Q1

1. Pharmacokinetics. Pharmacokinetic curve. The area under the concentration-time curve. The
maximum concentration. Control of the concentration of drug in clinical practice.
a) Pharmacokinetics
= Pharmacokinetics describes how the body affects a specific xenobiotic/chemical after
administration through the mechanisms of absorption and distribution, as well as the
metabolic changes of the substance in the body (e.g. by metabolic enzymes such as
cytochrome P450 or glucuronosyltransferase enzymes), and the effects and routes of
excretion of the metabolites of the drug. Pharmacokinetic properties of chemicals are
affected by the route of administration and the dose of administered drug. These may
affect the absorption rate.
= 4 levels: Absorption, Distribution, Metabolism, Excretion
b) Pharmacokinetic curve

c) Area under the concentration-time curve (AUC)

= area under the curve in a plot of concentration of drug in blood plasma against time
= AUC is proportional to the total amount of drug absorbed by the body
= It is often use to calculate the bioavailability of a drug
d) Maximum concentration
= Also known as Cmax, it refers to the maximum (or peak) serum concentration that a
drug achieves in a specified compartment or test area of the body after the drug has been
administrated and before the administration of a second dose.
= Short term drug side effects are most likely to occur at or near the Cmax.
e) Control of the concentration of drug in clinical practice
= Understanding how the body affects a given drug can help us to choose the best way
of drug administration, how much drug to give, & to choose the best drug dosage
regimen in order to get optimal amount of drug inside the body without causing adverse
effects.
2. Modern classification of NSAIDs. Pharmacodynamics effects. Methods for evaluating the
efficacy and safety of non-steroidal anti-inflammatory drugs in pharmacotherapy of chronic
pain.

a) Modern classification of NSAIDs

  Non-selective COX inhibitors
 Salicylates: Aspirin
 Propionic acid derivatives: Ibuprofen, Ketoprofen
 Acetic acid derivatives: Diclofenac, Aceclofenac
 Fenamic acid derivatives: Mefenamic acid
 Pyrrolo-pyrrole derivatives: Ketorolac
 Oxicam derivatives: Piroxicam, Meloxicam
 Indole derivatives: Sulindac, Indomethacin
 Pyrazolone derivatives: Phenybutazone
 Selective COX-2 inhibitors
 Celecoxib, Rofecoxib
 Preferential selective COX inhibitors
 Nimesulide, Meloxicam, Nabumetone
 Analgesic-antipyretic with poor anti-inflammatory effect
 Paracetamol

b) Pharmacodynamics effects
= Most NSAIDs act as nonselective inhibitors of the enzyme cyclooxygenase (COX),
inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2)
isoenzymes. This inhibition is competitively reversible (albeit at varying degrees of
reversibility), as opposed to the mechanism of aspirin, which is irreversible inhibition.
COX catalyzes the formation of prostaglandins and thromboxane from arachidonic acid
(itself derived from the cellular phospholipid bilayer by phospholipase A2).
Prostaglandins act (among other things) as messenger molecules in the process of
inflammation.

c) Methods for evaluating the efficacy and safety of non-steroidal anti-inflammatory drugs
in pharmacotherapy of chronic pain.
= NSAIDs, like all drugs, may interact with other medications. For example, concurrent
use of NSAIDs and quinolones may increase the risk of quinolones' adverse central
nervous system effects, including seizure.
= Cardiovascular: NSAIDs aside from aspirin, both newer selective COX-2 inhibitors
and traditional anti-inflammatories, increase the risk of myocardial infarction and stroke.
They are not recommended in those who have had a previous heart attack as they
increase the risk of death and/or recurrent MI.
= GI tract: Clinical NSAID ulcers are related to the systemic effects of NSAID
administration. Such damage occurs irrespective of the route of administration of the
NSAID. NSAIDs cause a dual assault on the GI tract: the acidic molecules directly
irritate the gastric mucosa, and inhibition of COX-1 and COX-2 reduces the levels of
protective prostaglandins. Best way to check: GI endoscopy.
= Kidney: The mechanism of these renal adverse drug reactions is due to changes in
renal hemodynamics (kidney blood flow), ordinarily mediated by prostaglandins, which
are affected by NSAIDs. Evaluate by monitoring GFR level. Do not give NSAIDs to
patient who is also taking anti-hypertensive therapy such as ACE-inhibitors & diuretics.
 Q2

1. List the main pharmacokinetic parameters. Bioavailability and Bioequivalence.

a) Pharmacokinetic parameters
= Levels: Absorption, Distribution, Metabolism, Excretion
= Definitions:
a. Bioavailibily - the amount of unchanged drug reaching the systemic circulation
after extravascular administration (i.e., oral, intramuscular) compared with the
amount administered.
b. Distribution - the movement of drug within the intravascular space and from the
intravascular space to extravascular fluids and tissues.
c. Half-life (t/2) - the time required for the serum concentration to fall by one half.
d. First-pass effect - this refers to the hepatic or gastrointestinal wall metabolism of
a drug that occurs upon oral absorption, but before the drug reaches the systemic
circulation.
e. Clearance (Cl.) - a measure of the ability of the body to remove a substance (i.e.
a drug) from a specified body fluid (i.e. serum, plasma) by all processes (e.g.,
metabolism, renal, biliary).
b) Bioavailability and Bioequivalence.
= When two drugs have the same bioavailability, they are said to be biological
equivalents or bioequivalents. This concept of bioequivalence is important because it is
currently used as a yardstick in the authorization of generic drugs in many countries.
= In determining bioequivalence, for example, between two products, pharmacokinetic
studies are conducted whereby each of the preparations are administered in a cross-over
study to volunteer subjects. Serum/plasma samples are obtained at regular intervals and
assayed for parent drug (or occasionally metabolite) concentration. For a
pharmacokinetic comparison, the plasma concentration data are used to assess key
pharmacokinetic parameters such as area under the curve (AUC), peak concentration
(Cmax), time to peak concentration (Tmax), and absorption lag time (tlag).

2. Call adverse drugs reactions of glucocorticosteroids

= Osteoporosis, hyperglycemia, hypertension, adrenal insufficiency
= Cushing’s syndrome
a) a fatty hump between your shoulders
b) round face
c) weight gain
d) pink stretch marks
e) weakened bones
f) diabetes
g) high blood pressure
h) thin skin
i) slow healing
j) irregular menstrual cycles
Question Card No.3
1. List the main pharmacokinetic parameters. Title the concepts of: total
clearance: definition, affecting factors, significance for the optimization of drug
therapy.

Pharmacokinetic Parameters:
 Clearance - Rate of drug elimination divided by plasma
concentration, giving a volume of plasma from which drug is
completely removed per unit of time.
Total CL= Renal CL+ Hepatic CL+ other CL
 Volume of distribution – Fluid volume that required to contain
the amount of drug present in the body at the same
concentration as in the plasma

 Bioavailability - Fraction of a dose of drug that is absorbed

from its site of administration and reaches, in an unchanged
form, the systemic circulation."
 Absorption rate constant - Fractional rate of drug absorption
from the site of administration into the systemic circulation.
 Half-life - Time it takes for the plasma concentration or the
amount of drug in the body to be reduced by 50%. The half-life
of a drug depends on its clearance and volume of distribution.
The elimination half-life is considered to be independent of the
amount of drug in the body.
Total Clearance – Definition-refer above
Factor affecting clearance – Blood flow to the organ responsible for drugs
clearance, condition of the organ (diseases)

2. C a l l t h e assessment methods of e f f i c a c y a n d s a f e t y o f l o n g -
term NSAIDs therapy.
 Evaluate the function status (recovery? Worsen?).
 Hypersensitivity to the drug (aspirin) or give an alternative
NSAIDS
 Prescribe PPI for long term NSAIDS to prevent peptic ulcer
 Monitor prothrombin time especially for haemophilic patient
Question Card No.4

1. Clinical pharmacogenetics. Genetic factors affecting the pharmacodynamics of

drugs.
Clinical pharmacogenetics is the study of inherited genetic differences in drug
metabolic pathways which can affect individual responses to drugs, both in
terms of therapeutic effect as well as adverse effects.

