Musculoskeletal System Pharmacology Flashcards
NSAIDS
Nonsteroidal anti-inflammatory drugsare anti-inflammatory, analgesic, and antipyretic agents
Examples of NSAIDS
Ibuprofen, naprozen, indomethacin, ketorolac and aspinr
MOA NASIDS
Reversible inhibition of cox1 and cox2 which blocks prostaglandin synthesis, along withthromboxane and prostacycline synthesis
What can NSADS decrease
Inflammation, pain, fever, and platelet aggregation
Side effects NSAIDS
Renal ischemia, interstitial nephritis, and gastric ulcers
Indications for NSAIDS
Anti-inflammatory
Analgesic
Fever
Closure of PDA
Anti-inflammatory NSADIS
Inhibit cox2
Analgesic NSAIDS
Inhibition COX 1 and 22
NSAIDs fever
Block PGE2 via COZ inhibition
NSAIDS closure of PDA
PGE1 is responsible for the potency of ductus arteriosus NSAID block PGE1 and close PDA
MOA NSAIDS
Reversible inhibit COX1 and 2 which results in inhibition of production of prostagladins and thromboxanes
If COX is inhibited, ___ cannot turn into prostagladins
Endoperoxides, preventing PGs from performing their role in inflammatory responses, pain processing and fever production
Side effects NSAIDS
Interstitial nephritis
Gastric ulcer
Renal ischemia
Interstitial nephritis from NSAID
Fever, rash, hematuria, CVA tenderness
Gastric ulcer nsaids
COX1 make PGs that help maintain the protective GI mucosal barrier in the stomach and intestines.
Renal ischemia NSAIDS
Decrease renal blood flow and renal damage from the vasodilator PGs
Aspirin /acetylsalic acid
Anti inflammatory, antipyretic, analgesic and antiplatlet drug
It is an NSAID
Asprin is an NSAID, but its MOA differs.
Irreversibly inhibits COx1 and 2 others do irreversibly
Indications for asprin
Fever, pain and headache, CVD
Fever asprin
Blocks PGE2
Asprin pain and headache
Inhibits COX1 and 2
Asprin CVD
Prevent MI and ischemic stroke
MOA asprin
Irreversible inhibition of COx1 and 2 inhibiting production of PG and TX
Cell membrane phospholipids are turned into arachidonic acid by _____
Phospholipase a2
Arachidonic acid is turned into COX 1 and 2 by what
Cyclooxygenase pathway
Arachidonic acis is turned into leukotrienes by what
Lipooxygenase pathway
COX1 (physiologic)
Prostagladins, thromboxane (stomach, intestine, kidney, platelets) mucosal protection, renal blood flow and haemostasis
COX2 (inducible)
Prostagladins
(Inflammatory sites, macrophages, synovocytes) inflammation pain and fever
Leukotrienes (inflammatory sites) inflammation
Inflammation
Side effects asprin
Reye’s syndrome Tinnitus Peptic ulceration Mixed acidosis/alkalosis Nephropathy
Reye’s syndrome asprin
In kids with viral infection -cause microvesicular stratosphere of hepatocytes, hepatoencephalopathy and potentially death
Tinnitus asprin
3g or more a day may cause ruining possibly due to activation of cochlear NMDA receptors
Peptic ulcer asprin
PG by COX1 help maintain the protective GI mucosal barrier in the stomach and intestines. Block can get ulcer
Asprin and mixed acidosis/alkalosis
Initial respiratory alkalosis due to hyperventilation and then metabolic acidosis
Presents as a mixed respiratory alkalosis and metabolic acidosis
Nephropathy asprin
Renal ischemia due to decreased renal blood flow, renal papillary necrosis or intestinal nephritis
Functions of asprin
Inhibiting platelet aggregation and as NSAID
Indication for asprin
Fever, pain, inflammatory conditions, prevention of thrombotic events
Side effects asprin
GI ulcer, bleeding, pancytopenia
Who should not be given asprin. Why
7-10 days after surgery or kids under 12
Reye’s syndrome
How does asprin inhibit platelet aggregation
Irreversible and by inhibiting cyclooxygenase
Effects will last as long as lifespan of the platelet (8 days)
NSAID asprin
Inhibit COX
Low dose-pain
