DRUG

Definition: Drug is any substance or product that is used or intended to be used

to modify or explore physiological system or pathological state for the benefit of
the recipient is called drug.

Benefit of the recipient:

A. For diagnosis of disease
 Histamine → Pernicious Anaemia.
 Barium Sulphate → GIT lesion by Barium meal X-ray.

B. For prevention of disease

 BCG→ for prevention of Tuberculosis (TB)
 Tetanus toxoid→ for prevention of tetanus.
 Polio vaccine→ for prevention of polio myelitis.

C. For control of disease

 Antihypertensive drug for control of hypertension.
 Oral antidiabetic drug/Insulin for diabetes mellitus

D. For treatment of disease

 Antibiotic→ Treatment of Infection
 Analgesic→ Treatment of Pain

Route of administration:
A.Systemic Administration:
a.Enteral
 Oral → Tablet, Capsule, Syrup
 Sublingual → GTN ( Glyceryl tri-nitrate)
 Buccal → GTN ( Glyceryl tri-nitrate)
 Rectal → Bisacondyl
b. Parenteral
1. Injection:
 Intravenous (IV)→ IV fluid
 Intramuscular(IM)→ Penicillin G
 Subcutaneous→ Insulin
 Intradermal→ Vaccine (BCG), Norplant
 Intra-arterial→ Tolazoline
 Intra-articular→ steroid
 Intra-cardiac→ Adrenaline
 Intra-peritoneal→ Cytotoxic drug
 Epidural → Anaesthesia
 Intrapulmonary →

2. Inhalation :
 Salbutamol
 Steroid

B. Local Administration
 Epidermis→ Ointment, Cream
 Conjunctival→ Chloramphenicol
 Nasal→ Steroid, Xylometazoline
 Ear→ Antifungal or Antibiotic drug
 Transdermal→ GTN ( Glyceryl tri-nitrate)
 Oral Route
Advantages of oral route:
1. Safe and painless.
2. Self-medication is possible.
3. Most economical or cheap.
4. No need sterilizations.
5. Less chance of hypersensitivity reaction.

Disadvantage:
1. Slow onset of action.
2. Not suitable for emergency.
3. Irritant and unpleasant drug can’t be administered.
4. Certain condition of the patient are unsuitable for oral administration.
The conditions are:
 Unconscious
 Non co-operative or psychotic patient.
 Vomiting

5. First pass metabolism occurs.

Intravenous Route
Advantage:
1. Quick onset of action.
2. Emergency route.
3. Rapid drug blood level obtained.
 4. Avoid first pass metabolism.
5. Certain condition of the patient are suitable for intravenous administration.
 Unconscious
 Non co-operative or Psychotic patient.
 Vomiting

6. Administration of drug can be stopped if adverse effect developed.

Disadvantage:
1. Self-medication is not possible.
2. Strict aseptic, sterile and precaution is required.
3. Invasive painful procedure.
4. Risk or Complication:
 Infection
 Hemolysis or Hemorrhage
 Local venous thrombosis
 Hypersensitivity & Pyrogenic reaction

Definition
Agonist: A drug that binds with receptor and activates the receptor to produce
pharmacological response is called agonist.
Example :
 Sulbutamol → Beta-adrenoceptor agonist.
 Pilocarpine→ Muscarinic agonist.

Antagonist:A drug that binds with receptor (as agonist) but not activating effect
are called antagonist.
Example :
 Propranolol→ Beta-adrenoceptor antagonist.
 Atropine→ Muscarinic antagonist.

Partial agonist: A drug that bind with receptor are capable of low degree of
activating effect is called partial agonist.

Inverse agonist: A drug that bind with receptor and then produce opposite
effect that is produced by true agonist.

Affinity: It is the tendency of a drug to bind with receptor and it is determined

by association/disassociation constant.

Efficacy: Ability of a drug upon binding with receptor to produce

pharmacological response is called efficacy.

Potency: Potency refers to concentration or dose of a drug required to produce

50% of that drugs maximum effect.

Synergism: The combine action of two or more drug could be greater than
simple edition of individual drug effect.
Example : Sulfonamide+ Trimethoprim→ Cotrimoxazole.

Potentiation: It occurs when one drug increase the action of another drug.
Example: In asthma, Salbutamol+ Aminophylline.

Drug antagonism: It occurs when the action of one drug opposite the action of
others drug.
 Example: Morphine + Naloxone (Antagonist of morphine)
If morphine overdose.

Summation or addition: The combine action of two drugs having some action
is equal to the arithmetic sum of effect of the individual drug.
Example: ß blocker+ diuretics

Difference between potency and efficacy:

Potency Efficacy
1.Potency refers to concentration or 1.Ability of a drug upon binding with
dose of a drug required to produce 50% receptor to produce pharmacological
of that drugs maximum effect. response is called efficacy.
2.Determined the administered does of 2.Determined the clinical effectiveness of a
the chosen drug. drug.
3.It is affected by affinity of receptor for 3.It is affected by characteristics of a
binding the drug and also by efficacy of particular drug receptor interaction(also
drug receptor interaction host factor)
4. Potency does not help to choose 4. Efficacy help to choose among the drug.
among the drug.

