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Merits
Demerits
Future prospects
Pilo-20 and Pilo-40: release 20g and 40g of pilocarpine per hour respectively for 7days.
Advantages:
Rapid absorption. Ease of administration. Good local tolerance. Avoids the need for repeated administration of eye drops.
PROGESTASERT:
An intrauterine contraceptive device
Uses: Contraception.
Menorrhagia, dysmenorrhoea.
Contraindications: Weight gain Pregnancy, ectopic pregnancy. Immediately after septic abortion, Postpartum puerperal sepsis. PID Endometrial cancer, cervical cancer.
Mirena (1990-present): 1st marketed in Finland in 1990. approved by U.S. FDA in 2000. 20 g of levonorgestrel per day. uses - +endometriosis, DUB. May be used for 5 yrs. Products in development: Femilis: a lower-dose (14g levonorgestrel per day) T-frame IUS, developed by the Belgian company Contrel. FibroPlant-LNG: a frameless IUS, initially releases 14g of levonorgestrel per day, and may be used for a period of 3 yrs.
Designed to last for 1-7 days. The sites of application: chest abdomen upper arm
lower back
buttock mastoid region (efficient) GTN, fentanyl, nicotine and estradiol - India. Isosorbide dinitrate, hyoscine and clonidine.
The potential advantages: Minimize inter individual variations (drug is subjected to little hepatic first pass metabolism). Provide smooth plasma concentration of drug without fluctuations.
Disadvantages:
Transderm Scop: Transdermal preparation of scopalamine. Post auricular area 1.5 mg/2.5cm2
Novel delivery system in development Polymers Liposomes Suspensions. A mutlivesicular liposomal formation of bupivacaine (Depo Bupivacaine) is in the advanced stages of clinical development. - Action lasting up to 72 hrs.
IONTOPHORESIS [Electromotive Drug Administration (EMDA)]: is a technique using a small electric charge to deliver a medicine or other chemical through the skin. basically an injection without the needle. unlike transdermal patches, this method relies on active transportation within an electric field. galvanic current
Uses: anti-inflammatory medications (physiotherapy) plantar fasciitis, of hyperhidrosis bursitis and some types
Adverse effect: mild skin irritation transient. Future aspects: - local anaesthetics - ocular iontophoresis
- Drug is deposited in loose subcutaneous tissue, richly supplied by nerves but is less vascular
- Repository (depot) preparations can be injected for prolonged action Pellet implantation: - Drug in the form of solid pellet is introduced with a trochar and cannula. - Provides sustained release-over weeks and months Eg: testosterone.
- Crystalline drug is packed in tubules or capsules made of suitable materials and implanted under skin.
- release drug over months
- up to 5yrs
Dermojet: - a high velocity jet of drug solution is projected from a microfine orifice using a gun like implement. - needle is not used- painless - suited for mass inoculations - insulin
DRUGELUTING STENTS:
Peripheral or coronary stent (a scaffold) placed into narrowed, diseased peripheral or coronary arteries that slowly releases a drug to block cell proliferation. These stents consist of a metallic stent backbone covered by a polymer, containing a drug (SIROLIMUS OR PACLITAXEL). The first successful trials were of sirolimus - eluting stents
Expensive. Indications: - coronary stenting - improve the diameter of the coronary artery lumen Risks: - new clot/thrombosis formation with stents - Stent occlusion because of thrombosis may occur during the procedure, in the following days, or later.
PRODRUGS
It is an inactive form of drug which gets metabolized in the body to an active drug, or one or more active metabolite. Overcome the pharmacokinetic disadvantages of the useful drug. More stable Better bioavailability
like
Methenamine prodrug for formaldehyde. It is converted to formaldehyde and ammonia at acidic urinary PH (Site specific delivery of drugs) Altering polarity of ampicillin by esterifying ampicillin to form talampicillin - improves bioavailability of ampicillin.
The advantages: reduction in the frequency of the dosages taken by the patient having a more uniform effect of the drug reduction of drug side effects
1.
4. Polymeric micelles
5. Dendimers
3.
4.
The types/sources of MAbs: 1. Murine (rodents) MAbs: shorter life, - induce a human antimouse antibody allergic reactions. 2. Chimeric MAbs: murine MAbs partly humanized by genetic manipulation (part human part mouse antibody) 3. Humanized MAbs: obtained by recombinant DNA technology or by grafting of complimentarity determining regions (CDRs) of murine MAbs on human Ig framework - least antigenic
Nomenclature of MAbs:
Prefix + Target subsystem + Origin subsystem + Suffix. Suffix- mab. Origin- depending on source zu- human (zumab), xi- chimeric (ximab), o- murine (omab).
