+ Safest and most common; convenient, and economical route of administration - Limited absorption of some drugs; food may affect absorption, patient compliance is necessary, drugs may be metabolized before systemic absorption

Chapter 1 Flashcards by Briana Lieberman

Pharmacokinestics

What the body does to a drug

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Pharmacodynamics

What the drug does to the body

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4 Pharmacokinetic properties that determine onset, intensity, and duration of drug action

Absorption
Distribution
Metabolism
Elimination

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Enteral adminitration

administering a drug by mouth; most common

Can be oral or sublingual/buccal

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Two types of oral preparations

Enteric-coated preparations (ex. omeprazole, aspirin)

2. Extended-release preparations (ER or XR) (ex. morphine)

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Half life of morphine

2 to 4 hours; therefore, must be administered 6x per day to provide continuous pain relief

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Parenteral administration

drugs introduced directly in to the systemic circulation (ex. heparin poorly absorbed in GI tract; insulin unstable in GI tract)

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3 Major Parenteral Routes

Intravenous (IV) - Ex. Rocuronium, a NM blocker
Intramuscular (IM) - Ex. haloperidol, medroxyprogesterone
Subcutaneous (SC) - Insulin and heparin

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Types of Administration Routes

Enteral (Oral, Sublingual/buccal)
Parenteral (IV, IM, SC)
Oral/Nasal inhalation
Intrathecal/Intraventricular
Topical
Transdermal
Rectal

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Desmopressin

Administered intranasally in the treatment of diabetes insipidus

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Oral Absorption Pattern

Variable; affected by many factors

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Intravenous Absorption Pattern

Absorption not required

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Subcutaneous Absorption Pattern

Depends on drug diluents:

Aqueous solution: prompt
Depot preparations: slow and sustained

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Transdermal (patch) Absorption Pattern

Slow and sustained

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Rectal Absorption Pattern

Erratic and Variable

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Inhalation Absorption Pattern

Systemic absorption may occur; this is not always desirable

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Sublingual Absorption Pattern

Depends on the drug:
Few drugs (ex. nitro) have rapid direct systemic absorption
Most drugs erratically or incompletely absorbed

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Oral Pros and Cons

+ Safest and most common; convenient, and economical route of administration

Limited absorption of some drugs; food may affect absorption, patient compliance is necessary, drugs may be metabolized before systemic absorption

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Intravenous Pros and Cons

+ immediate effects, ideal if dosed in large volumes, suitable for irritating substances and complex mixtures; valuable in emergencies, dose titration possible, ideal for high molecular weight proteins and peptide drugs

unsuitable for oily substances, bolus injection may result in adverse effects; most substances must be slowly injected, strict aseptic techniques needed

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Subcutaneous Pros and Cons

+ Suitable for slow-release drugs, ideal for some poorly soluble suspensions

pain or necrosis if drug is irritating, unsuitable for drugs administered in large volumes

Intramuscular Pros and Cons

+ suitable if drug volume is moderate, suitable for oily vehicles and certain irritating substances, preferable to intravenous if patient must self-administer

affects certain lab tests (creatine kinase); can be painful, can cause IM hemorrhage (precluded during anticoagulation therapy)

Transdermal (patch) Pros and Cons

+Bypasses the first-pass effect; convenient and painless, ideal for drugs that are lipophilic and have poor oral bioavailability, ideal for drugs that are quickly eliminated from the body

-some patients are allergic to patches, which can cause irritation; drug must be highly lipophilic, may cause delayed delivery of drug to pharmacological site of action, limited to drugs that can be taken in small daily doses

Rectal Pros and Cons

+ partially bypasses first-pass effect, bypasses destruction by stomach acid, ideal fi drug causes vomiting, ideal in patients who are vomiting, or comatose

drugs may irritation the rectal mucosa, not a well-accepted route

Inhalation Pros and Cons

+ Absorption is rapid; can have immediate effects, ideal for gases, effective for patients with respiratory problems, dose can be titrated, localized effect to target lungs: lower doses used compared to that with oral or parenteral administration; fewer systemic side effects

most addictive route (drug can enter the brain quickly); patient may have difficulty regulating dose; some patients may have difficulty using inhalers

