PCL218 Final

homestasis

- constant rebalancing

- the environment causes a change, causes a chemical change in the body (neurotransmitters), which leads the brain and body to change in response to change in environment

stress response

danger in the environment increases adrenaline in the body and causes the fight or flight response

- increase in heart rate and sweating, decrease in digestion

pharmacodynamics

explains how a natural substance, drug, or natural product has an effect on the body

pharmocokinetics

explains the way that a drug or natural substance is processed by the body

- drugs are absorbed, distributed, metabolized and eliminated by the body

natural substance

natural compound made in the body

drugs

synthetic compound

natural product

compound derived from plants

receptor

target/site of drug action of a compound in the body or a drug

induced fit model (lock and key)

drug acts as a key, receptor as lock, combination makes a response

effects of adrenaline

bronchiole dilate, blood pressure increases, heart rate increases, digestion decreases, pupils dilate, liver converts glycogen to glucose

natural agonists

substances within the body that have evolved to produce a response when the bind to receptor

agonist drug

mimic natural agonists within the body, binding to receptors to create the same effect but often with more significant physiological response

where are alpha adrenergic receptors found

in the heart

- binding of adrenaline causes heart rate to increase

where are beta adrenergic receptors found

in the lungs

- binding of adrenaline causes bronchioles to dilate

Ventolin inhaler (salbutamol)

synthetic drug that is a beta agonist, causing bronchioles to dilate

clinical use of adrenoceptor agonists

- anaphylactic shock (epipen)

- cardiac arrest

- asthma

- decongestant (when have cold)

antagonists

bind cell's receptor and blocks access to receptor from agonists in the body

clinical use of adrenoceptor antagonists

- high blood pressure (a and b blocker)

- migraine (a and b blocker)

- tremor (b blocker)

- anxiety (b blocker)

examples of natural products

- foxglove (digitalis)

- cannabis (THC)

- poppy (morphine)

- tobacco (nicotine)

- deadly nightshade (atropine)

foxglove (digitalis)

used in heart failure

poppy (morphine)

pain reliever

ma huang

natural supplement herb that has ephedrine (similar to epinephrine)

- can cause seizures, strokes, heart palpitations

what was ma huang marketed for

weight loss, athletic enhancement, asthma

side effects of ma huang

heart palpitations, heart attack, seizure, death

drug interactions of ma huang

caffeine, epinephrine, oral corticosteroids

dose response curve

relationship between drug dose and magnitude of drug effect

- drugs can have more than one effect

how do drugs vary in effectiveness

- different sites of action

- different affinities for receptors

enkephalins and endorphins

natural opioids (pain killers)

example of enkephalin and endorphin drug agonists

morphine, heroin, fentanyl, oxycontin

heroin

semi synthetic, made from morphine

fentanyl

completely synthetic, especially potent

- need less of drug to get effect

oxycontin

semi-synthetic

risks of opioids for pain relief

opioid use disorder (addiction) and respiratory depression (overdose)

naloxone

antagonist that blocks opioid receptors or remove agonists, and reverses effects of overdose (used for fentanyl overdoses)

- can deliver as nasal spray or inject to leg

-

tolerance

- decreased response to same dose with repeated exposure

- more drug needed to achieve same effect

- receptors are downregulated

withdrawal

- if opioids are stopped suddenly, the few receptors left are turned off

- leads to muscle aches and pain, diarrhea, nausea, vomiting, sweating, chills, tremors, skin-crawling

ways of medicine administration

inhaled, oral, intramuscular, intravenous, topical

faster absorption methods

injection and inhaled through lungs

- the faster, the more addictiveness, shorter duration

slower absorption methods

orally and topical

accumulation of drugs in fatty tissue

- fat soluble drugs like THC can accumulate in fat, muscle, organs, bones

- can prolong drug action by slowly releasing it into blood

absorption

how will drug get in

distribution

where will it go and what organs

metabolism

how is it broken down

- most of the time it's the liver

excretion

how does it leave

- needs to leave body or else will accumulate

liver

enzymes like cytochrome P-450 transform drugs into more water-soluble metabolites

kidney

traps water-soluble compounds for elimination through the kidney

lungs

can excrete alcohol in the breath

breast milk

can excrete alcohol and drugs through breast milk

purpose of clinical trials

- provide evidence of safety and efficacy of a new medicine (but expensive)

- scientific validity and integrity

- require regulatory approval by FDA or Health Products and Food Branch

FDA drug approval process

basic science research, pre-clinical testing, clinical trial and FDA approval

basic research (how long and what)

- 2-5 years

- look at cells and tissues, identifying target molecule and test activity, efficacy, toxicity

pre-clinical testing (how long and what)

- 1-2 years

- testing in animals or cells

- testing for safety and potential efficacy

- have to submit a Clinical Trial Application for authorization to go to clinical trials

clinical trials (how long and what)

- around 9 years

- phase 1, 2, and 3

- testing in humans

Phase 0

- first study in a very small number of people

- figure out how body metabolizes to decide where to start dosage

Phase 1

study of small number of healthy individuals to evaluate safety and dosage, identify adverse drug reactions

Phase 2

- study of larger group with the disease (few hundred)

- study effectiveness of drug to further asses safety and best dose

Phase 3

- study in even larger group of people with disease (thousands)

- confirm drug's effectiveness, monitor side effects, compare the drug to other commonly used treatments and collect further info

Phase 4

- monitoring phase post approval

- assess long term benefits and risks of the population

how long is does FDA approval normally take

6 months to 2 years

new drug submission (NDS)

if clinical trials show potential, company submits NDS where they analyze the drug's efficacy and safety data, and Risk/Benefit analysis