I am professionally pharmacist. These slides for clinical subject especially for pharmacy department students. I hope students get more benefits about it.

1. Topic One: Rationale Use of Drugs
Dr. Tahir Mehmood Khan, Associate Professor
Institute of Pharmaceutical Sciences
UVAS, Pakistan

2. Learning Outcomes
 At the end of the session students should be in a position to:
 Define rationale use of drugs (RUD)
 Describe the benefits of RUD and consequences of IRUD
 Understand the reasons underlying irrational use
 Discuss strategies and interventions to promote rational
use of medicines
 Discuss the role of government and WHO in solving drug
use problems

3. Defining RUD
RATIONAL means “prescribing right drug, in
adequate dose for the sufficient duration &
appropriate to the clinical needs of the patient at
lowest cost”
 In simple words, prescribing and dispensing drugs to
patients as per formulary or therapeutics guidelines
can be referred as RUD
 Most of the guidelines always recommend cost
effective treatments

4. Explanation of RUD
 RATIONAL means “prescribing right drug, in adequate
dose for the sufficient duration & appropriate to the clinical
needs of the patient at lowest cost”
Right drug ? Acetaminophen/ PCM
to relief fever in a new
born?
Aspirin to relief fever in
a new born?
Adequate
dose?
Warfarin 5mg OD ? Warfarin 10mg OD ?
Sufficient
duration
665 mg Panadol Osteo
PRN?
500 mg Panadol 2 Tab
QID?
Adequate
dose
15mg/kg IV
vancomycin?
25mg/kg IV
vancomycin?
Cost 5 RS/ Pill 50 RS/ Pill

5. Why RUD is essential
 RUD a prime pillar in pharmaceutical care
 To achieve the primary and secondary
outcomes in an effective manner its vital to
practice RUD
 Right/ appropriate dose is always based on;
 Body surface area/ Weight ; Age;
 Physiological function
 Genetic deficiencies of enzymes
 Availability of drugs
 Medication Stewardship program

6. How Genetic deficiencies of
enzymes effect dose and
effect?
 Example of amitriptyline

7. Right route of drug is also
important
 When vancomycin will be beneficial for a
patients who is suffering from high grade fever/
sepsis?
1. When given IV?
2. When given orally?
 When Saline solution will be effective for sinusitis?
1. IV
2. Intranasal

8. Factors Influencing RUD
Treatment
Choices
Prior Knowledge
Habits
Scientific
Information
Relationships
With Peers
Influence
of Drug
Industry
Workload &
Staffing
Infra-
structure
Authority &
Supervision
Societal
Information
Intrinsic
Workplace
Workgroup
Social &
Cultural
Factors
Economic &
Legal Factors

9. Why RDU implementation is
essential?
 Increase in the number of drugs available.
Especially availability of generics have a +ve
impact in getting a cost effective treatment
 Drug resistance [ Antibiotics, Anti-TB, HAART ]
Efforts to prevent the development of resistance,
DOTS will effective
 Growing awareness: Today, the information
about drug development. Todays consumers are
more aware.

10. How to increase RDU
implementation
 Increased cost of the treatment led to the
identification of cheaper regimens
 Guideline implementations & Developments of
new standards of practice
 Specialty and pharmacotherapy services
 Appropriate counselling for the OTC product
over the counter

11. Why there is a irrational use?
 Lack of information/ training/ CMEs for consumers
and health care professionals
 Role model – Teachers or seniors
 Poor communication between health professional &
patient
 Esp. between Pharmacist and Physician
 Lack of e-prescription in community pharmacy

12. Why there is a irrational use?
 Lack of diagnostic facilities/Uncertainty of diagnosis
 In Pakistani setting, 90% Anti-Biotics are
prescribed without any culture sensitivity report
 INR testing follow up is poor
 TDM services are almost negligible
 Demand from the patient: NEED more MEDs
 Defective drug supply system & ineffective drug
regulation, Lack of guidelines
 Promotional activities of pharmaceutical industries

13. Adequacy of diagnostic process
Source: Thaver et al SSM 1998, Guyon et al WHO Bull 1994, Krause et al TMIH 1998, Bitran
HPP 1995, Bjork et al HPP 1992, Kanji et al HPP 1995.
0 10 20 30 40 50 60
Tanzania
Angola
Senegal
Burkino Faso
Bangladesh
Pakistan
% observed consultations where the diagnostic process was adequate

