Drugs Flashcards
Atracurium Mechanism
Isoquinoline Derivative
Atracurium Pharm
Intermediate-acting
-hepatic met. + hofmann elimination
main product (laudanosine) causally related to seizures
-cisatracurium<histamine
Succinylcholine Pharm
- short duration (5-10min)
- rapid hydrolysis by butyrlcholinesterase (liver) and high capacity pseudocholinesterase (plasma)
- neuromuscular junction -sees only small percentage of IV dose, action terminated by diffusion from cleft, plasma cholinesterase strongly influences durability
- genetically variants of plasma cholinesterase
- increased risk for abnormally long effect
- dibucaine test used for identification (inhibits normal enzyme by 80% and abnormal enzyme by only 20%)
Succinylcholine Toxicity
- Hemodynamic changes:brady/tachycardia, ventricular arrythmias, HTN
- hyperkalemia in: large burn injuries, trauma/crush, upper/lower motor neuron injuries, muscular dystrophies, prolonged immobilization
- Prolonged neuromuscular blockade: phase II blockade, atypical pseudocholinesterase
- Increased intraocular or intercrainial pressure
- Muscle Pain
- Myoglobinuria
- Malignant HTN
- Anaphylaxis
Malignant Hyperthermia
treat with dantrolene to correct hyperkalemia/acidosis/cool core temp
-avoid Ca2+ channel blockers
Neostigmine Mechanism
AchE inhibitor
Neostigmine Pharm/Toxicity
Doesn’t cross BBB
- lasts 1.5 hr
- anticholinergic: glycopyrrolate
Pyridostigmine Mechanims
AchE inhibitor
Pyridostigmine Pharm/Toxicity
Doesn’t cross BBB
- lasts 1-2hr
- anticholinergic: glycopyrrolate
Methotrexate Mechanism
-inhibition of AICAR transformylase (which catalyzes the last step in the de novo biosynthesis of inosine monophosphate)
-leads to AICAR riboside accumulation, which inhibits adenosine deaminase, increasing circulation adenosine conc.
-adenosine inhibits lymphocyte proliferation & suppresses secretion of IL-1, INF gamma, TNF, increases IL-4, impairs histamine release, decreases chemotaxis of neutrophils
IMMUNOSUPPRESSION
Methotrexate Pharm
- undergoes polyglutamation-drug stays intercellular
- Elimination: kidney
- Metabolism: hepatic
Methotrexate Toxicity
-Bone marrow suppression/anemia
-Pulmonary toxicity-acute/chronic interstitial pneumonitis, pulmonary fibrosis
Contrindication: HIV, Pregnancy (CAT X), no breastfeeding
-avoid vaccine
-malignant lymphomas, fatal dermatologic rxns, GI toxicity with PUD/ulcerative colitis
Sulfasalazine Mechanism
- metabolized to active - sulfapyridine and mesalamine by bacteria in the colon
- absorbed sulfapyridine is acetylated an dhydroxylated in the liver
- anti-inflammatory properties of mesalamine (inhibitor of PF and LT production)
Sulfasalazine Pharm
Elimination: Renal
Oral
Sulfasalazine Toxicity
Hematotoxicity-fatal blood dyscrasias infrequent
Contraindications: known hypersensitivity to 5-aminosalicylate, salicylate, or sulfonamide drugs
Leflunomide Mechanism
active primary metabolite A77 1726 that inhibits dihydroorotate dehydrogenase (enzyme located in cell mitochondria that catalyzes a key step in de novo pyrimidine synthesis.
