Over The Counter Medications:

NSAIDs; Headaches; Allergy & Nausea

Burchum: Ch. 30, 70, 71, 79, 80 & 81

Module Game Plan:

NSA Ds
Antihistamines
Laxatives & Antiemetics
Vitamins
Migraine Medications
 Over-The-Counter {OTC} Drugs
• Available without prescription

• OTC status determined by FDA/Health Canada

• Common complaints treated by OTCs:

• Mild Pain;
• Fever
• Allergies;
• Constipation;
• Motion Sickness/Nausea
• Many more.

• Save time, $$ & resources for healthcare system & patients

• Redirect patients toward OTC whenever possible & appropriate
 When t hurts 2-3/10.NSA Ds (Ch. 71)

Mechanism of Action
COX Inhibitors Classification
Aspirin
Other 1st Gen
NSAIDs Coxibs
Acetaminophen
Nursing Capsule

Rao, P., & Knaus, E. E. {2008}. Evolution of Nonsteroidal Anti-Inflammatory Drugs {NSAIDs}:
Cyclooxygenase {COX} Inhibition and Beyond. Journal of Pharmacy & Pharmaceutical Sciences, 11{2}, 81-110.
doi:10.18433/j3t886
Mechanism of Action

https://www.youtube.com/watch?v=9mculcSO-DE Summary
of NSAlDs Action - 4 mins
COX Inhibitors Classification

Platelets ➔ No Nucleus!!
Irreversible COX-1 inhibition = Forever
Coxibs: ,.I, Vasodilation ➔ 1' Vasoconstriction
 Aspirin {ASA) - General Infos
'Acetylsalicylic Acid'
Irreversible COX
Inhibitor
COX-1 Actions: Prevents MI & Stroke Prophylaxis
COX-2 Actions: Minimize Pain, Fever & Inflammation
Adverse Effects: Watch for Gastric Ulcers & Renal
Impairment

Pharmacokinetics
Excellent Oral Availability
80-90% Plasma Protein-Bound
Half-Life Low Dose = 2h {1st-order)/ High Dose = 20h {0-order) Kidney
Excretion: ASA = Weak acid ➔ Alkaline Urinary pH 1' Clearance
 Aspirin - Therapeutic Uses
Action Examples
Drug of Choice: Arthritis (Rheumatoid, Osteo, Juvenile)
Anti-Inflammation Other indications: Rheumatic Fever; Tendinitis Dosage give
> Dosoge required for Analgesia or Antipyretic
Mild to Moderate Pain
Analgesia Best in Joints, Muscles & Headache / Poor for intense Visceral pain No
tolerance/dependence ➔ Safer than Opioids

Antipyretic Drug of Choice for Adults / Contraindicated in children!!

Only � Temperature induced by inflammatory pyrogens
� Prostaglandins in Uterus ➔ '1, Cramps Ibuprofen >
Dysmenorrhea Aspirin

Antiplatelet Aggregation #1 Use of Aspirin Today ➔ More on that in cardio lecture

Recommended if risk/previous history of Strokes or Myocardial Infarcts
Help prevent Colorectal Cancer: Low dose � incidence & mortality via
Cancer Prevention COX-2 Inhibition
Mixed evidence for all other solid tumors
 Aspirin - Adverse Effects
Most common during long-term anti-inflammatory use Most
are uncommon unless risk factors present

Gastric Ulcers, Perforation & Bleeding

• Risk Factors = Age; Smoking & Alcohol; History of Ulcers
• Prophylaxis : Proton Pump Inhibitor & H2-Antagonists (both reduce acid
formation}

Bleeding: Antiplatelet action

• Discontinue 1 week before elective surgery

Acute Renal Impairment: Edema & 1' Blood Urea Nitrogen

• Risk Factors = Age; Hepatic Cirrhosis; Heart Failure; Kidney Damage

• Salicylism (aspirin overdose): Light early signs of aspirin toxicity (ex.: Tinnitus)
Reye's Syndrome: Rare but mortality :: 30-40% / Affects children
• Link between NSAIDs + Chickenpox/Influenza in kids

