Psychopharm exam 1 imports from quilt

pharmacokinetics

the effects of the body on the drug

What is an acronym for the phases of pharmacokinetics?

ADME

Pharmacodynamics

the effects of the drug on the body (affinity and intrinsic activity)

Absorption rate

how quickly the drug is absorbed

agonistis

drug that acts or mimics natural chemicals

antagonists

drugs that block the effects of natural chemicals

bioavailability

concentration of a drug in the blood that is free to interact with target sites

plasma proteins

these bind to the drugs in the blood stream and keep the drug in circulation

Routes of administration on the GI tract/alimentary canal

oral, buccal, sublingual, rectal

oral

______ administration means “by mouth”

Benefits include self-administration, safer, more economical, time-release formulations

Considerations/caveats include gastric degradation, first-pass metabolism, water-solubility

Gastric proteases

enzymes found in the stomach that can degrade proteins and peptides

EX: pepsin (enzyme) and HCl (acid) making gastric juices, mucus

epithelial cells

cells that make up the lining of the GI tract. The pores between them are very small (~4 A)
It is very important for the drugs to be lipid soluble so they can be dissolved THRU the membrane since the pores are too small for anything to pass thru

First pass metabolism

This happens when drugs pass thru the portal vein into the liver. There, the majority of the drug gets degraded before it even makes it to the arteries.
Solutions to getting around this problem include upping the dose and changing route of administration

Buccal

______ administration
"placed in mouth"
EX: Nicotine and chewable
Benefits include: self-administration and it avoids first pass metabolism.
Disadvantages: increases risk of mouth and throat cancer

Sublingual

_______ administration
drug is placed below the tongue
Advantages: avoids gastric degradation and first pass metabolism

Rectal

_______ administration (administered in the anus)
substitute for oral administration. Good to give if a patient is nauseated, old or unconscious.
Its problems include irregular absorptions and FPM varies based off how deep it was inserted

Intravenous

______ administration
and injection directly into the veins.
This bypasses FPM completely and results in immediate absorption. This is a very accurate route of administration and the dose is adjustable. Disadvantages: OD and allergy risk

Intramuscular

_____ administration
This is an injection directly into the muscle. It is very slow release (even slower when administered in an oil vehicle)
Antipsychotics and Contraceptives are given this way

Subcutaneous

_______ administration
It's dealt by an injection into the subcutaneous tissue of the skin.
This leads to a relatively slow release, however there is risk of an allergic reaction, bruising and it's painful
Silastic Capsules

Intraperitoneal

________ administration
Injection into the peritoneal cavity. This is good for animal injections and injecting large volumes. There is a risk of peritonitis, and for this reason it is rarely used in humans

transdermal

_______ administration
The drug is applied directly to the skin, has to be lipid soluble to be absorbed or on an active patch if the drug is not lipid soluble

Inhalation

______ administration
bringing drugs into the lungs. Leads to immediate absorption

Intrathecal

________ administration
spinal needles administers the drug into the cerebrospinal fluid. This grants the drug access into the brain into the choroid plexus. (a way to bypass the BBB)

Factors that affect the GI absorption rate

Concentration of drug
weak acid or weak base
pH of absorbing surface
pKa (pH=50% ionization)
Area of absorbing surface

Villi

____ & microvilli increase the surface area of the small intestine, therefore increasing the absorption rate
Food slows the absorption of a drug because it slows gastric movement to the small intestine

small intestine

the best place for drug absorption because is has a larger surface area, longer transit time, less mucus and a higher pH for bases

Endothelial cells

the best place for drug absorption because is has a larger surface area, longer transit time, less mucus and a higher pH for bases

fenestration

Pore in a capillary endothelial cell that may be open or covered by a delicate membrane, allows for freer passage of fluids and small solutes between capillaries and tissue cells.

Albumin

plasma protein that mostly binds acidic drugs

Alpha-1-Acid Glycoprotein (AGP)

plasma protein that binds mostly basic drugs

Depot binding

When drug molecules bind to bone and fat. This binding prevents/reduces/prolongs action
Thiopental (fat)
Heavy Metals (bone)
Tetracycline (Enamel)

Blood brain barrier

Structural barrier of tightly apposed ENDOTHELIAL cells
Protects/stabilizes/preserves brain
It's bidirectional and uses active transport to move glucose and amino acids across the membrane

Routes of elimination

these routes are ways for drugs to leave the body
Urine, Bile, Feces, Saliva, Sweat, Breast Milk, Expired Air

Nephron

Functional unit of the kidney, consisting of a glomerulus, renal tubule, and collecting tubule. Drugs are eliminated thru this by way of urine synthesis

Glomerulus

A ball of capillaries surrounded by Bowman's capsule in the nephron and serving as the site of filtration in the vertebrate kidney

Rental filtration

Water and solute enter kidney tubules thru Bowman's Capsule and filtered out. However 99% of the filtrate is reabsorbed by blood (the drugs that are lipid soluble when in the kidney tubule are reabsorbed)

aquaporins

protein channels in renal epithelial cells that allows the passage of water molecules

anti-diuretic hormone

(Peptide Hormone) Regulates the Renal Reabsorption thru water reabsorption by increasing Aquaporins at collecting tubule. It's synthesized in the hypothalamus and stored in the pituitary

ALdosterone

(Steroid Hormone) synthesized and released by adrenal cortex. This regulates renal reabsorption by facilitating sodium reabsorption in the collecting tubule

Biotransformation

the conversion of a drug within the body also known as metabolism. This comes about thru enzymes in the liver that activate/deactivate the drug, transform the drug into a more water-soluble form to promote excretion

Phase 1 reactions

Biotransformation catabolic reactions. (subtractions) These reactions usually require Cytochrome P450

Phase 2 reactions

these reactions require Transferases to transfer whole groups to drug molecules (anabolic) conjugations

first order metabolism

exponential decline on graph, 50% reduction every time, occurs from surplus of enzymes

zero order metabolism

linear decline (slow) until enough drug is metabolized then it goes into first order

factors affecting biotransformation

age, gender, species, illness, drug history (tolerance, meaning that enzymes are induced by prior exposure to drug)

potency

dose necessary to produce a given effect

k1

rate at which drug associates with receptor

k2

rate at which drug dissociates

intrinsic activity

ability of a drug to activate a receptor upon binding

therapeutic index

=TD50 / ED50
If the TI ratio is greater then the drug is safer