neuropharm lecture 1

Question 1

What is pharmacology?

Answer 1

the scientific study of the actions of drugs and their effects.

Question 2

What is neuropharmacology?

Answer 2

the scientific study of drug-induced changes in the functioning of the brain.

Question 3

What is psychopharmacology?

Answer 3

the scientific study of drug-induced changes in mood, thinking and behavior.

Question 4

What is Neuropsychopharmacology?

Answer 4

objective is to identify chemical substances that act upon the nervous system to alter behavior that is disturbed due to injury, disease, environment.

Question 5

What are psychoactive drugs?

Answer 5

are any chemical substance capable of changing your brains function, and which results in alterations in perception, mood, consciousness, cognition, and/or behavior.

Question 6

What is drug action?

Answer 6

specific molecular changes produced by a drug when it binds to its target site or receptor (neuropharmacology).

Question 7

What is drug effect?

Answer 7

widespread alterations in physiological and psychological function produced by a drug (psychopharmacology).

Question 8

Therapeutic effect vs. side effect

Answer 8

Therapeutic Effect: drug-receptor interaction that produces desired physical or behavioral change.
Side Effect: anything else.
Can range from mild to severe;
Many people take drugs for their “side effects” (e.g. amphetamines for weight loss).

Question 9

Specific effects vs nonspecific effects

Answer 9

Specific effects: those based on the physical and biochemical interactions of a drug with a target site.
Nonspecific effects: based not on chemical activity but on unique characteristics of the individual.
Experience, mood, expectations, attitude, genetics.
E.g. placebo

Question 10

Pharmacokinetics

Answer 10

the study of how drugs move through your body.

Question 11

factors that contribute to how a drug moves through your body:

Answer 11

1.Route of administration;
2.Absorption & distribution;
3.Binding;
4.Metabolism/inactivation;
5.Elimination/excretion.

Question 12

Possible routes of administration:

Answer 12

-Oral;
-Intravenous (IV);
-Intraperitoneal (IP);
-Subcutaneous (SQ);
-Intramuscular (IM);
-Inhalation.

Question 13

What is Oral administration and what are its advantages and disadvantages?

Answer 13

Oral administration is the consumption of drugs via mouth (e.g. prescription pills, MDMA pills, THC gummies).

Advantages:
-Safest, most convenient and economical;
-Self administered.
Disadvantages:
-Individual differences make it difficult to know how much drug will be absorbed into blood stream (genetics, food in stomach, etc.);
-Stomach acids destroy drugs rapidly;
-Least efficient.

Question 14

What is Intravenous (IV) and what are its advantages and disadvantages

Answer 14

IV administration is injecting drug/substance directly into the venous blood stream.

Advantages:
-Dosages can be extremely precise;
-Extremely fast onset of pharmacological action;
-Less strain on liver.
Disadvantages:
-Extremely dangerous;
-Very few barriers between drug and brain, gives very little time for intervention (should it be required);
-Requires (or should require) a health care professional for administration.

Question 15

What is Intramuscular (IM) and what are its advantages and disadvantages?

Answer 15

IM administration is directly into the (skeletal) muscle tissue.

Advantages:
-More rapid absorption than from the stomach (but less than IV);
-Absorption is more gradual (tends to form a pocket, slowly diffuses);
-Can be combined with other drugs to further control of absorption (e.g. immunosuppressant, oil).
Disadvantages:
-Rate of absorption depends on rate of blood flow to that specific muscle tissue;
-It hurts!

Question 16

What is Subcutaneous (SQ) and what are its advantages and disadvantages

Answer 16

Absorption is slow and steady but can be variable.
Depends on derma layers, adipose
layers, blood flow to that particular area,
etc.
Can use pellet or other delivery device.
E.g. Insulin bolus, osmotic mini-pumps.

Question 17

What are Epidural Injections

Answer 17

Nerve fibers that travel up and down the spinal cord bring sensory information back-and-forth between the brain and the periphery (arms, legs, neck, etc.)
Injecting drugs into the epidural space can temporarily mute communication from these nerves.

Question 18

Inhalation

Answer 18

Most preferred route of administration for recreational drug use (e.g. tobacco, nicotine, cannabis, cocaine, heroin, etc.)
Lungs have very large surface area which allows for extremely rapid absorption of drugs into the blood stream.
Blood capillaries of the lungs go straight to the brain!
Blood leaving lungs is already oxygenated;
First priority for oxygenated blood à deliver oxygen to brain.

Question 19

What is the fastest way to get drugs to the brain?