Drug interaction
Definition: Interaction between two or more drug administered simultaneously
result in alteration of pharmacological response of active drugs.
Objective of drug interaction:
1. To obtain a desired therapeutic effect.
2. To treat co-existing disease.
3. To broaden the spectrum in case of antibiotic therapy.
4. To resist the development of microbial resistance to antibiotic.
5. To minimize the adverse drug reaction.
6. To delay the emergency of malignancy cell in cancer chemotherapy.

Drug absorption
Definition:
The rate at which drug molecules cross the biological membrane to enter into the
systemic circulation from the site of administration.

Factor of drug absorption/absorption depend on:

A. Properties of cell membrane.
B. Physiochemical properties of the drug (Nature of the drug)
 Polar / non-polar
 Acidic / alkaline
 Lipid soluble / water soluble
 Ionized / non-ionized

Process of drug absorption:

1. Passive process
- Simple diffusion (About 99%)
 - Filtration

Criteria of passive process:

a) Along concentration gradient
b) No energy required
c) No carrier required

2. Active process
- Active transport (About 1%)
- Facilitate diffusion
- Pinocytosis

Criteria of active process:

a) Along or against concentration gradient
b) Energy needed
c) Carrier required
d) Quick process

Factor affecting gastrointestinal absorption:

1. Factor related to GIT or site
a) Blood supply to the absorptive surface (more in intestine than stomach)
b) Surface area proportionate to absorption( More in intestine)
c) Gastro intestinal motility
 Increase motility-diarrhea → Decrease absorption
d) PH of the GIT fluid
 Acidic PH – Acidic drug being non-ionized, so increase absorption
 Alkaline PH – Alkaline drug being non-ionized, so increase
absorption.
 e) GIT disease
 Mal absorption syndrome
 Crohn’s disease
 Coeliac disease
f) Presence of food in GIT
 High lipid soluble drug are better absorption in presence of food.
g) Physiochemical interaction in the GIT
 Warfarin + Bile acid→ decrease absorption.

2. Factor related to the drug.

a) Particle size and formulation
b) Molecular weight
c) Chemical nature of the drug
d) Ionization constant and partition co-efficient.

Factor affecting absorption from per-enteral site except IV:

1. Site of injection
 Intramuscular > Subcutaneous
2. Blood flow to the absorptive area
 Muscle→ more blood flow→ more absorption
 In Subcutaneous tissue → less blood flow → less absorption
3. Dosage formulation
 Drug in aqueous solution→ Rapid absorption
 Drug with vasoconstrictor → Slow absorption
4. Area of absorptive surface
5. Application of heat massage→ Increase
blood flow→ Increase absorption
6. Concentration gradient
7. Type of contact
Factor affecting absorption of skin:
1. Surface area
 More surface area→ More absorption
2. Thickness of the skin
3. Blood supply to the respective area.
4. Concentration gradient of the drug.
5. Liquid/Water perfusion co-efficient of the drug.
6. Lipid and water solubility.

Type of barriers for drug:

1. Single layer
 Lipid bilayer of cell membrane.

2. Multiple layer
 Blood placenta barrier
 Blood brain barrier

Diabetes mellitus
Definition: It is clinical syndrome characterized by hyperglycemia due to
absolute or relative deficiency of insulin.

Types of Diabetes mellitus:

1. Type II : Insulin dependent diabetes mellitus (IDDM)
2. Type II : Non – insulin dependent diabetes mellitus (NIDDM)
3. Nutrition related diabetes mellitus.
- Malnutrition
4. Gestational diabetes mellitus

Difference between diabetes mellitus:

Point IDDM NIDDM

Body weight Normal or low Obese
Age of onset Juvenile onset (less than30 Adult onset (more than 40
years) years)
Genetic Moderate or low Very strong family history
predisposition
ß– cell destruction → no Inability of ß cell to produce
Cause production of insulin. appropriate quantity of
insulin and insulin
resistance.
Ketonurea common No
Autoantibody Yes No
Treatment with insulin Treatment with oral
Treatment antidiabetic drug , mainly if
fail oral antidiabetic drug
treatment with insulin

Insulin

Basal insulin: Continuous low level secretion of insulin (approximately 1

unit/hour) between the meal and throughout night (24 unit/day).
Bolus / prandial insulin: Meal related secretion of insulin per day 24 unit.
 Insulin
Types of insulin:
1. Conventional
a) Short acting (6 – 8 hours)
 Regular
b) Intermediate acting (12 – 18 hours)
 NPH (neutral protamine hagedorn)
 Lente
c) Long acting (24 – 36 hours)
 Ultralente
2. Analogues (Mainly ß chain modify)
a) Rapid acting
 Aspart
 Lispro
 Glulisine
b) Long acting (24 – 36 hours)
 Glargine
 Detemir
c) Ultra long acting
 Degludec
3. Biphasic or combination
a) Conventional
i) Short acting (6 – 8 hours)
 Regular
ii) Intermediate acting (12 – 18 hours)
 NPH (neutral protamine hagedorn)
 Lente
 Indication of insulin:
1. Insulin dependent diabetes mellitus (IDDM)
2. Non – insulin dependent diabetes mellitus (NIDDM),if oral drug fail.
3. Non – insulin dependent diabetes mellitus (NIDDM) with complications
 Diabetic neuropathy
 Diabetic retinopathy
 Diabetic nephropathy
 Diabetic keto-acidosis
4. Non – insulin dependent diabetes mellitus (NIDDM) with stressful condition
o Pregnancy
o Surgery
o Infection

