Exam 2- Physiology of a Primer Flashcards
Pharmacology
study of substances used to prevent, diagnose, and treat disease
Toxicology
study of undesirable effects on living systems
Pharmacodynamics
what the drugs does to the body
Ex: Potency, Efficacy and Receptor/Drug Interactions
Pharmacokinetics
what the body does to the drug
Ex: ADME
What are the goals of drug therapy
- get the drug into the body
- reach the target organ
- stay at the site of action long enough to have a therapeutic effect
- cause no harm
Routes of administration
enteral vs. parenteral
Enteral
administration via the GI tract
Ex: Oral, rectal
Parenteral
administer by routes other than the GI tract
Ex: Intravenous (IV)- vein, arteries, heart, joints, skeletal muscles
Absorption
the process by which a drug reaches the circulation
- Primary organ: small intestine for oral route because of the large surface area for contact w drug
Metabolism
alternation or breakdown of drugs
- Primary organ: liver
- because many enzymes that can break down drugs
Distribution
movement of drugs throughout the body
- Primary organ: heart
- pumps blood throughout the body
Excretion
- removal of drugs from the body
-Primary organ: kidney
Many drugs are water soluble and readily pass into urine
Oral administration
passes through the liver before reaching systemic circulation
First pass metabolism
inactivation of a drug that occurs before it reaches the systemic circulation
Passage of taking a drug orally through the body
- Mouth -> esophagus -> stomach-> small intestine -> large intestine -> rectum -> (all lead to liver through portal vein) -> finally it reaches systemic circulation
The rectum can go straight to systemic circulation
3 Parts of small intestine
Ileum, duodenum, jejunum
What kind of cells are in the small intestine
enterocytes, polarized cells and some metabolic capacity
What increases absorption in the small intestine
a single layer of epithelial cells and lots of surface area (villi and microvilli) which increases absorption
- lots of blood flow supplied by the mesenteric artery
Intravascular
within the blood vessels
Blood is made up of
plasma + blood cells
Plasma is
the fluid between RBCs and WBCs in the blood
Intracellular fluid
fluid within the RBCs and WBCs
Extravascular
outside of blood vessels
Interstitial fluid
fluid between tissue cells in the extravascular space
Intracellular fluid
fluid within tissue cells
Cardiovascular system
- involved in distribution
- Blood: RBCs, WBCs, platelets, plasma
- carries oxygen and nutrients to body (tissues)
- oxygenated blood is pumped away from the heart (arteries)
- carries CO2 and wastes from the body (tissues)
Distribution: Lymphatic system
- circulatory and immune system
- open system, slower flowing-not pressurized
- spleen, bone marrow, lymph nodes, thymus
- connected by lymph vessels
Two major cardiovascular circulatory systems
Systemic and pulmonary systems
What feeds into the liver?
portal vein and hepatic artery
What empties into the hepatic vein
the central vein from the liver
How do we reach the target of interest?
Perfusion, Permeability, Size-Exclusion, Concentration, Surface Area, Contact Time
Perfusion
Pertains to blood flow to a tissue
- Poorly perfused (muscle, skin, bone and fat are slowest)
- Richly perfused (heart, kidney, liver)
Size Exclusion
Processed by the kidney. Small particles will go into urine. Larger proteins/particles will stay in blood. (if this gets into the urine then it’s an issue)
Blood brain barrier
Permeability limited, but not perfusion limited
Rectal Drug Delivery
can be first pass or directly depending on the position where it’s inserted
How does the drug reach the liver
Portal circulation via the portal vein
Arteries
away from the heart
- carries oxygenated blood except for pulmonary artery
What happens in the veins in the cardiovascular system?
