Week 1 (23 questions) Flashcards
ADME
Describe each
Absorption- when the drug is released from the formulation//administration site and enters the bloodstream
Distribution- the movement once it is in the bloodstream
Metabolism- the body using the drug and giving off a byproduct
Excretion- getting rid of the by product
ABSORPTION
fastest to slowest absorption
Fastest to slowest absorption:
Oral disintegration, buccal tablets, and oral soluble wafers
Liquids, elixirs, and syrups
Suspension solutions
Powders
Capsules
Tablets
Coated tablets
Enteric-coated tablets (broken down not in stomach but in intestines)
ORAL
What can influence ORAL drug BIOAVAILABILITY?
The most common of all routes
Most drugs are ABSORBED in stomach or small intestine
pH of the GI tract (Absorption)
Co-Administration w/ Drugs or Meals(Absorption)
Drug Formulation/Pharmaceutics(Absorption)
P-Glycoproteins(Absorption)
First Pass Effect (Metabolism)
EXAMPLES OF ORAL DOSAGE FORMS (most common route):
Oral Liquids/Suspensions
Already in dissolved form and thus absorbed quickly
Sometimes called IR= Immediate Release
In general, you should SHAKE an ORAL suspension (powder will go to the bottom)
EXAMPLES OF ORAL DOSAGE FORMS (most common route):
Enteric Coated Tablets
Whereis drug absorbed?
and why?
Extra coating on the outside prevents drug from being broken down by the acidic pH of the stomach
Drug is not absorbed until they reach the small intestine (higher pH)
Commonly made to PROTECT the gastric mucosa from irritation
Famous Example: Enteric Coated Aspirin (EC)
EXAMPLES OF ORAL DOSAGE FORMS (most common route):
Extended Release/Sustained Release Tablets
Release drug over a prolonged period
Abbreviations => SR, SA, CR, XL, XT, ER, and more
Oral Drug Bioavailability Influences:
1.pH of the GI Tract (ABSORPTION)
Some drugs need an acidic environment (may prefer the stomach)
Some drugs need a basic environment (may prefer the intestines)
Factors that influence pH of the GI Tract:
Time of day (pH can fluctuate throughout the day)
With or without food
Medications (Tums®)
Lifespan (neonates, geriatrics)
Diseases/Conditions
- Co-Administration with Drugs or Meals (ABSORPTION)
Co-Administration with Drugs or Meals (ABSORPTION)
Can be GOOD or BAD!
A) Certain drugs may adhere to one another, others may change the pH of the GI tract
B) Food alters pH of the GI tract and transit time
Example : Doxycycline (a Tetracycline Antibiotic)
Avoid administering with other medications (like Tums®). Calcium carbonate (Tums®) will bind to the doxycycline and prevent the body from absorbing the antibiotic
- Pharmaceutics (ABSORPTION)
Different formulations will have different dissolution rates
Liquid vs. Enteric Coated vs. Extended-Release Tablet
- P-Glycoproteins (ABSORPTION)
Part of our “defense system”
Located in essentials areas of body
Blood Brain Barrier, GI Tract
Sometimes called “Anti-absorption pumps” or Efflux Pumps designed to pump out xenobiotics (toxins, drugs)
Net Result= Less absorption of oral drugs into the general circulation
P-glycoprotein Inhibition
In the past several years, we have discovered that certain drugs and foods may block/prevent normal P-glycoprotein function
Famous example of P-Glycoprotein Inhibitor:
Grapefruit and Grapefruit Juice (Pomelo too)
Real World Example:
There is a cholesterol lowering drug class commonly known as “Statins”
“Statins” have a risk of rhabdomyolysis or rapid muscle breakdown (risk increases based on dosage)
If you take Atorvastatin and drink Grapefruit Juice, the Grapefruit Juice inhibits the P-glycoproteins, allowing the body to absorb more Atorvastatin than anticipated= increased risk for toxicity
Best to tell patients to avoid grapefruit while taking certain medications
- First Pass Effect (METABOLISM)
Oral drugs are the only route subjected to what’s known as the “First Pass Effect”.
- Drug is swallowed,
- Goes to GI tract
- Gets absorbed into GI mucosa
- The gastric/intestinal mucosal blood flow goes to portal vein
- Portal Vein carries the blood to the Liver
- Liver metabolizes drugs (FIRST PASS EFFECT)
- Metabolized drug reaches general blood circulation
Enteral Routes
The drug is absorbed into the systemic circulation through the GI tract
The Enteral route has variable Bioavailability
Parenteral Routes
Non-GI-Tract administration, aka injections
The drug is absorbed into the systemic circulation
Intravenous: 100%: Blood stream
Intramuscular/Subcutaneous/ Intradermal:
Variable: Depends on location
Epidural: Variable: Epidural space around the spinal cord
DISTRIBUTION
Permeability of the Cell Membrane
Lipid Soluble vs Water Soluble
Blood Brain Barrier, Placenta
Lipid Soluble
Easily distribute into fatty tissues where they may store or concentrate
Have the potential to cross the Blood Brain Barrier (BBB) and the Placenta
Water Soluble
Typically remain in highly vascularized spaces and can easily leave the body via elimination (urine!)
DISTRIBUTION
PROTEIN BINDING
most common blood protein?
