

Naloxone (Narcan) mechanism of action

Naloxone competitively blocks CNS opioid receptors. It has an affinity for delta, kappa, and mu receptors but higher affinity for *mu* receptors. In a patient that has overdosed on a narcotic analgesic or narcotic derivative such as Fentanyl, Morphine, and Heroin, Naloxone will "compete" for the opioid receptor site that the overdose narcotic has bound to, displacing it off that receptor site, and will almost instantly reverse the symptoms of the overdose.

Penicillin groups

Natural Penicillin: Pen. V and Pen. G 1st Generation: Cloxacillin, Dicloxacillin 2nd Generation: Ampicillin, Amoxicillin 3rd Generation: Ticarcillin 4thGeneration: Piperacillin

Adverse effects with Penicillin

Nausea Superinfections: candida Antibiotic-associated colitis Blood dyscrasias: anemia and granulocytopenia Interstitial nephritis

Physical signs of drug use

Needle marks Dilated pupils Red eyes High levels of energy, excitability Exuberant speech Weight loss Irritability HTN is possible (sympathetic activity) Personality changes Mood changes eg. depression, edginess, paranoia, suspiciousness. Memory problems Sleep problems Fatigue

Schedule I controlled substances

No currently accepted medical use in the US. Lack of accepted safety for use under medical supervision and a high potential for abuse. Examples: heroin, lysergic acid diethylamide (LSD), marijuana (cannabis), methaqualone, and 3,4-methylenedioxymethamphetamine ("Ecstasy").

Dental management of patients undergoing chemotherapy

No routine dental care in acute phase. OHI and aggressive preventive fluoride prescription. Soft, non-acidic diet and maintain hydration. Standard oral care: antimicrobial prophylaxis. Strong analgesics/narcotics for pain from mucositis. Emergency dental care: conservative (Abx and cleaning).

Are drug PD the same in all individuals?

No, pharmacodynamics can be affected by physiologic changes which results from medical disorders including: Insulin resistant diabetes mellitus Genetic mutations Malnutrition Myasthenia gravis Parkinson disease Thyrotoxicosis

Medical consults for pregnant patients

Not required: For routine care such as an oral exam, cleaning, and simple restorations. Recommended: When the patient is being treated for a pre-existing medical condition other than pregnancy. For clarification of medical or medication history; medical complications that may be the result of pregnancy; special treatment recommendations incl. pain management medications; N2O administration, etc.

Drug dependence

Occurs *when tolerance and withdrawal develop*. However, an *individual may develop physical dependence without addiction*, and vice-versa. For example, certain HTN medications (used chronically) may cause physical dependence but not addiction, and cocaine use can result in addiction without leading to physical dependence.

Comorbidities and preparation / training in caring for organ transplant patients

Often, organ transplant patients have complex medical histories. Chronic comorbid conditions are common in patients with end-stage organ failure eg. patients with end- stage kidney disease are likely to also have diabetes, pulmonary, and CVS disease. Organ transplant patients are usually weak and tired: it is recommended that you become ACLS-trained and that your staff are prepared to handle medical emergencies as these patients are more likely to have a medical emergency during their visit. Ensure all medical equipment is functioning well and your emergency protocols are clearly documented.

Methadone

Opioid analgesic Uses: moderate to severe pain relief, detoxification treatment of opioid dependence, and maintenance therapy in narcotic addiction. *Longer duration of action vs morphine* Suppresses opiate withdrawal symptoms. Remains efficacious for an extended period of time with repeated administration. Used for decades for the treatment of heroin and narcotic addiction. Safe and effective if taken as prescribed. Available in tablet, liquid, and wafer forms. Usually taken once daily. Used "recreationally" for its sedative and analgesic effects.

Candidiasis - etiology and predisposing factors

Opportunistic infection with C. albicans Infection proliferates with the use of broad-spectrum antibiotics, corticosteroids, xerostomic medications, cytotoxic agents, etc. Predisposing conditions include: Asthma (due to the regular use of steroid puffers) HIV/AIDS Immuno-suppression Poor oral hygiene Prolonged use of prosthetic appliances Uncontrolled diabetes Xerostomia

Most fungal organisms are not overt pathogens: they are ________________. Some impairment needs to be present for them to cause disease. Antibiotic and steroid treatment can disturb the balance leading to __________________. Historically, ____________ was the main culprit in fungal infections. However, with medical interventions and changes in medicine, other species are now causing most of the fungal infections.

Opportunistic; Fungal infections; C. albicans.

Treatment of Oro-pharyngeal Candidiasis with the Polyenes and Azoles classes:

Oral Fluconazole: tablet, systemic administration Miconazole (Oravig): adhesive 50mg tablet - FDA approved in 2010; 85mg oral gel - (outside the U.S) Clotrimazole troche: small 10mg lozenge Nystatin suspension: polyene, loses activity soon after preparation.

Which route of administration of a drug is most known for its significant *hepatic* "first pass" metabolism?

Oral. -Advantages of oral administration: Easy, most acceptable and convenient (tablets/capsules contain an exact dose). -Disadvantages of oral administration: A drug is absorbed through the small intestine prior to being transported to its site of action. Blood from the intestinal tract passes first to the liver: some drugs are metabolized in the liver - this is referred to as "first-pass effect" and others may be stored there to be released slowly. Therefore, *oral administration is usually unsuitable in emergencies*.

