Pharmacokinetics Flashcards
Metabolism Vs Excretion
Metab - change in structure
Excretion - removal of unchanged drug
Reason why these are poorly absorbed:
Penicillin G and Insulin?
Tetracyclines?
Aminoglycoside antibiotics?
destroyed by stomach acid/digestive enzyme;
chelated to components of food to form insoluble complexes;
Polar compounds cannot cross the wall
Is drug distribution reversible?
Yes
Factors affecting drug distribution
Cardiac output, Perfusion, Permeability, Protein Binding
Displacement of drug from protein binder will cause adverse effects only when: 2 reasons
the drug has a very narrow therapeutic index and when most of the drug is located in the intravascular compartment
PK - Distribution:
@ liver and spleen?
@ brain?
liver and spleen are very leaky, drug leaves the capillary regardless of its solubility
brain capillaries have tight jxns, use of transporters to diffuse drugs, lipophilic drugs can diffuse across
What are the 2 amines that has limited brain penetration capacity;
Give their precursors that allow them to cross
Dopamine and Serotonine;
Levodopa and 5-hydroxytryptophan;
Molecular function of Microsomal CYP450 Monooxygenase
transfer electrons from NADPH to an oxygen molecule and thus oxidize drugs
What is an inducer drug? What are its effects
causes the expression of more CYP enzymes
greater drug elimination, more metabolites (can include toxic), inc prodrug activation
A transporter moves one drug from one compartment to another. What is the transporter protein that involved in drug resistance of cancer patients?
P-glycoprotein
It is overexpressed in tumor cells; pumps out anticancer drugs
Assumptions in a One-compartment Model
- the body is one single process
- drug is distributed instantaneously and is mixed well
- Equilibrium exists between blood and tissue
2 Types of Compartments
- Central - high blood flow, rate of elimination = rate of entry, brain, liver, spleen, kidney
- Peripheral - slow blood flow, rate of entry > rate of elimination, adipose and muscles
Rule of Parsimony
Use simplest model possible
Graph of a drug in:
single compartment and IV route
Semi-log graph
The only assumption in a Non-Compartmental Model
The terminal phase of the graph/curve should act like a 1-compartment model
Factors affecting Absorption
SSSGR:
State, Solubility, Surface Area, GET, Route
Protein Binding:
Acidic drugs bind to?
Basic drugs bind to?
Albumin
Alpha-glycoprotein
Give the reaction involved in metabolizing these:
Ethanol, Chloramphenicol, Paracetamol, Isoniazid,
Oxidation;
Glucoronization;
Sulfation;
Acetylation;
Common Liver Enzyme Inducers
P - Phenobarbital (a barbituate), Phenytoin (blocks Na channels, anticonvulsant)
R - Rifampicin (Anti-TB drug)
C - Carbamezapine (same w/ Phenytoin), Chronic alcoholism
What is an Inhibitor? What are the effects of inhibitors?
Inhibitor inhibits hepatic enzymes;
Active drugs are not inactivated hence prolonged drug effect,
Prodrugs are not activated
Examples of Liver enzyme inhibitors
MEDVICK-GA:
Metronidazole, Erythromycin, Disulfiram, Valproic acid, Isoniazid, Cimetidine, Ketoconazole, Grapefruit Juice, Acute Alcoholism
Which is filtered more or favored?
Ionized vs non-ionized drug?
Bound or free drug
Both are filtered.
Only free drug is filtered.
Only _____ form is favored to be actively secreted and reabsorbed
non-ionized
fastest route of absorption?
Inhalation; IV route does not involve absorption.
When do you see the first pharmacologic effect of a drug?
When the drug reaches Minimum effective conc.
In a graded response graph, where can you see the duration of action?
Found between two points. These points are the Minimum Effective Concentration. the 1st is during absorption and the 2nd is during elimination
Two properties that enable a drug to cross Blood Brain Barrier
High Lipid solubility
Low Molecular weight
True to False
All drugs that can cross the Blood-Brain Barrier can also cross the placenta
True
Characteristics of a drug safe for pregnant women
Large molecular size
Hydrophilic drug
Protein bound drug
What is Redistribution?
When lipid soluble drugs are redistributed to the fat tissues. Contributes to bigger half life. Multiple doses leads to greater effect.
Zero Order Elimination Rate:
Amount eliminated?
Rate of elimination?
Half life? Saturation?
Constant AMOUNT eliminated;
Rate of elimination is independent of concentration;
No fixed half-life; There is saturation;
Zero Order Elimination Rate:
Examples: Zero PEAs for me
Phenytoin
Ethanol
Aspirin
Graph of Zero Order:
In units of drug scale?
In log units scale?
Linear, negative slope;
Parang ihi
1st Order Elimination Rate:
Amount eliminated?
Rate of elimination?
Half-life?
Constant FRACTION eliminated;
Half-life is constant
Graph of 1st Order:
In units of drug scale?
In log units scale?
Exponential decay;
Linear, negative slope
The Steady state is dependent on what variable?
It is dependent ONLY ON HALF LIFE.
It is independent of dose size and frequency/
How many half lives does a CLINICAL steady state entail?
4-5 half lives, 95%
How many half lives does it take to reach MATHEMATICAL steady state?
7+ half lives, 99-100%
Rate of infusion does not affect the time it takes to reach steady state, neither does Maintenance Dose. What does it affect?
The plasma concentration of a drug at steady state
When will the Loading dose be equal to twice the Maintenance dose?
When you administer the drug at each half time (assuming normal clearance and same F)
Dose Response Curve:
Same and parallel slope?
Same receptor; nearer to the left, greater affinity for receptor
Dose Response Curve:
Potency?
Nearer to the left, greater potency;
Can only compare potency if curves dont cross each other
Dose Response Curve:
Efficacy?
The more it is shifted along the Y axis, towards the North, the greater its efficacy
When can a partial agonist be an antagonist?
When it is administered along with the full agonist. It will compete for the same receptor sites. Effect will be intermediate.
What is the effect of a partial agonist?
noncompetitive agonist? competitive agonist?
decrease efficacy;
decrease efficacy;
decrease potency;
Pharmacologic vs Physiologic Antagonistm
Pharma: 2 drugs bind to same receptor
Physio: 2 drugs bind to 2 different receptor. The receptors have antagonistic effects.
