OA/RA/AD Pharmco Flashcards
Aspirin
- Non-selective COX Inhibitor
- pseudo- irreversible
- Uncouples mitochondrial oxidative phosphorylation
Aspirin ADR
- NVD
- GI upset + Bleed
- heartburn
- tachycardia
- Asthma
- Blood in vomit and stool
Which PG gives GI protection?
COX-1: PGE2
What happens when you inhibit PGE2?
GI Bleeding + peptic ulcer
Which COX and PGs are important for cardio?
COX-1 and COX 2
PGI2 and TxA2
Which NSAIDs are NON-selective but has more COX-2 activity?
- Diclofenac
- Etodolac
- Ketorolac
- Meloxicam
NSAID Prodrugs?
- Diclofenac
- Nabumetone
- Sulindac
NSAID Therapeutic use
- Headache
- Fever
- Pain
- RA/OA
- Dysmenorrhea
- Bursitis, tendonitis
What occurs when you take Aspirin with another NSAID?
You lose antiplatelet effect
NSAID ADR
- NVD
-Ulcers - Neutropenia
- Aplastic or Hemolytic Anemia
- Eosinophilia
- Hypersensitivity
- decrease in GFR
NSAID is associated with?
- Nephrotoxicity
- hematuria
- fluid retention
- colitis
COX-2 Inhibitors
- Celecoxib
Celecoxib Use
- OA/ RA
- Pain
- Dysmenorrhea
Celecoxib DI
- Fluconazole
- Lithium
- Loop diuretic
- Warfarin
- Rifampin
- MTX
Acetaminophen
Cox-3 inhibitor
Analgesic
Antipyretic
(Not anti-inflammatory)
High activity when Low ROS
APAP ADR
- Hematological effects
- CNS depression
- GI irritation + bleeding
- Metabolic acidosis
Arthritis treatment
- anti-inflammatory drugs
- Steroids
- Immunosuppressants
Other drugs for Arthritis
- capsaicin
- tramadol
- opioids
- duloxetine
Capsaicin
Desensitizes TRPV
Depletes Substance P
Tramadol
- opioid
- mu receptor agonist
- Suppresses 5-HT and NE- mediated nociceptors
Duloxetine
- SNRI
- 5-HT2A agonist
Anti-inflammatory Corticosteroid Class
Class 1 - Most potent
Class 7 - Least Potent
Corticosteroid MOA
Stimulate the synthesis of lipocortin which inhibits PLA1 from synthesizing AA
Corticosteroid effects
- Anti-inflammatory
- anti-mitotic
- immunosuppressant
- vasoconstriction
Corticosteroid ADR (short-term)
- GI issues
- Fluid retention
- insomnia
- agitation
- concentration difficulties
- irregular menses / vaginal yeast infection
Corticosteroid ADR (rare)
- psychosis
- diabetes
- Aseptic necrosis (skeletal)
Corticosteroid ADR (long-term)
- myopathy
- fragile skin
- osteoporosis
- lipodystrophy
- hair loss or facial hair
- cataracts
What are DMARDs?
Disease Modifying Anti-rheumatic Drugs
- immunosuppressants
- Stop underlying progression (without analgesic and inflammatory effects)
DMARD drugs
- hydroxychloroquine
- leflunomide
- methotrexate
- sulfasalazine
- tofacitinib
- baricitinib
- upadacitinib
Biologics are DMARDs
- TNF-inhibitor
- IL-1 Inhibitor
- IL-6 inhibitor
- T-cell inhibitor
- AntiCD20 Antibody
Anakinra
(Biologic)
- IL-1 inhibitor
- immunosuppressant
Anakinra ADR
- Immunosuppression
- Inj Site rxn
- Upper respiratory infection
- NVD
- Allergic rxn
- autoantibody dyscrasias
Methotrexate
- Inhibits Dihydrofolate reductase (DHFR)
- inhibit the synthesis of polyamine
- Anti-folate properties
Methotrexate ADR
- NVD
- Hepatic/renal Failure
- anemia
- rigidity
- GI issues
- CNS toxicity
- pharyngitis
- cirrhosis
- portal vein fibrosis
Methotrexate Contraindication
Do NOT take with NSAIDs
- NSAID compete with MTX which causes toxic levels of mtx in the blood
Leflunomide
- antirheumatic, immunosuppressant, immunomodulator
- Inhibits DHODH and pyrimidine synthesis (t-cell)
- analgesic, anti-pyretic, histamine-blocking
Leflunomide ADR Common
- alopecia
- Diarrhea
- increased LFTs
- rash
Leflunomide ADR serious
- bronchitis
- HTN
- Respiratory infection
- Hepatotoxicity
- SJS
Apazone + Nimesulide
- weak COX inhibitors
- inhibits interleukin and leukocytes
Tumor Necrosis Factor inhibitor
- blocks signals from macrophage to Helper T-cells (TNF-alpha)
- for severe RA
- May be toxic, but for QoL
What receptors are on the Osteocyte surface?
