06/15/2024

GASTRO-INTESTINAL TRACT,
RESPIRATORY, ENDOCRINE &

Dr. N. Ramanujam
AUTACOID PHARMACOLOGY:
ALLIED HEALTH SCIENCES

1 Dr. RAMANUJAM NARAYANAN, MBBS, MD

(Pharmacology), PhD,
PROFESSOR (PHARMACOLOGY),
PSG IMS & R
PHARMACOTHERAPY OF ACID-PEPTIC

06/15/2024
DISEASE (APD)

Dr. N. Ramanujam
2 GASTROINTESTINAL PHARMACOLOGY
OVERVIEW

06/15/2024
 Pathophysiology of peptic ulcer

Dr. N. Ramanujam
 Drugs for APD:
 Classification
 Individual drug classes

 APD treatment with H.pylori regimes

3
 INTRODUCTION
GASTRIC

06/15/2024
DUODENAL

Dr. N. Ramanujam
APD

STRESS
ZOLLISON PEPTIC ULCERS
ELLISON
SYNDROME
NSAID INDUCED

GERD / GORD

HELICOBACTER
INFECTION
4
GASTRIC & PEPTIC ULCERS

06/15/2024
Dr. N. Ramanujam
Gastric ulcer Duodenal ulcer

Low-normal acid High-normal

output acid output

5
 PHYSIOLOGY OF ACID SECRETION
MECHANISM SOURCE EFFECTS NET EFFECT

06/15/2024
NEURONAL: HA Oxyntic Cell Increased INCREASED
(H2) (ECF-Like) Adenylyl Cyclase PUMP

Dr. N. Ramanujam
(Gs) ACTIVITY
NEURONAL: Ganglion cells Mobilization of HA RELEASE
ACh (M1, M3) calcium (PLC;
IP3-DAG)
HORMONAL: Antral cells
GASTRIN
(CCK2)
HORMONAL: _ Reduced acid REDUCED
SST production PUMP
ACTIVITY /
LOCAL: PG E2 Parietal cells Reduced Adenylyl ACID OUTPUT
Cyclase (Gi)
6
PHASES OF ACID SECRETION

06/15/2024
 BASAL CHARACTERISTICS OF HCl

Dr. N. Ramanujam
Volume
 PSYCHIC
Rate

 NEUROGENIC Pepsin content

Intrinsic factor secretion

 GASTRIC
PH

7
 PATHOPHYSIOLOGY:
RISK FACTORS FOR APD

06/15/2024
• Mucus
• Bicarbonate

Dr. N. Ramanujam
• Rich mucosal blood flow
• PGE
• EGF, TGF
• Competent sphincter
• NO
• Acid hyper secretion • Innate resistance
• Heredity
• Decreased mucosal blood flow
• Incompetent Sphincter
• High acid output states
• Diet – spicy, smoking
• Drugs – CS, NSAID, Alcohol,
Caffeine, Cola, Etc. 8
• Bile
 THE ‘IMPORTANT’ BALANCE: AIM OF
TREATMENT -

06/15/2024
Dr. N. Ramanujam
• AGGRESSIVE FACTORS

• DEFENSIVE FACTORS

9
 10
ANTI MICROBIALS ULCER PROTECTIVESACID NEUTRALIZERSANTI
/ ANTACIDS
SECRETORY
• CLARITHROMYCIN • COLLOIDAL BISMUTH SUBCITRATE
• SYSTEMIC
(CBS) • HISTAMINE H2 RECEPTOR BLOCKERS
• TINIDAZOLE • SUCRALFATE • NON SYSTEMIC • PROTON PUMP INHIBITORS
• METRONIDAZOLE • ANTI CHOLINERGICS
• AMOXICILLIN • PROSTAGLANDIN ANALOGS
• TETRACYCLINES

Dr. N. Ramanujam
06/15/2024
DRUGS USED IN APD: CLASSIFICATION
06/15/2024 Dr. N. Ramanujam
11
www.ispub.com/
 1. H2-BLOCKERS

06/15/2024
 Mechanism:

Dr. N. Ramanujam
 Famotidine:mixed
 Others: competitive

 Individual H2-blockers:

 Cimetidine: PROTOTYPE
 Ranitidine
 Famotidine
 Roxatidine
12
 CIMETIDINE:

06/15/2024
 ACTIONS:
 Antagonize HA

Dr. N. Ramanujam
 Suppress all 4 phases; dose dependent
 Anti ulcerogenic
 No action on tone

 PHARMACOKINETICS:
A- P/O
 D – BPB, no BBB
 M – First pass high
 E – CRF: Reduce dose
13
 06/15/2024
 ADE:
 CNS

Dr. N. Ramanujam
 GIT
 CVS: HA release
 Anti androgenic
 Liver

 Drug Interactions:
 CYP Inhibitor
 Antacids  2 hrs  H2 Blockers

14
 06/15/2024
 RANITIDINE: 300 mg h.s.
 5X Potent

Dr. N. Ramanujam
 Longer duration
 Advantages over Cimetidine

 FAMOTIDINE: 40 mg h.s.
 ZE syndrome
 Aspiration pneumonitis

 ROXATIDINE: 150 mg h.s.

 10X potent
 Longer action 15
 Intravenous H2 blockers

06/15/2024
 Uses:
 DU
1. Ranitidine
–
2. Cimetidine

Dr. N. Ramanujam
 Pain: 2-3 d
 Healing: 4 w
3. Roxatidine
 GU
 Stressulcers / gastritis 4. Famotidine
 ZE syndrome
 GERD
 Prophylaxis in Aspiration pneumonitis
 Urticaria

 Over-The Counter (OTC): H2-blockers

 Tolerance ++ vs. PPI 16
 2. PROTON PUMP INHIBITORS (PPIS):
BENZIMIDAZOLES

06/15/2024
 Mechanism
 InhibitsH+-K+ ATPase irreversibly

Dr. N. Ramanujam
 Final common step
 Active at low p H (2-4)

 Individual PPIs
 Omeprazole: PROTOTYPE
 Esomeprazole
 Lansoprazole
 Pantoprazole, S-Pantoprazole
 Rabeprazole
17
 OMEPRAZOLE

Dose

06/15/2024
 MOA:
 Sulphenicacid + Sulphenamide 20 mg o.d.

Dr. N. Ramanujam
 SH groups of PP Covalently
 CAase inhibitor

 ACTIONS:
 High binding
 Bioavailability reduced by food (empty stomach)
 Food req. 1 hour later to activate PP
 CYP 2C19, 3A4
 Hit and run drug till 3-5 days
18
 06/15/2024
 PANTOPRAZOLE: 40-120 mg/d o.d.
 Safest

Dr. N. Ramanujam
 Oral, i.v.
 LANSOPRAZOLE
 Reduced dose in CLD
 RABEPRAZOLE: 40-80 mg/d o.d.
 Higher pk a  fastest,
 Increases mucin
 ESOMEPRAZOLE
 Higher bioavailabl,
 Longer t ½ (GERD)

 S-PANTOPRAZOLE 19

2 X POTENT
 06/15/2024
 Treatment for:
 Peptic ulcers, esp. bleeding ulcers, stress ulcers
 GERD, ZE syndrome

Dr. N. Ramanujam
 H.pylori, aspiration pneumonitis

 Caution:
 Hepatic impairment
 Fracture

 G.I. disturbances: atropic gastritis, gastrinemia

 DDI – CYP inhibitor

 Achlorhydria

 Leucopenia

 Reduced testosterone
20
3. ANTICHOLINERGIC

06/15/2024
 Pirenzepine –
 Action – antagonizes M1 receptors

Dr. N. Ramanujam
 Reduced acid; no p H change
 Side effects –
 Dry mouth
 Dry eye

 Urinary retention
Older drugs
 Constipation Propatheline
Oxyphenonium
 Dicyclomine – Atropine
 Adjunct in APD, ZE syndrome

