Pharmacology

MCI Batch Handouts

Dr. Ranjan Kumar Patel

Types of Drugs

Orphan drug Drug used for treatment of rare disease.

Essential drug Drug that satisfies the health care need of majority of population.
Efficacious, Single molecule, Safe, Easily available, Not costly

Spurious drug These are counterfeit or nakli drugs.

Illicit or street drug These are drugs of abuse like heroin.

Prescription drugs These are schedule H drugs which are given to patients only after producing prescription.
Receptors
Ligand gated ion channel Enzymatic Nuclear
GABAA
Receptors
Glutamate (AMPA, kainate and NMDA
Tyrosine kinase receptors
EGFR
Located in nucleus
Thyroid receptor
subtypes) VEGFR Vitamin A (Retinoic acid) receptor
Nicotinic Her-2 PPAR (Peroxisome Proliferator Activated
5HT3 Insulin Receptor)
Estrogen receptor
Serine/threonine kinase receptors Progesterone receptor
TGFR
Located in cytoplasm
Mineralocorticoid receptor
Janus kinase receptors
Glucocorticoid receptor
Cytokine receptors
Androgen receptor
Growth hormone receptor
Vitamin D receptor
Prolactin receptor

Guanylyl cyclase linked receptor

Receptor of ANP and BNP
GPCRs
Gs Gq Gi/o

Receptors
4. GPCR
Preclinical Trials - Animals
Clinical Trials – Humans
Phases Features

I Human Pharmacology and Toxicity Study

Pharmacokinetics Toxicity 20-100 normal healthy volunteers
Pharmacodynamics Safety 1-2 years
Maximum tolerable dose Open label trial Except- Anti cancer & Anti HIV

II Therapeutic Exploratory Trial 100-500 patients

Dose range 2-3 years
Safety RCT
Efficacy
III Therapeutic Confirmatory Trial 500-3000 patients
Safety 3-5 years
Efficacy RCT/RUCT

IV Post Marketing Surveillance Many thousands

Rare ADR No specific duration
Long term ADR Open label trial
Others Phase 0 – Microdosing
Phase V – Pharmacoepidemiology
ADR types Examples
Adverse drug reaction

A (Attenuated) Antihypertensive causing hypotension

Dose Dependent

B (Bizarre) Drugs causing hypersensitivity

Dose independent

C (Chronic) Steroids causing HPA suppression

Dose and Duration dependent

D (Delayed) Drugs causing teratogenicity

E (End of use – Withdrawal) Opioid withdrawal

Clonidine withdrawal hypertension

F (Failure of drug) Enzyme inducers causing OCP failure

Therapeutic Drug Monitoring Important Drugs
Principle: The plasma concentration of drug should have a good Digoxin:
correlation with effect/side-effect.
Therapeutic range: 0.5 – 0.9 ng/ml
Indications: Toxicity: > 2 ng/ml
1. If clinical effect of a drug can not be easily quantified. Increased mortality in A.fib: >1.2 ng/ml
2.
(If can be quantified – TDM not done) Lithium:

Therapeutic range:
2. Drugs with low therapeutic index 1. Mania prophylaxis: 0.6 – 1.0 mEq/L
Digoxin, Lithium, Theophylline 2. Mania treatment: 1.0 – 1.5 mEq/L
Antiepileptics, Antipsychotics, Methotrexate 3.
Toxicity: >1.5 mEq/L
3. Drugs with variable metabolism Dialysis: >4 mEq/L
e.g. Drugs metabolized by acetylation
Theophylline :
4. To check compliance
E.g. Antipsychotics Therapeutic range: 5 – 15 mg/L
Toxicity: >15 mg/L
Important Drug Schedules In India
Drug Schedules

Receptors
Schedule G
List of drugs that requires a mandatory text on label “Caution: It is dangerous to take this preparation, except
under medical supervision”. E.g. antihistaminics, metformin, insulin, anticancer drugs, antiepileptics etc.

List of drugs that can be sold only when a prescription is produced. Most drugs belong to this category. The
Schedule H drug label must display the text “Rx” in black colour and “Schedule H drug. Warning: To be sold by retail on the
prescription of a Registered Medical practitioner only”.

Schedule H1 Introduced in 2013 to deal with unauthorized sale of antibiotics. Drugs are labelled with “Rx” in red.