IL-1 receptor
IL-6 receptor
TNF receptor
TNF Inhibitor (drug names)
- adalimumab
- certolizumab
- etanercept **
- golimumab
- infliximab **
IL-6 Inhibitor Drugs
- Tocilizumab
- Sarilumab
B-cell Inhibitor (Anti- CD20)
Rituximab
CD80 and CD86 inhibitor
Abatacept
Infliximab
(biologic)
TNF-alpha NEUTRALIZER
- chimeric antibody
- reduces synovial inflammation, bone resorption, cartilage degradation
- binds to both transmembrane and soluble form of TNF
Infliximab ADR
(common) Abdominal pain, NVD
Serious
- delayed hypersensitive rxn
- infusion rxn
- an invasive fungal infection
- tuberculosis
- epilepsy
- worsening of CHF
Etanercept
(biologic)
- TNF-alpha BINDER
recombinant DNA technology
Etanercept ADR COMMON
- GI effects
- NVD
- Inj site rxn
- respiratory symptoms
- exacerbation of CNS disorders
Etanercept Serious ADR
- allergic rxn
- anemia
- leukopenia
- neutropenia
- pancytopenia
- thrombocytopenia
- sepsis
- optic neuritis (permanent )
Abatacept
(biologic)
- T-cell co-stimulatory inhibitor
- blocks release of co-stimulatory factors from APCs (prevent activation of T cells)
- binds to B7 protein
Abatacept ADR
- NVD. fever, chill flu-like symptoms, weight loss
- trouble breathing, chest pain, wheezing, painful urination
- skin infection
- stomach pain, indigestion, back pain
Tocilizumab
IL-6 inhibitor
- reduce pain + inflammation
- blocks metalloproteases
Tocilizumab ADR
- NVD
- Flu-like symptoms
- trouble breathing, chest pain, phlegm, painful urination
- Skin infection
- blistering rash
- bruising, tarry stool, coffee ground vomit
- stomach pain, indigestion, back pain
Sarilumab
IL-6 Inhibitor
- Human monoclonal AB
- IL-6 receptor inhibitor
- reduces pain and inflammation
- slows/ prevents joint dmg
Rituximab
(biologic)
- B-cell CD20 inhibitor
- B-cell lysis
Rituximab ADR
- NVD
- CV
- inj site rxn
- allergic rxn
- abdominal pain
- flu, bronchitis
- vertigo
- Heart failure
Tofacitinib
- JAK 1/3 inhibitor
- blocks STAT activity, affecting gene expression
- reduction in t- and b- lymphocytes
Tofacitinib ADR
- Systemic infection (nose, throat, UTI)
- NVD, headache
- increase in TG/ cholesterol
Upadacitinib
JAK 1 inhibitor
Baricitinib
Oral
JAK 1 AND 2 inhibitor
Baricitinib ADR
- IMMUNOSUPPRESSION
- Flu-like symptoms
- increased urination + pain (?)
- stomach pain
- diarrhea
- SoB
- pink/ red mucus
Cutaneous Drug Reaction
- can be mildly discomforting or life-threatening
- often associated with anti-infective and anti-convulsant medications
Major classes that Cause cutaneous rxn
- NNRTI
- Anticonvulsant
- sulfonamides
- antibiotics
- NSAID (oxicams)
- Antifungal
- Antimalarial
- allopurinol
(Main) 4 drugs Cutaneous Rxn
- sulfamethoxazole-trimethoprim
- sulfasalazine
- phenytoin
- carbamazepine
Exfoliative Dermatitis
- aka erthema multiforme
- mainly seen on extensor surface
- may be associated with herpes, systemic infection, Disease-drug rxn
- sudden onset with history of occurrance
Erythema multiform MAJOR (SJS)
- more than 50% of skin has fallen off
- erosive involving 2 or more mucosal surface
- commonly: coral, conjunctiva
Drug-Induced EM
Toxic Epidermal Necrolysis
- most severe vesiculobullous disease on this spectrum
- more than 20% BSA in 24 hrs
- Skin peels in large sheets
- accompanied by: constitutional (flu-like) symptoms
SJS Treatment
- supportive
- fluid balance; acid-base
- pain management
- prednisone
- Cyclosporine or azathioprine
- IgG
- Biologics (infliximab)
loss of skin - loss of protein
Low dose Aspirin Inhibits?
COX-1
Heteroaryl propionic acid
- contains heteroaryl ring
- more cox-2 than cox-1
- this selectivity lowers GI risks
Oxicams
Tautomer B is more potent than Tautomer A.
Why?
In Tautomer A, there is NH which allows the H to constantly travel. In tautomer B, Instead of NH, it’s a N= which stops the movement of H
COX-1 enzymes
- constitutive
- Produces TxA2
COX-2 enzymes
- Induced by cytokines and GFs to produce PG
- Produces PGI2
PGI2 (prostacyclin)
- vasodilator
- anti-platelet
Phospholipase A2
Cleaves AA from cell membrane phospholipids
Misoprostol
- Semi-synthetic derivative of PGE1 (prodrug)
- reduced gastric ACID secretion
- stimulates gastric MUCUS secretion
- Vasodilation (increased blood flow)
TxA2 (thromboxane)
- vasoconstriction
- platelet aggregation
Antidote to APAP?
N-Acetyl Cysteine
