Chapter: Pharmacy Foundation II (other) Flashcards
DEFINE
- Urticaria (hives)
- Pruritis (Itching)
- Erythema
- Angioedema
- Morbilliform
1. Urticaria (hives): A rash with red/pinkish raised patches. The patches have varied shapes and sizes.
2. Pruritis (Itching): Any rash or reaction that causes itching can be referred to as with pruritus.
3. Erythema: Redness on skin from superficial (near the surface) capillaries, often due to inflammation, often with pruritis. When pressed down. the red skin that is ue to erythema will blanch (whiten) temporarily because the blood flow is blocked. Erythematous refers to an area on the skin, such as a patch, with erythema.
4. Angioedema: Angioedemam swelling caused by edema in the deeper dermal, cutaneous and sub-mucosal tissue
5. Morbilliform: Macular or maculopapular (or both), with 1-10 mm lesions. In between the lesions is healthy skin.
Adverse Drug Reaction (ADR) vs. Error
Medication error - something wrong occurred
ADRs are categorized into two types: predictable (Type A) and unpredictable (Type B) reactions
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TYPE A REACTION - what is it ?
Type A reaction are dose dependent, related to the known pharmacologic properties of the drug. Can occur to any patients. Type A reaction are the most common and account for ~85% of ADRs. Examples are: orthostatic hypotension with doxazosin and nephrotox with aminoglycoside
ADRs are categorized into two types: predictable (Type A) and unpredictable (Type B) reactions
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TYPE A REACTION - what is it ?
Type A reaction are dose dependent, related to the known pharmacologic properties of the drug. Can occur to any patients. Type A reaction are the most common and account for ~85% of ADRs. Examples are: orthostatic hypotension with doxazosin and nephrotox with aminoglycoside
ADRs are categorized into two types: predictable (Type A) and unpredictable (Type B) reactions
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TYPE B REACTION - what is it ?
Type B reactions are adverse drug reactions that are not dose-dependent and are unrelated to the pharmacologic actions of the drug. These reactions can be influenced by patient-specific factors, such as genetics. While the majority of type B reactions are caused by exposure to the active ingredient in the drug, inactive ingredients (excipients) can also be implicated.
Type B reactions can be categorized as immediate or delayed. Immediate reactions occur within 60 minutes after exposure, while delayed reactions occur days to months after exposure.
There are several types of type B reactions:
1. Drug allergies: These reactions have a definite immune mechanism, such as antibody- or T cell-mediated responses. Drug allergies are not hereditary.
2. Drug hypersensitivity reactions (DHRs): These reactions clinically resemble drug allergies but may or may not be immune-mediated. DHRs do not always result in a contraindication to future administration of the drug.
3. Idiosyncratic reactions: These reactions arise from genetic differences. Certain medications are more likely to cause idiosyncratic reactions in patients with specific genetic traits. For example, certain drugs can induce hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Type of Drug Allergies (Type I - IV)
Intolerance VS. Allergies?
List of Drugs That Are Assoiated With Photosensitivity
Thrombotic Thrombocytopenic purpura: what is it/ what drug can cause it?
Thrombotic thrombocytopenic purpura (TTP) is a blood disorder characterized by widespread clot formation, resulting in consumption of platelets and bleeding under the skin, leading to purpura (bruises) and petechiae (dots). TTP can be life-threatening and requires immediate treatment with plasma exchange.
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Common drug that can cause it: Oral P2Y12 inhibitors (e.g. clopidogrel), Sulfamethoxazole
There are several severe skin reactions that can be caused by drugs, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). All of these can be life-threatening and require prompt treatment. LIST THE DRUG MOST ASSOCIATED WITH SEVERECUTANEOUS ADR
Note: Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) involve severe skin detachment equivalent to third-degree burns, usually occurring 1-3 weeks after drug administration, often more than 72 hours after. These reactions lead to mucosal erosions, high body temperature, fluid loss, and organ damage. Treatment involves stopping the offending agent promptly, fluid/electrolyte replacement, wound care, and pain management. Systemic steroids are C/I for TEN but may be used cautiously in SJS, though their benefit is debated.