List of narcotic and psychotropic drugs which need special license for manufacture and sale. Drugs are labelled
Schedule X with “NRx” and prescription copy should be retained by the retailer for minimum of 2 years. E.g. Amphetamine,
Methylphenidate etc.

Schedule P It is about drug expiry period i.e. maximum period till which drug can be used with intact potency.

Schedule W List of drugs marketed under generic names only.

Pregnancy Drug Categories
Categories Significance Examples
Cat A
Receptors
No risk to fetus in human studies Levothyroxine
Potassium
MgSO4
Cat B Animal studies show no risk Penicillins
Human studies are lacking Cephalosporins
Macrolides
Brimonidine
Cat C Animal studies show positive teratogenic risk Albuterol
Human studies are not available Zidovudine
CCB
Morphine
Atropine
Cat D Human and animal studies show positive teratogenic risk Corticosteroids
Can be used in pregnancy because of benefits greater than risk might be Azathioprine
acceptable Carbamazepine
Valproate
Methotrexate
Lithium
Cat X Human and animal studies show positive teratogenic risk Thalidomide
Absolutely contraindicated in pregnancy because of risk greater than Isotretinoin
Beta blockers – 1st gen (Nonselective) Cardioselective 3rd gen
Propranolol Mr – Metoprolol Alpha blocker – Labetalol, Carvedilol,
Pindolol Bevantolol, Bucindolol
Penbutolol B – Bisoprolol, Betaxolol
Timolol Beta 2+ - Bopindolol
Oxprenolol E – Esmolol
Nadolol CCB – Carvedilol
A – Atenolol, Acebutolol
NO release – Nipradilol, Nebivolol
N – Nebivolol
K channel + - Tilisolol
Cardiologist – Celiprolol
Beta blocker with partial agonism/ Beta blocker with Na channel block/LA Water soluble beta blockers
Intrinsic sympathomimetic eff activity/Membrane stabilizing effect
C – Celiprolol Can – Carvedilol (Max) B – Betaxolol, Bisoprolol
L – Labetalol Blow – Betaxolol (Min) A – Atenolol
A – Acebutolol L – Labetalol N – Nebivolol
P – Penbutolol, Pindolol (Max) A – Acebutolol A – Acebutolol
M – Metoprolol N – Nadolol
P – Propranolol (Max), Pindolol A
S – Sotalol
Chips - Celiprolol
Drugs MOA Use Side-effects
Prostaglandin analogs Increase uveoscleral DOC in open angle Iris pigmentation
Latanoprost outflow glaucoma Trichomegaly
Bimatoprost Dry/Sandy eyes
Cystoid macular edema

C/I – Uveitis/Herpetic keratitis

Beta blockers Decrease aqueous 2nd line in open angle Timolol – NLD obstruction
Timolol production glaucoma Metipranolol – Granulomatous anterior uveitis
Metipranolol
Levobunolol C/I – Systemic beta blockers
Carteolol
Betaxolol

Epinephrine Decrease aqueous Open angle glaucoma Ocular allergy

Dipivefrine production Black pigmentation of conjunctiva
Alpha-2 agonists Decrease aqueous Open angle glaucoma Apraclonidine – Lid retraction, Mydriasis, Conjunctival
Apraclonidine production blanching
Brimonidine Brimonidine – Apnea in neonates, drowsiness/
somnolence, hypotension
Drugs MOA Use Side-effects
Miotic agents Increase trabecular Pilocarpine is DOC in Common – Accommodation spasm, brow ache, corneal
Pilocarpine outflow closed angle edema retinal detachment
Physostigmine glaucoma
Echothiophate Echothiophate – Iris cysts
Carbachol
Echothiophate/Physostigmine – Cataract

Carbonic anhydrase Decrease aqueous Acetazolamide – Acetazolamide – Systemic side-effects

inhibitors production Acute congestive
Oral/IV Acetazolamide glaucoma Brinzolamide/Dorzolamide –
Transient myopia
Topical Brinzolamide/ Periorbital dermatitis
Brinzolamide Dorzolamide – Open Corneal edema
Dorzolamide angle glaucoma

