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pharm 2 > unit 1 adrs/ddi > Flashcards

unit 1 adrs/ddi Flashcards

1
Q

Adverse Drug Reaction Versus Allergy
Type A [Side Effect] - common?
* Predictable?
* Overdose
* Side Effect -
Type B [Allergy] - common?
* predictable?
* mechanisms

A

Type A [Side Effect] - common
* Predictable (pharmacologic action), Dose Related, Can Affect Anyone
* Overdose - Hepatic failure (acetaminophen)
* Side Effect - Nephrotoxicity (with aminoglycosides); diarrhea (amoxicillin)

Type B [Allergy] - uncommon
* Unpredictable (hypersensitivity reaction), Not dose related, Cannot affect anyone
* Anaphylaxis; photoallergy
* Antibody or T-cell Stimulatio

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2
Q

Low-Risk factors of Penicillin Allergy Assessment

A

utacaria may be a reuslt of viral infection and misinterpreted aas an allergy.
Low-risk allergy symptoms – most commonly rash and itching – likely do not represent true IgE allergy

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3
Q
A
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4
Q

high risk factors of penicillin allergy

A
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5
Q

Questions to ask when assessing an allergy
 Describe reaction
 route?
 How long ago?
 Timing of reaction?
 tx?
 Use of what before reaction?
 Use of what since reaction?

A

 Describe reaction
 Administered PO or IV?
 How long ago did the reaction occur?
 Timing of reaction?
 Immediate (< 4hrs)
 Delayed (>24 hrs)
 Any treatment required?
 Use of penicillins or cephalosporins before reaction?
 Use of penicillins or cephalosporins since reaction?

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6
Q

ADRs of non-Beta lactams compared to beta lactams, significance of this?

A

‘Non-beta-lactam antibiotics were associated with more adverse drug
reactions than penicillins or cephalosporins, independently of the penicillin skin test result.

Cephalosporins can be used as safely or more safely than non-beta-lactam antibiotics in penicillin skin test positive and negative individuals.

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7
Q

Penicillin Allergy Summary
* True allergy?
* Review?
* Family history of penicillin allergy, GI symptoms, headache, yeast infection?
* Hive and non-hive rash reports [not SJS-like]?
* Severe/high-risk reactions [e.g. SJS, Anaphylaxis-like, DRESS, Serum sickness?

A

ñ True allergy (IgE) is rare; Penicillin-Cephalosporin cross-reactivity NOT 10%
ñ Review the documented allergy or Interview the patient

  • Family history of penicillin allergy, GI symptoms, headache, yeast infection
    ►Not Allergy
  • Comfortable giving any penicillin or cephalosporin
  • Hive and non-hive rash reports [not SJS-like]
    ►Likely not Type-1 Allergy
  • May give amoxicillin, especially with distant history and penicillin benign skin reaction
  • Can use a cephalosporin without concern
  • Severe/high-risk reactions [e.g. SJS, Anaphylaxis-like, DRESS, Serum sickness]
    ►Type-1 or CTC Allergy
  • Use an alternative antibiotic [reasonable to consider later generation cephalosporin]
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8
Q

2021 AHA Statement for those with cillin allergies

A

More cautious approach- not to use cepph in those with hx to pencillin allergies (anaphylaxis, utacaria, angioedema)

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9
Q

Amoxicillin/Clavulanate
Pediatric Antibiotic Associated Diarrhea

A
  • 35 articles reporting on 42 studies were included for analysis
  • 33 trials reported on amoxicillin/clavulanate
  • 6 trials on amoxicillin
  • 3 trials on penicillin V
  • In total, the 42 trials included 7729 children treated with an oral penicillin
    about 19.8% incidence
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10
Q