21
4. PROSTAGLANDIN ANALOG
Inhibits acid
Inhibits gastrin

06/15/2024
 Misoprostol Stimulates HCO3
 PGE1: short duration Stimulates mucin

Dr. N. Ramanujam
 Mechanism of Action Increases Blood flow
 Uses – Cytoprotective
 NSAID-induced ulcers: prophylactic, treatment
 Bleeding DU

 ADE –
 OXYTOCIC
 DIARRHEA

 Poor compliance, ulcer pain initially

 Contraindications
 Pregnancy (stimulates uterine contractions)
22
 5. SYSTEMIC ANTACIDS

06/15/2024
 Alkalies

 Inactivates pepsin by changing p H to 2-4

Dr. N. Ramanujam
 Sodium bicarbonate
 Sodium citrate

 ANC: Acid Neutralizing capacity

1 N HCl  3.5 p H in 15 mins (m Eq)

 Taken with food

 Takes 2-3 hrs for action
23
 06/15/2024
 Side effects
 Hypernatremia Water retention

Dr. N. Ramanujam
 Hypercalcemia
 Alkalosis
 Acidrebound
 CO2 release  perforation

 Uses
 Heartburn
 Alkalinization
 Treating acidosis 24
 6.NON SYSTEMIC ANTACIDS

06/15/2024
 Nonsystemic antacids
 Aluminium hydroxide: CI in CRF

Dr. N. Ramanujam
 Dihydroxyaluminium sodium
 Calcium carbonate
 Magnesium hydroxide / milk of magnesia

 Side effects
 Diarrhea: osmotic & CCK release (magnesium)
 Constipation, encephalopathy, osteoporosis
(aluminium)
 Electrolyte imbalance, milk alkali syndrome
25
(calcium)
DRUG INTERACTIONS & USES

06/15/2024
 Tetracyclines
 Iron

Dr. N. Ramanujam
 Quinolones Increase p H, form
complexes
 H2 blockers

 Phenytoin

 Nitrofurantoin (urine alkalosis)

 Uses:
 Painrelief in GERD
26
 Acid eructation / heartburn
 7. PEPSIN INHIBITORS / ULCER
PROTECTIVES

06/15/2024
 Sucralfate (Aluminium + Sucrose)

Dr. N. Ramanujam
 Actionby polymerization at 4 p H  gel (2 layers)
 PG synthesis
 Administration schedule:
 1 HR before 3 meals + bedtime once (qid): 1 gm
 Storage

 Other ulcer protectives:

 Bismuth subcitrate

27
USES

06/15/2024
 Healing peptic ulcers

Dr. N. Ramanujam
 Stomatitis

 Bile reflux

 Gastritis

 Prophylaxis of stress ulcers

28
ADVERSE DRUG EFFECTS

06/15/2024
 Constipation

Dr. N. Ramanujam
 Pneumonia

 Interactions

 Black tongue, diarrhea

 Osteodystrophy

 Encephalopathy

29
HELICOBACTER PYLORI –

06/15/2024
 Warron & Marshall, 1979
 2005 Nobel

Dr. N. Ramanujam
 Gram (-) bacillus
 Acquired by fecal-oral route in childhood
 Transmitted within families
 Secretes:
 Urease
 Exotoxin
 Not invade mucosa  attach to epithelia
30
 H.PYLORI REGIMENS –
DRUG REGIMES DURATION

06/15/2024
•TETRACYCLINE 500 MG Q.I.D. + 14 DAYS
•METRONIDAZOLE 200 MG Q.I.D. +
•BISMUTH SUBSALICYLATE 2 TAB. Q.I.D. +

Dr. N. Ramanujam
•OMEPRAZOLE 20 MG / RANITIDINE 150 MG B.D.

•CLARITHROMYCIN 500 MG B.D. + 14 DAYS

•METRONIDAZOLE 400 MG B.D. +
•OMEPRAZOLE 20 MG B.D.