Others: Hypersensitivity Reactions; Teratogen + Prolong Labor

 Aspirin - Interactions & Poisoning
Significant Interactions Acute Poisoning
Anticoagulants: 1' Antiplatelet Effect
Acute medical emergency
Glucocorticoids: 1' Gastric Ulcers Alcohol: :: 20-25g for adults; 4g for children
1' Risk of Gastric Bleeding Other NSAIDs:
Salicylism Alkalosis ➔ Respiratory Depression
� MIl/Stroke prophylaxis �
Acidosis + Electrolyte Imbalance
Angiotensin Inhibitors: 1' Renal Impairment �
Coma &
� Vaccine Effectiveness Death

Treatment:
Respiratory Support + Bicarbonate infusion
Other 1st Gen NSAIDs
Main difference vs. Aspirin ➔ Reversible COX Inhibitors
As Such:
1) Slightly less Renal & GI Adverse Effects
2) 1' Risk of Stroke & MI

All have similar clinical safety & efficacy

Unexplained individual variations in response & tolerance
Ibuprofen (Advil, Motrin, etc.)
Dysmenorrhea relief > Aspirin GI
Bleeding & Antiplatelet < Aspirin

Recent study:
Ductus Arteriosus Closure: Indomethacin � need for surgery
 nd
2 Gen NSAIDs: Coxibs
Theory: COX-2 Selective Inhibition = � Pain/Fever/Inflammation + No GI Ulcers

Reality: Only small � GI Ulcers & 1'1' Risk MI & Stroke

VIOXX Scandal Hidden Data

Prototype: Celecoxib
Similar Uses & Adverse Effects as other NSAIDs
Extra Use: � Colorectal Cancer Risks in FAP patients
GI Ulcers: 1' Safety at 6 Months disappears at 12 Months
 The black sheep: Acetaminophen
NAPQI
Analgesia & Antipyretic Actions ➔ Best Option
No Antiinflammatory & Antiplatelet Effects
No Gastric Ulcers; Renal Impairment & Reye's
Syndrome
Hypothesis: CNS-Selective COX Inhibition
Potential risk of Hypertension with daily intake
Interactions: 1' Warfarin Action / � Vaccine Power

Metabolism

Acute Toxicity: Liver Damage

Overdose + Alcohol Hepatic
Necrosis :: 48-72hrs
Tx: Acetylcysteine ➔ 1' Glutathione
 Nursing Capsule: AHA Statement
Chronic Pain & COX Inhibitors
Musculoskeletal Pain Managament in Cardiovascular Event High-Risk Patients
Only move to next step if previous one fails

Step 1: Non-drug Interventions ➔ Physical Therapy; Heat/Cold Applications; Weight Loss

Step 2: Acetaminophen or Aspirin
Step 3: Other non-selective NSAIDs (ex.: Naproxen, Ibuprofen)
Step 4 (Last-Resort!): COX-2 Selective Inhibitors (ex.: Celocoxib)
� Opioids if pain too intense

Minimum Effective Dose for shortest effective time

For high risk of thrombosis patients: Add
Low-Dose Aspirin + Proton Pump Inhibitor
 When Hay Fever Starts:
Ant h stam nes (Ch. 70)

Histamine
Hl-Blockers: Pharmacology
Hl-Blockers: Preparations
 Histamine
Clinical Significance:
1) Mild Allergic Responses
2) Peptic Ulcers

Storage/Synthesis
Mast Cells ➔ GI, Lungs & Skin CNS
Neurons

Histamine Receptor Effects

1) Vasodilation
2) 1' Capillary Permeability ➔ Edema
H1-Receptors 3) Bronchoconstriction (Exogenous Histamine only)
Cognition; Memory & Sleep Cycle
5) Pain; Itching & Mucus Secretion

