Combined Exam 1

What is pharmacology?

The study of actions, effects, and interactions of drugs on the body

Pharmaceutical phase

Presents drug to be absorbed/distributed in the body

Pharmacokinetic phase

Makes a drug available in the body to act

Pharmacodynamic phase

The action of the drug (therapeutic or non-therapeutic)

What is a drug?

• A chemical that affects physiologic processes to achieve a desired effect

• Alter what is already present, increase/decrease existing processes, don’t create anything new

Therapeutic response

Desired/intended

Nontherapeutic response

Undesired/unintended effect

Plants as a drug source

• natural source

• Processed using synthetic versions of active chemicals

Animals as a drug source

• Natural source

• Replace human chemicals that are not produced due to disease

• Genetically modified (transgenic animals)

• Synthetic production is considered purer and safer than animal derivation

Inorganic compounds as a drug source

• natural source

• Salts of chemical elements that can have therapeutic effects

Aluminum

• Inorganic compound

• Antacid

• Urinary stone prevention

Fluorine

• inorganic compound

• Dental cavity and osteoporosis prevention

Gold

• inorganic compound

• Rheumatoid arthritis treatment

Iron

• inorganic compound

• Anemia treatment

Synthetic drug sources

• groups of drugs with slightly different properties

• Genetic engineering alters bacteria to produce therapeutic chemicals

Prototype

• often first drug discovered in a class, most widely used

• Pharmacodynamically > pharmacokinetically

Generic drug name

• all lower case

• Preferable to trade names

• Can be made after patent expires

• Many manufacturers use same generic name

• Cheaper

Brand/trade drug name

• product name

• Capitalized

• Developer has exclusive rights for 17 years

• Once off-patent, manufacturer can brand its own version

• Many names for same drug (Ibuprofen, advil, Motrin)

Chemical drug name

• assigned via IUPAC nomenclature

• Described physical/chemical properties

• Complicated names

Pharmacological classification of drugs

shared characteristics, usually mechanism of action

Chemical structure classification of drugs

Classified based on chemical composition

FDA pregnancy categories drug classification (risk of birth defects)

• A: adequate human studied show no first trimester risk, no evidence in later trimesters

• B: animal studies show no risk but no adequate human studies or animal studies show adverse affects

• C: animal studies show adverse effects, no adequate human studied, benefit may be acceptable despite risk

• D: evidence of human fetal risk but benefit may be acceptable despite risks

• X: animal or human studied show fetal abnormalities, risk outweighs any benefit

DEA schedules drug classification (abuse/dependence potential)

• I: high abuse potential, no accepted medical use (heroin, LSD)

• II: medically useful, high abuse potential, severe dependence (opioids)

• III: less abuse than II, moderate dependence (stimulants)

• IV: less abuse than III, limited dependence (benzodiazepines)

• V: limited abuse, small amounts of narcotics, limited quantities may be bought without

-statin

• HMG-CoA reductase inhibitor

• For elevated cholesterol

-olol

• beta-adrenergic blocker

• For hypertension and angina

-pril

• ACE inhibitor

• For hypertension and heart failure

-prazole

• proton pump inhibitor

• For peptic ulcer disease

-dipine

• calcium channel blocker

• For hypertension

Pharmacokinetics

What the body does to the drug (ADME)

Pharmacodynamics

What the drug does to the body

Absorption

From introduction into the body until it reaches the circulating tissues/fluids

Bioavailability

• how much of the drug is absorbed and reaches systemic circulation

• Affected by dose, route

• A bio available drug can reach its target and produce a response

What is the bioavailability of an IV

100%, it bypasses absorption

PO absorption

• most common

• First pass effect directly influences bioavailability

IV plasma curve

Rises instantly, high peak, falls

Oral plasma curve

Rises slowly, lower peak, longer lasting

What IV route factors can affect absorption

None, it goes directly into venous system

What IM route factors can affect absorption

• blood flow to muscle

• Solubility in water

• Muscle temp

What SQ route factors can affect absorption

• blood flow to tissue

• Fat content

• Temp

What oral route factors can affect absorption

• stomach acidity

• Time in stomach

• GI health

• Blood flow to GI tract

• Interacting food/drugs

First-pass effect

• liver: first stop for all oral drugs before entering systemic circulation

• Each pass lowers drug in circulation vis metabolism

• More metabolism = less bioavailability (why oral does not equal IV dosing)

First-pass effect outcomes

• passes unchanged

• Metabolized into active or inactive metabolite

• Metabolized into parent compound (prodrug)

Distribution

Transports drug from bloodstream to tissues

What actors affect distribution

• blood flow/perfusion

• Protein binding

• Membrane permeability

Unbound “free” drugs

• unbound to plasma proteins

• Drug acts on targets in tissue to cause an effect

• Needs to leave circulation to get to receptors

• Only unbound drugs with be metabolized/excreted

Bound drugs

• bound to plasma protein and form a drug protein complex

• Reversible

• Ratio of bound vs free remains stable

Exceptions to the ratio of bound vs free drugs being stable

• competition for binding sites (drug-drug interactions)