•CLARITHROMYCIN 500 MG B.D. + 14 DAYS

•AMOXICILLIN 1000 MG B.D. +
•A PPI B.D. (LANSOPRAZOLE): FDA
31
 06/15/2024
Dr. N. Ramanujam
ENDOCRINE PHARMACOLOGY

32 THYROID & ANTITHROID DRUGS

 3
3

PHARMACOLOGICAL ACTIONS / PHARMACODYNAMICS - I

 Growth & Development

 Metabolism:
 Enhances lipolysis
 Stimulates carbohydrates
 Catabolic - negative nitrogen balance

 Calorigenesis - increases BMR

 3
4

PHARMACOLOGICAL ACTIONS / PHARMACODYNAMICS - II

 CVS: Hyperdynamic state of circulation induced

 Neurodevelopment: induction & maintenance both

 To maintain skeletal muscle tone

 GIT: Increases propulsive actions

 Pathological diuresis in myxoedema

 Facilitates erythropoiesis

 Male & female reproductive function

 3
5

CLINICAL PHARMACOLOGY OF LEVO-THYROXINE - I

 Cretinism: 8-12 mcg/kg/day - Reduces mental
retardation
 Myxoedema: 50 mcg/day (>50 years) / 12.5 -25
mcg/day (elderly) / >50 mcg/day (adults < 50 years /
pregnancy) initiation dose, adjusted after 2-3 weeks
and 4-6 weekly - thyroid hormone replacement therapy
 Subclinical hypothyroidism (only raised s.TSH):
replacement
 Myxoedema coma: 200-500 mcg IV followed by 100
mcg IV OD till oral compliance achieved - rapid
thyroid replacement
 3
6

CLINICAL PHARMACOLOGY OF LEVO-THYROXINE - II

 Non-toxic Goitre:- replacement therapy - sporadic
(prevents defect in hormone synthesis); endemic (dietary
iodine deficiency correction)
 Endemic: Prevented in pregnancy by 150-200 mcg of
Iodide; 100 mcg/g of iodine as iodised salt
 Sporadic & endemic: treatment with levothyroxine (may
be for 1 year / life-long), dosing as for myxoedema
 Thyroid nodule, TSH-non-responsive - regress by TSH
suppression by T4
 Non-resectable papillary carcinoma - regress by TSH
suppression by T4
 3
7

GOITROGENS
 Thioamide class of anti-thyroid drugs
 Ionic thyroid inhibitor class of anti-thyroid drugs
 Lithium (antimanic drug) - inhibits thyroxine release
 Amiodarone (antiarrhythmic) — Interferes with
peripheral conversion & actions
 Sulfonamides (antibacterials), PAS (anti-tubercular) -
inhibits iodination & coupling
 Enzyme inducers: Phenobarbitone, Rifampin,
Phenytoin, Carbamazepine (induce metabolism)
 Goitrin from cabbage, turnip & mustard plants
 3
8

Anti-thyroid drugs: mechanistic classification

 Inhibits hormonal synthesis (THIOAMIDES):
Propylthiouracil, Methimazole, Carbimazole
 Inhibits Iodide trapping (IONIC INHIBITORS):
-SCN / Thiocyanates, -ClO4 / Perchlorates, -
TcO4 / Pertechnates, -NO3 / Nitrates
 Inhibits hormone release:
Iodine, Iodides of Na & K, Organic Iodide
(Wolff-Chaikoff effect & Jod-Basedow
phenomenon)
 Destroy Thyroid tissue:
I131 / Radioactive iodine (gamma-ray—
emitter)
 3
THIOAMIDES (Propylthiouracil, methimazole, carbimazole) - I 9

 MOA:
 Bindthyroid peroxidase - prevent oxidation of iodine &
iodothyrosyl residues - inhibit iodination of tyrosine in
TG - inhibit coupling of iodotyrosine to Thyroid
hormones - (For Propylthiouracil: also inhibits
peripheral conversion)

 ADRs:
 Reversible hypothyroidism, GIT adverse effects & skins
rashes, joint pain, hepatotoxicity, fever, hair graying /
loss, dysgeusia, agranulocytosis, teratogenic / lactational
ADRs (less with propylthiouracil)
 4
THIOAMIDES (Propylthiouracil, methimazole, carbimazole) - ii 0

 Clinical uses:
Definitive therapy:
 Graves’ disease - 1-2 years
 Toxic multi nodular Goitre - lifelong
Pre-operatively:

 Young patients before subtotal thyroidectomy -

euthyroid state
With I131 in severe hyperthyroidism (C.I. in pregnancy)
Propylthiouracil in thyroid storm treatment
 4
1

IONIC INHIBITORS
 MOA:
 Monovalent ions - Bind NIS - inhibit trapping of
Iodide by thyroid gland - No synthesis of thyroid
hormones
 Goitrogenic drugs: very toxic - not used clinically
 Order of potency: Perchlorate > thiocyanates >
nitrate
 Pertechnates are newer diagnostic ionic inhibitors
/ radio contrast agents with 99mTcO4- specific to
thyroid glandular uptake scans
 4
2

IODINE & IODIDES - I

WOLFF-CHAIKOFF EFFECT JOD-BASEDOW PHENOMENON

EXCESS IODIDE - LESS IODINATION - IODINE / IODIDE EXOGENOUS -
HYPOTHYROIDISM HYPERTHYROIDISM
THYROID CONSTIPATION WITH THYROID ESCAPE WITH IODINE
IODINE & IODIDES & IODIDES

PREPARATIONS: LUGOL’S IODINE (5% IODINE IN 10% KI) SOLUTION; SODIUM /

POTASSIUM IODIDE (ORAL)
 4
3

IODINE & IODIDES - II

 Clinical uses:
Pre-operative (10 days) preparation for thyroidectomy in
Grave’s disease: with Propranolol orally
Thyroid storm - Lugol’s Iodine 6-10 drops / Iodine-contrast
media (Ipodate / Iopanoic acid) to prevent release & peripheral
conversion
Prophylaxis of endemic goitre - iodised salt (100 mcg Iodine / g
salt x 1.0-1.5 g/day
Antiseptic - tincture iodine (2% iodine in alcohol) / povidone
iodine (1-10% iodophore -1% mouthwash / 7.5 % scrub
solution / 5% spray with freon propellant / 5% ointment / cream
/ 200 mg Vaginal pessary): Powerful protoplasmic oxidiser:
Mandel’s paint (1.25 % Iodine in KI), Iodex ointment (4%)
 44

IODINE & IODIDES: ADVERSE EFFECTS

 Acute reaction -
Swelling of lips, eyelids, angioedema of larynx, fever, joint pain, petechial
haemorrhages, thrombocytopenia, lymphadenopathy - resolves on termination
of iodine exposure in sensitive individuals
 Chronic / Iodism -
Inflammation of mucous membranes, salivation, rhinorrhoea, sneezing,
lacrimation, eyelid swelling, GIT symptoms, burning sensation in mouth,
headache, rashes = IODISM
Goitre on chronic use
Fetal goitre (teratogenicity)
Flareup of acne in adolescents
Iodine in multi nodular goitre - aggravates thyrotoxicosis
 RADIOACTIVE IODINE - II
 Simple procedure, undertaken as OP procedure
 No surgical risks
 Permanent cure

 Hypothyroidism risk
 Long latency of response
 Teratogenicity (Cretinism in first trimester)
 Not suitable in young adults (require life-long levo- 45

thyroxine)
 GRAVE’S DISEASE
Propylthiouracil 50-150 mg TDS - 25-50 mg BD / TDS for
upto 1-2 years in young patients
Radioactive iodine 3-6 m Curie (as defined by prior tracer
study) - may be repeated after 3 months if required after
TFTs assessment
Surgery in older patients:
 Carbimazole 5-15 mg TDS - 2.5 - 10 mg /day in OD / BD
maintenance doses
 10 days prior to thyroidectomy, administer iodine orally as
sodium / potassium salt 100-300 mg / day
 Thyroidectomy 46

 Propranolol for acute relief

 THYROTOXIC CRISIS / THYROID STORM
 PROPRANOLOL 1-2 mg slow IV - 40-80 mg orally
every 6 hours till thyroxine levels normalise
 Propylthiouracil (PTU) 200-300 mg orally Q6 H
 6-10 drops of Lugol’s Iodine orally OR Iodine with radio
contrast media (iopanoic acid / ipodate) orally - Iopanoic
acid 0.5-1.0 g OD one hour after PTU
 HCS 100 mg IV Q8 H - Oral Prednisolone
 Diltiazem 60-120 mg BD oral added i/c uncontrolled
tachycardia
 Rehydration, external cooling, anxiolytics & antibiotics as 47
required
 06/15/2024
Dr. N. Ramanujam
ENDOCRINE PHARMACOLOGY