Amoxicillin/Clavulanate
Antibiotic Associated Diarrhea

A

seen in 25% with 250: Amoxicillin 250 mg /clavulanate 62.5mg per 5mL

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11
Q

reducing augmentin shits

A

Goal 14:1 ratio of amoxicillin to clavulanate to lessen this side effect
ideal: 600: Amoxicillin 600 mg /clavulanate 42.9mg per 5mL *

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12
Q

what can be used for prohylaxis with G+ suspected

A

penicillin

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13
Q

when would ceph not be used in those with a hx of rxns to cillins? what is used instead

A

use macrolides or doxy

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14
Q

Why risk using amoxicillin rather than clindamycin?
Risk of using amoxicillin:
* No risk if the reaction is?
* Any non-SJS rash history to amoxicillin? re-exposed?
* Risk of a severe reaction is ?
* Risk for sever reaction if initial ‘allergy’ was immediate onset, ?

A

Why risk using amoxicillin rather than clindamycin?
Risk of using amoxicillin:
* No risk if the reaction is GI, headache, yeast infection, family history
* Any non-SJS rash history to amoxicillin, re-exposed to amoxicillin 93-94% tolerate with no subsequent reactions
* Risk of a severe reaction is 0.001%
* Risk for sever reaction if initial ‘allergy’ was immediate onset, 0.29%

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15
Q

Risk of Clindamycin

A

Among oral antibiotics commonly prescribed by dentists, clindamycin has
the highest fatal (2.9/million prescriptions), serious (233.2/million
prescriptions), and overall (337.3/million prescriptions) ADR rates.
* Double any other dental antibiotic
* >15 times higher than amoxicillin
* Amoxicillin has the lowest fatal
(0.1/million prescriptions), serious
(11.9/million prescriptions), and overall
(21.5/million prescriptions) ADR rates

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16
Q

Risk of C. difficile Infection By Antibiotic
* Clindamycin
* Augmentin
* Cephalexin
* Amoxicillin
* Penicillin

A
  • Clindamycin 25-fold increased risk (greatest risk)
  • Augmentin 8.5-fold
  • Cephalexin (Keflex) 3-fold
  • Amoxicillin 2-fold
  • Penicillin 1.8-fold
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17
Q

Recurrence and Mortality of c dif

A
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18
Q

Antibiotic Duration Impacts CDI Risk

A

use under 3 days to decrease risk

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19
Q

PPI and Abx

A

lower ph of stomach reduicing sporicidal emzyme ability

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20
Q

probiotic use with Abx?who can benefit?

A

May consider for higher risk individuals:
* 65yo+
* recent hospitalization or nursing home
* weak immune system (HIV/AIDS, cancer, or
taking immunosuppressive drugs)
* previous C. diff infection
* taking proton pump inhibitors

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21
Q

metro ADRs

A
  • Metallic taste, dry mouth
  • Dark urine
  • Skin rashes
  • Disulfiram reaction? (headache, flushing, N/V) avoidance of alcohol no longer required
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22
Q

metro interactions

A
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23
Q

warfarin interactions

A

majority activtity from s isomer which is increased due to CYP2C9 inhib= INR increased

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24
Q

Empiric Warfarin Dose Reduction with metro

A
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25
Q

clindamyacin Disadvantages
* infection?
* oral suspension?
* High doses of oral clindamycin (>450 mg Q6H) may cause?

A
  • C. difficile infection
  • Clindamycin oral suspension unpleasant taste
  • High doses of oral clindamycin (>450 mg Q6H) may cause esophagitis
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26
Q

tetracycline and c dif as respiratory agent

A
  • Tetracyclines demonstrated no increased risk (OR, 0.92) vs no antibiotic
    exposure
    safe agent for those with hx of CDI
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27
Q

which tetracycline does not discolor peds teeth

A

doxy

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28
Q

Doxycycline Considerations
* Tooth Discoloration? recomendations?
* Avoid during?
* GI? More common with? which form is better tolerated?
* esophogus?
* Peak plasma concentration may be reduced ~20% by?
* skin?
* Renal/hepatic disease?