Adverse effect of insulin:

1. Hypoglycemia
2. Weight gain
3. Immune Insulin allergy (due to IgE antibody)
4. Immune insulin resistance (due IgG antibody)
5. Insulin oedema
6. Lipodystrophy.
Contraindication of insulin: Hypoglycemia
Treatment of insulin allergy: 1. Purified insulin
2. Steroid
3. Desensitization

Lipodystrophy:
It is two types
1. Lipoatrophy due to immune reaction (mainly)
 2. Lipohypertrophy due to lipogenesis
Treatment of lipodystrophy:
1. Changing the site of injection
2. Liposuction

Anti – diabetic action of insulin:

Insulin

Liver Muscle Adipose tissue/Fat

(1) Stimulation hepatic glucose (1) Stimulation glucose
uptake
(2) Inhibition glycogenolysis
(3) Inhibition gluconeog-
enesis
(4) Increase lipid and protein
synthesis
(1) Stimulation glucose
uptake uptake
(2) Inhibition flow of (2) Inhibition flow of
glucogenic precursion glucogenic precursion
to the liver(alanire,lactate) to the liver
(3) Increase protein and (alanine,lactate)
glycogen synthesis (3) Increase fatty acid
(4)Decrease protein synthesis
catabolism (4) Increase TG
deposition

Decrease blood glucose level

 Insulin Resistance
Definition: A diabetic patient requiring more than 200 unit per day insulin is
regarded as insulin resistance.

Causes of insulin resistance:

1.Physical inactivity
2.Obesity
3.Decrease number of insulin receptor.
4.Decrease affinity of receptor to insulin.
5.Associated with antibody direct against insulin receptor.

Treatment of insulin resistance:

 Life style modification
 Dietary modification
 Use of less antigenic insulin preparation(soluble insulin)
 Additional of oral hypoglycemia agent to release endogenous insulin
 Use of corticosteroid

Oral Anti – diabetic drug

A.Oral Hypoglycemia agent (Insulin secretagogues):
1. Sulfonyl urease derivatives
a) 1st generation
 Tolbutamide
 Acetohexamide
 Chlorpropamide
 b) 2nd generation
 Glibenclamide
 Glicazide
 glipizide

c) 3rd generation
 Glimepiride

1. Non – sulfonyl urease derivatives

 Repaglinide
 Nateglinide

B.Oral euglycemic agent:

1. Insulin sensitizers
a) Biguanide derivatives
 Metformin
 Buformin
 Phenformin

b) Thiozolidinedione
 Rosiglitazone
 Pioglitazone
 Troglitazone

2. Alpha glucosides inhibitor

 Acarbose
 Miglitol

2. Dipeptidyl peptidase – 4 inhibitor

 Sitagliptin
 Linagliptin
 Vildagliptin
 Saxagliptin
 Sulfonyl Urease

Indication of sulfonyl urease: Non-insulin dependent diabetes mellitus

(NIDDM) except in over weight patient.

Adverse effect of sulfonyl urease:

1. Hypoglycemia
2. Weight gain
3. Nausea
4. Vomiting
5. Headache
6. Facial flaccid
7. Hypersensitivity
8. Leucopenia
9. Thrombocytopenia

Contraindication of sulfonyl urease:

1. Pregnancy
2. Insulin dependent diabetes mellitus(IDDM)
3. Post operative patient
4. Known allergy to drug.
5. Severe renal insufficiency and hepatic failure
Mechanism of sulfonyl urease:
Sulfonyl urease binds to pancreatic ß cell potassium channel receptor.
↓
Inhibit ATP sensitive potassium channel in pancreatic ß cell.
↓
Potassium efflux if inhibited causing depolarization.
↓
Depolarization activates a voltage gate calcium channel, causing calcium influx.
↓
Insulin is released by exocytosis.

Biguanide
Indication of Biguanide :
1. Insulin dependent diabetes mellitus
2. Non insulin dependent diabetes mellitus
3. Obese person with NIDDM, Not control by sulfonyl urease
4. NIDDM with primary hyperlipidemia
5. Secondary failure with sulfonylurease

Adverse effect of Biguanide :

A.GIT:
 Anorexia
 Nausea
 Diarrhea
 Abdominal discomfort
 B.Vitamin B12 deficiency
C. Lactic acidosis
D. Metallic taste

Mechanism of Action Biguanide :

1. Decrease glucose production by liver by inhibited hepatic

gluconeogenesis.
2. Increase number of insulin receptor on muscle and fat tissue.
3. Direct stimulation of glycolysis in tissue with glucose remove from
blood.
4. Slow of glucose adsorption from GIT with increase glucose to lactate
conversion by enterocyte.
5. Reduction of plasma glucagon level.

