U1 medicine - principles of pharmacology

steps of prescribing process

1. history and physical exam

2. diagnosis

3. treatment plan (pharmacologic and nonpharmacologic)

patient education

advice patient before prescribing medication about intended therapeutic effect, potential side effects, how to deal with adverse drug reactions, warnings (black box warnings- highest warning there is know them if there is one!)

6 parts of a prescription

1. demographic (name/DOB/address/date)

2. prescriber's name/address/phone/signature

3. medication name

4. dosage/amount of medication

5. route of administration (oral/rectal)

6. frequency/time of administration

generic vs brand medications

-for many brand names, there is a generic equivalent

-It is the LAW in most states that when a generic is available, it will be dispensed UNLESS the prescriber indicates: DISPENSE AS WRITTEN or DO NOT SUBSTITUTE

medication names

Chemical name - more organic chemistry driven

Generic name - Name of active ingredient in medication, does not change depending on which company makes it (ex: ibuprofen, acetominophen)

Brand name - temporary, when patent runs out any company can make the generic name drug; name given by the manufacturer or pharmaceutical company to make it recognisable and memorable; branded names are 'Advil' and 'Motrin' which both contain the same active ingredient - ibuprofen.

BID, TID

twice a day, three times a day

Q6h, q8h, q12h

every 6, 8, 12 hours

HS

at bedtime (hour of sleep)

PRN

as needed

AC

before meals; PC (post consumption) = after meals (ante cibum)

PO/NPO

by mouth/nothing by mouth

PR

rectally

IV

intravenous

SQ

Subcutaneous

IM

Intramuscular

Rx

prescription

STAT

immediately

NKA

no known allergies

NKDA

no known drug allergies

NKMA

no known medication allergies

D5W

5% dextrose in water

NSS/0.9%NSS

normal saline solution

0.45%NSS

"half normal" saline solution

Tsp

teaspoon (5mL)

Tbsp

tablespoon (15 mL)

mL

milliliters

Mg, mcg, g

milligrams, micrograms, grams

ER, CR, SR

extended release, controlled release, sustained release

adherence decreases

When...

-the treatment regimen is very complex

-the prescriber isn't very approachable or motivating

-patients take more medications

-high out of pocket cost

-patients feel the medication does not work

-the dosage route isn't best for them or they are experiencing side effects

ABCDX

Drugs are classified on a scale for safety use in pregnancy based on their ability to harm the fetus

Phasing out the "ABCDX" categories:

A - well controlled studies in pregnant females: no increased risk of fetal abnormalities

B - animal studies reveal no increased risk but studies in women either aren't well-controlled or adequate

C - no adequate, well -controlled studies in pregnant females; benefits may outweigh risk

D - studies have demonstrated a risk; in life-threatening situations, benefits may outweigh risk

X - studies may have demonstrated positive evidence of fetal abnormalities; drug is contraindicated in women who are or may become pregnant.

New "Pregnancy Categories:" The PLLR (pregnancy and lactation labeling rule)

Removes ABCDX categories

Risk summary, clinical considerations, data

labeling for drugs approved after June 30, 2015 must include instead

pharmacokinetics

the effect of the body on drugs

the process by which drugs are absorbed, distributed within the body, metabolized, and excreted

pharmacodynamics

the effect of drugs on the body

the process by which a medication works on the body

gated ion channels

function: open or close channels to allow certain ions to pass through the cell membrane

-binding of ligands to receptors produces a conformational change that widens or narrows the channel, thereby regulating the access to soluble ions

transmembranous receptors

-has a ligand-binding domain on the cell's surface and the enzymatic portion of the receptor is in the cell cytoplasm

-the receptor-ligand complex produces a conformational change in the receptor and triggers a response OR the ligand-receptor complex can pass through the cell membrane and trigger an intracellular response directly

g protein coupled receptors

drug naming

-amount

-form

-NDC number

-brand name

-generic name

-dosage strength

-manufacturer

-contraindications

-directions

intracellular receptors

-lipid soluble drugs can transverse the lipid bilayer and enter the cytoplasm

-once inside, these drugs attach to intracellular receptors and initiate direct changes in the cell by affecting DNA transcription

absorption

movement of a drug from its site of administration into the blood

Rate and amount can vary due to:

-pH of drug and stomach: acidic drugs are absorbed better than alkaline drugs

-Lipid solubility: fat-soluble compounds are more easily absorbed through stomach (alcohol), insoluble compounds like fiber stay in gut

