PHARMACOLOGY

& Med Chemistry

 SCIENTISTS’ CONTRIBUTION

1. Father of Medicine: Hippocrates

2. Father of Pharmacy: Prof. William Procter
3. Father of Pharmacy (India): Prof. Mahadeva Lal Schroff
4. Father of Modern Pharmacology: Oswald Schmiedeberg
5. First Pharmacist: Louis Heberg
6. First Physician: Galen

DEFINITIONS

Pharmacology (Greek: Pharmakon – drug; logos – discourse in).

It is the science of drugs.

Pharmacodynamics (Greek: dynamis – power)

What the drug does to the body.

Pharmacokinetics (Greek: Kinesis – movement)

What the body does to the drug.

Drug (French: Drogue – a dry herb)

It is the single active chemical entity present in a medicine that is used for diagnosis,
prevention, treatment / cure of a disease.

Chemotherapy

It is the treatment of systemic infection / malignancy with specific drugs that have selective
toxicity for the infecting organism / malignant cell with no / minimal effects on the host cells.

Pharmacy

It is the art and science of compounding and dispensing drugs, or preparing suitable dosage
forms for administration of drugs to man or animals.

Toxicology

It is the study of poisonous effect of drugs and other chemicals with emphasis on detection,
prevention and treatment of poisonings.

Orphan drugs

Drugs used to treat a rare disease are called as orphan drugs. Where there are less than 2 lakh
cases per year, or where sales of the drugs do not ensure adequate returns, the drugs are
classified as Orphan drugs.
List of orphan drugs: (acronym : “SAD SO FAR”)

 Somatotropin
 Ancrod
 Digoxin
 Succimer / Sodium nitrite
 LiOthyronine
 Fomepizole
 Amphotericin B
 Rifabutin

PHARMACOKINETICS

Pharmacokinetics is the quantitative study of drug movement in, through and out of the body.

Biological membrane

This is a bilayer (about 100 Å thick) of phospholipid and cholesterol molecules, the polar
groups (glyceryl phosphate attached to ethanolamine / choline or hydroxyl group of
cholesterol) oriented at the two surfaces and the non-polar hydrocarbon chains.

Passive diffusion

 Majority of drugs cross biological membrane by passive diffusion.

 A more lipid-soluble drug attains higher concentration in the membrane and diffuses
quickly.

Influence of pH: Most drugs are weak electrolytes, i.e., their ionization is pH-dependent.

For weakly acidic drugs,

pH = pKa + log [ionised drug]

[unionised drug]

For weakly basic drugs,

pH = pKa + log [unionised drug]

[ionised drug]

Under sink conditions, pH = pKa

Drugs Form salts with Ionise more at Examples

Weakly acidic Cations Alkaline pH Sod. phenobarbitone,
sod. sulfadiazine, pot.
Penicillin-V
Weakly basic Anions Acidic pH Atropine sulphate,
ephedrine HCl,
chloroquine phosphate

Implications of this consideration are:

(a) Acidic drugs, e.g. aspirin (pKa 3.5) are largely unionised at acid gastric pH and are
absorbed from stomach, while bases, e.g. atropine (pKa 10) are largely ionised and are
absorbed from intestines.
(b) The unionised form of acidic drugs, which crosses the surface membrane of gastric
mucosal cells, reverts to the ionised form within the cell and slowly passes to the
extracellular fluid. This is called Ion Trapping.
(c) Basic drugs attain higher concentration intracellularly.
(d) Acidic drugs are ionised more in alkaline urine.

Filtration

(i) Hydrostatic pressure

(ii) Osmotic pressure gradient

Majority of cells have very small pore size (4 Å), and drugs with MW > 100 or 200 are not
able to penetrate them. However, capillary walls (except those in brain) have large pores (40
Å) and most drugs can penetrate them.

Specialised transport

This can be carrier-mediated or by pinocytosis.

Carrier transport:

Substances permitting transit of ions across membranes are called ionophores.

(a) Active transport: movement occurs against the concentration gradient, needs energy and
is inhibited by metabolic poisons, e.g. levodopa and methyldopa are actively absorbed
from gut by aromatic amino acid transport process.
(b) Faciliated diffusion: This translocates non-diffusable substrates, along their
concentration gradient, and does not need energy.

