Drugs Flashcards
Albuterol
B2 specific (Rescue inhaler)
• Fast onset; intermediate duration (3-6 hours)
• Relaxes bronchial smooth muscle
• Use in acute exacerbations (rescue inhaler)
• “Albuterol used Acutely”
• Overuse can down-regulate ß-2 receptors; short course inhaled corticosteroids can bring this back up
• Major Side Effect: hypokalemia/QT prolongation
Salmeterol
B2 specific, slow onset (LABA)
• Slow onset; long duration (approx. 12 hrs)
• Prophylactic treatment for asthma
o The added steroid is to reduce inflammation
• Major Side Effect: hypokalemia/QT prolongation/arrhythmia
• BBW increased mortality (typically have monthly visits after prescription)
Formoterol + Steroid
B2 specific, slow onset (LABA)
• Slow onset; long duration (approx. 12 hrs)
• Prophylactic treatment for asthma
o The added steroid is to reduce inflammation
• Major Side Effect: hypokalemia/QT prolongation/arrhythmia
• BBW increased mortality (typically have monthly visits after prescription)
Ipratropium
Cholinergic antragonist
• Binds to Muscarinic Acetylcholine receptors to inhibit
o Allows for parasympathetic tone (bronchoconstriction) to be diminished
• Long lasting (24 hr)
• Used for COPD
• Actually is poorly absorbed, so little absorbtion (thus few systemic effects) and only local lung effects
• Major Side Effect: hypokalemia/QT prolongation
Tiotropium
Cholinergic antragonist
• Binds to Muscarinic Acetylcholine receptors to inhibit
o Allows for parasympathetic tone (bronchoconstriction) to be diminished
• Long lasting (24 hr)
• Used for COPD
• Actually is poorly absorbed, so little absorbtion (thus few systemic effects) and only local lung effects
• Major Side Effect: hypokalemia/QT prolongation
Theophyllin
Methylxanthine
• Induces bronchodilation via phosphodiesterase inhibition
o Less phosphodiesterase (no cAMP→AMP degeration) = Increased cAMP
• Stimulates PKA, thus inhibiting mysosin light chain kinase = smooth muscle relax!
• Also blocks adenosine (which would have promoted bronchoconstriction)
• Narrow therapeutic range (5ng-10ng = minor symtpoms; 20ng = severe symptoms)
o Cardiotoxicity (arrhythmias, tachycardia)
o Neurotoxicity (seizure, tremors, neuromuscular irritability)
• Metabolized by CYP450 (worry of drug-drug interactions)
Cromolyn sodium
- Inhibits degranulation of mast cells/eosinophil inflammatory contribution in the lung
- Common side effects: cough/bronchospasm upon inhalation
- Some rare side effects (heart/CNS problems)
Budesonide (w/formoterol)
Corticosteroid
• Used often in chronic asthma
• Blocks nuclear transcription on inflammatory genes (stops inflammation cytokine release)
o Inactivates NF-kB (which normally induces TNF-a production)
• Promotes anti-inflammatory gene expression
o Also upregulates ß2-receptors
• Adverse effects
o Oral candidiasis (local inflammatory response diminished) rinse and spit after use
o Bond demineralization/ decreased growth rate
o Cushingoid syndrome (moon face, weight gain, weakness, easy bruising, acanthosis, high blood pressure)
o Bone demineralization, decreased growth in children
Fluticasone (w/Salmeterol
Corticosteroid
• Used often in chronic asthma
• Blocks nuclear transcription on inflammatory genes (stops inflammation cytokine release)
o Inactivates NF-kB (which normally induces TNF-a production)
• Promotes anti-inflammatory gene expression
o Also upregulates ß2-receptors
• Adverse effects
o Oral candidiasis (local inflammatory response diminished) rinse and spit after use
o Bond demineralization/ decreased growth rate
o Cushingoid syndrome (moon face, weight gain, weakness, easy bruising, acanthosis, high blood pressure)
o Bone demineralization, decreased growth in children
