Lecture 1- Allergies and Side Effects

adverse drug event (ADE)

harm cause by a drug at any dose

• includes ADR and toxicity

adverse drug reaction (ADR)

• harm cause by a drug at NORMAL DOSES AND USE

• expected or unexpected (causal relationship)

toxicity

• formal: ADE caused by excessive dosing

  • ex .respiratory depression, coma, and death from opioid overdose

• real world: severe ADR/ADE regardless of dose

  • ex. drugs causing cardiotoxicity, hepatotoxicity,

allergy

• ADR caused by an IMMUNE RESPONSE

  • ex. anaphylactic response to penicillin

side effect

• expected, known effect of a drug (other than intended effect) at NORMAL dosees with normal use

  • ex. antihistamines used for allergies→ drowsiness

medication error

• mishaps during prescribing, transcribing, dispensing, administering adherence, or monitoring of a drug

• may or may not cause harm (if harm= causal relationship)

  • ex. wrong dose, wrong drug, wrong instructions, etc

mild adverse drug reaction

• digestive disturbances

  • nausea, diarrhea, constipation

• headaches

• fatigue

• vague muscle aches

• malaise

• changes in sleep patterns

moderate adverse drug reactions

• rashes

• hives

• visual disturbances

• muscle tremor

• difficulty with urination

• any perceptual change in mood or mental functions

• changes in blood components such as temporary, reversible decrease in whole WBC count or in blood levels of some substances such as glucose

severe adverse drug reactions

• liver failure

• anaphylaxis

• abnormal heart rhythms

• certain types of allergic rxns

• persistent or significant disability or hospitalization

• cause birth defects

lethal adverse drug reactions

• cause death

• ex. anaphylaxis

most important aspect of identifying adverse druf reactions

timing

• did sympoms appear shortly after beginning drug?

• did symptoms resolve after stopping use?

• did symptoms reappear when restarted?

• do symptoms align with drug therapy or could other drugs/supplements explain?

drug interaction

when one substance (or multiple) affects to efficiency, effects, or safety of a drug

outcomes of drug interactions

• increase drug actions (therapeutic effects or side effects)

• decrease drug actions (therapeutic effects or side effects)

• novel effects

  • create intense new rxn

additive drug interaction

combined effect of two drugs equals the sum of the effect of each agent given alone (1+1=2)

• ex. insulin and sulfonylurea → increase in hypoglycemia risk

synergistic drug interactions

combined effect exceeds the sum of the effects of the efrfects of each drug given alone (1+1=4)

• potentiation: creation of toxic effect from oe drug due to the presence of another drug

• ex. tylenol and alcohol → increase liver failure risk

antagonistic drug interactions

interference of one drug with the action of another (1+1 = 0.5)

• morphine and nalozxone combo will decrease morphine effects

direct chemical or physical interactions

• usually when combining IV drugs, renders BOTH drugs inactive

• nothing is mediated by the body

pharmacokinetic interactions

what your body does to the drug

affects:

• absorption

• distribution

• metabolism

  • enzyeme inhibition/induction

• excretion

pharmacodynamic interactions

what the drug does to your body

• potentiation: creation of toxic effect from one drug due to the presence of another drug

• inhibitory: when one drug cancels out or reduces the effect of another drug

combined toxicity

if drug A and B are both toxic to the same organ, then taking them together will cause more injury

enzyme inducers

• increase rate of drug metabolism- INCREASED CYP450

• may decrease effectiveness/concentration/action of drug

• may need higher dose to achieve desired effect

enzyme inhibitors

• decrease rate of metabolism- decreased CYP450

• may increase risk of toxicity/adverse effects

• may need lower dosage

evaluating risk vs benefit

frequency→ likelihood → monitoring → risk → alternatives

expected duration/use of medication

• length of drug exposure may impact clinical significance of interaction

• ex1.

  • fluconazole x 1 dose prn is not elevated risk of bleeding with concomitant use

  • fluconazole 400mg PO BID x 1 year→ elevated risk of bleeding with concomitant use

minimizing drug adverse reactions

• FDA approved medications guides

• patient package inserts (PPI)

• boxed warnings

• REMS

REMS (risk evaluation and mitigation strategies)

• include communication component about the specific safety risk or risks that the REMS in intended to mitigate

• some include additional requirements such as clinical activities that the health care providers may need to perform prior to prescribing or dispensing a medication to the pt

• can require medication guide as part of REMS program

• ex. acutane- pregnancy tests, contraception

side effect

expected, unavoidable, known effects pf drug at normal doses

ADR

expected or unexpected harm caused by a drug at normal doses

drug hypersensitivity reaction (DHR)

• reproducible S/Sx from drug exposure

• an ADR tha tis mostly unpredictable, caused by immune or non-immune mechanism

drug allergy

• immunologically mediated drug hypersensitivity reaction

• hyper-response to antigenic drug leads to organ-specific or systemic reaction

type I (allergic rxn)

• IgE mediated immediate release of inflammatory mediators

• immediate (within 1 hour)

• anaphylaxis, seasonal allergies, food allergies, hives, eczema, asthma, angioedema

• common triggers: PCN, blood products, vaccines

type II (cytotoxic hypersensitivity)

• cytolysis by IgG and complement

  • mistakenly attack own cells

• delayed (>72 hours)

• hemolytic anemia

• common triggers: PCN, heparins, sulfonamides

type II ( immune complex)

• antigen -antibody (IgG or IgM) complexes activate complement and deposit on blood vessels

• delayed (>72 hours)

• common triggers: PCN, sulfonamides

type IV allergic reaction

• t cell activation (NO antibodies)

• delayed (1day - 6 weeks)

• tuberculin rxn (a)

• DRESS (b)

• SJS/TEN (c )