Anaphylaxis Treatment: S/Sx urticaria (hives), swelling of the mouth and throat, difficulty breathing or wheezing sounds, abdominal cramping and hypotension
Treatment includes epinephrine injection ± diphenhydramine ± steroids± IV fluids
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a single-use epinephrine auto-injector (EpiPen, Auvi-Q, Adrenaclick, Symjepi) - concentration of 1 mg/mL.
Epi Auto-injector Admin
Common Drug Associated with Allergic Reaction
Beta Lactams
Beta-lactam antibiotics, including penicillins, cephalosporins, carbapenems, and monobactams, are commonly associated with drug allergies. Reactions can range from mild rash to severe anaphylaxis. If someone is allergic to one beta-lactam antibiotic, they are usually considered allergic to others in the same class. It is generally recommended to avoid the entire class unless evaluated by a healthcare provider. There is a small risk of cross-reactivity between penicillins and cephalosporins/carbapenems, so caution should be exercised. HOWEVER, ON THE NAPLEX IF SOMEONE HAS BETA LACTAM ALLERGIES BETA LACTAM SHOULD BE AVOIDED.
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In the case of non-severe penicillin allergies, 2nd- or 3rd-generation cephalosporins may be used for acute otitis media. Aztreonam, a monobactam, is considered safe for patients with an immediate-type penicillin allergy.
Common Drug Associated with Allergic Reaction
Sulfa Drugs
Reactions are commonly associated with sulfamethoxazole (Bactrim), and patients should avoid sulfasalazine, sulfadiazine, and sulfisoxazole. While some medications like thiazide diuretics, loop diuretics, sulfonylureas, acetazolamide, zonisamide, celecoxib, cidofovir, darunavir, fosamprenavir, and tipranavir have warnings for sulfa allergy, they usually don’t cross-react with sulfamethoxazole. Cross-reactivity risk with sulfamethoxazole, thiazides, and loop diuretics is low.
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On the NAPLEX exam you should recognize the possible interaction. Sulfite or sulfate allergies
do not cross react with sulfonamides
Common Drug Associated with Allergic Reaction
PEANUTS AND SOY
Drugs to avoid with a peanut or soy allergy include clevidipine (Cleviprex), propofol (Diprivan)
Common Drug Associated with Allergic Reaction
EGGS
If a patient has a true allergy to eggs, they cannot use
clevidipine (Cleviprex), propofol (Diprivan) or Yellow Fever vaccine.
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Flublok and Flucelvax contain no egg proteins and can be used in patient with severe egg allergies
What are the implications of a reported penicillin allergy, and how can penicillin skin testing help manage patients’ antibiotic options and risk of hypersensitivity reactions?
Penicillin allergy is the most common drug allergy in the U.S., reported in about 10% of the general population. However, a true penicillin allergy is found in only about 10% of those reported cases. Some patients incorrectly report a penicillin “allergy” when their reaction was more appropriately categorized as an intolerance, such as nausea or diarrhea. Over time, antibodies to penicillin can wane, allowing patients who previously had a true allergic reaction to safely receive penicillins.
Due to concerns about cross-reactivity with cephalosporins and carbapenems, a reported penicillin allergy can severely limit the selection of antibiotics available to treat infectious diseases. Patients who report a penicillin allergy are more likely to receive broad-spectrum antibiotics, like quinolones, and antibiotics with greater toxicity potential, such as vancomycin.
The goal of penicillin skin testing is to identify patients at the highest risk of a Type I hypersensitivity reaction if exposed to systemic penicillin. The test uses the components of penicillin that most often cause an immune response. Pre-Pen (benzylpenicilloyl polylysine injection) is used with very dilute solutions of penicillin G for a step-wise skin test, including a skin prick test followed by intradermal testing. A localized reaction around the Pre-Pen or penicillin G test site indicates a high risk of a reaction to systemic penicillin, and the patient should not receive it.
A patient with a negative skin test, showing no reaction to the test solutions, can be considered to be at the same risk as a patient in the general population who does not report a penicillin allergy. It’s important to note that skin testing only predicts an IgE-mediated reaction. Regardless of skin test results, a patient should never be re-challenged with an agent that caused an allergic reaction or severe adverse event.
How does induction of drug tolerance (desensitization) work, and when might it be recommended for patients with drug allergies?
