FA.Pharm.Pharmacodynamics Flashcards
Km is the…
Affinity of the enzyme for the substrate
Vmax is directly proportional to the ….
(aka efficiency) is directly proportional to the enzyme concentration
How does a \/ Km effect affinity?
/\ affinity (/\ potency)
Lineweaver Burke plot:
/\ y-intercept –> effect on Vmax
\/ Vmax
Fill in the blank:
On a lineweaver burke plot, the further to the right the x-intercept, the ______ the Km and the ______ the affinity
Greater, Lower
b/c Km and Affinity are indirectly proportional
Lineweaver Burke:
Competive inhibitors do/do not cross each other?
DO.
Competitive inhibitors cross competitively, while noncompetitive inhibitors do not cross.
Competitive Inhibitors:
Resemble substrate? Overcome by /\ [s]? Bind active site? Effect on Vmax? Effect on Km? Pharmacodynamics?
Resemble substrate? Yes Overcome by /\ [s]? Yes Bind active site? Yes Effect on Vmax? No change Effect on Km? /\ Pharmacodynamics? \/ potency
Noncompetitive inhibitors:
Resemble substrate? Overcome by /\ [s]? Bind active site? Effect on Vmax? Effect on Km? Pharmacodynamics?
Resemble substrate? No Overcome by /\ [s]? No Bind active site? No Effect on Vmax? \/ Effect on Km? No change Pharmacodynamics? \/ Efficacy
Pharmacokinetics:
Volume of distribution relates the ______ to the ______.
Relates the AMOUNT of the drug to the PLASMA CONCENTRATION.
What disease processes can alter the Vd of plasma-protein bound drugs?
Liver and Kidney disease ( \/ protein binding, /\ Vd )
Vd formula
Vd= (amount of drug in body) / (plasma drug concentration)
Drugs with LOW Vd (4-8 L) distribute in ______. These are examples of (small / large) or (charged / uncharged).
Large or charged drugs will distribute primarily in the BLOOD, .: these have a LOW Vd.
Medium Vd: distributes in the _________ or _________;
General description of this class?
Medium Vd distribute in EXTRACELLULAR SPACE or BODY WATER.
These are SMALL hydroPHILIC molecules that do NOT bind plasma proteins
High Vd (> body weight): distribute to ______?
General description?
Distribute to ALL body tissues
SMALL lipoPHILIC that STRONGLY bind to EXTRAvascular proteins
Clearence (CL): relates the _______ to the ______
CL relates the RATE of ELIMINATION to the PLASMA CONCENTRATION
CL formula
CL = (Rate of elimination of drug [vol. cleared/ time]) / (Plasma Drug Concentration)
= Vd * Ke (elimination constant)
Half-life (t 1/2): The time required to…
Is a property of what kind of zero/first order elim?
decrease the drug in the body by 50% during constant infusion.
Property of first order elimination
A drug infused at a constant rate (IV) takes ____ half lives to reach steady state?
4-5 half lives
of half lives –> concentration:
1–>
2–>
3–>
4–>
1 –> 50%
2 –> 75%
3 –> 87.5%
4 –> 93.75%
Formula for Half Life
Half Life = (0.7 * Vd) / CL
Bioavailability (F) is the…
fraction of administered drug that reaches circulation (F for Fraction)
Bioavailibility (F) for:
IV –>
Oral –>
IV –> 100%
Oral –> % that survices first pass thru liver or gut
Loading dose calculation
Loading dose = Cp * Vd / F
Cp –> target plasma concentration
Maintenance dose calculation
Maintenance dose = Cp * CL / F
Frequency [is / is not] affected by time to steady state but [is / is not] affected by half-life.
Frequency IS NOT affected by time to steady state but IS affected by half-life.
How does renal or liver dz change the maintenance or the loading dose?
\/ maintenance dose
NO CHANGE for the loading dose
In Zero-order elim. the ____ is constant regardless of the Cp.
rate of elimination is constant regardless of Cp.
Cp \/ LINEARLY with time
Examples of zero-order elimination drugs
Phenytoin, Ethanol, Aspirin
¶ PEA: a pea is round, like the “0” in zero-order
First order elimination: a constant _____ eliminated per unit of time.
a constant FRACTION eliminated per unit of time
Cp \/ exponentially with time
[true / false ] ionized drugs are trapped in urine
True.