14. 5-55% of PHC patients receive injections -
90% may be medically unnecessary
0% 10% 20% 30% 40% 50% 60%
E astern Caribean
Jamaica
E l S alvador
Guatemala
E cuador
L.AM E R. & CAR.
Nepal
Indonesia
Y emen
AS IA
Zimbabwe
T anzania
S udan
Nigeria
Cameroon
Ghana
AFRICA
% of primary care patients receiving injections
Source: Quick et al, 1997, Managing Drug Supply
ä 15 billion injections per year globally
ä half are with unsterilized needle/syringe
ä 2.3-4.7 million infections of hepatitis B/C
and up to 160,000 infections of HIV per
year associated with injections

15. 0
5
10
15
20
25
30
35
FR GR LU PT IT BE SK HR PL IS IE ES FI BG CZ SI SE HU NO UK DK DE LV AT EE NL
DDD
per
1000
inh.
per
day
Variation in outpatient antibiotic use in
26 European countries in 2002
Source: Goosens et al, Lancet, 2005; 365: 579-587; ESAC project.

16. IRDU a common problem in
developing countries?
 The use of drugs when no drug therapy is
indicated, e.g. antibiotics for viral upper
respiratory infections.
 The use of the wrong drug for a specific
condition requiring drug therapy, e.g.
tetracycline in childhood diarrhea that can be
treated well with ORS.
TC are CI among individuals age less than 12 years

17. IRDU a common problem in
developing countries?
 The use of drugs with doubtful or unproven
efficacy, e.g. the use of anti-motility agents in
acute diarrhea
 Failure to provide available, safe and effective
drugs, e.g. failure to vaccinate for measles or
tetanus, or failure to prescribe ORS for acute
diarrhea.

18. IRDU a common problem in
developing countries?
 The use of correct drugs with incorrect
administration, dosage and duration, e.g. using
intravenous route where oral or suppository
routes would be appropriate.
 The use of unnecessarily expensive drugs, e.g.
the use of a third generation, broad-spectrum
antimicrobial when a first line, narrow spectrum
agent is indicated.
 Antibiotics misuse

19. % compliance with guidelines by WHO
region
0
10
20
30
40
50
60
1982-1994 1995-2000 2001-2006
Sub-Saharan Africa (n=29-48) Lat. America & Carrib (n=5-13)
Middle East & C. Asia (n=4-8) East Asia & Pacific (n=7-11)
South Asia (n=6-12)

20. Public / private treatment of acute
diarrhoea by doctors, nurses, paramedical
staff
0
10
20
30
40
50
60
70
80
% diarrhoea cases
prescribed antibiotic
% diarrhoea cases
prescribed anti-
diarrhoeals
% diarrhoea cases
prescribed ORS
Public (n=54-90) Private-for-profit (n=5-10)

21. Treatment of ARI by prescriber type
0
10
20
30
40
50
60
70
80
% viral URTI cases
prescribed antibiotic
% pneumonia cases
prescribed antibiotic
% ARI cases treated with
cough syrup
Doctor (n=26-62) Nurse/paramedic (n=12-86) Pharmacy staff (n=9-17)

22. Hazards of Irrational drug
use
 Ineffective & unsafe treatment
 Over-treatment of mild illness
 Inadequate treatment of serious illness
 Exacerbation or prolongation of illness
 Distress & harm to patient

23. Hazards of Irrational drug
use
 Increase the cost of treatment
 Increased morbidity and mortality
 Increased Adverse drug reactions and drug
Resistance
 Loss of patient confidence in health system

24. Overuse and misuse of antimicrobials
contributes to antimicrobial resistance
 Malaria
 choroquine resistance in 81/92 countries
 Tuberculosis
 0-17 % primary multi-drug resistance
 HIV/AIDS
 0-25 % primary resistance to at least one anti-retroviral
 Gonorrhoea
 5-98 % penicillin resistance in N. gonorrhoeae
 Pneumonia and bacterial meningitis
 0-70 % penicillin resistance in S. pneumoniae
 Diarrhoea: shigellosis
 10-90% ampicillin resistance, 5-95% cotrimoxazole resistance
 Hospital infections
 0-70% S. Aureus resistance to all penicillins & cephalosporins
Source: WHO country data 2000-03

25. How to improve the
situation?
What should be done to
improve the situation in
Pakistan ?

26. How to improve the
situation?
 Make a specific diagnosis as per protocols
 Consider the pathophysiology of diagnosis selected
: If the disorder is well understood the prescriber is in
a better position to select effective therapy.
 Select a specific therapeutic objective or goal and
medications should be selected based on it.
 Select a drug of choice based on guidelines;
Empirical, Preventive or Direct.

