Pharmacokinetics, Pharmacodynamics Flashcards
RATE and EXTENT of DRUG ABSORPTION from dosage form
Bioavailability
RATE and RELATIVE AMOUNT at which intact form of drug appears systemic circulation
Bioavailability
study of rate processes and their relationship to responses in humans and animals
Pharmacokinetics
Rate processes
Absorption
Distribution
Metabolism
Excretion
Changes in concentration of drug in body
Pharmacokinetics
What the body does to drug
Pharmacokinetics
Relationship between drug concentration at site of action and pharmacologic response
Pharmacodynamics
What the drug does to the body
Pharmacodynamics
Entry of drug into systemic circulation
Absorption
Form of administration with no absorption
Form of administration with 100% bioavailability
No loss of drug
IV
Bioavailability formula
(AUC ORAL/AUC INJECTED) x 100
Most to least available forms of administration
IV > IM > Subcutaneous > Oral
Acidic drugs are best absorbed in
the stomach
Basic drugs and stomach acid:
rapidly solubilized
most important site for drug absorption
small intestine
Slowly absorbed drugs are absorbed in the
large instestine
rate at which the drug solution leaves the stomach and enters duodenum
Gastric Emptying Rate
Decrease in Gastric Emptying rate
Decrease in rate of absorption (drug possibly degraded)
Decrease in onset of action or therapy (drug stays in stomach too long)
Factors affecting Gastric Emptying (5)
1 Volume 2 Temperature 3 Body position 4 Drug property 5 Patient factors (disease, hunger, anxiety)
Volume of ingested increased material affects GER
Initially an increase in GER -> decrease
Bulky materials vs liquid…
Empty more slowly
Fatty meal: GER
decreases
Carbohydrate-rich meal: GER
decreased
Hot temperature-meal: GER
increased
Lying on the left: GER
decreased
lying on the right: GER
increased
lying down vs standing: GER
decreased
Anticholinergics: GER
decreased
Narcotics: GER
decreased
Analgesics: GER
decreased
Antidepressants: GER
decreased
Antiemetics: GER
INCREASED
Disease states that DECREASE GER (3)
Gastric ulcer
DM
Hypothyroidism
Physiologic conditions that promote INC GER (3)
1 Hunger
2 Anxiety
3 Stress
First Pass Effect
drugs are absorbed in the portal circulation and distributed to liver for metabolism
When drugs undergo rapid first pass effect, what happens to bioavailability
Decreased
route of first pass
oral/rectal -> lumen of GI -> portal circu -> liver
DRUGS UNDERGOING SIGNIFICANT FIRST PASS (9)
ILMMNPPPS
1 Isoproterenol -nonselective B agonist isopropylamine analog of epinephrine
2 Lidocaine -blockade of voltage gated Na ch reversible AP prop
3 Meperidine - opiod morphine like on mu receror
4 Morphine
5 Nitroglycerine
6 Pentazocine - opiod agonist at kappa and blocker of mu receptor
7 Propoxyphene - full opiod agonist
9 Propranolol
10 Salicylamide - aspirine-like
REVERSIBLE transfer of drug from one compartment to another
Distribution
Distribution is affected by (2)
Rate of BLOOD FLOW into the tissue
PROTEIN binding
Drugs bound to albumin (2)
1) canNOT cross biomembranes (bec too large)
2) NOT excreted
Displacement of drug from albumin may
Enhance effect of displaced drug
Acidic drugs are bound to
Albumin
Basic drugs eg Propranolol are bound to
Alpha 1 glycoprotein
When albumin is saturated, drugs bind to
Lipoproteins
Hypothetical volume of BODY FLUID in which drug is dissolved
Volume of distribution
Volume of distribution formula:
Dose of drug/ Drug in plasma
When the drug is distributed EXTRAvascularly, the VD is
increased
When more drug is in VASCULAR SPACE/PLASMA, VD is
bec?
decreased
protein bound (albumin)
conversion of drug to EXCRETABLE form
Metabolism
METABOLIC conversion of drugs
Biotransformation
Phase 2 reactions:
Convert parent drug to a polar (water-soluble) form
How are drugs converted to polar form?