Carries CO2 and wastes from tissues
- carries deoxygenated blood to the heart
The hepatic vein empties into
the inferior vena cava
portal vein-> central vein from liver -> hepatic vein-> inferior vena cava
Blood from the upper torso enters the
superior vena cava
Deoxygenated blood passes through
the pulmonary artery to the lungs
Oxygenated blood leaves the lungs
via the pulmonary vein
Blood enters the kidney though
the renal artery
Blood leaves the kidneys
through the renal vein
Liver is aka
Primary fctn
hepatic
Primary function- break down drugs between GI tact and systemic circulation
Lots of blood flow
Primary function of liver
serves to breakdown drugs between blood from GI tract and system circulation
Portal triad
- Hepatic artery (Blood inlet: 20% flow)
- Portal vein (80% flow)
- Common bile duct (Outlet for bile)
Livers primary cell type
Hepatocytes
Sinusoids
large capillaries between rows or hepatocytes
All drugs will eventually pass through
the liver
Lymph
Recycling of used interstitial fluid to blood
Enterohepatic cycling
A drug enters the liver via the portal vein and then is returned to the small intestine in the bile via the gall bladder
- or its reabsorbed into portal circulation
- Distributed to systemic circulation via the central vein
Kidney aka
renal
Primary functions of kindey
- remove waste
- controls fluid balance
- regulates the balance of electrolytes
lots of blood flow
Kidney processes a lot of fluid
- 173 L water per day via renal artery
- 171-172 L water per day returned to body via renal vein
- 1-2 L excreted as urine
Excretion by the kidney is regulated by 3 processes
- Filtration
- Secretion
- Reabsorption
Removal of wastes happens how
Glomerular filtration and tubular secretion
Re-uptake of nutrients/ drugs
Reabsorption
What processes are passive transport?
Filtration and Reaborption
What processes are facilitated transport?
Secretion
Filtration happens in
Drug Protein binding
the glomerulus
Only free drug
Secretion happens in
the proximal tubule
Drug protein binding- Some effect
Reabsorption happens in
the distal tubule
Drug protein binding - not applicable so not no effect
Direction of blood flow from the heart
Aorta Arteries Arterioles Capillaries Venules Veins Vena Cava
Which parts of blood flow is oxygenated and deoxygenated
- Aorta, arteries, arterioles are oxygenated
- Venules, veins and vena cava are deoxygenated
- Capillaries are where the exchange of oxygenated and deoxygenated blood happens
To get from the intravascular to extravascular space, a drug must pass through what?
capillary endothelial barrier
What does the vascular endothelial layer do
it lines the interior surface of all the blood vessels in the circulatory system
Endothelial cell characteristics
- porous to ionized/ non- ionized species <600 Da
- not porous to plasma proteins
- some exchange through vesicle formation
- permeability is location dependent
Lipid soluble substances pass through what?
endothelial cells
Small water- soluble substances pass through what?
pores
Plasma proteins cant passes
capillary wall
Exchangeable proteins are moved across
by vascular transport
Capillary endothelial barrier characteristics
- leaky
- easy passage of molecules from vascular lumen into extravascular space
What are some more permeability limited barriers?
- cell membrane barrier
- blood brain barrier
- blood-CSF barrier
- blood-placental barrier
- blood-testes barrier
Cytosol
fluid compartment of the cell
Cytoskeleton
helps to maintain cell shape and structure
Lysosomes
intracellular digestion
Ribosomes
protein synthesis
Endoplasmic reticulum
smooth- lipid synthesis
rough- protein synthesis
Golgi apparatus
folding and transport of proteins
Small molecule drugs target
intra or extracellular targets
- If intracellular, the drug not only has to get to the organ, but also into the cell and possibly to a specific organelle
Large molecule drugs tarrget
extracellular targets
Different types of molecules are used as drugs such as:
Calcium, CaCO3, TUMS
Lithium, Li2CO3, Lithobid
Xenobiotic
a chemical that is not synthesized within the body
Toxins
poisons of biological origin
bacterial, animal or plant
What happens if we increase the dose,
we increase the plasma concentration
Drug-Receptor Interactions
- The drug must have the appropriate size, shape, charge and atomic composition to interact with its intended receptor
Most drug targets are
proteins
- ion channels, enzymes, receptors, transporters