Prednisone (oral)
Corticosteroid
• used to treat Aspirgillus induced asthma
Monteleukast
Leukotriene Receptor Blocker
• Block Leukotriene D4 (LTD4) receptors so they cannot exert effects:
o Pro-inflammation
o Bronchoconstriction
o Mucosa edema
o Increased mucus secretion
• Work well in aspirin induced asthma
o This is due to aspirin blocking COX1/COX2 so all arachidonic acid gets shunted down the leukotriene pathway
o Because this blocks the last step in tidal wave leukotriene effect
Zafirlukast
Leukotriene Receptor Blocker
• Block Leukotriene D4 (LTD4) receptors so they cannot exert effects:
o Pro-inflammation
o Bronchoconstriction
o Mucosa edema
o Increased mucus secretion
• Work well in aspirin induced asthma
o This is due to aspirin blocking COX1/COX2 so all arachidonic acid gets shunted down the leukotriene pathway
o Because this blocks the last step in tidal wave leukotriene effect
Zileuton
Leukotriene synthesis inhibitor
• Inhibits 5-lipoxygenase so no arachidonic acid gets put on the Leukotriene pathway
• Liver enzymes increase with this drug → regular liver function tests necessary
• Interaction with theophylline because CYP1A2 substrate
Omalizumab
Anti-IgE Antibody
• Binds IgE to stop IgE mediated degranulation of mast cells (reduced allergic response)
• Often combined with inhaled corticosteroids (reduce overall inflammation mediators)
• Shown to decrease severity/frequency of asthma attacks
• Often used in patients simply not responding to traditional therapy
Contraindicated drugs in Airway Disease
- Sedatives – depresses already impaired respiration
- ß-blockers – nullify ß-2 bronchodilators (will thwart rescue therapy!)
- aspirin/COX inhibitors – may shunt arachidonic acid down leukotriene pathway (aspirin induced asthma)
- ACE inhibitors – dry cough (a common side effect) due to depressed Kininase II activity can exacerbate asthmatic symptoms
Isoniazid
• Mechanism
o Interferes with mycolic acid synthesis to halt fatty cell wall production of TB
o “cidal” for rapidly dividing bacteria – extracellular bacteria
o “static” for slow growing bacteria – caseous lesions/macrophage housed
• It will penetrate host cells
• Resistance
o Never used as a single agent – there are ALWAYS about 100 resistant bacteria per lesion
• Blocking up take of the drug
• Alteration of enzymes responsible for mycolic acid synthesis
• Overproduction of enzymes for mycolic acid synthesis
• Pharmacology
o Absorption is good via oral or IM dose
o Distribution into all tissues and fluids
• Penetrates CSF
• Crosses placenta and distributes into breast milk
o Metabolism is in the liver
• N-acetyl transferase will alter it for excretion
• Speed of acetylation and presence of chronic liver disease are of interest
• Half-life varies from 1-4 hours because of patient differences
• CYP inducer in the liver; may be cause for drug-drug interactions
o Excretion in urine (75%)
• Kidney function is of interest
• Adverse Effects
o Peripheral neuropathy – “stocking and glove” pattern of burning sensation
• Caused by isoniazid competing with pyridoxal phosphate (helps produce Dopamine and GABA) which can be alleviated by vitamin B6 (pyridoxine) supplementation
o Hepatotoxicity – dose dependent due to toxic metabolite buildup
• Do not give with other hepatotoxic drugs (rifampin)
o Allergy
• Drug interactions
o Antacids with Al3+ salts – decrease absorption orally; take one hour before INH
o Levodopa – inhibits dopa decarboxylase, limiting this drug’s effectiveness
o Acetaminophen – induces CYP2E1, which increases the toxic metabolite of acetamenophen
o CYP metabolized drugs – inhibits other CYPs, so look out!
