Absorption Routes of Administration PDF

Absorption  routes of administration By rida jamil  Different Oral ways a Sublingual or buccal (drug stayed connected with oral mucosa) drug can Rectal be Application to other epithelial surfaces (skin, vagina and nasa...

Absorption  routes of administration By rida jamil  Different Oral ways a Sublingual or buccal (drug stayed connected with oral mucosa) drug can Rectal be Application to other epithelial surfaces (skin, vagina and nasal mucosa) administere Inhalation d? Injection Subcutaneous Intramuscular Intravenous Intrathecal Intravitreal  Most small drugs are taken orally Absorption begins in the small intestine Non-polar drugs are absorbed directly in the mouth (e.g. buccal mucosa or under the tongue) Examples: organic nitrates, buprenorphine Peptides and proteins are digested in the GI tract Not suitable for biopharmaceuticals Pharmaceutical methods to address these issues have limited Oral success Drug absorption occurs through passive transfer across the administrat epithelial barriers Absorption rate is determined by drug ionisation and lipid ion solubility Strong acids and bases cannot be absorbed by GI tract because they are in full ionisation Intestinal drug absorption can involve carrier mediated transport Levodopa uses carrier for phenylalanine Fluorouracil (cytotoxic drug) uses carrier for pyrimidines (thymine & uracil) Iron absorption via specific carriers in the jejunal mucosa epithelial cell membranes Calcium absorption is facilitated by vitamin-D-dependent carrier  75% of orally administered drugs are absorbed within 1-3 hrs Factors influencing drug absorption are Gut content (fed vs. fasted) GI motility Splanchnic blood flow Particle size & drug formulation Physiochemical factors & drug-drug interactions Genetic polymorphisms and drug competition for transporters Feeding affects gut content, splanchnic blood flow, influencing T max and C max Factors that GI motility impacts absorption; disorders like migraine & diabetic neuropathy slow absorption due to gastric stasis affect GI Muscarinic receptors blockers reduce motility *e.g. Metoclopramide increases motility to facilitate drug absorption* Diarrhoea can impair drug absorption absorption Splanchnic flow reduced by exercise, hypovolaemia & heart failure Particle size (e.g. Digoxin plasma concentrations varied due to different tablet formulations) Therapeutic drug formulations aim to achieve desired absorption characteristics: Capsules/tablets may delay absorption or mix-slow- and fast release particles Modified-release preparations reduce dosing frequency and adverse effects from high peak plasma concentrations Some drugs are intended for local effect in the gut rather than systemic absorption: Vancomycin for Clostridium difficile in pseudomembranous colitis Mesalazine for inflammatory bowel diseases w/ pH-dependent coating for targeted disease (Crohn’s disease) Olsalazine (pro-drug) for distal colitis, cleaved by colonic bacteria  Oral drugs must penetrate intestinal mucosa and survive presystemic/ first-pass metabolism by gut wall and liver enzymes Bioavailability (F) indicates the fraction of orally administered dose reaching systemic circulation as intact drug F considers both absorption and local metabolic degradation Bioavailabili Measurement of F involves comparing plasma drug concentration vs. time curves after oral & intravenous ty and administration AUC (area under the curve) provides an integrated Bioequivale measure of drug exposure nce F is estimated as AUC oral/ AUC intravenous Bioavailability is influenced by: Enzyme activity in the gut wall or liver Gastric pH Intestinal motility Bioavailability varies among individuals under different conditions & reflects total drug reaching systemic circulation, NOT RATE OF ABSORPTION Rate of absorption affects peak plasma concentration & drug effect  Absorption from oral cavity is useful for rapid response and for drugs unstable at gastric pH or rapidly metabolized by the liver Examples of sublingual administration: Glyceryl trinitrate (for rapid response) Buprenorphine Sublingual or Buccal midazolam is effective and safe for terminating early status epilepticus Buccal in children, comparable to intravenous or rectal diazepam administration Reduces time to drug administration and seizure cessation in emergency settings Easier to administer Drugs absorbed from the mouth enter the systemic circulation directly, bypassing the portal system and first- pass metabolism by gut wall and liver enzymes  Mainly used for local effects and systemic effects Local effects (e.g. mesalazine suppositories/enemas for ulcerative colitis) Absorption characteristics: Can be rapid and more complete than oral administration May be unreliable Rectal Only a fraction of the drug enters systemic administrat circulation via the portal vein Situational use: ion Useful for patients unable to take medication orally (e.g. vomiting, post-surgery, palliative surgery) Adoption: Despite potential benefits of rectal administration, it is not widely adopted Examples of underutilised suppositories: ergotamine-containing suppositories for migraines, gastric stasis and vomiting limit oral tablet effectiveness Application to epithelial surfaces Cutaneous administration Nasal sprays Eye drops  Used for local skin effects (e.g. anti-inflammatory gels like ibuprofen) Can lead to systemic effects through absorption Absorption through unbroken skin: Most drugs are poorly absorbed Some substances, like organophosphate insecticides, are well- absorbed and can cause poisoning Historical case: Cutaneous 1932, a