Thiazolidinadione
Indication: NIDDM, Only when insulin resistance is present.
Side effect of thiazolidinedione :
1. Fluid retention
2. Leg swelling
3. Weight gain
Contraindication of thiazolidinedione :
1. Pregnancy
2. Oedema
3. Congestive heart failure
4. Liver and kidney disease.
 Hypoglycemia
Definition : Blood glucose level less than 2.5 milimole/litre is called
hypoglycemia.

Signs or Clinical feature of Hypoglycemia:

1. Mild to moderate hypoglycemia
A. Autonomic:
 Sweating
 Irritability
 Hunger pain
 Tremor
 Palpitation

B. Neuroglycopenic
 Headache
 Visual disturbance

2. Severe hypoglycemia
 Confusion
 Drowsiness
 Behavioral abnormality
 Convulsion
 Coma

Treatment of hypoglycemia:
A.Mild to moderate hypoglycemia ( conscious patient)
→ 15 gm glucose/equivalent food.
Example : Glass of soft drinks or Fruit juice or Snacks or meal.
(Safe blood glucose limit / RBS limit 5.5 millimole/L)
B.Severe hypoglycemia (unconscious patient)
→ Hospitalization 25% dextrose 50-100 ml is given IV instant, then 10% destrose
infusion.
→Injection glucagon 1 gm in intra-muscular/ Subcutaneous.

Blood glucose volume

In diabetics patient:
 Fasting blood glucose level (FBS) equal or more than 7 milimole /Litre(126
miligram/dL)
 RBS (Random blood glucose level)>11.1 milimole / litre (200 miligram/dL)

In pre-diabetic patient:
 Fasting blood glucose level (FBS) → 6.1 milimole /litre
 Random blood glucose level (RBS) → 7.8 milimole/litre

Investigation:
A. Blood sugar level
a) FBS (Fasting blood glucose level)
b) RBS (Random blood glucose level)
2. Urine – Glucose and ketone body
3. Oral glucose tolerance test (OGTT)
4. Plasma Hb A1 C level
- গত ৩ বছরে Blood Glucose Level এর গড় হিসাব।

- বছরে দুইবার করতে হবে।

Clinical feature of diabetes mellitus:

1. Classical feature:
(a) Typical feature
→Polyuria
→Polyphagia
→Polydipsia
→Weight loss
→Weakness
(b) Atypical feature
→ Fatigue
→ Infertility or repeated pregnancy loss.
→ Non healing infection
→ Dryness of mouth and throat
→ Pruritus of vulva and balanitis

2. Features of complication
 Diabetic neuropathy
 Diabetic retinopathy
 Diabetic nephropathy
 Diabetic keto acidosis
 Ulcer and delay healing
 Unconscious due to hypoglycemia lactic acidosis,keto,acidosis
  Stroke

Insulin independent glucose intake:

1. Brain
2. RBC
3. Gut epithelium
4. ß cell of pancreas
5. Nephron

Hypertension

Definition : Persistence rise of blood pressure systolic equal or more then 140
mm of Hg and diastolic equal or more then 90 mm of Hg within 3 separate
occasion within one month where in subject are not taking anti-hypertension
medication .

Causes of hypertension :
A. Essential hypertension or primary hypertension :
(i) Genetic factor
(ii) Socio-economical factor
(iii) Environmental factor.
(1) Obesity
(2) Smoking
 (3) Salt intake
(4) Alcohol intake
(iv) Hormonal factor
(1) High Renin
(2) Reduce nitric oxide (NO2)
(v) Neurotransmitter
(1) Acetylcholine.
(2) Nor- adrenaline.
B. Secondary Hypertension:
a) Renal or kidney
 Chronic glomerulonephritis
 Chronic atrophic pyelonephritis
 Congenital polycystic kidney disease
b) Cardiovascular cause
(1) Coarctation of aorta
(2) Renovascular hypertension
c) Endocrine cause.
(1) Acromegaly
(2) Cushing’s syndrome
(3) Adrenal hyperplasia
(4) Crohn’s disease
(5) Pheochromocytoma
d) Pregnancy
e) Drug
 Oral contraceptive pill ( estrogen containing OPC)
 Corticosteroid
  Vasopressin.