Rifampin/Rifabutin/Rifapentine
• Mechanism
o Inhibits RNA synthesis by binding B-subunit of RNA polymerase; halting protein synthesis
• Low affinity for mammalian polymerase
• Bactericidal for intra/extracellular TB
• Resistance
o Alteration of B-subunit of RNA polymerase (quite common, never use this drug alone)
• Pharmacology
o Absorption is good orally
• Food/para-aminosalicyclic acid can decrease absorbtion
o Distribution into all tissues and fluids
• Penetrates CSF
• Largely protein bound
o Metabolized in the liver via deactylation
• Liver dysfunction will change metabolic dynamics of the drug
• Increased deacetylation will be noted in the first two weeks of treatment
o Excreted in bile in the GI tract; will be reabsorbed via enterohepatic circulation if unchanged
• Adverse Effects
o Hepatotoxicity – jaundice will occur in people with liver disease/alcoholics/elderly/slow acetylators
o Body fluid discoloration is not really bad, but kinda weird
• Patients are advised to wear glasses because tears will stain contacts
• Drug interactions
o CYP inducer, worry of drug-drug interactions
Ethambutol
• Mechanism
o Inhibits arabinosyl transferase to halt arabinogalactn synthesis for cell wall
• Helps increase cell wall permeability
o Bacteriostatic, may be bacteriacidal at high concentrations
o Only works on actively dividing cells (making cell walls)
• Resistance
o None that’d been demonstrated
• Pharmacology
o Absorption is good orally (75% of oral dose)
o Distribution into all tissues and fluids
• Penetrates CSF
• Crosses placenta and distributes into breast milk
o Metabolized partially in the liver
o Excreted in the urine (50% of drug is unchanged)
• Renal dysfunction can seriously increase the half life (needs decreased dose)
• Adverse Effects
o Optic neuritis – decreased visual acuity/color discrimination/visual field
• Worrysome but reversible after therapy
• Visual exams are recommended
o Antacids with Al3+ salts – decrease absorption orally; take 3-4 hours before EMB
o Hyperuricemia – increased uric acid may lead to gout!
o Allergy
• Drug interactions
o None that’d been demonstrated
Pyrazinamide
• Mechanism
o Primary drug mechanism incompletely understood
o Some TB strains with enzymes converting [PZA→pyrazinoic acid (POA)] will result in lowering of pH that slows TB growth
o ‘Cidal’ or ‘static’ depending on what drug concentration is
• Resistance
• Pharmacology
o Absorption is good orally
o Distribution into all tissues and fluids
• Penetrates CSF
• Crosses placenta and distributes into breast milk
o Metabolized in liver in pyrazinoic acid (that active metabolite) then again into hydroxyl- pyrazinoic acid (the excretory compound)
o Excreted renally; if renal dysfunction is present, dose adjustment must be made
• Adverse Effects
o Hepatotoxicity (large doses for long times)
o Arthralgia/hyperuricemia – may be gout…if it is, discontinue immediately
• Drug interactions
Cycloserine
• Mechanism
o Blocks L-ananine racemase and D-alanine synthase
• Both needed for D-alanine incorporation into peptidoglycan for cell walls
• Causes weak bacterial walls/lysis
• Structural analogue that essentially clogs up the proteins
• Resistance
o None has been demonstrated
o Often this is used in complex pneumonias or resistant ones
• Pharmacology
o Absorption is good orally
o Distribution into all tissues and fluids
• Penetrates CSF
• Crosses placenta and distributes into breast milk
• Not protein bound
o Metabolized
o Excreted renally; renal dysfunction needs decreased dose
• Adverse Effects
o Neurological effects – headache, vertigo, suicidal thoughts (worry with depression), paranoia, seizures (worry with alcohol use)
• Drug interactions
o None noted
Ethionamide
• Mechanism
o Inactive pro-drug that’s activated within the mycobacterium
• Analog of isoniazid;
• Mechanism isn’t totally understood
• Resistance
o None has been demonstrated
• Pharmacology
o Absorption is good orally
o Distribution into all tissues and fluids
• Penetrates CSF
o Metabolized in the liver
o Excreted
• Adverse Effects
o GI disturbances – very common, drug is best taken with meals
o Hepatotoxicity – often these will resolve with stopping the drug
o Neurologic effects – depression, dizziness, tremors….etc.
• Pyridoxine is commonly given as condomodant therapy
• Drug interactions
o None is noted
Capreomycin
• Mechanism o Unknown o Only given by IM injection • Resistance o Always given with another drug o Last line of defense because of very bad side effects; often to resistant TB strains • Pharmacology o Not much known about this drug • Adverse Effects o Nephrotoxicity o Ototoxicity • Drug interactions o None noted
