AMNA MEDANI, 2015DRUG ABSORPTION

IT IS THE RATE AND COMPLETENESS WITH WHICH THE DRUG ENTERS THE BODY FROM THE SITE OF ADMINISTRATION OR THE PASSAGE OF A DRUG FROM ITS SITE OF ADMINISTRATION INTO THE PLASMA.

FACTORS:

-DRUG PHYSICAL AND CHEMICAL PROPERTIES (e.g. DRUG SOLUBILITY IN WATER AND LIPIDS AS A SUSPENTION OR AS SOLID IMPLANTS).

AMNA MEDANI, 2015-ROUTE OF DRUG ADMINISTRATION(e.g.I/V ROUTE IS RAPID AND AT THE SAME TIME IT CAN BE IRRITANT).

 

-THE AMOUNT AND CONDITION OF CONNECTIVE TISSUE AT THE SITE OF S/C AND I/M INJECTIONS.

 

-THE AREA OF ABSORPING SURFACE TO WHICH THE DRUG IS EXPOSED(e.g. LARGE INTESTINAL AND PULMONARY EPITHELIUM).

 

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-THE RATE OF CAPILLARY FLOW (e.g.TRAUMA AT THE INJECTION SITE MAY DECREASE THE RATE OF CAPILLARY FLOW).

 

-THE ACTIVITY OF STOMACH CAN GREATLY INFLUENCE THE RATE OF ABSORPTION (e.g.WHEN EMPTY AND THE DRUG IS GIVEN IN LARGE QUANTITIES).

 

-THE REMOVAL OF CALCIUM IONS (e.g.BY A CHELATING AGENT) FROM THE INTESTINES CAN AFFECT ABSORPTION.

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-PERMEATION THROUGH SKIN VARIES IN DIFFERENT AREAS (e.g.THE UNDER ARM IS A GOOD ABSORPING AREA ,WHERE AS THE DAMAGED SKIN MAY ALLOW FOREIGN SUBSTANCES MORE READILY

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ABSORPTION WITH REGARD TO ROUTE:-SUBLIGUAL ADMINISTRATION:

 

-USEFUL WHEN A RAPID RESPONSE IS REQUIRED AND THE DRUG IS UNSTABLE AT THE GASTRIC pH OR IS RAPIDLY METABOLISED BY THE LIVER (e.g. GLYCEROL TRINITRATE AND ISOPRENALINE). THEY PASS INTO THE BLOOD WITHOUT ENTERING THE LIVER (DRUGS CAN ESCAPE THE FIRST PASS EFFECT . HIGH MOLECULAR WEIGHT DRUGS ARE NOT ABSORPED BY THIS ROUTE e.g. INSULIN AND PEPTIDES.

 

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-ORAL ROUTE:

-USEFUL FOR THE MAJORITY OF DRUGS:

-STOMACH ABSORPT ION : ABSORPTION USUALLY HAPPEN AFTER THE DRUG PASSES THE PYLORIC SPHINCTER (e.g.ALCOHOL AND ASPRIN).

- INTESTINAL ABSORPTION:

I / BY PASSIVE DEFUSION:

-STONG BASES WITH pK 10 OR HIGHER(e.g. MUSCLE RELAXANT TUBOCURINES ARE GIVEN I/V AND HYPOTENSIVE GUANETHIDINE AND SUXAMETHONIUM ARE GIVEN ORALLY) AND STRONG ACIDS WITH pK 3 AND LESS ARE FULLY IONIZED AND HENCE , POORLY ABSORPED.

-OTHER HIGHLY POLAR MOLECULES(e.g.AMINOGLYCOSIDES ANTIBIOTICS) ARE POORLY ABSORPED AND HENCE, GIVEN ORALLY TO STERILIZE THE GUT WITHOUT CAUSING A SYSTEMIC EFFECT.

II/BY CARRIER MEDIATION(e.g. LEVODPA IS TAKEN BY THE CARRIER SYSTEM THAT TRANSPORTS PHENYLALANINE, FLUOROURACIL”CYTOTOXIC” IS TRANSPORTED BY THE SYSTEM THAT CARRIES NATURAL PYRIMIDINE, IRON IS ABSORPED IN ASSOCIATION WITH TRANSFERRIN AND CALCIUM IS ABSORPED BY MEANS OF VITAMIN- D-DEPENDANT CARRIER SYSTEM.

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FACTORS AFFECTING INTESTINAL ABSORPTION:

-GIT MOTILITY IS REDUCED BY DISEASE AND DRUGS LIKE MUSCURINIC RECEPTOR BLOCKERS AND HENCE,REDDUCE THE ENTRIC ABSORPTION .EXCESSIVE MOTILITY OF THE GUT BY A DRUG LIKE METOCLOPRAMIDE MAY ALSO REDUCE ABSORPTION.A DRUG TAKEN AFTER A MEAL IS OFTEN SLOWLY ABSORPED AS ITS PROGRESS TO THE INTESTINE IS DELAYED.

