1. Drug dosage forms and routes of administration 2. Information about drugs 3. Drug legislation in CZ What is a dosage form? •It is a final form, in which •the drug is given to the patient. • • Dosage Form •Mixture of substances with therapeutical effect and excipients •Excipients: antioxidants, fillers, pigments (dyes), fragrances, ointment bases, solvents etc. •No pharmacological effect •Allergies (parabens), intolerance (lactose) •Shape and characteristics of a medical preparation •Adjusted to the route of administration •Influence pharmacokinetics of a medical substance • •Generations of dosage forms: –1st = classic dosage forms –2nd = controlled release –3rd = controlled biodistribution • Excipients of AERIUS tablets: Core: calcium hydrogen phosphate dihydrate, microcrystalline cellulose, maize starch, talc. Coating: lactose monohydrate, hypromellose, titanium dioxide, macrogol 400, indigotin, carnauba wax, white wax. Classification of Dosage Forms •According to the consistency: •solid •semi-solid •liquid •gaseous •According to the usage: •for internal use (Ad usum internum, e.g. Peroralia, Parenteralia) •for other use (Ad usum alium, e.g. Ocularia, Nasalia, Unguenta). Liquid Dosage Forms •a) For internal use: –1. (Per)oral liquids •– solutions, suspension, emulsion for per os administration •– tinctures, drops, syrups –2. Parenteral liquids •– injections •– infusions • • • •b) For external use: •– eye drops, ocular waters, ear drops, nasal drops •– liquids for cutaneous use, for compresses •– liquids applied to the mucosa (douche – irrigation, gargle) » – – Semi-solid Dosage Forms lApplied on the skin or mucosa lLocal effect (dermatology) l lSystemic effect (TTS) • l l lOintment (unguent) lCreme lGel (jelly) lPaste lTransdermal patch (TTS, Emplastra) Solid Dosage Forms •Specific in shape: lTablet lSuppository lVaginal pessary (suppository) lCapsule lLozenge (pastilles) Non-specific in shape: lDusting powder lHerbal mixture lPeroral powder: •Classic •Grained •Effervescent Tablets and Capsules •Tablets: •Uncoated •Coated •Gastro-resistant •Effervescent •Tablets disperged in the mouth •Chewable •Sublingual •etc. • • •Capsules: •Hard •Soft •Gastro-resistant •With modified release •etc. Gaseous Dosage Forms = Aerodispersions •Topical •ear, nasal, oral, sublingual and cutaneous spray •Preparations for inhalation •liquids (scattering of liquid drops) •powders (particle size determines the place of absorption) •Foams •cutaneous, rectal, vaginal foams • • •Making of an aerodispersion: •Mechanically by a nebulizer (spray) •By liquefied/compressed gas (pressure container) Routes of administration •Systemic administration •= drug is absorbed into the circulation → it influences all the body •Enterální aplikace: –enteral –parenteral •Local (topical) administration •= drug is NOT absorbed into the circulation → it affects only the place of application •: –skin, mucosa, e.g. conjunctiva: –GIT, but the drug in not absorbed from GIT •How could a drug be administered? Systemic administration – enteral •(Per)oral (per os, p.o.) Enteron (ancient greek) = intestine •Onset of effect depends on phys-chem. properties of the medical substance and excipients •Possibility of lower bioavailability: first-pass effect (liver) • • • • • •Rectal (per rectum) •Do not irritate stomach, do not cause nausea •Lower bioavailability – lesser surface of rectum walls •Sooner onset of effect – plexus venosus rectalis flows into vena cava inferior („bypass of the liver“) • „First pass“ effect Systemic administration – parenteral •Para enteron (ancient greek) = out of the intestine •1. Non-injection (non-invasive) •a) oral •Absorption by oral mucosa (e.g. subligual) •Lipophilic substances – quick absorption (2 mins), e.g. nitroglycerin •b) inhalation •Gases, vapours nebo small particles •Respiratory diseases (asthma, COPD...) •c) transdermal •TTS = transdermal therapeutic system (controlled release) •E.g. hormonal contraception patch, nicotine patch, analgesic patch •d) transnasal •Good perfusion of nasal mucosa •Substances could irritate it, or impair cilia function •E.g. calcitonin, antimigraine drugs •e) vaginal – e.g. hormonal contraception ring Systemic administration – parenteral •2. Injection (invasive) •- non-physiological • •a) injection •small volume of liquid •i.v. administration – quick onset of effect •i.m., s.c. – gradual absorption into circulation •b) infusion •larger volume of liquid •parenteral nutrition, minerals, glucose, ATBs, cytostatics etc. • What is this tablet? What is this drug used for? How frequently should I use it? What are possible adverse effects? Who must not use it? What is an appropriate dose? How to store it? Does it influence vigility? Could this drug influence the effect of other drugs? ? ? ? ? ? Information about Drugs •PIL & SPC •PIL = patient information leaflet = package leaflet for patients •SPC = summary of product characteristics = information for medical specialists (physicians, pharmacists, nurses etc.) •EMA – European Medicine Agency (ema.europa.eu) •Database of RMPs granted central authorisation by EC/EMA •Reports concerning drugs‘ safety – alerts •List of newly authorized drugs •SUKL – State Institute for Drug Control (sukl.eu) •Database of RMP authorized in CZ •Free access to all PILs and SPCs (in czech) •European Pharmacopoeia = european standard for the quality of drugs (Czech Pharmacopoeia = text from EP + czech specialities) •Computer databases of medical preparations •AISLP (czech↔english, in most pharmacies and doctor‘s offices) Jdi na web SÚKLu a ukaž vyhledávání Jdi na web EMA a ukaž vyhledávání www.ema.europa.eu > Find medicine >Human >Product information Ukaž AISLP Pharmacopoeia •Purpose: to guarantee safe, effective and quality drugs •Information about medical substances, excipients, dosage forms •Instructions for production, preparation, control, storage of drugs •Used mostly in pharma industry • •What could we found there? •Analytical and instrumental examination methods •Materials for drug containers and cases •Instructions to ensure sterility of medical preparations •Instructions concerning radiopharmaceuticals, vaccines etc. •Monographs of specific substances •Tables with usual dosage of drugs in adults, children, animals •etc. • •NO: mechanism of actions, adverse effects, pharmacokinetics, contraindications, pregnancy safety etc.! Rozdej monografie Basic Drug Legislation in CZ •Act No. 378/2007 Coll., on pharmaceuticals • •Research •Authorization of new drugs („registration“) •Production, preparation and distribution •Prescribing and dispense of medical preparations •Destroying of unusable drugs •Pharmacy duties •Pharmacovigilance = drug safety service •Controls and sanctions Medical Prescription (Rx) in CZ •Validity: •classic Rx: 14 days •Rx for ATBs: 5 days •Rx for local ATBs: 14 days •Drugs of abuse and psychotropic substances (special Rx form): 14 days •Rx for repeated use: 6 months, max. 1 year •Rx from ED: day after the day of making up (= max. 48 h) • Legislation – Drugs of Abuse •Act No. 167/1998 Coll. on Dependency Producing Substances & Order of the Government 463/2013 Coll. regarding the lists of dependency producing substances • •Specified narcotic and psychotropic drugs •should be strictly monitored: • •Keeping files of accepting and dispensing • – „Opiates Book“ •SUKL require this information • •Special Rx form – with oblique blue strip • •Medical preparations and Rx forms should be stored in a safe or vault! Classification of narcotics •Group 1 → Rx with blue strip •Highly addictive •E.g. strong opioid analgesics •morphine •oxycodone •fentanyl etc. • •Group 2 •Lower risk of addiction •Classic Rx form •E.g. codeine • •Group 3 = „forbidden substances“ •No therapeutic use •Misused •Sometimes used in the research •E.g. hashish, heroin etc.. Classification of psychotropic drugs •Group 1 = „forbidden substances“ •Hallucinogens, psychostimulants •E.g. MDMA (exstasy) •Group 2 → Rx with blue strip •Misused psychostimulants, addictive •E.g. methamphetamine and other amphetamins •Therapeutically used: e.g. methylphenidate, buprenorphine •Group 3 •Barbiturates, risk of addiction, limited therapeutic use •E.g. pentobarbital • •Group 4 •Benzodiazepines, barbiturates and other potentially addictive drugs •Classic Rx. form •Hypnotics, sedatives, antiepileptics etc. •E.g. diazepam, oxazepam, phenobarbital… Precursors •= substances used in the production of addictive and psychotropic substances • •classic Rx (except pseudoephedrine) • •ephedrine – nasal drops in sinusitis •pseudoephedrine – medical preparation for cold treatment »→ OTC with restriction •ergotamine – antimigraine suppositories •ergometrine – obstetrics •