Prescriptions and pharmacokinetics
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Dispensing drug label (12)
- 1. hospital name, address, phone #
- 2. DVM name
- 3. Client name
- 4. animal name, species, ID #
- 5. date
- 6. Drug name (trade and generic)
- 7. dosage strength
- 8. number of units dispensed
- 9. directions for use
- 10. manufacturer's expiration
- 11. precautions
- 12. prescription expiration date
- an order for a medication, therapy or therapeutic device given by an authorized person.
- Legal document, order to a pharmacist.
Prescription must contain (10)
- 1. DVM name, address, phone #
- 2. client name and address
- 3. animal name and species
- 4. date
- 5. name of drug
- 6. dosage strength
- 7. directions to pharmacist
- 8. directions to client
- 9. # refills permitted
- 10. precautions
- Route of administration
Route of administration
How the drug is introduced into the body.
via some part of alimentary canal (oral, buccal/transmucosal, rectal)
factors that influence route of admin (5)
- available form
- is it irritating, etc.
- rate of onset of action
- behavior of patient
- nature of condition
factors that influence GI absorption (6)
- pH (must closely match where absorbed)
- fat/water solubility
- size and shape of molecule
- presence or absence of food
- degree of GI motility
- presence and nature of disease
- cheap, convenient
- distasteful, patient must be conscious, capable of swallowing, not vomiting, cats are hard to pill
- dry swallowing may cause esophagitis and stricture formation (Doxy)
- Any route other than via alimentary canal
- Usually by injection
Routes of parental administration
IV, IM, SQ, ID, IP, intraarterial (IA), Intraarticular, IC, intramedullary (IO), epidural, subdural
injectable administration + and -
- +: total absorption, rapid absorption, rapid effect
- -: shortest duration, painful, can't be used at home, requires restraint, sterile equipment and skill.
- inject slow, so you can stop. Some cause death if too fast
- irritating agents IV only
- oil-based drugs, suspensions and milky-looking drugs not given IV
IM injections given at __________ angle
- goes into interstitial fluid, absorbed into capillaries.
- Aqueous agents, rapid absorption, rapid effect.
- Can use repository/depot preparations
formulated to release a sustained dose of drug that is absorbed into bloodstream over an extended time period
SQ administration given at ___________ angle
slower to act, longer duration. Never use irritating substances if possible. Avoid hyperosmotic (won't absorb)
injection into skin, allergy skin testing mostly
into abdominal cavity. Rarely used in clinical medicine due to possible infection, puncture of organs, adhesion on abdominal organs.
- rare clinically, plunger will pull back on its own.
- In horses, can shoot into carotid, go right into brain. Fatal drug dose in brain.
- into joint. Rare in clinical medicine. Joint taps for diagnosis or local block in equine for lameness.
only life-threatening due to possibility of lung puncture, pericardial adhesion, pericarditis. Also, in cardiac arrest in heart doesn't help, want in circulation.
- proximal humerus, proximal tibia, trochanteric fossa of femur, wing of ilium (ilial crest).
- Tiny patients, when you can't get a catheter. STERILE
between L7 and SI vertebrae, epidural space between ligamentum flavum and dura mater.
subdural. past epidural into subarachnoid space.
- absorbed through mucus membranes of respiratory tract and alveolar membranes.
- Potential to move into pulmonary capillaries.
Intratracheal administration (IT) (NAVEL)
- absorbed through mucous membranes of respiratory tract and alveolar membranes. Double dose, + 3-5 ml sterile water, catheter in intratracheal tube, put in to carina, follow with two breaths.
- Drugs that can go this way are NAVEL (Naloxone, Atropine, Vasopressin, Epinephrine, Lidocane.
application on skin, mucous membranes, eyes, ears. Local effect.
- application on skin for systemic circulation.
- Vehicle must penetrate epidermis.
- Disadvantages (risk of local inflammation, ingestion during grooming, owner must avoid, absorption variable)
- the movement of drug from its site of administration into the blood circulation
- depends on route, usually faster the greater the blood supply.
Routes that end up with 100% absorption
- Intraveinous, Intracardiac, Intraarterial, Introosseus
- slow--intramuscular, subcutaneous (via interstitial fluid)
Three ways for drug to get into capillaries through passive transport.
- 1. lipid-soluble substances diffuse across endothelial cells
- 2. small, water-soluble substances pass through pores
- 3. pinocytosis (vesicles break off from membrane).
- Active--electrolytes. Use the pores but uphill, so uses energy.