Genetic factors - mutations to the gene that transcript for the synthesis of
specific receptor change receptor binding, alter the level of binding proteins, or
decrease receptor sensitivity.
Indirect effect -

2. Methods for estimation of the effectiveness and safety of pharmacotherapy

with penicillins.
Serological test is carried out to make sure the causative agent is sensitive to
penicillin
Make sure no history of penicillin allergy before prescribing
Cautious when using in patient with kidney failure as penicillin is excreted
by kidney
Q5
Q6
Q7
Q8
Q9
Q10
Q11
1. A first line drugs for the treatment of type 2 diabetes mellitus. Principles of combined
therapy.
2. Methods for evaluation the effectiveness and safety of cardiac glycosides pharmacotherapy.

a) First line: Oral glucose-lowering therapy

Drug MOA AE Contraindication
Biguanides  Hepatic glucose production, Lactic acidosis, Serum creatinine
(metxformin) weight loss, diarrhea, >1.5 mg/dL(men),
— Fasting  glucose utilization, nausea > 1.4 mg/dL (women)
hyperglycaemia  Insulin sensitivity
Nonsulfonylureas  Insulin secretion Hypoglycemia Renal/liver disease
(nateglinide,
repaglinide)
—post-prandial
hyperglycaemia
Combined therapy:
a. Statins;
b. metformin-based combination therapies:
metformin + oral agents (DPP-4 inhibitors, SGLT2 inhibitors, sulfonylureas, Thiazolidinediones),
injectable glucagon-like peptide 1 (GLP-1) agonists, or basal insulin
c. Non–metformin-based combination therapies:
sulfonylurea + metformin/ thiazolidinedione/ acarbose
d. diet

b)
Cardiac Pharm. Effects Usage
Glycosides
Digoxins, + inotropic effect Congestive heart failure
Digitoxins - chronotropic effect Supraventricular arrhythmias: especially rapid atrial fibrillation and
Slowing of AV flutter in heart failure (digoxin is drug of choice).
conduction
AE
1. Atrial or ventricular dysrhythmias especially ventricular ectopic beats and ventricular fibrillation at toxic dose
(precipitated by hypokalemia).
2. Decreased appetite
3. GI effects: nausea, vomiting, diarrhea
4. CNS effects: visual disturbances, drowsiness, confusion, delirium, headache and fainting.
5. Overdoes (intoxication) leading to cardiac arrest. (Treatment of overdose: withdrawal of drug, correction of
electrolyte imbalances, administration of antiarrhythmic drugs and digoxin antibodies (Fab fragments)).
Q12
1. Antiplatelet drugs: classification, mechanism of action, indications and contra-indications.
2. Methods for evaluation efficacy and safety of thiazide diuretics.
a) Classification of Antiplatelet drugs:
Drugs MOA Indication
Aspirin COX-1 inhibitor 1.Prevention of cardiovascular
events such as stroke, MI
2.Acute treatment of cerebral
infarction, MI
3.Thromboprophylaxis due to
atrial fibrillation
Indobufen TXA2 synthase & 1.Ischemic heart disease,
COX inhibitor atherosclerosis and peripheral
vascular diseases
2. Thrombosis of cerebral
circulation,
3.Diabetes and hyperlipidemia
Clopidogrel ADP- 1.Acute Coronary Syndrome
Ticagrelor receptor(P2Y12) 2.Recent MI, Recent Stroke, or
inhibitor Established Peripheral Arterial
Disease
Abciximab Glucoprotein 2b-3a percutaneous coronary
receptor inhibitor intervention
Eptifibatide acute cardiac ischemic events
Tirofiban in patients with unstable
angina or non-ST-segment-
elevation MI,
percutaneous coronary
intervention
Dipyridamol Phosphodiesterase peripheral arterial
e inhibitor disease and coronary artery
disease, stroke
pulmonary hypertension
Contraindication
1.Allergy to ibuprofen or naproxen or who have
salicylate intolerance or a more generalized
drug intolerance to NSAIDs
2.Asthma or NSAID-precipitated
bronchospasm
3.Active stomach bleeding
4.Hemophilia or other bleeding tendencies
5.glucose-6-phosphate dehydrogenase
deficiency,
6.hyperuricemia, or gout
7.Age < 12 years, as this has been linked with
Reye's syndrome.
8.Pregnancy
9.Lactation
Allery to aspirin, or NSAID
Peptic ulcer disease
Bleeding disorders
Active stomach bleeding
Hepatic/renal insufficiency
1.Allergy to any ingredient in clopidogrel.
2.Active bleeding problem (eg, bleeding
stomach ulcer, bleeding in the brain)
Use of dabigatran or certain proton pump
inhibitors
risk of bleeding,
Thrombocytopenia
Thrombocytopenia
Renal insufficiency
Risk of bleeding
Allergy
Severe, uncontrolled hypertension
Pregnancy
Lactation
Allergy to Theophylline, PPIs,
Anticholinesterases, Adenosine
Pregnancy
Asthma,
Arrthymia

2.
MOA Usage AE
decrease Na and H2O Hypertension (mild to severe) in patients with Hypokalemic metabolic alkalosis
retention by acting at low plasma renin and increased plasma Hyponatremia
early part of proximal volume. Hypochloremia
convoluted tubules Edema associated with CHF, hepatic disease, Hypomagnesemia
renal disease and corticosteroids therapy. Hyperuricemia leading to gouty attacks
Nephrogenic diabetes insipidus: Hypercalciuria: leading to kidney-stone formation
Ca nephrolithiasis Orthostatic hypotension (hypovolemia)
Allergic reactions
Hyperglycemia: decrese insulin release
Hyperlipidemia: increase cholesterol and triglycerides
Photosensitivity
Q13
1. Classification of antiplatelet agents. Pharmacodynamic effects and adverse drug reactions of
antiplatelet agents. Factors gastropathies risk in the application of antiplatelet agents.
Possible approaches to the prevention of gastrointestinal side effects of antiplatelet agents.

Pharmacodynamics and adverse effects

Aspirin
 irreversibly acetylates and inactivates cyclo-oxygenase: enzyme responsible for
conversion of membrane arachidonic acid to prostaglandin endoperoxides and
thromboxane A2
 platelets lack nuclear machinery to replenish enzyme so platelets are affected for
their lifespan
 platelet release inhibited and platelet aggregation impaired
 clinically translates into a prolonged bleeding time and potential for bleeding
during surgical procedures for up to 8 days after last dose of aspirin. In most
bleeding tendency mild and causes no problems during surgical procedures
however in some patients, particularly those with mild associated haemostatic
problems, bleeding can be pronounced and troublesome
 GI haemorrhage

 diarrhoea, upper GI symptoms, neutropaenia, intracranial haemorrhage

Prevention of gastrointestinal side effects of antiplatelet agents
 Induce low dosage of drugs
 Intake gastroprotective dugs (eg. Prostagladins)
 Eradication of H.pylori

2. Methods for evaluation the efficacy and safety of anti-ulcer agents.

Use combination of drugs and observe improvement in 7 days by endoscopy.
Q14
1. Digoxin in clinical practice in patients with CHF. Glycoside intoxication: symptoms,
pharmacotherapy correction methods.