-GI motility: slower transmit means more contact time between substance and gut

-Presence or absence of food: some drugs do better with food and some are better on empty stomach as food can slow absorption

-Surface area available for absorption

-Blood flow to an area: more blood flow= more absorption, massage and heat can increase blood flow

distribution

the movement of drugs throughout the body

-Drugs are carried by blood to the tissues and organs of the body

-Drugs pass between capillary cells rather than through them

-Uptake of drug depends on tissue's capacity to accept the drug

Drug uptake is enhanced by:

Increased lipid solubility

Unbound protein fraction of the drug

drug uptake is enhanced by

Increased lipid solubility

Unbound protein fraction of the drug

metabolism

goals are to convert substances into water soluble forms for excretion and to convert to pharmacologically active or inactive forms

Most often takes place in the liver

excretion

removal of drugs from the body

Drugs and metabolites can exit through:

urine (kidneys)

saliva, stool (lower GI tract)

breast milk (mammary glands)

expired air (lungs)

affinity

the attraction between a drug and a receptor

drugs with higher affinity for a receptor require a small concentration to elicit a response

whereas those with low affinity require higher concentrations

bioavailability

The extent to which a drug reaches the systemic circulation; measured as the fraction (F) or percentage of drug that reached the systemic circulation

IV drugs are ~ 100% bioavailable (F=1)

Degree of bioavailability is based on

-route of administration

-ionization

-protein binding

-metabolism

-ability of drug to pass through membranes

-ties into first-pass effect: drugs with low bioavailability usually have a high first-pass effect

bioavailability

may be decreased due to:

-Physicochemical properties of the drug

i.e. lipid and water solubility, molecular size

-Presence of food or other drugs in GIT

-Gastric emptying times

-pH of Gastrointestinal tract

-Characteristics of the specific pharmaceutical formulation

clearance

removal of a drug from the plasma or organs

enterohepatic recirculation

the process by which a drug excreted in the bile flows into the gastrointestinal tract, where it is reabsorbed and returned to the general circulation

first pass effect

the phenomenon by which a drug first passes through the liver, where it is degraded before distribution to the tissues

half life

the time required for half of a total drug amount to be eliminated from the body

steady state

equilibrium between the amount of drug entering the body and the amount leaving the body

hydrophilic

molecules that do not readily cross the plasma membrane because they are water soluble

hydrophobic

molecules that easily cross the plasma membrane because they are lipid soluble

prodrug

a drug that is transformed from an inactive parent drug into an active metabolite; in effect, a precursor to the active drug

receptor

the site of drug action

therapeutic window

the range of drug concentration in the blood between a minimally effective level and a toxic level

volume of distribution

the extent of distribution of a drug in the body

Vd is a THEORETICAL pharmacokinetic parameter

The volume that would accommodate the total drug in the body if the concentration was the same as in plasma

The Vd of a drug in the body stems from the presumption that the body behaves as a single compartment, into which the drug is evenly distributed

Vd is calculated: the dose of drug injected intravenously (mg) is divided by the resulting plasma concentration of drug (mg/L) before elimination starts

Vd (in L) = total amount of drug in body (in mg)/ plasma drug concentration (in mg/L)

If a drug is extensively distributed, the blood concentration will be lower, which equates to a larger volume of distribution

influence Vd

-Lipid solubility

-Affinity for different tissues

-Blood flow: Brain vs. Fat

-Plasma protein binding

5

after how many half lives is steady state reached?

ex: drug has a half life of 4 hours, it would take 20 hours to reach steady state and be nearly eliminated (97%) from the body after the last dose

half life

if half life is 24 hours, dose every 24 hours, if half life is 12 hours, dose is every 12 hours

ideal drug

ideal properties

1. effectiveness

-treats illness effectively

2. safety

-no adverse events

3. selectivity

-no side effects/interactions

minimum dose

smallest dose required to reach therapeutic window

indications

conditions for which the drug is used

contraindications

conditions in which the drug is not used or is never used

cautions

conditions in which drug can be used but with great care

side effects

predicted, unwanted effects of a drug

maximum dose

Highest dose that causes therapeutic effect without entering into toxic levels

therapeutic dose

average dose that produces therapeutic response that we want (based on 150 lb patient)

toxic dose

drug level at which drug becomes too toxic for patient

lethal dose

drug level at which drug would kill patient

LD50/ED50

therapeutic index

Ratio between the median lethal dose (LD50) and the median effective dose (ED50)

