Flashcards in Pharma Deck (202)
Give 3 reasons why someone may make a prescribing errors
-Loss of attention due to exhaustion
-Illiterate hand writing
-Study of the movement of a drug into and out of the body ie what the body does to the drug
-Study of the drug effect and mechanism of action oe what the drug does to the body
Define pharmacogenetics. Give an example
-The effect of genetic variability on the pharmacokinetics or pharmacodynamics of a drug on an individual
-CYP450 enzymes have genetic variation within the population eg 2D6 and thus some people will not react or over react to a drug which is metabolised by this enzyme eg codeine
Give some factors which may effect the pharacokinetics of a drug
-Liver and renal function
What is bioavailability of a drug? How do you calclulate it? Give some factors which affect bioavailability
-The fraction of a dose which finds its way into the circulation unchanged
-[AUC Oral] plasma/[AUC IV]plasma
-Route of administration, age, lipid solubility of drug, absorption of drug, first pass metabolism
What is first pass metabolism?
-The metabolism of a drug which occurs before it reaches the systemic circulation. Includes metabolism in the gut lumen by gastric acid/enzymes, gut wall by absorption and the liver
Broadly describe the 2 phases of drug metabolism in the liver
-Can either enter phase I or go straight into phase II
-Phase I involves cyp 450 and is a oxidation or reduction reaction which usually inactivaes the drug
-Phase II is a conjugation reaction with glucaronide, glutathione, sulphate which makes the drug water soluble so it can be eliminated
What are the two key factors which affect drug distribution and how do they do this?
-Protein binding -> Unbound drugs are able to bind to receptors and pass across cell membranes and have a pharmacological affect. Bound drugs remain in the circulation, therefore if a drug is highly bound the distribution will be less
-Volume of distribution -> a hypothetical measure of instantaneous distribution of drugs into available body compartments. If there is a low volume of distribution it means that the drug will be at high concentration in the body compartments which it can dissolve in
If there was a change in protein binding eg drug interactions, what properties of certain drugs would make you concerned?
-If a drug is highly bound -> displacement would rapidly increase the concentration of active drug
-If there was a low volume of distribution -> means the drug is in high conc in the places it is. displacing the drug from protein binding would raise the concentration more
-If the drug had a narrow therapeutic window because displacement could push the drug to toxic levels
Give 3 things which may affect protein binding
-Displacement by other drugs
What factors have an effect on volume of distribution?
-Regional blood flow
-Specific receptor sites in tissues
What is a pro-drug?
-A drug which is inactive when administered and becomes activated by the body eg codeine to morphine
Name some CYP inhibitors. What affect do inhibitors have on metabolism?
-Grapefruit juice (simvastatin)
-Decrease metabolism of drugs prolonging the effects
Name some CYP inducers. What affect do inducers have on metabolism?
-Cranberry Juice (warfarin)
-St Johns Wort/Sulphonylureas
-Induce the production of the enzymes to increase metabolism of drugs and thus decrease their effects
What 3 processes determine the renal excretion of drugs? What is the relationship between clearance and half life?
-Passive tubular resorption
-The lower the clearance (GFR) the longer the half life
What is first order and zero order kinetics? Why do most drugs exhibit zero order kinetics at high doses?
-1st order = rate of elimination is proportional to drug level and a constant fraction is eliminated -> half life can be calculated
-Zero order= rate of elimination is constant regardless of drug level. half life not easily calculated
-Enzymes and receptors become saturated
Why does digoxin need a loading dose? Why does renal failure affect its toxicity?
-It has a long half life and steady state would take 3-5 half lives and you need rapid affect
-In renal failure there is less excretion of digoxin meaning that the drug will remain at toxic levels for longer and the same dose may reach toxic levels as that in a normal kidney
Describe the metabolism of paracetamol at therapeutic and toxic doses
What is the treatment for paracetamol overdose?
-Therapeutic -> 90% Paracetamol enters phase II metabolism and excreted, 10% enters phase II and converted to NAPQI but quickly undergoes conjugation with glutathione and inactivated
-Toxic -> Phase II saturated so much higher conc enters phase I metabolism. Produced large amounts of NAPQI and not enough glutathione to reduce so oxidative damage to the liver
-Activated charcoal within 1 hour
How do competitive antagonist change the dose response curve? How is this over come?
-Keeps the same shape but shifts it to the right
-Adding more agonist (its surmountable)
How do non-competitive antagonist change the dose response curve? How is this over come?
-You get the same shape but the total response is decreased
-It cannot as it alters the conformational shape of target
What is the difference between drug selectivity and drug specificity?
-Selectivity refers to how well a drug binds to one group of receptor targets without binding to other targets and producing undesirable effect
-Specificity refers to how well the drug binds to a receptor subtype allowing it to be organ specific
What is affinity? What pharmacological term is used to measure affinity and how is it interpreted?
-A measure of the tendancy of a ligand to bind to its target
-Kd -> The lower the Kd the higher the affinity
What is efficacy? What is potency?
-The abolity of a drug to be able to activate the receptor and produce a response once it is bound
-Potency is how much of the drug is needed to generate a response taking into account affinity and efficacy
What is the therapeutic window? How is it calculated?
Give 3 drugs with a narrow therapeutic window
-The range of doses which can effectively treat a condition whilst still remaining safe. It is between the lowest concentrations which cause the desired affect and lowest concentrations causing adverse effects
-Warfarin, digoxin and gentamicin
How can drug interactions be caused during the absorption of a drug?
-Something may prevent the drug being absorbed due to inducible/inhibitable active transporters in the gut
Name some drugs which prolong the QT interval
How can renal disease affect the pharmacodynamics/kinetics of drugs?
-Disturbances in electrolytes may predispose to toxicity eg digoxin and hypokalaemia
-Nephrotoxins will further damage the kidney
How can hepatic disease affect the pharmacodynamics/kinetics of drugs?
-Decreased albumin production affects protein binding
-Decreased CYP450 production will change metabolism of drugs
-Reduced hepatic clearance of drugs