Antihypertensive drug
A. Sympatholytic or Sympathoplegic drug
a) Centrally acting drug
 Methyldopa (Safe in pregnancy)
 Clonidine
b) Ganglion blocker
 Trimethaphan
c) Adrenergic neuron blocking drug
(1) Reserpine
(2) Guanethidine
d) Receptor blocker
( Beta adrenergic antagonist / Beta blocker)
*According to selectivity
(i) Non- selective ( 1st generation)
 Propranolol
 Sotalol
 Pindolol

(ii)Selective ( 2nd generation)

a) Beta-1 :
 Atenolol
 Metoprolol
 Acebutolol
 Bisoprolol
 b) Beta-2
 Butoxamine

(iii)Alpha +Beta blockers

 Labetalol
 Carvedilol

*According to solubility:
 Lipid soluble
 Propranolol
 Oxonol
 Metoprolol
 Water soluble
 Atenolol
 Sotalol

Alpha adrenergic antagonist

(a) Alpha -1 antagonist
 Prazosin
 Terazosis
 Doxazosin
(b) Alpha -2 antagonist
 Idazoxan
(c)Alpha -1 + Alpha-2 antagonist
 Tolazoline
 Phentolamine
  Phenoxybenzamine

B. Calcium channel blocker ( According to generation )

1.First generation
 Verapamil
 Nifedipine
 Diltiazem
2.Second generation
 Amlodipine
 Nicardipine
 Felodipine
 Isradipine
3.Angiotensin receptor antagonist (ARB)
 Losartan
 Valsartan
 Eprosartan
 Olmesartan
 Candesartan
 Saralasin
C. Angiotensin converting enzyme inhibitor (ACEi)
a) Sulphahydral group containing
 Captopril
 Zofenopril
b) Dicarboxyl group containing
 Lisinopril
 Enalapril
c) Phosphorus group containing
 Fosinopril
D. Diuretics
 Beta Blocker
Indication:
1. Cardiac indication
a) Mild to moderate hypertension
b) Angina pectoris
c) Cardiac arrhythmia
d) Cardiac failure
e) Post myocardial infarction
2. Endocrine
a) Hyperthyroidism
b) Pheochromocytoma
3. Central nervous system indication
a) Anxiety
b) Migraine prophylaxis
c) Essential tremor.
4. Eye
a) Glaucoma

Adverse effect of beta blocker:

হাত ঠান্ডা ঠান্ডা লাগবে, due to peripheral pooling of blood.

1. Beta -1 mediated
a) Bradycardia
b) Hypotension
2. Beta -2 mediated
a) Bronchospasm
b) Hypoglycemia ( Insulin mediated treatment of DM)
c) Raynaud’s phenomenon
 d) Inerease plasma lipoprotein (dyslipidema)
e) Sexual interference ( Not to administered to productive age
boys, because it create Impotency)

Contraindication
(1) Asthma
(2) Congestive Cardiac Failure
(3) Cardiogenic shock
(4) Sinus Bradycardia
(5) Insulin dependent diabetes mellitus(IDDM)

Mechanism of beta blocker :

Beta blocker
—————————————————————————
↓ ↓ ↓
Action on heart Action on kidney Inhibition of vasomotor

canter

↓ ↓ ↓
Inhibit chronotropic Decrease renin release Decrease sympathetic

discharge

↓ ↓ ↓
Inhibit ionotropic effect Decrease aldosterone secaction Inhibit vasoconstriction

↓ ↓ ↓
Decrease cardiac output Decrease blood volume Vasodilation

↓
—————————————————————————
↓
 Decrease blood pressure

Angiotensin Converting Enzyme inhibitor (ACEi)

Mechanism :

(ACEi)
Angiotensin (-) ↓ Bradykinin

(-) Peptydal-dipeptidase (-)

No angiotensin-ii No activation of bradykinin

↓ ↓
—————————————————— Increase bradykinin

↓ ↓ concentration

Decrease sympathetic discharge No aldosterone Secretion

↓ ↓ ↓
Decrease vasoconstriction No water and salt retention Vasodilation

↓
Decrease total peripheral resistance

↓
Renal vasodilation

——— ——————————————————————————

↓
 Decrease blood pressure

Angiotensin Converting enzyme inhibitor (ACEi)

Indication :
(1) Hypertension patient with diabetes mellitus
(2) Hypertensive patient with chronic kidney disease
(3) Myocardial infarction
(4) Stroke
(5) Heart failure

Adverse effect :
(1) Dry cough ]due to bradykinin
Rx,
 stop the drug and
 Salt intake
(2) Hypotension
Rx,
 Start with low dose
(3) Hyperkalemia
(4) Proteinuria
(5) Acute renal failure
(6) Angio-oedema
(7) Skin rash
(8) Fever
(9) Altered sense of taste.

Contraindication :
(1) Systolic blood pressure less than 100 mm of Hg
(2) Acute Renal failure
(3) Bilateral renal artery stenosis
 Calcium channel blocker
Indication :
(1) Angina
(2) Hypertension patient with asthma
(3) Atrial fibrillation
(4) Supraventricular tachycardia
(5) Migraine prophylaxis
(6) Raynaud’s phenomenon

Adverse effect :
 Postural hypotension
 Ankle Oedema (Peripheral Oedema)
 Atrioventricular block
 Gingival hyperplasia
 Headache
 Dizziness
 Feeling or fatigue
 Nausea
 vomiting
 Constipation

Contra-indication :
(1) Cardiac arrest
(2) Severe hypotension
(3) Bradycardia
(4) Heart block
(5) Malignant hypertension