Digoxin increases myocardial contraction which acts mainly on the heart by:
a) cardiac slowing and reduced rate of conduction through the AV node
b) increased force of contraction
c) disturbances of rhythm, especially:
a. block of AV conduction
b. increased ectopic pacemaker activity.
The main mechanisms of action of cardiac glycosides (Digoxin) are increased vagal activity
and inhibition of the Na+/K+ pump. Cardiac glycosides bind to a site on the extracellular
aspect of the α subunit of the Na+/K+ ATPase (which is an αβ heterodimer), and are useful
experimental tools for studying this important transport system.
Glycoside intoxication
Symptoms:
a) Extracardiac:
b) GI: Anorexia, nausea, vomiting, diarrhea
c) Altered color vision (xanthopsia)
d) Others: Weight loss, confusion, HA, gynecomastia
e) Cardiac:
 Bradycardia
 Multiple ventricular ectopics
 Ventricular bigeminy
 Atrial tachycardia w variable blocks
 V- tach
 V- fib

Pharmacotherapy correction methods

 Stop Digoxin
 Serum electrolytes, creatinine and digoxin level should be checked.
 Correction of electrolytes, if any
 If bradycardia: IV atropine, sometimes need pacing
 Correction of arrhythmia (amiodarone DOC)

2. Methods for evaluation the effectiveness and safety of beta-blockers in the treatment of
cardiovascular diseases
 Titrate doses to the maximum dose of the drug (‘start slow, go slow’) in
the recommended range (eg. Metoprolol 25-100mg bid), provided that
SBP does not fall below 95mmHg and HR does not fall below 55bpm.
 Contraindicated drug intake patients (i.e. asthmatic patients) should
avoid.
 Patients with significantly LV dysfunction should be monitored closely
for the development of CHF.
Q15
Question Card 15

1. The minimum therapeutic concentration, the therapeutic range, the average

therapeutic concentration, the therapeutic index of the drug: definitions, significance
in pharmacotherapy optimization.

2. Role of ACE inhibitors and AT1 receptor blockers in the treatment of CHF.

Answers:
a) Minimum therapeutic concentration: Minimum concentration of the drug in
plasma required to produce therapeutic effects. It reflects the minimum
concentration of the drug at the receptor site to elicit the desired
pharmacological response. The concentration of drug below minimum
therapeutic concentration is known as sub-therapeutic effect.

Therapeutic range: Drug concentration between minimum effective concentration

(MEC) and maximum safe concentration (MSC), also known as therapeutic window.

Average therapeutic concentration: Range between minimum therapeutic dose and

the maximum tolerated dose.

Therapeutic index of the drug: Ratio of maximum safe concentration (MSC) to

minimum effective concentration (MEC). Ratio of dose required to produce toxic or
lethal effects to dose required to produce therapeutic effect.

b) In patients with left ventricular dysfunction but no edema, an ACE inhibitor

should be the first drug used. Several large studies have showed clearly that
ACE inhibitors are superior to both placebo and to vasodilators and must be
considered, along with diuretics, as first-line therapy for chronic heart failure.
However, ACE inhibitors cannot replace digoxin in patients already receiving the
glycoside because patients withdrawn from digoxin deteriorate while on ACE inhibitor
therapy. By reducing preload and afterload in asymptomatic patients, ACE inhibitors
(eg, enalapril) slow the progress of ventricular dilation and thus slow the downward
spiral of heart failure.
Consequently, ACE inhibitors are beneficial in all subsets of patients—from those who
are asymptomatic to those in severe chronic failure. This benefit appears to be a class
effect; that is, all ACE inhibitors appear to be effective.
The angiotensin II AT1 receptor blockers (ARBs, eg, losartan) produce beneficial
hemodynamic effects similar to those of ACE inhibitors. However, large clinical trials
suggest that angiotensin receptor blockers are best reserved for patients who cannot
tolerate ACE inhibitors (usually because of dry cough).
Q16
1. Clinical pharmacogenetics. Genetic factors influencing the pharmacodynamics of
drugs

2. Methods for evaluation the efficacy and safety of digoxin. Glycoside intoxication:
symptoms, ways for pharmacotherapy correction.

Answers:

a) Clinical pharmacogenetics: Study of genetic factors that underlie variation in

drug response in which it implies recognition that more than one genetic variant
may contribute to variation in drug response.
Genetic factors that influence the pharmacodynamics of drugs are divided as follows:
a. Genetic variations in enzymes:
a.i. Phase I enzymes – CYP2D6; CYP2C19; DPD (Dihydroxypyrimidine
Dehydrogenase)
a.ii. Phase II enzymes – UGT1A1 (Uridine 5’-Diphosphoglucuronosyl
Transferase 1); TPMT (Thiopurine S-Methyltransferase)
a.iii. Other enzymes – G6PD
b. Genetic variations in transporters: Organic anion transporter (OATP1B1)
c. Genetic variations in immune system function *drug-induced hypersensitivity
reactions e.g. polymorphism in HLA genes associated with Stevens-Johnson
Syndrome, toxic epidermal necrosis, or drug-induced liver injury
d. Polygenic effects i.e., the combinatorial effect of multiple genes on drug
response, may more accurately describe individual differences with respect to
clinical outcomes.
b) Digoxin has multiple direct and indirect cardiovascular effects, with both therapeutic and
toxic consequences. It has undesirable effects on the CNS and gut.
Efficacy and safety of digoxin is by monitoring plasma digoxin levels (therapeutic range:
0.5-2.0 ng/ml). Investigations of ECG, BUSE, glucose, calcium, magnesium and serum
creatinine should be included.
ECG sign of glycoside overdose: tachycardia + fibrillation; arrest at extremely high dosage.
(Therapeutic dosage: increase PR-interval, decrease QT-interval)

Clinical features of digoxin overdose include:

GIT – anorexia, nausea, vomiting, diarrhea
CNS – disorientation, hallucinations; elderly often presented with visual disturbance
(aberrations of color perception)
Heart – arrhythmias, heart block
Pharmacotherapy correction:
Stop digoxin administration, gastric lavage + repeated doses of activated charcoal.
Correct electrolyte imbalance. Administer Digoxin-specific Fab antibody fragments in
which indications include ventricular fibrillation, arrhythmia, hypotension and plasma
digoxin level >10ng/ml in patient.
Q17

1. The main pharmacokinetic parameters.The half-life and the equilibrium concentration:

definition significance to optimize pharmacotherapy.