A

Doxycycline Considerations
* Tooth Discoloration: Updated recommendations from the American
Academy of Pediatrics permit doxycycline for ≤21 days in children of all ages
* Avoid during pregnancy, teratogenic
* GI upset: More common with hyclate salt but Monohydrate less acidic, better tolerated
* Erosive esophagitis – avoid taking at bedtime, drink full glass of water
* Peak plasma concentration may be reduced ~20% by high-fat meal or milk
* Phototoxicity (skin rashes) may occur
* Renal/hepatic disease patients can use doxycycline

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29
Q

do we fw ERTHYROMYCIN?
●spectrum?
■ Adverse effects:
■ Strong inhibitor of?
■ Highest risk of?

A

NOT USED
●Narrow spectrum: LOTS of resistance
■ Adverse effects: Prokinetic, GI disturbances, diarrhea (can be used with gastroparesis, cramping
■ Strong inhibitor of CYP3A –many drug interactions.
■ Highest QTc prolongation risk among antimicrobials

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30
Q

Clarithromycin (Biaxin) –used?
Liver metabolism?
metabolim?
Less drug-drug interactions than?

A

AVOID USE
Liver metabolism: Moderate CYP3A inhibitor.
Prodrug: metabolized to active compounds
Less drug-drug interactions than Erythromycin but more than azithromycin

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31
Q

clarithromyacin adr

A

metallic taste

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32
Q

Both Erythromycin and Clarithromycin slow what? implications of this?

A

Both Erythromycin and Clarithromycin slow CYP3A4
Accumulation of other drugs that are metabolized through 3A4
* Benzodiazepines
* Transplant Drugs (cyclosporine, tacrolimus)
* HIV Drugs
* CCBs (amlodipine, diltiazem)

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33
Q

does azithromyacin influence CY3A4

A

limited effect

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34
Q

azithrhomyacin Side Effects:

A
  • Possible reversible tinnitus with large doses
  • Liver reports – jaundice, necrosis, failure
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35
Q

why are macrolides not top choice for odontogenic infections?
■ No activity against?
■ Alternative?
■ Less effective than?
■ Overall limit use due to?
■ % of viridans group Streptococci resistant? implications?

A

■ No activity against Bacteroides, common in dental abscesses
■ Alternative antibiotic in odontogenic infections.
■ Less effective than b- Lactams (2nd choice)
■ Overall limit use due to already high resistance rates.
■ 50% of viridans group Streptococci resistant, not good for prophylaxis

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36
Q

Pregnancy and Lactation
* Good Safety abx

A
  • Cephalosporins, penicillins, clindamycin, azithromycin
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37
Q

Pregnancy and Lactation bad abx

A
  • Doxycycline – Ca++ chelation
  • Fluoroquinolones – kidneys/cartilage
  • Sulfamethoxazole/trimethoprim – various/kernicterus
  • Metronidazole in 1st Trimester – limited data
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38
Q

other antimicrobials increasing warfarin con./ INR

A

TMP-SMX and fluconazole

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39
Q

acyclovir interactions

A

tizanidine

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40
Q

acyclovir adrs

A

GI upset, malaise; Local pain (topical)

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41
Q

valcyclovir interaction

A

tizanidine

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42
Q

valcyclovir Adverse Effects

A

GI upset, headache

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43
Q

maternal use of valcyclovir

A

Following maternal administration of valacyclovir, acyclovir is detectable in cord
blood and amniotic fluid; Pregnancy Category B
Higher than serum concentrations present in breast milk (caution)