High does-anti inflammatory
Indications for asprin
Thrombotic event prevention
General pain
Inflammatory conditions
Fever
Asprin thrombotic event prevention
Stroke, MI, also colorectal cancer
Inflammatory conditions that asprin can help
Arthritis, RA, osteoarthritis, rheumatic fever, tendinitis, bursitis
Side effects asprin
Pancytopenia
GI ulcers
Bleeding
Pancytopenia and asprin
Aplastic anemia, agranulocytosis, thrombocytopenia
Why not give asprin 7-10 days after surgery
It inhibits platelet aggregation for the entire lifespan of the platelet around 8 days
What is patient is on asprin before surgery
Increased risk of hemorrhage
Reye’s syndrome
Kids under 12 taking asprin
usually when taking when recovering from chickenpox or other viral
Never give kids asprin when recovering from an illness
Asprin poisoning is called what
Salicylism
Early symptoms of salicylism
Nausea vomiting (pH)
Tinnitus
Confusion (pH affect brain caused by hyperventilation or metabolic acidosis)
Hyperventilation (compensatory response—>respiratory alkalosis
Late symptoms of asprin poisoning
Metabolic acidosis (compensatory) Coma (pH changes ) Hyperthermia (may result in seizure or diaphoretic state)
Reye’s syndrome
Asprin in kids with viral illness such as chicken pox or flu
What can we use in kids recovering from illness instead of asprin
Acetaminophen
What is Reyes
Affects various organs throughout the body including fatty changes int he liver. As the child s liver begins to fail, lab results may show increased liver enzymes, such as ast, ALT and increased ammonia levels.
Characterization of Reyes
Acute encephalopathy
Early detection and treatment of Reyes is essential as death may result within hours if left untreated
Oh god
Assessment for Reyes
Cerebral edema-seizures/decreased consciousness
Lethargy-tired weak
Vomiting-common
Liver failure-fatty changes should check AST ALT and ammonia
Treat reyes
Early detection
Monitor OCP, respiratory rate, and bp
Give mannitor
Increased ICp
Cerebral edema
Changes in consciousness, headache, vomiting, abnormal/asymmetrical pupils and posturing
Mannitor
Osmotic diuretic treats ICP. Works by creating an osmotic gradient that pulls fluid from the brain into the vasculature and provides an immediate plasma expanding effect that reduces hematocrit and blood viscosity and leads to diuresis
No asprin for kids
Use acetaminophen
Ibuprofen (Advil Motrin)
NSAID that functions by inhibiting COX
Indication ibuprofen
General pain, fever, inflammatory conditions
Side effects ibuprofen
GI ulcers, nephrotoxicity, rash
Why no take ibuprofen with alcohol
Increase risk of GI irritation and bleeding, decreases platelet aggregation which is further produced with alcohol use
Risk of thrombotic event with ibuprofen
Selective COX2 inhibitor
Why do we not get risk of thrombotic event when COX1 and 2 are inhibitred
COX1 decreases platelet aggregation which does not occur with selective COX2 inhibitors
Acetaminophen(Tylenol)
Anti-pyretic and analgesic drug that lacks the anti-inflammatory or anti platelet effects seen with asprin and NSAIDS
Acetaminophen reversible or irreversible
Reversible inhibiting COX and having centrally activity
Indications acetaminophen
Fever
Pain
MOA acetaminophen
Reversible inhibit COX
Acts in CNS -useful for fever and headache
Side effects acetaminophen
Hepatic necrosis
N-acetylcysteine antidote
Hepatic necrosis acetaminophen
5% metabolized by CYP enzymes to NAPQI, which is conjugated with glutathione
What happen with high doses of acetaminophen
NAPQI accumulate and cause centrilobular hepatic necrosis due to biding and damage to hepatic proteins and increased susceptibility to reactive oxygen species
N-acetylcysteine
Antidote to acetaminophen toxicity.
