[Study7] Adverse Drug Reactions - Part I

Adverse drug reaction

Harmful unpredictable drug reaction

• Most frequent in cardiovascular, nervous system, aninfective drugs

Adverse reaction increases with

• Old age, disease, polypharmacy (taking ≥5 medications

Five mechanisms of ADRs

1. On-target

2. Off-target

3. Cytotoxic

4. Immune-mediated → Part II

5. Idiosyncratic → Part II

"On-target" Mechanisms of ADRs

The drug interacts with the receptor it was intended to interact with, but the response becomes undesirable

Why?

• response too strong

• Drug reaches unintended tissue w/ same receptor

• Drug react with other drugs, food, herbs, disease

Dental example: Local anesthetics

Local anesthetics are intended to block sodium channels in nerves.

• But if too much enters the bloodstream, it can affect sodium channels in the heart

→ AV block, cardiac arrest, arrythmia

"Off-target" Mechanisms of ADRs

The drug interacts with a different receptor than the one it was intended to target

On-target = wrong response/location involving intended target
Off-target = drug interacts with unintended receptor

• Example: B2 agonist is used for asthma but it can also affect B1 receptors → increased heart rate

= Drugs aren’t perfectly selective

Cytotoxic Mechanisms of ADRs

Cyto = cell
Toxic = harmful

drug related damage or death of cells

• Apoptosis = programmed cell death

• Necrosis = uncontrolled cell death

Drug interactions

Two or more drugs can:

• act independently

• increase each other's effects

• decrease each other's effects

• produce an unintended effect

Interactions can be:

• drug-drug

• drug-food

• drug-herbal

• drug-disease

→ May reduce ADME process at any step

Margin of safety

• Large margin of safety → ADRs are more likely with overdose

• Small margin of safety → ADRs can happen even at therapeutic doses

Under whether medication can affect treatment, anesthesia, bleeding, vital signs etc

Overdose

Taking more than the medically recommended amount

• Children ingest med

• Patient take wrong med

• Patient take wrong dose

3 clinical signs of overdose

• Pinpoint pupils (miosis)

• Unconsciousness

• Respiratory depression (<12 breaths/min)

Any opioid + CNS depressants = respiratory depression and death

Pharmacokinetics (ADME/ ADMC)

what the body does to the drug

• Absorption

• Distribution

• Metabolism

• Excretion/ Clearance

ADR clinical manifestation

• Dailymed is official source for FDA approved drug labeling/ packaaging inserts

ADRs affecting oral tissue

Xerostomia

• Dry mouth/ reduce salivary flow

Taste disturbance

• Bitter/ metallic taste

= If patient complains about these, check medication history

Stomatitis

Inflammation of mucous membrane in mouth

• Patches

• Papules

• Plaques

• Ulcers

Candidiasis

White/ cheese milk like plaques

Caused by

• Antibacterial and corticosteroid therapy

Why?

→ kill bacteria
→ Candida has less competition
→ Candida can overgrow

Corticosteroids:
→ suppress immune response
→ Candida can grow more easily

Gingival Enlargement (due to meds)

Firm and painless or pain and gigival bleeding

Caused by

• calcium-channel blockers

• phenytoin

• cyclosporine

Bleeding from Platelet-related Drugs

Interferes with platelet function

• aspirin/ASA

• NSAIDs

• clopidogrel

Clinical manifestations:

• petechiae

• purpura

• ecchymosis

Bleeding from Anticoagulants

Interfere with clot formation

• warfarin

• DOACs such as apixaban/rivaroxaban

• heparin

Clinical manifestations

• spontaneous gingival bleeding

• hematoma

• increased perioperative/postoperative bleeding

ADRs Affecting the Gastrointestinal System

• NVD

• constipation

• abdominal pain

• dyspepsia (upper abdomen pain)

• anorexia

ADRS affecting liver/ bilary system

Acetaminophen (tylenol)

• APAP — leading cause of acute liver failure in U.S

• Unintentional overdose

• Jaundice (liver dmg)

ADR affecting the ears

• Dizziness

• Vertigo

• Tinnitus

= Ototoxic (affect hearing/ balance)

ADRs affecting cardiovascular system

• Hypotention

• Orthostatic hypotentsion

  • Drop from baseline of:

    • ≥20 mmHg systolic
      OR

    • ≥10 mmHg diastolic

• Syncope

  • Loss of consciousness bc of decrease cerebral perfusion

• Palpitations

  • Irregular heartbeat — arrhythmias

• Drug induced arrhythmias

  • impulse generation/ conduction — torsades de pointes

ADRs Affecting the Respiratory System

• Dyspnea

  • shortness of breath

ADRs Affecting the Urinary System

• analgesic nephropathy

  • reduced renal blood flow
    → acute renal failure

• Urinary incontinence

  • Can’t pee

  • increase pee production/ urgency

    
    

ADRs Affecting the Neuropsychiatric System

• Somnolence

  • Sleepiness/ drowsiness

• Insomnia

  • Difficulty falling asleep

• Depression

• Anxiety

ADRs Affecting the Peripheral and Central Nervous Systems

• Headaches

  • Primary or secondary

• Fatigue/weakness

  • Medical condition/ med withdrawals

• Tremors

• Tardive dyskinesia

  • Dopamine 2 receptor blockage from antipsychotic drugs

  • Oral movement during examination

• Paresthesia

  • Abnormal numbness, tingling

• Fever (>37.8°C orally)

ADRs Affecting the Endocrine/Metabolic System

• Hypoglycemia

  • low blood sugar