If a drug produces its usual effect at an unexpectedly high dose, the pt is said to be what?
hyporeactive
If a drug produces its usual effect at an unexpectedly low dose, the pt is said to be what?
hyperreactive
What are 2 idiosyncratic types?
hypo and hyper-reactive
idiosyncratic responses are most often related to What?
genetic variations affecting the biotransformation activities among CYP450 enzymes in the liver
among the CYP450 enzymes, which has been studied the most extensively?
CYP2D6
pts who lack CYP2D6 will exhibit ______ metabolism of certain drugs, pts who have normal enzyme activity will exhibit _______ metabolism, pts with markedly enhanced enzyme activity will exhibit __________ metabolism
poor
normal
ultrarapid
If the consequence is reduced metabolism it leads to what? If the consequence is accelerated metabolism it results in what?
excessive therapeutic effecs and adverse reactions
insufficient therapeutic response
a substance recognized as 'foreign' to host antibodies
antigen
When are drugs immunogenic (antigenic)?
if the immune system is able to recognize it as a foreign, and if the molecular weight of the drug is large
a substance (drug) of lower molecular weight than an antigen
hapten
What is an example of a hapten? And what does it bind to before id can induce antibody synthesis?
penicillin
albumin
true or false. the production of antigens occurs in genetically predisposed individuals, is not related to the dose administered, and is unpredictable.
true
the first time a predisposed individual is exposed to an allergenic chemical and plasma cells form antibodies to destroy the antigen
sensitization
drug allergies are seen twice as frequently in men or women?
women
What are the 4 main types of antigen/antibody hypersensitivity reactions?
immediate
cytotoxic
immune-complex
delayed
Exposure to an allergen results in antigen-specific antibody production dominated by what isotype?
immunoglobulin E (IgE)
IgE antibodies bind to specific sites on what 3 areas?
mast cells
basophils
eosinophils with mucosal and epithelial tissues
allergic reaction that includes; antigens binding to IgE molecules degranulating mast cells and basophils resulting in inflammatory response, bronchoconstriction from histamine release, dilation of arterioles, escape of plasma proteins and fluid leading to edema,mucous secretion and impaired mucous clearance
type I (immediate) hypersensitivity reaction
What is the most dangerous form of hypersensitivity reaction and includes anaphylactic shock?
type I (immediate) reaction
The IgE molecules are related to what type of reaction?
type I
allergic reaction that involves IgG antibodies involved in basic cytotoxic immun reaction; antibodies bind to antigen coated host cells, lyse the cell induced by active by-products; K-cells can also cause lysis of effected cells
type II (cytotoxic) hypersensitivity reaction
What is a practical example of a type II (cytotoxic) hypersensitivity reaction?
drug-induced hemolytic anemia
______ antibodies also mediate immune-complex reactions and result in the formation of large, insoluble antigen-antibody complexes
IgG
immune complexes mediated by IgG antibodies adhere to target tissues and initiate intense complement activation; resulting in leukocytes and platelets migrating to affected tissue to form thrombi producing localized or systemic complications
type III (immune-complex) hypersensitivity
What is an example of a type III (immune-complex) hypersensitivity reaction?
drug-induced mucositis
What type of reactions are closely related to cellular immunity in the specifically sensitized CD4+ T-lymphocytes intitiate the reaction?
type IV (delayed) hypersensitivity reaction
Is cellular immunity associated with T or B lymphociyte immune responses?
T lymphocyte
Are type IV (delayed) hypersensitivity reactions life threatening?
no
What are 3 examples of type IV (delayed) hypersensitivity reactions?
dermatitis
stomatitis
induration produced in a positive TB test
reactions that cannot be explained on an imunologic basis; ADEs occur in pts with no prior exposrue to the drug; possible mechanisms may include direct activation of mast cells through non-IgE receptor pathways releasing histamine
pseudoallergic reactions (anaphylactoid)
What are 4 types of drugs that are said to be involved in a pseudoallergic type of reaction?
penicillin
codeine
morphine
vancomycin
what is a critical time period for introduction of drug or metabolite concentrations in the fetus?
3rd to 12th week of gestation
What drug caused teratogenic malformations including depression of limb formation (phocomelia)?
thalidomide (a drug used in England to reduce morning sickness)
What drugs are placed in pregnancy category X?
drugs likely to cause malformations
oncogenic effect that can be produced by certain procarcinogenic drugs, which are converted into carcinogens by polymorphic oxidation reactions, covalent binding of these oxidized metabolites to DNA leads to mutagenic and carcinogenic effects
primary oncogenic effects
oncogenic effects associated with therapeutic immunosuppression, such as drug induced immunosuppression to prevent regection of an organ following organ transplant; leading to reactivation of latent infection with oncogenic viruses; hep viruses, CMV, HSV, HPV, and EBV
secondary oncogenic effects
Clinical manifestations of adverse drug effects may reflect ________ or ________ adverse effects
primary (direct)
secondary (indirect)
effects associated with _______ reactions are those dose-dependant effects that are not desired for the given therapeutic use of a drug. These adverse effects account for most of the ADEs and may be exaggerations of direct effects or multiple concurrent 'side effects.
