Ocular Pharm: L1: Review of Pharmacokinetics and Pharmacodynamics

Question 1

Absorption

1. Passive Diffusion
   a. Mechanism for what kind of drugs?
   b. BEST for what kind of Drugs?
2. Active Transport:
   a. Topical or Oral?
   b. For drugs that resemble what?
3. Endocytosis: For what kind of drugs?
4. What 4 Factors AFFECT ABSORPTION? (B CAP)

Answer 1

1. a. Topical Drugs
   b. For Lipid-Soluble Drugs
2. a. For drugs that resemble Natural Molecules
   b. Natural drugs
3. Large Drugs (like Vitamins)
4. a. Blood Flow at the Site
   b. Contact Time w/Surface Area
   c. Available Surface Area
   d. Polarity of Drug/pH of Site

Question 2

Polarity of Molecules

1. What do POLAR MOLECULES HAVE?
   a. So 1 Part of the Molecule is more what?
   b. Do they Dissolve in water?
   c. Hydrophilic/Hydrophobic?
2. What about NON-POLAR MOLECULES?
   a. Dissolve best in what?

Answer 2

1. a Dipole or Multi-Pole Moment
   a. 1 Part of the molecule is more Positively Charged and Another more Negatively
   b. Yes (which is Polar…So negatively Charged)
   c. Hydrophilic and Lipophobic
2. Little to No Dipole Moment
   a. in NON-POLAR SOLVENTS (like LIPIDS): so Lipophilic (Hydrophobic)

Question 3

pH and Absorption

1. Polar Compounds dissolve in what solutions better?
   a. Body is what % Water?

b. Most biological Actions of drugs take place in what Compartment types?
2. Non-Polar Compounds get through what better?
a. Body is what % Lipid?
b. Lipid Containing structures usually separate what compartments from the outside world?

Answer 3

1. Aq. Solutions
   a. 50-70%
   b. in Liquid Compartments (interstitial Space or w/in Cells)
2. Membranes better
   a. 3-16%
   b. Liquid Compartments

Question 4

pH and Absorption

1. Most drugs are what kind of acid/base?
   a. Lower pH (stomach acid) –>?

b. Higher pH (blood Plasma) –>?
2. Uncharged forms get thru what and into what compartment?
a. They then become CHARGED again in what compartments with what pH type?

Answer 4

1. Weak Acids (Orally…they work well) or Weak Basis (won’t protonate in a Higher pH…so it will act more like an acid in this case)
   a. Weak acids stay protonated and DONT GAIN a (-) charge (-CO2- –> -COOH)
   b. Weak bases DO NOT Protonate and Gain (+) Charge (-NH3+ –> -NH2)
2. thru membranes and into the liquid compartment
   a. in liquid compartments with neutral pH

Question 5

Bioavailability

1. How is it measured (comparing to what type of administration)?
2. Plasma levels are measured as AUC of a graph of what?
3. What 4 factors affect Bioavailability? (CAFF)
4. Bioequivalence: Compares Bioavailability and TIME to what?
5. Therapeutic Equivalence: What does it compare?

Answer 5

1. Plasma Level after a specific route of administration vs. AFTER i.v. Administration
2. of Plasma concentration of drug vs. time
3. Chemical stability, Absorption, Formulation, First-Pass (hepatic) metabolism (for oral drugs)
4. to Peak Plasma drug level (basically you look at generic drug and brand name drug, and see how well it gets into the plasma…with generic, you want to make sure you get the same effect)
5. comparable Efficacy and Safety (generic drug needs to be MADE as WELL as the brand drug…but it’s not a guarantee)
   * You will SELDOM have therapeutic equivalence. (Pred Forte cannot be substituted…some cases will dictate that you have to use Brand name drug over generic drug)

Question 6

Distribution

1. Process by which drug leaves Bloodstream and Enters what?
   a. A Topically Administered drug would first have to ENTER what in order to get systemic Distribution?

a. This depends on what 4 things?
2. Volume of Distribution (Vd) is what equation?
3. Increase Vd does what to Half Life?
4. Steady state level of drug is achieved in how many half lives for i.v. Administration?

Answer 6

1. the Interstitium
   a. the Bloodstream
   a. Blood flow, Capillary Permeability (like liver (high) vs. BBB (low)), Protein binding of drug (warfarin alone vs. with sulfonamide), and Lipophilicity of the drug
2. total drug in body (D) divided by the Plasma concentration (C)

Vd = D/C

C = D/Vd

3. Increases Half-life
4. in 3.3 Half Lives for i.v. Administration

Question 7

Metabolism

1. Kinetics
   a. First order?
   b. Zero Order
2. Phase 1
   a. Generally involves what system?

b. Drug is modified (oxidized) to make it less what?
c. Drugs that INDUCE or INHIBIT CYP isozymes can affect what?

2. Phase II
   a. Phase I metabolite may still be too Lipophilic for what?

b. Here, it Gets CONJUGATED to make it more what?

Answer 7

1. a. [C]

Question 8

Elimination *Know this really well….

1. Routes of Elimination?
2. Renal Elimination
   a. Glomerular Filtration: what kind of drugs?
   b. Proximal Tubule Secretion: For what drugs?
   c. Distal Tubule Re-absorption: Inhibited by keeping drug in what form?
   d. Extraction Ratio: Declines from what side to what side of the kidney?
   e. Excretion Rate: What is it?