H2-Receptors Gastric Acid Secretion

 Hl-Antagonists Pharmacology
Actions
Block Histamine Action (not release!)
Some are also Muscarinic Blockers
Periphery: -J. Pain; Edema & Mucus secretion CNS
Sedation: 1st Gen »» 2nd Gen
Sedation Tolerance Develops within Days
Toxicity/Overdose = CNS Stimulation ➔ Convulsions Large
Margin of Safety

Therapeutic Uses Adverse Effects

Mild Allergic Responses ➔ Hay Fever; Acute Urticaria
Anti Motion Sickness Effects: -J. Nausea & Vomiting
Insomnia ➔ 1st-Gen via CNS Sedation
Fun Fact: OTC Insomnia meds = Ineffective Dose
GI Effects: Nausea / Constipation / Diarrhea
Elderly Patients: Dizziness & Confusion
Anticholinergic Effects: Dry Mouth & 1' Bronchial Mucus
Interactions: Alcohol & CNS Depressants
Caution with Pregnancy & Breast-Feeding
Hl-Antagonists Preparations

1st Gen Agents

Promethazine: Avoid if possible 2nd Gen Agents
Alkylamines: Least Sedation Similar Efficacy & Safety ➔ Choose Cheapest
Advantage over 2nd gen: Cost Low CNS Distribution
Fexofenadine: Best Efficacy/Safety Ratio
When there is a traffic jam:
Laxatives (Ch. 79)

General Considerations
Stimulant Laxatives
Bulk-Forming Laxatives
Osmotic Laxatives
Colonoscopy Bowel Cleansing
Nursing Capsule
https://www.youtube.com/watch?v=EEBjuiqEp4w&ab_channel=SciShow
- How Laxatives Work (3m00s)
 Recommended PATHOPHYSIOLOGY
REVIEW SLIDES
Large Intestine + Constipation from 210
BACK TO PHARM ☺
General Considerations
 General Considerations
Definitions:
Laxative Effect = Slow production of soft stool
Catharsis = Prompt evacuation of bowels (bowel
cleansers)
Other Laxatives Applications
Antihelmintic (Parasites) Therapy Adjunct
Pre-Surgery Bowel Emptying (Group I)
Removing Ingested Poisons
Constipation
Diagnostic: Stool Hardness > Infrequent Evacuation
Best Treatment: 1' Fluid & Fiber Intake
Good Adjuncts: Mild Exercises & Group III Laxatives
Laxatives Contraindications
Any GI Inflammation/Injuries
Long-Term management of Constipation
Caution during Pregnancy/Breast-Feeding
 Stimulant Laxatives
Examples Bisacodyl; Senna (Group II} Castor Oil (Group
Stimulate Peristalsis (even small intestines)
Actions Inhibit intestinal absorption & 1' GI Secretions
Opioid-Induced Constipation
Indications Slow-Transit Constipation

Adverse Effects Frequently Abused

Very Fast Action

Suppository can act in
Risk:Benefit ratio for constipation 15 mins!!
mangement is not very good
 Bulk-Forming Laxatives
Examples

Actions
Psyllium / Methylcellulose (Group
Indications III}
:: Dietary Fibers
Adverse Non-digestable or absorbable
Effects Colon stretch ➔ 1' Peristalsis
Best for Mild Constipation
Irritable Bowel Syndrome (IBS) & Diverticulosis
No absorption = No Systemic Effects May
exacerbate existing intestinal obstruction
Esophageal Obstruction if insufficient Fluid with intake
Expert Nurse Advice
Remind Patients to take their laxatives with a full
glass of water/juice to limit adverse effects!!
 More Group lll Laxat ves
Surfactant Laxatives Docusate Sodium or Calcium (Group lll}
-.I Feces Surface Tension ➔ 1' Water Penetration
Actions +
Inhibit intestinal absorption & 1' GI Secretions
Other Laxatives Lubiprostone (Group lll}
Actions Chloride Channel Activator
1' Intestinal Secretions & Motility
Chronic Idiopathic Constipation
lndications IBS with Constipation in women
Opioid-Induced Constipation
Adverse Effects GI Distress {Nausea & Vomiting) & Headaches Rare:
Chest Pain + Difficulty Breathing
PEG also used for chronic constipation therapy

