1

Lecture 14: NSAIDs & Autacoids.

2

I. NSAIDs & Other Analgesics:

Drugs For Gout: Drugs for Arthritis: NSAIDs=

inflammatory Drugs-AntiNon Steroidal

*Allopurinol.

*Febuxostat.

*Colchicine.

*Probencid.

*Sulphinpyrazone.

*Abatacept

*Adalimumab

*Golimumab

*Infliximab.

*Rituximab

*Anakinra.

*Certolizumab.

*Chloroquine

*Etanercept.

*Gold salts.

*Methotrexate

*D-penicillamine.

*Leflunomide.

4. Oxicam deriv.:

*Piroxicam

*Meloxicam

.:5. Fenamate deriv

*Meclofenamate

*Mefenamic acid

6. Heteroacyl acetic

acid derivatives:

*Diclofenac.

*Ketorolac.

*Tolmetin

7. Celecoxib.

1. Aspirin.

2. Propionic à deriv.:

*Ibuprofen

*Naproxen

*Fenoprofen

*Ketoprofen

*Furbiprofen

*Oxaprozin

:3. Acetic à deriv.

*Indomethacin

*Sulindac

*Etodolac

Acetaminophen:Other Analgesics:

*Prostaglandin Synthesis:

"EXAM" 2?-1 & Cox-Q) What is the difference between Cox

gastric cytoprotection, platelet→"1 "house keeping enzyme-COX*

aggregation & kidney function.

during inflammation in brain, kidney & bone. →2-COX*

3

1. CV events, M.I & Stroke. I. NSAIDs:

2. C.I in perioperative pain in Coronary bypass.

3. GIT events, Ulceration & bleeding.

COX.acetylates Irreversibly*The only NSAIDs that

tissues.y centers & target synthesis in thermoregulatorPG 1. Inhibit M.O.A:*

2. Pain sensitization receptors to mechanical & chemical stimuli.

Actions:*

inflammatory action.-Anti1. *In musculoskeletal pain.

*Diflunisal > 3-4 folds than Aspirin in Analgesia & Anti-

inflammatory but No antipyretic effect.

2. Analgesic action:

synthesis & release. 2PGE -3. Antipyretic:

Respiratory ventilation. *At toxic doses: resp. paralysis action:4. Resp. Gastric à & protective mucous→ ∴Ulcers & bleeding. 5. GIT:

81 mg.-) at doses 602TXAplatelet aggregation ( 6. Platelets: except with may cause nephritis →O retention2/H+Na

Aspirin.

7. Kidney:

Therapeutic Uses:*

inflammatory, Analgesic & Antipyretic:-1) Anti

-Used in Rheumatoid Arthritis, gout, osteoarthritis & rheumatoid fever

.For corns & warts- 2) External application:

-Methyl Salicylate (Oil of Winter green)→ Counterirritant in liniments.

3) CV application:

Platelet aggregation in: 1) M.I 2) CAD 3) Revascul. pts.

< 15 years.C.I in children - *Pharmacokinetics:

-Viral Infection (Influenza & Chicken pox)→ Toxicity of Aspirin → Reye's synd.

Prophylaxis from M.I →162 mg/day-1) 81: Dosage*

Analgesia. →2) 325 mg x 2 x 4

Prophylaxis from Stroke. →325 mg/ day-3) 50

RA. →4) 3 g/day

taken with food. ∴ →: Epigastric distress & Ulcers) GIT1 :EffectsAdverse * Stop 1 week before surgery. →Platelet aggregation 2)

in high doses.) Resp. depression 3 .Hypersensitivityin toxic doses. 5) Hyperthermia4)

(hepatitis & Cerebral edema in children) Reye's Syndrome6) ∴ use Acetaminophen instead.

.Valproic acid& Phenytoin, Warfarinconc. of : 1) Aspirin Interactions* hese twhile àUric as Aspirin Probencid& Sulphinpyrazone2) C.I with

agents Uric acid (antigout).

1. Aspirin:

Warnin

gs:

4

platelet aggregation. bleeding & : Ketorolac3) C.I. With ). rdtrimester & D in the 3 nd& 2 st(Cat C in 1 Pregnancy4) C.I. in

Hyperventilation, tinnitus & Vomiting. →: SalicylismToxicity*

.Ketoprofen* . Fenoprofen* .Naproxen* . Ibuprofen*

.Oxaprozin* . Furbiprofen*

-Analgesic, Anti-inflammatory & Anti-pyretic.