2. Role of RAAS in pathogenesis of CVD

 metabolizes a number of peptides, including the vasodilator peptides bradykinin and
kallidin, to inactive metabolites
 induce cellular hypertrophy or proliferation, prothrombotic and proinflammatory effects,
and superoxide formation
 mediate vasodilation and antiproliferative and apoptotic effects in vascular smooth muscle
and inhibit growth and remodeling in the heart
 upregulation of ACE levels, contribute to the development and maintenance of left
ventricular hypertrophy
 contribute to the pathophysiology of sodium-retaining states
 increases in blood volume and arterial pressure, fibrosis, a prothrombotic state, and
progression of vascular lesions
 deleterious vascular effects
 induces endothelial dysfunction contribute to disrupting the balance of vasodilation and
vasoconstriction
Pharmacological approaches to the regulation RAAS activity
Q18
1. drug interaction at stage of distribution and binding with blood protein

1 . the extent of drug distribution depends on

1. lipid solubility
2. The higher the lipophilicity of a drug, the stronger its binding to protein and the
greater its distribution
3. ionizaion at physiological pH (pKa)
4. degree of binding to plasma and tissue protein
5. difference in regional blood flow
6. disease (e.g CHF, uremia, cirrhosis)
2. movement of drug until equilibration between unbound drug in plasma and tissue fluids
3. In liver and spleen, the capillaries have gaps between their cells that allow larger
proteins to pass through the capillary basement membrane.
4. In brain, there's blood brain barrier. To penetrate into th brain, drug must be fairly small
and lipid soluble or must be picked up by carrier-mediated transport mechanism in CNS.
5 . For example anesthetic gases quickly and easily penetrate brain as it is small and highly
fat soluble while other larger and water soluble molecules (e.g penicillin) penetrate CNS
in lesser degree
6 . volume of distribution = dose (amount in body) / plasma concentration
7 . Drugs with high molecular weights or extremely hydrophilic tend to stay within the
circulatory system and organs with rich blood supply, and have a smaller apparent
volume of distribution. Small, highly lipophilic drugs have a large apparent volume of
distribution.
8 . most drug possess physicochemical affinity for plasma protein.
9. Acidic drugs bind plasma albumin
10. basic drugs bind alpha-1 glycoprotein
11. The strength of binding is measured by the association constant between drug
and protein
1 2. The larger the association constant the more avid the binding
1 3. Binding to plasma protein affect drug distribution into tissues because only drug
that is not bound is available to penetrate tissues, bind to receptors and exert activity
1 4. Some drugs have a high affinity for binding to serum proteins. In
hypoalbuminemia, binding may reduced and high concentration of free drug may
attained (e.g phenytoin). If patient's serum albumin level is low, with highly protein
bound drugs may lead to toxicity due to fewer binding sites.
15. Competition for binding sites may happen when the patient is using two higly
protein bound drugs at the same time.
16. The drug with the greatest affinity for the albumin will bind and is thought to
disrupt the normal ratio of free to bound drug for the second medication. This cause the
second medication more available to distribute to the site of action and potentially cause
side effects.
 1. Role of diuretics in the pharmacotherapy of cardiovascular diseases. Classification,
pharmacodynamic effects. Examples.

Role of diuretics in pharmacotherapy of CVD

 reduction of edematous fluid
 reduce plasma volume which contributes to hypotensive effect
 long term use decrease in peripheral vascular resistance

Classification of diuretics:

Direct Examples Mechanisms Side-effects

action
Loop 1. Furosemide  Acts on ascending  Electrolyte abnormalities
diuretics 2. ethracrynic limb of loop of ◦ hypochloremia
acid henle ◦ hypocalcemia
3. bumetanide  inhibit Na+/ K+/ ◦ hypomagnesemia
4. piretanide 2Cl- carrier in the ◦ etc
luminal membrane  ototoxicity (esp.
 vasodilator action ethacrynic acid)
(piretanide most  hypotension
potent)  metabolic effects
◦ hyperuricemia
◦ hyperglycemia
◦ increase triglyceride
and cholesterol level
◦ increase LDL &
decrease HDL
 arrhythmia

Thiazides 1. Indapamide  Inhibit the carrier  Electrolyte abnormalities

2. chlorothizide of Na+/ Cl co- ◦ hypokalemia
transport systema ◦ hyponatremia
◦ hypercalcemia
◦ etc
 decrease glucose
tolerance and reduce
efficacy of hypoglycemic
drugs
 increase plasma level of
LDL and triglyceride
 impotence
 drug-drug interactions
◦ decrease efficacy of
drugs (eg
anticoagulants and
uricosorics)
◦ increase risk of
toxicity of cardiac
 glycosies and
antiarrhythmic drugs
◦ increase blood levels
of lithium
Potassium 1. Spironolactone  Inhibit sodium  hyperkalemia
sparing 2. amiloride retaining action of
3. triamterene aldosterone =>
decrease K+
secretion
 acts on collecting
tubules and
collecting ducts
 blocks luminal
sodium channels
 act on cortical
collecting duct
Indirect Example Mechanisms
action
Osmotic 1. mannitol 3. Prevent H2O 4.
diuretics reabsorption in the
proximal tubule
Carbonic 1. Acetazolamide 5. Acts on proximal 6. Increase excretion of all
anhydrase 2. dorzolamide tubule and electrolyte
inhibitors interfere 7. increase in extracellular
reabsorption of fluid volume exacerbate
HCO3- CHF or pulmonary
congestion
Q19
Q20
Q21
Q22
Q23
Q24
Q25
Q26
Q27
27-1. Pharmacodynamic interactions: de finition, developmental mechanisms, examples.

De finition
Pharmacodynamic: The study of biochemical and physiological effects of the drugs and their
mechanisms of action. (Sometimes described as what a drug does to the body)
Pharmacodynamic interactions: refers to interactions in which drugs in fluence each other’s
effects directly. As a rule, for example, sedatives can potentiate each other. The same is true of
alcohol, which can potentiate the sedative effects of many drugs.

Developmental mechanisms
Drug-drug interactions (DDIs)
Pharmacodynamic: may be divided into three subgroups:
(1) direct effect at receptor function,
(2) interference with a biological or physiological control process and
(3) additive/opposed pharmacological effect.

Examples
of pharmacodynamic interactions are simultaneous administration of a NSAID and phenprocoumon
(additive interaction), or of aspirin and ibuprofen (antagonistic interaction).

Pharmacodynamic interactions of NSAIDs

Platelet-related interactions—It is generally known that simultaneous administration of NSAIDs
increases the COX-1-mediated inhibition of thromboxane synthesis and hence the risk of
gastrointestinal bleeding in a synergistic manner. A particular property of the acidic anti-
in flammatory ibuprofen is its speci fic, reversible binding to COX-1, which prevents acetylsalicylic
acid (ASA) from acetylating the serine residue at position 529 of the COX-1 protein. Irreversible
and hence long-lasting inhibition of COX-1-mediated thromboxane A2 synthesis by ASA can thus
be prevented and the cardiac risk of patients with coronary heart disease can increase (8).
Long-term clinical observations con firm these ex vivo observations (e5), which appear also to hold
for naproxen (e6). Accordingly, patients with coronary heart disease on ASA prophylaxis should
not take ibuprofen or naproxen on a regular basis.

27-2. Principles of pharmacotherapy of hyperlipidemia. Combined therapy

Antihyperlipidemic drugs target the problem of elevated serum lipids with complementary
strategies. Some of these agents decrease production of the lipoprotein carriers of cholesterol and
triglyceride, whereas others increase the degradation of lipoprotein. Still others decrease cholesterol
absorption or directly increase cholesterol removal from the body. These drugs may be used singly
or in combination. However, they are always accompanied by the requirement that dietary saturated
and trans fats be low, and the caloric content of the diet must be closely monitored.

DRUGS THAT LOWER THE SERUM LIPOPROTEIN CONCENTRATION:

a) HMG CoA reductase inhibitors

b) Niacin (nicotinic acid)

c) The brates: Feno brate and gem brozil

d) Bile acid–binding resins

e) Cholesterol absorption inhibitor

Combination drug therapy :

It is often necessary to use two antihyperlipidemic drugs to achieve treatment goals in plasma lipid
levels. For example, in Type II hyper- lipidemias, patients are commonly treated with a
combination of niacin plus a bile acid–binding agent such as cholestyramine. [Note: Remember that
cholestyramine causes an increase in LDL receptors that clears the plasma of circulating LDL,
whereas niacin decreases synthesis of VLDL and, therefore, also the synthesis of LDL.]