48 CORTICOSTEROIDS
GLUCOCORTICOID IMBALANCE

06/15/2024
EXCESS = CUSHING’S SYNDROME

Dr. N. Ramanujam
• ENDOGENOUS CUSHING’S
SYNDROME
• CUSHING’S DISEASE –
PITUITARY ADENOMAS
SECRETING ACTH
• IATROGENIC CUSHING’S
SYNDROME

DEFICIENCY ==
ADDISON’S DISEASE
• PRIMARY ADRENAL
INSUFFICIENCY
• SECONDARY ADRENAL
INSUFFICIENCY

49
CLASSIFICATION OF ADRENAL STEROIDS

06/15/2024
CORTISONE (Prodrug)  CORTISOL (Liver)

GLUCOCORTICOIDS

Dr. N. Ramanujam
MINERALOCORTICOID
INTERMEDIATE S
SHORT ACTING LONG ACTING
ACTING
CORTISOL PREDNISOLONE DEXAMETHASONE DEOXYCORTICOSTER
(HYDROCORTISONE) ONE ACETATE (DOCA)
METHYLPREDNISOLO BETAMETHASONE FLUDROCORTISONE
NE
TRIAMCINOLONE ALDOSTERONE

DEFLAZACORT

50
CLINICAL USES

06/15/2024
 REPLACEMENT IN ENDOCRINOLOGICAL CONDITIONS
 Acute adrenal insufficiency
 Addison’s disease

Dr. N. Ramanujam
 Congenital adrenal hyperplasia

 HYDROCORTISONE ORALLY / DEXAMETHASONE IV ±

FLUDROCORTISONE ORALLY

51
CLINICAL USES

06/15/2024
 PHARMACOTHERAPY: ALLOGRAFT OF SKIN
 ARTHRIDES  SEPTIC SHOCK
 COLLAGEN DISORDERES  THYROID STORM

Dr. N. Ramanujam
 SEVERE ALLERGIC REACTIONS  DIAGNOSTIC USE – HPA AXIS
 AUTOIMMUNE DISORDERS FUNCTION TESTING
 BRONCHIAL ASTHMA
 LUNG DISEASES
 INFECTIONS
 OCULAR DISORDERS

 DERMATOLOGICAL
CONDITIONS
 INTESTINAL DISORDERS
 NEUROLOGICAL CONDITIONS
 NAUSEA / VOMITING
 MALIGNANCY
 ORGAN TRANSPLANT &
52
ADVERSE EFFECTS

06/15/2024
 GLUCORTICOID
 CUSHING’S HABITUS  MINERALOCORTCOID
 DERMATOLOGICAL  Sodium / water retention

Dr. N. Ramanujam
 HYPERGLYCEMIA  Hypokalaemia & alkalosis
 MYOPATHY  Hypertension (rapid)
 SUPERINFECTIONS
 INCISIONAL HEALING
 PEPTIC ULCERATION
 OSTEOPOROSIS &
ORTHOPEDIC EFEFCTS
 CATARACT
 GLAUCOMA
 GROWTH RETARDATION
 TERATOGENICITY
 PSYCHIATRIC DISTURBANCES
 HPA AXIS SUPPRESSION
 HYPERTENSION (Gradual)
53
MINIMIZING HPA AXIS SUPPRESSION –
PRECAUTIONS

06/15/2024
 Short acting steroids in lower doses preferred
 Shorter duration of treatments preferred

Dr. N. Ramanujam
 OD in morning (circadian rhythm) preferred to repeated
doses in a day
 Alternate day treatment regimens preferred

