Pharmacokinetics Absorption Flashcards
Pharmacokinetics
Passage of drugs across the cell membrane
Drug movement in the body: Absorption, distribution, metabolism, and excretion (ADME)
Pharmacodynamics
What the drugs do to the body (therapeutic effects)
Absorption
Process where drugs enter the blood stream without being chemically altered
OR
Movement of a drug from its site of application into the blood
Increased drug concentration and drug action…
Increases absorption and distribution
Decreased drug concentration and drug action…
Decreases metabolism and excretion
Factors that influence absorption rate
- Types of transport
- Routes of administration
- Physiochemical properties of the drug
- Concentration of the drug
- Protein binding
- Dosage forms
- Circulation at the site of absorption
Passive diffusion
Continues till equilibrium is attained on either side of the membrane
What is passive diffusion dependent on?
Concentration gradient
Drug molecular size
Lipophilic nature of the molecule
Temperature
Thickness of the membrane
Lipophilic gradient and passive diffusion
Higher the lipid solubility, higher the diffusion
Temperature and passive diffusion
Lower the temperature, slower the diffusion
Enteral administration
Through GI tract
Oral: min to hrs
Sublingual/ buccal: 3-5 minutes
Rectal: 5-30 min
Parenteral administration
Through injection
IV: 100% F, 30-60 sec
IM: 10-20 min
SubQ: 15-30 minutes
Dermal administration
Epidermic, installation and irrgation
Inhalation administration
Vaporization, gas inhalation, nedbulization
Transdermal administration
Patch, microneedle
Major factors in small intestine diff species that effect absorption
pH
Epithelial surface
Surface area
Motility
Efflux proteins: P-glycoprotein (takes drug out of cell)
_______ and _________ are rapidly and efficiently absorbed
Lipid soluble and Unionized drugs
Water parturition coefficient (PC)
High PC= more absorption
(higher lipid to water= more absorption)
What solution causes drugs to be absorbed rapidly?
Drugs in aqueous solutions
Rate of absorption
solutions –> emulsions –> suspensions –> capsules –> tablets –> sustained release products
What drugs cross the capillary membrane?
Drugs with molecular weight less than 50-600 Da
What drugs enter the cell via aqueous filled channels?
Small, water-soluble molecules and ions below 50 Da
What happens when the ph and pKa are equal
50% of drug ionised and 50% unionised
What happens when pH is one unit below the pKa?
Acid is 9% ionized and base is 91% ionized
What happens when pH is 2 units below pKa?
Acid becomes 1% ionized and base becomes 99% ionized
What is an exception to the pH and pKa rules?
Strong acids and strong bases remain ionized at all body pH
Weak acids and bases are unionized
pH- partition hypothesis
Basic drugs in the blood (pH 7.4) readily enter into acidic tissues and fluids
Acidic in acidic medium: unionized
Ion trapping
Ionized drug gets trapped on one side of a membrane that divides 2 compartments that contains fluids of different pH values
When would ion trapping occur
When a drug found in low concentration in the blood (pH7.4) is found in a higher concentration in the urine (pH5)
Why does ion trapping occur?
Because only unionized, hydrophobic, uncharged, lipid soluble drugs can pass through cell membranes
Example of ion trapping
Weak organic base diffused passively from blood (pH- 7.4) to rumen fluid (pH5.5) –> once passing, base drugs in acids become ionized (broken down, bad) –> ion trapping because they cannot pass the membrane –> cycle of reabsorption and not being excreted –> overdose
Where will acidic drugs be more absorbed?
Stomach because stomach is more acidic (like/like= unionized= more absorption)
In the intestine (pH 7.8), which will be better absorbed, a weak acid or a weak base?
Weak base because base/base = unionized and better absorption
If we alkalinize the urine of 7.8, will a lower or higher percentage of a weak acid be ionized, compared when the urine pH was 6.0?
Higher percentage because a weak acid is ionized in the basic solution
Other factors influencing absorption
- Blood circulation at site (increase blood flow= increased absorption
- Absorption surface area
- GIT functional integrity
GIT functional integrity
An increase in gastric emptying time, the drug absorption will be more
ex: diarrhea drug absorption is reduced due to increased peristaltic activity
Bioavailability (F)
The % or fraction of administered drug by any route that reaches circulation in a chemically unchanged form
Which route should have 100% bioavailability?
Intravenous route because it’s put directly into circulation
Oral bioavailability
F=60%
How is bioavailability described?
- Cmax (peak plasma concentration)
- Time to reach Cmax
- AUC
Bioavailability equation
F= (AUC)oral / (AUC) iv
Bioavailability equation with different doses
F= 100 ( ( AUC po x Div) / (AUC iv x Dpo) )
What factors affect bioavailability?
First pass effect
Gastric emptying
Drug solubility/ dissolution (salt forms will increase dissolution)
Drug stability in GI fluids
First-Pass metabolism
Increased FPM will decrease F
Absorbed drug moves via protal circulation to liver
High extracted drug may be removed with “first pass”
Should give these drugs via IV not orally
Which drugs have extensive first pass effect?
Morphine
Propanolol
Buprenorphine
Diazepam
Midazolam
Pethidine
Efflux proteins or transporters
Move drugs and other chemicals out of the cell
Normal protective mechanism
Important for drug resistance (brain)
Distribution
Process where drug reversibly leave the blood stream and enter the extravascular fluid and tissue
Determines the transport of drugs to their site of action
Highly perfused organs
Liver, kidney, GI tract, brain, lungs
Receive rapidly high levels of drug
Less perfused organs
Muscle, bones, fat tissue
Plasma-protein binding
Reduces efficiency of drug distribution
PP bound drugs non-diffusible
Plasma protein bound drugs
Pharmacologically inactive and less efficacious and potent
Don’t undergo metabolism and excretion via glomerular (limits filtration)
Long plasma half-lives
Narrow therapeutic index and small volume of distribution
What are acidic and basic drugs bound to?
Acidic: albumin
Basic: a1-acid glyco protein
What does drug binding do?
Slows the rate where the drug reaches a concentration sufficient to produce a pharmacologic effect
Blood brain barrier
Formed by endothelial cells
Doesn’t permit ionized and non-lipid soluble drugs
TJs!!!!
Placenta
Highly ionized drugs and drugs with low lipid solubility excluded
Tetragenic drugs (causing birth defects) blocked
Milk
Mammary gland- lipid barrier and many drugs readily diffuse from plasma into milk
Max residue levels in milk
Volume of distribution (Vd)
Dose / plasma concentration
Decreased by plasma protein binding
Increased by tissue binding