Pinocytosis:

It is the process of transport across the cell by formation of vesicles, mainly applicable to
uptake of proteins.

ABSORPTION
Absorption is the movement of drug from its site of administration into the circulation.

Factors affecting absorption:

Aqueous solubility - For poorly water-soluble drugs (aspirin, griseofulvin), rate of

dissolution governs rate of absorption.

Concentration - Drug from a concentrated solution is absorbed faster than from a dilute
solution.

Area of absorbing surface - Larger the area, faster is the absorption.

Vascularity of the absorbing surface - Increased blood flow hastens drug absorption.

Route of administration:

(i) Oral:
 Non-ionized, lipid-soluble drugs, e.g. ethanol, are readily absorbed from the stomach as
well as intestine.
 Acidic drugs, e.g. salicylates, barbiturates etc., are unionized in the acidic gastric juice
and are absorbed from stomach, while basic drugs, e.g. morphine, quinine etc., are largely
ionized and are absorbed only on reaching the duodenum.
 For acidic drugs, absorption from stomach is slower, because the mucosa is thick and the
surface area is small. Thus, faster gastric emptying accelerates drug absorption.
 Presence of food dilutes the drug and retards absorption.
 Highly ionised drugs, e.g. streptomycin, neostigmine, are poorly absorbed when given
orally.
 Certain drugs are degraded in the GIT, e.g. penicillin G by acid and insulin by peptidases,
and are ineffective orally.
 Luminal side effects can occur due to formation of insoluble complexes, e.g. tetracyclines
with iron preparations and antacids, phenytoin with sucralfate.
 Gut wall effects can occur by altering motility, e.g. anticholinergics, TCAs, opioids,
metoclopramide; or causing mucosal damage, e.g. neomycin, methotrexate, vinblastine.

Subcutaneous and Intramuscular

 In this, the drug is deposited directly in the vicinity of the capillaries.

 Very large soluble drugs are absorbed through lymphatics. Thus, many drugs not
absorbed orally, are absorbed parenterally.
 Application of heat and muscular exercise accelerate drug absorption, by increasing blood
flow, while vasoconstrictors, e.g. adrenaline injected with the drug, retard absorption.
 Incorporation of hyaluronidase facilitates drug absorption from SC injection by
promoting spread.
 Many depot preparations, e.g. benzathine penicillin, protamine zinc insulin, depot
progestins etc., can be given by this route.

Topical sites (skin, cornea, mucous membranes)

 Systemic absorption, after topical application, depends primarily on lipid solubility of
drugs.
 Corticosteroids applied over extensive areas produce systemic effects and pituitary
adrenal suppression.
 Tannic acid applied over burnt skin has produced hepatic necrosis.
 Cornea is permeable to lipid-soluble, unionized physostigmine, but not to highly ionized
neostigmine.
 Mucous membranes of mouth, rectum and vagina absorb lipophilic drugs, e.g. estrogen
cream applied vaginally.

BIOAVAILABILITY

 It refers to the rate and extent of absorption of a drug from a dosage form as determined
by its Concentration-Time curve in blood, or by its excretion in urine.
 It is a measure of the fraction (F) of administered dose of a drug that reaches the systemic
circulation in the unchanged form.
 Differences in bioavailability may arise due to variations in disintegration and dissolution
rates.
 Reduction in particle size increases the rate of absorption of aspirin (microfine tablets).
 The amount of griseofulvin and spironolactone in the tablet can be reduced to half, if the
drug particle is microfined.

DRUGS MAINLY GIVEN BY RECTAL ROUTE: (acronym : “PEDIA”)

 Paraldehyde
 Ergotamine
 Diazepam
 Indomethacin
 Aminophylline

DISTRIBUTION

Factors affecting distribution:

 Lipid: water partition coefficient of the drug

 pKa value of the drug
 Degree of plasma protein binding
 Affinity for different tissues
 Fat: lean body mass ratio
 Diseases like CHF, uremia, cirrhosis

Apparent Volume of Distribution (V) = Dose administered IV

Plasma concentration

DRUGS BOUND TO PLASMA PROTEIN

 To Albumin To α1-acid glycoprotein
Barbiturates β-blockers
NSAIDs Bupivacaine
Valproic acid Lignocaine
Phenytoin Disopyramide
Penicillins Imipramine
Sulfonamides Methadone
Tetracyclines Prazosin
Tolbutamide Quinidine
Warfarin Verapamil

Clinically important displacement interactions:

 Phenylbutazone and salicylates displace tolbutamide.