The increased resistance to traditional antifungals

Outgrowth of non-albicans candida species.

Misuse of antibiotics

Overuse of broad spectrum Abx's Inadequate pathogen coverage Poor compliance Use of Abx's for treating viral infections!!! Retaining unused Abx's for later use (self-prescribing) Inadequate: frequency of Rx, duration of Rx, and dosage.

The ideal antibiotic

Pathogen-specific Rapid onset of action Narrow spectrum: does not disturb non-pathogenic bacteria No or minimal side-effects Inexpensive

Components of a prescription

Patient information incl. name, address and DOB Superscription (meaning recipe inscription) Subscription (directions to pharmacist) Signa (*directions* to patient) Date Signature lines, signature, degree Brand name indication Prescriber information such as: contact details, prescriber's DEA #, refills, and warnings/label.

Candidates for local anesthetic reversal

Patient preference - loss of function can result in difficulty with speech, smiling, and drinking. Children - reduces self-inflicted injuries and reduces uncontrolled drooling.

Beta Lactams - Penicillins

Penicillin VK: tablets (250mg, 500mg) oral suspension (125mg, 250mg per 5ml) Amoxicillin: capsules (250mg, 500mg) oral suspension (50mg, 125mg, 200mg, 250mg, 400mg per 5ml) chewable tablets (125mg, 200mg, 250mg, 400mg) tablets (500mg, 875mg)

Beta Lactams

Penicillins and Cephalosporins. Mode of Action: inhibit bacterial cell wall synthesis via acetylation of transpeptidase enzyme, resulting in defective cell wall synthesis which ultimately leads to defective bacterial cell wall. *Bactericidal*.

Drug affinity

Pertains to the "tightness" that a drug binds to a receptor with.

Intrinsic activity of a drug

Pertains to the ability of a drug, once bound to a receptor, to generate an effect that results in activating a stimulus and producing a change in cellular activity.

Drug diversion

Pertains to the illegal use of prescribed substances for recreational purposes, not as the prescriber intended. Has the potential to impact the frequency of misuse and modes of administration. *Opioids* such as codeine, morphine, hydrocodone and oxycodone are the most diverted drugs.

First Pass Effect [FPE] AKA First Pass Metabolism and Pre-Systemic Metabolism

Pertains to the process where a drug administered orally is absorbed from the gut then transported to the liver *via the portal vein* where it is metabolized. Can occur in the gut and the liver, for example: for benzylpenicillin and insulin, FPE occurs in the gut; for propranolol, lignocaine and glyceraltrinitrate (GTN for angina pain), FPE occurs in the liver. Oral administration is the most common and easiest drug route.

Therapeutic window (TW)

Pertains to the range between the lowest therapeutic concentration and the beginning of toxicity. > the Minimal Effective Concentration [MEC] but < the Minimal Toxic Concentration [MTC]

Which term refers to a drug that binds to physiological receptors to result in a specific cellular effect producing a predictable pharmacological response?

Pharmacologic agonist. Explanation: Drugs that bind to physiologic receptors and mimic the regulatory effects of endogenous signaling compounds will produce a pharmacologic effect as a result of binding to the receptor. A drug that elicits a full response through this process is referred to as a pharmacologic agonist. -A partial agonist is a drug which acts on the physiologic receptor but elicits an effect which is only partly as effective as an agonist drug. -An antagonist is a drug which binds to the physiologic receptor but does not trigger an effect. When antagonist is present, the agonist drug cannot reach the receptor site to produce an effect.

Medication considerations in transplant patients

Polypharmacy is common in organ transplant patients: be familiar with the side effects of these medications which usually include orthostatic hypotension, hyperglycemia, xerostomia, and gingival hyperplasia. Medications prescribed in dental medicine are metabolized by the liver or the kidney and in organ transplant patients these medications are not removed from the circulation as quickly relatively to healthy patients. Prescribing medication is best coordinated with the patient's MD. Patients on steroid therapy are at risk for acute adrenal crisis. Discuss the need for dose adjustment with the patient's MD prior to invasive dental procedures.

Schedule III/IIIN controlled substances

Potential for abuse is less than substances in Schedules I or II. Abuse may lead to *moderate or low physical dependence* or *high psychological dependence*.

Medications in pregnancy

Pregnancy Category A: adequate research has been done with the conclusion that drugs in this category are *not likely to cause any harm to the fetus* in the first trimester as well as later in pregnancy. Pregnancy Category B: studies carried out on animals have shown *no adverse effects on the fetus*; however, there is a lack of controlled studies on human pregnancy. Pregnancy Category C: animal studies have shown *evidence of harmful effects on the fetus*; however, no controlled study has been done on a human pregnancy. The medicines may be prescribed in cases where the potential benefits outweigh the possible adverse effects. Pregnancy Category D: studies done on human pregnancy have shown *positive risks to the fetus*. However, doctors might prescribe them in certain cases where the potential benefits outweigh the risks. Pregnancy Category X: both human and animal studies have shown *positive risks to the fetus, with the adverse effects extending to serious birth defects, miscarriage and fetal death*. The possible risks of using these medicines outweigh any potential benefits. Examples: triazolam, warfarin, methotrexate, androgens, estrogens, and isotretinoin.

