Straight Pharm Flashcards
Describe the treatment for cyanide poisoning
- amyl nitrite (NOT nitrate) → oxidize Hb to methemoglobin → binds CN-
- give thiosulfate to bind CN- → forms thiosulfate → renally excreted
What is pKA?
pH at which 50% of drug is ionized and 50% unionized
What form of weak acids crosses membranes?
non-ionized form
What are 5 important drugs to remember as weak acids?
- aspirn (acetylsalicylic acid)
- penicillins
- cephalosporins
- loop diuretics
- thiazide diuretics
What are 4 important drugs/groups to remember as weak bases?
- morphine
- local anaesthetics
- amphetamines
- PCP
If you have a weak acid drug with a pKA of 5, would it be more effectively absorbed in the stomach or small intestine?
the stomach, because it would have to be in an acid environment to be in its unionized form - for a drug with a pKA of 5, an acidic environment for it would be a pH < 5; stomach pH = 1-2; sm. intestine pH = 6
What is the pH in the following locations?
- Stomach
- Sm. intestine
- Blood
- Urine
- Stomach: 1-2
- Sm. intestine: 6
- Blood: 7.4
- Urine: 5-8
When would you want to acidify urine?
To eliminate a weak base drug (e.g. amphetamines, morphine, PCP, local anaesthetics) → ionizes the drug so becomes trapped in kidney tubule
What three things can you give patients to acidify urine (thus help to eliminate weak bases)?
- NH4Cl (ammonium chloride)
- vitamin C
- cranberry juice
What can you give to help eliminate weak acid drugs (eg. asprin)?
- NaHCO3 (sodium bicarb) - base → ionized form
2. Acetazolamide (CA inhibitor → lots of bicarb in urine→ ↑ pH → ionize WA)
What can you give to help prevent ammonia (NH3) toxicity in hepatic encephalopathy?
Lactulose → lactic acid by gut bacteria → donates a proton to NH3 → NH4+ → NH4+ can’t leave gut
Most drugs are transported via passive diffusion. What are two examples of drugs that are actively transported? What does this imply?
- penicillins
- diuretics
Since carriers are required for facilitated and active transport, the systems are saturable
Give two examples of competition between a drug and another substrate in the body for protein binding sites
- Sulfonamides displace bilirubin from albumin → kernicterus in newborns
- Sulfonamides displace warfarin (which is 98% protein bound) → ↑ plasma concentrations → bleeding/bruising
What are the 2 characteristics which allow a drug to penetrate the placenta or BBB?
- small size - e.g. Li+ (charged), EtOH (polar)
- Lipid soluble
Note: if a drug can cross the BBB, it will easily cross the placenta
What are the 3 drug characteristics that increase the likelihood it is safe in pregnancy?
- large
- charged
- highly protein bound (e.g. phenobarbital)
If a drug is highly bound to plasma proteins, will the Vd be low or high?
low
Thiopental has a long half life (9 hours), but only works for < 1 min in the brain. What pharmacological concept explains this?
redistribution - a property of lipid soluble drugs: there is a fall in plasma concentration soon after delivery because of redistribution to fat tissue; consequently, multiple doses will have increasing effectiveness as fat becomes saturated
Side note: remember that THIO indicates there is a sulfur group → lipid soluble
What 3 drugs have zero order elimination?
- phenytoin
- ethanol
- salicylates (asprin)
What does a zero order elimination drug look like on a linear vs. a log scale? 1st order?
Zero order:
1. linear scale - linear decrease
2. log scale - curved (convex) decreased line
1st order:
1. linear scale - curved (concave) decrease
2. log scale - linear decrease
If a drug is 80% protein bound and GFR = 120 ml/min, what is the clearance rate?
Cl = free fraction x GFR = .20 x 120 ml/min = 24 ml/min
How can you determine F experimentally for a drug?
give equivalent doses orally and by IV, then take area under curve for oral dose / AOC for IV administration; if different doses you can multiply the oral dose by the IV dose and the IV dose by the oral dose in the above equation
How do you calculate the T1/2 if given the Vd and CL?
T1/2 = (Vd x ln2) / CL; ln2 is about .7 so (Vd x .7)/CL
What does it mean to induce p450? Would the Vmax or Km be affected?
↑ gene expression → ↑ Vmax
What drug has the side effect of livedo reticularis?
amantadine
