ODISHA STATE BOARD OF PHARMACY
D. Pharm - II Examination - 2008 (I)
HOSPITAL & CLINICAL PHARMACY (THEORY)
Time - 3 Hours Full Marks - 80
__________________
(Answer any five questions including question no-1)
1. (a) Give the normal value of the following:
[2x5
(i) Differential W.B.C. Count
(ii) Haemoglobin Level
(iii) Blood Sugar Level
(iv) B.T.C.T
(v) E.S.R.
(b) Write the Latin Terms and meaning of the following:
[1x10
(i) b.i.d.
(ii) lot
(ii) m.ft.m
(iv) p.p.a.
(v) sum
(vi) o.n.
(vii) qq.h.
(viii) a.c.
(ix) s.o.s.
(x) auri
2. (a) Describe the objectives and functions of the Hospital Pharmacy Services
[8
(b) Describe in short the requirements and abilities required for Hospital Pharmacists?
[8
3. Discuss in details about
[8+4+4
(i) Unit dose Dispensing Systems
4. What is Drug Information Bulletin ? Discuss the function of Drug Information Services in a Hospital Pharmacy and the qualification of the Pharmacist to run DIS.
(4+8+4
5. What is Hospital Formulary ? Briefly discuss about the PTC.
[4+12
6. (a) Discuss about the Diseases manifestations and patho Physiology of
[2x4
(i) Diabetes
(ii) Epilepsy
(b) Write a note on Mechanism of Drug Interaction
[8
7. Write short notes on the followings
(i) Drug Induced Diseases
(ii) Bioavailability of Drugs
[2x8
ANSWER TO 2008
1. (a) Give the normal value of the following:
Ans.
(i) Differential W.B.C. Count :
Neutrophil= 40-70%
Eosinophil = 2-4%
Baso phil0 = 5-1%
Monocyte = 2-8%
Lymphocyte= 20-30%
(ii) Haemoglobin Level:
Ans.
13-18 g/dl male, 11.5-16.5 g/dl female
(iii) Blood Sugar Level:
Ans.
70-110 mg/dl fasting, <140 mg/dl - 2 hr post prandial
(iv) B.T.C.T.:
Ans.
BT-2 to 5 min, CT -4 to 9 min.
(v) E.S.R.:
Ans.
0-20 mm/hr
(b) Write the Latin Terms and meaning of the following:
Ans.
(i) b.i.d.: Bis in die - Twice a day
(ii) lot: Lotion
(iii) m.ft.m: Misce fiat mistura - Mix to make the mixture. well
(iv) p.p.a.: Phiala Prius agitata - Shake before use/The bottle being first shaken.
(v) sum: sum endus - to be taken
(vi) o.n.: Omni nocte - every night
(vii) qq.h. : quaque quarta hora - every fourth hour
(viii)a.c.: ante cibos - before meals
ante cibum - before food
(ix) s.o.s.: si opus sit - when necessary
(x) auri: auri - To the ear
2. (a) Describe the objectives and functions of the Hospital Pharmacy Services
Ans.
Hospital Pharmacy may be defined as a service which receives drugs and medicines, stores and dispensses them to patients. This is responsible for the entire gamut of pharmacy service for the hospitalized and ambulatory patients viz purchase, manufacture, compounding and dispensing, storage and distribution and maintenance of record for the same.
Objectives of a Hospital Pharmacy :
The objectives of hospital pharmacy are:
1. To professionalize the working of the hospital pharmacy so as to effectively meet the objectives of the hospital.
2. To ensure availability of the required medication at an affordable cost at the time it is required and without compromising with the quality and/or the efficacy of the medicament.
3. To plan, organize and implement the policies of the pharmacy which are in accordance with those of the hospital.
4. To perform functions of management of material, purchase, storage of essential items and medicaments and to maintain a strict inventory of all items received and issued.
5. To counsel the patient, medical staff, nurses and others involved in patient care on the use of drugs. possible side effects, toxicity, adverse effects, drug interactions etc.
6. To serve as a source of information on drug utilization.
7. To manufacture drugs, large/small volume parenterals which are critical for use in patients and especially those which are not readily available from the drug manu turing companies.
8. To participate in and implement the decisions of the Pharmacy and Therapeutics Committee.
9. To organize and participate in research programmes, educational programmes and to provide training to various members of the patient care team on various aspects of drug action, administration and usage.
10. To engage in public health activities to improve the well-being of the population.
11. To interact, cooperate and coordinate with various other departments of the hospital.
Functions of Hospital Pharmacy :
The functions performed by a hospital pharmacy are:
1. To obtain supply of drugs, chemicals, biologicals and other pharmaceutical preparations from approved vendors and manufacturers.