The combination of an HMG CoA reductase inhibitor with a bile acid–binding agent has also been
shown to be very useful in lowering LDL cholesterol levels (Figure 21.13). Simvastatin and
ezetimibe as well as simvastatin and niacin are currently available combined in one pill to treat
elevated LDL cholester- ol.

However, more clinical information is needed to determine whether the combination statin-
ezetimibe produces equal or better long-term bene ts that the use of a high dose of a statin. Until this
uncertainty is resolved, many experts recommend maximizing statin dosages and adding niacin or
brates to achieve goal HDL-cholesterol and triglyc- eride levels. However, combination drug
therapy is not without risks. Liver and muscle toxicity occur more frequently with lipid-lowering
drug combinations. Figure 21.14 summarizes some actions of the anti- hyperlipidemic drugs.
Q28
1. Short-acting beta2-agonists and anticholinergic agents in the treatment of
asthma. Indications and contraindications, the principles of choise, side effects
Short-acting beta2-agonists
Indication: Quick relief: Most clinically useful agonists have a rapid onset of action (5 to 30
2
minutes) and provide relief for 4 to 6 hours. They are used for symptomatic treatment of
bronchospasm, providing quick relief of acute bronchoconstriction.

Direct-acting -selective agonists, such as albuterol, offer the advantage of providing maximally
2
attainable bronchodilation with little of the undesired effect of or stimulation.
1

Contraindicated in persons with a history of hypersensitivity reaction (urticaria, angioedema, rash)

to albuterol, or any of its components.

Adverse effects such as tachycardia, hyperglycemia, hypokalemia, and hypomagnesemia are

minimized with delivery via inhalation versus systemic routes.

Anticholinergic agents are generally less effective than -adrenergic agonists. The anticholinergic
2
agents block the vagally mediated contraction of airway smooth muscle and mucus secretion.
Inhaled ipratropium, a quaternary derivative of atropine, is useful in patients who are unable to
tolerate adrenergic agonists. Ipratropium is slow in onset and nearly free of side effects. These
agents are not traditionally effective for patients with asthma unless COPD is also present.

The main contraindication for inhaled ipratropium is hypersensitivity to atropine and related
substances. For oral administration, contraindications are similar to other anticholinergics; they
include narrow angle glaucoma and obstructions in the gastrointestinal tract and urinary system.

Side effects of 2 agonists are primarily due to excessive 2 - receptor activation. One of the most
common side effects of these agents is tremor, but patients tend to develop tolerance to this effect.
Other side effects include restlessness, apprehension, and anxiety. The adverse effects may be
reduced by starting with low doses and then titrating to higher doses as tolerance to the tremor
develops
 2. Methods for estimation ef ficacy and safety of NSAIDs in the treatment of
rheumatoid arthritis.

NSAIDs -- or nonsteroidal anti-in flammatory drugs -- are commonly used to treat rheumatoid
arthritis. They help manage the chronic pain, in flammation, and swelling tied to RA. They block
your body’s “Cox” enzymes. This cuts down on in flammation and reduces pain and stiffness.

Aspirin, Diclofenac, Clecoxib, Ibuprofen.

NSAIDs work to decrease in flammation, pain and fever. NSAIDs block enzymes in the body that
help make prostaglandins. Prostaglandins are a group of naturally occurring fatty acids that play a
role in pain and in flammation. Older NSAIDs like ibuprofen block two of these enzymes, COX-1
and COX-2, but celecoxib (Celebrex) targets mainly COX-2.

Safety of NSAIDs
All prescription NSAIDs are linked to a higher risk of heart attack and stroke.
The risk is likely greatest for people who have heart disease risk factors, such as high blood
pressure, high cholesterol, diabetes, and smoking.
Possible risks of all NSAIDs include, among others:
a) Stomach problems like bleeding, ulcer and stomach upset
b) High blood pressure
c) Fluid retention (causing swelling, such as around the lower legs, feet, ankles and hands)
d) Kidney problems
e) Heart problems
f) Rashes

Ef ficacy estimates (sorry Im really not sure about this)

All estimates were evaluated for each combination of measure and biologic number (that is, first,
second, and so on), as well as for relevant subgroups. All estimates were evaluated as weighted
averages using sample size as the weight in the following formula:

where Ratej represents the average response rate for measure j, i indexes the group, ni is the sample
size for the ith group and N is the combined sample size of all groups.

Estimates were also evaluated within the following subgroups: type of study (observational study
versus RCT), duration of follow-up (<6 months versus 6 months or longer), type of biologic (TNF-
inhibitor versus other) and reason for discontinuation (lack of response, loss of response or
intolerance).
Q29
Q30
Q31
Q32
Q33
1.Clinical pharmacogenetics. Genetic factors affecting the pharmacokinetics of drugs.
1. Pharmacogenetics is clinical testing of inherited genetic variation to study the differences in
drug metabolic pathways which can affect individual responses to drugs, both in terms of
therapeutic effect as well as adverse effects.

2. The term pharmacogenetics is often used interchangeably with the term pharmacogenomics
which also investigates the role of acquired and inherited genetic differences in relation to
drug response and drug behavior through a systematic examination of genes, gene products,
and inter- and intra-individual variation in gene expression and function.

3. Example : single-nucleotide polymorphisms affecting genes coding for liver enzymes

responsible for drug deposition and pharmacokinetics), whereas pharmacogenomics refers to
somatic mutations in tumoral DNA leading to alteration in drug response ( KRAS mutations
in patients treated with anti-Her1 biologics).
Genetic factors affecting the pharmacokinetics of drugs.
a) Pharmacokinetics is the study of how a drug is affected by the body, which includes a
drug’s absorption, distribution, metabolism and excretion.
b) Differences in drug effects among patients may be influenced by genetic differences in
patients’ ability to respond to a drug. There have been numerous enzymes identified as
important to drug metabolism. Genetic polymorphisms have been identified for many of
these drug-metabolizing enzymes, particularly, the cytochrome P450 enzymes.
c) Several of the more common Cytochrome P450 enzmes are: CYP2C9, CYP2C19 and
CYP2D6. Differing phenotypes have been associated with deficient, reduced, normal, or
increased activity in these enzymes leading to variable drug responses.
d) CYP2C9 is involved in the metabolism of many common drugs such as glypizide,
phenytoin and warfarin. Differences in enzyme active lead to phenotypes that are poor
metabolizers have reduced warfarin clearance and are at increased risk of excessive
anticoagulation.
e) Cytochrome P450 2C19 enzymes are involved in the metabolism of proton pump
inhibitors and antidepressants. Omeprazole is a drug metabolized to CYP2C19 to its
inactive metabolite. Patients who are CYP2C19 poor metabolizers can have five-fold
higher blood concentrations of omeprazole resulting in higher acid suppression reflux
“cure” rates. Conversely, rapid metabolizers may experience therapeutic failure at
standard doses.
f) The presence of polymorphisms in drug metabolism is diverse and complex, and may
account for 20-95% of patient variability in drug responses.
g) Cytochrome P450 2D6 is particularly important to anesthesiologists and pain physicians
as it metabolizes codeine, tramadol, oxycodone, and hydrocodone to active metabolites.
Thus, patients deficient in 2D6 (or patients taking a 2D6 inhibitor) will have less
analgesia.
2. Stable angina. The principles of the selection of antianginal drugs for the prevention and relief of
angina pectoris.
Stable Angina
a) Often related to Artherosclerosis
b) Chest discomfort due to myocardial ischemia
c) Coronary circulation blocked by plague
d) Ischemia due to low blood oxygen supply.
e) Classic type of angina associated symptoms induced by exertions.
f) Relieved by administration of sublingual nitroglycerin / at rest
g) induced by cold weather, heavy meals, and emotional stress.

h) Clinical pic : retrosternal pain, radiates to left arm & jaw, chest pain during
exercise,cold, stress
i) Pain last 20-30 mins
j) Treatment ( below )
The principles of the selection of antianginal drugs for the prevention and relief of angina
pectoris.

