Chapter 1-3 Intro pharm

Pharmacology

Study of drugs

Pharmacodynamics

Action of drugs on living tissue

• What the drug does to the body

(Mechanism, effects, dose response etc)

Pharmacokinetics

• How drugs are processed in the body (ADME)

  • What the body does to the drug

Pharmacotherapeutics

Study of drugs in treating disease

Pharmacy

Preparing and dispensing medication

Posology

Study of the amount of drugs required to produce a therapeutic effect

Toxicology

Study of harmful effects of drugs on living tissue

What is ADME?

• Absorption

  • How the drug enters

• Distribution

  • Where the drug travels (tissues, organs)

• Metabolism

  • How the liver metabolizes the drug

• Excretion

  • How the kidney gets rid of the drug —> urine

What is a drug?

• Substance given to a living organism to produce a change in function

• Drug — Medication used for diagnosing, curing, or treating disease. Both chemical and biological properties

  • Water, metal, insecticides etc.

What are physical and chemical properties of a drug?

• Drug properties determines the effects on the body

• Chemical: Structure

• Physical: Solubility (water, fat), selectivity, affinity for receptors, metabolism

• All drugs produce more than 1 effect

Where do drugs come from?

• Animals

  • Premarin (horse urine for estrogen)

• Plants

  • Foxglove (lowers HR)

  • Poppy (morphine)

• Microorganisms (bacteria)

• Chemical synthesis (man-made)

Drugs will have 2 effects..

• Therapeutic

• Undesirable

Difference between therapeutic effect, side effect, adverse effects, and toxic effects

• Therapeutic effect

  • Intended use

• Side effect

  • Unintended use / Undesirable effect / Tolerated

  • More nuisance than harmful (dry mouth)

• Adverse effects

  • Harmful or damage to organs when used for long time

  • Diarrhea, vomitting

• Toxic effect

  • Extremely life threatening

  • Anaphylaxis

Drug indication and contraindication

• Indication

  • Therapeutic use of drug —> Why drug is used

  • Ex: Insulin —> manage diabetes

• Contraindication

  • Why the drug should NOT be used

  • Ex: Liver disease can’t take aspirin (bleeding)

What are the 4 drug interactions? (I—ASS—A)

• Incompatibility

  • Precipitate before administration

• Additive effect

  • 2 drugs, same biological response, same mechanism of action

  • 1 advil (50%) + 1 aleve (50%) = 100%

• Summation

  • 2 drugs, same biological response, different mechanism of action

  • Zantac + Prilosec (H2 blockers)

• Synergism

  • 2 drugs combined together enhance each other for greater effect

  • Alcohol + sleeping pills = 110% enhancement

• Antagonism

  • 1 drug blocks another
    Opioids + narcan
    

Biological response: (end goal of drug)

Mechanism of action: how the drug is produces its effects

Describe the mechanism of action, site of action, receptor site, agonist, antagonist

• Mechanism of action: How drug produce pharmacological effect

  • Does it block an enzyme, activate a receptor? etc.

• Site of action: Where the drug exerts its therapeutic effect

  • Location (blood vessels, lungs)

  • Not always known

• Receptor site

  • Site where drug binds to receptor

• Agonist

  • Produces a drug action

• Antagonist

  • Block other drugs from producing an effect

• Competitive antagonism

  • competes with same receptor

What is the dose response relationship?

• Dose: Amount of drug given to produce an effect

• Response: Effect from dose

Effective dose (ED50)

• Produces 50% of max therapeutic effect

• Dose where 50% of population experience therapeutic effect

• Used to compare potency between drugs

A drug gives 100% pain relief at 80mg.
60mg give 50% relief. In this case, the ED50 is 60mg, even though that’s not half the dose (or strength) — it's the dose that gives half the effect.

Purpose of the dose response curve?

• Drug is proportional to dose (drug increase, response increase)

Helps compare the potency between drugs

• Potency

  • ED50 of drug A is 10 mg

  • ED50 of drug B is 20 mg.

  • Therefore, drug A is twice as potent as drug B.

  • Twice the concentration of drug B is needed to produce the same response as drug A.

  • 20/10 = 2x more potent

Ceiling effect

• Increasing dose doesn’t increase effects

• Nothing past 100% — Will cause toxic effects

Time plasma concentration curve

• Drug dose in blood over time (time response)’

3 parts to curve

• Onset of action

  • Drug first start working

• Duration of action

  • Time the drug continues to product its therapuetic effect (effective range)

• Termination of action

  • Therapeutic effect wears off — not effective range

Purpose

• Used to predict frequency of when drug is administered to keep effective drug response (duration of action)

• Shows the concentration of drug over time

Whats the 2 FDA guidelines for drugs? Drugs are tested on ______ first before humans

• Safety

• Efficacy

Why? Flipper baby incident

Animals

What is LD50?

Lethal dose at 50% (first test)

• Dose that kills 50% of animals tested

• Dose where 50% of population would die from the drug

Purpose

• Predict safety of drug OR how toxic it is

Therapeutic index (TI)

TI = LD50 / ED50 =

• Bigger TI = safer drug

  • bc need higher dose to product toxicity

Margin between therapeutic and lethal dose

→ TI = 10 means lethal dose is 10x higher than effective dose (safe)

→ TI = 2 means lethal dose is 2x higher than effective dose (risky)

Tells you how safe a drug is

Whats the goal of drug therapy?

• To achieve therapeutic effects without producing any harmful effects

Controlled substances (5 schedules)

• Regulate dispensing of drugs that have potential for abuse

Schedule I – Drugs with high abuse potential and no accepted medical use (heroin)

Schedule II - Drugs with high abuse potential and accepted medical use  (morphine) 

Schedule III – Drugs with moderate abuse potential and accepted medical use (tylenol) 

Schedule IV — Drugs with low abuse potential and accepted medical use  (valium) 

Schedule V – Drugs with limited abuse potential and accepted medical use

How are drugs named? What is the difference between generic names, brand names and chemical names?

• Generic names

  • Official, simplified, nonproprietary, FDA approved

• Brand name

  • Pharmaceutical company / trademark (product) / proprietary

• Chemical name

  • IUPAC — molecular structure

Which biological factor affects drug action?

• Dosage

• Routes of administration

• ADME

• Half life

• Blood drug levels

• Bioavailability

• Genetics

3 types of drug preparations

• Aqueous preparation

  • syrups and suspensions (solid in liquid shake)

• Alcoholic preparations

  • Elixirs, spirits, tinctures, extracts

• Solid and semi preparations

  • Solid most common

List the different forms of drug products (solids and semisolids)

• Powder

• Tablet

  • compressed powder

• Troches and lozenges

  • dissolve in mouth (cough drops)

• Capsules

  • Gelatin shell with drug powder

• Delayed release product

  • Tablet or capsule with special coating — dissolve at different times

  • bypass parts of GI

• Enteric coating

  • Type of delayed release product

  • Special coating to protect from stomach acid — Dissolves when reach basic pH

  • Irritate stomach or destroy drug

2 delayed release system for drugs?

• SODAS (Spheroidal Oral Drug Absorption System)

  • Pellet with different coating — release at different times (delayed)

  • Less frequent dosing

  • Not affected by food or GI

• GITS (Gastrointestinal Therapeutic System)

  • Constant release rate over time

Semi solid drug forms (topical preparations)

• Cream

  • Emulsion of oil + water = water based

• Ointment

  • Oil based

• Suppositories

  • Inserted into rectum/ vag

• Transdermal patches

  • Controlled release patch

What type of preparation are creams and ointments?

Topical preparaion

Routes of administration

• Oral

  • Mouth

  • Most safe but slow

• Enteral

  • Through GI tract

  • Suppositories

• Parenteral

  • Not GI tract

  • Inhalation, topical, IV (injection)

  • Fast but can’t be withdrawn (risk of overdose)

Factors affecting absorption of drugs

• Lipid solubility of drug

  • More lipid soluble = pass faster

• Ionization

  • Unionized form = better absorption

• pH

  • Acid = readily absorbed in acidic environment (stomach)

  • Base = readily absorbed in basic environemnt (Urine)

What is the role of drug ionization and lipid solubility in pharmacokinetics?

• Ionization and lipid solubility affect the speed and rate of drug transportation

What conditions do acidic and basic drugs prefer and why?

• Acidic drugs

  • Prefer acidic

  • Stays unionized in stomach

  • Becomes ionized in urine

• Basic drugs

  • Prefer basic

  • Stays unionized in urine

  • Becomes ionized in stomach

Unionized = easily diffuse through phospholipid bilayer, more lipid soluble

Ionized = can’t pass through membrane —> excreted

Different ways drugs can cross cell membrane

1. Passive diffusion

   • High to low concentration

2. Facilitated diffusion

   • Passive through protein channel

3. Active transport

   • Use ATP — Low to high

What factors affect distribution of drugs?

• Plasma protein binding

  • Only free unbound drugs (not attached to plasma protein) can cause pharmacological response

  • Bounded drugs = Inactive drug protein complex (can’t cross membrane)

• Blood flow

  • Organs with higher blood flow —> drugs delivered faster

  • High blood flow (Liver, kidney, brain)

  • Low blood flow (Adipose tissue) except for lipid soluble drugs

• Blood brain barrier (BBB)

  • Lipid soluble drugs easily pass through

  • Restricts water soluble

What is metabolism? What organ? DMMS? First pass effect?