Mechanism : Calcium channel blocker

 ↓
↓ ↓ ↓
Inhibit influx of calcium Bind with voltage Inhibit phosphatidyl
through receptor dependent calcium channel inositol metabolism.
mediated channel (L-type) in depolarized
membrane
↓
Inhibit influx of ca + +
(through L-type of voltage sensitive calcium)
↓
———————— Decrease calcium influx ———————
↓
Inhibit interaction of acting myosin
↓
↓ ↓
On smooth muscle On cardiac muscle
↓ ↓
Relaxation Inhibit chronotropic effect
↓ ↓
Vasodilation Inhibit ionotropic effect
↓ ↓

↓
Decrease blood pressure
 Angiotensin receptor blocker

Indication :
(1) Hypertensive patient with diabeles mellitus.
(2) Hypertensive patient with bronchial asthma.
(3) Diabetic nephropathy.
(4) Heart failure
(5) Following myocardial infarction (MI)

Adverse effect :
(1) Hypotension
(2) Hyperkalemia
(3) Acute renal failure
(4) Teratogenic effect

Contra-indication :
(1) Pregnancy
(2) Hyperkalemia
(3) Renal failure
(4) Bilateral renal artery stenosis

Mechanism :
 Angiotensin receptor blocker (ARB) drug
↓
Block angiotensin -ii receptor
↓
Angiotensin -ii can not bind with receptor
↓
Decrease angiotensin mediated effect.
↓
(1) Decrease output of sympathetic nervous system →
decrease adrenaline and noradrenaline
(2) Increase vasodilation of vascular smooth muscle →
decrease peripheral resistance
(3) Decrease aldosterone production → decrease
retention of sodium and water → decrease blood volume
(4) Increase level of bradykinin concentration
↓
Decrease blood pressure.

Analgesic
Definition: Analgesic is a group of drug that can relieve the pain. They also called
pain killer.

Types of analgesic:
 A. Opioid (Narcotic)
B. Non opioid ( Non narcotic)
C. Local anesthetic

Classification of Non-opioid:
A. According to selectivity
a) Relatively selective for cox-1 ( Cyclooxygenase
enzyme-1)
 Aspirin
 Indomethacin
 Sulindac
 Piroxicam.
b) Less selective for cox-1 ( Cyclooxygenase enzyme-1)
 Ibuprofen
 Paracetamol

c) On Both enzyme.
 Naproxen
 Diclofenac

d) More selective for cox-2 ( Cyclooxygnase enzyme-2)

 First generation
 Meloxicam
 Nimusulide

 Second generation
 Calecoxib
 Rofecoxib
 Valdecoxib

B. According to anti-inflammatory effect.

 (1) Strong
(i) Salicylic acid derivatives
 Aspirin
 Sodium salicylate

(ii)Heteroaryl acetic acid

 Diclofenac
 Ketorolac

(iii)Enolic acid
 Piroxicam
 Indole and indene acetic acid
 Sulindae
 Indomethacin

(iv)Indole & Indene Acetic Acid

 Indomethacin
 Sulindac

(2)Mild to moderate :
(i) Propionic acid derivatives
 Naproxen
 Ibuprofen
 Ketoprofen
(ii) Anthranilic acid derivatives
 Meclofenamic acid
(3)Weak
 Paracetamol

Common adverse effect of NSAID

(1) GIT (Gastro intestinal tract)
  Gastric erosion
 Gastric ulceration
 Dyspepsia
 Nausea, Vomiting
(2) Kidney
 Analgesic nephropathy.
 Allergic type of interstitial nephritis.
 Reversible acute renal failure.
(3) Liver
 Liver damage.
(4) Blood
 Impaired clotting
 Decrease platelet aggregation.
 Thrombocytopenia
(5) CVS ( cardio vascular system)
 Exacerbation of hypertension
 Congestive cardiac failure
(6) CNS ( central nervous system)
 Tremor
 Headache
 Hallucination
 Depression
 Confusion
(7) Hypersensitivity
 Rash
 Asthma
 Urticaria
 Rhinitis

Aspirin
 Indication :
A.To relief pain (Non- Visceral pain)
 Headache
 Myalgia
 Arthralgia
 Osteoarthritis
 Acute dental pain
 Dysmenorrhea
B. Acute rheumatic fever
C. Rheumatoid arthritis
D. Myocardial infarction (MI)
E. Arterial thromboembolism
F. Migraine
G. Sperm motility

Adverse effect :
(1) Ulceration
(2) Hepatic and renal damage
(3) Impaired clotting
(4) Reye’s syndrome
(5) Tinnitus deafness
(6) Allergic manifestation
 Rhinitis ( Inflammation of nasal mucosa)
 Urticaria

Contraindication :
 Pre-existing ulceration
 Hepatic and renal disease
 Coagulation disorder
o Haemophilia
o Hypoprothombineamia
 Gout
 Pregnancy
 Known case of previous sensitivity reaction

 How aspirin prevent thromboembolism / thrombolytic effect?

