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INTRAMUSCULAR AND SUBCUTANENOUS (COMPARE TO ORAL (MACROMOLECULES (not…
INTRAMUSCULAR AND SUBCUTANENOUS
COMPARE TO ORAL
SMALL MOLECULAR WEIGHT
cut off of a small molecule 2000 g/ mol
gentamicin (ex)
water-soluble
ionized
polar bases
MW 449 g/mol
has a hard time absorbed in the GI tract but completely systemically absorbed from an IM
PERFUSION RATE-LIMITED
:arrow_up: blood flow - :arrow_up: drug absorption
characteristic of the capillary wall
the barrier between the interstitial fluid and blood
more loose than the epithelial lining of GI tract
little impedance to movement of drug independent of
pKa
degree of ionization
MW < 2000 g/mole
site of injection
SQ - subarachnoid- brachial plexus-lumbar epidural-caudal-paracervical - intercostal (highest peak)
overall MUCH FASTER THAN ORAL
MACROMOLECULES
not readily cross the capillary membranes in IM and SQ
enter lymphatic capillaries
reach blood via lymphatic system
REASON FOR SLOW AND INCOMPLETE SYSTEMIC AVAILABILITY
SMALL MOLECULE PRECIPITATION AT INJECTION SITE
occurs when
sparingly soluble acid
sparingly soluble base
when drug given in
oil solution
solvent that is rapidly diluted and systemically absorbed
example drug
chlordiazepoxide hydrochloride
sparingly soluble
to achieve high concentration of 50 mg in the injection solution
vehicle must contain
20% propylene glycol
4% polysorbate 80
precipitation because
rise in pH
upon injection, buffer capacity of t
issue and blood
recover at the injection site to pH=7.4
strong acid - weak base,
final pH = 3
absorption of injected water & water-miscible
no space to spread - large mass of drug deposited at the injection site
rate of absorption - dissolution of the precipitated drug
sometimes slow because
4 more items...
stay there for hours or days
oral counterpart is rapidly absorbed
3 more items...
+diazepam characteristic
neutral drug
kept in solution with propylene glycol (glycol)
solvent is rapidly absorbed
precipitation stuck at the injection site
phenytoin sodium injection solutions
sparingly soluble weak acid
STAGES OF DISSOLUTION
SOLID
DISINTEGRATION TO FORM GRANULES
DISINTEGRATION TO FORM FINE PARTICLES
MACROMOLECULE
LYMPHATIC SYSTEM
GENERAL
transport fats
from digestive tract
blood
produce lymphocytes
develop immunity
drain, from interstitial space, protein containing fluid that escapes from from blood capillaries
LYMPHATIC VESSELS
LYMPH CAPILLARIES
terminal capillaries
slightly larger
more permeable than the blood capillaries
occur in all tissues, except
CNS
nonvascular tissue
cornea
lens
cartilage
COLLECTING LYMPHATICS
thinner walls
one-way valves, much more frequent than veins
distance between valves/ diameter of vessel = 10
GENERAL
body contains 500-1000 lymph nodes at various intervals
all lymphs pass thru at least one lymph nodes
some pass thru several
duct that return lymph to blood
thoracic duct
right lymphatic duct
lymph flows much slower than the bloodstream
not enough concentration going into the lymph
macromolecule goes into lymph, travel much slower
MECHANISM OF LYMPH FLOWING
~2L/day
pressure differential
muscular coat in collecting lymph
rhythmic contraction regulated by
transmural distension
humoral mediator
neural stimulation
extrinsic factors
skeletal muscle contractions
breathing
motility of GI tract
FACTORS DETERMINE EXTENT AND DURATION
SMALL MOLECULE MEAN INPUT TIME
delay time
blood flow 0.01 - 0.07 mL/min per mL of tissue
5-40 minutes
slower than IV
faster than oral
slow down blood flow by
vasoconstrictor
adding epinephrine
increase time drug stay at administration site
injection solution with local anesthetic
SQ is slower than IM
depends on
volume injected
IM > SQ for larger volume
slow input b/c
larger volume to surface area ratio
greater distance for diffusion of drug within the injected volume
IM- 5 mL
SQ - 1-2 mL
specific site of administration
MACROMOLECULE/PROTEIN
PROTEOLYTIC ENZYME
break down protein
in the lymphatic system
:ARROW_DOWN: BIOAVAILABILITY
exception of octerotide
100% bioavailability
small protein 1000 g/mole
not go into lymphatic system
go straight into the bloodstream
large protein
proteolytic sensitive protein
RATE
slow because
slower rate movement across the capillary membrane
slow movement of lymphs
movement of interstitial fluid into lymphatic system is 500 times
return of lymph to blood is 5000 times
SLOWER THAN BLOOD FLOW
binding with lymph nodes
ABSORPTION RATE
FLIP FLOP KINETIC
drug measured in plasma
when we compare to IV dose
mean input time
regular macromolecule 5 - 48 hours range
antibody drugs 2-8 days (9000 g/mol)
depends on how much enters via blood capillaries (3000-4000)
how long drug retained in lymph nodes
how long drug retained at the injection site
FACTORS AFFECT ABSORPTION
molecular size
the bigger the size
the longer it stays in the lymph
OVERRIDING FACTOR
site of injection
SQ GENERALLY SLOWER THAN IM
fat is less perfused than muscle
SQ is better injected in the abdomen than the thigh (graph on 49)
Co-administration of albumin
slow down absorption for
IM
SQ
decrease the frequency of drug administration
excersie
rubbing works for both types of administration
increase systemic delivery of drugs
increase C max
decrease T max - absorb faster in less amount of time
depth of injection
injection volume
LONG ACTING PARENTERAL PRODUCTS
available in IM
given IM once a month
IM dosage is 10-20 times oral daily dose of haloperidol lactate
orally - 2-3 times a day
peak earlier than given orally
IM solution is already in solution
go directly into the bloodstream
more permeable into capillaries
haplperidol
first of butyrophenone antipsychotics
tablets
solution for injection
haloperidol decanoate
ester
available as solution in sesame oil for IM
psychotic drug