Answer 8

1. Kidney –> Urine (MOST IMPORTANT), Bile, Intestine, Lung, Milk (nursing mothers)
2. a. Drugs not bound to protein
   b. Active transport of charged species
   c. in Charged Form (e.g. Varying pH)
   d. from Arterial Side to Venous Side of the Kidney
   e. Fraction of Drug Eliminated per unit time (CLEARANCE)/[Plasma]

Question 9

Pharmacodynamics: Sites of Action: Receptors

1. what do receptors do?
2. Substances that bind receptors are called what?
3. What do they do w/the Chemical signal?
4. Receptors can become what?

Answer 9

1. Bind and release NT or drug unchanged
2. Ligands
3. Tranduce it into an Electrical Response (Depolarization), 2nd messenger stimulation or inhibition, change in gene expression, etc.
4. de-sensitized (chronic heroin use) or SUPERSENSITIZED (Polocarpine for Addie Pupil)
   * Supersensitized: It’s a Third NERVE (if not, then it’s something before that)

Question 10

Pharmacodynamics: Sites of Action: Other

1. Enzymes:
   a. What do they do?
   b. Substrate proteins can effect what?
   c. Drugs are generally what?
2. Ion Channels
   a. Control excitability of what cells?
   b. Drugs can Open/Close Ion channels?
3. Many more: Like…?

Answer 10

1. a. Bind and modify a substrate
   b. any biological processes
   c. inhibitors
2. a. of Electrically Polarized Cells
   b. Both
3. DNA, RNA, Metabolic, etc.

Question 11

Pharmacodynamics:

1. Michaelis-Menton Saturation Plot (How we study substrate binding to enzyme…or ligand receptor)
   a. What is this looking at?
   b. What usually happens as you add more substrate?
   c. Lower Km = ?
   d. Higher Vmax = ?

Answer 11

1. a. Substrate concentration vs. Reaction Rate
   b. You get a faster reaction rate until everything is saturated (enzymes, or receptors) then the reaction time slows out.
   c. Higher affinity (don’t have to add as much to keep/fill up the chairs)
   d. Higher rate

Question 12

Pharmacodynamics: Lineweaver-Burk Plot

1. What does it do?
2. Place where the line crosses the Y axis is what?
3. Place where line crosses the X-Axis is what?
4. X Axis is what?
5. Y axis?
6. BIGGER Vmax =?
7. Smaller Km = ?

Answer 12

1. Takes the INVERSE of Vmax and the Inverse of Km, and makes the PLOT LINEAR (instead of hyperbolic…Like M-M Saturation Plot)
2. 1/Vmax
3. -1/Km
4. 1/[S]
5. 1/v
6. More capacity
7. More affinity

Question 13

Pharmacodynamics: Types of Drug Actions at Receptors

1. Agonist: does what?
2. Antagonist (Inhibitor)
   a. any action by itself?
   b. Blocks what?
3. Partial Agonist
   a. Same effect as agonist but…
   b. Reduces effect of what?
4. Inverse Agonists
   a. Has what effect

Answer 13

1. Same effect as natural ligand
2. a. None *Important Point: No effect on its own, but will block ACTIONS of the NATURAL LIGAND or AGONIST. KNOW THIS!!!!
   b. Blocks action of NATURAL ligand or Agonist
3. a. to a lesser degree
   b. of Natural ligand or Agonists to its Own level of Effect (i.e. Acts antagonistically)
4. a. The Opposite effect of the natural Ligand or its agonists

Question 14

Types of Antagonism

1. Competitive
2. Noncompetitive
3. Uncompetitive
4. 2 other types of Antagonism

Answer 14

1. reversed by Increasing concentration of AGONIST (think an antagonist and agonist competing for the same site of action)
2. Can’t be reversed by increasing concentration of agonist…(antagonist act at a different site from agonist that prevents action of the agonist) (steric or Allosteric inhibition)
3. Inhibitor binds to enzyme-substrate complex (agonist takes up the site but can’t come off…takes up site but has high Affinity and can’t get out…they’re not in a form that still stimulates, but are in a form where the ligand can’t get out)
4. Reversible; Irreversible

Question 15

A. Competitive Inhibition

a. Vmax: does it change?
b. Km

B. Noncompetitive Inhibition
a. Km: Adding more and more noncompetitive inhibitor. What happens to the Km?

b. What happens with the chairs?

C. Uncompetitive Inhibitor

Answer 15

1. No. It does not decrease (number of chairs has not decreased)
   b. Km has to INCREASE in the presence of the Antagonist (so increasing the Agonist can beat out the antagonist)
2. a. It doesn’t Decrease. (You get into a chair, you get in.)
   b. Chairs get folded up so they aren’t there to get into. (Chairs are acting like chairs that are available, but there aren’t that many available).
   * Km stays the same, and Vmax Decreases (noncompetitive inhibitor)

C. Both Vmax and Km are changing.

Question 16

Drug Action: Terminology

1. Efficacy
2. Potency
3. EC50
4. ED50
5. IC50
6. LD50
7. Therapeutic index

Answer 16

1. Degree of effect (Ex: Prostaglandin decreases IOP 30% and B-Blocker decreases IOP 20%: Prostaglandin is more efficacious)
2. Dosage at which effect is achieved (Beta blocker (1 nanomore concentration), Prostaglandin (1 micrometer); so beta blocker is more potent.
   * So drug can be more efficacious and less potent (don’t go together. tend to use a drug that’s more potent)
3. Concentration that produces 50% of the Max effect (Where potency is measured)
4. Dose that produces the desired effect in 50% of subjects (Human trials…) (25% of lowering of IOP in patients…how much drug do i need to give to get 50% of patients IOP to drop 25%)
5. Concentration that inhibits the effect by 50% (or dose that inhibits the effect in 505 of subjects)
6. Concentration that kills 50% of the treated subjects (normally extrapolated from animal studies)
7. ED50/LD50 (Lowest TI: is 2 for Lithium)