Rho-kinase inhibitor Increase trabecular Open angle Conjunctival hyperemia

Hypolipidemic Drugs MOA Uses Side-effects
Statins Inhibit HMG-CoA Reductase DOC Type II Myopathy
Most Potent: Decrease LDL (Max) hyperlipoproteinemia Hepatotoxicity
Pitavastatin>Rosuvastatin Primary and secondary Insulin resistance
Longest acting: Rosuvastatin > prophylaxis of MI and stroke
Atorvastatin
Ezetimibe Blocks NPC1L1 and inhibits Add on to statins Allergy
absorption of cholesterol in GIT upset
small intestine
Decrease LDL
Bile Acid Binding Resins Inhibit enterohepatic Add on to statins Hypertriglyceridemia
Cholestyramine circulation of bile acid Preferred in pregnancy and Hyperchloremic alkalosis
Colesevelam Decrease LDL children GIT upset
Colestipol
PCSK-9 inhibitors Prevent degradation of LDL Add on to statins Nasopharyngitis
Evolocumab receptors Influenza
Alirocumab Decrease LDL
Fibrates Stimulate PPAR-alpha and DOC Hypertriglyceridemia Cholelithiasis
Clofibrate increase synthesis of LPL DOC Chylomicronemia Myopathy
Fenofibrate Decrease triglycerides, syndrome
Bezafibrate chylomicrons and VLDL
Gemfibrozil
Carbonic Anhydrase Loop Diuretics Thiazides Potassium Sparing Osmotic diuretics
Inhibitors Diuretics
Mechanism – Block Block Na/K/2Cl pump in Block Na/Cl Spironolactone – Blocks Promotes solute free
carbonic anhydrase in TAL cotransporter in DCT aldosterone water loss
PCT (Indirect vasodilators – (Direct vasodilators – Amiloride – Blocks ENaC
Increase prostaglandin) Open K channels) In CD
Acetazolamide – DOC in Furosemide – DOC in Chlorthalidone – Mild to Spironolactone – DOC in Mannitol – DOC in
Acute mountain sickness pulmonary edema moderate hypertension cirrhotic edema and Cerebral edema
Familial hypokalemic Torsemide Metolazone – Effective resistant hypertension Acute congestive
periodic paralysis Bumetanide in GFR < 40 Amiloride – DOC in glaucoma
Ethacrynic acid Lithium induced
(Effective in GFR < 40) diabetes insipidus
Side-effects Side-effects Side-effects Common Side-effects Side-effects
Metabolic Acidosis Metabolic Alkalosis Metabolic Alkalosis Metabolic Acidosis Hyperkalemia
Hypokalemia Hypokalemia Hypokalemia Hypokalemia Hypokalemia
Hypomagnesemia Hypomagnesemia Hypernatremia
Hyperuricemia Hyperuricemia Spironolactone – Hyponatremia
Hypocalcemia Hypercalcemia Gynecomastia Dehydration
Pulmonary edema
Renal stones Ototoxic Hyperglycemia Triamterene – Folic acid
(Nephrolithiasis) deficiency
Drowsiness
Hyperammonemia
Drugs Uses Side-effects
Vasopressin Antagonists SIADH Hypokalemia
Conivaptan Hepatotoxicity (Tolvaptan)
Tolvaptan
Mozavaptan

Vasopressin analogs Acute esophageal variceal bleeding Facial pallor

Vasopressin NE resistant shock Nausea vomiting
Central diabetes insipidus
Postoperative ileus, Abdominal distention

Terlipressin DOC Acute variceal bleeding

Desmopressin DOC Central diabetes insipidus Water intoxication

DOC Nocturnal enuresis Headache
vWD type I
Hemophilia A
Monoclonal
Antibodies Target Uses
Abciximab GP IIb/IIIa Acute coronary syndrome
Multiple sclerosis
Alemtuzumab CD 52 Low grade lymphoma
Renal cell cancer
Bevacizumab VEGF Colorectal cancer
Diabetic retinopathy
Basiliximab CD25/IL2 receptor Acute graft rejection
Belimumab B lymphocyte activator SLE
Bezlotoxumab Clostridium difficile toxin B Pseudomembranous enterocolitis prophylaxis
Cetuximab Head and neck cancer
Panitumumab EGFR Colorectal cancer
Daclizumab CD25/IL2 receptor Multiple sclerosis
Eculizumab
Ravulizumab Complement 5 PNH
Palivizumab RSV RSV prophylaxis
Ranibizumab VEGF Macular degeneration
Gastric cancer
Colorectal cancer
Hepatocellular cancer
Ramucirumab VEGFR
Tyrosine Kinase
Inhibitors Target Uses
Abemaciclib
Rivociclib Cyclin dependent kinase 4 and 6 ER/PR positive breast cancer
Palbociclib
CLL
Waldenstorm macroglobulinemia
Ibrutinib Bruton’s tyrosine kinase Mantle cell lymphoma
Marginal zone lymphoma
Acalabrutinib Bruton’s tyrosine kinase Ibrutinib resistant mantle cell lymphoma
Sunitinib VEGFR tyrosine kinase Renal cell cancer, GIST
Sorafenib VEGFR tyrosine kinase Hepatocellular carcinoma
Imatinib – 1st generation BCR-ABL tyrosine kinase Drug of choice for CML/GIST
Bosutinib
Dasatinib 2nd generation
Nilotinib BCR-ABL tyrosine kinase Imatinib resistant CML
Ponatinib – 3rd generation
Omacetaxine BCR-ABL Protein Multi tyrosine kinase resistant CML
Myelofibrosis
Rheumatoid arthritis
Ruxolitinib Janus Kinase Psoriasis
Ulcerative colitis
Contraception
Regular contraception Mechanism
Combined OCPs Inhibit ovulation