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44
Q

DDIs: Acyclovir and Valacyclovir

A
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45
Q

penciclovir ddi

A

minimal

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46
Q

penciclovir adr

A

Erythema, headache

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47
Q

maternal penciclovir

A

not used

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48
Q

famciclovir ddis

A

minimal

49
Q

famiciclovir adrs

A

Nausea, headache

50
Q

famciclovir in pregnancy

A
51
Q

docosanol ddi

A

none

52
Q

docosanol adrs

A

well tolerated

53
Q

Oseltamivir ddi

A

minimal

54
Q

Oseltamivir adr

A

gi, headache

55
Q

Oseltamivir maternal

A

Oseltamivir phosphate and its active metabolite oseltamivir carboxylate cross the
placenta. Use during pregnancy and breastfeeding is acceptable.
Limited excretion into breast milk

56
Q

Baloxavir marboxil ddi

A
57
Q

Baloxavir marboxil adrs

A

gi upset

58
Q

Baloxavir marboxil pregnancy

A

Pregnancy: No adverse events in animal reproduction studies; minimal data; not
recommended
Unknown if excreted in breast milk

59
Q

NRTI adrs

common and serious adrs

A
  • Common: N/V/D, upset stomach, headache
  • Serious: bone marrow suppression (and associated increased risk of bleeding or oral ulcers), peripheral neuropathy, pancreatitis, lipoatrophy, hepatic steatosis, lactic acidosis
60
Q

NRTI contraindications

A
  • Abacavir and moderate or severe hepatic insufficiency
61
Q

NRTI ddi

A
  • Tenofovir products and high-dose or multiple NSAIDs  May enhance nephrotoxic effects of tenofovir
  • Category D: Consider Therapy Modification
62
Q

nnrtis adr

common ones, sedation? serious adr?

A
63
Q

Rilpivirine must be administered with?

A

Rilpivirine must be administered with a full meal to increase absorption
(better absorbed with acids)

64
Q

Rilpivirine*
PLUS ddi

A
65
Q

Efavirenz or Etravirine ddi

A
66
Q

Protease Inhibitors and P450

A
  • CYP3A4 substrates
  • Often “boosted” by pharmacokinetic enhancers
67
Q

protease inhibitors adrs

A
68
Q

oral adverse effects of these PIs
* Fosamprenavir -
* Atazanavir -
* Ritonavir -

A
  • Fosamprenavir - Perioral numbness (lips), taste changes
  • Atazanavir - Dental (tooth) pain, taste changes
  • Ritonavir - Taste changes
69
Q

Darunavir ddi with:

A
70
Q

Atazanavir ddi with:

A
71
Q

Fosamprenavir ddi with:

A
72
Q

INSTIs general adrs

A
  • Generally well tolerated
  • Increased weight gain, insomnia, dizziness
73
Q

INSTIs: DDIs
* Raltegravir PLUS:

A
  • Proton pump inhibitors= may increase concentrations of raltegravir
  • Category B: No Action Needed
74
Q

Pharmacokinetic Enhancers general adrs

A

gi upset

75
Q

Pharmacokinetic Enhancers dentistry related adrs

A
  • Ritonavir: Metallic or bitter taste, oral ulcers or inflammation, perioral numbness/tingling, increased bleeding risk (if DDI with anticoagulants)
  • Dry mouth
76
Q

Ritonavir ddis with:

A
77
Q

Cobicistat ddis with:

A
78
Q

allylamines adrs/ddi

A
  • Little drug interaction potential
  • Few side-effects
79
Q

Clotrimazole (Mycelex) dosage
* Metabolized in? contraindicated in?
* Avoid in combination with?
* Oral Troche?