It is a glutathione precursor that when given can help result in conjugation and NAPQI.
What is rumack Matthew normogram
Used to determine whether treatment with N-AC is required and N-AC can be given within 8 hours of acetaminophen ingestion
Celecoxib
COX2 selective NSAID that lacks many of the toxic GI effects of other NSAIDS that have COX1 inhibitory effects in addition to COX2
Indications for celecobix
RA, osteoarthritis, pain
MOA celecobix
NSAID but selectively blocks COX2 little effect on 1
SO NO GI effects
Side effects celecoxib
It is a sulfonamide-sulfa allergy increased risk of thrombosis (COX2 on vascular endothelial cells get decreased prostacyclin production and platelet aggregation)
GI bleed-spares COX1, but patients with history still occur
Who should not take celecoxib
Pregnan tover 30 weeks
Category D drug
Describe passage of acetaminophen
Rapidly absorbed from the stomach and AI and primarily metabolized by conjugation in the liver to nontoxic water soluble compounds that are eliminated in the urine,
Overdose acetaminophen
Metabolism by conjugation becomes saturated and excess acetaminophen is oxidatively metabolized by CYP enzymes to the reactive metabolite NAPQI
NAPQI
Extremely short half life and is rapidly conjugated with glutathione stores and really excreted
Excess NAPQI
From increased formation or decreased glutathione
Covalently binds to cysteinyl sulfhydryl groups of hepatocellular proteins causing a cascade of oxidative damage and mitochondrial dysfunction
This inflammatory response propagates hepatocellular injury, death, and centrilobular (zone III) liver necrosis
Antidote to acetaminophen poisoning
N-acetylcysteine which is.a precursor of glutathione among other mechanisms
Prednisone
Ok
Alendronate (fosamax)
Bisphosphonate that suppresses bone resorption and inhibits bone breakdown in individuals with pages disease or those experiencing post menopausal or corticosteroid induced osteoporosis
Side effects alendronate (fosamax)
Esophageal ulcers, musculoskeletal pain, changes in vision, atrial fib, osteonecrosis of jaw with IV solendronate
Why should we take alendronate on empty stomach and upright for 30 min
Idk but they must do that to prevent inflammation or irritation of the throat
MOA alendronate
Inhibits osteoclasts
It incorporates into bone and this inhibits bone resorption which decreases the activity of osteoclasts
Indications for alendronate
Osteoporosis
Pager
Osteoporosis and alendronate
Estrogen inhibits osteoclast During menopause we lose And osteoclast activity Can lead to increased risk of bone loss In men aldonrate works to increase bone mineral density, prevent fractures, and reduce loss of height related to osteoporosis
Pa gets disease and alendronate
Cause by excessive bone breakdown and abnormal remodeling of the bone
Can prevent further breakdown
Given ca while on it to prevent secondary hyperparathyroidism caused by decrease Ca related to inhibition of bone resorption
Calcitonin may be prescribed for pain relief that occurs with paget
Side effects alendronate
Esophageal ulcers, MSK pain, vision changes, a fib, osteonecrosis of jaw
BRONJ
Bisphosphonate related osteonecrosis of the jaw associated with intravenous infusion of zolendronate
What is gout
Acute inflammatory mono arthritis related to uric acid content which is painful, debilitating, and deforming
Treatment of gout
- Drugs which are give for acute attacks
2. Drugs given for chronic maintence and prevention
Chronic drugs for gout
Inhibitors of da thing oxidase such as allopurinol and febuxostat,
Inhibitors of uric acid reabsorption in the proximal tubule of the kidney like probencid
Acute gout meds
NSAIDS, glucocorticoids, colchicine
Colchine
Impaired leukocyte chemotaxis