 Indomethacin and phenylbutazone displace warfarin.
 Sulfonamides and vitamin K displace bilirubin (kernicterus in neonates).
 Salicylates displace methotrexate.

BIOTRANSFORMATION (METABOLISM)

 Most hydrophilic drugs, e.g. streptomycin, neostigmine, decamethonium etc., are not
biotransformed and are excreted unchanged.
 Primary site for metabolism is liver. Others are kidney, intestine, lungs and plasma.
 Convert lipid-soluble drug into non lipid-soluble metabolites.

Biotransformation may lead to the following:

(i) Inactivation of active drug

(ii) Active metabolite from an active drug
(iii) Activation of inactive drug

Active drug Active metabolite

Chloral hydrate Trichloroethanol
Phenacetin Paracetamol
Phenylbutazone Oxyphenbutazone
Primidone Phenobarbitone,
Phenylethylmalonamide
Trimethadione Dimethadione
Diazepam Desmethyldiazepam,
Oxazepam
Digitoxin Digoxin
Imipramine Desipramine
Amitriptyline Nortriptyline
Codeine Morphine
Spironolactone Canrenone
Losartan E 3174
Types of Biotransformation reactions:

(a) Non-synthetic/Phase I reactions – metabolite may be active or inactive

(b) Synthetic/Conjugation/Phase II reactions – metabolite is mostly inactive.

Prodrug Active form

Levodopa Dopamine
Enalapril Enalaprilat
α-Methyldopa α-methylnorepinephrine
Dipivefrine Adrenaline
Sulindac Sulfide metabolite
Hydrazide MAO inhibitors Hydrazine derivatives
Proguanil Proguanil triazine
Prednisone Prednisolone
Bacampicillin Ampicillin
Sulfasalazine 5-Aminosalicylic acid
Cyclophosphamide Aldophosphamide,
Phosphoramide mustard,
Acrolein
Fluorouracil Fluorouridine monophosphate
Mercaptopurine Methylmercaptopurine ribonucleotide

Reactions:

Nonsynthetic reactions Synthetic reactions

Oxidation Glucuronide conjugation
Reduction Acetylation
Hydrolysis Methylation
Cyclization Sulfate conjugation
Decyclization Glycine conjugation
Glutathione conjugation
Ribonucleoside/nucleotide synthesis
Glucuronide conjugation: Adds an ionic hydrophilic moiety; facilitating its urinary
elimination.

MAJOR METABOLIC ENZYME INDUCERS AND INHIBITORS:

Enzyme Inducers Enzyme suppressors

Phenytoin Hydrocortisone
Phenobarbitone Erythromycin
Phenylbutazone Ketoconazole
Carbamazepine Aspirin
Chloral hydrate MAO inhibitors
Griseofulvin Testosterone
Alcohol Corticosteroids
Rifampicin Grapefruit juice
Cigarette smoke (3,4-benzopyrene)
EXCRETION:

Excretion is the passage of drugs out of the body, for systemically absorbed drugs. Drugs and
their metabolites are excreted in:

1. Urine (kidney)
2. Faeces (MW > 300 eliminated in bile)
3. Exhaled air
4. Saliva and sweat
5. Milk

Renal excretion:

Glomerular filtration of a drug depends on plasma protein binding and renal blood flow.

G.F.R. declines progressively after the age of 50. It also declines due to renal failure.

Substances used to measure G.F.R:

 Inulin
 Cr-EDTA

Tubular reabsorption

 Weak bases ionize more and are less reabsorbed in acidic urine.
 Weak acids ionize more and are less reabsorbed in alkaline urine.

Urine is alkalinized in barbiturate and salicylate poisoning, while it is acidified in morphine

and amphetamine poisoning.

Tubular secretion:

If renal clearance of a drug is greater than 120 ml/min (g.f.r.), additional tubular secretion can
be assumed.