florist experienced nicotine poisoning from nicotine solution (Nico-Fume liquid) absorbed through skin contact administrat Symptoms include nausea, faintness, sweating and unconsciousness ion Incident repeated when he wore the same contaminated clothes, leading to lasting sensitivity to nicotine Transdermal dosage forms: Skin on patches for steady drug delivery & avoiding presystemic metabolism Examples; Nicotine patches for smoking cessation Oestrogen and testosterone patches for hormone replacement Fentanyl patches for breakthrough pain Suitable for lipid soluble drugs Relatively expensive  Peptide hormone analogues administered as nasal sprays include: Antidiuretic hormone Gonadotrophin-releasing hormone Calcitonin Absorption: Occurs through mucosa overlying nasal-associated Nasal lymphoid tissue Like absorption through mucosa overlying Peyer’s sprays and patches in the small intestine, which is also unusually permeable eye drops Eye drops used for drug delivery through the conjunctival sac epithelium Local effects within eye are achieved, minimizing side-effects Example: Dorzolamide (carbonic anhydrase inhibitor) lowers ocular pressure in glaucoma without causing kidney-related acidosis Systemic absorption from eye drops can cause unwanted effects Example: Timolol eye drops for glaucoma can cause bronchospasm in asthmatic patients  This technique is used for volatile and gaseous anaesthetics, alongside drugs affecting the lungs Anaesthetics: Lung serves as route of administration and elimination Rapid exchange due to large SA and blood flow allow rapid adjustments of plasma concentration Drugs for lung effects: Administrat Administered as aerosol mist of liquid droplets or solid particles ion by Examples: glucocorticoids (e.g. beclomethasone dipropionate) and bronchodilators (e.g. salbutamol, inhalation formoterol) Objective: Achieve high local concentrations in the lung while minimizing systemic effects Partial absorption into circulation can occur, leading to systemic side-effects (e.g. tremor with salbutamol) Chemical modification of drugs can minimise absorption Example: Ipratropium, quaternary ammonium ion analogue of atropine, used as an inhaled bronchodilator with poor absorption, prolonging local action and reduces systemic adverse effects Administration by injection Intravenous injection: Fastest and most certain route of drug administration Bolus injection produces rapid, high drug concentration Initially right heart and pulmonary vessels Then in systemic circulation Peak tissue concentration depends on the injection rate Intravenous infusion: Administered using mechanical pump Avoids absorption uncertainties from other sites Prevents high peak plasma concentrations seen with bolus injection Subcutaneous or intramuscular absorption: Faster effect than oral administration Rate of absorption is influence by: Injection site Local blood flow Rate limiting factors in absorption: Diffusion through tissue Removal by local blood flow Factors affecting absorption: Increased blood flow enhances absorption Hyaluronidase increases drug absorption by breaking down intracellular matrix and increasing diffusion Absorption reduced in circulatory failure (shock) due to decreased tissue perfusion  Why delay absorption? Can be desired for producing a local effect or prolonging systemic absorption Examples: Addition of adrenaline to local anaesthetic reduces absorption, prolonging anaesthetic effect Formulation of insulin with protamine and zinc produces long-acting form Longer acting insulin analogues like insulin glargine, insulin detemir & insulin degladec provide basal insulin levels with once daily dosing Insulin degladec provides basal insulin for up to 42 hrs after a single injection Procaine penicillin, a poorly soluble salt of penicillin, when injected as an aqueous suspension is slowly absorbed, exerting prolonged action Esterification of steroid hormones and antipsychotic drugs increases solubility in oil, slowing absorption when injected in oily solution Subcutaneous implantation: Achieves slow and continuous absorption of certain steroid hormones (e.g. oestradiol) Drug substance formulated as solid pellet Absorption rate proportional to implant surface area  It is a sub-arachidonic space injection via lumbar puncture needle used for specialised purposes: Methotrexate for certain childhood leukaemia's to prevent CNS relapse Regional anaesthetics with local anaesthetics like bupivacaine Opioid analgesics for pain relief Baclofen for disabling muscle spasms Administered intrathecally to minimize Intrathecal peripheral effects Antibiotics (e.g. aminoglycosides) in rare cases of injection nervous system infections resistant to other antibiotics Given intrathecally or directly into cerebral ventricles via a reservoir Nusinersen, an antisense oligonucleotide for spinal muscular atrophy, administered intrathecally Increasing importance due to therapeutical potential of biopharmaceuticals in neurological disorders and challenges posed by the blood- brain barrier  Ranibizumab: Monoclonal antibody fragment targeting vascular endothelial growth factor (VEGF) Administered via intravitreal injection Used in treatment of: Wet age-related muscular degeneration (AMD) Macular oedema Chronic neovascularization Aflibercept: Intravitreal Fusion protein injection Binds to VEGF Administered via intravitreal injection Indicated for: Wet AMD Muscular oedema Chronic neovascularization Intravitreal implants Release corticosteroids slowly over several months Examples: Fluocinolone and Dexamethasone Used primarily in the management of muscular oedema