27. How to improve the situation?
 Determine the appropriate dosing regimen to obtain
desired therapeutic levels and the drug must be
inexpensive, easily available and should be
prescribed in generic name.
 Drug interaction and adverse effects must be taken
into account before initiating combination of drugs.
 Device a plan for monitoring the drugs action and
determine an end point for the therapy.
 Plan a program for patient education and
counselling

28. Economic:
 Offer incentives
– Institutions
– Providers and patients
Managerial:
 Guide clinical practice
– Information systems
– Drug supply / lab capacity
Regulatory:
 Restrict choices
– Market or practice
controls
– Enforcement
Educational:
 Inform or persuade
– Health providers
– Consumers
Use of
Medicines
Strategies to Improve Use of Drugs

29. Educational Strategies
 Training for Providers
 Undergraduate education
 Continuing in-service medical education (seminars,
workshops)
 Face-to-face persuasive outreach e.g. academic
detailing
 Clinical supervision or consultation
 Printed Materials
 Clinical literature and newsletters
 Formularies or therapeutics manuals
 Persuasive print materials
 Media-Based Approaches
 Posters
 Audio tapes, plays
 Radio, television

30. Managerial strategies
 Changes in selection, procurement, distribution
to ensure availability of essential drugs
 Essential Drug Lists, morbidity-based quantification, kit
systems
 Strategies aimed at prescribers
 targeted face-to-face supervision with audit, peer
group monitoring, structured order forms, evidence-
based standard treatment guidelines
 Dispensing strategies
 course of treatment packaging, labelling, generic
substitution

31. Economic strategies:
 Avoid perverse financial incentives
 prescribers’ salaries from drug sales
 Insurance policies that reimburse non-essential drugs
or incorrect doses
 Flat prescription fees that encourage polypharmacy
by charging the same amount irrespective of number
of drug items or quantity of each item

32. Regulatory strategies
 Drug registration
 Banning unsafe drugs - but beware unexpected
results
 substitution of a second inappropriate drug after
banning a first inappropriate or unsafe drug
 Regulating the use of different drugs to different
levels of the health sector e.g.
 licensing prescribers and drug outlets
 scheduling drugs into prescription-only & over-the-
counter
 Regulating pharmaceutical promotional
activities

33. Role of Doctors and Pharmacist
 They can establish a common approach to
the rational use of drugs by giving advice and
information to patient regarding the proper
use of drugs.
 They have more opportunity to interact
closely with the prescriber and therefore, to
promote the rational prescribing and use of
drugs.

34.  By having access to medical records, they are in
a position to influence the selection of drugs,
dosage regimens, to monitor patient
compliance and therapeutics, response to drugs
and to recognize and report adverse drug
reactions. DUEs
 They can control hospital manufacture and
procurement of drugs to ensure the supply of
high quality products.

35. Impact of multiple interventions on
injection use in Indonesia
0%
20%
40%
60%
80%
100%
1 3 5 7 9 11 13 15 17 19 21 23 25
Months
Proportion
of
visits
with
injection
Comparison group Interactive group discussion
Source: Long-term impact of small group interventions, Santoso et al., 1996
Interactive group discussion (IGC group only)
Seminar (both groups)
District-wide monitoring
(both groups)

36. Conclusion :
 The demands of rational drug use are:
• Availability of essential & life saving drugs and
unbiased drug information with generic name.
• Adequate quality control & drug control.
• Withdrawal of hazardous & irrational drugs.
• Drug legislation reform.

37. Reference
 WHO guidelines on the rationale use of drug

38. Topic Two: Essential Medication List
Dr. Tahir Mehmood Khan, Associate Professor
Institute of Pharmaceutical Sciences
UVAS, Pakistan

39. Learning Outcomes
 At the end of the session students should be in a position to:
 Define Essential Medication List
 Describe the benefits of EML

40. What is EML
 EML is comprised of minimum medicine
needed for a basic health‐care system,
listing the most efficacious, safe and
cost–effective medicines for priority
conditions.
 Priority conditions are selected on the
basis of current and estimated future
public health relevance, and potential
for safe and cost‐effective treatment

41. What is EML
 These EML that contain minimum
medicine needed for a basic
health‐care system, for priority conditions
is also called as core list

42. EML: The complementary list
 Essential medicines for priority diseases, for which
specialized diagnostic or monitoring facilities,
and/or specialist medical care, and/or specialist
training are needed.
 In case of doubt medicines may also be listed as
complementary on the basis of consistent higher
costs or less attractive cost‐ effectiveness in a
variety of settings.

