Drug Action Exam 2 (Khasanweh)

Route of administration

The path by which a drug, fluid, poison or other substance is brought into contact with the body.

What is the purpose of finding the best route of administration?

They are chosen to enable the drug to penetrate barriers effectively. It will determine absorption, bioavailability, and reduce toxicity.

What is used to select the optimal route?

Target, nature of drug, patient age, patient condition

What are the 3 route of administration?

Enteral (GI tract; systemic effect)

Parenteral (other than enteral; systemic effect)

Topical (skin, mucus membrane; local or systemic effect)

What is the pH of the stomach and intestines?

Stomach (pH 1-3)

Intestines (pH 6-8)

What is the most common enteral route?

A. Oral

B. Nasogastric

C. Vaginally

D. Rectally

A. Oral

The by mouth route exploits __________ in human barrier defenses.

Weaknesses

Do hydrophobic, neutral, hydrophilic, or charged drugs cross membranes more efficiently?

Hydrophobic and neutral cross easier than hydrophilic and charged drugs

Advantages of enteral route

Convenient and easy to administer, safer (infection less likely), less expensive

Disadvantages of enteral routes

Slow onset of action, chemical interactions (food), irritation of GI tract, first-pass metabolism, inactivation by stomach acid/enzyme

What is first-pass metabolism?

Must pass first through liver to get to circulation. This is when the drug is significantly metabolized for the first time.

When the liver excretes the drug into the bile =

Biliary excretion

T/F Only certain oral drugs are subject to first-pass metabolism.

False. All oral drugs are subject to first-pass metabolism.

Significant first-pass metabolism can occur in ________________.

GI epithelial cells

In this route, the drug is introduced directly across the body's barrier defenses into systemic circulation or some other tissue space

Parenteral route

What are key points of IV administration?

Must be sterile and particle free

Avoid arteries

These are examples of what type of route of administration?

IV, IM, SC, intradermal (ID), intraperitoneal (IP)

Parenteral route

Where is the common site of IM injection?

Deltoid muscle

Highly vascular->faster absorption

Put these in order of fastest absorption to slowest

IV

SC

IM

IV, IM, SC

What are other IM sites of admin?

Gluteus medius/Maximus (butt) - not ideal in Obese

Vastus lateralis (thigh) - ideal for kids under 1 year old

What is the intraperitoneal site located?

At the tummy area (around belly button)

Primary used in animals

Does go through first-pass metabolism

Provides large absorbing surface

Advantages of parenteral route

Fast onset

Valuable in emergency

Bypass first pass in liver

Better control of delivered dose

Useful if GI not available or unconscious

Disadvantages of parenteral route

Must be sterile so more expensive

Often painful

No retreat

Difficult to perform

Increased risk of infection

Examples of topical routes

Skin (cutaneous), ocular (eye), otic (ear), nasal, rectal, vaginal

What are transdermal dosage forms ideal for?

Ideal for a drug that must be slowly and continuously administered over extended periods.

T/F Ocular and otic medications must be sterile since there is a high risk on infection by these routes.

False. Otic can be non-sterile. Ocular must be sterile.

What type of effects do ocular and otic administration usually have?

Local effects

Advantages for topical route

Safer, ideal for local effects

Disadvantages for topical route

Inconvenience, systemic effect (can sometimes be an advantage), retention difficult

What is important about the sublingual route (under tongue)?

It bypasses first-pass metabolism

What is the goal of drug therapy?

Achieved a desired beneficial effect with minimal adverse effects

A relationship exists between the beneficial or toxic effect of a

drug and its plasma concentration

which regimen is better

Regimen A is better than Regimen B (dose too high, causing toxicity)

What the body does to the drug?

Pharmacokinetics

what relationship is shown in pharmakinetics

the relationship of drug dose and drug concentration

what the drug does to the body

pharmacodynamics

what relationship is shown in pharmacodynamics

the relationship of drug concentration and drug effect

Refers to the fate of a drug after its absorption

Drug distribution

the combined process of drug metabolism and excretion

Drug elimination

What does ADME stand for?

Absorption, Metabolism, Distribution, Excretion

Movement of a drug from its site of administration to the systemic circulation

Absorption

active transport movement

i) energy dependent; ii) saturable; il) against an electrochemical gradient; iv) selective carrier-mediated.

facilitated diffusion movement

i) requires NO energy; il)saturable; iii) NEVER agaınst an electrochemical gradient; iv) selective carrier-mediated.

pinocytosis movement

Drugs of large molecular weight (MW > 900) may enter cells by pinocytosis or phagocytosis.

principles of absorption

the physicochemical nature of the drug

the formulation of the drug (drug vehicle)

the route of administration

the state of the patient

What is the most common mechanism for drug transport?