- in T&B cell cycle progression is arrested & their collaborative interaction interrupted
- Immunoglobulin production is suppressed
- cytostatic at normal doses
Leflunomide Pharm
Elimination: feces, other metabolites, flucuronide
uricosuric effect
Oral drug
Leflunomide Toxicity
-Hepatic (no alcoholics)
Contraindicated: immunodeficiency, bone marrow dysplasia, uncontrolled infection
CAT X
Hydroxychloroquine Mechanism
- increases intracellular vacuole pH and alters processes (protein deg by acidic hydrolases in lysosome, assembly of macromoleules in endosomes, post-translation modification of proteins in the Golgi apparatus)
- decreases immune response against autoantigenic peptides
Hydroxychloroquine Pharm
Elimination: extensive and slow renal elimination, following partial hepatic metabolism
Oral
Hydroxychloroquine Toxicity
Hepatic disease (alcoholism)
Blood dyscrasias
CNS toxicity: polyneuritis, ototoxicity, seizures, neuromyopathy
Contraindications: ocular disease b/c drug can cause corneal opacities, keratopathy, retinopathy
Abatacept Mechanism
Binds CD80 and CD86 prevents T-cell co-stimulatory signal engaging with CD28
(fusion protein: human CTLA4/IgG1 Fc fragment)
Adalimumab Mechanism
Binds TNF-alpha, blocks its interaction with the p55 and p75 cell surface receptors
(TNF-alpha monoclonal ab)
Anakinra Mechanism
Competitively inhibits IL-1 alpha & IL-1 beta binding to interleukin-1 type 1 receptor (IL-1R1)
Certolizumab pegol Mechanism
Neutralizes membrane-associated and soluble human TNF alpha (Fab fragment of humanized TNF-alpha ab)
Etancercept Mechanism
Endogenous p75 acts as a TNF antagonist. As a recomninant TNFR p75 bound to the Fc fragment of the human IgG1, etanercept binds to and inactivates TNF but does not affect TNF production or serum levels
Golimumab Mechanism
Binds to and neutralizes both soluble and transmembrane TNF-alpha
Infliximab Mechanism
Binds to and neutralizes both soluble and transmembrane TNF-alpha
Rituximab Mechanism
Fab domain binds CD20 & Fc domain recruits immune effector functions to mediate B-cell lysis (complement-dependent cytotoxicity, antibody dependent cellular cytotoxicity and induction of apoptosis are possible mechanisms) Sensitizes drug-resistant human B-cell lymphoma cell lines to cytotoxic chemotherapy
Tocilizumab Mechanism
binds to both soluble (serum & synovial fluid) & membrane-bound IL-6 receptors & inhibit signaling
Abatacept Toxicity
-Immunosuppression
-complicate blood glucose tests (has maltose)
INJECTION SITE ROTATION
Adalimumab Toxicity
-Immunosuppression
-Malignancy
-CHF/hypotension/angina/dysrhythmia
-Lupus-like syndrome
INJECTION SITE ROTATION
Anakinra Toxicity
-Immunosuppression
-Blood Dyscarsias
INJECTION SITE ROTATION
Certolizumab Toxicity
-Immunosuppression
-Malignancy
-Blood Dyscarsias
-Lupus-like syndrome
INJECTION SITE ROTATION
Etancercept Toxicity
-Immunosuppression
-Malignancy
-Lupus-like syndrome
INJECTION SITE ROTATION
Golimumab Toxicity
-Immunosuppression
-Malignancy
-CHF/hypotension/angina/dysrhythmia
Liver function test
INJECTION SITE ROTATION
Infliximab Toxicity
-Immunosuppression
-Malignancy
-CHF/hypotension/angina/dysrhythmia
Contrindication: moderate-severe CHF
-Lupus-like syndrome
Liver function test
Rituximab Toxicity
- Immunosuppression
- CHF/hypotension/angina/dysrhythmia
- Blood Dyscarsias
- Stevens-Johnson Syndrome (toxic epidermal necrolysis)
- shouldn’t get pregnant during or 4-6 months after (B-cell depletion b/c IfG crosses placenta)
Tocilizumab Toxicity
- Immunosuppression
* need serum lipid profile*
Celecoxib Mechanism
NSAID
COX-2 selective
Ketorolac Mechanism
NSAID
COX-1»COX-2`
Ibuprofen Mechanism
NSAID
COX-1=COX-2
Ketorolac Toxicity
highest GI risk
Ibuprofen Toxicity
lowest GI risk
high vascular risk
Acute hepatitis, ductopenia
Diclofenac Mechanism
NSAID
Diclofenac Toxicity
high vascular risk
Acute and Chronic Hepatitis
Mixed damage & pure cholestasis (liver)
Celecoxib Toxocity
GI risk
Acetaminophen Mechanism
NSAID
Acetaminophen Toxicity
IV or oral
IV-constipation/diarrhea
hepatic failure
Aspirin Mechanism
NSAID
irreversibly inhibits COX-1 in platelets
Aspirin Toxicity
GI risk
Acute & Chronic hepatitis
Reye’s Syndrome
Renal Toxicity
Salicylate poisoning (resp. alkalosis, met. acidosis)
-central respiratory depression & CV collapse
Indomethacin Mechanism
NSAID
Indomethacin Toxicity
GI risk
Ketoprofen Mechanism
NSAID
Ketoprofen Toxicity
GI risk
Naproxen Mechanism
NSAID
Naproxen Toxicity
Cholestatic, mixed damage (liver)
Piroxicam Mechanism
NSAID
Piroxicam Mechanism
GI risk