Unmasking or insert functional groups luke OH SH NH
Phase 1 reactions (4)
1 Oxidation CYP450, MFO
2 Reduction
3 Deamination
4 Hydrolysis
Phase 2 reactions are synthetic reactions wherein there is
Conjugation of drugs bound to OH SH NH (1st phase) into (6)
Glucoronate Acetate Glutathione Glycine Sulfate Methyl groups
Drugs that underwent phase 2 reaction are more
Polar and less lipid soluble
Most important site of drug metabolism
Liver
Minor role in drug metabolism
Kidneys
Heart, Intestine, Skin
Enzyme inducers (7)
PCRABS
1 Phenobarbital - inc amount of time Cl channels are open on GABA-A receptor units
2 Phenytoin - block of voltage-dependent Na channels and AP
3 Rifampicin - inhibits bacterial DNA dependent RNA polymerase of B subunit
4 Carbamazepine - blocks voltage-gated Na channels in their inactive conformation preventing AP
5 Barbecued food / Cigarette
6 Chronic alcoholism
7 St John’s Wort/Hypericum perforatum- for depression;inhibits serotonin, dopamine, norepinephrine in synaptic cleft binding GABA-A and GABA-B receptors and increasing serotonin receptors
Inhibits MAO and COMT enzyme allowing more dopamine to be converted to norepinehrine
- Griseofulvin
- Modafinil
- Cyclophosphamide
Enzyme inhibitors (9)
G PACMAN
Metronidazole Erythromycin (Macrolide except Azithromycin) Disulfiram INH Cimetidine Ketoconazole Valproic acid Acute alcoholism Grapefruit juice Protease inhibitors Amiodarone Ritonavir
constant AMOUNT per unit time is metabolized
ZERO ORDER KINETICS
rate does NOT increase even if drug concentration increases
Zero Order Kinetics
Aspirin
Non linear on semilog paper
Horizontal straight line
Zero order kinetics
Rate or amount eliminated any time is constant
Zero Order Kinetics
constant FRACTION per unit time metabolized
First Order Kinetics
Rate INCREASES as drug concentration INCREASES
First Order Kinetics
Linear relationship of concentration and time on semilog paper
First Order Kinetic
Rate or amount of chemical elimination is PROPORTIONAL to the concentration or amount
First Order Kinetics
Half life is INdependent of dose
First Order Kinetics
True halflife or elimination constant does NOT exist
Zero Order Kinetics
Concentration of chemical in plasma decreases by constant fraction per unit time
First Order Kinetics
Saturable Kinetics
Zero Order Kinetics
Michaelis Menten Kinetics
Zero Order Kinetics
Capacity-Limited Kinetics
Zero Order Kinetics
removal of drug in a system
Excretion
Clearance
is Volume of Drug cleared of the drug in unit time
Major route of drug elimination for polar molecules
Renal
Major route of drug elimination for water soluble drugs
Renal
Major route of elimination for drugs with low molecular weight <500
Renal
Major route of elimination for drugs that are biotransformed slowly
Renal
Excretion (3)
Glomerular filtration
Tubular reabsorption
Active tubular secretion
PASSIVE process where small molecules are filtered through glomerulus and nephron
Glomerular filtration
drugs bound to albumin are
not excreted
GFR excretes
creatinine
decrease in clearance indicates kidney problem
CARRIER MEDIATED
active tubular secretion
Volume of PLASMA CONTAINING DRUG that is cleared by liver per unit time
Hepatic clearance
Competes with active tubular secretion of penicillin
Probenecid - blocks pannexin channel URAT1 (uric acid reabsorption) and OAT organic acid transport pump inhibiting organic anion secretion into tubule where penicillin is secreted in exchange for dicarboxylate anion
Increased Penicilloic acid (metabolite)
increases concentration of Penicillin
Excretory pathway for drugs >500 MW
Biliary
Excretion pathway for anticancer drugs (2)
Mammary
Genital
Excretion pathway for metals, alcohols
Sweat
Doxycycline excreted via
Intestine
Volume of PLASMA ELIMINATED OF DRUG per unit time
Drug Clearance
Clearance formula
Elimination rate/Plasma concentration
Maintenance Dose
Dosing Rate x Dosing Interval
PASSIVE process
Lipid soluble, non ionized drugs reabsorbed
Tubular Reabsorption
Tubular reabsorption is affected by
pH urine
G6PD results in (2)
Dec NADPH
Dec Glutathione
Hemolysis occurs in G6PD
Bec of lack of NADPH and glutathione that will protect RBCs once induced with oxidative stress like infection, drugs, fava beans