Aspirin (low dose)

↓
75 to100 mg ( > 350 mg)
↓
Inhibit platelet cyclooxygenase (cox) enzyme
↓
Decrease thromboxane A2
↓
Inhibit platelet aggregation
↓
So prevention of thromboembolism
  Role of NSAID (Aspirin) in inflammation:

Aspirin
↓
Inhibit cyclooxygenase (Cox) enzyme
↓
Inhibit prostaglandin (PG) Synthesis
↓
——————————————————————
↓ ↓ ↓
Inhibit synthesis of PGI 2, PGD2 Inhibit of PGE2 Inhibition of CNS2 Synthesis
in hypothalamus
↓ ↓ ↓
No vasodilation No potentiation of bradykinin No fever production
and histamine
↓ ↓
Decrease blood flow No pain perception

↓
No oedema and redness

↓
Decrease inflammation
  Antipyretic action of Aspirin :

Aspirin
↓
——————————————————————
↓ ↓ ↓
Inhibit PGE2 synthesize in Inhibit thermoregulatory Inhibition of CNS response
Hypothalamus center in hypothalamus to interleukin-1
↓ ↓
Decrease PGE2 Vasodilation and Increase sweating
and histamine
↓ ↓
Hypothalamic set point of Increase heat lose
Temperature break to normal level

↓
Decrease Pyrexia

Why aspirin is contraindicated in pregnancy?

(1) First trimester
→ Teratogenic effect ( cleft lip plate)
(2) Second trimester
 → Close of PDA then IUD
(3) Last trimester
 Intracranial Hemorrhage
 Inadequate uterine contraction→ Prolonged labor→
Then fetal distress syndrome

Selective cox-2 inhibitor

Indication :
A. Osteoarthritis
B. Rheumatoid arthritis
C. Acute gout arthritis
D. Primary dysmenorrhea
E. Acute musculoskeletal pain
F. Primary familial adenomatous polyposis

Adverse effect :
A. Abdominal pain
B. Hypertension
C. Fluid retention
D. Heart burn
E. Dyspepsia
F. Dizziness

Contraindication:
a. Asthma
b. Urticaria
c. Acute Rhinitis
d. Pruritus
e. Headache
f. Diarrhea
g. Known case of hypersensitivity reaction
 Paracetamol
Indication :
A. As Antipyretic
 Febrile condition
B. As Analgesic
 Headache
 Dysmenorrhea
 Musculoskeletal pain
 Dental pain (Toothache)
C. In child to avoid race syndrome

Adverse effect :
 Therapeutic dose
o Skin Rash
o Allergy
 Acute large dose
o Liver damage
o Dizziness
 Prolonged large dose
o Renal tubular necrosis
o Hypoglycemia

Contraindication:

o Liver damage
o Kidney damage
o Asthma
Antipyretic action of Paracetamol :

Paracetamol
↓
Inhibit synthesis of PGE2 in hypothalamus
↓
Hypothalamus set point of temperature return to normal
( thermoregulatory center also)
↓
Antipyretic Action.

Analgesic Action of Paracetamol :

Paraectamol
↓
Inhibit cyclooxygenase enzyme
↓
Inhibit synthesize of PGE1 and PGE2
↓
Inhibit synthesize of bradykinin
↓
Analgesic Action.
 Steroid
Definition:
Steroids are organic compound fat soluble, water insoluble unsaponifiable
fraction of lipid that contained “Cyclopentano-perhydrophenanthrene” nucleus.
They are release from 3 zone of adrenal cortex:
A. Zona glomerulosa ( mineralocorticoid )
a) Aldosterone ( mainly natural )
b) Fludrocortisone ( synthetic )
c) Deoxycorticosterone ( synthetic )
B. Zona fasciculata ( glucocorticoid )
a) Short acting (1 – 12 hours)
→ Cortisone ( Natural )
→ Hydrocortisone ( Synthetic )
b) Intermediate acting ( 12 – 36 hours )
→ Prednisone ( Synthetic )
→ Prednisolone ( Synthetic )
→ Methylprednisolone ( Synthetic )
→ Triamcinolone ( Synthetic )
c) Long acting ( 36 – 55 hours )
→ Betamethasone ( Synthetic )
→ Beclomethasone ( Synthetic )
→ Dexamethasone ( Synthetic )
C. Zona reticularis ( Sex hormone, endogen )
a) Dehydroepiandrosterone ( natural )
b) Testosterone ( natural )
c) Androstenedione ( natural )

Route of Administration:

A. Oral
o Prednisone
 o Prednisolone

B. Intravenous ( IV )
o Hydrocortisone
o Dexamethasone
o Methylprednisolone

C. Inhalation
a) Beclometasone
b) Fluticasone
c) Budesonide
D. Tropical
a) Beclomethasone
b) Triamcinolone

Pharmacological effect of steroid:

o Permissive effect
o Metabolic effect
o Anti – inflammatory effect
o Immunosuppressive

Permissive effect:
In the absent of corticosteroid certain normal action cannot take place in the
body.
Example:
Vascular and bronchial response to catecholamine depends upon presence of
corticosteroid.