2. To maintain an inventory of all the supplies. received and to inspect the items.
3. To dispense drugs, chemicals, pharmaceutical preparations or biologicals for use in the patients and for doing so the pharmacist may have to repack the medicament in appropriate containers and label them.
4. To maintain a record of all the supplies dispensed.
5. To manufacture large volume parenterals and other drug preparations if these are not readily available or are too expensive or if their purchase from vendors is otherwise not desirable or prudent..
6. To exercise control over the quality of all the supplies received, manufactured and dispensed.
7. To provide drug related information to the medical staff, residents nurses, members of the health care team and the patients.
8. To assist in reducing the incidence of illness and improve the general health of the population.
(b) Describe in short the requirements and abilities required for Hospital Pharmacists?
Ans.
The requirement of trained manpower in pharmacy varies according to the size of the hospital and the services it offers. The required number of pharmacists for a hospital is calculated on the basis of some workload norm like the number of prescription received and dispensed (and the time taken to do so) or the number of beds available in the hospital and its occupancy rate.
As a rule, there must be a minimum of 3 pharmacist for a small hospital (50 beds), for larger hospitals the requirements vary with the bed number being 5, 8, 10 or 15 for bed number up to 100, 200, 300 and 500 respectively. Thereafter, it increases by one pharmacist for every increase in 100 beds number.
Academic and Profesional Requirements:
The manufacturing division of the hospital pharmacy should be placed under the charge of a manufacturing chemist, approved to undertake manufacture by the Drug Control Authority. The incumbent should possess a post graduate degree in pharmacy or pharmacology. Likewise the quality control chemist should control division works under the supervision of the quality control chemist. He should preferably be a post graduate in analytical chemistry and approved by the Drug Control Authority. All dispensing work conducted in the hospital pharmacy should be by a person who has a bachelor's degree in pharmacy. The drug stores of the pharmacy may, however, be entrusted to a diploma holder.
3. Discuss in details about
(i) Unit dose Dispensing Systems
Ans.
Unit Dose Drug Distribution System (UDDDS) ;
Unit dose drug distribution system has been found to be the safest and the most efficient means of delivering drugs from the pharmacy to the patients. Once a prescription is written, the nurse forwards it to the pharmacy. The pharmacist enters the drug on the patient's profile card, places the drug in a ready-to-administer form in sufficient quantities so as to last until the next time the unit dose cassettes are exchanged and sends it to the nursing station. The nurse then removes the initial dose of the medication and shifts it to the patient's room. The dose is then administered to the patient and the event recorded. A physician's order notifies the pharmacy about the discharge of the patient or discontinuation of the drug. The pharmacy will then not dispense any further drug Billing is at the time of discharge or at specific intervals.
Features:
(i) Safe and efficient
(ii) Package mentions relevant details
(iii) Drugs dispensed in a ready to use form
(iv) chances of medication error minimized
(v) Wastage reduced as amount dispensed at one time is less
(vi) Reduction is nursing time, no recordering of drug
(vii) Record keeping is simple unit
(viii) Dose package can be returned to the pharmacy in case drug is discontinued
(ix) Reduction in cost of medication
The advantages of UDDDS are:
1. he package identifies the drug name, strength. expiry date and, therefore, minimizes wrong administration.
2. Accurate delivery of medication due to stringent repackaging requirements.
3. Minimum wastage of drug.
4. Reduction in nursing time.
5. Maintenance of records is simple.
The advantages of UDDDS over the traditional method are many while in the traditional system the nurse must prepare the drug for each administration, in UDDDS, the pharmacy dispenses the drug in unit dose package which is ready for administration. The unit dose package is one which contains the particular dose of the drug ordered for the patient. The package mention the name of the drug, its strength, expiry date etc. Preparation of unit dose packages are subject to stringent repackaging controls which ensures accurate medication. UDDDS also minimizes wastage of drugs. If the drug is discontinued, unit packed drugs can be placed back in the pharmacy inventory and reused provided the package is not opened. In the traditional system, unused drug has to be discarded for safety reasons. Reduction in nursing time is also effected as the nurse has no longer to transcribe orders of the patient's treatment to medication profile and the medication record. Maintenance of record is also simplified as this can be done immediately after administration of the drug. Besides the need to reorder medication is eliminated since the pharmacy will automatically send the next dose for further administration. Therefore in the UDDDS, there is a decreased possibility of mistakes and medication errors. due to crosschecks. It also saves nursing time and brings about a reduction in costs. Reduction in cost is brought about by (i) storage of drug gets limited to those currently in use and the emergency drugs: (ii) re-inventory of unused unit packed drugs not used by the patient; and (iii) dispensing off with medication cups. prescription labels. vial forms etc. which were necessary under the traditional drug distribution system.