Mini pills/POP Increase cervical mucous viscosity and decrease sperm

penetration
Inhibit blastocyst implantation
Mifepristone Blastocyst detachment

Emergency contraceptive Doses

Levonorgestrel 0.75 mg 2 tab 12 hours apart within 3 days

Ulipristal 30 mg 1 tab within 5 days

Mifepristone 600 mg 1 tab within 3 days

Steroids Potency Half life Uses

Hydrocortisone 1 8-12 hours DOC Replacement in CAH

patient, Addison’s disease
Asthma exacerbation
Prednisone 4 12-36 hours Inflammatory disorders like
Prednisolone rheumatoid arthritis, gout,
inflammatory bowel disease
Autoimmune disorders like
myasthenia gravis
Methylprednisolone 5 12-36 hours DOC Acute attack of multiple
sclerosis

Triamcinolone 5 12-36 hours Intraarticular in rheumatoid

arthritis

Dexamethasone 30 36-72 hours CAH pregnancy

Betamethasone Preterm labour
Antiasthmatic drugs
Drugs
Beta-2 agonists
SABA – Salbutamol/Terbutaline
LABA – Salmeterol /Formoterol
Anticholinergics – Tiotropium
Methylxanthines
Theophylline
Aminophylline
ICS
Fluticasone Most potent
Ciclesonide
Beclomethasone Soft steroids
LOX inhibitor Zileuton
LT C4/D4 inhibitors – Monteleukast
Mast cell stabilizers
Cromolyn sodium
Nedocromil
Anti Ig E- Omalizumab
Anti IL-5 – Reslizumab, Mepolizumab
Anti IL-5 R – Benralizumab
Uses Side-effects
SABA/Formoterol – Acute attack Palpitation
LABA – Persistent BA/Prophylaxis Tremor
Hyperglycemia/Hypokalemia
COPD DOC/Asthma Add on Dry mouth M.C
Asthma acute attack/persistent as 2nd line Adenosine A1 block – Seizure, Arrhythmia,
Diuresis
PDE-4 block – GIT upset, Headache
DOC Persistent BA Hoarseness of voice
TOC in acute attack – ICS + Formoterol Oropharyngeal candidiasis
Persistent bronchial asthma add on Hepatotoxic
EIA
Prophylaxis of allergen induced asthma Safest drugs
Severe persistent bronchial asthma Not effective in atopic dermatitis
Severe eosinophilic asthma Hypersensitivity
Antitussives
Centrally Acting Drugs Peripherally Acting Drugs
Opioids Local anesthetics
Codeine
Pholcodine Benzonate
Hydrocodone Lidocaine
Bupivacaine
Methadone
Morphine
Nonopioids Moguistine