43. Instructions to interpret
medication list
 The square box symbol □ is primarily intended to
indicate similar clinical performance within a
pharmacological class.
 The listed medicine should be the example of the
class for which there is the best evidence for
effectiveness and safety.

44. Instructions to interpret
medication list
 In some cases, this may be the first medicine that
is licensed for marketing; in other instances,
subsequently licensed compounds may be safer
or more effective.
 Where there is no difference in terms of efficacy
and safety data, the listed medicine should be
the one that is generally available at the lowest
price, based on international drug price
information sources. Not all square boxes are
applicable to medicine selection for children

45. Instructions to interpret
medication list
 The a symbol indicates that there is an
age or weight restriction on use of the
medicine

46. Instructions to interpret
medication list
Where the [c] symbol is placed
next to the complementary list it
signifies that the medicine(s)
require(s) specialist diagnostic or
monitoring facilities, and/or
specialist medical care, and/or
specialist training for their use in
children

47. Instructions to interpret
medication list
Where the [c] symbol is placed
next to an individual medicine or
strength of medicine it signifies that
there is a specific indication for
restricting its use to children

48. % deaths in Pakistan

49. Referral system in Pakistan

50. Examples of Explanatory
notes in EML Pakistan

51. Updates in WHO EML 2017
 There is a revised grouping for Antibiotics keeping in
view the principle of Anti-biotic stewardship programs
 Mainly Abs are classified in to 3
1- ACCESS GROUP – empirical or first line therapy
2- WATCH GROUP- higher resistance potential and that
are still recommended as first or second choice
treatments
3- RESERVE GROUP- ‘last-resort’ options, or tailored to
highly specific patients and settings

55. Topic Three: STROKE
Dr. Tahir Mehmood Khan, Associate Professor
Institute of Pharmaceutical Sciences
UVAS, Pakistan

56. Learning Outcomes
 At the end of the session students should be in a position to:
 Understand pathophysiology of stroke
 Understand ttypes of strokes
 Understand stroke progression and complications
 Understand Pharmacotherapy of stroke

57. Background / Definition
 Stroke is the 2nd leading cause of death world
wide.
 Stroke can be either ischemic (87%) or
hemorrhagic (13%) and the two types are
treated differently
 Stroke is defined as sudden death of brain cells
due to lack of oxygen, caused by blockage of
blood flow or rupture of an artery to the brain.

58. Common symptoms
 Weakness,
 Paralysis of one side of the body can be symptoms

59. Common symptoms
 Hemiparesis, monoparesis, or (rarely) quadriparesis
 Monocular or binocular visual loss
 Visual field deficits
 Diplopia
 Dysarthria [Sudden loss of speech]
 Facial droop
 Ataxia
 Vertigo (rarely in isolation)
 Aphasia [comprehension of speech]
 Sudden decrease in the level of consciousness

60. Common symptoms

61. Types of stroke
There are three main types of stroke:
 Ischemic stroke: This is the most common type of stroke. A
blood clot prevents blood and oxygen from reaching the
brain.
 Hemorrhagic stroke: This occurs when a weakened blood
vessel ruptures and normally occur as a result of aneurysms or
arteriovenous malformations (AVMs).
 Transient ischemic attacks (TIAs): Also referred to as a mini-
stroke, these occur after blood flow fails to reach part of the
brain. Normal blood flow resumes after a short amount of
time, and symptoms cease.

62. Types of stroke

63. Classification of Stroke
based on root causes

64. Risk Factors

65. Pathophysiology
 Acute ischemic strokes result from vascular
occlusion secondary to thromboembolic
disease.
 Ischemia causes cell hypoxia and depletion of
cellular adenosine triphosphate (ATP).
 Without ATP, there is no longer the energy to
maintain ionic gradients across the cell
membrane and cell depolarization.

66. Pathophysiology
 Influx of sodium and calcium ions and
passive inflow of water into the cell lead
to cytotoxic edema
 Based on the amount of flow to each
region of brain the stroke affected areas
can be classified as Ischemic core and
penumbra

67. Pathophysiology
 Affected regions with cerebral blood
flow of lower than 10 mL/100 g of
tissue/min are referred to collectively as
the core.
 These cells are presumed to die within
minutes of stroke onset
 irreversible damage to the brain occurs,
and this is also called as infarction

68. Pathophysiology
 Zones of decreased or marginal
perfusion (cerebral blood flow < 25
mL/100g of tissue/min) are collectively
called the ischemic penumbra.
 Tissue in the penumbra can remain
viable for several hours because of
marginal tissue perfusion

69. Ischemia Cascade

70. Ischemia Cascade
 Cerebral ischemia impairs > abnormal sodium-
calcium exchange > influx of calcium >release of
a number of neurotransmitters > large quantities
of glutamate > N -methyl-D-aspartate (NMDA) at
neurons> neurons then become depolarized >
calcium influx > further glutamate release.
 This massive calcium influx also activates various
degradative enzymes, leading to the destruction
of the cell membrane and other essential
neuronal structures.

