Principles of Psychopharmacology Flashcards
What is pharmacology? What are the different roles of medical professionals in this feild?
Pharmacology: science of sticky molecules that stick to proteins and receptors that alter system’s functions.
Pharmacist: prescribe medicinal drug, know therapeutic effects. Can’t make the molecules.
Medicinal Chemist: Create molecules to bind targets
(NeuroPsycho) Pharmacologist: studies how drugs affect receptors, physiology of systems, and behavior. Bridge the gap from preclinical to clinical research. What the sticky molecules do!
What is pharmacology and neuropsychopharmacology and its derivatives?
Pharmacology: study of action of drugs and effects on living organisms (before 20th century all drugs naturally occuring, then synthetic drugs occured in specialized feilds)
Neuropsychopharm: chemical substances to act on nervous system to effect behavior.
Neuropharmacology: how drugs cause changes in NS cell function, cellular level. How drugs alter cell function.
-Psychopharmacology: drug induced mood/thinking. Behavioral measures
Drug Actions vs Effects and Therapeutic vs Side Effects.
Explain the site of action and its effects.
Show some examples.
Drug Action: molecular change when a drug binds a target/receptor
- Specific, nitty gritty
Drug Effect: broader effects AFTER action. Alter physiological or psychological functions.
- Behavior - In body - Site of action differs from site of drugs effects - Different drugs have similar effects but work at different sites of action. ○ Muscarine (stimulates ACH) -directly in eye ○ Morphine (stimulates opiod receptors) -works in brain Both cause pupillary constriction (eye vs brain) But work on different receptors Work in different parts in body/brain.
Ingested by humans: systemically gets into bloodstream and circulated through body (oral, injection, into brain)
- Can act on several target sites
- Anywhere there is a receptor, it can effect that system
- Drugs have MULTIPLE effects
Therapeutic effect: produces what you want
Side effect: what you DON’T want. Often working on another area
What is risperdal?
antipsychotic, blocks D2 dopamine receptors and help schizophrenia BUT it also makes you gain weight
Some systems have an imbalance, but some systems don’t! Given a drug can have bad consequence of a working normal system.
What are specific vs nonspecific effects? Provide examples. Also explain the placebo effect please.
Specific Effects: Physiological interaction with a target site that causes the same effect across all living organisms. Drug always does in every individual.
- Alcohol: depress neural activity. At high doses, reduces firing of neurons. Cause sedation. - Alcohol does this in EVERYONE.
Nonspecific Effects: Same drug, same dose, show different reactions. Mood, background, perceptions etc.
- Alcohol can make have different effects (make you happy, some make you sad) Moods can be amplified.
- Placebo effect. When you give nothing compound can produce effect. Makes you THINK that it will so it does.
§ Parkinsonian (reduced dopamine in striatum)
Give a drug, tell them its L-DOPA even though its sugar. See lesser symptoms. See an increase in dopamine
Describe pharmacokinetics and the 5 factors which determine bioavailability (plus some other factors)
Pharmacokinetics: How effective drugs are when taken systemically
Bio-availablility of a drug: how much of the drug is available in the system to bind to the target site
- Route of Admission
- Absorption/Distributoin
- Binding
- Inactivation
- Excretion.
In detail…
5 factors (see the slides)
1. How its getting into system: influence how readily they get into bloodstream
2. How easily it’s absorbed from initial site into the bloodstream. Gotta get into system, dissolve in plasma, go throughout the body. Structure of drug will effect how quickly
3. Can go to any receptor in body and brain. How well does it bind to these sites? Target site* Usually a receptor on neurons in the brain.
Most drugs stick to other sites OTHER THAN the target site. (Inactive depot sites)
How well will it stick to inactive sites and target sites. Balance.
How much of the drug will go to inactive and how much is available to bind to target.
4. Molecule will be inactivated through enzymes. Often in the liver. Makes it easier to get out of the body. How fast it’s inactivated influences how much will get to its target site and how long it will last in the system.
5. Once its been inactivated, it will be excreted.
Other factors
How quickly drug reaches it’s target
Frequency/history of prior drug use (repeated use, drug target sites become less effective, or body is more effective at metabolizing it, metabolic/functional tolerance)
Describe oral route of administration. (Advantages, Disadvantages, Factors that influence absorption, and an example.
Most common: Orally (PO: Paroral)
- Safe - Self administered - Economical - Entry into plasma is slow and variable amount (variable plasma levels) - Not as consistent amount per individual and day to day in the same person
Orally: absorbed into bloodstream through the gut
- Some are absorbed through stomach lining if small enough (alcohol) - Most are taken up through small intestine (capillaries around small intestine)
How resistant it is to stomach enzymes and acid.
i. e. Insulin for diabetes - Must be injected BECAUSE - It’s a peptide and stomach breaks down peptides
Factors: richer foods, more food, slows absorption
How quickly stomach empties (to get to intestines)
How active you are (slows digestive process)
Describe 1st pass metabolism.
Liver: garbage processing. Oral toxins are denatured here before general circulation.
1st pass metabolism. (through portal vein)
- Could be chemically altered - Drugs must be resistant to this first pass. - Some need to be administered by injection or really high doses.