How does it work

Q34

1. Clinical pharmacogenetics. Genetic factors affecting the pharmacodynamics of drugs.

• Pharmacogenetics is clinical testing of inherited genetic variation to study the differences in
drug metabolic pathways which can affect individual responses to drugs, both in terms of
therapeutic effect as well as adverse effects.

• The term pharmacogenetics is often used interchangeably with the term pharmacogenomics
which also investigates the role of acquired and inherited genetic differences in relation to drug
response and drug behavior through a systematic examination of genes, gene products, and inter-
and intra-individual variation in gene expression and function.

• Example : single-nucleotide polymorphisms affecting genes coding for liver enzymes

responsible for drug deposition and pharmacokinetics), whereas pharmacogenomics refers to
somatic mutations in tumoral DNA leading to alteration in drug response ( KRAS mutations in
patients treated with anti-Her1 biologics).
Genetic factors affecting the pharmacodynamics of drugs.
Pharmacodynamics is the study of the biochemical and physiologic effects of drugs (especially
pharmaceutical drugs)
Genetic polymorphisms for many drug-metabolizing enzymes and drug targets (e.g., receptors)
have been identified.
Genetic influences on drug metabolism interact with other intrinsic ( physiologic) and extrinsic
( cultural, behavioral, and environmental) characteristics of a person to determine the outcome from
treatment with any pharmacologic agent.

Genetic factors : (intrinsic )

Rate of Absorption, distribution, metabolism, excretion
Body weight
Genetic conditions
Genetic polymorphism of drug-metabolizing enzymes
Height
Race
Receptor sensitivity
Sex
Each gene’s nucleotide sequence encodes (provides a template for) a molecular product, usually a
protein. Sequence variation may result in alterations in the gene’s product, which in turn may have
an effect on phenotypes (traits or characteristics, such as a disease or response to a drug) that the
product influences.
Example : Typically, black patients require a high dosage of angiotensin-converting enzyme (ACE)
inhibitors or combined therapy with low-dose diuretics to reduce blood pressure effectively.
Although the risk of ACE-related angioedema is generally low, there is some evidence that it is
more common in blacks.

2. Methods of assessing the efficacy and safety of aminoglycosides

a) By manipulating the dosing strategy
b) Concentration-dependent bactericidal activity and postantibiotic effect suggests that the
aminoglycosides may be administered in larger doses and at longer dosing intervals
c) once-daily regimens are as efficacious as conventional intermittent injections in the
treatment of gram-negative infections including urinary tract infections, cystic fibrosis,
and bacteremia in nonneutropenic patients.
d) Decreased accumulation in renal cortex as a result of saturable renal uptake after the
single daily dose may even reduce the incidence or severity of renal damage
Q35

1. Methods for evaluation of the efficacy and safety of theophylline pharmacotherapy

Answer: Do comparative study between different doses of theophylline used, with other similar
methylxanthine drugs, consider the age of patients receiving theophylline therapy and current
medical condition of patients using theophylline.
For example, comparative study of the efficacy and safety of theophylline and doxofylline in
patients with bronchial asthma and chronic obstructive pulmonary disease. Patients in study
received theophylline or doxofylline in addition to standard therapy, for a period of 2 months.
Each patient was followed up fortnightly for the assessment of efficacy parameters using a
pulmonary function test (PFT), clinical symptoms and emergency drug use, and safety was
assessed by recording adverse drug reactions.

2. ACE inhibitors and blockers of AT1-receptors: classification, mechanism of action, the

main pharmacodynamic effects, pharmacokinetic characteristics, side effects, contra-
indications. Role of ACE inhibitors and AT1-receptor blockers in the treatment of
arterial hypertension/

Answer:
Classification of ACE inhibitors:
Sulfhydryl-containing agents:
-Captopril (trade name Capoten), the first ACE inhibitor
-Zofenopril

Dicarboxylate-containing agents:
This is the largest group, including:
-Enalapril (Vasotec/Renitec)
-Ramipril (Altace/Prilace/Ramace/Ramiwin/Triatec/Tritace)
-Quinapril (Accupril)
-Perindopril (Coversyl/Aceon/Perindo)
-Lisinopril (Listril/Lopril/Novatec/Prinivil/Zestril)
-Benazepril (Lotensin)
-Imidapril (Tanatril)
-Trandolapril (Mavik/Odrik/Gopten)
-Cilazapril (Inhibace)

Phosphonate-containing agents:
-Fosinopril (Fositen/Monopril)

Mechanism of action: ACE inhibitors reduce the activity of the renin-angiotensin-

aldosterone system (RAAS). They block the conversion of angiotensin I (AI) to angiotensin
II (AII). The production of AII is decreased, leading to decreased blood pressure.
Pharmacodynamic effects of ACE inhibitor:
a) Lower arteriolar resistance and increase venous capacity
b) Decrease cardiac output, cardiac index, stroke work, and volume
c) Lower resistance in blood vessels in the kidneys and lead to increased natriuresis
(excretion of sodium in the urine).
d) Renin increases in concentration in the blood as a result of negative feedback of
conversion of AI to AII.
e) AI increases for the same reason
f) AII and aldosterone decrease.
g) Bradykinin increases because of less inactivation by ACE.

Pharmacokinetics characteristic: Most ACE inhibitors are prodrugs which are converted
by hepatic esterolysis to an active diacid metabolite. Only captopril and lisinopril have
sufficient oral bioavailability and are given as active drugs. The predominant elimination
pathway of ACE inhibitors is excretion via the kidneys. Therefore, renal insufficiency is
associated with reduced elimination of most ACE inhibitors and, thus, altered
pharmacokinetic properties.

Side effects of ACE inhibitor: Hypotension, cough, hyperkalemia, headache, dizziness,

fatigue, nausea, and renal impairment. Adverse hematologic effects, such as neutropenia,
agranulocytosis and other blood dyscrasias. In pregnant women, ACE inhibitors taken
during all the trimesters have been reported to cause congenital malformations, stillbirths,
and neonatal deaths. Commonly reported fetal abnormalities include hypotension, renal
dysplasia, anuria/oliguria, oligohydramnios, intrauterine growth retardation, pulmonary
hypoplasia, patent ductus arteriosus, and incomplete ossification of the skull.
Contraindications of ACE inhibitor:
-Previous angioedema associated with ACE inhibitor therapy
- Hypersensitivity to ACE inhibitors
-Impaired renal function
-Aortic valve stenosis or cardiac outflow obstruction
-Hypovolemia or dehydration
-Hemodialysis with high-flux polyacrylonitrile membranes

Angiotensin II receptor antagonists, also known as angiotensin receptor blockers (ARBs),