It inhibits microtubule polymerizationby binding to tubules. As tubules is important for mitotic function, it works as a mitotic poison . This inhibits cytoskeleton recruitment, impairing leukocyte chemotazis and degranulation
Allopurinol and febuxostat
Inhibit xanthine oxidase
Probenecid
Inhibits reabsorption or uric acid in proximal tubule of kidney so excrete more
MOA probenecid
Interfering with kidneys organis anion transporter, which reclaims uric acid from the urine and returns it to the plasma. Preventing reabsorption or uric acid so it is in pee
For chronic gout
TNF-alpha inhibitors
Work to block tumor necrosis factor
TNFa
Released by macrophages and is the master regulator of the inflammatory response in many organ systems and directs other cytokines and lymphocytes to cause cell destruction and inflammation
What causes autoimmune disease
Overactive immuneresponse
What drugs inhibit TNFa
Etanercept and infliximab
MOA tnfa inhibitors
Prevent activation of macrophages and destruction of phagocytosis material helping to treat autoimmune disorders
MOA TNFa inhibitors
Downregulates proinflammatory cytokines
Decreased lymphocyte activation and migration (fever and hypotension by leukocyte recruitment so this is blocked)
Granuloma breakdown (tnfa needed to induce and maintain granuloma)
Indication for TNFa inhibitor
Crowns disease RA Juvenile RA Psoriasis Ankylosis spondylitis
Crowns
Characterized by noncaseating granuloma and lymphoid aggregates leading to transmural bowel wall inflammation
RA TNFA inhibitors
Cytokines and type III and IV hypersensitivity mediated destruction of synovial joints
Juvenile RA and TNFA inhibitors
Seronegative arthritis and inflammation of synovial joints, without cause. Treated with newer TNFa inhibiting drugs
Ankylosis spondylitis
Chronic inflammatory arthritis associated with bamboo spine on x ray and HLAB27 serum protein can be treated with TNFa inhibitor
TNFa does what
Inflammatory. Process and leads to cachexia and is a potent pyrogen and plays a large role indiseases such as ankylosing spondylitis, RA, crohns and other.
Complications of TNFA inhibitors
Infection, TB reactivation or dissemination
Etanercept
TNF decoy receptor which binds to TNF and blunts the immune response
Etanercept works as a __ protein, which acts as a TNF decoy receptor
Fusion
What does etanercept do
Mimics the inhibitory effects of naturally occurring TNF receptors but has a longer half life and more profound long standing inhibitory effect
Anti TNF a antibody neutralizes the actions of TNFa by working as an anti TNFa antibody. It binds with high affinity to TNF, blunting the inflammatory response by autoantibodies in various disorders
Ok
Adalimumab
Monoclonal antibody and has a high specificity and affinity for TNF a . It has the capability to lyse cells involved in the inflammatory process helping to alleviate symptoms
Infliximab
Monoclonal antibody and has a high specificity and affinity for TNFa . It has the capability to lyse cells involved int he inflammatory process, helping to alleviate symptoms
Complications of TNFa inhibitors infection
Predispose to TB reactivation
Ok
Why do TNFa inhibitors increase risk of infection
Blunting recruitment of other cytokines and lymphocytes preventing activation of macrophages and inflammation leads to an increased risk of infection and patients should be considered immunocompromised
Why do TNFa inhibitors predispose to TB reactivation
Latendresse TB deactivated as macrophages are inhibited. Granuloma are effectively broken down with these medications, which release and disseminate TB which was encapsulated and isolated
What do before put on TNFa inhibitor
PPD skin test
Quantiferon gold in tubeorder heat x ray
QFT
Interferon y release assay used in TB diagnosis . The QFT-GIT assay in Elisa based, whole blood test that uses peptides from there TB antigens in an in tube format. This test has 99% specificity and sensitivities 92