Give super high dose, overwhelm liver and get into general circulation.
- Some are metabolized but others slip through
Some drugs are inactive when you take them as a pill form and activate when they go through the liver.
Some drugs chemically formulated that they get into general circulation, and when they go back into the liver, the metabolite induces the same effect as the drug.
Describe injection and inhalation routes of administration.
Injection: hypodermic needle/syringe
- Bypass 1st pass of the liver - Gets drug into bloodstream without stomach acids or liver. - IV (directly into venous) - Rapid - Accurate - Reliable § i.e. Gets into the brain in less than a minute (psychoactive drug) - Need specialized training and equipment - Greatest risk of overdose. - SC: under the skin - IM: into the muscles § Both through capillaries (slow and even absorption but bypasses liver) - Inhalation: drugs absorbed by capillaries in the lungs. - Cause irritation and damage to the lungs. Difficult to get accurate reliable dosing.
What are different factors that affect Absorption time?
Route (IV, PO), vehicle its in (saline or oil)
Size of individual
Sex differences
In detail…
Orally: small increase, lasts 6 hours, a lot of it is chewed up to 1st pass liver
IV: rapid increase, maximal dose, short lived 4 hours (gets metabolized quick)
IM: Oil: doesn’t cause the same peak, but slow steady and lasts longer. In saline: like IV
Vehicle impacts how long it says: saline vs oil (oil lasts a lot longer)
- Oil slows absorption steadily. Not as much metabolized as rapidly.
Other factors
- Size of person (more person has more body fluid, needs more drug)
§ Amount of drug per body weight.
- Sex differences (women have less boy fluid and different physiology)
§ Not eveyrone is a 70kg white male
How are drugs absorbed?
Drug has to be absorbed in the plasma and get to it’s target
Target inside the brain.
- How easily can pass through cell membranes. - Phospholipid bilayer thin fatty walls. - Only ones that can pass through are LIPID SOLUBLE (dissolve in fat and don't dissolve in water - hydrophobic) § Can pass through membranes through passive diffusion - Ie. Steroid hormones, opioid drugs are lipid soluble
Two opioid Drugs
- Heroin (diacetylmorphine) is a more lipid soluble version of morphine. More rapid onset, more potent.
How do drugs get from the bloodstream to targets?
Now its in the bloodstream, how does it get to a target?
Carried through whole body 1-2 minutes
- Receptors for that drug.
In the body: pretty easy. The capillaries are porous
- Can just diffuse out and come into contact with receptors on tissues. OR - Transported outside capillaries through pinocytosis (in vesicles and shoved out)
Brain is DIFFERENT: BBB
- Only some substances can get in. Want to keep out (disruptive effects if they could cross) - Even substances we make ourselves! - i.e. Adrenaline (by adrenal glands) Hormone that has effects, but its also a NT in the brain. - Don't want to mix signals! We don't want body adrenaline to effect brain. Cannot cross.
Describe the BBB in detail. Where is it not as tight?
BBB is a series of glial cells that wrap all capillaries in the brain
- Reduces passing of ionized particles that dissolve in water
- Will not prevent lipid soluble molecules.
Carrier Mediated Transport
If brain needs certain nutrients from bloodstream that are large and not lipid soluble the BBB has transporters for molecules like GLUCOSE from blood plasma and put them in CSF
- Actively take it
If you want a drug to have an effect on brain function given systemically it has to be lipid soluble in blood plasma at certain pH
BBB is pretty tight. EXCEPT FOR
- Area Prostrema (vomit center)
- Median Eminence: release hormones into blood
Hypothalamus: access and moniter contents of the bloodstream
Describe Drug Clearance and the two different ways drugs are elimated.
1st order (exponential): many more sites to molecules, usees the concept of half lives. concentration dependent. zero order (when supersaturated - more molecules than clearance sites, not concentration depedent) - like alcohol because we drink so much of it (grams compared to mg) - metabolized at 10-15ml/hour
Describe the process of biotransformation in the liver. Describe the two phases.
Cytochormo p450 is a family that oxidizes most psychoactive drugs. (can also be found in nasal passages
- alters structure of molecules and makes it inactive/easier to get out of body.
Phase 1: non synthetic biotransformation
- Oxyidze/reduce/hydrolyze molecule
- Not complex.
- Taking off or putting on an Ion.
- Converts molecule to less lipid soluble, less active, easier to excrete.
- Make it more polar. What is polarity?
- Can also convert it to another active form
§ EX: Diazepam (Valium) antianxiety medication
□ Liver converts valium to oxazepam and has a similar action.
□ Induce same types of effects.
Phase 2: synthetic biotransfomation
- Conjugation
- Attaches another whole small molecular group (sulphase, methyl)
- Makes it larger, bulkier, polar, ionizes it
- Easier to excrete
§ EX: morphine has glucournoride 3 making it huge
§ Makes it polar, big, inactive, easier to get rid of.
Some go through phase 1/2 multiple phase 1 phase 2,
Different drugs biotransformed in different ways (1/2/both)
Excreted through bile or kidneys