Osmotic Laxatives
Most commonly
Examples used atGlycol
Polyethylene MUHC!!(PEG) /Magnesium or Sodium Salts
Poorly Absorbed Salts ➔ Osmotic Pull of Water
Actions Stretching of Intestinal Wall ➔ 1' Motility
Low-Dose = Group II vs. High-Dose = Group I
Indications Poison or Parasite Purge/Evacuation
Pre-Surgery Emptying
Adverse
Effects Dehydration
Kidney Impairment ➔ 1' Magnesium Imbalances
Sodium Imbalances ➔ 1' Heart Condition
 Colonoscopy Bowel Cleansing
Bowel Cleansers Infos
PEG+Electrolyte Safest option: Isotonic ➔ No dehydration or electrolyte imblance
Solution Drawback: Requires significant fluid intake
Discussed under osmotic laxatives
Sodium Phosphate Advantage over PEG: Easier Administration
Drawback: Hypertonic ➔ Dehydration/Electrolyte Imbalances
Stimulant + Osmotic Laxatives
Salt Combination Advantage over PEG: 1' Cleansing Efficacy
Drawback: Same as Sodium Phosphate

Salt
PEG- Combination
 Nursing Capsule: Laxative Abuse
Causes
:
False belief of mandatory daily bowel movement + Aggressive OTC Laxative Marketing Bowel
emptying inhibits evacuation until :: 2-5 days later ➔ Misdiagnosed as Constipation

Consequences:
Inhibition of normal defecation reflex ➔ Laxatives Dependence
Similar to Nasal Spray Dependence Dehydration; Electrolyte Imbalances; Colitis

Best Tx: Abrupt Laxative Discontinuation

Patient Education:
Anticipate few days without evacuation Stool Quality > Daily Movement Suggest Dietary Fiber + Daily Exercises
If Laxative used again: Short-Term + Lowest Effective Dose
 When things want to come back up:
Antiemetics {Beginning of Ch. 80}

Antiemetic Agents
Serotonin Antagonists
Drugs for Motion Sickness
Chemotherapy-Induced Nausea & Vomiting (CINV)
Nausea & Vomiting of Pregnancy
 Antiemetics Agents
Main Uses:
1) Manage side effects of:
Opioids / General anaesthetics
Chemotherapy {CINV)
2) Motion sickness prevention
3) Migraine Trherapy
 Antiemetics Agents
Combination
Very Effective
for CINV

Toxicity ➔ 2nd-line drugs

Toxicity: Extrapyramidal Effects Anticipate change in uses
Ex.: Tardive Dyskinesia following more research
Serotonin Antagonists
Prototype Ondansetron
Actions 5-HT3 Antagonists at CTZ & GI Afferent Neurons
Chemotherapy-Induced Nausea & Vomiting (CINV)
Indications Nausea/Vomiting from Radiotherapy & Anesthesia
Adverse Headache / Diarrhea / Dizziness
Effects Prolong QT interval

Special Usage of Palonosetron:

Delayed Emetic Response
Thanks to longer Half-Life
 Drugs for Motion Sickness
Efficacy: Prophylaxis »» Reactive Therapy

Most Effective Colombia = 'Burundanga'

Less Toxicity with Transdermal patch Devil's Breath Robbery
Common ADE = Drowsiness & Theft

Review 1st Gen Antihistamines

Less Effective vs. Scopolamine + Sedation Effects = 2nd choice
 Nursing Capsule: Chemotherapy
Chemotherapy-Induced Nausea & Vomiting (CINV):
Severe Nausea & Vomiting ➔ Fluid/Electrolyte Imbalances ➔ Patients discontinue Tx