(ii) Bed side Pharmacy
Ans.
It is related to drug dispensing by the pharmacist beyond OPD & IPD service to the ward of hospital by checking every patient bed by bed to evaluate patient's presumptions during ward visit with a interprofessional team of physician, nursing staff & pharmacist.
The main objective of this type of service is to carefully observe and record the pharmacokinetics of prescribed drugs and their adverse effects also.
The challenge of managing quality in the healthcare field is becoming increasingly difficult. New technology is now available that provides computerized record keeping in the patient care area. These bed side information systems also known as point of care systems. They have many applications in hospital pharmacies. especially in relation to the administration of medications.
(iii) Satellite Pharmacy Services
Ans.
lt is a smaller pharmacy that is located elsewhere from the main pharmacy in a hospital. When pharmacy services are provided round the clock, the satellites are operati for 8-16 hours a day. There can be a central pharmacy unit and a number of satellite units to provide care to all areas of the hospital. There can be separate satellite services for ICU, Psychiatry, eye etc.
The professional staff can be divided into several categories as a means to overcome the difficulties and take full advantage of all the benefits of the satellite system. The Associate Director and Assistant Director perform primarily administrative functions in order to maintain overall control, co-ordination and quality assurance of the department. The Education co-ordinator helps maintain the level of basic competence of the staff and co-ordinates the development and implementation of new department programs. Senior pharmacists provide both administrative and professional functions in their roles as team leaders of individual satellite units. Junior Pharmacist serve the traditional staff functions in a satellite unit or in the central pharmacy.
4. What is Drug Information Bulletin ? Discuss the function of Drug Information Services in a Hospital Pharmacy and the qualification of the Pharmacist to run DIS.
Ans.
Drug Information Bulletin :
It is the responsibility of the Clinical Pharmacist to provide information about drugs relevant to patient care to all members of the patient care team. This may conveniently be done through Drug Information Service or through a bulletin which publishes the latest development in medical sciences, new drugs introduced, new indications for drugs, newer drug delivery system, update of drug interactions and adverse drug reactions. etc. A regular publication of the bulletin will update the knowledge of the patient care staff on the latest development in their area of specialization.
Functions:
The hospital pharmacist today faces a stupendous task of providing drug related information to medical, nursing and paramedical staff of the hospital. He is also required to respond to the queries of the patient in the out-patient pharmacy. With considerable advancements in information technology, and the growing awareness of the patient both with respect to the nature of illness and its current therapy, the pharmacist needs to keep his knowledge updated. The source of available information may be classified as primary, that is directly obtained from the author without any evaluation or comments; secondary, in which the original information has been reviewed, modified or commented upon by some other person or tertiary, where the information available from the primary or secondary source is presented in composite form. The hospital pharmacist is also responsible to provide relevant information about drugs to all members of the patient care team and respond to drug related queries. For this the pharmacist has to classify the question, obtain background information and - make a systematic search of literature. The usual sequence is tertiary, secondary and primary. The pharmacist answers such queries through Drug Information Centre of Drug Information Services of the hospital. The scope of these services can be extended to answer poison related queries and making available useful information regarding the treatment and availability of antidotes and monitoring and treating adverse reactions to drugs. The Centre also publishes a Drug Information Bulletin for transmission of information to members of the health care team.
5. What is Hospital Formulary? Briefly discuss about the PTC.
Ans.
Hospital Formulary:
A hospital formulary is a list of the pharmaceutical preparations (including important ancillary information) that reflects the current clinical acumen of the medical staff. The list is continuously revised to reflect the changes with respect to the use of new drugs or drugs for new indications. There is an increasing number of new drugs for various conditions in the market. Each pharmaceutical company will obviously highlight the merits of their product. There may be, as a consequence, some bias in advertising or in the drug literature. The medical staff, working through the Pharmacy and Therapeutic Committee should, therefore, evaluate, appraise and select some drugs or drug products which are necesary to be constantly available in the hospital for patient care, through Hospital form
Characteristics :
1. It is a compilation of selected drugs which should be available in the hospital
2. It contains sections on prescription writing, diagnostic agents, reagents for biochemical and pathological investigation, normal laboratory values, poisons and their antidotes, and first-aid measures.
3. It needs to be periodically revised.
4. Drugs incorporated are those which are cheap but of proven efficacy, safety and usefulness with low toxicity.
5. Drugs are listed as per their generic names.
6. Formulary is sponsored by the medical staff and
7. It has the approval of the hospital administration • It has to be widely circulated amongst the medical and nursing staff.
