-
Name different Prostoglandins (PGs)
- PGE1
- PGE2
- PGF2-alpha
- PGI2 (prostacyclin)
-
Rx of NSAIDS ulcers
Protective on GI mucous
Misoprostol
-
drug that Maintains PDA
Alprostadil
-
-
Contraindication for PGE1
Abortificient
-
Example for PGE2
Dinoprostone
-
Dinoprostone
Cervical ripening
-
PGF2-alpha action
- Uterine and
- bronchiolar muscle contraction
-
example of PGF2-alpha
- Dinoprost
- Carboprost (Abortificient)
- Latanoprost (Rx of glaucoma)
-
What is elevated in dysmenorrhea?
PGE2 & PGF2-alpha
-
PGI2 (Prostacyclin) action
- inhibits platelet aggregation
- vasodilator
-
Example of PGI2 and use of it
- Epoprostenol:
- Used in pulmonary HTN
-
Mechanism of action of Aspirin
Inhibits thromboxanes
-
thromboxanes (TXA2) action
- Oppose the effects of PGI2
- Promotes platelets aggregation
- Bronchoconstriction
- vasoconstriction
-
Effects
of PGI2 on Platelets
PGI2 activates cAMP--> inc. internal Ca++ pump--> dec. free Ca++ --> platelet stabilization
-
Effects
of TXA2 on Platelets
TXA2 activates Phospholipase C -->inc. IP3--> mobilization of bound Ca++ --> inc. free Ca++ --> Platelets aggregation
-
Name all Leukotrienes (LTs)
-
LTB4 action
Mediates inflammation --> Chemotaxis --> inc. free radical --> cell injury
-
action of LTA4 - LTC4 - LTD4
- -Release of slow-reacting substance of anaphylaxis
- -Bronchoconstriction
- -Vasoconstriction
-
what drugs affects Leukotrienes pathway and their action
- 1.Corticosteroids: Inhibits Phospholipase A2 enzyme
- 2.Lipoxygenase inhibitors
- 3.Leukotrienes Inhibitors
-
Zileuton action
Lipoxygenase inhibitors
-
Zafirlukast - Montelukast
Leukotrienes Inhibitors
-
Block cyclooxygenase
Antiinflammatory effects
-
Block lipoxygenase:
Immunosuppressant effects
-
MOA: NSAIDs
Block cyclooxygenase pathways COX1 & COX2 --> dec. PGs and TXA2
-
Only NSAIDs that irreversibly inhibits both COX1 & COX2 and is dose dependent
Aspirin (Acetyl Salicylic Acid)
-
5 Pharmacological Effects of Aspirin
- 1. Analgesic
- 2. Antipyretic
- 3. Anti-inflammatory effect
- 4. Antiplatelets aggregation
- 5. Uricosuric effect
-
MOA: Aspirin
Analgesic effect
Inhibition of PGs --> inhib. of sensitization of pain receptors by pain mediators as bradykinin and histamine
-
MOA: Aspirin
Antipyretic
- presence of pyrogens --> inc. production of
- IL-1 --> inc. PGE2 production --> inc. the "set point" of temp. to a higher level
-
MOA: Aspirin
Anti-inflammatory
- Through inhibition of COX2
- Aspirin
- affects signal transduction proteins
- interfers with cell surface selectins and
- integrins --> dec. neutrophil adhesion
-
MOA: Aspirin
Antiplatelets
aggregation
- Through
- inhibition of TXA2
-
MOA: Aspirin
Uricosuric
effects ???