Sublingual Pros and Cons

+ Bypasses first-pass effect; bypasses destruction by stomach acid, drug stability maintained because the pH of saliva relatively neutral; may cause immediate pharmacological effects - limited to certain types of drugs, limited to drugs that can be taken in small doses; may lose part of the drug dose if swallowed

Mechanisms of Absorption of Drugs from the GI tract

1. Passive Diffusion 2. Facilitated Diffusion 3. Active transport 4. Endocytosis and Exocytosis

Factors influencing Absorption

1. Effect of PH 2. Blood flow to absorption site 3. Total surface area available for absorption 4. Contact time at the absorption surface 5. Expression of P-glycoprotein

pKa

Ionization constant; ratio between charged and uncharged forms determined by the pH at the site of absorption and by the strength of the weak acid or the weak base

pKa relationship to acidicty

Lower pKa = more acidic | Higher pKa= more basic

Distribution Equilibrium

permeable form of a drug achieves an equal concentration in all body water spaces

Why do the intestines have more absorption than the stomach?

1000- fold surface area | Receives more blood flow

When pH < pKa, what forms predominate?

Protonated forms of HA and BH+ predominate

When pH> pKa, what forms predominate?

Deprotonated forms A- and B predominate

P -glycoprotein

Transmembrane transporter protein responsible for transporting various mmolecules, including drugs, across cell membranes; transports drugs from tissues to blood (pumps drugs out of cells); multidrug resistance

Where is P-glycoprotein expressed?

Tissues throughout the body including liver, kidneys, placenta, intestines, and brain capillaries

Areas of high expression of P-glycoprotein ___________ drug absorption.

reduces

Bioavailability

Rate and extent to which an administered drug reaches the systemic circulation; important for calculating drug dosages for nonintravenous routes of administration

IV administration confers ______ % bioavailability.

100%

Factors that Influence Bioavailability

1. First-Pass Hepatic Metabolism 2. Solubility of the drug 3. Chemical Instability of the drug 4. Nature of the drug formulation

Bioequivalence

Two drugs formations are bioequivalent if they show comparable bioavailability and similar times to achieve peak blood concentrations.

Therapeutic Equivalence

Two drug formulations show therapeutic equivalence if they are pharmaceutically equivalent (same dosage, same active ingredient, same route of administration) with similar clinical and safety profiles.

What does clinical effectiveness depend on?

Both the max serum drug concentration and the time required (after administration) to reach peak concentration

Drug Distribution

process by which a drug reversibly leaves the bloodstream and enters the interstitium (Extracellular fluid) and the tissues

Distribution of the drug from the plasma to the intersititium depends on....

``` CO & Local Blood Flow Capillary Permeability Tissue volume Degree of binding of the drug to plasma and tissue proteins Relative lipophilicity of the drug ```

Volume of Distribution (Vd)

fluid volume that is required to contain the entire drug in the body at the same concentration measured in the plasma Vd = (Amount of drug in body) / (plasma concentration at time zero)

Drugs with high molecular weight or is extensively protein bound gets trapped where?

Plasma Compartment (Ex. Heparin) Low Vd that approximates plasma volume

Drug has low molecular weight but is hydrophilic ends up where?

Extracellular Fluid (Ex. Aminoglycoside antibiotics) It can pass through endothelial slit junctions of capillaries into interstitial fluid; hydrophilic drugs cannot move across lipid membranes into intracellular fluid

Drug has low molecular weight but is lipophilic ends up where?

Total body water (ex. ethanol) It can move into interstitium through slit junctions and also pass through cell membrane into intracellular fluid. 60% of body weight.

An increase in Vd ______ the half-life and ________ the duration of action of hte drug.

Increases, extends