Basics of Pharmacology

pharmaceutics

The science of preparing drugs for administration (dosage forms)

pharmacokinetics

the study of the absorption, distribution, metabolism, and elimination of drugs (what the body does to the drug)

pharmacodynamics

the study of the action or effects of drugs on living systems (what the drug does to the body)

which general area of study is the main focus of pharmacology?

pharmacodynamics

general properties of drugs

- modify existing functions
- exert multiple effects
- typically interact (bind) with something to exert an effect

ways in which drugs can modify existing functions

- replace: iron in anemia
- interrupt (slows down a process): ipratropium is given to COPD patients to low down mucous production
- potentiate (speed up a process): cathartics or laxatives are given before a sigmoidoscopy to speed up the waste removal process

an example of a drug exerting multiple effects?

minoxidil lowers blood pressure and prevent hair loss

levels of drug activity

1. Body Systems
2. Component Tissues
3. Cellular Level
4. Molecular Level

beta blockers action on body systems

reduce pulse rate

beta blockers action on component tissues

negative chronotrope (slow rate)

beta blockers action on cellular level

prevents elevation of cAMP

beta blockers on a molecular level

competitive antagonism of NE to beta 1 receptors on the heart

the better fit of binding a drug has to a receptor _________________

the greater effect the drug has

what levels do agonists and antagonists act at?

cellular and molecular levels

agonism/agonist

an interaction between a molecule and receptor that activates the receptor

full agonist

increasing concentrations of the agonist will produce an increase in biologic effect up to an intrinsic activity of 1

neurochemical transmitters that result in physical effects

NE/epi, AcH, dopamine, serotonin

do you need to bind all receptors to reach max activity in full agonism?

no, and adding more agonists after max activity is reached will not change anything

partial agonist

increasing concentrations of the agonist will produce an increase in biologic effect up to an intrinsic activity of less than 1 (will never reach full potential)

opioid full agonists example

methadone

opioid partial agonists example

buprenorphine

antagonism/antagonist

binding of a drug to a receptor that does not activate the receptor and prevents a response to an agonist

noncompetitive (irreversible) antagonism/antagonist

block cannot be overcome by increasing the dose of an agonist

competitive (reversible) antagonism/antagonist

block can be overcome by an increasing the dose of the agonist

pharmacologic antagonism

two drugs compete at the same receptor

effect antagonism

two drugs act at different receptors but counter each other

what would you use if you want a ligand gated ion channel to stay open?

agonist

what would you use if you want a ligand gated ion channel to stay closed?

non-competitive antagonist

what does it mean to get drug into the body?

it has to pass through the biological membrane

enteral administration routes

- mouth
- sublingual
- buccal
- rectal

property of the mouth

thin lining and rich blood supply

property of the stomach

medium surface area, rich in blood supply, acidic pH (little to no absorption)

property of the small intestine

huge surface area, rich blood supply, basic pH (lots of absorption)

property of rectum

small surface area, rich blood supply, basic pH (lots of absorption)

main reason for rectal administration

helps drug to be more concentrated in that area in a more immediate way

parenteral administration

using a needle to bypass the biological membrane for whatever reason

advantages of parenteral administration

- can be used for drugs that are poorly absorbed (vancomycin)
- can provide immediate onset of action (IV)
- can provide longer lasting effects (antipsychotics for months)
- can concentrate drug at a specific location (joint)
- can provide a more predictable response (antibiotics in a septic patient)
- can be titratable (can easily change dosage on IV drip)

parenteral administration disadvantages

- painful
- irreversible
- extravasation/phlebitis
- contamination/infection

extravasation

escape of blood from the blood vessel into the tissue

phlebitis

inflammation of a vein

intravenous parenteral administration

directly into vein

why are veins used more than arteries in parenteral administrations?

because they have a lower pressure and are less susceptible to severe blood loss

intra-arterial parenteral administration

directly into arteries

intramuscular parenteral administration

injection into a muscle (usually a vaccine)

epidural parenteral administration

assist in localized block during childbirth (in epidural space NOT the CSF)

intrathecal parenteral administration

directly into CSF

subcutaneous parenteral administration

beneath the skin

intra-articular parenteral administration

directly into a joint

skin topical administration

- ointments, creams, patches
- local and systemic

eye topical administration

- drops and ointments
- local

ear topical administration

- only used for external issues
- local

intranasal topical administration

- spray and drops
- local an systemic

inhalation topical administration

local and systemic (anesthetics)

vaginial topical administration

- local and systemic

most common form of dosage to give

oral

disintegration of oral dosage

increases the surface area by breaking drug up into a bunch of little pieces

dissolution of oral dosage

dissolving the drug down to its molecular particle to pass through the biological membrane

oral dosage forms listed in order from fastest to dissolve to slowest

- dissolved liquid (elixer, syrup)
- suspensions
- powders
- capsules
- tablets
- coated tablets
- enteric coating
- sustained release

dissolved liquid (elixer or syrup)

already been dissolved down to its molecular form

suspensions

must shake before taking because the drug has not yet been dispersed (has been disintegrated but not dissolved)

powders

not a common form or drug anymore

capsule

powder inside a gelatin capsule that is dissolved in the stomach

tablets

has to disintegrate and dissolve

coated tablets

has a spray coating to delay absorption, mask a bad taste, make the pill easier to swallow, or just hold the tablet together

enteric coating tablets

coating that only allows capsule to dissolve in basic pH and protects the drug from acidic environments

sustained release

made to last longer so people don't have to be inconvenienced by taking a drug multiple times a day

types of absorption of a drug

passive or facilitated

rate of absorption can determine

- onset of action
- duration of action
- intensity of response

variables affecting absorption

-nature of absorbing surface
-surface area
-blood flow to site of administration
-pH at the site of absorption

drug elimination

- removal of the active drug from the body
- either biotransformation or excretion

biotransformation (hepatic metabolism)

changing the active drug into something that is no longer active

tissue enzymes in biotransformation

GI tract, lungs, kidneys

excretion

moving the active drug out of the body
- kidneys
- lungs
- sweat glands
- mammary glands
- GI tract

onset of action

time it takes for the drug to work after it is given

duration of action

how long the drug exhibits physical effects

therapeutic range

a range for proper dosage of a drug to determine safety and efficacy - lies between the toxic level and minimum effective concentration

variables that affect dose/response of a drug

- body weight
- age
- gender
- genetics
- tolerance
- psychological factors/beliefs
- comorbid medical conditions

how can body weight affect dose/response of a drug?

- larger doses are often given to patients with greater weight or BMI
- common to use the mg per kg method
- dosage depends on where the drug distributes to in the body (muscle, adipose, body water)

how can age affect dose/response of a drug?

- altered capacity to metabolize and/or excrete drugs (usually decreased)
- most common in very young and very old people

how can gender affect dose/response of a drug?

differences in body composition and hormonal activity but we mostly look at difference in body size

how can age genetics affect dose/response of a drug?

- enzymatic differences can lead to alterations in magnitude of effect (decrease or increase)
- therapeutic failure or toxicity

how can tolerance affect dose/response of a drug?

- larger doses must be given to maintain the same effect

- commonly seen with opioids

- not all body effects experience tolerance in the same way

how can psychological factors/beliefs affect dose/response of a drug?

- placebo effect (typically not long lasting)
- if you believe a drug will work it is going to have more efficacy than if you believe it won't work

how can comorbid medical conditions affect dose/response of a drug?

- can affect all phases of pharmacokinetic and pharmacodynamic response
(a condition like kidney failure effects the excretion of drugs)