Pregnancy and Heparin

Pregnant patients with a diagnosis of thrombophilia (increased tendency to form clots) are likely to be receiving daily heparin injections or low molecular weight heparin (LMWH) such as Enoxaparin. *Heparin and LMWH increase bleeding risk during surgical and dental procedures*. Consult with the Ob-Gyn as needed.

Preventing overuse of antibiotics as clinicians

Prescribe Abx's appropriately and stay scientifically up-to-date and "relevant" with your Abx prescribing rationale. Use EBM and the latest evidence-based guidelines.

Prescribing principles for pregnant patients

Prescribe category A drugs whenever possible. Give the lowest effective dose. Treat for the shortest duration possible (to reduce unnecessary risks).

PMP Maine Public Law 488

Prescribers are required to check the PMP for any new benzo or opioid prescription and *recheck every 90 days thereafter*. A patient receiving treatment for *chronic pain is limited to a 30 day supply of an opioid medication*. A patient receiving treatment for *acute pain is limited to a 7 day supply of an opioid medication*. Opioids must be electronically prescribed. Existing prescriptions for opioid medication will be limited to *100 MME (Morphine Mg Equivalent) per day*. Continuing education - By December 31, 2017, an individual licensed under this chapter must successfully complete 3 hours of continuing education every 2 years on the prescription of opioid medication as a condition of prescribing opioid medication. The board shall adopt rules to implement this subsection.

Doctor shopping

Refers to a patient obtaining controlled substances from multiple healthcare practitioners without the prescribers' knowledge of the other Rx's. In the US, most states have adopted the Uniform Narcotic Drug Act of 1932 or the Uniform Controlled Substances Act of 1970, both of which prohibit it by any means.

Facts of illicit drug use and prescribed substances

Prescription drug abuse in Western countries is considered an *epidemic*. That CDC has stated that "... prescription drugs are now involved in more overdose deaths than heroin and cocaine combined" An estimated 21.8 million Americans 12 years of age or older were illicit drug users in 2010 [NSDUH study]. Prescribed medications such as opioids are the second most commonly misused drugs after marijuana among persons aged 16-25, followed by cocaine, prescription tranquilizers, ecstasy, and prescription stimulants. In the US, large metropolitan centers such as New York City, Los Angeles, San Francisco, and Chicago are a hub for the misuse of prescription drugs.

Maine Laws relating to Naloxone

Prescription, Possession, and Administration (22 M.R.S.A. § 2353(2)): A health care professional may directly or by standing order prescribe Naloxone to a opioid user or the user's family member, friend, etc. An individual who has been prescribed Naloxone can provide the Naloxone to a family member to administer (no mention of friends - only "immediate family member"). A family member or friend who has been prescribed Naloxone can administer the drug if that person believes in good faith that an individual is experiencing a opioid-related drug overdose. Administration by Law Enforcement Officers and Firefighters (22 M.R.S.A. § 2353(3)): Law enforcement officials and firefighters may administer intra-nasal Naloxone if they have received the appropriate training. Community-Based Drug Overdose Prevention Programs (22 M.R.S.A. § 2353(4)): Under standing orders from a health care professional, a public health agency may store and dispense Naloxone to anyone who has successfully completed the training program. Pending Legislation (LD 1547): This bill, if it becomes law, will allow for the dispensing of Naloxone by pharmacists without a physician, PA or nurse practitioner's prescription. NOTE: This bill is not yet law, since it has not been voted on in the Legislature or signed by the Governor.

Effects of glucagon

Prevents hypoglycemia: powerful system that degrades glycogen and increases glucose synthesis from amino acids. Increases with exercise independent of blood glucose. Exerts effects through cAMP second messenger system.

Candidiasis signs and symptoms

Pseudomembranous form: soft, white, slightly elevated plaques that wipe away. Erythematous form: generalized erythematous sensitive areas. Hyperplastic form: confluent (flowing together or merging) white areas that cannot be wiped away. Angular Cheilitis: white (open?) lesion on the corner of the mouth. Susceptible populations: the very young, the very old, immuno-compromised, patients on long-term antibiotics, and immuno-suppressants.

Antifungals in the Pipelines

Pseudomycin B Sordarin Xylitol: replacement of dietary sugar with this sugar substitute leads to reduced virulence of c. albicans in an animal model of oro-pharyngeal candidiasis, and clearance of severe infections.

Example of drug receptors:

Receptors for hormones, growth factors and neurotransmitters. Enzymes of regulatory pathways (eg. acetylcholinesterase). Proteins involved in transport processes (eg. Na+, K+, -ATPase). Structural proteins (eg. tubulin).

Drug abuse and dietary issues

Recreational drugs have both appetite suppressing and enhancing effects: result is starvation and binge eating. Excessive consumption of sugary carbonated drinks coupled with induced bruxism results in tooth surface loss. Anorexia and/or malnutrition are common in chronic drug users and may impair soft and hard tissue healing.

Treatment of medication induced hypo-salivation

Reduce total number of drugs: MD consult Eliminate or substitute worst offenders Reduce dose Modify dosing schedule Saliva substitutes, gum and hydration If unable to alter, provide symptomatic and preventive treatment (aggressive fluoride) Secretagogues, Salagen/Evoxac, are typically not advised (due to higher doses and hence side effects)

Antimicrobial Stewardship

Refers to coordinated interventions designed to improve and measure the appropriate use of antimicrobials by promoting the selection of the optimal antimicrobial drug regimen, dose, duration of therapy, and route of administration.