Treatment: Antiemetics most effective for Prevention

Administer before chemotherapy

3 Types of CINV:
Anticipatory = Memory from previous CINV
Acute = Minutes to 1 day post treatment
Delayed = >1 day post treatment
Nursing Capsule: Pregnancy Nausea
Nausea and Vomiting of Pregnancy
75% during 1st Trimester 90%
resolves before week 20

Treatments
1) Non-Drug Behaviors
2) Doxylamine (Antihistamine) +
Vitamin B6 combination
Eat Small portions Avoid
fatty & spicy foods
Best & Safest Rx Option

3) Metoclopramide; Odansetron or Last resorts

Methylprednisone
More toxicity - Use with caution
Break Time!
 Flintstones Anyone?
Vitamins (Ch. 81)

Basic Considerations & Classification

Fat-Soluble
Water-Soluble Vitamins
 V tam ns
Organic compounds required in small amounts for
Energy Trans/ormation & Metabolic Processes

Multivitamin Supplements??
Mixed Evidence ➔ 'Don't Stop - Don't Start' Healthy
Diet = Best behavior
Watch out for Excessive Vitamin A & E
Evidence for 3 Individual Vitamins:
Vitamin B12 ➔ Everyone 50+ years old Folic
Acid (B9) ➔ Childbearing age females
Vitamin D + Calcium ➔ Postmenopausal females
 Dietary Reference Values
Adequate Intake Tolerable Upper Level Intake
Estimation of RDA when not
enough evidence available
Maximum dose without significant ADR risk ➔ Safety Index

Estimated Average Requirement

(EAR)
Level required for 50% of individuals
(regardless of conditions)
Used to establish the RDA following
extensive research
Recommended Daily Allowance (RDA)
Average daily intake necessary for healthy individuals
Varies according to sex, age, pathologies
 V tam n A (Ret na )
Hormone!
Dim light adaptation
Physiological Embryogenesis & Spermatogenesis
Functions Skin & Mucous membrane integrity
Immunity & Growth
Night Blindness
Deficiency Corneal or conjuctiva lesions Skin/Mucous
membrane lesions
Liver injury
Toxicities Bone-related disorders
Birth defects
Therapeutic Deficiency prevention
Use
Retinol derivatives ➔ Acne & skin disorders
 Vitamin E
Functions Antioxidant with unknown metabolic role
Deficiency Neurologic Deficits
1' Heart failure risk, Cancer progression & All-cause mortality
Toxicity Inhibit exercise benefits on insulin sensitivity Inhibit
platelet aggregation ➔ 1' Hemorrhagic stroke risk
Potential Benefits Hemolysis & Age-related macular degeneration prevention Many other
false claims
The Case against Antioxidants

Vitamin A, E, C
Theory & Observational Studies ➔ Promising Results!!

Actual Robust Scientific Inquiries

• Excessive beta-carotene (Vitamin A} ➔ 1' Lung Cancer risk in smokers
• Excessive vitamin E ➔ 1' Prostate cancer risk & Strokes
• Other antioxidants ➔ Drug Interactions
The Case against Antioxidants
 Vitamin K
Physiological Prothrombin synthesis
Functions Activation of clotting factors VII, IX & X
Deficiency Malabsorption syndrome or -.I. [Bile Salts]
Causes Antibiotics ➔ -.I. GI Flora Vit. K synthesis
Warfarin toxicity
Deficiency
Bleeding/Spontaneous hemorrhage
Symptoms
Therapeutic
Warfarin antidote
Use
Adverse IV Admin➔ Hypersensitivity/Anaphylaxis risk
Effects Hyperbillirubinemia ➔ Kernicterus of newborn
Hormone! Vitamin D (Fat soluble)
Proven benefit = Bone Homeostasis

Debated evidence ➔ Prevention of:

• Arthritis & Autoimmune disorders
• Breast, prostate & colon cancer
• Heart Diseases & TlDM

Deficiency
Many dubious
claims!
Vitamin C {Water
soluble)
True!

True!

Yes
but.
True!
Water-Soluble Supplements are not stored!!

