Flashcards in Pharmacodynamics Deck (33):
What does the Km reflect and how is it reflected on a velocity vs substrate graph?
Km reflects the affinity of an enzyme for its substrate and is equal to the substrate level at 1/2 Vmax.
What is the relationship between Km & affinity that an enzyme has for a substrate?
Km & affinity are inverses of each other.
What is Vmax and how does it relate to the enzyme concentration?
Vmax is the maximum initial rate of a reaction. It is directly proportional to the enzyme concentration.
Compare Competitive inhibitors and Noncompetitive inhibitors in regards to:
Overcome by increasing the substrate?
Bind the active site?
Effect on Vmax?
Effect on Km?
Resemble substrate? Yes
Overcome by increasing the substrate? Yes
Bind the active site? Yes
Effect on Vmax? None
Effect on Km? Increased
Pharmacodynamics? Decreases potency
Resemble substrate? No
Overcome by increasing the substrate? No
Bind the active site? No
Effect on Vmax? decreased
Effect on Km? Unchanged
Pharmacodynamics? Decreases efficacy
On a graph of 1/V on y-axis and 1/s on x-axis, how is the line of a Noncompetitive inhibitor vs a competitive inhibitor?
On a graph of 1/V on y-axis and 1/s on x-axis, the line of a Noncompetitive inhibitor is at a higher 1/v (lower Vmax)
On a graph of 1/V on y-axis and 1/s on x-axis, the line of a competitive inhibitor
What is the Vd? How is it calculated? What factors may affect it?
Vd is the volume distribution of the drug. It relates the amount of drug in the body to the plasm concentration. The volume distribution of a Protein-bound drugs can be altered by liver and kidney disease which will decrease plasma protein binding and therefore increase Vd.
Give an example and characteristic of a drug with a low Vd (4-8 L)?
A drug with a low Vd is largely distributed in the blood. It is usually large or charged. Ex: warfarin and aspirin are basic drugs.
Give an example and characteristic of a drug with a medium Vd?
A drug with medium Vd distribute in the extra cellular space or body water. They are small hydrophilic molecules that do NOT bind plasma proteins.
Give an example and characteristic of a drug with a large Vd?
A drug with a high Vd (higher than body weight) distributes in all tissues. It is a drug that is small, lipophilic that can bind strongly to extravascular proteins. Ex: amphetamine which is a basic drug.
What is clearance pertaining to and what two ways can it be calculated?
Clearance relates the rate of elimination of a drug to the plasma concentration of the drug.
1- CL = rate of elimination of the drug/plasma concentration of the drug.
2- CL = Vd x Ke
Ke is the elimination constant of the drug.
What is does the half life of a drug pertain to ?
T1/2 is the time required to change the amount of drug in the body by 1/2 during elimination or constant infusion. It is a property of First order elimination in which the same Fraction of the drug is eliminated.
A drug infused at a constant rate with first order elimination takes how many half lives to reach steady state?
A drug with first order elimination infused constantly takes 4-5 half lives to reach constant state.
What is the formula for half life of a first order elimination drug?
T1/2 = (0.7 x Vd)/ CL
What is the bioavailability and what sign denotes it? How if the bioavailability via IV administration compared to oral?
Bioavailability is denoted by F, it is the fraction of administered drug that reaches circulation.
IV the F is 100%
Orally the F is the % that survives first pass in the liver or gut.
How is the loading dose calculated for a drug? How do renal or liver disease affect your loading dose?
Loading dose = (Cp x Vd)/F and in renal or liver disease the loading dose is not changed.
Cp is the target plasma concentration.
How is maintenance dose calculated? How do renal or liver disease affect your maintenance dose?
Maintenance Dose = Cp x CL/F
Cp = target plasma concentration
In renal or liver disease your maintenance dose decreases.
What is the frequency of dosing affected by?
The frequency of dosing is affected by the t1/2 Not the time to steady state.
What is the steady state defined as?
The steady state is the amount of drug in plasma that has built a concentration that is therapeutically effective.
What is the characteristic of a drug with Zero-order elimination? Give 3 drugs that best represent Zero-order mechanics.
In Zero-order elimination the rate of elimination is constant regardless of Cp ( constant amount of drug is eliminated per unit time. The Cp will decrease linearly with time. 3 drug examples that best represent Zero order mechanics are the PEA (a pea is round like the number zero):
Phenytoin, Ethanol, & Aspirin.
What is the characteristic of a drug with First-order elimination?
First order elimination drugs have a constant Fraction eliminated which is proportional to the drug concentration. The Cp decreases exponentially with time.
In regards to urine pH and drug elimination, how do ionized species compare to neutral forms?
Ionized species are trapped in urine and cleared quickly while neutral species are reabsorbed.
Give examples of drugs that are weak acids. Where are they trapped and how do you treat overdose?
Examples of drugs that are weak acids: phenobarbital, methotrexate, aspirin.
They are trapped in acidic environments. Treat overdose with bicarbonate.
Give examples of drugs that are weak bases. Where are they trapped and how do you treat overdose?
Drugs that are weak bases are amphetamines. They are trapped in acidic environments such as the stomach. Treat overdose with ammonium chloride.
Compare pharmacodynamics to pharmacokinetics.
Pharmacodynamics simply pertains to what the drug does to the body. Pharmacokinetics refers to what the body does to the drug.
What is phase I metabolism, what occurs and what does it yield?
Phase I involves cytochrome P-450 metabolism which consists of reduction, oxidation, and hydrolysis. It yields slightly polar, water-soluble metabolites which are often still active!
What is phase II metabolism, what occurs and what does it yield?
Phase II metabolism is the conjugation step which involves Glucuronidation, Acetylation, and Sulfation : "GAS"
It yields a very polar, inactive metabolite that is renally excreted.
How are geriatric patients and patients with different acetylator activity affected in regards to drug metabolism and what what stage of drug metabolism?
Geriatric patients lose phase I (cytochrome P-450) and only have "GAS" (Phase II: Glucuronidation, Acetylation, & Sulfation).
Patients that are slow acetylators have a greater side effects from certain drugs due to a decreased rate of metabolism.
Define efficacy and give examples of high efficacy drugs.
Efficacy is the maximal effect that a drug can produce. High efficacy drug classes are analgesic medications, antibiotics, antihistamines, and decongestants,
Define potency and give examples of drugs with high potency.
Potency is the amount of drug needed for a given effect. High potency means high affinity for Receptor. Highly potent drugs: chemotherapy drugs, high BP meds, and cholesterol meds.
How does a competitive antagonist affect potency and efficacy. How does the curve on the agonist dose (x) versus percent of maximum effect (y) graph change. Give an example.
A competitive antagonist will decrease the potency (decreased receptor avail.), but has no change on the efficacy. It shifts to curve to the right. An example is Diazepam and flumazil on GABA receptor.
How does a noncompetitive antagonist affect potency and efficacy. How does the curve on the agonist dose (x) versus percent of maximum effect (y) graph change. Give an example.
A Noncompetitive antagonist decreases the efficacy but does not affect the potency (no change of receptors available). It shifts the curve down. Examples include: NE + phenoxybenzamine on alpha-receptors.
How does a partial agonist affect potency and efficacy. How does the curve on the agonist dose (x) versus percent of maximum effect (y) graph change. Give an example.
A partial agonist acts on the same receptor site as a full agonist but with decreased maximal effect so decreased efficacy. Potency is variable and can increase or decrease. Ex: morphine + buprenorphine at opioid receptor.