Clinical PK

Refers to the application of pharmacokinetic principles - the safe and effective therapeutic management of drugs to enhance the efficacy and decrease the toxicity of drug therapy. The factors that determine variability in the plasma concentration (Cp) and its time-course, within the therapeutic window.

Effective Dose (ED50)

Refers to the dose at which 50% of people will respond. The drug with a lower effective dose considered more *potent*. For example: Drug #1 in a dose of 10 mg produces the same magnitude of response as Drug #2 in a dose of 50 mg. Thus: Drug #1 is 5 times as potent as Drug #2.

Lethal Dose (LD50)

Refers to the dose at which, in theory, 50% of people will die. They are always determined in mice, not people.

Half life of a drug

Refers to the time required for the body to eliminate half of the dose of a drug. Also refers to the time required for half of a drug to be redistributed.

Primary Herpetic Gingivostomatitis management rationale

Relieve symptoms, prevent secondary infection, and support general health. Systemic Acyclovir is effective in immuno-compromised patients. Treatment must be provided early to be effective. *Topical steroids are to be avoided* as they allow the spread of the viral infection on mucous membranes, particularly ocular membranes. Patients should avoid touching the herpetic lesions and then touching their eyes or other body areas in order to prevent self-inoculation.

A network of circuits involved with drug addiction:

Reward - saliency Motivation/drive - internal state Memory - learned associations Control - conflict resolution These work together and result in "change". In drug addiction, these overcome the inhibitory control exerted by the *prefrontal cortex*. This results in favoring a positive-feedback loop initiated by drug consumption and perpetuated by the enhanced activation of the motivation/drive and memory circuits.

Alcohol and drug abuse

Robb ND et al reported a higher rate of non-carious tooth surface loss in alcohol abusers likely due to chemical erosion. Trauma: facial injuries and mandibular fractures are common as a result of alcohol-related assaults.

Burning mouth syndrome topical anesthetics and coating agents

Rx: *Diphenhydramine (Benadryl)* elixir 12.5mg/5mL (note: elixir is Rx, and syrup [Benylin] is OTC) 4oz, mixed with *Kaopectate* (OTC) 4oz, to make a 50% mixture by volume. Disp: 8oz Sig: rinse with 1 tsp q2h, and spit out. *Maalox* (AL/Mg antacid), OTC can be used in place of Kaopectate.

Pharmacological management of primary herpetic gingivostomatitis

Rx: Lidocaine (Viscous) 2.0% or 1%, dispense 1oz bottle, rinse with 1 tsp for 2 minutes before each meal, and spit out. Rx: Acyclovir (Zovirax) capsules 200mg, dispense 50 (or 60) capsules, take 1 capsule 5 times a day for 10 days (or 2 capsules TID for 10 days). Rx: Valacyclovir (Valtrex) caplets 500mg, dispense 20 caplets, take 2 caplets BID for 5 days. For secondary bacterial infection in susceptible patients: Rx: Penicillin V tablets 500mg, dispense 40 tablets, take 1 tablet QID Rx: Erythromycin tablets 250mg (in penicillin allergy) , dispense 40 tablets, take 1 tablet QID

Cefaclor

Second generation cephalosporin. Effective for oral Strep., Staph., most oral anaerobes, and H. influenza. Resistant: Enteric flora, B. fragilis

Becoming a drug addict

Shortly after being consumed, drugs such as cocaine, give the individual a "high", described as: increased sense of energy and alertness, an extremely elevated mood, and a feeling of supremacy. Also feelings of irritability, paranoia and anxiety.

Drug tolerance, withdrawal, and dependence in dentistry

We use narcotics in dental medicine. Narcotics show tolerance to the analgesic effect. Cross-tolerance can develop between different narcotics eg. codeine and morphine. Narcotics show dependence.

Burning mouth syndrome signs and symptoms

Signs - none clinically. Symptoms - Certain patients compare the symptoms of BMS to burning their mouth with hot tea/coffee. The burning sensation may affect all soft tissue incl. the tongue, the gingivae, the palate, the buccal areas, the posterior areas of the oral cavity and the throat. A bitter or metallic taste. BMS tends to persist for many years. Symptoms usually progressively worsen throughout the day. BMS may cause irritability and anxiety.

The majority of drugs penetrate bio-membranes by ____________ through membrane phospholipids.

Simple diffusion. Explanation: lipid-soluble substances move across the lipoprotein membrane by simple diffusion. The majority of drugs penetrate bio-membranes by this process through membrane phospholipids. The amount of drug dissolving in the membraneat any time is directly proportional to the concentration gradient and its degree of lipid solubility (Note: Only non-ionized drugs are soluble in lipid).

Bactericidal vs Bacteriostatic Abx's

Some Abx's can be both bacteriostatic and bactericidal, such as *aminoglycosides, metronidazole and fluoroquinolones*. They exert concentration-dependent "cidal" characteristics; their rate of killing increases as the drug concentration increases. Clinical implications: The onset of action for bacteriostatic ABs is slower vs that of bactericidal ABs. *Bacteriostatic ABs* command a healthy immune system for effectively eliminating bacteria by the patient, therefore they are *NOT advisable in immuno-suppressed patients*.