Weak acids get trapped in basic urine
Weak bases are trapped in acidic urine
Weak acid drugs (name 3) get trapped in [basic / acidic] urine?
Tx:
Phenobarbital, Methotrexate, Aspirin
Trapped in basic environments
Tx: BICARBONATE
RCOOH RCOO- + H+
Weak bases (1 example) are trapped in _____ environments.
Tx overdose with ____
Generalized dissociation formula
Trapped in ACIDIC environments
Tx overdose with AMMONIUM CHLORIDE
RNH3+ <=> RNH2 + H+
Phase 1 metabolism occurs via the ______, and involves _____, _____, and _____ of drugs. This yields [polar / nonpolar], [water soluble / NON water soluble] metabolites, which are often [active / inactive]
Phase 1 metabolism occurs via the CYTOCHROME P450 system, and involves REDUCTION, OXIDATION, and HYDROLYSIS of drugs. This yields POLAR, WATER-SOLUBLE metabolites, which are often ACTIVE.
Phase 2 metabolism:
Modifies drugs in 3 ways, _____,_____, and _____.
Usually yields [polar / nonpolar], [active / inactive] metabolites which are subsequently _____ by the _____.
Phase 2 metabolism:
Modifies drugs in 3 ways, Glucuronidation, Acetylation, and Sulfation.
Usually yields very POLAR, INACTIVE metabolites which are subsequently EXCRETED by the KIDNEY.
Phase 2 metabolism mnemonic: GAS
Glucuronidation
Acetylation
Sulfation
¶ Geriatric patients lose phase I first, therefore
¶ Geriatric patients have GAS (phase 2)
Patients who are slow acetylators have [greater / lesser] side fx from certain drugs.
Why?
Give 1 drug as an example.
Patients who are slow acetylators have GREATER side fx from certain drugs.
Why? Because of the \/ rate of metabolism
Ex: Isoniazid (INH) p. 212
Efficacy is defined as the…
Efficacy is defined as the MAXIMAL EFFECT a drug can produce.
Analogous to Vmax
Name four broad drug classes that have HIGH efficacy
- Analgesics
- Antibiotics
- Antihistamines
- Decongestants
Potency is defined as the…
Potency is defined as the AMOUNT of DRUG needed for a GIVEN EFFECT
/\ Potency –> /\ Affinity for receptor –> \/ Km
Name 3 broad drug classes with HIGH potency.
- Chemotherapeutic drugs
- Antihypertensive (blood pressure) drugs
- Antilipid (cholesterol) drugs
Competitive agonists [right / left] shift the ∫ curve?
[increase / decrease] the [efficacy / potency]?
Competitive agonists right shift the ∫ curve
DECREASE the POTENCY
Thus, more drug needed to reach same effect.
∫ –> ∫
Noncompetitive antagonists [increase / decrease] the [efficacy / potency]?
How does this effect the ∫ curve?
Noncompetitive antagonists DECREASE the EFFICACY.
\/ the height of the ∫ (\/ the Vmax)
Pharmacodynamics
Partial agonists act at same site as full agonist, but with [increased / decreased] maximal effect.
Efficacy is [increased / decreased]?
Potency is [increased / decreased]?
Partial agonists act at same site as full agonist, but with DECREASED maximal effect.
Efficacy is DECREASED.
Potency can be increased or decreased. It is a different variable.
Diazepam + Flumazenil on GABA receptors
Example of Competitive antagonist.
Flumazenil is the Tx for a benzo OD.
Example of a Noncompetitive antagonist of Norepinephrine and receptor
Norepinephrine + phenoxybenzamine on A-receptors
Give an example of a Partial agonist and receptor
Morphine + Buprenorphine at opioid µ-receptor
Buprenorphine will potentiate withdrawal in an addict
Therapeutic Index is measurement of ______ ______.
[steep / flat] slopes that are [near / far apart] are best.
Formula?
Mnemonic
Therapeutic index is a measurement of DRUG SAFETY.
STEEP slopes that are FAR APART are best.
LD50 / ED50 —> Median Lethal (or toxic) dose / Median effective dose.
¶ TILE: TI = L / E
4 Examples of drugs with LOW therapeutic index!!!
- Theophylline (p.576)
- Digoxin (p.309)
- Warfarin (p.395)
- Lithium (p.499)
