Pharmacokinetics Ctd. Flashcards
Define Prodrug
Drug given in inactive form and must undergo metabolism to be acctivated
Most phase I reactions involve which enzyme system of the liver?
CYP450
What occurs during a phase I reaction?
Oxidation reactions that will activate, change, or unchange a drug
What occurs during Phase II reactions
Conjugation reactions (most drugs don;t retain therapeutic actions after conjugation
Which CYP450 group is likely to have genetic variability( some people won’t metabolize the medication wekk)
2D6
- What occurs during CYP450 competition?
CYP450 competes with other substrates for the CYP450 subgroup enzymes
- What occurs during CYP450 inhibition
Some drugs inhibit CYP450 enzymes
- What occurs during CYP450 induction?
Some drugs induce (enhance) CYP450 enzymes
Name the types of 1A2 substrates
- Tricyclic Antidepressants (TCAs)
- Warfarin (Coumadin®)
- Theophylline
- Caffeine
Name the types of 2C9 substrates
- Non-Steroidal Anti-inflammatories (NSAIDs)
- Oral hypoglycemics
- Warfarin (Coumadin®)
Name the types of 2C19 substrates
Proton Pump Inhibitors (PPIs)
Antiepileptic drugs
Name the types of 2D6 substrates
Beta Blockers Antidepressants TCAs Selective Serotonin Reuptake Inhibitors (SSRIs) Antipsychotics Codeine
- What is one of the most common 2D6 substrates?
Codeine
Name the types of 2E1 substrates
Anesthetics
Acetaminophen (Tylenol®)
Ethanol
*Name the types of 3A (4, 5, 7) substrates
- Antibiotics-Macrolides
- Benzodiazepines (BZDs)
- Immunosuppressants
- HIV antivirals
- Calcium Channel Blockers (CCBs)
- Statins
- Hormones (estrogen, progesterone)
- Describe CYP450 Induction
More activity of CYP450 enzymes Increased metabolism Lower plasma concentration
- What effect will CYP450 induction have on an inactive metabolite?
Decreased drug activity/therapeutic effect
- What effect will CYP450 induction have on an active metabolite?
Increased drug activity/therapeutic effects
- What are the overall common CYP450 Inducers?
- Phenobarbital
- Phenytoin
- Rifampin
- Carbamazepine
- Describe CYP450 Inhibition
Less activity of CYP450 decreased metabolism higher concentration of plasma drug levels possible side effects or toxicity
- What are the overall common inhinbitors?
- cimetidiIne
- grapefruit juice
- amiodarone
- azole antifungals
- Which order kinetics do most drugs follow?
1st order kinetics
- Describe 1st order kinetics
Rate of drug metabolism is directly proportional to the concentration of free drug
- Describe Zero order kinetics
Rate of metabolism remains constant over time
- Is zero order kinetics linear or nonlinear?
Nonlinear
** Which drugs follow zero order kinetics?
-Ethanol, Aspirin, Phenytoin
- Which order of kinetics is describes as a constant fraction is eliminated per time?
1st order kinetics
- Describe the elimination of zero order kinetics
Constant amount of drug is eliminated per time
What is the most common route of excretion?
Renal
What is the purpose of metabolism in Phase I and II
To make the compounds more polar, preventing then from reabsorption
- What is the formula for total body clearance?
Total body CL=hepatic Cl + renal Cl + other Cl
Define extraction ratio
decline in drug concentration from the arterial to the venous side of the kidney
- What is the formula for extraction ratio?
Extration ratio= C2/C1
- C1 = concentration of drug entering kidneys
- C2 = concentration of drug leaving kidneys
*What is the formula for clearance?
Cl = k * Vd = 0.693 * Vd/t1/2
-k is the elimination constant = 0.693/t1/2
- What is the formula for Excretion rate?
Excretion Rate = (Cl) (plasma concentration)
- In the Crockcroft-Gault equation, what value is used for females only?
0.85
*What is the Crockcroft-Gault Equation (used to adjust dosage in proortion to kidney dysfunction)?
CrCl=(140-age) x 1bw/SrCr x 72 (all x 0.85)
- What is the formula for half-life?
t½ = 0.693/k
Describe steady state concentration
When an infusion is started, the plasma concentration rises until the elimination of the drug balances the infusion of the drug.
Describe the kinetics of continuous IV infusions
Rate of elimination increases as the plasma concentration of drug increases
Is steady state concentration inversely or directly proportional to the rate of elimination?
Inversely
What will occur if the metabolism or the Clearance of a drug is decreased?
The steady state concentration increases
- What is the formula for infusion rate?
Ko = Css * Cl
- How long does it take a drug to reach steady state?
4 half lives
Does the drug infusion rate affect the time to reach steady state?
No, only the steady state is affected
Define loading dose
A higher single dose of drug given at the start of therapy to achieve the desired plasma concentration more rapidly
*What is the formula for Loading dose?
Ld = (Vd)(desired Css)
When giving multiple IV injections are the steady state and time required affected?
No
- Calculate the Vd when the dose is 120 and the concentration is 4 mg/l
Vd = Dose/Concentration
120 mg / 4 mg/L = 30 L
- Calculate the needed dosage adjustment to reach the desired concentration if
- Vd = 10 L
- Current concentration = 100 mg/L
- Desired concentration = 150 mg/L
-Vd (C2-C1)
10 L (150 mg/dl – 100 mg/L) = 10(50) = 500 mg
- Calculate the t½ of the drug when
K = 0.23
t½ = 0.693/k 0.693/0.23 = 3 hrs
- Calculate the clearance of the drug when Vd = 42 L
K = 0.38 hr-1
Cl = k * Vd
0.38 hr-1 * 42 L = 15.96 L/hr = 266 ml/min
- Calculate the clearance of the drug when Vd = 30 L
t1/2 = 5.4 hr
Cl = 0.693 * Vd/t½ Cl = 0.693 * 30 L / 5.4 hr = 3.85 L/hr = 64.2 ml/min
*Calculate estimated CrCl of for a patient
Female, Age 65 years; IBW = 75 kg; SrCr = 1.2 mg/dl
CrCl=(140-age) x 1bw/SrCr x 72 (all x 0.85)
(140 – 65) * 75 / 1.2 * 72 = 65.1 ml/min
65.1 * 0.85 = 55.3 ml/min