Vitamin C
Vitamin B Group
 Niacin (B3)
Functions Precursor of NAD & NADP ➔ Major
coenzymes of the Krebs cycle!
Pellagra:
Deficiency Dermatitis, skin scaling, GI
distress (cramps, diarrhea)
CNS: Irritability + Insomnia + Memory loss
Therapeutic Use Pellagra prevention & treatment
Adverse Effects Low doses = None
Very high dose = Dizziness + Nausea

Nicotinamide = Preferred for Pellagra Tx

Has Less toxicity + No vasodilation
 Pyridoxine (B6)
Functions Starts as an Amino acid synthesis coenzyme
Deficiency lsoniazid (Tuberculosis) Therapy
Causes
Poor Diet
Inborn Metabolism Error
Deficiency Peripheral neuritis, convulsions, depression
Symptoms Anemia, Seborrheic dermatitis
Therapeutic Use Deficiency prevention & treatment
Low doses = None
Adverse Effects Very high dose = Neurologic injuries
Drug lnteraction: � L-DOPA efficacy
Folic Acid {B9) & Cyanocobalamin {B12)

Involved in RBC development Discussed

in the Hemodynamic Lecture
 Types of Anemias - Summary
Name Mechanism RBC Characteristics Primary Cause
B12 Deficiency Abnormal DNA/RNA Macrocytic 1} Congenital
(Pernicious) Synthesis Normochromic
2} Intrinsic Factor Deficiency
Abnormal DNA/RNA Macrocytic
Folate (B9) Deficiency Synthesis Normochromic 1} Dietary folate deficiency

Insufficient hemoglobin Microcytic 1} Chronic Blood Loss 2}

Iron Deficiency synthesis Hypochromic Dietary iron deficiency
Insufficient Normocytic
Aplastic Erythropoiesis Normochromic 1} Bone marrow suppression

Normocytic
Posthemorrhagic Significant Blood Loss Normochromic 1} Bleeding

Premature Destruction of Normocytic

Hemolytic RBC Normochromic 1} Increased fragility of RBCs

Abnormal hemoglobin Normocytic

Sickle Cell synthesis Normochromic 1} Congenital
B12-Deficiency (Pernicious) Anemia
Pathophysiology:
• Pernicious = highly injurious/destructive
• Absence of intrinsic factor
• Parietal cell destructions (congenital; autoimmune)
• Stomach or Distal Ileum surgical removal
• Malnutrition

Mani/estations:
• Common anemia Sx
• Slow onset (20-30 years)
• Specific Sx: Demyelination ➔ Neuronal death
• Not reversible!!
 Folate (B9) Deficiency Anemia
Pathophysiology:
■More common than B12
Mani/estations:
■Folate = Essential for DNA/RNA synthesis
■Most common causes: • Ulcerations and inflammation of bucco-oral area
• No
■ 1) Malnutrition ➔ Often neurological
reated manifestation
to Alcoholism
■ 2) Folate malabsorption ➔ Ex.: Inflammatory bowel disease
 Section on Headache
Medications (slides 54-69}
are covered in-person
during Seminar #2
 When the Migraine hits:
Headache Medications (Ch. 30}

Treatment Strategies & Overview

Abortive Treatments
Preventive Treatments
Other Treatments
Non-Pharmacological Strategies

Preventative Non-
pharmacological
Interventions Abortive Non-
Pharmacological
Interventions
 Pharmacological Strategies

Abortive Treatments
{Reduce duration of attacks & Preventive Treatments Other Treatments
manage Sx of pain, nausea &
vomiting) {Reduce Recurrence & Intensity {Specific Usage or Limited
of future migraines) Evidence)
Dealing with the « here and now
»

Dexamethasone
NSAIDs/Acetaminophen 5- Antihypertensives Antiemetics
HT Agonists {Triptans) Antidepressants Opioids & Barbiturates
Dihydroergotamine Anticovulsants Sodium Valproate
CGRP Antagonists Estrogens Neuromodulation
Lasmitidan CGRP Antagonists Peripheral Nerve Block
 Abort ve Treatment Overv ew

