Unit 4: Pharmacology 1 Flashcards
What is volume of distribution? How is it calculated?
Volume of distribution (Vd): relationship between a drug’s plasma concentration following a specific dose
-theoretical measure of how a drug distributes throughout the body
Vd = amount of drug / desired plasma concentration
It assumes two things:
- drug distributes instantaneously (full equilibration occurs at t = 0)
- drug is not subjected to biotransformation or elimination before it fully distributes
What are the implications when a drug’s Vd exceeds TBW? What if Vd is less than TBW?
If Vd > TBW (>0.6 L/kg or >42 L) – drug is assumed to be lipophilic
- distributes into TBW + fat
- requires higher dose to achieve a given plasma concentration
- ex: propofol, fentanyl
If Vd < TBW (<0.6 L/kg or <42 L) – drug is assumed to be hydrophilic
- distributes into some or all of the body water, but doesn’t distribute into fat
- requires a lower dose to achieve a given plasma concentration
- ex: NMBs (ECF), albumin (plasma)
How do you calculate the loading dose for an IV medication? How about a PO medication?
Loading Dose = Vd x Desired Plasma Concentration / Bioavailability
For IV Drug: bioavailability is always 1 (all of the drug enters the bloodstream)
For PO Drug: bioavailability will be less than 1
*any other route than IV may not be absorbed completely and/or may be subject to first-pass metabolism in the liver – reduce bioavailability
What is clearance? What factors increase/decrease it?
Clearance = volume of plasma that is cleared of a drug per unit of time
Directly proportional to:
- blood flow to cleaning organ
- extraction ratio
- drug dose
Inversely proportional to:
- half life
- drug concentration in the central compartment
What is steady state? How many 1/2-times does it take to occur?
Occurs when the amount of drug entering the body is equivalent to the amount of drug eliminated from the body – Stable Plasma Concentration
-each of the compartments has equilibrated
**Achieved after 5 half-times
Describe the alpha- and beta distribution phases on the plasma concentration curve
Alpha Distribution Phase:
- describes drug distribution from the plasma to the tissues
Beta Distribution Phase:
- begins as plasma concentration falls below tissue concentration
- concentration gradient reverses, which causes the drug to re-enter the plasma
- describes drug elimination from the central compartment
**plasma concentration curve graphically depicts the biphasic decrease of a drug’s plasma concentration following a rapid IV bolus
What percentage of initial drug dose REMAINS in the blood after each half-life?
0 half-time = 100% 1 half-time = 50% (50% eliminated) 2 half-time = 25% (75% eliminated) 3 half-time = 12.5% (87.5% eliminated) 4 half-time = 6.25% (93.75% eliminated) 5 half-time = 3.125% (96.875% eliminated)
What is context sensitive half-time?
It is the time required for the plasma concentration to decline by 50% after discontinuing the drug
Discuss the context sensitive half-time of fentanyl, alfentanil, sufentanil, and remifentanil. Which has the longest? Which has the shortest, why?
Longest = Fentanyl (context sensitive half-time for an infusion increases as a function of how long it was infused)
-also true for alfentanil and sufentanil
Shortest = Remifentanil (it is quickly metabolized by plasma esterases so it has a similar context sensitive half-time regardless of time infused)
What is the difference between a strong and weak acid or base?
Difference is the degree of ionization
- if you put a strong acid or strong base in water it will ionize completely
- if you put a weak acid or weak base in water a fraction will be ionized and the remaining fraction will be non-ionized
*acid donates a proton – base accepts a proton
What i s ionization? What 2 factors determine how much a molecule will ionize?
Ionization describes the process where a molecule gains a positive or negative charge
Amount of ionization is dependent on:
- pH of the solution
- pKa of the drug
What occurs when pKa and Ph are the same?
50% of the drug is ionized and 50% is non-ionized
How does ionization affect solubility?
Ionized = Water Soluble
- hydrophilic
- lipophobic
Non-Ionized = Lipid Soluble
- lipophilic
- hydrophobic
How does ionization affect a drugs pharmacologic effect?
Ionized = Not Active
Non-Ionized = Active
How does ionization affect hepatic biotransformation?
Ionized – hepatic biotransformation is LESS likely
Non-Ionized – hepatic biotransformation is MORE likely
How does ionization affect diffusion across lipid bilayer?
Ionized: does not cross blood brain barrier, GI tract, or Placenta
Non-Ionized: does cross blood brain barrier, GI tract, and Placenta
What is the basic rule about acids and bases being put in acidic and basic solutions?
- In ACIDIC solution, weak BASES are more IONIZED and water-soluble
- In BASIC solution, weak BASES are more NON-IONIZED and lipid soluble
- In ACIDIC solution, weak ACIDS are more NON-IONIZED and lipid soluble
- In a BASIC solution, weak ACIDS are more IONIZED and water-soluble
How can you tell if a drug is an acid or a base by looking at its name?
Most drugs are weak acids or bases and usually prepared as a salt that dissociates in solution
- Weak acid is paired with a positive ion such as sodium, calcium, or magnesium
- Weak base is paired with a negative ion such as chloride or sulfate
What are the three key plasma proteins? Does each bind acidic drugs, basic drugs, or both?
- Albumin: primarily binds to acidic drugs (also binds to some neutral and basic drugs)
- Alpha1-acid Glycoprotein: binds to basic drugs
- Beta-globulin: binds to basic drugs
What conditions reduce the serum albumin concentration? (5)
- Liver disease
- Renal disease
- Old age
- Malnutrition
- Pregnancy
What conditions increase alpha1-acid glycoprotein concentration? (5)
- Surgical stress
- Myocardial infarction
- Chronic pain
- Rheumatoid arthritis
- Advanced age
What conditions decrease alpha1-acid glycoprotein concentration? (2)
- Neonates
- Pregnancy
How do changes in plasma protein binding affect plasma drug concentration?
Decreased PP Binding –> Increased Cp
Increased PP Binding –> Decreased Cp
How do you calculate changes in plasma protein binding?
[Free Drug] + [Unbound Protein Binding Sites] [Bound Drug]
- if a drug is 98% bound and the bound fraction reduces to 96%, the unbound or free fraction has increased by 100% (free fraction went from 2% to 4%)
*Calculate the percent change to complete the calculation
% change = [(New Value - Old Value) / Old Value] x 100