-SPLANCHNIC BLOOD FLOW (TO VISCERA AND INTERNAL ORGANS) IS REDUCED IN HYPOVOLAEMIC STATES LEADING TO DECREASED ABSORPTION(e.g. ADRENORECEPTOR BLOCKING DRUGS LIKE PROPRANOLOL EVEN IF TAKEN AFTER A MEAL).

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-PARTICLE SIZE AND FORMULATION(e.g. PHENACETIN ALTHOUGH RAPIDLY METABOLIZED ,SLOW ABSORPTION MAY REDUCE THE PLASMA PEAK AND DIGOXIN IF TAKEN IN A LARGE PARTICLE SIZE A WEAK PLASMA CONCENTRATION WILL BE ABTAINED, i.e. A SMALL DIFFERENCE IN PHARMACEUTICAL FORMULATION CAN MAKE A LARGE DIFFERENCE IN THE EXTENT OF ABSORPTION. AS WELL, FORMULATIONS LIKE CAPSULES MAY DELAY ABSORPTION OR TABLETS MAY HAVE A RESISTANT COATING TO GIVE THE SAME EFFECT. TO OBTAIN SUSTAINED ABSORPTION A MIXTURE OF SLOW AND FAST RELEASE PARTICLES ARE OBTAINED IN THE SAME CAPSULE.

- CHEMICALLY THE DRUG STATUS IN THE INTESTINE MAY AFFECT ABSORPTION (e.g. TETRACYCLINE BOUND TO CALCIUM IONS AND CALCIUM RICH FOOD MAY PREVENT ITS ABSORPTION AND LIQUID PARAFFIN MAY RETARD THE ABSORPTION OF LIPOPHILIC SUBSTANCES LIKE VITAMIN-K).

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BIOAVAILABILITY: IS THE OVERALL PROPORTION OF THE DRUG THAT PASSES INTO THE SYSTEMIC CIRCULATION AFTER ORAL ADMINISTRATION TAKING INTO ACCOUNT BOTH ABSORPTION AND LOCAL METABOLITE DEGRADATION.IT IS INDIVIDUAL-SPECIFIC AND TIME-IGNORING.

 

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III/RECTAL ADMINISTRATION:

IT IS USED FOR LOCAL DRUGS (e.g. ANTI-INFLAMMATORY DRUGS IN ULCERATIVE COLITIS) OR SYSTEMIC DRUGS BY-PASSING THE LIVER ENTRAL ROUTE(e.g.PROGESTERONE AND TESTESTERONE) OR AVOIDING GASTRIC IRRITATION(e.g.ANTI-INFALMMATORY DRUGS) OR AVOIDING VOMITING.

 

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IV/APPLICATION TO EPITHELIAL SURFACES :

A/CUTANEOUS ADMINISTRATION: ALTHOUGH MOST DRUG BEING WEAKLY LIPID-SOLUBLE , ARE POORLY ABSORPED FROM AN UN-BROKEN SKIN ,A NUMBER OF ORGANOPHOSPHATE INSECTICIDES MAY CAUSE POISONING THROUH SKIN.

 

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B/ TRANSDERMAL: USED IN STICK-ON PLASTERS APPLIED ON AN AREA OF THIN SKIN(e.g. GLYCERYLTRINITRATE(ANGINA), FENTANYL(ANALGESIC),HYOSCINE(SEA SICKNESS), CLONIDINE(ANTIHYPERTENSIVE),OESTROGENS AND ANDROGENS) TO PRODUCE A STEADY RATE OF DELIVARY.THIS APPLIES TO RELITIVELY LIPID-SOLUBLE DRUGS AND IS EXPENSIVE .

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C/NASAL SPRAYS:THESE ARE USED TO REPEATED INJECTIONS AND GIT DESTRUCTION (e.g. VASOPRESSIN PEPTIDE IS RELATED TO THE PITUTARY HORMONE).

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D/ EYE DROPS:THESE ARE ABSORPED THOUGH CONJECTIVAL SAC DUE TO THEIR ADEQUATE LIPID SOLUBILITY(e.g .PHYSOSTIGMINE”A TERTIARY AMINE” OR DYFLOS “AN UN CHARGED ANTICHOLINESTERASE” CAN TREAT GLOUCOMA BETTER THAN A QUATERNARY COMPOUND LIKE NEOSTIGMINE). SYSTEMIC EFFECT AFTER ABSORPTION MAY INCLUDE SIDE EFFECTS .PASSAGE INTO THE NASOLACRIMAL DUCT MAY CAUSE ABSORPTION OR SWALLOWING OF THE DRUG.

 

AMNA MEDANI, 2015V/ ADMINISTRATION BY INHALATION:

THESE DRUGS ARE ADMINISTERED AND ELEMINATED VIA LUNGS WHERE THE LARGE ABSORPING AREA AND THE BLOOD FLOW RAPIDLY ADJUST THE DRUG PLASMA CONCENTRATION(e.g.ANAESTHETIC DRUGS ).