Laws regarding medical emergencies in the dental office

Some states may require that dentists have emergency drugs and equipment. In 2010 Illinois became the first state to enact a law requiring dental offices that administer deep sedation to not only have an automated external defibrillator (AED) available, but also a written medical emergency plan. This new law does not apply to practices that use local anesthetics for routine dental care. Many states require dentists, whether they administer general anesthesia or deep sedation, to have an AED available.

Prescription Monitoring Program (PMP)

State run programs that collect and distribute data (electronic database) about the prescribing and dispensing of federally controlled substances (addictive Rx'ed drugs). PMPs assist prescribers, dispensers and law enforcement by supporting the legitimate medical use of controlled substances while limiting the abuse and diversion of these agents. Their goal is for prescribers to use it as a tool to reduce the risk of opioid addiction, diversion and overdose. Data is submitted by pharmacies at least weekly, cleaned and stored in a centralized, relational database for all Schedule II, III, and IV drugs dispensed in the state (Maine included)

Corticosteroids

Steroid hormones produced by the adrenal cortex, they consist of 2 major groups: Glucocorticoids (GC's) - have important effects on metabolism, catabolism, immune responses and inflammation. Mineralocorticoids (MC's) - regulate Na+ and K+ reabsorption in the collecting tubules of the kidney. The major natural mineralocorticoid in humans is aldosterone. Other mineralocorticoids include deoxycorticosterone and fludrocortisone. Corticosteroids do not cure any disease. Contraindications to corticosteroid use include: latent TB or fungal infection, AIDS, herpes infections, and patients with peptic ulcer disease (specifically, gastric ulcers). Corticosteroids are likely to cause peptic ulcers. Their toxic effects include growth inhibition, hyperglycemia, osteoporosis, psychosis, and salt retention.

Teratogenic effects of drugs - X category medications

Studies in animals or humans have demonstrated fetal abnormalities or there is positive evidence of fetal risk based on adverse reaction reports from investigational or marketing experience, or both, and the risk of the use of the drug in a pregnant woman clearly outweighs any possible benefit eg. safer drugs or other forms of therapy are available.

Commonly abused substances

THC [Tetra Hydro Cannabinol], is the active substance in cannabis (marijuana), the most commonly used "recreational" drug. Opiates and narcotics: they cause sedation and euphoric feelings; they include heroin, opium, codeine, hydromorphone (Dilaudid), and oxycodone (Oxycontin). CNS Stimulants: Amphetamines, methamphetamine, Cocaine, dextroamphetamine, methylphenidate [Ritalin] and LSD. Sedatives (sedative, anxiolytic): Benzodiazepines [Valium, Ativan, Xanax] . Alcohol Molly, MDMA, GHB Hallucinogens: they cause hallucinations leading to psychological dependence eg. LSD, mescaline, psilocybin aka "mushrooms", and PCP [PhenCyclidine] aka "angel dust". Methadone: diverted from legal sources.

Mechanism of action of glucagon

Target tissues include adipose tissue, muscle, and liver. Binds to a Gs-coupled receptor. This coupling results in increased cAMP and increased protein Kinase A (PKA) activity. Activates IP3 (inositol 1,4,5-triphosphate pathway), increasing Ca2+.

Mechanism of antibiotic antagonism

Tetracycline eventually stops bacterial replication. No replication ⇒ no synthesis of new peptidoglycans. No new peptidoglycans ⇒ no cross-linking. No cross-linking ⇒ Penicillin is unable to act. Some researchers have stated that Tetracycline reduces Penicillin action into half!

Clinical relevance of protein binding

The *non-ionized, lipid-soluble form* of a drug is free to act and have an effect on the body: this is due to the fact that this form is able to pass through the membrane which is made of lipids. Simple diffusion. The *unbound* drug ie. drug that is not bound to plasma proteins, is also free to diffuse through membranes and act/have an effect on the body.

Substance abuse by health professionals

The ADA states: "...10-15 percent of dentists will have a drug and/or alcohol problem sometime in their lives". This is not unlike the general population! A unique aspect of addiction in the dental profession is the access to large amounts of N2O. Continued use of N20 can result in a syndrome that mimics multiple sclerosis. Factors that influence drug abuse by dental practitioners: stressful jobs, easy access to controlled substances, the temptation to self-medicate, the stress of litigation, and genetics (inheritable predisposition) expressed through changes in the biochemistry of the brain.

The Emergency Kit

The OHC emergency kit is compliant with state regulations and is consistent with the recommendations from the ADA, JADA and the HealthFirst Independent Medical Advisory Board. It contains the following: Albuterol Inhaler x1 Ammonia Inhalants x3 Aspirin 2-pack x2 Color-coded medication instructions x1 CPR Pocket Mask x1 Diphenhydramine 50mg/1mL x2 Epinephrine auto-injector for Adult 0.3mg x1 Epinephrine auto-injector for Pediatric 0.15mg x1 Epinephrine ampules 1:1000, 1mg/1mL (Back-up) x2 Epinephrine auto-injector training unit x1 KMCA medication tracking and refill service Nitroglycerin spray 0.4mg/spray 60 doses x1 Nitroglycerin tablets x25 Oral Glucose x1 Syringes x2 Optional content: Medications for sedation-related emergencies such as Flumazenil 0.5mg/5mL and Narcan nasal spray Dedicated O2

Drug efficacy

The ability of a drug to produce a desired therapeutic effect, *regardless of dosage*. Can be related to the number of receptors that require activation to produce a max. response: *high efficacy drugs stimulate a small proportion of receptors, and lower efficacy drugs need to activate a larger proportion of receptors*.