Type A reactions
effects that are either primary or secondary but they may or may not be dose dependant.
Type B reactions
true or false. The management of oral ulceration is the same whether it is a type A or type B reaction
true
true or false. Signs and symptoms of type-A reactions can develop in some clients with the normal dose of a drug, or they can result from excessive doses
true
What are the two main types of cytotoxic effects in clinical manifestations of type-A reactions?
hepatocellular toxicity
Methemoglobinemia
drug-induced liver injury is a potential complication of nearly every medication that is prescribed. What is one of the most common drugs associated with hepatotoxicity?
APAP (acetominophen)
What is an excessive dose of APAP resulting in toxicity?
more than 4 grams in a 24 hour period (less with alcoholics)
If someone had the following symptoms, what would you suspect?
nausea, vomiting, anorexia, abdominal pain, elevated bilirubin causing jaundice
liver toxicity
excessive amounts of acetominophen causes hepatic cell function; what substance accelerates this process?
alcohol
a realtively uncommon toxic reation to some local anesthetics, including, prilocaine, articaine, and benzocaine; metabolites of these drugs bind with hemoglobin and interfere with its oxygen carrying ability
methemoglobinemia
If a pt presented with the following symptoms, what would you suspect?
cyanosis in the absence of cardiopulmonary symptoms, nausea, sedation, seizures, and coma
methemoglobinemia
When ulceration of oral mucosa membranes occurs during cancer chemotherapy
mucositis
What condition appears clinically as erythematous or generalized ulcerative lesions in the oral environment?
mucositis
What are 3 palliative management strategies used in patients with pain associated with cytotoxic ADEs?
mouth rinses containing:
topical anesthetic
liquid antihistamine
covering agent (miracle mouthwash)
What mouth rinse ins contraindicated for pts experiencing pain from cytotoxic ADEs?
mouth rinses with alcohol
What type of ADEs are among the most common listed in drug reference texts?
disturbances in the GI tract:
nausea
vomitting
abdominal pain
constipation or diarrhea
What is the purpose of nausea? What is the purpose of vomitting?
prevent food intake
expel food or toxic substance present in the upper part of the GI tract
What type of drugs can affect emesis, depending on their affinity for opioid-receptor subtypes in the brain?
opioid analgesics:
codeine - induce
morphine - block
naloxone - reverses overdose of opioids
the passage of excessively dry stool, infrequent stool, or stool of insufficient size involving the subjective sensations of incomplete emptying of the rectom, bloating, passaage of flatus, lower abdominal discomfort, anorexia, malaise, headache, weakness, and giddiness
constipation
What affect can the following drugs have?
anticholinergic drugs
antiparkinsonian drugs with antocholinergic properties
antihistamines
neuroleptics
antidepressants
anticonvulsants
opioid analgesics
antacids
they can lead to constipation
passage of liquefied stool with increased frequency; can be due to lactose intolerance, inflammatory bowel disease, malabsorption syndromes, endocrine disorders, and irritable bowel syndrome
diarrhea
What 3 factors are the usual causes of acute diarrhea?
infection (viral or bacterial)
toxins
drugs (antibacterial agents)
What is a helpful appointment management to help with pts experiencing GI disturbances?
use the semisupine chair position for treatment
characterized by frequent urination, and is often caused by diuretics
urinary incontinence
drugs that can cause urinary incontinence cause it as a result of overflow stemming from urinary retention, what are 2 types of drugs that act in this manner?
anticholinergic agents
adrenergic agonists:
ephedrine
theophylline
What is a frequent consequence of treatment with antihypertensive agents, beta-adrenergic antagonists, cardiac glycosides, benzodiazepines, barbiturates, levodopa, indomethacin, phenothiazines, and steroids? Delirium can also be attributed to drug therapy
depression
What is a helpful mangement tip for the treatment of pts with depression?
encouragement to set specific goals for oral hygiene practices to help them remember
occurs when there is a drop in the blood pressure after the pt arises from a prone position, putting them at risk for loss of consciousness
postural hypotension
antihypertensive agents, antidepressants, drugs for erectile dysfunction and other psychotropic agents, alcohol, and levodopa are all drugs that have been known to produce what?
postural hypotension
What are 2 drugs known to cause an increase in blood pressure?
oral contraceptives
decongestants
What is a drug that is used to treate congestive heart failure, but is also associated with causing cardiac arrhythmias?