AT1-receptor antagonists or sartans are used primarily for the treatment of hypertension
where the patient is intolerant of ACE inhibitor therapy.
Classification according to structure:
-Losartan, irbesartan, olmesartan, candesartan, valsartan and fimasartan include the
tetrazole group (a ring with four nitrogen and one carbon).
-Losartan, irbesartan, olmesartan, candesartan, and telmisartan include one or two imidazole
groups.
Mechanism of action of AT1 receptor blockers:
They block the activation of angiotensin II AT1 receptors. Blockage of AT1 receptors
directly causes vasodilation, reduces secretion of vasopressin, and reduces production and
secretion of aldosterone, among other actions. The combined effect reduces blood pressure.
Pharmacodynamic and pharmacokinetics of AT1 receptor blockers:
 Pressor inhibition (relates to the degree of blockade or inhibition of the
blood pressure-raising ("pressor") effect of angiotensin II)
 AT1 affinity (relates to how specifically attracted the medicine is for the
correct receptor)
 Biological half-life

Adverse effects: Dizziness, headache, and/or hyperkalemia

Q36
Question card №36
1. Pharmacokinetics. Pharmacokinetic curve. The area under the concentration-time curve.The
maximum concentration. Examples of application.
Answer: Pharmacokinetics (Pk) = movement of drugs within the body or what the body does to
the drug.

a) Absorption - the process of a substance entering the blood circulation.

b) Distribution - the dispersion or dissemination of substances throughout the fluids and
tissues of the body.
c) Metabolism (or biotransformation, or inactivation) – the recognition by the organism
that a foreign substance is present and the irreversible transformation of parent
compounds into daughter metabolites.
d) Excretion - the removal of the substances from the body. In rare cases, some drugs
irreversibly accumulate in body tissue.

Clinical monitoring is usually carried out by determination of plasma concentrations as this

data is usually the easiest to obtain and the most reliable. The main reasons for determining
a drug’s plasma concentration include:
-Narrow therapeutic range (difference between toxic and therapeutic concentrations)
-High toxicity
-High risk to life.
2. Adverse drug reactions because of systemic use of glucocorticosteroids.
Answer:
-Increase blood sugar level, which can trigger temporary and possibly long-term diabetes
-Suppress body’s ability to absorb calcium, which can lead to osteoporosis
-Increase cholesterol and triglyceride levels
-Increase risk of ulcers and gastritis
-Delay wound healing, which requires a certain amount of inflammation
-Suppress immune system and make patient more prone to infections
-Sodium and fluid to be retained in the body and cause weight gain or swelling of the legs
(edema)
-High blood pressure
-Loss of potassium
-Headache
-Muscle weakness
-Puffiness of the face (moon face)
-Facial hair growth
-Thinning and easy bruising of the skin
-Slow wound healing
-Glaucoma
-Cataracts
-Ulcers in the stomach and duodenum
-Loss of diabetes control
-Menstrual irregularity
-"Buffalo hump," a condition described as a rounding of the upper back
Q37
Q38
Q39
Question 1

Principles approach – airway management (bronchospasm, mucosal edema), cardiac monitoring

(BP, oxygen saturation), removing source of antigen if possible (drug, bee sting etc)

Pharmacologic approach – 3 main group of drugs which consist of epinephrine, antihistamine, and
corticosteroids. Other group which may be necessary are beta agonist (albuterol), leucotriene
receptor antagonist (montelukast, zafirlukast), anti IgE antibody (omalizumab), fluid infusion

If patient show laryngeal angioedema

 Epineprine administer intramusculary or subcutaneous 0.3-0.5mg IM/SC
If patient show bronchospasm
• nebulized beta agonist (e.g. albuterol)
If patient show hemodynamic instable e.g. low BP
 Epinephrine 0.3-0.5mg IM/SC
 IV fluid

First line drug for all the situations – Antihistamines

Antihistamine H1 2nd generation (are preferable due to less adverse effect and non-sedating)
1. Loratadine 5-10mg/day PO
2. Cetirizine 5-10mg/day PO
3. Desloratidine 5mg/day PO
4. Levocetirizine 5mg/day PO

Antihistamine H1 1st generation

1. Diphenhydramine 25-50mg/6-8 hour/day PO, not to exceed 300mg/day
2. Hydroxyzine 25mg/day PO

Antihistamine H2 (combined with H1 antagonist show higher effectiveness)

1. Ranitidine

Additional of Glucocorticoids if antihistamine inadequate or ineffective and severe condition

1. Prednisolone, short term use at lowest effective dose (e.g. 15mg/day PO for 5-7 days) in
non-acute situation
2. Prednisolone, short term use 40-60mg/day PO for 2-3 days in acute situation
Question 2

Systemic glucocorticoids indications

1. Adrenal insufficiency
2. Autoimmune and inflammatory diseases e.g. SLE, graft rejection, ulceritive colitis
3. Severe asthma attack
4. Severe COPD exercebation
5. Ocular inflammation e.g. uveitis, keratoconjunctivitis
6. Allergic reaction e.g. allergic rhinitis, anaphylactic shock, interstitial lung diseases

Efficacy of systemic glucocorticoids can be evaluate by observing improving of patient condtion,

resolving of symptoms, improving lab test

• Adrenal insufficiency
◦ improving in general condition of patients e.g. no fatigue, weight gain, no dizziness
◦ Normalizing lab test figure e.g. normalizing K+
◦ Clinical improvement e.g. BP normalisation
• Autoimmune diseases
◦ Ceases of diseases progression e.g. stop of diarrhea, inducing remission, stop of
proteinuria
◦ Normalise of lab test result e.g. ESR normalize, CRP normalize, improving Hb count,
AB count normalize, normalizing GFR
◦ Instrucmental test improvement e.g. endoscopy show remission of diseases
◦ Improving biochemical test e.g. normalizing creatinine, normalizing urea
• Asthma/COPD
◦ Improving of symptoms e.g. dypsnoe, wheezing, tight chest, tachycardia
◦ Improving of spirometry result e.g. PEF, FEV1, FEV1/FVC ratio
◦ Improving of ABG e.g. SPO2
• Inflammation and allergic
◦ Resolve of signs and symptoms e.g. pruritis, angioedema, redness, mucus production,
nasal discharge, bronchospasm
◦ Stabilising vital sign e.g. BP normalize, pulse normalize
◦ Lab test improvement e.g. normalize WBC, normalize CRP, normalize ESR

Safety of systemic glucocorticoids should be evaluate the following

1. Assess osteoporosis by spine x-ray, recording the growth of height, check for bone density
2. Assess dyslipidemia, calculate CVS risk using Framingham Risk Score (Age, Gender,
Cholesterol, Smoking habit, DM record, BP, medical history of BP treatment) every 3-6
months
3. Assess hyperglycemia/DM for every 3-6 months
4. Assess opthamopathy (Glaucoma, cataract) by doing annual examination
5. Assess of body weight regularly (Edema AE)
6. If high risk of GIT bleeding, prescribe PPI (Hx of ulcer, NSAID usage)
7. Monitor closely if patient taking anticonvulsant (phenobarbitol), anticoagulants (warfarin),
antifungal (ketoconazole), antidiabetic, macrolides, antiviral, potassium wasting diuretic
drugs (furosemide), NSAID
Q40
Q40
Question 1
 First, run a spirometry to diagnose asthma.
- Criteria:
◦ FEV1/FVC <0.8
◦ FEV1 increase more than 12% after inhaling bronchodilator
◦ Average daily PEF variability is more than 10%
◦ FEV1 increase more than 12% after 4 weeks of anti-inflammatory treatment
 After putting diagnosis, evaluate the severity of asthma. Based on severity, recommend
patient to start treatment at corresponding step.
◦ Intermittent asthma – step 1
◦ Persistent asthma with mild severity – step 2
◦ Persistent asthma with moderate severity – step 3
◦ Persistent asthma with severe severity – step 4 or 5

