Adverse Effects Flashcards by Julia B

Susceptibility Alleles Associated with ADR for Ethanol

ALDH2*2 (G1510A; Glu487Lys) is an inactive allele →

‘Asian flush’ sx due to accumulation of acetaldehyde (genetic Disulfiram)

↑ ikelihood of esophageal ca in chronic alcoholics

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Susceptibility Alleles Associated with ADR for Phenytoin

Inactive CYP2C9 and CYP2C19
alleles → improper drug metabolism → drug accumulates → ADR (ataxia, slurred speech, decreased coordination and mental confusion)

Hyperactive MDR1 promoter allele → high levels of MDR1 protein at BBB → not enough drug available to inhibit VGSC → non- responder

Low affinity VGSC allele→ ↓ binding of drug to VGSC protein → non-responder

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Susceptibility Alleles Associated with ADR for 5-fluorouracil (5FU)

~3% of pt pop heterozygous for inactive ‘A’ allele found in intron (dominant allele)
→ improper splicing → inactive DPD enzyme → 5FU not properly inactivated

Potential fatal myelosuppression

2R/2G,2R/2Cor3R/3C allele of TS gene (also known as TYMS gene) has low transcriptional activity l→ low levels of TS enzyme → patients responsive to 5FU

3R/3GalleleofTS(or TYMS) gene has high transcriptional activity → high levels of TS enzyme→ patients non-responsive to 5FU

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Susceptibility Alleles Associated with ADR for Codeine

Inactive allele (poormetabolizer): multiple inactive alleles such as CYP2D6*10 → poor to no conversion of codiene

CYP2D6*2xN allele(ultra-metabolizer): ultra efficient conversion of codeine → too much conversion to morphine → fatal respiratory depression

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Susceptibility Alleles Associated with ADR for Warfarin

Multiple alleles including CYP2C92 and CYP2C93 (most prevalent inactive alleles in European American population) → ADR

VKORC1”A”allele has low transcriptional activity and associated with ADR (↑ likelihood of excessive bleeding)

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Benzimidazole

GI disturbance

Bone marrow suppression

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Ivermectin

Mazzotti-like rxn due to dying microfilariae → use steroids

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Pyrantel Pamoate

GI disturbances

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Diethylcarbamazine

Mazzotti-like rxn due to dying microfilariae → use steroids

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Praziquantal

GI disturbances

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Artemisinins

Rare, dose‐related and reversible

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ACT with Lumefantrine

Coartem

GI distress, HA, N/V

Cardiac arrhythmias/neuro sx w/ high doses

If vomit in 1st 30 mnin → reapeat dose

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Chloroquine Phosphate

Visual disturbances

Puritis on palms and feet in AA

Discoloration of nail beds/mucous mem

Parenteral doses >5g → fatal

Toxicities w/ high dosr → CV and CNS

Hemolysis (↑ w/ G6PD deficiency)

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Quinne Sulfate

Cinchonism: tinnitus, deafness, visual disturbance, HA, N/V dizziness, postural hypotension (reversible)

Blackwater fever: black urine, severe hemolysis, hemoglobinemia, hemoglobinuria →
STOP Tx

Hypoglycemia, hypotension

Fatal oral dose = 2-8 g

Hemolysis (↑ w/ G6PD deficiency)

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Primaquine

Hemolytic anemia in G6PD deficiency

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Isoniazid (INH)

Hepatic toxicity (especially in slow acetylators) → age dependent >35 yo

Potentially fatal hepatitis

Peripheral neuropathy (↑ in slow acetylateors) due to vit B6 AKA pyridoxine deficiency

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Pyrazinamide

Hepatic toxicity

Hyperuricemia 100% of pts → exacerbates gout

Arthralgias

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Ethambutol

Optic neuritis (rare) but causes red-green color blindness

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Rifampin

May turn urine, tears and other body fluids reddish orange → can premanently stain contact lenses