Digoxin
The cardiac effect cuased by macrolilde antibiotics used in combination with drugs that cause CYP34A isoenzyme inhibition can cause what?
a type of vetricular arrhythmia that can result in sudden death
What is the best way to manage a pt with cardiovascular dysfunction as a side effect of drugs such as hypotension or high BP?
allow pt to sit in chair for several minutes after they sit up and before they leave
take BP at end of appointment as well as at beginning
What are 7 drugs that frequently implicate falls and equilibrium problems?
benzodiazepines
antidepressants
neuroleptics
barbiturates
phenytoin
antiarrhythmic agents
alcohol
qualitative (mucoid not watery) and quantitative (reduced secretion) changes in saliva lead to a variety of oral problems, some of which can include reduced lubrication; reduced antibacterial, antiviral, and antifuncal activity; loss of mucosal integrity; loss of buffering capacity; reduced lavage and cleasing of oral tissues; interference with normal remineralization of teeth; and altered digestion, taste, and speech
xerostomia
These major drug classes can all cause what?
anticholinergic agents, antidepressants, antihypertensive agents, antipsychotics, diuretics, antihitamines, central nervous system stimulants, systemic bronchodilators, and a small number of chancer chemotherapeutic agents
xerostomia
What are some good ways to help pts with xerostomia?
chew xylitol gum or mints
home fluoride use
artificial saliva products
effective plaque control at 3-4 month intervals
antithrombolytic agents such as ______ and __________, alter the ability of platelets to stick or clump together to form a clot; which can increase the bleeding time and lead to increased intraoperative bleeding in association with invasive procedures
aspirin
clopidogrel (plavix)
What drug reduces intravascular clot formation by inhibiting the formation of vitamin - K dependent clotting factors, primarily factor VII?
anticoagulant warfarin (coumadin)
What anticoagulant drug interferes with the formation of factors II and X?
heparin
What is the most common side effect of both heparin and warfarin?
hemorrhage
When drugs that affect clotting factors are reported, what should be requested?
the prothrombin time, or international normalized ration (INR) blood test
What is an acceptable INR level for periodontal procedures that are likely to involve increased bleeding in pts taking an anticoagulant?
less than or equal to 3.5
If a pt complains of diarrhea with lower abdominal cramping and is currently taking or has recently taken an antibacterial agent, the clinician must consider tha possibility of what?
a bacterial superinfection
What is the most dangerous form of bacterial superinfection?
pseudomembranous colitis; associated with an overgrowth of clostridium difficile in the GI tract
What are the 2 most antibiotics that most commonly cause pseudomembranous colitis?
clindamycin
penicillins and cephalosporins
What are the most common signs of bacterial infections?
pain
fever
presence of oral lesion
Antibacterial chemotherapy and therapeutic immunosupreesion including inhaled corticosteroids, often lead to opportunistic infection with __________ and other fungal organisms
candidiasis albicans
What may appear as white, raised, or cottage cheese like growth that can be removed with gauze, leaving a red, sometimes hemorrhagic mucosal area?
oral candidiasis
true or false. If oral candidiasis is not treated it can spread and eventually affect all organ systems
true
How can you manage a pt with oral candidiasis?
prescribe nystatin (antifungal drug)
soak dentures in a nustatin or diluted sodium hypochlorite solution for 5 minutes
remove appliances at night during sleep
true or false. Immunosuppression drug therapy can exacerbate latent viral activity
true
What type of virus manifests itself in pts undergoing therapeutic immunosuppression, and may be observed on the lips and intraorally on all tissues?
secondary herpes simplex virus infections
what type of viral infection is a painful, unilateral vesiculation that may follow the distribution of a branch of the trigeminal nerve; lesions coalesce into large ulcerations and may linger for weeks before remission occurs?
recurrent infection with the varicella zoster virus - herpes zoster or shingles
What type of bacterial infection has been associated with a wide range of syndromes in solid organ transplant recipients; in the oral cavity has been casually related to leukoplakia, found on the lateral borders of the tonge in pts with therapeutic immunosuppression
Epstein Barr virus infection
What is an antiviral drug that the dentist or physician may prescribe for pts with oral viral infections?
valacyclovir
gingival hyperplasia is seen often in patients taking what 3 different medications?
anticonvulsant phenytoin (dilantin)
cyclosporine (immunosupressant)
calcium channel blocking agents
________ may be secondary to drug induced mucositis; during therapeutic immunosuppression, actue exacerbations of chronic periodontal or apical infections can also precipitate _______
oral pain
pain
pain or paresthesia may be associated with the administration of what cytotixic chemotherapeutic agents? 2
plant alkaloids:
vinblastine
vincristine
an example of an ADE produced by certanpsychotropic (antipsychotic) drugs; cahracterized by uncontrolled, repetetive movement of the lips, tongue, and mouth
tardive dyskinesia (TD)
taste disturbances caused by many angiotension converting enzyme (ACE) inhibitors; metronidazole, benzodiazepines, chlorhexidine mouth rinse, gold salts, and lithium
dysgeusia
true or false. nutrtional deficiency can delay the healing response