8. It permits flexibility with respect to newer or investigational drugs.
The selection is made on the basis of its proven benefits while considering its toxicity, untoward effects and interactions. It also takes into consideration its price viz-a-viz other similar drugs or preparations.
Role of PTC in hospital Formulary:
The medical staff should follow the policies and adopt procedures developed by the PTC. These serve as the guiding principle in the critical evaluationor appraisal, selection, procurement, storage, distribution and on the safe and rational use of drug entities and drug product. The hospital formulary, should contain all the above information and be made available for ready reference to the medical faculty. Listing of drugs in the formulary should be by their nonproprietary names and the medical staff is advised to prescribe drugs by their nonproprietary names. The pharmacist will be responsible for selecting which drug has to be dispensed on a physician's order form among the available generic equivalents. However, the physician has the option to specify the supplier or the brand name of the drug to be dispensed to a particular person. While suggesting a particular brand name, the physician's decision must, of course, be based solely upon sound pharmacological and therapeutic considerations.
The PTC shall decide upon drug products and entities which are generic equivalents and therapeutic equivalents. This will limit the number of drugs which are to be routinely available at the hospital pharmacy, for maintaining patient care and rational drug therapy. However, while selecting the drugs PTC will not sacrifice the quality for the cost of the preparation. Provisions should be made for the appraisal and use of drugs not listed in the hospital formulary. It will be the responsibility of the pharmacist to specify the quality, quantity and source of all drugs, chemicals, biologicals, raw materials and drug preparations for use in the hospital for the diagnosis, prophylaxis or treatment.
To develop an effective formulary system and to assist in rational drug therapy the PTC has to consult available references on a drug. The important aspects pertaining to drugs which need consideration are:
(i) the content of the preparation
(ii) its availability
(iii) its pharmacokinetic profile, namely, characteristics of absorption, distribution, metabolism and excretion
(iv) dosage form and the adult, paediatric, neonatal and geriatric dose
(v) drug-drug and drug-food interactions (vi) side effects, adverse effects, safety in use during pregnancy, effects of the fetus, carcinogenicity, mutagenicity
(vii) therapeutic potency and efficacy
(viii) toxicity and poisoning
(ix) propensity for abuse
PTC :
Modern day medicine utilizes so many drugs for the treatment of diseases that it is nearly impossible to be knowledgeable about all of them. The need, therefore, is to select the best and acquaint the medical staff with its use in patients. To develop an organized method by which rational, safe and effective drug use can be maximized is the prime responsibility of the Pharmacy and Therapeutic Committee. In different settings it may also be known as the Drug and Therapeutics Committee, Pharmacotherapy Committee, Formulary Committee or Rational Drug Use Committee.
Composition:
The PTC should comprise of at least physicians a pharmacist, a nurse and the administrator of the hospital. However, in many hospitals a number of physicians drawn from various specialities viz. surgery, anaesthesia, urology, cardiology, neurology, endocrinology, dermatology, gastroenterology, psychiatry, medicine, allergy, paediatrics are members of the PTC.
Functions of the PTC:
(i) PTC has an advisory role in all matters relating to rational and safe use of drug in a hospital.
(ii) It develops a formulary of drugs for use in the hospital. The drugs included in the formulary are, of course, a subject to constant revision. Drugs for the inclusion in the formulary are selected on the basis of their proven therapeutic value, safety and the cost. The PTC evaluates, approves or rejects drugs proposed for inclusion in the hospital formulary. Many authorities consider that developing and operating the hospital formulary constitutes the sole purpose of the PTC. This is not so as there are many hospitals with a PTC but without a formulary system and vice versa.
(iii) PTC participates in quality assurance activities related related to distribution, administration and use of medications.
(iv) PTC reviews and monitors adverse drug reactions and medication errors.
(v) It reviews the safety/efficacy profile of drugs. (vi) Prepares a list of drugs required to be available in the wards and emergency as also a list of charge and non-charge drugs.
(vii) Advises the pharmacy on cost effective drug distribution and control procedures.
(viii) Establishes procedures for cost effective drug therapy.
(ix) Develops training programmes for the staff on drug use.
(x) Participate in the developing of Standard Treatment Guidelines.