Evaluation based on symptom occurance rate, nighttime awakening, SABA use frequency to relieve
symptoms, inteference of daily activities, lung function (FEV1/FVC ratio, FEV1 and PEF) and
exercebation rate.
 After started therapy, review the patient every 1-3 months, evaluate the control of asthma
and adjust the treatment plan. There are 4 questions to ask the patient and it helps in
evaluating efficacy.
1. Daytime symptoms more than twice/week? Yes or No
2. Nightawakening due to asthma? Yes or No
3. SABA needed to relieve symptoms more than Yes or No
twice/week?
4. Activities limitation due to asthma? Yes or No

1 . All no = Well controlled = Maintain current step

2. 1 or 2 Yes = Partially controlled = Step-up 1 step
3. All yes = Uncontrolled = Step-up 1 or 2 step and consider short course of oral steroid

2. Step therapy consist of 5 steps

1 . Step 1 = As-needed SABA
2. Step 2 = Regular low dose ICS plus as-needed SABA (LTRA is alternative for ICS)
3. Step 3 = Low dose ICS + LABA plus as-needed SABA or low dose ICS/formoterol
(Low dose ICS + LTRA is alternative)
4. Step 4 = Medium dose ICS + LABA plus as-needed SABA or low dose ICS/formoterol
(Add tiotropium or high dose ICS+LTRA is alternative)
5 . Step 5 = Omalizumab plus as-needed SABA or low dose ICS/formoterol(Alternatively,
can add tiotropium or low dose ICS)

 Two LABA are available for asthma treatment which is salmeterol and formoterol.
◦ Indication of LABA is inadequate effectiveness of low dose ICS from step 3
onward.
◦ Contra-indications of LABA in asthma are hypersensitivity, status asmaticus
and treatment of asthma without concomitant long term asthma control
medications.
◦ Adverse effect include tachycardia, headache, cramps, myositis,
hypertension, hyperglycemia, hypokalemia and paradoxical bronchospasm.
Question 2

Thiazide uses to treat hypertension, combine with potassium sparing diuretic to treat different type
of edema.
Loop-diuretic and Potassium sparing diuretic use to treat CHF, hypertension and pulmonary
edema.
Carbonic anhydrase inhibitors use to treat glaucoma.
Osmotic diuretic use to treat cerebral edema and intraocular edema and acute kidney failure.C

Evaluation of the efficacy of diuretic drugs are by observing the improvement of patient condition
and symptoms.

5. Normalizing BP in hypertensive patients

6. Resolving of edema
7. Improving of CHF patient's condition e.g. resolve pulmonary edema, resolve peripheral
edema, increase physical exertion tolerance
8. Normalize introocular pressure in glaucoma patient
9. Regain consciousness in cerebral edema patients

Evaluation of safety of diuretic drugs

 Thiazides
◦ Closely monitor electrolytes in blood to prevent hypokalemia, hyponatremia,
hypochloremic alkalosis.
◦ Monitor serum urate especially in patient suffer from gout.
◦ Monitor glucose and lipid profile to prevent hyperglycemia, hypertriglyceridemia and
hypercholesterolemia
 Loop diuretics
◦ Monitor BP regularly to prevent hypotension and volume depletion
◦ Loop diuretics should prescribed carefully if patients are taking ototoxicity agent such as
ethacrynic acid and aminoglycosides
 Potassium-sparing diuretics
◦ Closely monitor electrolytes to assess hyperkalemia, hyperchloremic acidosis
◦ Closely monitor cardiac activity to assess arrhythmia
◦ Shouldn't prescribed to patient suffered from renal insufficiency
◦ Prescribed with extreme caution in patients taking ACEi
 Carbonic anhydrase inhibitors
◦ Monitor closely to prevent metabolic acidosis
◦ Monitor kidney closely to prevent kidney stone (by US)
◦ Prevent hypokalemia
◦ Contra-indicated to prescribed for cirrhosis patients
 Osmotic diuretics
◦ Closely monitor electrolytes to prevent electrolytes imbalance, metabolic acidosis
Q41
1. Classification of diuretics in pharmacotherapy of cardiovascular diseases
a) Drugs that affect thick ascending limb of loop of Henle
a. Furosemide, Ethacrynic acid, Bumetanide

b) Drugs that affect distal convoluted tubule

a. Hydrochlorothiazide, Chlorothiazide, Chlorothalidone, Metholazone, Indapamide

c) Drugs that act in collecting tubule

a. Triamterene, Amiloride
b. Spironolactone, Eplerenone

d) Drugs that act along nephron (in proximal convoluted tubule, descending loop of Henle)
a. Mannitol, Urea

e) Antagonist of ADH (vasopressin)

a. Conivaptan

*a), b) belong to potassium, magnesium-wasting diuretics

c) belong to potassium, magnesium-sparing diuretics
d) belong to osmotic diuretics

Side effects
• Furosemide
a) Hypokalemic and alkalosis
b) Hyponatremia, hypochloremia, hypomagnesemia
c) Hypocalcemia ; hypercalciuria can cause kidney stones
d) Hyperuricemia
e) Dyspepsia
f) Orthostatic hypotension
g) Ototoxicity

 Hydrochlorothiazide
a) Hypokalemia, hyponatremia, hypochloremia, hypomagnesemia
b) Hypercalciuria can cause kidney stones
c) Hyperuricemia, hyperglycemia, hyperlipidemia
d) Photosensitivity
e) Orthostatic hypotension
f) Allergic reaction

 Spironolactone
a) Hyperkalemia
b) Metabolic acidosis
c) Gynecomastia ; menstrual irregularities

2. Methods of assessing efficacy and safety of pharmacotherapy with fluoroquinolones

a) Assess pharmacodynamic
b) Integrate pharmacokinetic parameters with minimum inhibitory concentration
c) Correlate such resultants with clinical or bacteriologic outcomes (so-called PK/PD
modeling) to determine optimal regimens and dosages
Q42
1. Criteria for evaluation of efficacy and safety of antimicrobial therapy
a) Evaluate abnormal changes in lab values (either physiological or adverse changes),
taking into account underlying disease and complication
e.g. Hemoglobin <10g/dl
Hematocrit <35% (male) ; <30% (female)
Fasting blood glucose drop <55mg/dl, rise >160mg/dl

b) Assess severity of adverse events

a. Mild - Event does not interfere with daily activities
e.g. Abnormal changes in lab values without corresponding adverse
symptoms

b. Moderate - Event interferes with daily activities, including the case where
investigational treatment is discontinued
e.g. Abnormal changes in lab values which need follow-up exam and
treatment

c. Severe- Event that prevents daily activities

2. Clinical pharmacology of fluoroquinolones

1st generation – Cinoxacin, Rosoxacin
2nd generation – Ciprofloxacin, Ofloxacin
3rd generation – Levofloxacin
4th generation – Moxifloxacin

Mechanism of action
1st and 2nd generation fluoroquinolones selectively inhibit topoisomerase II ligase domain; 3rd
and 4th generation more selective for topoisomerase IV ligase domain.

a) Treat intracellular pathogens , e.g. Legionella pneumophila, Mycoplasma pneumonia

b) DNA gyrase is the target for gram –ve bacteria, while topoisomerase IV is the target for
gram +ve ones.

Mechanism of toxicity
Fluoroquinolones block GABA receptor complex, causing excitotoxic type effects and
oxidative stress.