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Spring 2020 - Pharmacology 1 > Pharmacokinetics > Flashcards

Flashcards in Pharmacokinetics Deck (73)
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1

Pharmacokinetics

What the Body does to the Medication

Absorption

Distribution

Metabolism

Excretion

2

Absorption

Medication moves to blood stream or final action site

3

What does the absorption of medication depend on?

  • Route of administration
  • Ionization of Molecule
  • Size of Molecule
  • Patient Factors
  • Bioavailability

4

Lipophilicty

Less Ionized, may move accross lipid bilayer

5

Hydrophilicty

More Ionized - More likely to stay in solution and blood

Requires carrier, channel, or energy to go through fat layers

EX: Electrolytes

6

Bioavailability (F)

Percentage of medication that reaches systemic circulation

  • Dissolution & Absorption Characteristics
    • ER Tabs can change F
    • F = 100% for IV drugs
  • Route of Administration
  • Stability in GI Tract
  • Metabolism prior to blood stream

New Dose = (FOLD x Current Dose) / FNEW

Useful for converting dosage forms

7

Calculating Bioavailability Examples

  • Ex: Levothyroxine
    • Oral Tablet Bioavailabilitiy Range: 40-80%
    • PO dose: 100mcg, then IV dose: ?
      • ​100mcg x 0.4 = 40 mcg
      • 100mcg x 0.8 = 80 mcg
      • IV Dose Range 40-80 mcg (may use 60 mcg)
  • ​​Phenytoin
    • ​Capsule & Salt S: 0.92
    • Suspension & Chew Tabs S: 1
      • ​May require dose adjustment if changing from capsule to suspension, IV to tabs, etc.
  • ​​Digoxin Tab F: 0.7
  • Digoxin Elixter F: 0.8
  • Currently taking 250 mcg tabs. How much elixer is equivalent?
  • New Dose = (FOLD x Current Dose) / FNEW
    • ​= (0.7 x 250 mcg) / 0.8 = 219 mcg
    • Less of tablet is absorbed than elixir, therefore a higher dose than elixer


 

 

 

8

What are all routes of administration?

  • Oral
  • Topical
    • Transdermal - cream, patch
    • Eye/Ear drops
    • Inhalation
    • SL/Buccal
  • Injection - IV, IM, SQ, IT
    • Peripheral vs. Central

9

What are GI considerations for Oral Adminstration

  • pH
  • Contents
  • Surface Area
  • Blood Flow
  • Motility
  • Flora
  • Complete GI Tract

10

How does pH of GI Tract affect absorption of medication?

Some meds need acidic environment for dissolution and/or absorption

Acid suppressants may reduce absorption

EX: Calcium, Iron, Magnesium, B12

11

How does contents in the GI tract effect absorption of meds?

Positively or Negatively depending on medication

12

How does the surface area of the GI tract effect medication absorption?

Short bowels, resections, IBD may have reduced oral absorption

13

How does Blood Flow of GI Tract effect med absorption?

Meds are absorbed from the small intestine into the blood stream.

Poor blood flow may reduce absorption

14

How does GI Motility effect med absorption?

Too Fast: possible reduced contact time and reduced absorption

Too Slow: possible increased absorption

15

How does GI Flora effect med absorption?

EX: E. lentum is needed for digoxin metabolism. Erythromycin kills this bacteria leading to digoxin toxicity.

16

Sublingual/Buccal Absorption

  • Drains directly into vena cava
  • Very fast
  • No first past metabolism, does not rely on GI tract
  • Must be HIGHLY lipid soluble and potent

 

Should have 100% Bioavailability if done correctly

17

What is First Pass Metabolism

Concentration of Oral drugs  is greatly reduced before it reaches systemic circulation.

  • Nasal: Med absorbs directly into veins
  • Venous System: transports blood from nose directly to heart - no liver metabolism
  • Heart: pumps out blood to body - no delay
  • Liver: 90% of oral meds metabolized and destroyed before it goes to heart
  • Portal Circulation: All blood from intestines taken to liver for detoxification
  • Oral meds: Sit in stomach for 30-45 minutes.

18

Consideration for Topical Administration

  • Skin
    • Intact - dont give if broken/dry
    • Solubility - need to be highly lipophillic 
    • Temperature - heat increase absorption
    • Blood Flow - PVD decrease absorption
  • Eye
    • May become systemic through nasolacrimal canal
  • Inhalation
    • Rapid d/t large surface area
    • Avoids first pass
    • Local site of action
    • Hard to control

19

Injection Adminstration

  • IV: Potentially immediate - Good for large doses
  • SQ: Depending on solution, rates may be slow (repository) or fast (aqueous)
    • slower onset
  • IM: Same as SQ. Be sure not to enter blood stream directly
    • Almost as fast as IV
  • Simple Diffusion
    • Rate limits: amount of capillaries, solubility, molecular size, composition

(Bioavailabilty of these all are pretty much 100%)

20

Volume of Distribution

  • Assumes the concentration of the medication is the same throughout all compartments
  • Average Adult Plasma Vd: 3 L
  • Total Body Water: 0.65 L/kg
  • Useful for Loading Dose

21

Loading Dose

Dose needed to reach desired concentration based on volume of distribution

Loading Dose = Vd x Cd (desired concentration)

EX:

Vancomycin Vd = 0.7 L/kg
Desired concentration ~ 30 mg/L
What is loading dose for 70 kg patient?

22

Multi-Compartment Models

  • Redistribution before elimination
  • Slow rate of adminstration for secondary redistribution
  • Target organ may be in inital or secondary compartment
  • Volume distribution assumes concentration of med is same in EVERY tissue

23

How do meds flow through multiple compartments?

  1. Given via any route  
  2. Goes to Compartment 1 - usually general circulation.
  3. Goes to Other Compartments or straight to elimination

(Normally 2nd Compartment - Major Organs & 3rd Compartment - Fatty Tissue)

24

Protein Binding

Some meds bind to proteins to move through circulation

  • Unbound/free drugs = active
  • Acidic Drugs: albumin
  • Basic drugs: alpha 1 acidic glycoprotein
  • Generally reversible
  • Saturable
  • Non-linear - binding plateau
  • Competitive

25

How does low albumin effect free drug concentration?

Increases concentration, which can increase toxicity

Ex: Burns, Malnutrtion, Kidney/Liver Disease

26

Tissue Binding

Some meds gravitate to certain tissues

  • Fat: Reservoir for lipid soluble drugs
  • Bone: Tetracyclines
    • Dont give to children who dont have all adult teeth - permanent yellow teeth
  • Heart Muscle: Digoxin

27

In order for a drug to enter an organ, what ability must it have?

The ability to permeate all membranes that separate the organ from the site of drug administration.

 

EX: Benzodiazepines are lipophilic and readily cross gut wall, capillary wall, blood-brain barrier; They get to the brain fast and are useful for anxiety and seizures.

28

Blood Brain Barrier

Super Compact Wrapping of the Blood Vessels

Very protective - only blood, glucose, and electrolytes that can normally pass 

29

What occurs in fetal plasma and why?

Ion trappig of basic drugs because fetal plasma is more acidic

30

Placental Transfer

  • More likely to absorb in fetal circulation:
    • Low molecular weight, high lipid solubility, unbound
  • P-glycoproteins limit transport in
  • Anything mom takes, baby takes