supp 1 Flashcards
the blood supply to the rectum is drained by
1- superior hemmorhoidal veins enters the portal circulation through inferior mesenteric vein
2- the middle and inferior hemmorhoidal enter directly into the general circulation and bypass the liver
suppositiotry
a solid or semisolid mass that is inserted into a body orifice to give a local or systemic therapeutic effect
local
-antiseptic
-anti stringent
-laxative
once a supp is inserted
it melts or dissolves (disperses) into the cavity’s aqueous secretions
(cavity- vagina, rectum, nasal)
melts- fat supp
dissolves- non fat supp
rectum
final section of the large intestine
12 cm
normally empty except for before or during defection
anus
or anal column
its below the rectum
has verticals ridges aka anal columns
4cm
in the walls of the anal canal there are
2 strong flat sheets of muscles:
internal and external sphincters
advantages of supp
-large dosage can be accommodated (the size is the size not like tablets with exits additives)
-rectal route is safe and convenient for everyone
-when administration by mouth is inconvenient
-partially bypasses the liver (FIRST PASS IS AVOIDED)
- high absorption because the rectum is generally empty ex- the adjuvants added have a more pronounced effect in promoting absorption (than in the upper GIT)
-degradative enzymes and pH conditions of the upper GIT are bypassed
-lymphatic circulation helps absorption
-therputic effect could be terminated
give reasons why the mouth is inconvenient sometimes
inconvenient for oral drugs due to
-gastric bleeding
-disease of upper GIT
-unpleasant taste
-acid or base or enzyme labile drug
better taken rectally bc rectum is neutral
disadvantages of supp
-not preferred by patients
-some supp leak or are expelled after insertion
-rectal absorption of drugs can be erratic and unpredictable
-bioavailability is limited
why is the bioavailability of supp sometimes limited
because of many factors such as:
-The rectal absorption site shows a minor absorption area
-lack of active drug transporters
-very limited fluid volume for dissolving the drug
-uncontrolled defecation
the drug release is ____ and depend on
is variable.
-properties of the drug
-properties of supp base
-physiological state of the colon
-the environment of the rectum.
describe the process of supp after administration and the obstacles that can be faced
1- after insertion, base must melt or dissolve for drug to be released
2- then the drug is released as ions or molecules in rectal fluids
3- drug must dissolve in limited rectal fluids (2-3 ml)
( ONE obstacle at this point is that available drug can be reduced thru degradation by luminal content )
4- the drug must diffuse through nonmotile, unstirred rectum to absorption membrane
5- unionized high conc drug is transported across rectal mucosa via simple passive diffusion
what is an obstacle that can be faced after drug diffuses across absorption membrane (rectal mucosa) ?
IF THE DRUG is delivered to the upper part of the rectum thus transported to the portal system
(undergoes first pass metabolism (liver metabolism) )
this can be avoided if drug is delivered to the lower part of the rectum (general circulation)
physiological state of the colon/ rectum factors that can affect drug release
1- colonic content
- absorption is greater with empty/void rectum
-bc rate and degree of absorption can be effected if there was colonic obstruction/ diarrhea
2- circulation route
-lower hemorrhoidal veins in colon and rectum enter inferior vena cava, bypassing liver
-lymphatic circulation assisting absorption
3- pH and lack of buffering capacity of the rectum fluids
-neutral pH (7.2)
-the nature of the drug whether its acidic or basic can effect the environment of the rectum , turn it to basic or acidic depending on drug nature
physiochemical factors
1- solubility
-in water and vehicle (base), there has to be a portioning coefficient btw the two.
-the rectal fluids are aqueous, so if drug is fat soluble then the drug release process will be slow , and vice versa
2-amount of the drug
-the higher the conc , the higher absorption, therefore more bioavailability (passive diffusion)
3- surface properties
-improve wetting btw drug and absorption membrane , required for drug dissolution
-use surfactants
4- particle size
smaller particles:
-have higher surface area therefore higher dissolution rate (solubility)
-have less sedimentation (directly prop with sed velocity)
-less irritation
5- surfactant
-absorption enhancers
-low conc of surfactants accelerate drug absorption due to accelerating drug release from lipid base to absorption membrane
what is the effect of surfactant conc on drug absorption
the conc should be low
bc high conc may entrap the drug in the micelles and reduce rate of absorption
nature of the base/vehicle
must be capable of dissolving , softening or melting
base must retain or release the drug
what are some ways in which the base could be irritating to the mucous membrane
- initiate bowel movement
-hygroscopic bases can absorb water in surrounding environment and cause irritation
will affect time of absorption
criteria for good supp bases
1-remains firm at room temp
-melts at body temp (37C) /dissolves rapidly in rectum fluids
2-The difference between melting and solidification points should be small
ex if it melts at 37, should solidify at 36 or 35
3- be inert and compatible with drugs
4- stable on storage , shrinks sufficiently on cooling to be easily removed from the mold
(less volume , high sp gravity=density)
5- have high water number and wetting and emulsify ing properties
6- fatty base has acid value less than 0.2 and iodine value less than 7