Answer 19

Inhalation

Question 20

Intranasal and Sublingual

Answer 20

Using the mucous membranes in both your nose and mouth, drugs can gain access to your blood stream.
Intranasal (aka insufflation) = snorting cocaine powder.
Sublingual = dropping LSD tablets

Question 21

Transdermal

Answer 21

Transdermal patches (e.g. nicotine patch, fentanyl patch) provides a slow, continuous, and highly controlled release of a drug.
Allow for continuous absorption of drugs over hours, or days.
Safe (but slow).

Question 22

Some factors that influence
how we absorb drugs.

Answer 22

-Transport across (phospholipid bilayer) membranes;
-Lipid (in)solubility;
-Ionization of drugs (polar vs. non-polar; hydrophobic vs. hydrophilic);
-Genetic differences at every step along the way;
-Current metabolic and homeostatic state.

Question 23

How are drugs distributed across the body?

Answer 23

There are many factors and membranes in your body that serve to regulate which drugs gain access to which parts of the body.

Blood circulation: regions of the body that are more vascularized get the most drug (brain, skeletal muscle > fat);
Solubility of drug in fat;
Binding of drug to proteins in blood stream (e.g. chaperones);
Permeability of membranes.

Question 24

What are capillaries?

Answer 24

Capillaries are small blood vessels that are the site of exchange of many substances between the arterioles and venules.

Small pores that allow transport of chemicals regardless of their solubility;
Protein-bound drugs cannot pass through capillaries.
Brain capillaries have distinct morphology:
No clefts or pinocytic sites;
Movement of water-soluble molecules is minimized.

Question 25

What is the purpose of the BBB?

Answer 25

serves to protect the brain from any exogenous chemicals and toxins.
Since the brain has such a high blood flow, and is priority #1 for receiving oxygenated blood, it is at high-risk for encountering blood-born toxins.
BBB is a highly-selective semipermeable membrane that separates circulating blood from the brain.

Question 26

What Certain areas of the brain are not covered by the BBB:

Answer 26

Area postrema;
Median eminence;
Arcuate nucleus of the hypothalamus (maybe).

Question 27

Placental barrier

Answer 27

a semipermeable membrane made up of placental tissues and limiting the kind and amount of material exchanged between mother and fetus

Question 28

Metabolism

Answer 28

Metabolism is the chemical alteration(s) of drugs that (typically) reduce the effects of the drugs and increase their likelihood of excretion.

Question 29

Enzyme induction

Answer 29

repeated use of a drug increases the # of enzymes capable of breaking the drug down (i.e. tolerance).

Question 30

Phase 1 vs. Phase 2 Metabolism

Answer 30

Phase I
Less reactive compound is converted to a more reactive molecule through oxidation, reduction or hydrolysis;
Oxidation makes compounds more water soluble and facilitates further reactions;
Cytochrome P450 enzymes

Phase II
Active or toxic molecules are converted to a less active metabolite;
Oxidized compounds are conjugated with endogenous molecules (e.g. glucuronide, sulfate, methyl groups, etc.)
Increases water solubility for excretion.

Question 31

How can drugs be eliminated from the body

Answer 31

1.Kidneys excrete water-soluble drugs and metabolites in the urine.
2.Liver bile excretes some drug molecules in feces;
3.Some drugs (e.g. alcohol) can be exhaled through lungs.

Question 32

What do kidneys do and where are they located?

Answer 32

-Kidneys are located on either side of the spine at the back of human body;
-They keep the right balance of water and salt in the body;
-Kidneys filter waste from the blood, collect it in the bladder, and then selectively reabsorb what is required.

Question 33

The elimination of drugs is primarily accomplished by: kidneys or liver

Answer 33

Kidneys

Question 34

Pharmacodynamics

Answer 34

PD is the study of the physiological and biochemical interaction of drug molecules with cell receptors in their target tissue.

Question 35

What are receptors and ligands

Answer 35

Receptors: proteins on cell surfaces or within cells.
Ligand: molecule that binds to a receptor with some selectivity.

Question 36

agonist vs. antagonist

Answer 36

Agonist: produces biological effect.
Antagonist: produces no cellular effect.

Question 37

affinity

Answer 37

the strength of the attraction between a ligand and a receptor.

Question 38

The absolute amount of drug necessary to produce
a specific effect indicates the …… of that drug

Answer 38

Potency

Question 39

ED50

Answer 39

the amount of drug that produces
the desired effect in 50% of patients. Therefore, comparing ED50 of different drugs
allows you to compare their potencies.

Question 40

TD50

Answer 40

the dose at which
a drug will be toxic to 50% of patients.

Question 41

Comparing TD50 with ED50

Answer 41

gives you an idea
of how safe a drug is.
Also allows you to determine the appropriate doses
to prevent toxic effects.