Role of PTC in Drug Safety;
Inappropriate use of drugs leads to serious health care problems resulting in increased morbidity, mortality, costs and emergence of antimicrobial resistance. Introduction of new classes of therapeutic agents has increased the responsibility of the hospital pharmacist to ensure its safe use. Fortunately, drug accidents due to a lapse on the part of the pharmacy are rare but there should not be a state of complacency. It is the role of the PTC to ensure that in the hospital, all pharmacy operations are supervised by a competent pharmacist and that dispensing of drugs should not be delegated to untrained persons. The nursing stations should be checked periodically for the storage condition and expiration date of all the drugs stored. The pharmacy should be staffed in a manner commensurate with the work load with adequate working space and appropriate and safe storage facilities. The supply and distribution of dangerous and habit forming drugs ought to be strictly regulated. Poison preparations should be segregated from other class of drugs as also external use preparations from drugs meant for internal use. If manufacturing is being undertaken, it should conform to the prescribed norms with strict quality assurance techniques. Such checks and counter checks at each stage in the operation of the hospital pharmacy helps in the safe use of drugs in the hospital.
PTC and Monitoring of Adverse Drug Reactions :
PTC should issue guidelines for prompt reporting of any ADR either to the clinical pharmacologist or to the chairperson of the PTC. The PTC should also devise systems for checking medication errors and inappropriate prescribing. All ADR should be recorded on the medical record as a diagnosis. In India, not many hospitals have units for recording adverse drug reactions. The Indian Council of Medical Research has four centres i.e. at the All India Institute of Medical Sciences, New Delhi: Post Graduate Institute, Chandigarh; Maulana Azad Medical College, Delhi and K.G. Medical College, Lucknow for monitoring and recording ADR.
The clinical pharmacist using the references for the above details, encourages the medical staff to adopt those drugs for inclusion in the formulary which are most effective and safe.
6. (a) Discuss about the Diseases manifestations and patho Physiology of
(i) Diabetes
(ii) Epilepsy
Ans.
(i) Diabetes Melitus commonly known as diabetes, is associated with a disturbance in glucose homeostasis and carries a potential risk of atherosclerosis. nephropathy,, retinopathy and neuropathy, if untreated. Diabetes may be of two types - Type I diabetes or insulin dependent diabetes mellitus (IDDM) is widely regarded to be an autoimmune disorder and is rapid in onset. Circulating insulin is virtually non-detectable. In its severe from ketosis results. It occurs commonly in juveniles and therefore, the eariler term was juvenile-onset diabetes. However, it is also seen in adults especially non-obese and in those where hyperglycemia occurs at an advanced age. The paneretic ß cells are not responsive to an insulin secretory stimulus and there is a raised glucagon level. Since the pancretic ß cells do not respond to an appropriate insulin secetory stimulus, exogeneous administration of insulin becomes inevitable.
Type II diabetes or noninsulin dependent diabetes mellitus (NIDDM) occurs predominantly in adults and occasionally in adolescents. This disorder was earlier known as maturity onset diabetes. It is a geterogeneous group of disorder usually of milder severity than the Type I diabetes. Though the pancreatic ßcells are functional. there appears to a lack of tissue sensitivity to insulin. The glucoreceptor on the ß cells are functional, there appears to a lack of tissue sensitivity to insulin. The glucoreceptor on the B cell membrane is defective which accoutns for the delay in insulin secretion.
Pathophysiology:
Diabetes due to lack of insulin, results in hyperglycaemia (high blood sugar). hyperlipaemia (high blood fatty acid), ketonaemia (high acetone bodies in blood) and azoturia (increased urea in urine). If deficiency of insulin is severe, diabetic ketoacidosis occurs. Hyperglycemia due to insulin deficiency is because of under-utilization of an of glucose. There is a marked reduction in the rate of transport of glucose across certain cell membrances. There is also a marked reduction in the activity of glycogen synthetase that is responsible for the conversion of glucose into glycogen and an increased rate of conversion of proteins and amino acid into glucose in the liver. The abnormally high conentration of free fatty acid in plasma is largely because of its enhanced mobilization from peripheral fat depots. In the absence of insulin. lopolysis proceeds unhindered. The liver takes up large amounts of free fatty acids thus liberated and oxidises them to acetyl coenzyme-A. Since the the capacity of the liver to synthesize fatty acids from acetyl coenzyme-A is markedly reduced, there is, therefore, a diversion of the substance to ketone bodies which thus appear in the blood. Over productionl of ketone bodies like acetoacetate and B-hydroxybutyrate (which are strong acids) causes acidosis. Urinary secretion of these anions results in loss of fixed cations and this is responsible for depletion of electrolytes which is characteristic of diabetic ketoacidosis: potassium loss may be specially very high. Increased coversion of proteins to glucose causes an increase in production of urea and ammonia.
(ii) Epilepsy:
Ans.