low dose
high dose
low dose: Hyperuricemia by dec. tubular secretion
high dose: Uricosuric by dec. tubular reabsorption
-
action of aspirin on Hyperthermia
Aspirin resets the "set point" back to normal
-
action of aspirin on Hypothermia
Aspirin resets the "set point" even lower
-
action of aspirin on Euthermia
no effect
-
Aspirin Dosage for:
a-Headache
b-inflammatory conditions
c-decrease MI by 44%
- a- 1-2 tablets (325mg/pill)
- b- 3-5 g/day (9-15 pills/day)
- c- 1 tablet every other day or 1 baby aspirin 81mg/day
-
Aspirin high dose effect
- 1- respiratory alkalosis
- 2- metabolic acidosis
- 3- gastritis
- 4-inc. bleeding time
- 5- inc. prothrombin time
- 6-uricosuric
- 7- salycylism
-
with Aspirin high dose
Gastritis due to:
inhibition of PGE2
-
with Aspirin high dose
inc. bleeding time due to
dec. platelets aggregation
-
with Aspirin high dose
inc. prothrombin time due to
inhibition of synthesis of vit K factor
-
in Chronic dosing of Aspirin
Salycylism:
what r the signs and symptoms
Tinnitus, vertigo, and decrease hearing
-
Acute Aspirin Toxicity
- 1. Respiratory alkalosis then Respiratory acidosis
- 2. Hypokalemia
- 3. Metabolic acidosis
- 4. Fever
-
Aspirin
Hypersensitivity:
- Triad
- of : Asthma, nasal polyps, and atrophic rhinitis
-
Aspirin + Viral infection
Reye's Syndrome:
-
Aspirin drug interaction
Ethanol:
Increase GI bleeding
-
Aspirin drug interaction
Uricosurics
Aspirin blocks their activity
-
Aspirin blocks their activity
Oral hypoglycemics
Aspirin increases their activity
-
Aspirin drug interaction
Warfarin:
Aspirin increase warfarin toxicity
-
what dose will give severe toxicity
Adult
kids
Adult: 30 tablets (high dose)
Kids: 4-6 tablets (high dose)
-
Emergency Management for Aspirin toxicity
- 1.Gastric lavage
- 2.Activated charcoal
- 3.Alkalinization of the urine
-
example of distinct analgesic and fever reducing drug that is not an anti-inflammatory
Acetaminophen
-
Acetaminophen over dose
Depletion of GSH stores lead to accumulation of reactive metabolite which reacts with the hepatocytes
-
MOA acetaminophen
- A reactive metabolite (N-acetylbenzoquinoneimine)
- produced in the liver by P450 and is conjugated with reduced glutathione (GSH)
-
action of Acetaminophen
- Inhibits only centrally found cycloxygenase
- (CNS)
- Has no effects on peripheral cyccloxygenases
-
Acetaminophen toxicity
Hepatotoxicity
-
Acetaminophen
Antidote:
- Acetylcysteine
- Supply-SH groups that inactivate the metabolite
-
Reversible
inhibitors of COX1 & COX2
(9)
- 1-Ibuprofen
- 2-Naproxen
- 3-Etodolac
- 4-indomethacin
- 5-Ketorolac
- 6-Nabumetone
- 7-Sulindac
- 8-Tolmetin
- 9-Diclofenac
-
#1 pain relief and why
- Ibuprofen
- Doesn't
- affect activity of warfarin or hypoglycemic
-
-
Indomethacin side effect
- Thrombocytopenia,
- agranulocytosis
-
Sulindac side effect
Pancreatitis
-
Diclofenac side effect
Hepatotoxicity
-
Cox inhibitors that has no effect on hypoglycemic drugs
-
NSAIDs action
- 1. All have analgesic, antipyretic and antiinflammatory activity
- 2. Cross sensitivity with aspirin may exist
- 3. At antiinflammatory doses aspirin is less well tolerated than other NSAIDs
-
Side effects of NSAIDs
- 1. GI: Dyspepsia
- 2. Renal: Interstitial nephritis
-
NSAIDs-Drugs
Interactions:
decrease clearance --> increase activity
OF:
- Hypoglycemic
- Methotrexate
- Lithium
-
NSAIDs-Drugs
Decrease activity:
OF:
- Hypertensive drugs:
- ACE inhibitors
- Loop diuretics
- Beta Blockers
-
name some
Selective COX2 Inhibitors
- Rofecoxib
- Celecoxib
- Valdecoxib
-
COX1
receptors found in
- Blood vessels causing platelets aggregation and
- Stomach and are protective against ulcer
-
COX2
Receptors are activated by
inflammation
-
Rofecoxib
(Vioxx)
what family?
indication
- Selective COX2 inhibitors But COX1 receptors are activated
- Good
- for inflammation (Arthritis)
-
Rofecoxib (Vioxx)
what is the advantage and disadvantage of having COX1 receptors are active?
- Good for the stomach because it is protected
- Bad for the heart because of platelet aggregation
- leading to blood clot and myocardial infarction
-
Celecoxib Cross allergy with
sulfonamides
-
Drugs
used for Migraine
- 1.drugs ending in "Triptan":
- Sumatriptan, Zolmitriptan, Frovatriptan
- 2.Ergotamine and Methysergide
- 3.Analgesics: ASA, acetaminophen, Oral or IM opioid-analgesics,Butorphanol (Spray)
-
MOA
drugs ending in "Triptan"
Agonist at 5HT1D (serotonin) receptors in cerebral BV
-
adverse effect
drugs ending in "Triptan"
Possible asthenia, throat pressure
-
MOA
Ergotamine and Methysergide
- Partial agonist at alpha1 and 5HT2 in BV
- Vasoconstriction lead to decrease pulsation
-
Ergotamine and Methysergide
indication
- in
- acute attack of migraine
-
Migraine
Prophylaxis:
6
- 1.Beta blockers
- 2.Tricyclic antidepressant
- 3.Calcium channel blockers
- 4.Carbamazepine
- 5.Gabapentin
- 6.Valproic acid
-
Mechanism
of action of triptan
Serotonin Agonist
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