Role of CGRP & 5-HT in Migraine

1) CGRP levels rise during migraine attack while 5-HT levels drop
2) Leads to vascular spasms & trigeminal nerve pain sensitization

Main Pharmacological Targets:

NSAIDs/Dexamethasone - Inflammation & Pain
2) Triptans & Ergots - 5-HT-related Vasospasms
3) CGRP Antagonists - CGRP-induced trigeminal pain transmission
4) Anti-Emetics (DA antagonists) - Nausea/Vomitting
 Abortive Treatment Strategies
Choice of Medication Administration Strategies
Mild ➔ NSAIDs/Acetaminophen
Early Admin > Late Admin
•Best Risk-Benefit Ratio
Severe ➔ Triptans (5-HT Agonists) Single large dose > Small repeated doses
•Best Migraine-Specific Class (start with this)
Combine if monotherapy ineffective Favor PO admin
•Combination NSAID + Triptan > Either alone
Alternatives if still unresponsive •Can use anti-emetics (ex.: Metoclopramide) if difficult due to
nausea/vomiting
•Dopamine Antagonists (i.e.: Anti-Emetics) •Parenteral admin if PO impossible
•CGRP Antagonists
•Lasmitidan
•Dihydroergotamine
 Nursing Capsule:

Medication Overuse Headache {MOH}

Chronic use of headache medication
CAN trigger Headaches!!
Intervention:
Drug Class Risk of Discontinue medication
MOH
Opioids & Barbiturates
Aspirin-Acetaminophen-Caffeine Highest
combination
Triptans Intermediate
Lowest
NSAIDs & CGRP Antagonists
Possibly protective
 Prevention:
1) Prioritize Non-pharmacological & Prophylactic Measures
2) Limit Abortive Drug Use: � 2-3x/week or 10 days/month
3) Alternate between abortive drugs (favor NSAIDs & CGRP Antagonists)
 Analges cs & Ant -Inflammatory Rx
Aspirin + Metoclopramide
NSAIDs Efficacy = Sumatriptan
Cost & Adverse Effects < Sumatriptan
• Available OTC ➔ Cheaper & Safer
• No NSAID superior to others
• If one fails, try another
• Ex.: Aspirin, Ibuprofen, Naproxen

• Special Formulations:
Acetaminophen + Aspirin + Caffeine
• Powdered Diclofenac Also efficient & cheap but high risk of MOH
• Faster onset than tablets
• IV Ketorolac
• Effective in ER settings

Review section on NSAIDs for more details

 5-HT1B/1D Agonists: Triptans
Action
Selective 5-HTlB/lD Agonist Uses:
Relief of all Migraine Symptoms
Migraine returns :: 40% patients

Kinetics:
PO, Nasal or Subcutaneous Administration Class of
enzyme: MAO Metabolism ➔ Tl/2 :: 2.Shours

Adverse Effects:
Teratogen
Increased risk of cardiovascular events

Interactions:
Other Triptans/Ergot Alkaloids ➔ Additive Effects
MAO & Reuptake Inhibitors ➔ 1' Effects
 Triptans: Choice of Drug
• Choice of Rx should be individualized as much as possible
• All triptans have strong evidence of efficacy
• If one fails, try another
• See table below for specific details

Triptan Special Comment

Most option of administration (only one available subcut)
Sumatriptan Subcut admin = Fastest onset of action
Naratriptan & Frovatriptan Slowest onset of all but lowest risk of toxicity
Rizatriptan, Elitriptan &
Almotriptan PO Most consistent therapeutic success

Elitriptan CYP3A4 metabolism = Higher interaction risks

Sumatriptan + Naproxen Most effective combination
More effective than any other treatment alone
 Dihydroergotamine (DHE)
Action: Kinetics:
a-adrenergic + 5-HTlB/lD Agonist Mechanism :: Triptans Weaker vasoconstriction Stronger venoconstriction
Parenteral & Nasal Spray only