Dextromethorphan

Diphenhydramine Cromolyn

Noscapine
Expectorants Mucolytics
Guaifenesin N acetyl cysteine

Ambraxol/Bromhexine

DNAse
Peptic Ulcer Disease
Drugs Uses Side-effects
PPI DOC GIT upset
Omeprazole – Max enzyme inhibition PUD, GERD, ZES, H. pylori, Barret’s Pneumonia
Pantoprazole – Min enzyme inhibition esophagus Pseudomembranous enterocolitis
Lansoprazole – Safest in pregnancy Osteoporosis
Rabeprazole – Longest acting and most Iron ,B12 deficiency
potent Hypergastrinemia
H2 blockers Same Same
Cimetidine – Least potent, Shortest acting DOC Prophylaxis of aspiration pneumonia Cimetidine – Impotence, Gynecomastia,
Ranitidine in postoperative patients Galactorrhea
Famotidine – Most potent, Longest acting
Anticholinergics Less preferred now a days Anticholinergic
Pirenzepine
Telenzepine
Misoprostol NSAID induced gastric ulcer Diarrhoea
Abdominal cramps
Sucralfate PUD, Rectal ulcer Constipation, Gastric bezoars
C/I Antacids
Bismuth subsalicylate/subcitrate H. pylori, Traveler's diarrhoea Constipation, Black discoloration of stool
and tongue
Antacids (Salts of Ca and Mg) PUD, Dyspepsia, GERD Decrease absorption of other drugs
Prokinetics
Drugs Uses Side-effects
D2 antagonists Chemotherapy induced nausea vomiting EPS
Metoclopramide Gastroparesis Hyperprolactinemia
Paralytic ileus Methemoglobinemia in neonates
Hiccups Diarrhoea

Domperidone GERD, Dyspepsia No EPS

5HT4 Agonists GERD Diarrhoea

Mosapride Chronic constipation Headache
Itopride Gastroparesis Insomnia
Prucalopride

Motilin Receptor Agonist Gastroparesis Diarrhoea

Erythromycin
Mitemcinal

CCK1/A receptor antagonist Gastroparesis Diarrhoea

Dexloxiglumide
Antiemetics
Drugs Uses Side-effects
5HT-3 Antagonists DOC Chemo/radiation/post operative Headache, Fatigue
Ondansetron – Shortest acting nausea vomiting
Palonosetron – Longest acting, Most Morning sickness
potent

NK1R Antagonists Chemo induced nausea vomiting Hypotension, Fatigue

Aprepitant
Rolapitant
Netupitant

CB1R Antagonists Chemo induced nausea vomiting Hypotension

Dronabinol Blood shot eyes
Nabilone

Dexamethasone Chemo induced nausea vomiting -

Laxatives: Ease the passage of formed stools
Purgatives: Evacuate the formed and preformed stool
Drugs MOA/Uses
Cl secretory agents

Lubiprostone Stimulates type II chloride channels

IBS associated with constipation

Linaclotide Stimulates guanylate cyclase, increases cyclic GMP, which stimulates CFTR
Plecanatide IBS associated with constipation

Probiotics Beneficial microorganisms (Lactobacillus, Saccharomyces, B. clausii)

Increase bulk of stool and used in both constipation and diarrhoea
Prebiotics Dietary fibers (Methyl cellulose, Psyllium husk, Bran)
Increase stool bulk and promote growth of beneficial microorganisms
Stimulant laxatives
Bisacodyl Promote low grade inflammation of large intestine and increase contraction
Senna Effect seen after 6-8 hours – Taken at night
Cascara Used for short term treatment of constipation – Max 10 days
Senna causes melanosis coli and pink/yellow-brown discoloration of urine

Castor oil Stimulates small intestine – Watery diarrhoea

Laxatives: Ease the passage of formed stools
Purgatives: Evacuate the formed and preformed stool
Drugs MOA/Uses
Mosapride 5HT 4 stimulation increases contraction of intestine
Prucalopride Chronic constipation
Osmotic Laxatives Draw water into intestine

Nondigestible sugars Costly – Used as second line drugs in constipation and Lactulose also used in hepatic encephalopathy
Lactulose Flatulence and abdominal pain as side-effect
Mannitol
Sorbitol

Saline Laxatives Powerful laxatives – used in bowel cleaning

Mg citrate/sulphate/ Contraindicated in renal failure – Mg toxicity
hydroxide

Na phosphate Contraindicated in CHF/HTN/Edema – Causes water retention

Polyethylene glycol DOC for Irritable bowel syndrome associated with constipation
Stool softening agents Surfactants: Decrease surface tension of stool
Docusate Na and Ca Take with full glass of water
Antidiarrheal agents
Drugs MOA/Uses

Alosetron 5HT3 antagonist

IBS associated with diarrhoea in female

Opioids
Loperamide DOC Nonsecretory diarrhea (IBS associated diarrhea)

Diphenoxylate Risk of abuse, so formulated with atropine

Difenoxin
Octreotide DOC Secretory diarrhoea

Bile acid binding Biliary diarrhoea

resins
Colesevelam
Colestipol
Cholestyramine