Method of absorption depends on
- water or lipid soluble (partition coefficient)
- size and shape of molecule
- degree of ionization of molecule (can depend on pH. Same diffuses readily, opposite becomes trapped
factors influencing absorption
- lipid-solubility of drug in body fluid (higher partition coefficient=higher solubility=faster absorption)
- total surface area for absorption (largest space is small intestine)
- contact time at site of absorption (GI motility)
- blood flow to absorption site (higher=higher)
- fraction of unchanged drug reaching systemic circulation following its administration.
- 100% (IM, SQ, IV, etc.)
factors influencing bioavailability
- cell membrane/lipid solubility
- first pass biotransformation
- chemical stability
- nature of drug formation/vehicle
- degree of GI motility/stomach emptying time
- inflammation of mucosa/damage to villi
- amount of composition of food
- altered microorganisms
- when liver metabolizes drug, leaves metabolites.
- Baytril very little, morphine, lidocaine, buprenorphine, a LOT. Some go through not at all.
Two drugs show same plasma concentration at same dose. FDA only requires that.
process by which drug leaves sytemic circulation and reaches its site of action in ISF or ICF (interstitial or intracellular)
major factors determining drug distribution
blood flow to tissues, concentration gradient, capillary permeability/lipid-solubility of drug, plasma-protein binding, barriers, disease processes
how pH effects absorption/distribution
a base in acidic medium will ionize, picks up an H+, then can't absorb. When it gets into intestines which have basic pH, loses the H+, absorbs.
- endothelial cells of capillary wall with tight junctions, no pores, a thick membrane. Has astocytes with astocytic end feet that provide biochemical support of barrier.
- small lipids can diffuse, specific proteins carry special molecules like glucose.
- P-glycoproteins also eject unwanted metabolites
Cells around capillaries in blood-brain barrier. Astrocytic end feet provide biochemical support of barrier.
specific transporter found in brain capillary endothelial cells needed to pump many drugs and toxins out of brain tissue
distribution into CNS
- lipid-solubility important. Some water-soluble might penetrate CNS.
- Specific uptake transporters that normally transport nutrients and endogenous compounds into brain and cerebrospinal fluid
MDR1 gene mutation
3 out of 4 collies have mutant multi-drug resistance gene, which makes p-glycoprotein. Can't pump some drugs out of brain. (washington state found)
Drugs that cause a problem with MDR1
Ivermectin, milbemycin, acepromazine, loperamide (immodium) and others.
- some drugs reversibly bind to plasma proteins, drug exists in both bound and free forms, extent variable
- when bound, drug is pharmacologically inactive (too big to leave capillaries, can't even do job in capillaries).
- After leaving site of action some drugs accumulate in tissues (don't continue to work inside tissues)
- Then slowly released into circulation, plasma levels of drug are too low to produce a pharmacological effect
- Usually in fat, muscle, bone and kidneys
- Thiopental redistributes to fat
- process by which chemical reactions carried out by the body convert a drug into a compound that is different from the originally administered drug (metabolite)
- Usually to make lipid-soluble substances more water-soluble so they can be more easily eliminated.
Sources of biotransformation
- liver (almost always)
- GI tract mucosa
- nasal mucosa
Reactions of phase I of biotransformation
- Oxidation (loss of electrons), Reduction (gain of electrons), Hydrolysis (splitting of parent compound molecule with water molecules), alcohol dehydrogenation
- catalyzed by enzymes called microsomal oxidases or cytochrome P450 enzymes in hepatocytes.
- can increase, decrease or not change pharacological activity
biotransformations, phase II
- Conjugation reactions, drug joined to body molecule
- makes water-soluble
- may be BEFORE OR AFTER phase I
- drug + glucuronic acid (glucuronyl transferase) --> "drug" glucuronide
- Cats are bad at this, why they die from Tylenol
factors influencing biotransformation
- age (very young or old)
- species (glucuronidation in cats)
- liver disease
- process by which drugs or their metabolites are removed from the body to the outside environment
- Routes include renal (urine), hepatic (biliary, defecation), lungs, mammary glands (milk), sweat, saliva
Lipid soluble drugs are excreted
by hepatic/biliary, goes into feces
water-soluble drugs are excreted
through the renal system into urine
2 ways kidney excretes drugs
- 1. passively through glomerulus, may get reabsorbed
- 2. active transport into lumen at proximal tubule
amount of time it takes for the plasma concentration of drug in the body to be reduced by half
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