-Used in Osteoarthritis & Rheumatoid arthritis (RA).

1/2longest t →Oxaprozin-

-S.E: dyspepsia & bleeding.

2.

Propionic à

derivatives:

Etodolac* Sulindac* Indomethacin*

-Analgesic, Anti-inflammatory & Anti-pyretic.

-ttt of gouty arthritis, Ankylosing spondylitis & Osteoarthritis.

à3. Acetic

derivatives:

Meloxicam* Piroxicam*

-Meloxicam inhibits both Cox-1 & Cox-2 (more selective to Cox-2).

-ttt of RA, Ankylosing spondylitis & Osteoarthritis.

-Meloxicam < Piroxicam in S.E.

Once daily dosing. →1/2*Long t

once daily at night to relieve morning stiffness. n: Piroxicam is giveEXAMN.B:

4. Oxicam

derivatives:

*Mefenamic à. Meclofenamate*

*Can cause severe diarrhea & inflammation of the bowel.

5.

Fenamate

derivatives:

.Ketorolac* Tolmetin* Diclofenac*

*ttt of RA, Ankylosing spondylitis & Osteoarthritis.

.(Voltaren eye dps) is available as Eye drops too Diclofenac*

*Ketorolac: → potent analgesic (post operative pain & topical conjunctivitis).

I.V dose. stShort term ttt 5 days after 1

S.E: Peptic ulcer & stomach perforations.

6.

Heteroacyl

:àacetic

inhibitor. 2-Selective Cox*

*ttt of RA, Ankylosing spondylitis & Osteoarthritis.

11 hrs (Once daily or twice with divided doses). →1/2t*

*C.I. in patients allergic to Sulfonamides.

*S.E: Abdominal pain & diarrhea.

.Less effect on peptic Ulcer than Aspirin* المعدة قرحة بيزود الاسبرين

*May M.I & Stroke.

inflammatory effect.-antiLeast *

7.

Celecoxib:

Acetaminophen. II. Other Analgesics:

inflammatory effect.-No antipyretic with -*Analgesic, Anti

*Doesn't interact with uricosuric agents.

*Doesn't cause in bleeding time.

*D.O.C in Children with Chicken pox.

No S.E. →1) Normal doses Adverse Effects:*

2) Toxic doses→ Hepatic necroses. → N-Acetyl Cysteine (Antidote within 10 hrs)

5

:Acetyl Cysteine-NN.B:

ttt of Cystic fibrosis. →Inhalation-

ttt Acetaminophen toxicity (hepatic necrosis) →Oral -

III. Rheumatoid Arthritis:

*Occurs in Women> Men.

*Common in young women.

*Clinical Symptoms: Usually last for 1 h before maximum improvement1. Morning stiffness ≥ 30 min:

ame joint on both sides of the body.: S2. Symmetrical arthritis

: Observable S.C nodules.4. Rheumatoid nodules

:For *Lab Tests

in more than 60 % of pts. 1. Rheumatoid Factor (RF):

in pts with RA. markers of inflammation & ESR & CRP: 2.

why? Because anemia is a common feature of RA. →3. CBC

*Therapy:

For Symptomatic relief of RA. →ttt inflammatory -A. Anti

They are given as 1. NSAIDs.

prednisolone) bridge until -(Prednisone & Methyl 2. Corticosteroids:

*Taken at low doses. therapeutic effects

*They also are immunosuppressant, of DMARDs occur.

So additional advantage in ttt of RA which is an autoimmune disease.

EXAM 2014:

Prednisone & Methyl prednisolone prevent recurrence of RA

Rheumatic Drugs (DMARDs):-Modifying Anti-B. Disease * They reduce or prevent joint damage.

I. More Commonly used DMARDs:

malarial.-see before anti →:Hydrochloroquine& Chloroquine1. *They are antimalarial used for ttt of SLE & RA.

2. Sulfasalazine:

*S.E: * Nausea & diarrhea. *Dizziness & Headache.

*Rash & abnormal Liver function tests.

6 weeks.-Response 3 →IMP 3. Methotrexate:

*Doses of Methotrexate required for ttt are much lower than that needed in

Cancer Chemotherapy & are given once / week→ ∴ S.E.

Mucosal ulceration & Nausea.Most Common S.E: *

with chronic administration Other S.Es:*

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so monitor CBC. →Myelosupression so monitor Liver function test. →Hepatotoxicity

ray.-Chest X → Pneumonia like syndrome so monitor serum creatinine →Renal toxicity

II. Less Frequently Used DMARDs: 2. Cyclosporin. 1. Azathioprine

*See before at immunosuppressive drugs.