A. Active transport

B. Facilitated diffusion

C. Pinocytosis

D. Passive diffusion

D. Passive diffusion

Fricks Law

J = D A (C1- C2)/ L

Oil/Water partition coefficient of the drug formula Kp

Kp = Coil/Cwater

what does fricks law find

concentration of drug and solubility in water

In gastric absorption,

A. Weak acids will be ionized and absorbed well

B. Weak bases will be ionized and absorbed well

C. Weak acids will be ionized and absorbed poorly

D. Weak bases will be ionized and absorbed poorly

D. Weak bases are ionized and poorly absorbed

Weak acids will be unionized and absorbed well

In intestinal absorption,

A. Most weak bases will be unionized and readily absorbed

B. Most weak bases will be ionized and readily absorbed

C. Most weak acids will be unionized and readily absorbed

D. Most weak acids will be ionized and readily absorbed

A. Most weak bases will be unionized and readily absorbed

Weak acids will be ionized and poorly absorbed

In gastric absorption how will weak bases act

they will be ionized and poorly absorbed. In IV, they may be trapped and can be absorbed later in intestines

in gastric absorption how will weak acids act

they will be unionized and be absorbed well

in intestinal absorption, how will weak bases act

they will be unionzed and readily absorbed

in intestinal absorption, how will weak acids act

they will be ionized and poorly absorbed

Epithelial cells in the Gi tract are joined to one another by occluding zonulae (tight junctions). Drug must ________ the cells.

Go through

Drugs cannot pass around the cells

T/F Large surface areas absorb drugs faster than smaller ones.

True

Will most drugs be absorbed by the intestines or stomach. Why?

Intestines. Because they have a larger surface area

What creates the large amount of surface area in the intestines?

Microvilli

In general, does the presence of food in the GI tract slow or speed up absorption?

Slow down absorption

The fraction of unchanged drug reaching the systemic circulation following administration by any route.

Bioavailability (F)

what does AUC show

the extent of bioavailability for a drug given by a particular route

What is the bioavailability of IV route?

F =1

What routes have the highest bioavailability?

IV, IM, SC, transdermal

Why are peptide and protein-based drugs typically given using parenteral routes?

Large molecule drugs like these have a very low bioavailability when given by non-parenteral routes.

Incomplete absorption may also result from activating the _________ efflux pump in epithelial cells.

P-glycoprotein

What has a major impact on bioavailability?

Formulation of the drug

2 separate pharmaceutical preparations may contain the same amount of compound, but may not exhibit the same bioavailability and therefore have different plasma drug concentrations.

factors determining oral bioavailability

extent of absorption
first pass elimination

What are 3 things the rate of absorption is determined by?

Physiological nature of the drug

Drug formulation

Route of administration

incomplete absorption could be due to

too high hydrophilicity of the drug because it cant go through the lipid cell membrane
too high lipophilicity of the drug because it cant dissolve in water

Be able to determine the parts of a drug absorption graph.

Onset of action, Cmax, peak effect, duration of action, therapeutic window, concen. for adverse response, concen. For desired response

what can influence the clinical effectiveness of a drug

the rate and the extent (F and Cmax) of absorption

temporal characteristics of drug effect and relationship to therapeutic window:

the concentration range between minimal effectiveness concentration for adverse response and minimal effective concentration for desired therapeutic response

two separate pharmaceutical preparations may contain the same amount of the same compound BUT

they may not exhibit identical bioavailability and may not yield identical plasma drug concentrations in the same patient

What is tmax?

It is the time needed to reach Cmax.

This is when a dug undergoes various transport processes which deliver it to various body areas away from the absorption site

A. Absorption

B. Distribution

C. Metabolism

D. Excretion

B. Distribution

Where is most of the body's water located?

Inside the cells (intracellular)

one compartment model says the whole body is regarded as what

one compartment

how are drugs eliminated in the one compartment model

drugs are usually eliminated exponentially

What are the 2 compartments in the 2-compartment drug distribution model?

Central and Peripheral

what are the two phases in the concentration time profile

fast distribution and slow elimination phase

How is distribution between organs within the same compartment in the 2 compartment model?

Distribution is the same in those organs

Factors that affect extent and rate of drug distribution.

Physiochemical nature of the drug

Organ perfusion rate

Permeability of tissue membranes

Plasma protein binding of the drug

Tissue binding of the drug

what is the principle on drug distribution

only the unionized and unbound form of the drug can permeate across biological membranes

How does a high organ perfusion rate affect distribution?

High rate = more distribution

What form of the drug can permeate across biological membranes?

Only the unionized and unbound (free) form

what can affect the distribution of a drug

protein binding

Many drugs are bound to plasma proteins. What binds to acidic drugs and what binds to basic drugs?

A. Phosphotase; albumin

B. Alpha1 glycoprotein; albumin

C. Albumin; alpha1 glycoprotein

C. Albumin; alpha1 glycoprotein

Is protein binding reversible or irreversible?

Reversible

What does it mean that protein-binding is saturable?

It means it is capacity limited at high drug concentrations.

how is tissue binding related to drug accumulation

Many drugs accumulate in tissues at higher concentrations than those in the extracellular fluids and blood

where does tissue binging usually occur

with cellular constituents such as proteins, phospholipids, or nuclear proteins

Tissue-bound drug may serve as a ___________.

Reservoir

A drug with high plasma protein binding usually has a _______ volume of distribution.

Small; This makes sense because plasma is only a small amount (2.8 L) of our total volume (42 L).

Many drugs accumulate in _______ at higher concentrations than those in the _____________.

Tissues; extra cellular fluids and blood

A drug with high tissue binding tends to have a _____ volume of distribution.

Large

The process of drug removal from the body.

Elimination

2 major processes and organs are responsible for elimination. What are they?

Metabolism = liver

Excretion = the kidney (major), bile, etc

The amount of drug in the body to the concentration of drug in blood or plasma.

Volume of Distribution (Vd)

What does fractional Vd equal?

L/kg body weight