Metabolism: Chemical alteration of drugs in the body

• Aka Biotransformation

  • Chemically altered before excreted by kidneys

• Liver does metabolism

• Drug microsomal metabolizing system (DMMS)

  • Enzyme in liver

  • Convert lipid soluble drugs —> water soluble (to be excreted)

• First pass effect

  • After oral administration, all drugs are absorbed into portal circulation

  • Reducing concentration or amount of drugs

  • Take drug —> absorbed in GI —> enters portal circulation —> Liver metabolism (greatly reduces amount of drugs entering blood stream)

  • Reduces bioavailability

All oral drugs enter portal circulation

Enzyme induction

• Repeated use of drug, liver makes more enzymes

• Result: Faster drug metabolism

What routes of administration bypass the liver (first pass?)

90% of oral medication is metabolized and destroyed by the liver before it reaches the heart

• Venous system (injection / IV)

• Nasal (goes to veins)

• Rectum/ transdermal patch (skin)

Different methods of drug excretion. Where can drug excretion occur and what state must the drug form be in to facilitate excretion

Methods of excretion

• Renal excretion (Kidneys → Urine)

  • Filtered by glomerulus in kidneys

  • Reabsorbed back except urinary waste

  • Must be in ionized and water soluble form

• GI excretion (Fecal)

  • Reabsorbed back into enterohepatic pathway

  • Liver → Bile → Intestines → Blood → Liver (repeat) (L—BIB)

    • Recycling of drugs/ substances

  • Prolong drug effects and increase half life

• Respiratory excretion

  • Lungs, breathing, alcohol

  • Anesthetic gases not metabolized by lungs

• Sweat, saliva, tears, bodily fluids

• Placenta through pregnancy

→ Must be ionized form

How does half life relate to drug response?

• Half life

  • Time it takes for blood concentration of drug to fall to half of its original level

Importance

• Determine frequency of drug administration

Relate to drug response (body’s response to drug)

• Longer half life = stays in body longer

• Shorter half life = doesn’t stay in body as long

  • Need more dosing

What are the 2 factors that affect half life and blood drug levels? (ME)

• Metabolism

  • How fast liver breaks down

  • Slow liver = Slow metabolism = longer half life

• Excretion

  • Slow kidney = drug stays longer = longer half life

How does blood drug levels relate to drug response?

• Blood drug levels

  • Concentration of drugs in blood

  • Dependent on ADME

Relate to drug response

• Too little = not effective

• Just right = therapeutic effect

• Too high = toxic

Goal is maintain therapeutic range

How does bioavailability relate to drug response?

• Bioavailability

  • How much drugs gets absorbed into the blood

Relate to drug response

• High bioavailability = More drug is available to exert on body

• Low bioavailability = Needs more doses for therapeutic effect

Ex: Expensive pee

Factors that influence bioavailability? DRIG + absorption factors

• Drug formation (lipid/ water sol)

• Route of administration

• Individual variations

• GI absorption (Movement, pH, food)

Individual variation factors (AW—GG—EPPP)

• Age

• Weight

• Gender and body fat

• Genetics

• Emotional state

• Placebo

• Presence of disease

• Patient compliance

Define loading dose and maintenance dose. What is the purpose of a loading dose?

• Need higher blood drug levels

• Loading dose

  • Initial dose to give therapeutic range (jumpstart)

• Maintenance dose

  • Dose after loading dose to maintain therapeutic range

Factors for pediatric drug administration and how it affects pharmacokinetics.

• Teratogenic risk (drug causes birth defects during pregnancy)

• Breastfeeding

  • Drugs pass onto milk

• FDA category X

  • Contraindicated drugs for pregnancy

  • Teratogenic risk

How it affects pharmacokinetics

• Faster drug processing in kids

• Dosing is based on weight, not age

Chronic drug use and tolerance

• Chronic drug use

  • Using drug repeatedly over time

• Tolerance

  • Repeated administration decreases drug effect

What are the 2 types of tolerance?

• Metabolic tolerance

  • Caused by Enzyme induction (body makes more enzymes)

  • Drug metabolized more quickly

• Pharmacodynamic tolerance (aka Down regulation)

  • Caused by decrease in receptors

  • Fewer receptors drug can bind to = weaken effect

  • Takes longer to occur

Differentiate between drug dependency vs drug addiction

• Drug dependency

  • Relying on drug to feel normal or function (well being)

Can be..

• Physical

  • Body needs drug to avoid withdrawal

• Psychological

  • Person craves and believes they can’t function w/o drug

  • Unpleasant feeling (not smoking tobacco for short time)

• Drug addiction

  • Dependence is severe and compulsive

  • Interrupts ADL (activities of daily living)