When faced with a drug allergy and no acceptable alternative, induction of drug tolerance (desensitization) may be recommended. This involves administering small doses of the medication, gradually increasing them to the target dose to modify the patient’s response temporarily. Desensitization must occur in a medical setting with emergency care available. Treatment with the drug must follow immediately and not be interrupted to avoid re-sensitization of the immune system. Desensitization protocols exist for various medications, but it’s crucial to avoid this process if the agent previously caused severe reactions like SJS or TEN.
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For example, if a pregnant patient has syphilis and a penicillin allergy, the CDC recommends desensitization and penicillin treatment, rather than using second-line agents
Assessing Causality of an ADR
The Naranjo Scale, a validated causality assessment tool, assists in determining the likelihood that a drug caused an adverse reaction. It assigns a probability score based on a questionnaire, with scores indicating: +9 = definite ADR, 5 - 8 = probable ADR, 1 - 4 = possible ADR, and 0 = doubtful ADR
How do healthcare professionals report side effects, adverse events?
Report side effects, adverse events, and allergies to the FDA’s MedWatch program, known as the FDA Adverse Event Reporting System (FAERS). Vaccines are reported separately under VAERS. The FDA may mandate Phase IV surveillance programs for approved drugs and biologics to gather real-world safety data, enhancing understanding of drug safety profiles.
PharmGenomics Terms
Deoxyribonuc Acid (DNA)
Genetic information Inherited from both parents that is present in two long chains of nucleotides, joined together by hydrogen bonds and twisted into a double helix.
PharmGenomics Terms
Nucleotide
Subunits. In DNA, the bases consist of two purines (adenine and guanine) and two pyrimidines (thymine and cytosine). In RNA, uracil is present instead of thymine.
PharmGenomics Terms
Chromosome
Chromosomes contain genes.
Human cells contain 23 pairs of chromosomes.
PharmGenomics Terms
Gene
Specific sequence of nucleotides that code (provide instructions) for a single protein. Think of it as blueprint of life!
PharmGenomics Terms
Allele
Specific form of gene. Wild-type is usually the most commonly occurring allele. Two identical alleles make up a homozygous genotype and two different alleles make up a heterozygous genotype
PharmGenomics Terms
Genotype vs Phenotype
Genotype: The set of unique genes that determine a specific trait in an individual
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Phenotype: An observable trait (outward expression) of the genotype, such as hair color and sickle cell disease
PharmGenomics Terms
Single nucleotide
polymorphism (SNP)
A change in a single nucleotide in a genetic sequence (e.g., C replaced by G). SNPs are the most common genetic alteration in DNA…SNPs are responsible for the majority of individual variability in response to a drug.
PharmGenomics Terms
Polymorphism
An inherited variation in the DNA sequence (such as a SNP or Structural variation).
PHARMACOGENOMIC TESTING AND PHARMACIST ACTION
Abacavir (Ziagen)
+ abacavir-containing combination
drugs (e.g., Triqumeq, Epzicom)
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Test? Result/ Action?
HLA-B*5701 - Test all patients prior to starting. Serious and fatal hypersensitivity reactions have occurred
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If positive, do not use!
PHARMACOGENOMIC TESTING AND PHARMACIST ACTION
Allopurinol (Zyloprim, Aloprim)
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Test? Result/ Action?
HLA-B*5801 - Increased risk of Stevens-Johnson syndrome (SJS) if positive
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If positive, do not use!
PHARMACOGENOMIC TESTING AND PHARMACIST ACTION
Carbamazepine (Tegretol;
Oxcarbazepine (Trileptal);
Phenytoin (Dilantin);
Fosphenytoin (Cerebyx)
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Test? Result/ Action?
HLA-B*1502 - Increased risk of serious skin reactions, including SJS and toxic epidermal
necrolysis (TEN), have occurred. Test all Asian patients before starting carbamazepine
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If positive, do not use!
Consider medications affected by CYP450 polymorphisms, as variations in these enzymes can contribute significantly to medication response variability. - Clopidogrel (Plavix)
CYP2C19- Clopidogrel, a prodrug, requires conversion to its active form by the CYP2C19 enzyme. The*1 allele of CYP2C19 is fully functional, while the 2 and3 alleles indicate reduced metabolism, resulting in poor metabolizers who produce less active metabolite.
