Week 1

Pharmacokinetics

Pharmacokinetics

what the body does to the drug (absorption, distribution, metabolism, and excretion)

Pharmacodynamics

what the drug does to the body

the biochemical effects and physiological effects of drugs and the mechanisms by which those effects are produced

what is a receptor?

a receptor is a molecule to which a drug binds to initiate its effect

agonist

binds tightly to a receptor to produce a desired effect

antagonist

competes with other molecules and blocks a specific action or response

four basic pharmacokinetic processes

• absorption

• distribution

• metabolism

• excretion

adverse drug reaction

any harmful, unintended and undesired effect that occurs at normal drug doses

frequency distribution curve

graphical representations of the number of people who respond to a drug at various doses

what is the peak of a frequency distribution curve called?

median effective dose (ED50)

what is the median effective dose (ED50)?

the largest number of people responding to a given drug

what is the median lethal dose (LD50)?

the dose required to kill 50% of the subjects

therapeutic index

used to examine the safety of a drug by comparing the median lethal dose and the median effective dose.

TI = median lethal dose / median effective dose

what is the graded dose response curve?

graphically show the relationship between the effect of the drug and the amount given

what is phase 1 of the graded dose response curve?

occurs at lowest dose ; few target cells effected by drug

affinity

how well the drug binds to the receptor site

what is phase 2 of the graded dose response curve?

slope ; most desirable range

what is phase 3 of the graded dose response curve?

maximal efficacy or ceiling effect ; greatest attainable response, higher dose has no therapeutic effect, but may produce adverse effects

what is the ceiling effect?

a drug reaches a maximum effect, so that increasing the dosage does not increase its effectiveness

potency

the amount of drug required to produce the desired effect

• a drug with high potency requires a lower dose to produce the desired effect

efficacy

the magnitude of maximum response that can be produced from a particular drug

side effect

drug effects that are predictable, caused by the drug binding to other sites in addition to the target site

idiosyncratic reaction

unusual responses to drugs caused by differences between patients (not related to the action of the drug)

what is a drug interaction

when a substance increases or decreases a drug’s actions

additive drug interaction

effect of two or more agents acting together

synergic drug interaction

effect of two drugs is greater than would be expected from simply adding the two individual drug responses

antagonistic drug interaction

effects of drugs actions “cancelled”

absorption

movement from site of admininstration, across body membranes, to circulating fluids

what is the primary factor in determining length of time for effect of drugs to occur?

absorption: the more rapid the absorption, the faster the onset

what are 4 different ways a drug can be absorbed?

• passive diffusion

• facilitated diffusion

• endocytosis

• active transport

passive diffusion (3)

• most common way drugs are absorbed.

• higher to lower concentration.

• usually small, non-ionized or lipid soluble molecules.

facilitated diffusion (2)

• higher to lower concentration.

• carrier proteins (to help molecules pass through membrane).

endocytosis (2)

• transports large molecules.

• involves engulfment of a drug molecule by the cell membrane and transport into the cell by pinching off the drug filled vesicle

active transport (2)

• needs energy (ATP) to work.

• transports molecules fromm low to high concentration.

distribution

the transport of drugs throughout the body

what are the 2 special barriers in the body

• blood brain barrier

• fetal placental barrier

what is the simplest factor for determining distribution of medication?

amount of blood flow to body tissues

what is the blood brain barrier?

• capillaries of the CNS have tight junctions that prevent free diffusion

what molecules can pass through the blood brain barrier?

only drugs that are lipid soluble or that have a transport system can cross the blood brain barrier

drugs exist in what 2 forms?

• free drug molecules

• drug-protein complex

what happens when a drug molecule forms a drug-protein complex?

drugs bind reversibly to plasma proteins, and thus never reach target cells (too big to cross membranes)

what is the significance of malnourishment to drug distribution?

malnourished people have less albumin, and therefore have more free drug molceules, making them very sensitive to medications

what is the most important protein for protein binding?

plasma albumin

where does drug metabolism take place?

in the liver: the body’s chemical processing plant

what is an important enzyme for the metabolism of medications?

Cytochrome P450

what is the first pass effect?

medications absorbed through the GI tract pass through the portal vein to the liver, which means some of the drug will be metabolized by the liver before it reaches circulation

metabolism

drugs are broken down by the liver by liver enzymes

elimination

remaining drug metabolites in the bloodstream are filtered by the kidney. a portion is reabsorbed into the bloodstream, and the remainder is excreted out of the body

what are the routes of excretion? (4)

• urine - kidneys.

• feces - bile from liver.

• exhalation - lungs.

• sweat, tears - glands.

xenobiotic metabolism

the process of biotransforming less polar compounds into more polar compounds that can be excreted more easily

• liver transforms lipid soluble drugs into water soluble drugs so it can be excreted via the kidneys.

minimum effective concentration

amount of drug required to produce a therapeutic effect

toxic concentration

level of drug that will result in serious adverse effects

therapeutic range

plasma drug concentration between the minimum effective concentration and the toxic concentration

half life

amount of time needed to reduce the drug concentration by half

loading dose

if there is not enough time to build up a drug to the therapeutic range, a loading dose is given, which is a bigger dose upfront

what causes an allergic reaction?

hyper-response of the immune system

what are characteristics of a drug allergy (3)

• small amount of drug

• symptoms unrelated to action of drug

• previous exposure to drug

what are the drugs / drug classes that are most likely to cause an allergic reaction? (6)

• penicillin

• iodine

• insulin

• NSAIDS

• preservatives (sulphites and paraben)

• antiseizure drugs

teratogen

drugs that cause birth defects

what is the most common cardiotoxic drug?

antineoplastics