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pharmacodynamics
how drugs work; mechanism of action
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pharmacokinetics
how drugs move through body
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pharmaceutical drug interactions (and 3 causes)
- drug reactions outside of body
- 1. incompatible drugs
- 2. a drug and it's carrier
- 3. a drug and receptacle
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Drug and receptacle interaction & remedy
- Typically decreases efficacy.
- EX: Lipid soluble drugs bind with plastic tubing. Diazepam, insulin, dextrose.
- Remedy: flush line with 50 mls to saturate plastic
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Drugs that have decrease absorption with food (3)
- 1. Ampicillin
- 2. Tetracycline
- 3. Theophylline
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Drugs that have delayed absorption with food (4)
- 1. Cephalexin
- 2. Cimetidine
- 3. Digoxin
- 4. fluoroquinolones
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Drugs that have increased absorption with food (2)
- 1. Diazepam
- 2. Propranolol
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Why does sucralfate inhibit action of other drugs?
Can prevent absorption of other drugs
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What drug interaction inhibits the action of sucralfate?
Sucralfate requires acidic environment, drugs that increase gastric pH so can inhibit the action of sucralfate.
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Drugs that can inhibit the absorption of other drugs in GI tract (4)
- 1. Sucralfate
- 2. aluminum hydroxide
- 3. antacids
- 4. activated charcoal
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Pharmacokinetic drug interactions:
One drug directly alters action of another drug
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Synergistic
Effect arising between 2 or more agents, entities, factors, or substances that is greater than the sum of their individual effects
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Pharmacokinetics includes (4)
- 1. absirotuib
- 2. distribution
- 3. biotransformation
- 4. excretion
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Parenteral administration
Injection or infusion (IV, SQ, IM, ETC)
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Administration route with the greatest potential for alteration:
Oral
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Hepatic recirculation
excreted through bile, delivered to GI tract, potentially absorbed. Recycled instead of excreted may prolong effects.
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What administration route(s) may be affected by hydration status and temperature
SQ and IM
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Dehydrated or hypothermic produces what absorption rate
- poor absorption for IM or SQ
- Once rehydrated or warmed may cause rapid absorption +/- overdose
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What can alter absorption of topical medications (3)
- 1. Skin inflammation
- 2. abrasion
- 3. body temp
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How are aerosolized drugs absorbed
Absorbed directly into bloodstream through alveoli
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What can impair absorption of aerosolized drugs? (3)
- 1. Parenchymal lung dz
- 2. vascular shunting
- 3. tachypnea
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How does tachypnea affect absorption of aerosolized drugs
Drug stays in physiologic dead space of bronchi instead of reaching alveoli
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Drug distribution can be affected by (4)
- 1. drug pH
- 2. ionization
- 3. lipid or water solubility
- 4. affinity for plasma proteins
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Lipid soluble drug distribution:
distributed to all body water, both intracellular and extracellular
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Water soluble drug distribution:
Extracellular fluid compartments only
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How can hydration/volume of ECF affect water soluble drugs
- Volume of ECF can be altered w/ dz (hypovolemia decreased ECF)
- Depleted water shifts to intracellular compartment, increased concentration of drug in ECF, poss toxicity
- Edema increases ECF, decreases drug concentration
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How do cavitary effusions benefit drug distribution
Cavitary effusions do not benefit drug distribution, care should be taken when calculating for added mass.
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What does blood brain barrier do?
Protects sensitive nervous tissue from exposure to certain chemicals and compounds.
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How does BBB work?
Capillaries in brain have tight junctions, restricting access to certain particles. Other particles can pass BBB with specific carrier-mediated transport. Glial cells from neurons also have astrocytic end-feet that can restrict access.
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How does cranial trauma affect BBB?
Can increase permeability
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Liver shunt effects on drug distribution
- Liver shunts prevent distribution of drugs to the liver
- Toxicity if drug is active and remains in circulation, failure of therapy if relies on liver biotransformation
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Major site of drug metabolism is _________
liver
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Hepatic metabolism
converts drugs to water soluble compounds that are excreted, primarily by kidney
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Prodrug
Drug administered in inactive form that is metabolized into active metabolite
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Phase 1 metabolism
Microsomal enzyme system (cytochrome P-450 or CYP) metabolizes many drugs. Hundreds of groups of CYP expressed in liver, intestines, kidney, brain, and other organs.
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What do CYP do to drugs (3)
- 1. Converts some to active prodrugs
- 2. Converts some to inactive metabolites
- 3. Converts some to toxic metabolites
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Drugs that CYP converts to active prodrugs (3)
- 1. codeine
- 2. tramadol
- 3. enalapril
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Drugs that CYP converts to inactive metabolites (2)
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Drugs that CYP converts to toxic metabolite (1)
Acetaminophen
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Phase 2 metabolism:
- Conjugation of drug or metabolite with certain pathways/functional groups to increase water solubility
- Ex: Cats lack glucuronidation (conjugation molecule that binds to substrate), causes increased toxicity of acetaminophen as CYP is utilized instead and produces a toxic metabolite
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Primary site of drug excretion
Kidneys
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Possible sites of drug excretion (5)
- 1. liver
- 2. GI tract
- 3. skin
- 4. mammary tissue
- 5. lungs
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Rate of excretion in kidneys can be affected by (8)
- 1. renal blood flow
- 2. glomerular filtration
- 3. protein binding
- 4. tubular secretion
- 5. tubular reabsorption
- 6. drug lipid solubility
- 7. molecular size
- 8. ionization
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What percent of cardiac output does kidney receive in bloodflow?
25%
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Drugs to avoid or use with caution with impaired renal function (8)
- 1. Aminoglycosides
- 2. tetracyclines
- 3. sulfonamides
- 4. NSAIDs
- 5. corticosteroids
- 6. ACE inhibitors
- 7. antiarrhythmics
- 8. diuretics
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