General Principles Flashcards
What is pharmacokinetics vs. pharmacodynamics?
Pharmacokinetics - what the body does to the drug
Pharmacodynamics - what the drug does to the body
What form(s) of a drug contribute to the concentration gradient?
Only the free, unionized form
Why is intramuscular injection usually more effective than subcutaneous?
Faster absorption because intramuscular is more vascular
What is the pKa?
pH at which 50% of drug is ionized and 50% is not ionized
Which form of the drug can cross membranes?
Non-ionized (uncharged) form - lipid soluble
Which form of the drug is better renally excreted?
Ionized (charged) form - water soluble
Name 4 common weak acid drugs.
Aspirin, penicillins, cephalosporins, loop/thiazide diuretics
Name 4 common weak base drugs.
Morphine, local anesthetics, amphetamines, PCP
Compare weak acid vs. base and their charged forms.
From acidic to basic environments:
Weak acid HA A- and H+
Weak base BH+ B and H+
In other words, a weak acid is in its charged form in a BASIC environment vs. a weak base is in its charged form in an ACIDIC environment
Which forms of a drug are filtered?
Kidney only filters unbound drug but it will filter BOTH the ionized and unionized forms.
Ionized forms are trapped in the filtrate while the unionized form can be involved in secretion/reabsorption.
What are 3 things you can give to try and acidify the urine (i.e. to get rid of a weak base drug)?
- NH4Cl
- Vitamin C
- Cranberry juice
What are 2 things you can give to alkalinize the urine (i.e. to get rid of a weak acid drug)?
- NaHCO3
2. Acetazolamide
What is the bioavailability of an IV administered drug?
100% - does not involve absorption
How can we define bioavailability in terms of oral vs. IV administration.
f = oral/IV since IV is 100% bioavailability (gold standard)
What is the first pass effect?
Hepatic metabolism when drugs are taken orally - absorbed into the portal circulation
If a drug crosses blood brain barrier it will also likely cross what other barrier?
Placenta
What are 3 characteristics of drugs that would tend to be safe to give to pregnant women?
- Large
- Protein-bound
- Water soluble
What does high vs. low Vd tell you?
High Vd = drug sequestered in tissues
Low Vd = drug is highly bound to plasma proteins
Because Vd = dose / plasma concentration
What are approximate Vd values for plasma, blood, ECF, total body water?
Plasma - 3 L
Blood - 5 L
ECF - 12 to 14 L
Total body water - 40 to 42 L
What are 5 classic CYP450 inducers?
Phenobarbital Phenytoin Carbamazepine Rifampin Chronic alcohol
What are 6 classic CYP450 inhibitors?
Cimetidine Macrolides (esp. erythromycine) Ketoconazole "avirs" Acute alcohol Grapefruit juice
What is a high yield clinical correlation of grapefruit juice inhibiting metabolism of a certain class of drugs?
Statins - e.g. if a patient tries to change their diet and starts drinking grapefruit juice
What are the main reactions in Phase I vs. Phase II metabolism?
Phase I - Redox, hydrolysis (think CYP450)
Phase II - Conjugation via transferases (think adding things onto the drug)
Why do babies get gray baby syndrome from chloramphenicol?
Reduced activity of Phase II metabolism (glucuronidation) - decreased activity of glucuronosyl transferase
What is zero order elimination vs first order elimination?
Zero order - constant amount of drug is eliminated per unit time
First order - constant fraction of drug is eliminated per unit time
What are three drugs that undergo zero order elimination?
Mnemonic: Zero “PEA”s for me
Phenytoin
Ethanol
Aspirin (salicylates)
What is a normal value for GFR?
120 ml/min - not secreted or reabsorbed
How do you calculate clearance for a drug taking into account the fact that protein-bound drug is not cleared?
Cl = Free fraction x GFR
The time to reach steady state (rate in = rate out) of a drug is dependent only on what?
The half life of a drug
About how many half-lifes does it take to reach clinical steady state?
4-5
How does rate of infusion effect the time to steady state?
It doesn’t - it may change the peak concentration of that drug at the steady state but it will still take just as long to reach the plateau
What is the equation for half life?
t1/2 = 0.7 x Vd/Cl
On a dose response curve, if drug A and B work on the same receptor and drug A has greater affinity and potency but the same efficacy what should you see?
Work on the same receptor - parallel curves
Greater affinity and potency - drug A’s curve should be shifted to the left (closer to the Y axis)
Same efficacy - reach the same plateau
Name 5 high yield noncompetitive antagonists.
- Phenoxybenzamine
- Digoxin
- Allopurinol
- PPI’s
- Aspirin
Compare and contrast competitive vs. noncompetitive antagonists in terms of dose-response curve.
Competitive - decreases potency, but efficacy is fine
Noncompetitive - decreases efficacy
Name 4 high yield drugs with low therapeutic index.
- Theophylline
- Digoxin
- Warfarin
- Lithium
How would you characterize the general signaling of intracellular receptors?
Elicited via modification of gene expression - usually slower in onset but longer in duration than other drugs
What are the main questions that clinical trials try to answer in each phase from 1 to 4?
Phase 1: Is the drug safe
Phase 2: Does the drug work?
Phase 3: Confirm effectiveness, look at common side effects
Phase 4: Look for rare side effects