Albumin is the most common blood proteiN
Some drugs preferentially bind to protein/albumin
Called “highly bound drugs“
DISTRIBUTION
Bound drug vs Free Drug
Free drug (active)
Drug is not bound to albumin
can distribute into extravascular tissue to its intended target
Bound drug (inactive)
Stuck to albumin, stays in the bloodstream
Cannot get to extravascular space and reach intended target
DISTRIBUTION
Give an example of a highly protein bound drug
Famous Example of a highly protein bound drug= PHENYTOIN
10% Free, 90% bound
DISTRIBUTION
Identify several conditions or diseases which may alter drug distribution
Diseases/Conditions can alter perfusion
Poor perfusion
Peripheral Vascular Disease
Heart Diseases (Heart Failure)
Shock (Sepsis)
METABOLISM
Describe the ultimate “goal” of drug metabolism, also known as biotransformation.
Goal: Convert drugs to become HYDROPHILLIC AND POLAR. A form that can be easily eliminated from the body.
Convert drug into an active metabolite or inactive metabolite
Metabolites could be weaker or stronger than the original drug
Liver is primary organ
METABOLISM
Discuss special considerations in drug metabolism.
Other influences?
Other drugs
Certain Foods (Grapefruit)
Smoking/Alcohol
Other influences:
Patient variables
Diseases (liver diseases)
Genetics*
Age
Infants have limited liver enzymes
Geriatric patients may have less liver enzyme activity
METABOLISM
What are Inhibitors and Inducers
Substances that decrease the activity of specific enzymes, slowing down the metabolism of drugs. Inhibition can lead to increased drug levels in the body, potentially resulting in enhanced therapeutic effects or an elevated risk of adverse reactions
Substances that increase the activity of specific enzymes, accelerating the metabolism of drugs. Induction can lead to reduced drug levels in the body, potentially resulting in decreased therapeutic effects or an increased risk of treatment failure.
METABOLISM
Describe the first pass effect and identify methods to bypass the first pass effects
anything that doesnt go through GI tract
METABOLISM
Describe the mechanism and role of a pro-drug
They are inactive drugs that becomes active
Once metabolized by liver or other system
Can help improve bioavailability
Allows for improved drug delivery, enhanced bioavailability, or reduced side effects.
METABOLISM
IMPAIRED LIVER FUNCTION
Signs/Symptoms
PHYSICAL
signs and symptoms of hepatic impairment (especially drug induced liver injury- DILI)
Dark urine- (bilirubin mixes with urine)
Jaundice
Swelling of abdomen
Bruising/Bleeding (lack of clotting factors)
Fatigue
Ammonia can concentrate (liver normally converts to urea)
Ammonia accumulation- neurological changes- encephalopathy
METABOLISM
IMPAIRED LIVER FUNCTION
Identify common lab values
AST
ALT
ALP
ALBUMIN
TOTAL BILIRUBIN
AST: Elevated
ALT: Elevated
ALP: Elevated
ALBUMIN: Decreased
TOTAL BILIRUBIN: Elavated
ELIMINATION
Discuss the importance of excretion of a drug from the body and some of the routes by which the drug may be excreted.
PRIMARY SITE OF ELIMINATION: KIDNEYS
Other Sites/Mechanism:
Liver, Breast milk, Sweat, Bowel
Identify common lab values of renal impairment.
Serum Creatinine (SCr)
Blood Urea Nitrogen (BUN)
Creatinine Clearance (CrCl)
Estimated Glomerular Filtration Rate (eGFR)
Urine Output
Serum Creatinine: Elevated
Blood Urea Nitrogen (BUN): Elevated
Creatinine Clearance (CrCl): Decreased
Estimated Glomerular Filtration Rate (eGFR): Decreased
Urine Output: Oliguria (Decreased)
Acute Kidney Injury
Acute Injury to the kidney
Sudden elevated SCr/BUN
Decreased eGFR/CrCl
Chronic Kidney Disease
Chronically elevated SCr/BUN
decreased eGFR/CrCl
Onset
Onset: The time it takes for the drug to elicit a therapeutic response
Example: Patient in pain and request morphine
IV: 5 to 10 minutes
Oral: ~ 30 minutes
Duration
The time a drug concentration is sufficient to elicit a therapeutic response
Example: Patient takes a morphine pill
Immediate release (tablet, oral solution, injection): 3 to 5 hours
Extended-Release capsule and tablet: 8 to 24 hours (formulation dependent)
Minimum Effective Concentration
The plasma drug level below which therapeutic effects will not occur
Therapeutic Index/Range
Enough drug present to produce therapeutic response, but not enough to be toxic
Toxicity
Plasma drug levels climb too high, toxicity occurs
Narrow Therapeutic Index
drugs where small differences in dose or blood concentration may lead to serious therapeutic failures
Half-Life
The time it takes for the concentration of the drug in the bloodstream (or any other relevant compartment) to decrease by half.
Steady State
The physiologic state when amount of drug removed equals amount of drug absorbed
The earlier we check, the better
The longer we wait, the higher the risk in delaying dose adjustments
Peak Level
Highest blood level (drawn ~30 minutes after a dose)
Trough Level
Lowest blood level
Check 30 minutes to 1 hour prior to the next dosing interval
Affinity
Degree to which a drug (Key) attaches to a receptor (Lock)
Who wins? The drug with the higher affinity
Agonist (morphine)
Partial Agonist
Drug binds to the receptor, there is a response
Drug binds to the receptor, the response is diminished
Antagonists (naloxone)
Drug binds to the receptor, there is no response.
Prevents binding of agonists.
Identify common causes of Adverse Drug Events (ADEs)
1)Medication Error
Wrong dose for example
2) Adverse Drug Reaction
Allergic reaction
Pharmacological Mechanism of the Drug
Describe Precautions, Contra-indications, and Drug Interactions
Precautions: Can still use the drug, but BE CAREFUL and MONITOR (Evaluate Benefit vs Risk)
Contra-indications: HARD RULE -DO NOT GIVE UNDER ANY CIRCUMSTANCES
Drug Interactions:
