Download Clinical pharmacology - Львівський національний медичний

МІНІСТЕРСТВО ОХОРОНИ ЗДОРОВ’Я УКРАЇНИ
НАЦІОНАЛЬНИЙ МЕДИЧНИЙ УНІВЕРСИТЕТ
імені О.О.БОГОМОЛЬЦЯ
Фармацевтичний факультет
Кафедра клінічної фармакології та клінічної фармації
“ЗАТВЕРДЖЕНО”
на методичній нараді кафедри
клінічної фармакології та клінічної фармації
Завідувач кафедри
професор М.В.Хайтович
___________
“______” _____________ 2016 р.
NOTEBOOK
For student’s self-guided work of discipline
«Clinical pharmacology»
for the 5th year students of the stomatological faculty
Kyiv - 2016
TOPIC. THE OBJECT AND PURPOSE OF CLINICAL
PHARMACOLOGY. MAIN THESIS OF PHARMACOKINETICS AND
PHARMACODYNAMICS
1. Hours – 2
2. Material and methodological support for the topic.
 set of "conceptual" tests (20)
 histories, case studies (3)
 tests from the database of "Step 2" (20)
Topic’s rationale. The list of drugs, that are used in dentistry is constantly
increasing. In their practice dentist should consider that the patient may have
related somatic diseases, and that he can already receive appropriate medical
treatment. This requires knowledge of drugs, their selection and optimal
management.
3. Purpose of the class:
General - master the basic concepts of clinical pharmacology.
Specific goals:
Know:
 basic
concepts of clinical pharmacology ("clinical
pharmacokinetics", "clinical pharmacodynamics", "clinical
pharmacogenetics", "INN" etc.);
 basic principles of pharmacodynamics of drugs;
 the basic parameters of the clinical pharmacokinetics;
 mechanisms of absorption, distribution, biotransformation and
excretion of drugs;
 concept of transporters of drugs;
 peculiarities of clinical pharmacology of drugs in people of all
ages, pregnant women and women who are breastfeeding;
 the concept of evidence-based medicine.
Be able to:
 use basic terms and concepts of clinical pharmacology;
 identify drugs with a narrow range of action;
 interpret basic parameters of the pharmacokinetics of drugs;
 identify main features of drugs' metabolism;
4. Graph of logical structure of the topic.
№ The main stages of
the class, their
functions
and
content
1 Preparatory stage:
Arrangements.
Setting educational
goals. Control of
initial
level
of
knowledge.
2. The main stage:
1. The work of
students under the
guidance
of
a
teacher.
2. Independent work
of students.
3.
4.
Methods
control
learning
of Materials
for Time
and methodological
minutes
support
Tests.
Method
of
specific
situations
(demonstration
of patients) or
discussion
of
educational
cases.
Definition of
the
main
symptoms and
syndromes
of
patients,
providing
treatment.
Discussion of results The method of
of independent work group
discussion.
Evaluation
of
diagnostic and
curative work of
students.
Tests (tests from
Final stage:
Control
and the database of
correction of level of "Step 2")
professional skills
and abilities.
Summing up, the
announcement
marks.
Homework.
Tests (2 options 15
with 10 tests).
Curation
of 40
patients, medical
history,
prescriptions
sheets, case studies
(3)
Workbook,
case 20
studies, discussion
of
problematic
patients
Tests (tests from 15
the database of
"Step 2" - 2 options
with 10 tests).
in
6. Student’s work map.
№
1.
2.
3.
4.
5.
6.
7.
8.
Main tasks
Directions Answers
Master terminology of clinical
Learn
pharmacology:
- clinical pharmacology
- clinical pharmacokinetics
- clinical pharmacodynamics
- clinical pharmacogenetics
Learn the mechanism of action
Learn
of drugs:
1. On specific receptors
2. On specific enzymes
3. Physico-chemical effect on
cell membranes
4. Direct chemical action with
metabolites of the cells
Type of drug’s action:
Learn
- main effect (local, reflex,
resorptive);
- resorptive effect (direct,
indirect, selective,
nonselective, reversible,
irreversible, main)
- side effect (accumulation,
addiction, allergy, idiocrasy,
dysbacteriosis, stability,
embryotoxic and
carcinogenic, withdrawal
syndrome)
- direction of pharmacological
correction (causal,
pathogenetic, symptomatic,
stimulating, replacement,
palliative, empirical)
Therapeutic margin
Learn
Therapeutic index
Learn
The dosage of drugs
Learn
- toxic
- lethal
- therapeutic (minimum, average,
maximum, shock and supportive,
one-time, daily, course)
Ways of drug administration
Learn
The pharmacokinetics of drugs
Learn
(absorption, distribution,
metabolism (biotransformation),
output (excretion, elimination))
9. Pharmacogenetics and factors
affecting metabolism (induction,
inhibition)
10. Clinical research: stages of
preclinical and clinical drug
trials
Learn
Learn
Main definitions:
Clinical pharmacology (CP) – is …
International Nonproprietary Name (INN) — is ….
Pharmacodynamics – is a part of pharmacology, that studies ….
Pharmacokinetics – is a part of clinical pharmacology, that studies ….
Therapeutic margin – is …..
Clinical relevance of pharmacokinetical values
Clinical relevance
Value
Bioavailability (F)
Time to maximum
observed drug
concentration (Тmax)
Steady state
concentration (Css)
The volume of
distribution (Vd)
circulating half-life
(Т1/2)
Clearance (Cl)
Phases of pharmacokinetics
a. drug admission
b._________________________
c._________________________
d._________________________
e._________________________
Phases of biotransformation
a.
_______________________________
b.
_______________________________
Mechanism of absorption
a. passive diffusion
b.__________________________
c.__________________________
d.__________________________
e.__________________________
Mechanism of drug recovery in
the kidneys
a. passive glomerular filtration
b.__________________________
c.__________________________
% of protein-binding show specifics of drug’s_____________________
Drug’s bioavailability depends on _____________________________________
Т ½ show drug’s_______________________________________
Drug’s clearance with kidneys shows ______________________________
_____________________________________________________________
Human liver P450s (CYPs), and some of the drugs metabolized (substrates),
inducers, and selective inhibitors
CYP
Substrates
Inducers
Inhibitors
1А2
theophylline
smoking
fluroquinolone
Genetic
polymorphism
No
2С9
2С19
2D6
2E1
3А4
Pharmacogenetics – science that studies ….
Clinical classification of genetically determined changes in pharmacological
response:
 may cause serious reactions….