(orally)Auranosin: 3. Gold salts Dermatitis, Conjunctivitis, Stomatitis & Proteinurea. *S.E:

& urine analysis.Monitor CBC, Renal function ∴

why? →It is less & less used with RheumatologistsQ) *

Because of high cost of administration & monitoring as well as its toxicity.

*Effect: 3-6 months.

"analog of Cysteine amino acid".Penicillamine: -4. D

*S.E: 1. Loss of taste.

2. Serious S.E ranging from dermatologic problems to nephritis & Aplastic

anemia so monitor CBC, Liver function tests & urine analysis.

Penicillamine is used as chelating agent in ttt of:-D N.B.

1. Poisoning by heavy metals.

level in body. 2+Cu 2. Wilson's disease:

All DMARDs have long onset of action (weeks). N.B

are associated with shortest onset of action. Infliximab& Etanercept

III. Newer DMARDs:

) DHODHinhibitor of Dihydro orolate dehydrogenase ( Reversible: M.O.A*

enzyme which is necessary for pyrimidine synthesis.

for RA. Monotherapy*Used as

S.E & Monitoring:*

-Hepatotoxicity. –HTN -Significant wt loss & immunosuppression.

-Allergic reactions. –Nausea & Diarrhea.

Liver function tests, Sr Cr, B.P & Eye examination. Monitor:*

lunomide:1. Lef *take 2 years to be

eliminated from body.

18 hrs & -: 141/2*t

loading dose is

necessary.

:(Biologic therapies) 2. Anticytokine drugs 1. All cause immunosuppression so risk

of infection (mainly respiratory tract inf).

2. All taken by injection→ they may cause

injection site reaction.

3. Headache is common.

4. All except Anakinra cause abdominal

pain.

: Binds to TNFM.O.A*

: is important in TNF N.B.

modulating immune

response by immune cells.

a. Etanercept:

→ M.O.A OF b,c

They are antibodies that

bind specifically to TNF-

b. Infliximab &

Adalimumab: c.

IL-1 receptor antagonist. d. Anakinra:

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used as monotherapy or with Methotrexate. →. a & dN.B: 1

approved only in combination with Methotrexate. →. b & c2

considered as standard therapy for pts with Rheumatoid →Anticytokine drug + Methotrexate3.

& psoriatic arthritis.

?How →sis Factor (TNF) & Interleukin (IL) are involved in the pathogenesis of RATumor necro4.

Synovial macrophages→ secrete TNF & IL→ Stimulate synovial cells to proliferate & synthesize

Collagenase→ Degradation of Cartilage & Stimulating bone resorption & inhibiting proteoglycan

synthesis.

*Uses:

-Used in moderate to severe RA in pts not responsive to other DMARDs or

TNF-I.

-Used alone or in combination except TNF-I & Anakinra due to serious

infections.

Nasopharyngitis & upper respiratory infections. S.E:*

infusion then once every 4 weeks. st: I.V infusion at week 2 & 4 after 1Dose*

e. Abatacept:

*Used in combination with Methotrexate.

Urticaria, hypotension & Angiodema. S.E:*

∴ Antihistamine, vasopressor & fluid are used.

methyl prednisolone is given 30 min before infusion. →: I.V infusionDose*

f. Rituximab:

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*Clinical symptoms of knee O.A:

& at least in of the following: OsteophytesKnee pain & radiographic evidence of

1. Age > 50 years. 2. Articular crepitus on motion.

3. Morning stiffness that lasts < 30 min.

*Treatment:

A. Non pharmacological treatment:

1. weight loss. 2. Assistive devices e.g. Canes

3. Aerobic exercise programs (bed rest & immobility are necessary).

4. Joint protection e.g. avoid long standing. 5. Thermal therapy (hot or

cold).

acological treatment:B. Pharm

1. Analgesics:

therapy for OA of hip or knee. line st1

Doses ≤ 4 g/ day to avoid toxicity. 1. Acetaminophen:

Used when response to acetaminophen is inadequate. 2. NSAIDs:

NSAIDs,patient's pain is unrelieved by Good choice when:

when patient can't take NSAIDs or

when patient experience break through pain while taking NSAIDs.

3. Tramadol:

Reserved for pts who fail to respond to multiple analgesic therapy.

