2 - Drug Absorption and Distribution Flashcards
What is Pharmacokinetics
Studies the movement of a drug through the body
4 Processes of Pharmacokinetics
1) Absorption
→Movement of drug into the blood - leaving the area it was administered
2) Distribution
→Where the drug is destined to go once in the blood
→ either in: extracellular fluids, intracellularly, or enters adipose tissue
3) Metabolism
→Process by which the body changes the chemical structure of the drug
→Primarily happens in the liver (can also happen in the GI tract)
4) Excretion
→Removal of the drug from the body
→Most drugs are removed by the kidney via urine
→Liver moves drugs into bile to be excreted in feces
Enteral Route of Administration
Enteral: a drug will end up in the GI tract
→When given orally, has bioavailability of 30-40%
→There is a lot of first pass metabolism; the drug has been changed before reaching systemic circulation
Ex.
1. Oral (PO): liquid or oil
2. Rectal: ex. Suppository
Parenteral Route of Administration
Parenteral: does NOT involve the GI tract
Ex.
1. Intravenous: directly in vein
2. Transdermal: local anaesthetic injected into the skin’s dermis
3. Subcutaneous: insulin injected under the skin
4. Intramuscular: an EpiPen being injected into the muscle
5. Intrathecal: epidural injection in CSF around the spinal cord
Enteral VS. Parenteral Route of Administration
Enteral
→Drugs given via the GI tract
Slow and variable absorption
→Drugs pass through the liver before reaching circulation
→Slower (minutes to hours) onset of action
→Easy, non-invasive
→Not used for unconscious patients
→Low risk of infection
Parenteral
→Drugs given directly into the bloodstream or tissues
→Fast and direct absorption
→Drugs avoid liver metabolism
→Faster onset of action
→Requires injection, more invasive
→Useful in unconscious patients
→High risk of infection
Other Routes of Administration
- Inhaled: breathing anaesthetic prior to surgery
- Topical
- Ocular: antibiotic eye drops
- Sublingual: nitroglycerin spray under the tongue for chest pain
- Vaginal: antifungal suppository
3 Properties needed to cross membranes
1) Drug needs to be lipophilic - it can easily dissolve through fatty acid core and cross membranes
→ Hydrophilic drugs cross membrane slowly but can be improved if there is the presence of uptake transporters
2) Ionization
→ If it is charged, the drug is water-loving
→ If it does NOT have a charge, more fat-loving
→Uncharged drugs cross membrane more quick than charged drugs
3) Surface Area
→For a drug to cross a membrane, it has to interact with the surface
→ Villi increase surface area and increase absorption
Factors affecting Oral absorption
1) Gastric emptying
→how fast will the drug move into the SI where most absorption occurs
2) SA: improves absorption
→Plays a large role in SI where the villi
3) Efflux transporter’s
→try to remove drug from cell and put it back into GI tract
→Work against absorption
→Efflux transporters pump drugs back into the gut, reducing absorption into the bloodstream.
→Result: Lower bioavailability
4) Drug formulation/ lipophilic/ drug ionization
→If a drug does noy completely disintegrate/ dissolve, it is not available for absorption
→Lipophilic drugs and non charged drugs have easier time crossing the membrane (than hydrophilic or charged drugs)
5) Blood flow
- Areas with high blood flow will have increased absorption
→Muscles have a lot of blood flow; greater absorption
→SC has much less blood flow
6 Factors affecting Drug Absorption
1) Lipid solubility
→More lipophilic; easier it is for a drug to cross the membrane and be absorbed
→Hydrophilic drugs - do not cross membranes by simple diffusion bc they can not dissolve in fatty acid tails of the phospholipid bilayer
2) Activity of drug transported
→Only uptake transporters will move a drug into a cell and increase its absorption
→Efflux transporters decrease absorption because that move drugs out of a cell
3) Drug ionization
→When not ionized, they are more lipophilic = easier to cross membranes = increase absorption
4) Surface Area
→More surface area = increased absorption
→Even though weak acids are not ionized in the stomach (bc of acidic pH), they are still better absorbed in the SI bc SA is a much more important factor in rate of absorption than ionization
5) How quickly a drug dissolves
→drugs must be dissolved in solution to cross membranes and be absorbed
→A tablet will dissolve much more slowly in the contents of the GI tract than small fine particles will
→When capsules dissolve and fine particles are released, they will dissolve much more rapidly in solution that tablets will
6) Blood flow
→No blood flow = no absorption
→Disease can affect blood flow
- Congestive heart failure: blood flow is reduced to many areas of the body
- Someone with CHF may have slower rate of absorption than healthy individual
Enteric Coated Drugs
- the coating prevents the disintegration in acidic stomach
- dissolving occurs in the SI
→ high pH allows for coating disintegration - drugs designed with an enteric coating
→ A drug can be irritating to the stomach; if it was released in the stomach it would cause issues
→ A drug can also be destroyed by stomach acid - Enteric coating drugs should never be crushed or chewed because the enteric coated is needed to protect the drug from the stomach
What is Bioavailability?