Target- specific letters vi- virus (Palivizumab), ci- circulation (Abciximab), tu- tumour (Trastuzumab), If no such prefix, then the MAb is generally an immunomodulator (Infliximab).
Prefix- different for each Mab.
Prefix
Target subsystem
Source subsystem
Old
vi (r) ba (c) li (m) fu (ng) Variable ne (r) ki (n) mu (l) o (s) co (l) me (l) ma (r) go (t) go (v) pr (o) tu (m)
New
v (i) b (a) l (i) f (u) n (e) k (i) s (o)
Meaning
Viral Bacterial Lower immunity Fungal Nervous system Interleukin as target Musculoskeletal Bone Colonic tumor Melanoma Mammary tumor Testicular tumor Ovarian tumor Prostate tumor Miscellaneous tumor u o a i xi zu axo xizu
Meaning
Human Mouse Rat Primate Chimeric Humanized Rat mouse hybrid Chimeric humanized hybrid
-t (u)
Mab
Target
Indication
Antiplatelet B cell CLL Colorectal Ca. Colorectal Ca. TR AML RSV infection B cell NHL Breast cancer
VEGF- vascular endothelial growth factor. EGFR- epithelial growth factor receptor. TR- transplant rejection NHL- non-Hodgkins lymphoma. AML- acute myeloid leukemia. RSV respiratory syncytial virus.
Application of MAbs: Diagnostic tests- Western blot test, immuno dot blot test, immunohistochemistry, immunofluorescence test, biosensors, microarrays. Therapeutic treatment
A.
MAbs act directly when binding to a cancer specific antigen and induce immunological response to cancer cells. Such as inducing cancer cell apoptosis, inhibiting growth or interfering with a key function. MAbs was modified for delivery of a toxin, radioisotope, cytokine or other active conjugates.
it is also possible to design bispecific antibodies that can bind with their Fab regions both to target antigen and to a conjugate or effector cell
B.
C.
Adverse reactions: Hypersensitivity reactions (rare) Suppression of physiologic function- may occur Activation of inflammatory cells
LIPOSOMES:
These are concentric, spherical shells of phospholipids in a watery medium, into which drugs are incorporated. Produced by sonificaton of aqueous suspension of phospholipids.
Drugs administered via liposomes are: - anti cancer drugs (daunorubicin and doxorubicin). - anti fungal drugs (amphotericin B)- less nephrotoxic and better tolerated. - antibiotic like gentamicin. Disadvantage: Biodegradable - immediate uptake and clearance by RE system.
NANOPHARMACOLOGY:
The application of nanotechnology to the development and/or discovery of methods to deliver drugs. a nanodrug can be a vector (nanovector) designed to deliver a pharmacological agent (drug).
= 10-9 m
was introduced by Norio
Drug and tumor targeting, imaging. Alzheimers disease Potential for treatment of tuberculosis (TB) FUTURE of drug delivery
Type of Nanoparticles
1. Polymeric nanoparticles 2. Quantum dots
Material used
Biodegradable polymers CdSe-CdS core-shell
Application
Controlled and T.D.D Targeting, imaging agent
3. Nanopores
4. Nanowires or carbon nanotubes 5. Nanoshells coated with gold 6. Liposomes 7. Ceramic nanoparticles 8. Polymeric micelles
Controlled and T.D.D Drug targeting, Bio-molecules delivery Systemic and controlled delivery of water insoluble drugs
MICELLES: prepared from certain amphiphilic copolymers consisting of both hydrophilic and hydrophobic monomer units. can be used to carry drugs that have poor solubility Limitations- offers little in terms of size control or function malleability.
have a core that branches out in regular intervals to form a small, spherical and very dense nanocarrier.
Application of T.D.D:
Cancer treatment Cardiovascular diseases Diabetes mellitus
Infectious diseases
Inflammatory diseases Transplant rejections
- can be programmed to deliver insulin at a low basal rate ( approx. 1 U/hr) and premeal boluses (4-15 times the basal rate to control post-prandial glycaemia. - costly, risk of pump failure, site infection Implantable insulin pumps: Consist of an electromechanical mechanism which regulates insulin delivery from a percutaneously refillable reservoir. - mechanical pumps, fluorocarbon propellant and osmotic pumps are being developed
References:
Essentials of medical pharmacology; KD Tripathi, 6th edition Principles of pharmacology; HL Sharma, KK Sharma, 2nd edition Review of pharmacology; Gobind Rai Garg, Sparsh Gupta, 4th edition Pharmacology and pharmacotherapeutics; RS Satoskar, SD Bhandarkar, Nirmala N Rege, 21st edition Goodman and Gilmans The pharmacological basis of therapeutics; Brunton, Chabner, Knollman, 12th edition Basic and clinical pharmacology; Bertram G. Katzung, Susan B. Masters, Anthony J. Trevor, 11th edition
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