 Local / topical steroids preferred if condition allows its

use

54
CONTRAINDICATIONS

06/15/2024
 PEPTIC ULCER

Dr. N. Ramanujam
 DIABETES MELLITUS
 HYPERTENSION  HERPES SIMPLEX
 VIRAL & FUNGAL KERATITIS
INFECTIONS  PSYCHOSIS
 TUBERCULOSIS &  EPILEPSY
INFECTIONS  CONGESTIVE HEART
 OSTEOPOROSIS FAILURE
 RENAL FAILURE

55
 06/15/2024
Dr. N. Ramanujam
ENDOCRINE PHARMACOLOGY

56 DIABETIC KETOACIDOSIS & HYPOGLYCEMIA

DIABETIC KETOACIDOSIS

06/15/2024
 Regular insulin 0.1-0.2 U/kg I.V.  0.1 U/kg/hr infusion [Goal:
fall in glucose ~ 10% /hr]  till RBG = 300 mg/dl  insulin ~ 2-
3U/hr

Dr. N. Ramanujam
 NS I.V. 1L/hr  0.5 L/hr  ½ NS (If BP & HR stabilizes) 
  RBG ~ 300 mg/dl  5% Glucose in ½ NS

 After 2-3 hours, add 10-20 mEq/hr KCl to IV fluid

 50 m Eq of sodium bicarbonate till p H > 7.1 (blood)

 3-4 m mol/hr potassium phosphate infusion (! Tetany)

57

 Antibiotics
HYPOGLYCEMIC COMA

06/15/2024
 Oral glucose 15-20 g / sugar  repeat after 15-20 mins.

Dr. N. Ramanujam
 30-50 ml of 50% Glucose I.V. over 10 mins.

 Glucagon 0.5-1.0 mg IV

 Adrenaline 0.2 mg SC [monitor CVS vitals]

 Other hyperglycemic drugs:

 Diazoxide

 Somatostatin 58

 Streptozotocin
EICOSANOIDS
[PROSTAGLANDINS &
LEUKOTRIENES] &
PLATELET-ACTIVATING FACTOR (PAF)

LIPID-DERIVED AUTACOIDS

5
9
CLINICAL USES OF PROSTAGLANDINS
THERAPEUTIC CLASSIFICATION

NATURAL PGs PG ANALOGUES

LATANOPROST,
DINOPROSTONE,
PGE2 TRAVOPROST,
GEMEPROST
BIMATOPROST

PGF2-Alpha DINOPROST CARBOPROST

PGE1 ALPROSTADIL MISOPROSTOL

PGI2 EPOPROSTENOL -

60
CLINICAL USES OF PROSTAGLANDINS
THERAPEUTIC FORMULATIONS

NATURAL PGs PG ANALOGUES

Vaginal gel, vaginal tablet,

extra amniotic solution, IV
0.005-.0.05% stand-alone eye drops / in
PGE2 & oral solutions, cervical
combination with Timolol as eye drops
gel,
Vaginal pessary

PGF2-Alpha intra-amniotic injection Intra-muscular injection

PGE1 IV solution Oral tablet (Combo with Mifepristone)

PGI2 IV for reconstitution -

61
CLINICAL USES
ABORTIVE EFFECTS
 Intravaginal PGE2 inserted 3 hours prior to dilatation procedure /
Methotrexate + Misoprostol - THERAPEUTIC ABORTION (first trimester,
7 weeks of gestation): minimises trauma to cervix
 Kit (400 mcg Misoprostol + 600 mg Mifepristone 2 days before the dose of
first component) / Intra-vaginal Misoprostol in MEDICAL TERMINATION
OF PREGNANCY: alternative to suction-evacuation after inducing uterine
contractions & expulsion of conceptus
 Mifepristone pre-treatment - EXTRA-Amniotic PGE2 injection - iv infusion
of oxytocin / INTRA-Amniotic PGF2-alpha - hypertonic solution (2nd
trimester) - MIDTERM & MISSED ABORTION, MOLAR GESTATION

62
CLINICAL USES
UTERINE & CERVICAL STIMULANT EFFECTS
 INDUCTION / AUGMENTATION OF LABOUR:
 DOC = OXYTOCIN; Intra-vaginal PGE2 (also Extra-amniotic) & PGF2-alpha
(also Intra-amniotic) in toxaemia of pregnancy & Renal failure patients (no fluid
retention, unlike oxytocin) / primipara gestation (slow augmentation)