→ the fraction of the dose of a drug that reaches general circulation
Factors affecting gastric emptying
1) Consistency of what we consume
→Liquids move into the small intestine faster than solid foods
→ Taking meds with water rather than food will increase rate of absorption
2) Composition of meal
→ Fatty meals slow down the movement of the stomach
→ Due to hormones released by the GI tract when fats are present which act on the stomach to slow motility
→Higher calorie meals slow gastric emptying
3) Body position
→Sitting or standing will increase gastric emptying
→A patient lying down will have faster gastric emptying if lying on their RIGHT side than LEFT side
□ Bc the pyloric sphincter “exit” site is on the right
4) Drugs that slow or increase GI motility
→Taking other meds that affect stomach motility can change the rate of absorption
1) Oral Route of Administration
→Variable bioavailability
→Affected by first-pass metabolism, gastric emptying, surface area of GI tract, and GI conditions
Advantages:
→Convenient and easy to take
→Safer than parenteral routes
→Can be removed naturally in case of overdose (e.g., vomiting)
Disadvantages:
→Slower onset
→Not suitable for patients who are vomiting, nauseous, or unconscious
2) Rectal Route of Administration
→Variable bioavailability: ; less first-pass metabolism than oral
→Absorption varies due to rectal blood flow
→Less 1st pass metabolism (only some blood passes through the liver, while rest goes to circulation)
Advantages:
→Useful when patient is vomiting, unconscious, or unable to swallow
Disadvantages:
→May cause irritation and discomfort
→Lower patient compliance
3) IV Route of Administration
→Bioavailability: 100% (directly enters circulation)
→Bypasses absorption and first-pass metabolism
→Immediate effects (good for use in emergencies)
Advantages:
→Rapid onset
→Exact dose delivered
→IV infusion allows for stable drug levels
Disadvantages:
→Inconvenient, must be administered by healthcare professional
→Risk of pain, bleeding, infection
→Irreversible once given
4) Intramuscular Route of Administration
→Bioavailability: High (~75%)
→Used for vaccines and antibiotics
→Influenced by blood supply to muscle
Advantages:
→Rapid absorption due to rich blood supply
→Suitable for slow-release drugs
Disadvantages:
→Pain, bleeding, infection risk
→Absorption varies with blood flow (e.g., exercise increased blood flow in muscle but decreases it to liver)
5) Subcutaneous Route of Administration
→Bioavailability: Low to moderate (less than IM)
→Slower absorption due to fewer capillaries
→Used for insulin and heparin
Advantages:
→Provides stable drug levels over time ( bc slower absorption)
→Safer than IV/IM (fewer nerves and vessels)
Disadvantages:
→Pain, bleeding, infection risk
→Repeated use may cause tissue damage
6) Sublingual Route of Administration
→Bioavailability: High (avoids first-pass metabolism)
→Absorbed under tongue directly into bloodstream
Advantages:
→Rapid onset
→Convenient and non-invasive
Disadvantages:
→Affected by saliva
→Some of the dose may be lost if swallowed
7) Topical Route of Administration
Bioavailability:
→Low (for local effects)
→Moderate (for transdermal/systemic effects)
→Transdermal: systemic effects (e.g., nicotine patch)
→Local: targeted action (e.g., anti-inflammatory creams)
Advantages:
→Minimal side effects for local treatment
→Transdermal: steady drug levels
Disadvantages:
→Slower onset for transdermal
→Bioavailability varies (increase absorption with damaged skin)
8) Inhalation Route of Administration
Bioavailability:
→Low (for local effects)
→High (for systemic effects)
→Local: asthma inhalers
→Systemic: anesthetics
Advantages:
→Minimal side effects for local drugs
→Very rapid absorption and onset (lungs have large surface area and high blood flow)
Disadvantages:
→Requires proper inhalation technique
→Some drugs may irritate the respiratory tract (coughing, discomfort)
Composition of Fluid
Total Body Fluid: 50–70% of body weight.
Intracellular Fluid (ICF): ~2/3 of total body water. - lipophilic can accumulate
Extracellular Fluid (ECF): ~1/3 of total body water, including:
→Plasma: ~20% of ECF.
→Interstitial Fluid: The remainder of ECF
What is Volume of distribution?
- calculated volume that describes the relative distribution of a drug in the body
- Vd is an imaginary volume and can exceed our total body fluid volume
- Vd = total amount of drug in the body/ plasma concentration of the drug
→If plasma concentration is low for a given dose, the Vd is large (low plasma concentration = large Vd drug)
→A drug with small volume of distribution will be contained within plasma (not leave capillaries)
→ A drug with a large volume distribution will be distributed to cells of our tissues
Continuous Capillary
→The blood-brain barrier (BBB) has tight tight junctions, making it impermeable to many drugs
→In the BBB, endothelial cells do not allow paracellular movement (between cells); drugs must cross via the transcellular pathway, meaning they must be lipophilic or use a drug transporter
→Large molecules, such as biologic drugs (proteins), cannot pass through these clefts and thus remain in the capillaries, resulting in a small volume of distribution (Vd)
Drug Binding to Plasma Proteins
→Albumin and alpha-1 acid glycoprotein are key plasma proteins that bind to drugs.
→Drugs in the bloodstream exist in two forms:
1. Free (unbound): dissolved in plasma and active
2. Bound: attached to plasma proteins and inactive
Bound drugs:
→Cannot cross intercellular clefts, so they stay in circulation
→Do not activate receptors, so they have no immediate effect
→Are not readily filtered by the kidneys (kidneys don’t filter proteins well)
→Are less likely to be metabolized by the liver because the protein binding protects them
→The bound drug portion acts as a reservoir, delaying action and elimination.
→Only free drug can bind to target receptors and be pharmacologically active.
→Bound drugs have a smaller volume of distribution (Vd) because they cannot leave the plasma compartment