I/DRUGS USED TO AFFECT THE LUNG (e.g. ISOPRENALINE OR SALBUTAMOL”BRONCHODILATORS” TO A ACHIEVE A HIGH CONCENTRATION IN THE LUNG THAN IN OTHER ORGANS.THESE DRUGS MAY REACH THE SYSTEMIC CIRCULATION LEADING TO SIDE EFFECTS(e.g. HYPOTENTION AND CONVULTION IN CASE OF LOCAL ANAESTHETIC SPRAYED INTO THE BRONCHIAL TREE IN PREPARATIONS FOR BRONCHOSCOPY).

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II/CROMOGLYCATE “AN ANTI-ASTHMA DRUG” IS GIVEN BY INHALATION.IT IS WATER INSOLUBLE AND IS INHALED AS A DRY POWDER DISPERSED AS A FINE CLOUD BY AN INHALER.

III/ ENDOTRACHEAL ADMINISTRATION IS USED IN CARDIAC EMERGENCIES FOR RAPID ACCESS TO THE HAERT VIA PULMONARY VIENS(e.g. ATROPINE AND ADRENALINE 10-20 ML VIA ENDOTRACHEAL TUBE).

 

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VI/ ADMINISTRATION BY INJECTION:

A/ I/V ROUTE: IS THE FASTEST AND THE MOST CERTAIN AFTER REACHING THE LUNGS AND THEN THE CIRCULATION. THIS IS AFFECTED BY THE RATE OF INJECTION WHICH SHOULD BE CAUTIOUSLY SLOW,USED USUALLY IN HOSPITAL PATIENTS(e.g. LIGNOCAINE”ANTI-DYSRYTHMIC” ,HEPARIN,CERTAIN ANAESTHTICS,ERGOMETRINE AND DIAZEPAM).

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B/ S/C AND I/M ROUTES:

THESE ROUTES ARE FASTER THAN THE ORAL ROUTE ,BUT THEIR RATE OF ABSORPTION DEPENDS ON THE SITE OF INJECTION AND THE PHYSIOLOGICAL FACTORS(e.g. THE BLOOD FLOW).THE S/C INJECTION RESULTS IN AN ABSORPTION RATE HIGHER THAN THAT OF THE I/M INJECTION. IN BOTH ROUTES, THE DIFFUSTION THROUGH TISSUE CAN BE INCREASED BY HYLURONIDASE ENZYME”INTRACELLULAR MATRIX BREAKING ENZYME”.APPLICATION OF HEAT OR MASSAGE MAY INCREASE THE RATE OF REMOVAL OF THE DRUG BY THE LOCAL BLOOD FLOW”CRITICAL IN PATIENTS WITH PERIPHERAL CIRCULATORY FAILURE”(e.g. MORPHINE IN TRAUMATIC PATIENTS).

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METHODS FOR DELAYING ABSORPTION:

DRUG ABSORPTION MAY BE DELAYED EITHER TO REDUCE ITS SYSTEMIC ACTION IN ORDER TO LOCALIZE ITS EFFECT OR TO ELONGATE ITS TIME OF ABSORPTION BY:

I/ THE ADDITTION OF ADRENALINE OR NORADRENALINE TO A LOCAL ANAESTHETIC REDUCES ITS ABSORPTION, PROLONGS ITS ACTION AND REDUCES ITS BLOOD TOXICITY.

 

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II/THE PRODUCTION OF LOCAL ANAETHESIA TO A WHOLE LIMB (e.g. TO RESET A FRACTURE) BY APPLICATION OF AN ARTERIAL PRESSURE CUFF TO ARREST BLOOD FLOW ,THEN I/V INJECTION OF AN ANAESTHETIC BELOW THE CUFF . THIS WILL WORK UNTILL THE CUFF IS RELEASED.

 

III/ADMINISTRATION OF SLOW RELEASE DRUGS “POORLY SOLUBLE SALTS AND ESTER OR COMPLEX IN AQUEOUS SUSPENTIONS OR OILY SOLUTIONS”(e.g. PROCAINE PEICILLIN ,OESTRADIOL,DEOXYCARTONE AND TESTOSTERONE).

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IV/CHANGE OF THE PHYSICAL PROPERTIES LIKE pH CHANGE (e.g.INSULIN ZINC SUSPENTIONS OF IMMEDIATE AND SUSTAINED RELSEASE.

 

V/STERIOD HORMONES ARE IMPLANTED S/C AS SOLID PELLETS TO ACHIEVE CONTINUIOUS ABSORPTION AT A RATE PROPORTIONAL TO THE SURFACE AREA OF THE IMPLANT (e.g. DEOXYCORTONE ACETATE IN THE TREATMENT OF ADDISON,S DISEASE, TESTOSTERONE AND OESTRADIOL).

 

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INTRATHECAL INJECTION:

THIS IS USED BY INJECTING INTO THE SUBARACHNOID SPACE VIA A LUMBER PUNCTURE FOR ADMINISTRATION OF SOME ANTIBIOTICS IN MENINGITIS AND FOR LOCAL ANATHESIA.