Adverse Effects:
Prominent Diarrhea
Cardiovascular complications

Usage:
2nd-line drug for Migraine Attacks {inferior to Triptans) Best
to combine with antiemetic

Interactions:
Triptans/ Other Ergot Alkaloids ➔ Additive Effects
CYP3A4 Inhibitors ➔ 1' Toxicity ➔ ERGOTISM!
History Capsule: Ergotism & Witches
Salem Witchhunt circa 1692
LSD :: Ergotamine

Witchcraft trials to locations & dates concordance:

Rye = Highly cultivated
Timing of rain & market price indicating bad crop years
Reported behaviors of 'witches' & their victims :: Ergotism Sx
5-HTlF Agonist: Lasmiditan
Approved by FDA in 2019
Main toxicity: CNS Depression (sedation & drowsiness)
Driving car or machinery contraindicated for 8h post-administration
 Major Benefit: Only class useful for both migraine abortion and prevention
Acute Context: Block CGRP-mediated trigeminovascular nociception
Good option for patient unresponsive or with contraindications to Triptans (ex.: Cardiovascular disease)
Prevention Context: Decrease migraine frequency + May counter Medication Overuse Headache (MOH)

CGRP Antagonists
Several approved in the past few years

Kinetics:
PO Available / CYP3A4 metbolism
Peak effects within 2 hours

Main adverse effects:

Somnolence, nausea & Dry-mouth
**Very well tolerated so far but still quite new! Must remain cautious**
 Severe Migraine in Emergency Setting
Best Regimen:
1) Sumatriptan Subcut
OR
Metoclopramide IV + DiphenHYDRAmine
IV
+
2) Dexamethasone IV/IM
Dexamethasone InformationMetoclopramide
Long-Acting Corticosteroid with strong Anti-Inflammatory Action Action Dopamine receptor antagonist reducing mostly nausea & vomiting but also p

Ruduces migraine recurrence in combination with Triptans No

evidence of abortive anti-migraine effect or preventive effect in Evidence Useful in monotherapy IV
monotherapy or combination PO with NSAIDs

Adrenal suppression in high-dose long-term Toxicity Irreversible Tardive Dyskinesia in high dose long-term
Only short-term use in ER to reduce migraine recurrence Usage Combine with DiphenHYDRAmine to mitigate dyskenesia
Endocrine Pharm Module More details in GI Pharm Module
 Preventative Agents
Goal = -.I Intensity + Frequency + Duration
Indications = Chronic Migraines / Severe Migraines / Failure of Abortive Drugs

strogens
Beta Adrenergic Blocking Agents ric clic Antidepressants (for menstrually associated migraine)
Antiepileptic Drugs

Only � Frequency For migraine ± 2 days of menses

Best Prophylaxis Option Benefits = Propanonol
Cost & Adverse Effects > Beta- Blockers Triptans can also help
Effective > 70% of patients Cardiac Adverse Effects

Estrogen gel
etroprolol 0 opressor] Divalproex 0Depakote E ]
Amitriptyline 0Elavil] Estrogen patch 0Alora, Climara, Vivelle-Dot]
Propranonol 0 nderal] Topiramate 0Topamax]
 Other Migraine Treatments
Just a few more options to be aware of. They all have limited or poor evidence.

Sodium Valproate Opioids & Barbiturates

Neuromodulation Nerve Block

Limited efficacy data Should be avoided Non-pharmacological intervention:

stimulate CNS & PNS using magnetic or
Poor risk-benefit ratio Higher risk of MOH Very very last resort
Inferior to other options electrical energy
Could be used as a last resort
Some evidence of benefits but small and
low-quality data.
Can be considered for nonresponsive
patients
Examples:
Noninvasive Vagus Nerve Stimulation
Transcranical Magnetic Stimulation
Using local anesthetics
Targets: Occipital & Trigeminal
Nerves
Limited, low-quality efficacy data
Can be considered for
nonresponsive patients with
severe and prolonged migraine
attacks