Epilepsy are a group of disorders. characterized by chronic, recurrent, paroxysmal changes in neurologic function caused by abnormalities in the electrical function of the brain. Seizures are referred to as a transient alteration of behaviour due to an abnormal, synchronized and repetitive burst of firing of neuronal population in the central nervous system. The term ictal refers to the seizure itself and interietal means between seizures. Convulsions ictal behaviour associated with aggressive motor activities. Status epilepticus refers to a prolonged seizures occuring so frequently that full recovery of brain function does not occur interietally. Seizures may also be manifested by other changes in neurologic function such as sensory, cognitive or emotional.
Partial seizure begins in a local area whereas generalized seizure shows widespread involvements of both hemispheres from the outset. Complex partial seizures are usually associated with impairment of the level of consciousness. Most of the complex partial seizures originate in the temporal lobe and are, therefore, also called temporal lobe seizures. When a simple partial seizure precedes a complex partial seizure it is called 'aura'.
Pathophysiology:
The altered, physiological state of epilepsy is a rhythmic repetitive firing of many neurons localized to a particular area of the brain as reflected in the electroencephalogram (EEG). In the epileptic focus, neurons in a small area of the cortex are activated in an unusually synchronized manner. This produces a larger, sharper wave form in the EEG which is called spike discharge. If the neuronal hypersynchrony is large a simple focal seizure results. If it spreads through the brain and lasts for a few seconds a complex partial seizure or generalized seizure results. The EEG in generalized seizure will have a variety of appearances depending upon the area of discharge and the spread of the seizure. Metabolic events in the brain may contribute to the development of an epileptic focus, the transition of seizures and the postictal dysfunction. For example, there is an observed increase in extracellular K and decrease in extracellular Ca concentration. These ionic changes mainly affect neuronal excitability. neurotransmitter release and the neurotransmitter metabolism. Certain neurotransmitters and neuropeptides. are released in large quantities during epilepsy and some of these can prolong the actions of certain neurons and postictal phenomenon. Furthermore, there is an increased blood flow to the primary area involved, increased utilization of glucose, an alteration in oxidative metabolism and a change in the local pH. All these factors may be contributory to the development of seizures.
Drugs which facilitate the actions of the inhibitory neurotransmitter gamma amino butyric acid (GABA) are potential anticonvulsants. Thus, a decrease in the level of inhibition of GABA may be involved in some forms of epilepsy. Some forms of generalized epilepsy could also be due to an abnormality in the GABAinhibitory system. Electrical stimulation can also result in the development of seizures. Epilepsy may also be a result of neurologic injury or a structural brain lesion or may occur as a manifestation of other systemic diseases.
(b) Write a note on Mechanism of Drug Interaction
Ans.
Interaction between two drugs can occur at various sites, namely:
(i) Outside the body;
(ii) At the site of absorption
(iii) During the distribution phaase;
(iv) At the metabolism stage; (v) At the site of action; and
(vi) During the phase of elimination.
(i)Interactions ocuring outside the body
During formulation and mixing of drugs: Thiopentone and suxamenthonium react chemically and, therefore, should not be withdrawn in the same syringe. Potamine zinc insulin contains excess of protamine which binds to soluble insulin if the two are combined together. Heparin is incompatible with drugs like hydrocortisone, tetracycline and the sympathomimetics.
(ii) Interaction at the site of absorption
(a) Chemical interaction: Antacids are drugs which neutralize the acid in the stomach. They usually contain aluminium and magnesium in basic forms. If given with tetracycline, iron or prednisolone, the aluminium and magnesium form insoluble complexes. Cholestyramine interferes with the absorption of thyroxine, digoxin and warfarin. Such interactions can be easily prevented if the drug administration is suitably timed.
(b) By affecting GIT motility: Drug which decrease motility e.g. atropine, opioids etc. delays the absorption of some drugs by reducing gastric emptying time. On the other hand, purgatives decrease the absorption of poorly soluble drugs like adrenal steroids, digoxin etc, by decreasing their sojourn in the intestines.
Use of antimicrobials alter the microbial flora of the GIT and may, therefore, potentiate the effects of oral anticoagulants by decreasing the bacterial synthesis of vitamin K.
Vasoconstrictors such as adrenaline are added to local anaesthetics to decrease their absorption into the general circulation and consequently to reduce toxicity. On the other hand, hyaluronidase may be added to increase the absoption of a drug following subcutaneous administration.
