PCL218

Pharmacodynamics

-Explains how a natural substance has effects on the body

-Explains how a drug has effects on the body

-Explains how a natural produce (e.g. cannabis) has an effect on the body

Pharmacokinetics

-Explains the way that a drug or natural substance is processed by the body.

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

Receptor

-Target/site of drug action of a compound in the body or a drug

Lock and key or induced-fit models

-Drug acts as key, receptor as lock, combination yeids a response

receptors, enzymes, protiens

-Drugs interact with or or other that are in the body

Natural agonist

Natural substance in the body that binds to a receptor and activates it

Ex. Adrenaline

Natural product agonist

Natural substance from a plant that binds to a receptor and activates it

Ex. Ephedrine

Agonist drug

Drug made in lab that mimics the natural substance in the body. It binds to a receptor and activates it

Ex. Salbutamol Ventolin

Antagonist drug

Drug made in a lab that binds to the receptor, but does not activate it. PRevents the agonist from accessing the receptor

Ex. Propranolol

Fentanyl

This is a synthetic opioid that is approximately 50x more potent than morphine

Injection and Inhalation

What ways are drugs taken to have faster absorption

Orally and Topical (through skin)

What ways are drugs taken to have slower absorption

the more rapid, more addictive, and shorter the duration is

The faster the absoption…

Clinical Trials

-Provide evidence of safety and efficacy of a new medicine

-Scientific validity and integrity

-Expensive

-Required for regulatory approval by the Food and Drug Administration (FDA) of the health products and food branch (HPFB)

1. Initial Drug Research

2. Pre-Clinical Studies

3. Clinical Trials

4. Drug approval process

What are the 4 steps in the FDA drug approval process

1. The safety phase

2. The Effectiveness phase

3. The confirmation phase

4. The monitoring phase

What are the clinical trial phases

Randomized Controlled Trial (RCT)

-A clinical trial in which consenting patients are randomly allocated to one of (at least) two treatments given a condition, one of which should be a placebo or current standard treatment

-The progress of patients on each arm is monitored to assess relative safety and efficacy.

Placebo

• Designed to appear identical to the treatment

• Prevents researches and subjects from knowing whether a treatment is active or not, as expectations about efficacy can influence results.

1. Neural Activators

2. Enzymes

3. Transporters

4. Receptors

What are the components of a pharmacological system

Endocannabinoid System

• Exists throughout life

• Its there in people who have never been exposed to cannabis

• It explains how cannabis words, but cannabis is not why it exists

Endocannabinoids

Neural activator for cannabis

Cannabinoid CB1 adn CB2

Receptors for the natural activators (for cannabis)

In the brain

Where are endocannabinoids made?

CB1

_ receptors affect neurotransmitters that control brain function

It inhibits neurotransmitter release

When do we make Endocannabinoids

We make these when these factors come into play:

Stress, Exercise, Hunger, Time of day

When CB receptors are activated, they reduce pain

Rimonabant

-CB1 Antagonist

-Loss in appetite

-Increase in depression/suicide

homeostasis, metabolism, stress

The endocannabinoid system plays a key role in maintaining , including the regulation of _ and _ responses.

exercise

The majority of samples that measured anandamine showed a significant increase in anadamie concentrations following

Single Nucleotide Polymophisms

• A change in DNA sequnce

• Leads to population differences the physiology

Reduced Stress and axiety responses

Increases fear extinction, less PTSD

What can happen when Anandamide levels are increased and the CB receptors are activated?

Cannabis effects

• Dizziness, drowsiness, lightheaded, fatigue

• Impared memory and attention, concentration, ability to make decision

• Diorientation, feeling confused, feeling of unreality, slow sensation of time.

• Suspiciousness, nervousness, axiety, panic, paranoia

• Imparement of motor skills

THC

is a CB receptor activator

Dopamine

Increase in leads to feelings of euphoria

Tolerance

• Decrease response to same dose with repeated exposure

• More drug needed to achieve same effect

• caused by compensatory mechanisms that oppose the effect of the drug

What THC can do to the body

• it can act as a CB1 activator mimic endocannabioids

• it can cause tolerance in CB1 effects and inhibit endocannabioids actions

Cannabis use disorder

• Can develop as a consequence of cannabis use and occurs in sub-sets of users

• Select symptoms include difficulties in use control, disruptions in functioning, and increased tolerance and withdrawal

• recent analysis suggests that this has increased more in adults in the US over time

• 1 in 5 users reported at least one of the symptoms to this in 2013

Non-psychoactive

-Inactive

-Detected in urine

-CBD

Duration of action

Inhaled lasts 2-4 hours

Oral lasts 6-24 hours

Injesting (eating) Cannabis side effects

Can result in over-intoxication including severe anxiety and panic, nausea, and vomiting, as symptoms of psychosis

Inhaling cannabis

-Smoke or vapour delivers THC, the chemial that gets you high, into your lungs where it passes directly into your blooodstream and then into yor brain

Ingesting Cannabis

-Travels first to your stomach then to your liver before getting into your bloodstream and brain.

-The liver converts THC into a stronger form and this combined with the THC from the original product adds to the intensity of the high

Edibles

-The high that accompanies ingesting this reported as being more intense

-It can take up to four hours to feel the full effects of this

• Wait at least four hours before consuming anothe one of these

The higher the THC levels, the "higher" the user

Different effects of THC on an individual

-Psychological effects can PEAK after THC peaks

-Lack of CORRELATION of THC levels and intoxication (Tolerance)

-Individual variation - genetics, dose, frequence of use, sex

FAAH A-allele

-This polymorphism variant may influence both the theraputic and adverse effects of THC

-Study showed that these carriers showed a trend towards increased sedation following administration of THC

Absorption, Distribution, Metabolism, Excretion

What does ADME stand for

Grapefruit Juice

• This increases the concentration of oxycodone in the body

• It may be harmful becuase of of the drug will pass into the bloodstream increasing the possibility of respiratory failure and overdose

Purpose of a Systematic reviews/meta-analysis

-To summarize the best evidence that answers a specific question