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What are the two drug types?
Water soluble and lipid soluble
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What is drug action?
- drug must get access to sites of action
- Drugs tend to bind to tissues, usually protein
- drug alter the action of enzymes, ion channels and receptors
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What do drugs do to receptors?
Drugs activate or block the receptor, activation of the receptor activates a cell signal
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What are the law of mass action that applies to drug receptor interaction?
- Pharmacological effects are reversible because the drug receptor complex is reversible
- Pharmacological effects are proportional to the number receptors occupied
- Pharmacological effect plataeu because they are limited by the total number of receptors
- Drug effects are proportional to the dose!!!
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define: potency
measure amount of drug required for effect
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define: efficacy
maximum effect obtained with drug
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define: variability
reproducibility of data
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What is the main determinant in the decline in GFR?
Renal disease
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What drug are eliminated directly by the kids?
- Water soluble
- involves no chemical change to the drug
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What drugs are readily reabsorbed?
highly lipid soluble
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How do you assess kid fxn?
serum creatine reflects GFR
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How does age affect renal fxn?
THere is a steady and proportional decline in the average GFR with increase of age
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What are the two mechanism how drugs are handled by kids?
- active tubular secretion
- passive diffusion, depends on ionization at certain pHs
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What should we know about gentamycin?
- ONce a day dosing, with kid failure dosing increases past once daily
- toxicity relates to trough concentrations
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What should we know about digoxin?
IN the presence of renal failure must increase the dosing frequency
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What are the results of drug concentations with renal failure?
Accumulation of drug in the body can lead to toxicity
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What is first pass metabolism?
Following non-parental dosage form a significant portion of the dose may be metabolically inactivated in the intestinal endothelium or the liver before it reaches systemic circulation
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What is the role of metabolism?
- Metabolites are less active
- metabolites are more water soluble and more polar
- Prodrugs that require metabolism to be active as active metabolites
- Metabolites are more toxic
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What is the phase I reactions of metabolism?
Convert the parent drug into a more polar metabolite introducing or unmasking a functional group, metabolites are usually inactive
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WHat is phase II reaction of metabolism?
Conjugate an endogenous substrate to a funcational gorup on the drug or phase I metabolite
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What happens to pharmacokinetic properties as people age?
- Acetylation and conjugation do not change
- Oxidative metabolism by CYP decreases with age resulting in a decreased clearance of drugs
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WHat does hepatocellular disease do to the liver?
Decreases liver perfusion
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WHat are the indicators of liver disease?
Establishe cirrhosis, splenomegaly, jaundice, increased prothrombin time
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How can cardiac failure affect the liver?
Decreas liver perfusion
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What are some pharmcodynamic consideration of liver disease?
Tissues may be excessively sensitive to low concentrations of the drug ex: morphine [] in the brain in the presence of liver failure
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What does the liver fxn test consist of?
- Transaminase
- Alkaline phosphatase
- Bilirubin
- Other liver labs
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Why is transaminase part of the LFT?
because it is released after liver heaptocellular injury
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What are the two forms of transaminases?
- Aspartate aminotransaminase
- Alanine aminotransaminase: more specific in myopathies
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elevated transaminases indicate:
- acute toxic injusty apap ischemia
- acute viral disease
- alcohol heapatitis
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What does an elevated AST:ALT
elevated in alcolic disease
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