A

10mg (1 troche) dissolved slowly 5 times daily for 7-14 days
* Metabolized in liver – 3A4. Contraindicated in liver disease.
* Avoid in combination with benzodiazapines; HIV
* Oral Troche for management of oral candidiasis

80
Q

triazoles ddi

A

Fewer drug-drug interactions and expanded spectrum
* Still metabolized via the cytochrome P450 enzyme system
* All azole agents are both metabolized by and slow down hepatic cytochrome P450 activity

81
Q

triazole side effect profiles

A

Safer side-effect profiles than ketoconazole for systemic use

82
Q

Fluconazole (Diflucan)
* absorb
* t1/2
* excretion where
* ddi
* preg category
*

A

second gen azole

83
Q

Drugs that Stimulate Metabolism of Azoles

A
84
Q

Viscous Lidocaine
* Relieves?
* IMPORTANT
* Use how much?
* action

A
  • Topical anesthetic
  • Relieves pain associated with irritated oral/pharyngeal mucous membranes
  • IMPORTANT: ingesting too much can lead to arrhythmias
  • Use minimal amounts
  • Swish and SPIT
85
Q

Dental Concerns: Bisphosphonates

associated with? mechanism? precipitated by?

A
86
Q

BP duration and MRONJ

A

increased incicdence when used over longer times

87
Q

Denosumab Risk of MRONJ

high and low doses

A

 High Dose Denosumab : High prevalence (2-5% Osteonecrosis)

88
Q

Mechanism of MRONJ

A

 Profound and prolonged inhibition of bone resorption with over-suppression of bone remodeling (ie, low bone turnover), and infection are the main mechanisms
 Postulated that MRONJ is a form of avascular necrosis, possibly caused by inhibition of angiogenesis.

89
Q

what limits chemotherapeutics use?

A

Adverse reactions limit use
 GI disturbances (N/V/D)
 Hair loss
 Bone marrow suppression
(anemia, increased infection risk)

90
Q

alkylating agents ADRs/toxicity

A

oppurtunistic infections possible=thrush

91
Q

platinum compounds nn adr

A

Neurotoxicity
 Drugs enter into the dorsal root ganglion and binds to DNA, causing apoptosis.
 Platinum compounds form intrastrand adducts and interstrand crosslinks altering tertiary structure of DNA. This promotes alterations in cell-cycle kinetics, leading to an attempt of
differentiated postmitotic dorsal root
ganglion neurons to re-enter cell cycle,
which leads to the induction of apoptosis
Regardless of the mechanism, apoptosis results in secondary damage to peripheral nerves

92
Q

Oxaliplatin association with:
 Cold-induced?
 breathing?
 Mm?
 Jaw?
 swallowing?
 mm appearence?
 Voice?
 Ocular?

A

pain triggered by exposure to cold liquids
Cold-induced perioral paresthesias – 95%
 Cold-induced pharyngolaryngeal dysesthesia – 92%
 Dyspnea – 40%
 Muscle cramps – 34%
 Jaw stiffness – 34%
 Dysphagia – 30%
 Visible fasciculations – 30%
 Voice changes – 6%
 Ocular changes – 0.7%

93
Q

methotrexate dental note

A

Dental Note: oral mucositis
 Oral pain; Erythema; Difficulty opening the mouth
 DNA cycle specific agents are most stomatotoxic
 Methotrexate, etoposide known to be secreted into the saliva
 further increasing stomato toxicity potential

94
Q

DNA cycle specific agents associated with oral mucositits

A

Methotrexate
5FU
Cytarabine
Doxorubicin
Etoposide
Bleomycin

95
Q

what can be seen orally with cytotoxic abx?

A

mucositis

96
Q

vinkaalkloids/ vincristine toxicity

A

 Peripheral neuropathy-numbness, tingling
 Neurotoxicity may also be persistent, deep aching and burning pain that mimics a toothache

97
Q

Side Effects: Cell Replication Inhibition

A

 Primarily GI tract, Bone marrow, Oral cavity
 Mucositis painful inflammation along GI
 Develops within 1-week of chemotherapy initiation
 Stomatotoxic (toxic effects on the oral tissues)
 Impairment of bone marrow (myelosuppression)
 suppressing white blood cells, red blood cells, and platelets
 GET LABS THE DAY BEFORE ANY PROCEDURE
 WBC >2000
 ANC >2000
 Platelets >75,000