What changes the spectrum of activity of Abx's?

The acquisition of "resistant" genes.

Drug potency

The comparative concentrations of 2 or more drugs that produce the same effect. The effect usually chosen is ED50. It's *determined mainly by the affinity of the receptor for the drug*.

Metabolic (pharmacodynamic) Tolerance

The decreased responsiveness to a drug following chronic administration. The result of a decrease in the effectiveness of certain drugs with continued/chronic use. Can occur with any drug, prescribed or not, regardless of the drug nature. May be caused by pharmacokinetic factors that decrease the concentrations achieved with a given dose, for example: increased drug metabolism can result in tolerance. Also occurs when the same concentration at the receptor site results in a reduced effect with repeated exposure, for example: patients on opiates for chronic pain management are likely to require increased doses of the opiate over time.

Maintenance dose [MD] or [DM]

The dose of that drug required to maintain the Cp of that drug within the therapeutic window.

Loading dose [LD]

The drug dose sufficient to produce a drug Cp (dose per volume of distribution) that falls within the TW following one or a few doses over a short time interval. *LDs are larger than doses required to maintain the concentration within the TW*. If given in repeated doses, a LDs produce toxic concentrations.

Receptor Theory of Drug Action (PD)

The effect of a drug present at the site of action is determined by that drug's binding with a receptor.

Aspirin in the dental office

The following are some suggestions: The dose for an emergency is either 2-4 (81 mg) "baby aspirin" tablets or one single standard aspirin tablet - they should be non- enteric coated or "plain" aspirin tablets. Call 911 at the sign of chest pain and administer the aspirin tablets.

Dental home care for drug abusers / addicts

The following dental home care plan is suggested: Regular dental check-ups, *every 3 months*. Fluoride: gel, rinse, or trays. Thorough cleaning using PreviDent 5000 ppm Adequate diet and hydration (suggest dietitian)

Drug addiction

The initial decision to consume drugs is voluntary for most people. With repeated use, the user loses the ability to resist urges, which can be persistent. Despite effective treatment, relapses are common. Being a chronic condition, therapy should be ongoing and adjusted based on how the patient responds.

The reward center of the brain

The limbic system, modulated by DA receptors, has an important role in the feeling of pleasure experienced following the consumption of recreational drugs. This system is "turned on" upon drug consumption. Upon repeated exposure, the brain "learns" the relationship between the drug and drug-related reward and stimuli, causing a stronger drug craving.

Main organs responsible for drug clearance

The liver by way of metabolism, and the kidneys, by way of removal of the unchanged drug.

The term bioavailability of a drug refers to:

The measurement of the rate and amount of therapeutically active drug that reaches the systemic circulation. Explanation - The bioavailability of a drug is affected by: the dissolution of a drug in the GI tract and the destruction of a drug by the liver.

Minimum Inhibitory Concentration (MIC)

The minimum concentration of an antibiotic which will inhibit the growth of the isolated microorganism. Each bacterium has a level of antibiotic which will inhibit growth *but not kill the organism*. *The most common measure used to define antimicrobial pharmacodynamics in an organism*.

Dental care in immuno-compromised patients

The overall management principles of immuno-compromised patients are similar to those of organ transplant patients.

Positioning of pregnant patients in the dental chair

The supine position leads to: SHS, reduced venous return to the heart, and decreased O2 delivery to the brain and uterus. To avoid: place a small pillow under the woman's right hip - this is referred to as *left uterine displacement* or have the pregnant patient lean on her left side - this moves the uterus off the vena cava and ensure that the patient's head is not lower than her feet while in the chair.

Drug clearance [CL]

The volume of plasma cleared of drug per unit time, or a constant, relating the rate of elimination to the Cp (ie. rate of elimination). CL x Cp . Cp = dose per volume of distribution.

Volume of distribution (VD)

The volume of plasma that would be necessary to account for the total amount of drug in the patient's body, if that drug were present throughout the body at the same concentration as found in the plasma. It is a theoretical volume (apparent). It describes the relationship between drug concentration and the amount of drug in the body. Its formula is: LD = Vd x Desired Concentration (The desired concentration of a drug is obtained from the literature)

Controlled substances are scheduled based on:

Their medical use in the US Their relative abuse potential Their likelihood of dependence Overseen by the Controlled Substances Act (CSA)

Imaging technologies and drug abuse

They allow us to investigate the integration of the various biological factors in drug abuse and how they relate to behavior and environmental variables. These technologies include: Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI).

Broad spectrum Abx's

They are active against both G+ and G-organisms. Examples include: Amoxicillin (broader spectrum of activity) Cephalosporins (3rd and 4th generation) Tetracycline Levofloxacin Streptomycin Chloramphenicol

Antimicrobials

They are agents that act against microbial organisms. They include: Antibacterials/Antibiotics (ABs), Antivirals, Antifungals, and Antiprotozoals.

