1 - Administration / Absorption / Distribution Flashcards
These cannot act at target sites, nor can they be metabolized. This affects 3 aspects of drug action:
Drug molecules that are bound to inactive depots, including plasma proteins.
- onset
- duration
- magnitude
Movement of the drug from the site of administration to the blood circulation. Some is taken in by stomach, but most drugs not fully taken in until they reach small intestine.
Absorption
A drug rarely acts where it contacts the body. Process by which drug must pass through variety of cell membranes to enter blood plasma, which transports it to virtually all of the cells in body.
Absorption and Distribution
Absorption is dependent on (4)
MISI
- MOA (movement to circulation influenced by factors like type of/food in stomach, physical activity, etc.
- ionizatoin of the drug
- solubility
- individual differences in age, sex, and body size
Acid / Base and Drug Absorption
Substances most fat-soluble (least ionized) absorb in solutions with pH most like their own
* Feces is a bit basic
Once in blood plasma, some drug molecules move to tissues for ___ to active target sites/receptors. While in the blood, a drug may also attach to plasma proteins (called ___ ___ ) or may be stored temporarily in bone or fat, where it remain inactive.
Binding | Depot Binding
The amount of drug in the blood that is free to bind at specific target sites to elicit drug action.
Bioavailability
This limits drug concentration in the CNS. It is formed by specialized capilaries that have few pores to allow drugs to leave the circulation.
Blood Brain Barrier
Drug Absorption Factors (5)
- Lipid bilayers (phospholipid membranes) keep charged (ionized) molecules out of the cell and allow fat-soluble (non-ionized) substances into cells (passive diffusion)
- Concentration gradient determines the rate of diffusion into cells
- Simple diffusion is how cells “breathe” (oxygen in, carbon dioxide out)
- Rate of passage through cell walls — More/faster movement to where there is less of the substance
- Drug redistribution: As plasma levels fall, drug concentration in highly vascularized organs will be greater than in the blood, so the drug will move from those organs back into the plasma to maintain equilibrium.
Drug Action
Molecular changes produced by a drug when it binds to a target site or receptor.
*The site of drug action may be different from the site of the drug’s effects.
Methods of Administration (8)
SORT IIII
- Subcutaneous (popping)
- Oral (subject to First Pass Metabolism)
- Rectal (Low in rectum / hemorrhoidal vein skips first pass metabolism)
- Transdermal
- Intramuscular
- Intravenous
- Inhalation
- Intranasal (bypasses blood-brain barrier; e.g., powder cocaine)
Drug Effects
The alterations of physiological or psychological functions caused by those molecular changes.
*The site of drug action may be different from the site of the drug’s effects.
Oral and rectal routes of administration are ________ because they involve the gastrointestical tract; all other methods are called ________
Enteral | Parenteral
Used when spinal anesthetics are administered directly into the cerebrospinal fluid surrounding the spinal cord of a mother during childbirth, bypassing the blood–brain barrier.
Epidural Injection
Interacting pharmacokinetic factors that determine free drug quantity in blood (5)
- Method of administration,
- Rate of absorption and distrubution,
- Binding at inactive sties,
- Biotransformation/Metabolism
- Excretion
Implanted under skin of scalp and programmed to deliver constant dose of antibiotic into cerebral ventricle. Permits treatment of brain infection and useful because antibiotics are normally prevented from passing blood–brain barrier.
Infusion Pump
Injected directly into the cerebrospinal fluid–filled ventricles. Experimenters can study electrophysiological, biochemical, or behavioural effects of drugs on particular nerve cell groups.
Intracerebro-Ventricular Injection
A microsyringe or a cannula enables precise drug injection into discrete areas of brain tissue.
Intracranial Injection
Alternative to IV injection; provides slower more even absorption over time. Can be slowed by combining drug with 2nd drug that constricts blood vessels. Slower sustained action by injecting drug in suspension of vegetable oil.
Intramuscular Injection (IM)
Drug injected through abdominal wall into peritoneal cavity around organs. Rapid effects but not as rapid as IV injection. Variability in absorption, depending on whereexactly drug is placed.
Intraperitoneal Injection (IP)
Most rapid, accurate method of drug administration. A precise quantity of agent is placed directly into blood and passage through cell membranes such as stomach wall is eliminated. Quick onset of drug effect is a potential hazard since drug cannot be removed from body (as with stomach pumping).
Intravenous (IV)
Only these drugs can readily enter the brain.