The smaller the window, the more potential we have to do harm

Carbamazepine, phenytoin, lithium, warfarin (all have narrow therapeutic windows

agonist

a drug that binds to a receptor and causes a strong effect

activates an effect

partial agonist

a drug that binds to a receptor and causes a small effect

antagonist

a drug that binds to a receptor and does not cause an effect

When an antagonist is binded to a receptor, it is taking up the space for an agonist or partial agonist, and therefore inhibiting an effect

efficacy

the maximum effect that a drug can produce, regardless of dose

"intrinsic activity"

the ability of a drug to produce a desired pharmacological effect

potency

the drug dose required to produce a specific effect

affinity (ability of the drug to bind at the receptor site and form a stable complex) determines the potency

enteral route

movement of drugs from the outside of the body to the inside using the gastrointestinal tract

oral (PO)

sublingual (SL)

buccal

rectal (PR)

enteral route

Advantages: works quickly, easy to do by yourself, cheap

Disadvantages: no medication if they forget to take it, could have trouble if nauseous and vomiting, rectal is not used in pediatrics who are in toilet training stage, if gut health is not good could be more difficult

parenteral route

taken into the body or administered in a manner other than through the digestive tract

intravenous (IV)

subcutaneous (SC, SQ)

intramuscular (IM)

inhalation (INH)

transdermal (TD)

topical (Top)

parenteral route

Advantages: quicker than enteral, topical is more direct to infection, can be more reliable because you know patient is getting meds because health care professional is doing it, IV goes directly into bloodstream

Disadvantages: risk of infection, fear of needles, SC and IM have less predictable absorption times/amounts

loading dose

use of a higher dose than what is usually used for treatment to allow the drug to reach the critical concentration sooner

maintenance dose

the dose of drug that maintains or keeps the drug in the therapeutic range

free

only the unbound or ____ fraction of drug is pharmacologically active

increase

__________ in available proteins will cause an increase in protein binding, leading to less available active/free drugs

albumin

found in plasma, most abundant/important protein for binding

may also bind with lipoproteins, alpha-1 acid glycoprotein

weak bond

the drug protein complex has this type of bond?

reversible

warfarin, phenytoin, propranolol, diazepam

drugs that are highly bound

changes in binding are important

cytochrome P-450 enzymes

a large family of heme-containing enzymes that catalyze the oxidation of organic substances, including drugs and toxins

CYP enzymes are primarily located in the liver and intestine and are responsible for metabolizing approximately 75% of clinically used drugs

site of most drug metabolism

serum concentration

of a drug will increase if there is another drug acting as an inhibitor of CYP450 enzymes

due to low metabolism of drug, more drug will remain in bloodstream

the concentration of the inhibitor drug will also increase

serum concentration

of a drug will decrease if there is another drug acting as an inducer of CYP450 enzymes

more CYP available for metabolism, concentration of both drugs in serum will decrease

active metabolites

metabolites that retain pharmacological activity

only after metabolism will the therapeutic/desired effect will be achieved

inactive metabolites

lack pharmacologic activity and are simply drug waste products awaiting excretion from the body

after metabolism the drug will no longer have the ability to carry out a therapeutic effect

high creatinine

correlates with poor renal drug excretion and kidney problems

creatinine is not being cleared out of the blood and into the urine as it should

poor drug excretion --> drug stays in bloodstream longer, prolonging effects

low creatinine

suggests kidneys are working efficiently to clear creatinine and drugs out of the body

correlates with high levels of renal drug excretion

doctor of pharmacy

A pharmacist with an advanced degree who works in conjunction with a medical doctor to prepare and/or dispense prescription drugs or compounds.

ahealthcare professional that specializes in drugs and medications

-responsible for administering prescription medication and providing patients with information about drugs and their use

-work closely with prescribing healthcare professionals to recommend the best medication for a patient

-the schooling for a Pharmacist typically consists of acquiring your bachelor's degree before attending pharmacy school for anywhere between 2-4 years.

bbb

blood brain barrier

drug must be lipid soluble or have a transport system (carrier mediated) to cross the barrier

-alcohol, caffeine, nicotine are lipid soluble

Vd

in L = total amount of drug in body (mg)/ plasma drug concentration

glomerular filtration

the movement of substances from the blood within the glomerulus into the capsular space

low molecular weight, unbound drugs, low volume of distribution

tubular secretion

occurs in PCT

drug passes from systemic circulation to tubular lumen via a transporter

tubular reabsorption

occurs in distal tubule

lipid soluble molecules are reabsorbed to systemic circulation