 did not lead to serious adverse disorders …

 inefficiency or low efficiency of drug ….
Drug therapy in pregnancy
Critical periods for teratogenic effect:
1)
2)
3)
The degree of drugs’ danger to the fetus is conventionally divided into groups
or categories from “A" (safe) to "D" (contraindicated during pregnancy). There is
also a category "X", which includes drugs, that are completely contraindicated in
pregnancy.
Features of clinical pharmacology in nursing mothers
Most drugs can be administered to a mother who feeds are excreted with milk.
The concentration of drug in the milk is equal to such level in the mother's blood.
When drugs with a narrow therapeutic range are administered, especially longterm, the child may develop undesirable adverse reaction.
Clinical pharmacology of drugs in the elderly
Pharmacotherapy of patients in this age group is complicated by the
presence of several diseases, and therefore the use of various drugs increase the
risk of unwanted side reactions (in patients over 60 years - 1.5 times more likely
than in youth), changes in pharmacokinetics and pharmacodynamics of drugs.
Appearance of the unwanted side effects may also be due to the fact that the
patient has mixed up the drugs or received an extra dose.
Polypragmasy is more oftenly noted when treating older people, than other
age groups.
Evidence-based medicine.
The basic principle of evidence-based medicine is that specific clinical actions
for treating a patient are made not so much based on personal experience or expert
opinion, but on a basis of proven scientific data obtained during the well-planned,
controlled clinical trials.
Evidence levels:
• Level I (А) –
• Level II (В) –
• Level III (С) –
• Level IV (D) –
Cochrane Library – is …
7. Tasks for self-guided work
7.1. List of terms to be studies:
1. The definition of "Clinical pharmacology".
2. The route of administration.
3. Mechanisms of absorption of drugs. The bioavailability.
4. Distribution of drugs, volume of distribution.
5. Phases of biotransformation of drugs, inducers and inhibitors of enzymes
of metabolism.
6. Presystemic metabolism of drugs.
7. The role of transporters in drugs bioavailability.
8. Mechanisms of drugs excretion. Half-life.
9. The mechanism of action of drugs and their pharmacological effects and
changes to functions of the body in response to the impact of drugs.
10. Pharmacogenetics.
11. Pecualrities of the use of drugs in children and the elderly, pregnant and
lactating women.
12. Evidence-based medicine.
7.2. The list of works to be studied:
1. Use the basic terms and concepts of clinical pharmacology.
2. Identify the drugs with a narrow range.
3. Interpret the main parameters of pharmacokinetics of drugs.
4. Identify the features of metabolic drugs.
7.3. The list of practical skills that are to be mastered:
1. Use the basic terminology.
2. To interpret the basic parameters of the pharmacokinetics of drugs.
8. Situational tasks to determine the final level of knowledge.
Task 1.
The pediatrician noted that an 8-month-old girl has no increase in body
length. The mother noted recurrent diaper rash. Objectively - manifestations of
Cushing's syndrome.
Collecting more detailed medical history revealed that the mother used
Advantan ointment on the baby's skin that she was prescribed for treatment of
eczema.
Explain what led to the development of Cushing's syndrome?
Why is this possible?
Task 2
A young man in a state of unconsciousness after an accident is taken to the
emergency room. He has hypoventilation and has traces of injections in his arms,
constricted pupils. Naloxone was administered intravenously and in 30 seconds the
patient became fully awake and started to breathe normally. He was excited and
aggressive.
Provide diagnosis.
What is he mechanism of action of naloxone?
Task 3
A patient of 68 years has been continuously using nitroglycerin for 2 months.
Recently he notes gradual decrease in clinical effect.
How is this phenomenon called? How to explain its origin?
9. Recommendations for the presentation of students’ results.
10. Literature
Main
1.
Katzung B.G., Masters S.B., Trevor A.J. Basic and clinical pharmacology.
The McGraw-Hill Companies. 2012. 1229 p.
Additional
2.
James M Ritter, Lionel D Lewis, Timothy GK Mant and Albert Ferro. A
Textbook of Clinical pharmacology and Therapeutics, FIFTH EDITION. 2008.
476 p.