: similar efficacy to acetaminophen.propoxypheneAlso 4. Opiate analgesics:

e.g. Codeine & Oxycodone

e.g. Capsaicin→ Deplete stores to substance p. 5. Topical analgesics:

articular injections:-2. Intra

not hip.For knee OA a. Corticosteroids:

For knee OA→ intended to improve elasticity & viscosity of synovial

fluid. e.g. Na hyaluronate & hylan polymers. b. Hyaluronic à

derivatives:

2 ml weekly for 5 weeks. Sodium hyaluronate:. N.B

2 ml weekly for 3 weeks. Hylan polymers:

*Most benefits occur after last dose: effects are superior to placebo & comparable to corticosteroid I

*These agents should be used with caution in pts with allergies to Avian proteins, feathers & egg pro

*Patients should be counseled to avoid strenuous or prolonged > 1 hr weight bearing activities

within 48 hrs following ttt.

:3. Adjunctive treatment

Promotes the synthesis of glucosaminoglycans.

S.E: GIT discomfort, fatigue, skin rash & hyperglycemia. a. Glucosamine:

9

Help to protect against breakdown of Collagen & proteoglycans.

-Usually found in combination with Glucosamine.

S.E: Prolong bleeding time & nausea.

b. Chondroitin:

(SAMe)→ also used as mild antidepressant. methionine -adenosyl-c. S

It is considered when pain →Joint replacement& Arthroscopye.g. Interventions:4. Surgical

is severe & not responding to medical treatment or when disability interferes with daily activity.

hypoxanthine Xanthine oxidase Xanthine →Purines →RNA, DNA Gout:Xanthine Oxidase Uric acid crystals phagocytosis of uric acid crystals by

Neutrophiles.

Release of leukotrienes & other inflammatory mediators→ Rupture of

Lysosomes, followed by death of phagocyte & release of hydrolytic enzyme→

∴Acute Inflammation.

Gout attacks may be:*

Intercritical gout: Chronic attacks: Acute attacks:

Prophylaxis & low doses of

Colchicine & NSAIDs

by: ttt

Allopurinol + Probencid

1) Colchicinettt by:

2) Steroids & NSAIDs

include:Treatment strategies *

1. Reducing inflammation during acute attacks (by Colchicine, NSAIDs & GCs).

2. Increasing renal excretion of Uric acid.

Inflammatory drugs:-A. Anti

*M.O.A: 1) Binds to Tubulin (microtubular protein)→ polymerization.

2) Leukocyte migration to site of action.

3) Inhibits synthesis & release of Leukotrienes.

*S.E: 1) Nausea, Vomiting & abdominal pain.

2) Myopathy, Neutropenia, Aplastic anemia & alopecia.

3) Dose adjustment in pts taking Cyt p 450 inhibitors.

4) Dose is reduced in pts with renal impairment.

1. Colchicine:

low doses 0.5-1 mg/day

production →Oxidase Inhibitors:-B. Xanthine

*M.O.A: Competitively inhibit xanthine oxidase uric à production.

*S.E: 1) Hypersensitivity reactions

2) NSAIDs or Colchicine are administered concurrently.

3) GIT S.E, N, V & Diarrhea ∴ taken with food.

A. Allopurinol:

2 hrs 1/2t

metabolismAlloxanthine

(oxypurinol) (active

15 hrs. 1/2t metabolite)

*New Xanthine oxidase Inhibitor.

*S.E: Like Allopurinol, with 6-mercaptopurine, Azathioprine & theoph. B. Febuxostat:

C. Uricosuric Agents:

by inhibiting urate →Renal clearance of uric à M.O.A:*

reabsorption in proximal tubules.

1) Gastric distress. S.E:*

& Probencid

:Sulphinpyrazone

10

2) Probencid blocks tubular secretion of Penicillin & level of

some AB.

3) Excretion of NSAIDs Naproxen, Ketoprofen, Aspirin.

Probencid is C.I in pts with Renal clearance < 50 ml/min.-: C.I

-Sulphinpyrazone is C.I in pts with Bone marrow suppression.

-C.I. In pts with Urinary tract Stones.

N.B. Rasburicase→ recombinant urate oxidase→ttt of Hyperuricemia.

Antagonists:VI. Autacoids, Autacoids Analogs &

Drugs Used to treat Migraine: Antagonists -1H

(Antihistamines):

Prostaglandins:

Sumatriptan

Eletriptan

Frovatriptan

Rizatriptan

Naratriptan

Almotriptan

Zolmitriptan

Dihydroergotamine.