Lipid Soluble
Drugs with high lipid solubility (not ionized) move through cell membranes by passive diffusion, leaving the water in the blood or stomach juices and entering lipid layers of membranes.
Lipid-Soluble Drugs
Method of Aministration influences absorption because (3)
- determines the area of the absorbing surface,
- number of cell layers through which the drug must pass,
- extent to whcih first-pass metabolism affects drug
Each method of administration provides advantages and disadvantages involving (6)
- rate of onset,
- level of drug acheived in blood
- duration of action
- convenience
- safety
- special uses
Pharmacokinetic factors determing drug action & bioavailability (5)
- Administration: drug moves through cell membranes into blood
- Absorption and Distribution; circulates to all cells in body.
- Binding: Some drug molecules may bind to active target sites (receptor). May also bind to inactive sites such as plasma proteins or storage depots (depot binding) or stored temporarily in fat or bone (inactive). Blood-borne drug molecules also enter liver for…
- Inactivation (biotransformation), (primarily a result of metabolic process) where they may be transformed into metabolites and travel to kidneys and other discharge sites for excretion. Inactivation influences both intensity and duration of drug effects.
- Excretion in feces, urine, water vapour, sweat, and saliva.
the pH value of a solution that would maintain ionization of half of the molecules of a drug
Aspirin = ______
pKa Value
pKa of Aspirin = 3.5 (50% ionized and 50% non-ionized)
Separatees maternal circulation from fetal circulation but does not impeded passage of most drug molecules.
Placental Barrier
Drug-filled suppository placed in rectum to dissolve. Depending on placement, drug absorbed from lower rectum into hemorrhoidal vein may bypass First Pass Metabolism. Deeper placement absorbed by veins drains to portal vein, then to liver. Bioavailability difficult to predict and absorption is irregular. Effective route for infants and those vomiting, unconscious, or unable to take orally.
Rectal Administration
Route of administration determines (2)
- Onset
- Duration of Drug Action
How and where a drug is administered. Determines how quickly and how completely it is absorbed into blood.
Route of Administration
Drug injected below skin and absorption dependent on blood flow to site. Absorption usually slow/steady but variability occurs. Rubbing skin dilates blood vessels and increases rate of absorption. Injection of a drug in a nonaqueous solution (peanut oil) or implantation of a drug pellet further slows rate of absorption.
Subcutaneous (SC)
Application involves placing drug under tongue, where it contacts mucous membrane and is absorbed rapidly into a rich capillary network. It is not broken down by gastric acid / enzymes. Absorption is directly into blood and not dependent on how quick stomach empties into small intestine. Not absorbed from the GI tract and avoids First-Pass Metabolism.
Sublingual (topical)
Involves application to nasal mucosa (mucous membrane) by sniffing powder or nasal spray. Drug moves rapidly across a single epithelial cell layer into bloodstream, avoiding First-Pass Metabolism and producing higher bioavailability than if taken orally.
Intranasal (topical)
Drug rapidly absorbed into blood by passing through lungs. Pulmonary absorbing surface is large and rich with capillaries. Effect on brain very rapid because blood from capillaries of lungs travels a short distance back to heart before being pumped quickly to brain via carotid artery. Preferred method for self-administration when oral absorption is slow. Avoids destruction of drug in GI tract.
Inhalation (topical)
Patches provide controlled and sustained delivery of drug by absorption through skin at a preprogrammed rate. Reduces danger of needle sticks / unsafe used needle disposal. Used for motion sickness (scopolamine), cigarette craving (nicotine), angina pectoris (nitroglycerin), and hormones after menopause or for contraception. Limited drugs work via this method because skin is designed to keep things out.
Transdermal
A _____ is a delivery system used to carry a gene into the nuclei of target cell in order to alter protein synthesis. They are usually injected directly into the brain region targeted for modification.
A _____ _____ is often considered because of their special ability to bind to and enter cells / nuclei but this process may carry risks.
Vector | Viral Vector
Volume of blood flow to the tissue…
affects Drug distribution
Drugs that are weak acids tend to remain ___ ___ or ___ ___ in acidic body fluids such as stomach juices. They are more readily absorbed there than in the more ___ intestinal fluid.
Non-Ionized or Lipid Soluble | Alkaline
Drugs that are weak bases are more ___ in acidic body fluids such as stomach juices. They are less readily absorved there than in the intestine, which is more ____ and where ___ is reduced.
Ionized | Basic | Ionization