 CERVICAL RIPENING / PRIMING:

 Low dose (less effect on motility) of intra-vaginal / in-situ in uterine canal PGE2
(makes cervix softer & compliant) followed by INDUCTION of labour with
oxytocin 12 hours later by IV infusion: CERVICAL RIPENING BEFORE
INDUCTION

 POSTPARTUM HEMORRHAGE:
 CARBOPROST [15-methyl-PGF2-Alpha] I.M. for PPH treatment due to uterine
atony [as alternative to ergometrine & oxytocin]

63
CLINICAL USES
OTHER USES
 WIDE ANGLE GLAUCOMA [PGF2-alpha topical]
 PEPTIC ULCER & NSAID-induced ULCERS [PGE1 / MISOPROSTOL]
 MAINTAIN PATENT DA IN NEONATES with congenital cardiac anamolies / till
corrective surgery undertaken [PGE1 / ALPROSTADIL IV after dilution]
 PRIOR TO TRANSFUSION, EXTRA-CORPOREAL PROCEDURES
[HEMODIALYSIS & CARDIOPULMONARY BYPASS] - PGI2 / EPOPROSTENOL
IV [increased platelet life]
 PULMONARY ARTERY HYPERTENSION [EPOPROSTENOL CONTINUOUS I.V.
into large vein]
 PERIPHERAL VASCULAR DISEASE - RAYNAUD’S DISEASE & ISCEMIC
ULCER-HEALING IN INTERMITTENT CLAUDICATION [IV INFUSION OF
PGI2 / PGE1] - Relieves rest pain & increases healing
 IMPOTENCE - Intra-cavernosal injection of PGE1 [second line to Sildenafil /
Tadalafil] - Penile erection lasting upto 1-2 hours due to smooth muscle relaxant
effects
64
RECENT DRUGS / NEWER
INDICATIONS
 ILOPROST (PGI2) - NYHA III / IV Pulmonary artery hypertension - dilates
systemic & pulmonary vessels - available as 0.01 mg/ml / 0.02 mg/ml, 10 mcg /
ml / 20 mcg / ml for inhalation route - Has two diasteroisomers (4S Isomer >> 4R
Isomer) - IP & EP1 receptors binding - II Generation PG analog - ADRs:
hypotension, diarrhoea, flushing
 UNOPRISTONE ISOPROPYL - Open angle glaucoma - 0.15 % ophthalmic
solution / 1.5 mg/ml drops for ocular use
 TAFLUPROST - Fluorinated analog in glaucoma (Experimental)
 MISOPROSTOL , LUBIPRISTONE (PGE1) - Chronic constipation & Opioid-
induced constipation (respectively)

65
 06/15/2024
Dr. N. Ramanujam
RESPIRATORY
PHARMACOLOGY

66 BRONCHIAL ASTHMA & STATUS ASTHMATICUS

BRONCHODILATORS

 Beta-2 agonists:
 SABA – Salbutamol
 LABA – Salmeterol

 Inhaled anti-cholinergics:
 Ipratropium
 Tiotropium

 Xanthines:
 Theophylline

67
INHALATIONAL CORTICOSTEROIDS

 Beclomethasone dipropionate

 Budesonide

 Ciclesonide

 Fluticasone propionate

 Flunisonide 68
STATUS ASTHMATICUS

 Hydrocortisone hemisuccinate 100 mg I.V. stat  100-200 mg Q(4-8) Hr. infusion

 Nebulized Salbutamol (2.5-5.0 mg) + Ipratropium bromide 0.5 mg intermittent

inhalations driven by oxygen flow

 High flow humidified oxygen

 Salbutamol / Terbutaline 0.4 mg SC / I.M.

 Intubation ± mechanical ventilation

 Antibiotics

 Saline & I.V. Sodium bicarbonate / Ringer lactate infusion

69
 Aminophyline 250-500 mg in 20-50 ml D5W I.V. over 20-30 mins infusion in
refractory cases