(iii) Interaction during distribution phase
(a) Displacement from plasma protein binding: Upon introduction of a drug which can displace another drug bound extensively to plasma proteins, the plasma concentration of the former, may be raised even to a toxic level. The displaced drug is, however, available for biotransformation and excretion. Warfarin is about 98%.
bound to plasma proteins and only 2% is found free in plasma. Administration of another drug, like phenylbutazone, which competes for the plasma protein binding sites can, therefore, displace warfarin, raising its plasma concentration. Since it is the free unbound drug. which is pharmacologically active, such an interaction results in profound anticoagulant effect of warfarin. Similarly, displacement of tolbutamide by dicumerol results in severe hypoglycaemia.
In certain cases, in addition to displacement, other mechanisms are also operational making an interaction more clinically important. Valproate sodium not only displaces phenytoin from binding sites but also inhibits its metabolism. Similarly, aspirin or other antiinflammatory drugs displace methotrexate from binding sites and reduce its elimination. Vitamin K or indomethacin can displace bilirubin which results in kernicterus especially in the newborn because of the limited capacity of the newborn to metabolize bilirubin.
(b) Displacement from tissue binding: Quinidine can displace digoxin from the tissue (as also plasma) binding sites leading to an increase in concentration of free digoxin and, consequently lead to digoxin toxicity. Quinidine also impairs renal excretion of digoxin.
(iv) Interactions during biotransformation
Many drugs are metabolised by the microsomal enzymes of the liver. Metabolism, in most instances, changes a drug to a polar metabolite which can be readily excreted. Some drugs like phenobarbitone, alcohol, chloral hydrate, chlorcyclizine, haloperidol, phenylbutazone, tolbutamide, chlorpromazine can increase the activity of the hepatic microsomal enzymes and are, therefore, called enzyme inducers. Such drugs when given over a period of time can induce the metabolism of othe drugs.
Cyclosporin which is metabolized to about 50% by the hepatic microsomal enzyme, if combined with rifampicin can cause lowering of the blood levels of cyclosporin with the consequent risk of inadequate immunosupression.
Some drugs can inhibit enzymes. Cimetidine is an inhibitor of phase 1 metabolism. It, therefore, potentiates the action of drugs like propranolol, theophylline, warfarin, Phenytoin etc. Erythromycin inhibits the oxidizing
enzymes and impairs the metabolism of theophylline, warfarin, carbamazepine, methylprednisolone etc. Sodium valporate inhibits the metabolism of phenytoin, phenobarbitone and primidone.
(v) Pharmacodynamic interaction at the site of action :
Pharmacodynamic interaction results in an altered drug response due to an interaction between two or more drugs at the same receptor site, or involving the same organ or system.
Interaction at the same receptor site are on numerous occasions desired, such as, the use of naloxone to treat morphine withdrawal or use of atropine in anticholinesterase excess and insecticide poisoning. However, in many cases the interactions may not be desired e.g. use of indomethacin with beta adrenoceptor antagonist results in loss of antihypertensive effect of the latter, the interaction may involve inhibition of prostaglandin synthesis by the kidney. Digoxin is more effective and also more toxic in the presence of hypokalaemia which may result with the use of thiazide type or loop diuretics.
Aminoglycoside antibiotics when given with loop diuretics e.g. furosemide can cause profound ototoxicity.
(vi) Interaction during excretion : Changes in glomerular filtration rate, tubularabsorption and tubular secretion can alter the renal clearance of a drug. Probenecid decreases the renal clearance of penicillin by competing with the same transport mechanism for secretion of penicillin by the renal tubules.
Phenylbutazone blocks the renal tubular reabsorption of uric acid leading to uricosuria. Ammonium chloride increases the urinary volume and acidifies the urine. Amphetamine is more ionized at acidic pH and therefore, not reabsorbed. Thus, ammonium chloride is usually given in patients with amphetamine intoxication to hasten its elimination. Similarly alkalinization of urine is useful in some cases of barbiturate poisoning.
7. Write short notes on the followings
(i) Drug Induced Diseases
Ans.
Drug-induced diseases are also called iatrogenic (physician-induced) diseases. Many of these persist even after the drug has been withdrawn and mostly eliminated. The most common are:
1. Parkinsonism by phenothiazines and butyrophenones.
2. Peptic ulcer by salicylates and corticoids.
3. Hepatitis by isoniazid.
4. Lupus syndrome by hydralazine.
(ii) Bioavailability of Drugs
Ans.
Bioavailability is defined as rate at which and the extent to which the active concentration of the drug is available at the desired site of action.