71. Ischemia Cascade
 Free radicals, arachidonic acid, and
nitric oxide are generated by this
process, which leads to further neuronal
damage.
 Ischemia also directly results in
dysfunction of the cerebral vasculature,
with breakdown of the blood-brain
barrier occurring within 4-6 hours after
infarction.


72. Ischemia Cascade
 Following the barrier’s breakdown,
proteins and water flood into the
extracellular space, leading to
vasogenic edema.
 This produces greater levels of brain
swelling and mass effect that peak at 3-
5 days and resolve over the next several
weeks with resorption of water and
proteins.

73. Prognosis
 In the Framingham and Rochester stroke studies,
the overall mortality rate at 30 days after stroke
was 28%, the mortality rate at 30 days after
ischemic stroke was 19%, and the 1-year survival
rate for patients with ischemic stroke was 77%.
 However, the prognosis varies greatly in individual
patients, depending on the stroke severity and on
the patient’s premorbid condition, age, and
poststroke complications

74. Diagnosis

75. Diagnosis
 Coagulopathy to be checked in the
case if the patients in a hyper co-
agulable condition.
 Protein C, protein S, and antithrombin III
are best measured in steady state rather
than in the acute stage

76. Goals of Therapy
 Reduce ongoing neurologic injury and
decrease mortality and long-term
disability
 Prevent complications secondary to
immobility and neurologic dysfunction
 Prevent stroke recurrence.

77. Work up and
Pharmacotherapy of IS
 Keep in your mind Infraction/ core is not
reversible
 Recanalization strategies, including the
administration of intravenous (IV)
recombinant tissue-type plasminogen
activator (rt-PA) and intra-arterial
approaches, attempt to establish
revascularization so that cells in the
penumbra can be rescued before
irreversible injury occurs

78. Work up and
Pharmacotherapy of IS

79. Work up and
Pharmacotherapy of IS
 Severity of stroke need to be assessed using NIH stroke
severity scale
https://www.mdcalc.com/nih-stroke-scale-score-nihss

80. Work up and
Pharmacotherapy of IS
 Acute response
 Call 911/2221
 In ER check vital/ ABC, O2,
Hypoglycaemia need to be corrected
 Rt-PA immediate

81. Work up and
Pharmacotherapy of IS

82. Work up and
Pharmacotherapy of IS
Oral anticoagulation is recommended for atrial fibrillation and a presumed cardiac source of embolism. A vitamin K
antagonist (warfarin) is first line, but other oral anticoagulants (eg, dabigatran) may be recommended for some
patients
• Statins reduce risk of stroke by approximately 30% in patients with coronary artery disease and elevated
plasma lipids

83. Work up and
Pharmacotherapy of IS
• Statins reduce risk of stroke by approximately 30% in
patients with coronary artery disease and elevated plasma
lipids
Oral anticoagulation is recommended for atrial fibrillation
and a presumed cardiac source of embolism. A vitamin K
antagonist (warfarin) is first line, but other oral
anticoagulants (eg, dabigatran) may be recommended for
some patients
Low-molecular-weight heparin or low-dose
subcutaneous unfractionated heparin (5000 units three
times daily) is recommended for prevention of DVT in
hospitalized patients with decreased mobility due to stroke
and should be used in all but the most minor strokes

84. Work up and
Pharmacotherapy of HS
 There are no standard pharmacologic strategies
for treating intracerebral hemorrhage.
 Follow medical guidelines for managing BP,
increased intracranial pressure, and other
medical complications in acutely ill patients in
neurointensive care units.
 Vasospasm of the cerebral vasculature is
thought to be responsible for the delayed
ischemia and occurs between 4 and 21 days
after the bleed.

85. Work up and
Pharmacotherapy of HS
 The calcium channel blocker nimodipine 60 mg
every 4 hours for 21 days, along with
maintenance of intravascular volume with
pressor therapy, is recommended to reduce the
incidence and severity of neurologic deficits
resulting from delayed ischemia

86. Monitoring Parameters

87. Rehabilitation

88. References
 American Heart Association
 Pharmacotherapy by Dipiro 10th Edition
 NIH guidelines for the Management of Stroke