Local anesthetics in pregnancy

They are safe to use when needed in pregnancy provided that: no contra-indications are present; they are prescribed when necessary; aspiration is performed; and doses used are well below the maximum recommended doses. Remember that: LA's are likely to exhibit a more rapid onset of action and a longer duration of action. *LA's cross the placenta freely* - potential for fetal toxicity is a concern. Vasoconstrictors: use with caution, consider the CVS changes in pregnancy. *Avoid inadvertent intravascular injection at all costs* as it can cause uterine artery vasoconstriction and decreased uterine blood flow. Consider using carpules with 1:200,000 concentrations of epi as an alternative.

Narrow spectrum Abx's

They have targeted activity and are primarily only useful against particular bacterial species. Examples: Penicillin Azithromycin Clindamycin Clarithromycin Erythromycin Vancomycin

Adverse effects of pain management combination therapy

They included in order of overall incidence: nausea, vomiting, headache, and dizziness. The adverse events were significantly less frequent in the ibuprofen/acetaminophen groups compared to the codeine combinations. Occurred in at least 5% of subjects in at least 1 of the 5 treatment groups.

Environmental factors for fungi

They require high sugar content. Low pH favors fungal growth and adhesion. Resident bacterial flora compete for binding sites, nutrients and production of anti-fungal compounds. Alteration of resident bacterial population by antibiotics leads to outgrowth of candida species.

Treatment planning

This applies to both substance abusers and those undertaking detox: be understanding and non-judgmental. Prepare for interruptions in treatment. Commencing of treatment and careful pain relief in consultation with the patient's PCP or drug addiction specialist. Be "aggressive" with prevention. Do NOT prescribe opioids.

Antibiotic prophylaxis in organ transplant patients

This is decided following discussion with the patient's MD: most cases require pre-medication in order to prevent systemic infection from probing and invasive dental procedures.

Amoxicillin / Clavulanic acid (Augmentin)

This product was created as a result of Amoxicillin resistance. Augmentin is resistant to degradation from beta-lactamase. It inhibits β-lactamase, a β-lactam ring destroying / hydrolyzing enzyme produced by bacteria. Inhibits plasmid and chromosomal mediated β-lactamases including Staph, Haemophilus, and Bacteroides. By inhibiting the destruction of the β-lactam ring, it enhances the effectiveness of amoxicillin. *Side effects: stomach cramps and diarrhea*

Topical corticosteroid prescription products:

Triamcinolone acetonide 0.1% (Kenalog in Orabase) Hydrocortisone acetate 1% ointment Betamethasone dipropionate 0.05% ointment

Antifungals and their Mechanism of Action

Two major targets: cell wall and cell membrane. The problem with anti-fungal therapy is that fungal organisms are eukaryotes which presents a toxicity problem: there is an ongoing search for new approaches of anti-fungal drugs in order to prevent toxicity.

Potency of topical steroid preparations

Ultrapotent: Clobetasol propionate (Temovate) 0.05% Halobetasol propionate (Ultravate) 0.05% Potent: Dexamethasone (Decadron) 0.5mg/5mL Fluocinonide (Lidex) 0.05% Fluticasone propionate (Cutivate) 0.05% Intermediate: Betamethasone valerate (Valisone) 0.1% Alclometasone dipropionate (Aclovate) 0.05% Triamcinolone acetonide (Kenalog) 0.1% Low: Hydrocortisone 1%

Burning mouth syndrome (BMS) - Etiology and predisposing factors

Unknown Neurogenic Vascular Psychogenic Xerostomia Menopause Cancer therapy, irradiation and chemotherapy Candidosis Chronic infections Reflux Medications Nutritional deficiencies Allergic and inflammatory disorders

Strategies in antibiotic treatment

Use a loading dose to rapidly achieve therapeutic blood levels. *Do NOT combine bacteriostatic and bactericidal abx's such as: Tetracycline (bacteriostatic) + Penicillin (bactericidal)*. Reason: cidal-static interaction cancel each other out due to opposing mechanisms of action or antagonism If indicated, start AB Rx. fast and early. Use the right drug! Use the right dose and dosing schedule (interval 4x plasma half-life). Use for the prescribed length of time: most infections, if managed appropriately, should improve if not resolve in 7 -10 days. Continue Rx. for 2-3 days after resolution of infection.

Disadvantages of Narrow Spectrum Abx's

Used preferably if the causative organism is identified. If not specific for the identified organism, the infection will continue.

Benzodiazepines

Used to treat alcohol withdrawal due to their interaction with the *GABA receptor*.