Streptomycin

Ototoxicity

Nephrotoxicity

Bedaquiline

↑ Hepatic transaminases → monitor liver fn

BBW: ↑ risk death due to arrhythmias and QT prolongation

Amhotericin B

Most related to binding to cholesterol in cells of host

Chills, fever, muscle spasms, HA, vomiting, hypotension → ↓ by slow infusion and premed w/ antipyretics and antihistamiens as wella s sodium loading to ↓ renal damage

Renal damage w/ LT use (reverisble at first then irreversible) → limit cumulative dose (2 g)

Nystatin

too toxic for parenteral administration

Azoles

Many drug-drug interactions because all inhibit human P450s

Fluconazole

Potent inhibitor of CYP2C9 → ↑ serum conc of phenytoin and warfarin Rash, Stevens-Johnson syndrome Nausea and alopecia w/ longer tx

Itraconazole

Congestive heart dz Potent CYP3A4- do not use with some statins, midazolam, triazolam Absorption ↓ by PPI and H2 antagonists

Voriconazole

Visual disturbances common → blurring, changes in color vision or brightness usually only during first 30 min of dose and is reversible CYP2CP, 2c!( and 3A4 inhibitor → drug interactions

Caspofungin

Hepatotoxicity (↑ in combo w/ cyclosporine) GI discomfort, flushing Drug interactions

Griseofulvin

P450 inducer → ↑ metabolism of drugs like warfarin and phenobarbital CNS effects, allergic syndrome, hepatotox, GI disturb

Terbinafine | Lamisil

Well tolerated w/ some GI disturbances and HA No P450 or drug interactions

Flucytosine

Hematotoxicity (anemia, leukopenia, thrombocytopenia)

Acyclovir

Well tolerated- N/D, HA IV admin- renal and neuro tox (prevent w/ hydration and slow infusion)

Ganciclovir

Myelosuppression

Foscarnet

Renal toxicity Hyperphosphatemia, hypokalemia/calcemia/magnesemia Chromosome damage, arrhythmias, seizures

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Mitochondrial toxicity Lactic acidosis w/ hepatic steatosis is May occur → life threatening (due to NRTI mediated inhibition of mitochondrial fn causes build up of Tg leading to hepatic steatosis)

Abacavir

MI Hypersensitivity rxn can be fatal → associated w/ HLA-B*5701 polymorphism Skin rash

Tenofovir (AF/DF)

Fatigue, muscle weakness, flatulence Renal accumulation → tubular necrosis, renal failure, Fanconi's Syndrome (Less w/ AF) Bone loss/osteopenia (much less w/ AF)

Efavirenz

Nightmares/psych disturbances as pt starts therapy → resolves over time Extensive metabolism/induction via P450 (CYP3A4) → drug-drug interactions

HIV protease Inhibitors

Lipodystrophy (redistribution and accumulation of body fat) ↑ TG/LDL MI, hyperglycemia, insulin resistance, bleeding in hemophilia, hepatotox CYP3A4 metabolism → drug-drug interactions

Ritonavir

↑ TG/LDL ↑ serum aminotransferase levels

St. John’s Wort

Photosensitivity Drug Interactions Sedation w/ SSRI ↑BP and ↑HR w/ MAOI ↓ levels of many other drugs including HIV protease inhibitors, oral contraceotives, anti-leukemia drug imatinib mesylate (Gleevec)

Ginseng

CNS excitation, abnormal menstruation, hypoglycemia Drug interaction: interferes w/ digoxin assays

Black Cohosh

Serious liver toxicity (rare) Should not be used if liver dz is present D/c if sx such as abdominal pain, dark urine or jaundice appear

Glucosamine

Not FDA approved, evaluated or recommended for OA→ not quality controlled/monitored

Fish Oil (Omega 3)

May ↑ LDL (“bad cholesterol”) At high doses (> 3 g qd) ↑ risk of bleeding→ caution w/ blood thinners and NSAIDS May ↓ Vitamin E levels

Kratom

Addiction, N/V, constipation, confusion Kratom is a controlled substance in 16 countries including Germany, Thailand, Malaysia, Sweden Kratom is banned in 15 US states 36 deaths confirmed in USA – most when mixed with other agents including opioids