98
Q

Oral Complications Common to Chemotherapy & Radiation

A

Oral mucositis (20-40%)
Infection
Xerostomia/salivary gland dysfunction
Functional disabilities
Taste alterations
Nutritional compromise
Abnormal dental development

99
Q

Oral mucositis with Chemotherapy & Radiation

A

inflammation and ulceration of the mucous membranes
 can increase the risk for pain, oral and systemic infection, and nutritional compromise

100
Q

Infection with Chemotherapy & Radiation

A

viral, bacterial, and fungal
 from myelosuppression, xerostomia, and/or damage to mucosa from chemotherapy or radiotherapy

101
Q

Xerostomia/salivary gland dysfunction with Chemotherapy & Radiation

A

dry mouth d/t thickened, reduced, or absent salivary flow
 increases the risk of infection and compromises speaking, chewing, and swallowing
 persistent dry mouth increases the risk for dental caries

102
Q

Functional disabilities with Chemotherapy & Radiation

A

impaired ability to eat, taste, swallow, and speak
 due to mucositis, dry mouth, trismus, and infection

103
Q

Taste alterations with Chemotherapy & Radiation

A

changes in taste perception of foods, ranging from unpleasant to tasteless

104
Q

Nutritional compromise with Chemotherapy & Radiation

A

eating difficulties due to mucositis, dry mouth, dysphagia, and loss of taste

105
Q

Abnormal dental development with Chemotherapy & Radiation

A

altered tooth development, craniofacial growth, or skeletal
development in children secondary to radiotherapy and/or high doses of chemotherapy before age 9

106
Q

Taste Alterations - Chemotherapy

A

Common occurrence following
chemotherapy administration
 Lasts 3-4 weeks post-treatment

107
Q

common meds of taste of alterations

A

 Cisplatin
 Cyclophosphamide
 Doxorubicin
 5-Fluorouracil
 Methotrexate
 Paclitaxel
 Vincristine

108
Q

Neurotoxicity of chemo

side effects of what rx’s

A

Persistent, deep aching and burning pain that mimics a toothache, but no dental or mucosal source can be found.
 side effect of certain classes of drugs (vinca alkaloids; platinum compounds)

109
Q

Bleeding with chemo

A

oral bleeding from the decreased platelets and clotting factors

110
Q

Radiation caries:

A

Radiation caries: lifelong risk of rampant dental decay that may begin within
3 months of completing radiation treatment if changes in quality or quantity of saliva persist

111
Q

Osteonecrosis with radiation

A

blood vessel compromise and necrosis of bone exposed to high-dose radiation therapy; results in decreased ability to heal if traumatized

112
Q

Cyclosporine – Side Effects

A
113
Q

Cyclosporine AND Tacrolimus DDIs

A

 Cimetidine (Tagamet)
 Clarithromycin (Biaxin)
 Erythromycin
 Corticosteroids
 Fluconazole (Diflucan)
 Itraconazole (Sporanox)
 Ketoconazole (Nizoral)

114
Q

Cyclosporine AND Tacrolimus Cimetidine DDI

A

Reports implicate cimetidine and
famotidine as increasing
cyclosporine concentrations and/or
decreasing cyclosporine clearance

115
Q

Clarithromycin and tarcolimus

A

One report describes 2 female
patients (aged 37 and 69
years), who each experienced
acute renal failure and more
than a 2.3-fold increase in
tacrolimus serum
concentrations after 9 doses of
clarithromycin therapy (250
mg daily)

116
Q

Corticosteroids and cyclosporine

A

Toxic effects of prednisone and/or
cyclosporine, if agents combined

117
Q

Azoles and cyclosporine concentrations

A

Serum cyclosporine concentrations have been reported to
increase as much as tenfold in transplant patients
following the initiation of azole antifungal agents

118
Q

what bp has the highest risk for MRONJ

A

zolendronate

pharm 2 (20 decks)

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