Herpes Simplex Virus Pharmacotherapy

Valacyclovir 500 mg (Valtrex), dispense (28) twenty-eight, take 1 tablet BID Acyclovir, 200 mg (Zovirax), dispense (70) seventy tabs, 2 tablets TID Acyclovir (Zovirax) 5%, Cream (5g) Penciclovir (Denavir) 1% Ointment (2g) Acyclovir (Zovirax) 5% Cream (5g): A nucleoside analogue DNA polymerase inhibitor. Indicated for patients 12 years or older with a competent immune system. Not a cure for cold sores. Most effective when used early, at the start of a cold sore. Good results seen when applied at the first signs. Adverse effects - dry or cracked lips, flakiness or dryness of skin, burning or stinging feeling, and itching of the skin. Instructions/dosing for topical: use only on affected skin; apply sparingly (a thin layer) to cover the lesion or tingly area up to 5 times daily for 7 days; and rub the cream in gently until it disappears. Geriatric Use "Clinical studies of acyclovir cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Systemic absorption of acyclovir after topical administration is minimal". Pregnancy category: B (no evidence of risk in humans). Penciclovir (Denavir) 1%, 2g ointment: A nucleoside analog HSV DNA polymerase inhibitor; it selectively targets cells infected with HSV-1 and results in the inhibition of viral replication. Indicated for patients 12 years or older with a competent immune system. Not a cure for cold sores. Most effective when used at the earliest signs. Not available for systemic dosing. Instructions/dosing: use only on affected skin, apply sparingly (a thin layer) to cover the lesion or tingly area every 2 (waking) hours for a period of 4 days. Rub the cream in gently until it disappears. Adverse effects: application site reaction hypesthesia /Local anesthesia, rash (erythematous), and taste perversion. Geriatric Use: adverse effect in patients > 65 years of age were comparable to those observed in younger patients. Pregnancy category: B (no evidence of risk in humans). Abreva (Docosanol) OTC. Evidence suggests that Docosanol renders target cells less susceptible to viral fusion by interfering with early intracellular events (not considered to be a true antiviral agent as it does not work by inhibiting viral replication). Treatment with topical anti-viral medications should be initiated soon after the onset of symptoms such as tingling or burning and blisters (during the pro-doromal phase or when the lesions appear). Patient should be instructed to wash hands before and after applying the ointment using a cotton swab to avoid spreading the virus. The safety and effectiveness in pediatric patients < 12 yo have not been established.

Clinical example of LD in dentistry

We use it to rapidly achieve therapeutic blood levels. A LD of 1g of Penicillin VK is prescribed PO, followed by 500 mg 4-6 hours (q4-6h) for 5-7 days. If facial swelling is present, this dosing regimen should result in improvement of the existing infection within 48-72 hours.

Pharmacokinetics (PK)

What the body does to a drug. The study of the time course of drug absorption, distribution, metabolism, and elimination.

Questions to ask yourself when treating patients with drug addiction:

Which drugs is the patient taking? Is the patient on drugs at the time of the appointment? How should I modify the treatment plan? What is the most suited pain management strategy? Does the patient inject drugs?

Advantages of Narrow Spectrum Abx's

Will kill less of the normal flora vs broad spectrum antibiotics; less able to cause superinfection; and will cause less bacterial resistance due to its specific bacterial target.

Principles of managing pregnant patients

With special precautions, emergent treatment such as acute infection or sources of sepsis can and should be performed during any trimester as delay could cause harm to mother and fetus. Routine dental care is important and recommended. Ideal treatment period: 2nd trimester. Elective treatment is deferred until after delivery. Apply good judgment when prescribing radiographs. Remember, when treating a pregnant patient, you need to consider 2 patients: the expecting mother and the developing fetus. Criteria for premedication is the same as for other individuals. First Trimester - Regular check-ups, non-invasive treatment are safe. Second Trimester - The safest time to perform elective dental procedures is in the early 2nd trimester. SHS is somewhat a concern. Third Trimester - Main concern is SHS.

Clinical relevance of MIC and prescribing antibiotics

With the recommended doses, peak drug levels in the blood are planned to exceed the MIC or MBC of the infecting bacterium. *Infections in immuno-compromised patients require a bactericidal drug at levels above the MBC*. Infections exposed to an active host defense system often respond to serum levels below the MBC.

Reasons for antibiotic failure

Wrong diagnosis Wrong AB Abx resistance: resistant organisms Immuno-suppression Non-compliance Drug not reaching site Drug dosage too low Loading dose not considered!

Oral pathologies and recreational drugs

Xerostomia Corrosion of dental restorations Cervical caries Fracture, attrition and tooth wear Gingival Recession Gingivitis and Periodontitis Loss of tooth color Bruxism Halitosis due to poor oral hygiene TMJ pain and Trismus Oral sores/ulcers referred to as "acid burns" Mucosal ulceration due to placing tablets in direct contact with the gingival tissue Intra-nasally: ischemic necrosis and ulceration of the palate and nasal septum (cocaine)

At the cellular level and at the site of infection, C. albicans has 3 different morphologies:

Yeast (blastoconidia): this is the colonizing form, usually found on the epithelial surface, past which it does not penetrate; also sets up infection Pseudohyphae Hyphae and germ tubes: they are nascent hyphae, or filamentous forms of candida; they detect and penetrate breaks in the epithelium and endothelium.

Carbapenems

β-lactam antibiotics resistant to β-lactamase enzymes. *Broad spectrum of coverage*. Coverage of G+, G-, and anaerobes. Examples: Imipenem (used IV - Cilastin is added to decrease renal excretion; causes seizures at high doses); Meropenem; Ertapenem; and Doripenem. *Not 1st line therapy for odontogenic infections*. Consider for: multi-space infections and descending necrotizing mediastinitis.

Cephalosporins

β-lactam antibiotics. Broad spectrum. Semi-synthetic. Multiple generations: 1st to 3rd available orally, 4th and 5th not available orally. Greater G-coverage with newer generations. Useful for prophylaxis for cardiovascular and orthopedic surgery. Toxicity similar to Penicillins. Newer generations have improved G-efficacy, less G + efficacy and improved efficacy against resistant organisms.