• Too few binding sites (low albumin)

• Both can result in an increase of the amount of free drugs available and increases likelihood of toxicity

Crossing membranes

• depends on protein binding, physiochemical nature, and membrane characteristics

• Lipid-soluble drugs cross easily

• Ionic/polar drugs do not cross easily

What is the main site for metabolism/biotransformation

The liver

Metabolism/biotransformation

Enzymatic chemical changes makes drugs water soluble for excretion into less active chemicals

What enzymes metabolism most meds

CYP-450

Enzymatic induction

introduction of a second drug that increases activity of hepatic enzymes (causes increased metabolism of original drug leading to sub therapeutic levels)

Enzymatic inhibition

The introduction of a second drug that causes a decreases in hepatic enzymes (causes decreased metabolism of the original drug leading to toxic levels)

Pharmacogenetics

• population divides into fast, normal, and slow metabolizers

• Same drug can be toxic but beneficial

Excretion

Through the kidneys, skin, saliva, lungs, bile/feces

Glomerular filtration

Free drug molecules (small molecules)

Active secretion in proximal tubules

Unwanted molecules being carried out of plasma by transporters

Tubular reabsorption in distal tubules

Drug molecules reabsorbed back into plasma and not excreted in urine

Half-life

• time for a drug concentration in the body to fall by 50%, guides dosing schedule/duration

• Affected by absorption, distribution, biotransformation(liver function), excretion (kidney function)

Drug interactions at absorption site

Change environment or form insoluble complexes

Drug interactions during distribution

Competition for protein-binding sites

Drug interactions during metabolism

CYP induction/inhibition

Drug interactions during excretion

Competition for renal absorption/secretion

Drug interactions at site of action

Competition for receptor site

Drug foods

• mostly in stomach

• Oral drugs absorbed faster on empty stomach

• Small meals may decrease nausea

Drug lab

• drugs can alter lab results

• Labs can monitor other meds

Therapeutic window/range

Blood concentration that produces effect without toxicity

Toxicity

Quantity that no longer gives intended response and produces toxic signs

Peak effect

Point of maximum therapeutic effect

Subtherapeutic

Dose/concentration lower than usually prescribed to treat effectively

Duration of action

How long a drug remains effective after administering

Onset of action

Time to begin producing intended effect

First pass effect

Oral drug metabolized by liver to useable form, directly influences bioavailability

Half-life

Time for concentration to decrease by half

Loading dose

Higher than usual dose so critical concentration is reached sooner

Dynamic equilibrium/steady state

• Actual amount reaching body

• Affected by ADME and biotransformation

Hypersensitivity reaction

Antibodies form to drug causing an immune response

Idiosyncratic reaction

• rare

• Can be life-threatening (organ failure/death)

• Not related to duration or dose

Receptor

Extra/intracellular proteins that mediate drug activity

Drugs can…

• directly/indirectly stimulate a receptors activity

• Block/inhibit receptor activity

• Interact with receptors on mutated/foreign cells to interfere with function

• Replace/substitute missing chemicals

Affinity

Strength of attraction between drug and receptor

Intrinsic activity

Ability to cause an effect once bound

Efficacy

Max response achieved

Agonist

Affinity + intrinsic activity

Partial agonist

Affinity + intrinsic activity but lacks full efficacy

Antagonist

Affinity but no intrinsic activity

Side effect

Unwanted but anticipated, usually not dangerous

Adverse effect

Unintended response, can be dangerous

What are the two types of adverse effects

• type A (primary actions)

• Type B (secondary actions)

Type A adverse effect

An overextension of desired affect

Overdosed/dose dependent reaction

• type A adverse effect

• Patient becomes overtly sedated and somnolent when receiving a dose of morphine for pain control

Drug-drug interactions/non-dose dependent reactions

• type A adverse effect

• Patient becomes hyper-anticoagulated from coumadin when prescribed bactrim for a UTI

Type B adverse affect

Undesired effects produced in addition to pharmacologic effect, happens at therapeutic dosing

Hypersensitivity reactions

• type B adverse effect

• Body forms antibodies to a drug causing an immune response

Idiosyncratic reactions

• type b adverse effect

• Not mediated by immunological or inflammatory mechanisms

Dermatological reactions

• idiosyncratic

• Rashes, hives, stomatitis

GI irritation

• idiosyncratic reaction

• Nausea, vomiting, diarrhea, constipation, abdominal bleeding

Superinfections

• idiosyncratic reaction

• Destruction of body’s normal flora

Blood dyscrasia

• idiosyncratic reaction

• Bone marrow suppression

Hepatotoxicity

• idiosyncratic reaction

• Impairs metabolism of drugs