ظلمها المو نار رز بتاكل و فروفا عملت اللى سوما

*Promethazine P

*Cetrizine C

*Meclizine M

*Fexofenadine F

*Acrivastine A

*Hydroxyzine H

*Levocetrizine L

*Loratidine L

*Diphenhydramine

*Dimenhydrinate 5

*Desloratidine D

*Doxepin

*Doxylamine.

analogues: 11. PGE

ttt of Impotence →Alprostadil

ttt GI Ulcers. →Misoprostol

:analogues 22. PGE

.cientafiAbort →Dinoprostone

analogues: −3. PGF2

Abortifacient. →Carboprost

& Travoprost, Latanoprost

Glaucoma. →Bimatoprost

analogues:4. PGE I

→Treprostinil& Epoprostenol

for ttt of pulmonary HTN.

they are 20 carbon atom fatty acids. I. Prostaglandins:

∴Chemically resembles lipids.

IMPORTANT. →SCHEDULE ABOVE FROM ANALOGUES STUDY

:Abortion1) *Uses:

-Use of Mifepristone (anti-progestin/ oral) followed by intravaginal Misoprostol.

2) Peptic Ulcer: - Misoprostol gastric acid secretion & enhance mucosal resistance to injury in peptic ulcer.

blockers. 2∴ use PPI & H →Cause GIT disturbance -

2. Histamine:

high amounts in lungs, skin & GIT. Location:- (stored in Mast cells). HistamineHistidine decarboxylase Histidine Synthesis:-

: Stimuli as Cold, Toxins, Venoms & Trauma.Release- Effects which occur due to stimulation of Histamine receptors:-

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1. Exocrine excretion→ mucous→ respiratory symptoms.

2. Bronchial smooth muscles→ Contraction.

3. Intestinal smooth muscles→ Contraction & Cramps.

4. Sensory nerve endings→ Itching & pain.

receptors:-11. H

Gastric acid secretion. receptors:-22. H 1. PR→ BP→ NO release. 2. Skin→ dilation of capillaries→ triple response.

(wheal formation- Reddening- Flare).

receptors:-2& H 13. H

Histamines:-II. Anti

*Second generation: *First Generation: *Desloratidine *Loratidine. *Fexofenadine (metabolite of Terfinadine).

.Cetrizine* *Acrivastine.

Motion sickness: Anti-allergic:

*Diphenhydramine. *Hydroxyzine. *Meclizine. *Cyclizine. *Dimenhydrinate.

*Diphenhydramine. *Hydroxyzine. *Promethazine *Chlorpheniramine. *Doxylamine.

*Characters: 1. CNS depression (mainly). 2. CNS stimulation (in some patients). 3. Local anesthetic activity→ relief itching (creams).

:*Therapeutic Uses

*D.O.C→ Allergic Rhinitis & Urticaria. *Not D.O.C in bronchial asthma. N.B. Anti-histamines have no anti-inflammatory activity. N.B. Epinephrine is D.O.C in Anaphylaxis

1. Allergies & Inflammatory conditions:

*Prevent Nausea & Vomiting mediated by chemoreceptor & vestibular pathways.

receptors.-& M 1emetic action due to blockade of central H-*Anti *N.B. Promethazine is potent anti-emetic & antihistaminic agent.

&2. Motion sickness Nausea: (along with Scopolamine)

*Diphenhydramine & Doxylamine→ ttt of Insomnia due to strong sedative properties. (OTC sleep aid). N.B. Azatadine: sedating antihistamine.

3. Sominafacients: القلق لعلاج

*Side Effects:

penetrate BBB →generation st: 1Sedation1) ∴ Less sedating. →Don't penetrate BBB →generation nd 2

Anticholinergic S.E: 2) a. Dry mouth. b. Blurred vision. c. Urinary retention. d. Tachycardia.

imp.*Drug Interactions: including alcohol.CNS Depressants 1)

potentiate anticholinergic effects of antihistamines. →MAOIs2)

12

→Rivastigmine & Galantamine)Donepzil, Choline Esterase Inhibitors (3) Antihistamines→ action of these drugs.

*Overdose: -Hallucination, Excitement, Ataxia & Convulsions. -Deeping Coma & Collapse of Cardio-respiratory system.

:HT)-(5 3. Serotonin

1. Serotonin antagonists:

: ttt of Nausea & Emesis associated with Cancer Ondansetron-chemotherapy.

