The BPS meeting in Cardiff, July 11-15, 2000 . Symposium on EpharNET, July 12

Jirina Martinkova, Stanislav Micuda
INNOVATION IN TEACHING PROGRAM FOR PHARMACOLOGY
CHARLES UNIVERSITY OF PRAGUE,
FACULTY OF MEDICINE, DEPT. OF PHARMACOLOGY
in HRADEC KRÁLOVÉ, CZECH REPUBLIC

Dear colleagues,
let me informed you about our experience with developing and using innovative teaching methods that are used at the medical faculty in Hradec Králové. As these methods were also accepted by most of medical faculties in our country, they can be taken as exemples of innovated process in the Czech Republic.

There are two main approaches:

1. SIMULATED PHARMACOLOGICAL PREPARATIONS
   (by PIDATA´S methods, developed at the University of Leeds, GB) based on computer assisted program.
   in PHARMACODYNAMICS
   • in vivo
   • in vitro
   and PHARMACOKINETICS
   we have been using these methods since 1993.
   
2. CASE REPORTS (STUDIES) were developed at the medical faculty in Hradec Králové we have been developing since 1990

I. Simulated pharmacological preparations.

The program is driven by a self - explanatory menu and available for analyses both in pharmacodynamics and pharmacokinetics. On initiation, the program displays a screen of explanatory text which briefly describes the preparation and the use of the program. A menu lists agents to be used for pharmacological analysis: agonists, antagonists, uptake inhibitors and so on. Output is generated on screen or as a permanent record via a standard printer.

There are 8 methods in our original package:

1. ISOLATED ILEUM SIMULATION
2. SIMULATED HEART RATE AND BLOOD PRESSURE (IN VIVO)
3. ISOLATED PHRENIC NERVE-DIAPHRAGM
4. SIMULATED ANTERIOR TIBIALIS-SCIATIC NERVE (IN VIVO)
5. FROG RECTUS ABDOMINIS SIMULATION
6. ISOLATED VAS DEFERENS SIMULATION
7. ARTERIAL AND VENOUS RINGS
8. PHARMACOKINETICS

• MCQ AUTHORING PACKAGE

Let me demonstrate for you methods in pharmacodynamics in vivo and in vitro and some methods in pharmacokinetics.

First, METHODS IN PHARMACODYNAMCS IN VIVO
simulate blood pressure (BP) and heart rate (HR) in experiments with tree models of laboratory animals

• reserpinised
• pithed
• normal

The students perform pharmacological analyses to describe the pharmacological properties of a variety of agonists and antagonists, agents influencing the synthesis and release of a neurotransmitters as follow:

NORADRENALINE, ADRENALINE, ISOPRENALINE PHENYLEPHRINE PHENOXYBENZAMINE, GUANETHIDINE, COCAINE, TYRAMINE, DMPP, YOHIMBINE, PRAZOSIN, PROPRANOLOL, ATENOLOL, HEXAMETHONIUM, ACETYLCHOLINE, NEOSTIGMINE, ATROPINE, HISTAMINE, MEPYRAMINE, RANITIDINE, NIFEDIPINE, ANGIOTENSIN, VASOPRESSIN, UNKNOWNS

for instance: See Figure No 1 by administering increased doses of catecholamines, the students differentiate the effects of adrenaline and noradrenaline on BP and HR. In the presence of an alpha blocker (prazosine) - Figure No 2 - adrenaline no longer increases blood pressure unless its dose is elevated (and a dose-response curve is schifted to the right) while heart rate is still elevated as beta receptors are not blocked.

Second, METHODS IN PHARMACODYNAMCS IN VITRO
can be used, for instance, to simulate the processes at the end plate using the methods of isolated rat phrenic nerve-diaphragm preparation , recording of resting tension and of twitch tension in response to: * single shocks stimulation to the phrenic nerve during supramaximal rectilinear shocks of 0.2 msec duration at frequency of 0.05 or 0.5 Hz * a brief tetanus (30 Hz supramaximal stimulation for 5 sec). suited to teach the art of experimental design

Drugs available:

• competitive neuromuscular (non-depolarizing) blocking agents
  TUBOCURARINE, PANCURONIUM, ATRACURIUM, GALLAMINE, FAZADINIUM
• depolarizing neuromuscular blockers:
  SUXAMETHONIUM, DECAMETHONIUM
• anticholinesterase agents:
  NEOSTIGMINE, PHYSOSTIGMINE, EDROPHONIUM
• a potassium channel blocker:
  4-AMINOPYRINE
• a choline uptake blocker
  TRIETYLCHOLINE
• nicotinic agonists
  ACETYLCHOLINE, CARBACHOL

and others For instance Figure No 3 demonstrates that neostigmine increases twich height of the striated muscle in the presence of tubocurarine due to a reverse of competitive blockade. In the presence of suxamethonium neostigmine decreases twich height because of an additive action.

C o n c l u s i o n: At the beginning students should be given designs of experiments and work schedules (in a workbook) Then they

• perform their analyses independently by following a set protocol or can design their own experiments to answer an assigned problem
• evaluate experiments: construct the dose response curves and evaluate their shifting or E max declining

SIMULATIONS IN PHARMACOKINETICS: PK SIM
describe some elementary pharmacokinetic properties of drugs.
Figure 4a shows importance of the route of administration for plasma concentration of a drug (diazepam given in dose of 10 mg orally and intravenously and plasma concentration achieved after these different routes of administration).
Figure 4b simulate plasma concentration of a drug with a narrow therapeutic window which is excreted (eliminated) mainly via glomerular filtration in a person with a normal renal function in comparison with a patient with renal insufficiency. In the latter one plasma concentration reaches toxic level in spite of the fact that he is given the same dose as the individuum without impaired renal function.

II. Case reports (studies)

SCHEME OF EACH STUDY:

• HISTORY
• LABORATORY AND PHYSICAL EXAMINATION
• DIAGNOSIS
• PHARMACOTHERAPY AND ITS COMPLICATION: ADVERSE AND TOXIC EFFECTS, DRUG INTERACTIONS)
• CONCLUSION
• SUMMARY
• REFERENCES

PROBLEMS:

• AN INTERDISCIPLINARY APPROACH
• NOT EASY, TIME - CONSUMING
• NECESSITATE INNOVATING
• AT THE INTERNATIONAL LEVEL
• COMPATIBLE WITH GUIDELINES FOR PHARMACOTHERAPY?
• DIFFERENT LABORATORY MEASURES

OUR "CORE" TOPICS:

• PHARMACOKINETICS
• ADVERSE REACTIONS
• DRUG INTERACTIONS
• THERAPEUTIC DRUG MONITORING (ANTIEPILEPTICS, AMINOGLYCOSIDES, THEOPHYLLINE, METHOTREXATE)
• DRUGS IN THE ELDERLY
• DRUGS IN INFANTS
• DRUGS AND THE KIDNEY
• HYPERTENSION
• CONGESTIVE CARDIAC FAILURE
• ANTICOAGULANT THERAPY AND ITS CONTROL
• DIABETES MELLITUS (DIABETIC FOOT)
• ANTIBIOTIC AND ANTIFUNGAL THERAPY
• SUBSTANCE OF ABUSE

DEMONSTRATION OF THE PROGRAM WITH : LONG Q-T INTERVAL SYNDROM