Metabolic effect:
A. On carbohydrate metabolism
 a) Increase blood glucose level by increase gluconeogenesis, increase
glycogenesis, decrease peripheral glucose utilization.
b) Then hyperglycemia causes blood stimulation of Insulin release &
Glycogen store in the liver.
B. On fat metabolism
a) Direct stimulation hormone sensitive lipase→ Lipolysis→ Fat & Serum
Fatty acid glycerol.
In large dose, lipogenesis due to insulin release→ fat deposition ( face,
neck, back ) →moon face and buffalo hump →Cushing Syndrome
C. Protein metabolism
a) Increase protein catabolism in muscle.
o Increase excretion of nitrogen.
o Decrease protein synthesis.
o Increase amino acid uptake in liver from peripheral tissue.
b) Growth retardation due to muscle wasting.
c) Osteoporosis due to negative nitrogenous balance.
Anti – inflammatory effect:
o steroid produce lipocortin→ inhibit phospholipase A2 enzyme in the cell
membrane →block the cyclooxygenase and lipoxygenase enzyme
pathway→there by inhibit synthesis of prostaglandin, leukotriene,
thromboxane A2. They also reduce migration of neutrophil to the site of
inflammation.

Immunosuppressive action:
1) Inhibit the ability of macrophage to phagocytosis and kill the micro-
organism.
2) Inhibit release of intraleukin-1 (IL-1) & 12 from T lymphocyte.
3) Decrease number of circulatory lymphocyte, monocyte, eosinophil→ so
decease cell mediate immunity.
4) Inhibit ability of complement.
5) Inhibit formation of antibody.
6) Impaired, delay hypersensitivity reaction.
 Clinical use of steroid:
A. Diagnostic use: Diagnosis of cushing syndrome by dexamethasone
suppressive test.
B. Maturation of fetal lung: Betamethasone to pregnant mother for
maturation of fetal lung.
C. Adrenal cause / Lipasement therapy
 Acute / chronic adrenocortical insufficiency
 Congenital adrenal hyperplasia

D. Non – endocrine use

a) Allergic condition
 Urticaria
 Angioneuratic oedema
 Serum secress
b) Bone and joint disease
 Arthritis
 Bursitis
 Sinovitis
c) Collagen vascular disease
 Rheumatoid arthritis
 Systemic lupus erythematous (SLE)
d) Dermatological
 Atopic dermatitis
 Xerosis
 Pemphigus
e) Eye
 Acute uveitis
 Allergic conjunctivitis
 Optic neuritis
f) GIT ( Gastro intestinal tract ) disorder
 Ulcerative colitis
g) Hematological
 Autoimmune hemolytic anemia
 ITP ( Idiopathic thrombocytopenic purpura )
 Leukemia
 h) Kidney
 Nephrotic syndrome
i) Lung disease
 Bronchial asthma
 Aspiration pneumonia
j) Neurological
 cerebral oedema ( Dexamethasone prescribed)
k) Organ transplantation
 To minimise graft rejection
l) CVS ( cardio vascular system )
 Rheumatic fever
 Rheumatic carditis
m) Others
 Thyroiditis
 Mountain sickness

Adverse effect of steroid:

1. GIT ( Gastro intestinal tract )
(3) PUD ( Peptic ulcer disease )
2. CVS ( Cardio rascular system )
(4) Hypertension
3. Eye
 . Cataract
 . Glaucoma
4. Bones an muscle
 Osteoporosis
 muscle wasting
 Pathological fracture of bone
5. Endocrine
 Weight gain
 Diabetes mellitus
 Impaired growth
 Iatrogenic cushing syndrome
6. Increase susceptibility to infection
 Opportunistic infection , tuberculosis , delays wound healing
7. CNS ( Central nervous system )
  Psychosis
 Depression
8.Adrenal / pituitary suppression by negative feedback mechanism.

Contraindication of steroid:
1) Absolute
 Cushing syndrome
2) Relative
 Diabetes mellitus
 Peptic ulcer disease ( PUD )
 Hypertension
 Congestive cardiac failure
 Osteoporosis
 Glaucoma
 Pregnancy
 Infection
 Psychosis

Adrenal suppression:
o When corticosteroid are administered for more than 2 weeks. Then adrenal
suppression may occur.
o If treatment with corticosteroid exceed over 2 weeks, then supplementary
therapy must be given at the time of minor stress ( two fold dose increase for
(24-48 hours ) or severe stress ( up to 10 fold dose increase for 48 to 72
hours ). Such as accidental trauma and major surgery.
o It may be taken 2 to 12 month for hypothalamus, pituitary, adrenal excess to
function normally.
o When corticosteroid therapy is stopped if should be done slowly / tapering
dose.

Effect of sudden withdrawal of steroid therapy:

1) Adrenocortical insufficiency
 2) Weight loss
3) Arthralgia
4) Conjunctivitis
5) Rhinitis
6) Itching
7) Skin nodule
NB: More than 40mg/day & duration (2-3) weeks sudden off result Acute adrenal
corticoid insufficiency, due to Impaired release of Endogenous steroid because of
negative feedback mechanism. So we should stop steroid in gradual tapering dose,
it will help to occur positive feedback.