.diarrheasymptom is ryIBS whose 1: used for ttt of women with Alosetron-

*S.E & Precautions: Headache, Constipation & Dizziness.

antagonists: 3HT-5

2. Serotonin agonists:

release of acetyl →receptors 4act on 5HT →Tegaserod &Cisapride *choline → gastric & intestinal motility.

: ttt of GERD.Cisapride-

whose 1ry symptom is constipation.: ttt of women with IBS Tegaserod-

S.E & Precautions:* -Diarrhea & Abdominal cramps. -Cisapride→ Torsade de pointes.

agonists: 4HT-*5

Naratriptan, Rizatriptan, , *Sumatriptan Frovatriptan. Almotriptan , Zolmitriptan

presynaptic release of serotonin/ NE Act at this autoreceptor to M.O.A:*

so vasoconstriction of Cerebral vessels can't occur.

: Chest tightness.*S.E & Precautions

coronary vasoconstriction.1) Angina patients due to *C.I:

2) Patient who received Ergotamine derivatives within past 24 hrs.

: with MAOIs: avoid use within 2 weeks after discontinuing MAOIs*D.I

agonists: 1D HT-*5

13

3. Serotonin partial agonists:

Ergonosine Dihydroergotamine Ergotamine .Bromocriptine sergide Methyl

: ttt of migraine & prevention of post partum hemorrhage.Ergots: Uses*

→Uterine Contraction →Methyl Ergonavine& Ergonavine- ∴ used in ttt of Uterine hemorrhage & to induce labor

Vasoconstriction so C.I. in:: S.E & Precautions*

1. Angina 2. Pregnancy.

*Ergot Alkaloids:

(VVV. Imp) **Drugs Used to treat Migraine:

Migraine:*Types of

72 hrs.-2 →:1. Without Aura -Accompanied by Nausea, Vomiting, Photophobia & Phonophobia (sensitivity to sound).

Neurologic symptoms called aura that precede the attack by →2. With Aura:

20-40 mins mainly visual & can be sensory or disturbance in speech or motor.

N.B. Females> 3 folds of men in migraine attacks.

*Symptomatic treatment: .NSAIDs-

emetic.-anti →Prochlorperazine- vasoconstriction & release of →agonist 1DHT-5 →Dihydroergotamine& Triptans-

pro-inflammatory Neuropeptides.

-Causes less nausea compared to Ergotamine. For cluster headache). →(Parentraloral, S.C & I.V →Sumatriptan-

Onset 20 mins while oral 1-2 hrs. more effective than Sumatriptan. →Eletriptan& Zolmitriptan- more tolerated. →& Almotriptan Naratriptan-

24 hrs. 1/2longest duration t →Frovatriptan-

B.P & CV events. S.E:-

200 mg/day. →100 mg-oral 25: Dose*

dose. ndgive 2 → headache may reoccur →Given as single dose N.B. Patient must wait at least 2 hrs, if no relief give another dose.

1. Triptans:

14

Agonist. 1DHT-& 5 1BHT-*5

IV administration→ as effective as Triptans.

S.E→ Nausea.

2. Dihydroergotamine:

Propranolol, Nadolol, Timolol & Atenolol. →blockers-1. B *For Prophylaxis:

fluoxetine →SSRIsAmitriptyline & →2. TCA

Divalproex, Gabapentin & Topiramate. → 3. Anticonvulsant

Verapamil & Diltiazem →4. CCB

Aspirin 6. 5. Clonidine

Triptans1. Acute attacks ttt:

Dihydroergotamine2.

3. NSAIDs→ Aspirin, Naproxen & Meclofenamate.

4. Opioids→ Codeine & mepridine

N.B. *Prodormal phase:

-visual disturbance that precede attack

-Arterial vasoconstriction & serotonin release

*Headache phase:

-pain, nausea & vomiting

-vasodilation & decrease serotonin

N.B Cromolyn & Nedocromyl→ mast cell stabilizers used in ttt of bronchial

asthma.

Prevention is exclusively prescription only

"(v)ery (v)oltaile (p)harmacotherapeutic (A)gents (F)or (M)igraine

(P)rophylaxis

V→ Verapamil

V→ Valproic à

P→Pizotifen (5HT2 antagonist with antihistaminic and weak anticholinergic properties).

A→Amitriptyline

F→Flunarizine/Fluoxetine

M→ Methyl sergide

P→ Propranolol

*Put (T) or (F):

Sumatriptan mimic serotonin action (T).

N.B. Sinus Headache:

1. Pain in periorbital area.

2. Pain is great on awakening→ why?

due to accumulation of fluids in Sinus cavities.

15

4. Leukotrienes