Pharmacokinetics/Dynamics EXAM REVIEW Flashcards
What is the definition of oxidation?
Loss of electrons; phase I reaction
What is reduction?
Gain of electrons: Phase I reaction
What is Hoffman degradation?
Example of non-organ metabolism
Site of metabolism is PLASMA
What is Hydrolysis ?
Splitting molecule with the addition of water/ PHASE I
What is the relationship between ph and pKa.
When pH=pKa, 50% of the drug is ionized and 50% in non- ionized.
Lower pKa stronger acid, Higher pKa stronger base.
How does ph and pKa relationship affect weak bases and weak acids?
- A general rule with weak bases states when the pKa minus pH < 0, then most of the drug will be in the non-ionized form.
- With weak acids the opposite is true. pKa minus pH < 0 then most of the drug will be in the ionized form.
What percentage of cardiac output is distributed to each tissue compartment?
HIGHLY PERFUSED (lungs, heart, brain, kidneys, liver) ~ 75%
- Explain when protein binding becomes a concern to the clinician?
- Protein binding and Vd
- Protein binding and metabolism
- Protein binding and lipid solubility
- when is alteration important
- Protein binding effects Vd because only
unbound drug can cross cell membranes.
Therefore the Vd is inversely related to
protein binding. - Only unbound drug can undergo
metabolism and glomerular filtration - Extent of protein binding directly related to
the lipid solubility - Alterations in protein binding are only
important for drugs that are highly
protein bound.
- What are methods of metabolism? What are considered to be phase 1? What are considered to be phase 2
Phase 1 (ORH)
Oxidation, reduction and hydrolysis are
Phase II reaction –> CONJUGATION
6.Which routes of drug administration undergo hepatic first pass effect? Which do not?
1.Drugs that undergo large first pass hepatic
effect (lidocaine, propranolol) PO and IV doses very different
2. AVOID first pass effect
Include sublingual, buccal and nasal route, IV
3. Drugs administered into to LOWER RECTUM avoid the first pass effect
- What drug characteristics will affect Vd?
Lipid solubility, protein binding, molecular
size.
• Drug with LOW LIPID SOLUBILITY and HIGH PROTEIN BINDING will have a LOW Vd
Vd is _______to protein binding
Inversely proportional
- Define zero order kinetics?
Definition
When does it occur?
Result of
A constant amount of drug in cleared per unit of time regardless of plasma concentration
Occurs when the plasma concentration of
drug exceeds the capacity of metabolizing
enzymes.
• Result of saturating the available enzymes
at high drug concentrations of some
compounds.
What drugs undergo zero order kinetics?
Alcohol, Aspirin, and Phenytoin
- Define first order kinetics? What drugs undergo first order kinetics?
Most drugs will follow linear of first-order
kinetics.
• Constant fraction of drug is metabolized
per unit of time.
In first order kinetics the metabolism of a drug is highest when?
when the drug concentration is greatest.
In first order kinetic; The fraction of drug eliminated is_________
independent of the drug concentration
For first order kinetic, It will take 1 half-life for the plasma________
At 5 half-lives the drug plasma
concentration declines by_______
concentration to decline by 50%.
96.9 %
- What are the mechanism for renal excretion of drugs? (3)
Glomerular filtration.
Passive tubular secretion.
Passive tubular reabsorption.
- What organ is responsible for drug metabolism
Liver
plasma for hoffman degradation
- Why do the elderly respond to drugs differently than younger patients? (DED-DI)
They all lead to ________and _________
Decreased cardiac output
Enlarged fat content
Decreased protein binding
Decreased renal function
all lead to drug accumulation and increased risk of toxicity
- What is the principal effect of metabolism?
The role of metabolism is to convert
pharmacologically active, lipid-soluble drugs
into water soluble inactive compounds that
can be easily excreted.
14a Define Enantiomer?
A pair of molecules existing in two forms
that are mirror images of one another but
cannot be superimposed. All contain a chiral carbon
Define stereoisomer
are a particular kind of isomer that are different from each other only in the way the atoms are oriented in space (but are like one another with respect to which atoms are joined to which other atoms)
Define Chiral Carbon
Chiral is a term used to describe a molecule
that has a center (or centers) of threedimensional asymmetry
Enzyme inducers drugs RPPCAC
Rifampin Phenobarbital Phenytoin, cigarette smoking Alcohol Chronic carbamazepine.
Enzyme Inhibitors drugs are
ProDiVE - CANVA
Protease inhibitors DI- ltiazem Verapamil Erythromycin Cimetidine Acute alcohol ingestion Nefazodone Valproic acid Amiodarone
- What affect will ionization, molecular size, lipid solubility, protein binding have on Vd?
the NON-IONIZED portion of the drug is more lipid soluble and therefore crosses the cell membrane better (higher Vd)
HIGHER IONIZED –> Lower Vd
Molecular size: higher molecular weight, low Vd
Lower molecular size: HIGH Vd
Therefore the Vd is INVERSELY related to
protein binding.
Low lipid solubility + high protein binding–>low Vd(locked in vessels)
High lipid solubility + low protein binding –> High Vd (distributes easily)
- Define pharmacokinetic.
The quantitative study of absorption, distribution, metabolism, and excretion of drugs and their metabolites
The movement of a drug through the body
over time.
“What the body does to a drug
Define pharmacodynamics.
The study of the intrinsic sensitivity of
responsiveness of receptors to a drug and
the mechanism by which these effects
occur.
“What the drug does to the body”
- Weak BASE given pKa and ph when will non-ionized or ionized from (general rule)
A general rule with WEAK BASES states when the pKa - pH < 0, then most of the drug will be in the NON-IONIZED form.
Weak ACID given pKa and ph when will non-ionized or ionized from (general rule)
With weak acids the opposite is true. pKa minus pH < 0 then most of the drug will be in the ionized form
- Understand the principles behind calculating a creatinine clearance.
•{140 - age ) x IBW /72 x Serum creatinine} x (0.85 for females.)
Formula used to calculate estimated creatinine clearance.
• IBW male 50 +(2.3 x each inch
>60) IBW in Kg
• IBW female 45.5 + (2.3 x each
inch >60) = IBW in Kg
Define drug clearance.
The volume of plasma cleared of drug by renal excretion and/or metabolism by the liver or other organs
Anaphylaxis
antigen-antibody interaction,
immune mediated and REQUIRES PRIOR EXPOSURE
Anaphylactoid
no previous exposure or sensitization, not a true allergic reaction but results in histamine release, vasodilation, wheals, and welts