Bioavailability = Rate & Extent of absorption = Area under the plasma conc Vs. time curve. (AUC)
Factors Affecting Bioavailability:
Factors affecting bioavailability can broadly be classified as:
1. Pharmaceutical factors
2. Pharmacological factors
1. Pharmaceutical factors:
When a drug is administered by a route other than iv, the drug must dissolve before it becomes available for absorption. An important influence on bioavailability is, therefore, the formulation of the drug in the form of tablet, capsule, suspension, solution etc.Generally, bioavailability would be expected to decrease in the following order solution > suspension> capsule > tablet > coated tablet. Various pharmaceutical of formulation factors affect disintegration and dissolution. Some of these are:
(a) Particle size: The smaller the particle size the greater would be the surface area which would result in greater rate of dissolution.
(b) Salt form: The dissolution rate of a particular salt is usually different from that of the parent compound. Salts of weakly acidic drugs, as a rule, are water soluble. Free acidic drug is precipotated from these salts in a micro crystalline form which has faster dissolution rate and hence enhanced bioavailability e.g. sodium tolbutamide and sodium secobarbital have better. bioavailability than tolbutamide and secobarbital.
(c) Crystal form: The absorption rate and bioavailability of a drug depends upon its crystalline form also e.g. amoprphous chloramphenicol palmitate and amorphous novobiocin have faster dissolution rate and better bioavailability as compared to their crystalline forms.
(d) Water of hydration: Many drugs can associate with water to produce crystalline forms called the hydrates. The anhydrous forms of caffeine, theophylline and ampicillin have faster dissolution rate and better bioavailability than the hydrous forms of these drugs.
(e) nature of excipients and adjuvants : These are the pharmacologically inert substances (e.g. starch, lactose, calcium sulphate, gums, polysorbate-80) which are added to the formulation as a filling material (when drug contents are too small) or as binding agents or to obtain a proper granular size. These too, have tremendous effect on the bioavailability of drugs like phenytoin, digoxin, levodopa, and warfarin etc.
(t) Degree of ionization: Nonionized lipid soluble drugs are better absorbed while strongly acidic or basic drugs or highly ionised drugs show reduced bioavailability e.g. streptomycin, sulphaguanidin, neostigmine, and d-tubocurarine.
2. Pharmacological factors:
In addition to the pharmaceutical factors other pharmacological and physiological factors also affect the absorption and bioavailability. These are
(a) Gastric emptying and gastrointestinal motility: Gastric emptying is promoted by fasting. anxiety, lying on right side, hyperthyroidism and with drugs like metoclopramide. Gastric emptying is retarded by fatty diet, endogenous depression, lying on left side, pyloric stenosis, hypothyroidism and with drugs like atropine, propantheline, imipramine and chlorpromazine.
The extent of absorption of drugs that are incompletely absorbed (e.g. digoxin), may be dependent on intestinal motility. For example, propantheline increases while metoclopramide decreases the bioavailability of digoxin by increasing or reducing the transit time of the unabsorbed drug respectively, through the small intestine.
(b) Gastrointestinal disease :
There are several pathophysiological factors that affect drug absorption. For example in achlorhydria, gastric acid secretion is decreased with a concomitant increase in gastric pH. This increases the absorption of weakly acidic drugs like aspirin because at higher pH its dissolution is faster.
(c) Food and other substances : In general, gastrointestinal absorption is favoured by an empty stomach while the absorption rate (not the extent) is reduced after the ingestion of food. However, both the rate and extent of absorption of certain antibiotics (e.g. rifampicin) is reduced after meals. Absorption of tetracyclines is also markedly reduced if taken with milk or milk products (forms poorly absorbed complex with calcium ions). Absorption of certain antifungal drugs (e.g. griseofulvin) is enhanced by administering the drug with a fatty diet.
(d) First pass effect: First pass effect means the drug degradation occurring before the drug reaches the systemic circulation. The net result is the decreased bioavailability and diminished therapeutic response.
(e) Drug-drug interactions : Differences in bioavailability can also be observed due to drug-drug interactions. For example, liquid paraffin decreases the bioavailability of vitamin A as it emulsifies fats and, therefore, causes deficiency of fat soluble vitamins like A, D and E. Antacid containing aluminium, calcium and magnesium and hematinics containing iron cause reduced bioavailability of tetracyclines.
(f) Pharmacogenetic factors: Large differences in bioavailability often exist among humans due to pharmacogenetic reasons. Obviously, slow acetylators of isoniazid and PAS show increased bioavailability and, therefore, are more subject to isoniazid and PAS toxicity (e.g. Eskimos, japanese and Chinese). Contrarily, fast acetylators, like Egyptians, Israelis and Scandinavians show reduced bioavailability.
(g) Miscellaneous factors: Besides these
factors, multiple other factors like
(i) route of administration
(ii) area of absorbing surface and
(iii) state of circulation at the site of absorption also affect the bioavailability.
Comments
Post a Comment