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*2 and *3 alleles? consider alternative treatment.
Consider medications affected by CYP450 polymorphisms, as variations in these enzymes can contribute significantly to medication response variability. - Codeine
CYP2D6- Codeine, a prodrug, is metabolized to morphine by CYP2D6. Ultra-rapid metabolizers, experiencing extensive conversion to morphine, face a heightened risk of opioid overdose due to excessive CNS effects, including respiratory depression. Infant deaths have occurred when nursing mothers, who were ultra-rapid metabolizers, took codeine, resulting in excessive morphine transfer to infants through breast milk.
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If a known CYP2D6 ultra -rapid metabolizer, do not use
Consider medications affected by CYP450 polymorphisms, as variations in these enzymes can contribute significantly to medication response variability. - Warfarin (Coumadin/ Jantoven)
CYP2C9*2 and *3 and VKORC1- increased bleeding risk due to decreased function of
~ lleles and haplotypes (CYP2C9’2 and 2C9”3) and
VKORC1 G > A variant
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If these allele variations are known to be present, start with a lower dose.
Other Pharmacogemonic Test
Trastuzumab (Herceptin) - and other HER2 inhibitors!: What test and that results/action to take
These drugs are HER2 inhibitors; they require overexpression of HER2 for efficacy!
If tumor is HER2 negative, drugs are not effective.
Other Pharmacogemonic Test
Cetuximab (Erbitux): What test and that results/action to take
KRAS mutation - Only patients who are KRAS mutation -negative (ie. are wild-type) should receive these medications. They are not effective in patients with colorectal cancer who are positive for the KRAS mutation
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If positive for a KRAS mutation , do not use.
Other Pharmacogemonic Test
Azathioprine (Azasan, lmuran): What test and that results/action to take
Thiopurine methyltransferase (TPMT)
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low/ absent TPMT activity increased risk of severe, life threatening myelosupp! If TPMT activity is low/absent , start at a very low dose or use alternative agent
Other Pharmacogemonic Test
Capecitabine (Xeloda); Fluorouracil: What test and that results/action to take
DPD deficiency
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Dihydropyrimidine dehydrogenase (DPD) deficiency increase risk of severe toxicity (diarrhea, neutropenia ,
neurotoxicity). If DPD deficient, do not use
SELECT DRUGS WITH
PHARMACOGENOMIC IMPLICATIONS
Supplements that can increase bleed risk
■ The “5 Gs”: garlic, ginger, ginkgo, ginseng and glucosamine
■ Fish oils (at higher doses)
■ VitaminE
■ Dong quai
■ Willow bark (a salicylate); do not use with anticoagulants
St. John’s Wort and what does it interact with?
■ SJW induces CYP450 3A4, 2C19, 2C9, 1A2 and p-glycoprotein (P-gp), which lowers levels of other drugs (with possible treatment failures) ….Do not use with many drugs, including oral contraceptives, transplant drugs and warfarin.
■ SJW is serotonergic and is often implicated in serotonin syndrome … Do not use with MAO inhibitors, including linezolid… Concurrent use with other serotonergic drugs can be dangerous, especially at higher doses, including SSRis
and SNRis.
■ SJW causes photosensitivity and requires counseling on sun protection and avoidance. Avoid with other photosensitive drugs
■ SJW may lower the seizure threshold.
SUPPLEMENTS WITH RISK OF LIVER TOXICITY
■ Black cohosh (used for menopausal symptoms)
■ Kava (used for anxiety)
■ Chaparral, comfrey
■ Green tea “extracts”
SUPPLEMENTS WITH RISK OF CARDIAC
TOXICITY
- Ephedra’s removal from the market stemmed from cardiac toxicity reports. Bitter orange (Citrus aurantium or synephrine) replaced ephedra in various products. Both ephedra and bitter orange/synephrine are stimulants known for dose-dependent cardiac toxicity, elevating blood pressure and heart rate.
- DMAA (dimethylamylamine) is an amphetamine derivative that is used in body-building/performance-enhancement products
- Yohimbe is used to increase libido and for erectile dysfunction.
- Licorice contains glycyrrhizin