(i) Salicylates block uricosuric action of probenecid and sulfinpyrazone and decrease
tubular secretion of methotrexate.
(ii) Probenecid decreases the concentration of nitrofurantoin in urine, increases the
duration of action of penicillin and impairs the secretion of methotrexate.
(iii) Sulfinpyrazone inhibits excretion of tolbutamide.
(iv) Quinidine decreases renal and biliary clearance of digoxin by inhibiting efflux carrier
P-glycoprotein (P-Gp)
Note: P-Gp (P – Permeability factor)

Hit and Run Drugs:

These are drugs that produce their action and are fully excreted; but their action remains for a
long time.
(acronym : “GONE ROME”)

 GONE – Guanethidine
 R – Reserpine
 O – Omeprazole
 M – MAO inhibitors
 E – GuanEthidine

Reserpine action:

 Reserpine depletes the Reserves of catecholamines.

Loading dose:

This is a single dose, or few quickly repeated doses, given in the beginning of the therapy, to
attain target drug concentrations rapidly.

Loading dose = target Cp  V

Maintenance dose

This dose is one that is to be repeated at specified intervals after the attainment of target Cpss,
so as to maintain the same by balancing elimination.

Drugs that increase Potassium (K+) levels:

(acronym : “PACKS”)

 Propranolol
 Aspirin
 Captopril
 KCl (Potassium chloride)
 Spironolactone
 PHARMACODYNAMICS

Greek: dynamis – power

“What the drug does to the body”.

Mechanism of drug action:

I. Physical Action
(acronym : “ROAR”)
 Radioactivity
 Osmotic (mannitol)
 Adsorptive (charcoal)
 Radioopacity

Physical action Drug

Mass of the drug
Adsorptive property
Osmotic activity
Radioactivity
Radioopacity
Bulk laxatives (bran),
Protectives (dimethicone)
Charcoal, kaolin
Magnesium sulphate, mannitol
131
I and other radioisotopes
Contrast media (barium sulphate, urografin)

II. Chemical Action

Drugs Chemical action

Antacids (AlOH3 and others) Neutralize gastric HCl
Acidifying agents (NH4Cl) React with buffers in plasma
Alkalinizing agents (NaHCO3) Alter pH of urine
Oxidising agents (KMnO4, I2) Germicidal & inactivate ingested alkaloids
Chelating agents (Cal. EDTA), BAL, Sequester toxic metals
penicillamine)

ENZYMES:

Stimulation

Drug Stimulated enzyme

Adrenaline Adenylyl cyclise
Pyridoxine Decarboxylase

Inhibition

A. Nonspecific inhibition
 Many chemicals and drugs are capable of denaturing proteins. They can alter the
tertiary structure of the enzyme and inhibit it.
  Heavy metal salts, strong acids and alkalies, alcohol, formaldehyde and phenol inhibit
enzymes nonspecifically.

B. Specific inhibition
(i) Competitive (equilibrium type)

Such inhibitors increase the Km value, but the Vmax remains unchanged.

Drug Compete with For

Physostigmine, Acetylcholine Cholinesterase
Neostigmine
Sulfonamides PABA Bacterial folate synthase
Allopurinol Hypoxanthine Xanthine oxidase
Carbidopa, Levodopa Dopa decarboxylase
methyldopa
Warfarin Vitamin K Synthesizing clotting factors in
the liver

Non-equlibrium type

 Such inhibitors increase the Km value, but the Vmax is reduced.

 Organophosphates react covalently with the esteretic site of the enzyme cholinesterase.
 Methotrexate has 50,000 times higher affinity for dihydrofolate reductase than the
normal substrate DHFA.

(ii) Non-competitive

In this, Km is unchanged, but Vmax is reduced.

Drug Non-competitive inhibitor

Acetazolamide Carbonic anhydrase
Aspirin, indomethacin Cyclooxygenase
Disulfiram Aldehyde dehydrogenase
Nialamide Monoamine oxidase
Digoxin Na+K+ ATPase
Theophylline Phosphodiesterase
Propylthiouracil Peroxidase in thyroid
Omeprazole H+K+ ATPase

DEFINITIONS:

1. Receptor: is defined as a specific binding site with functional correlate(s).

2. Agonist: It activates a receptor to produce an effect similar to that of the
physiological signal molecule. Have both affinity and maximal intrinsic activity.
3. Inverse agonist: It activates a receptor to produce an effect opposite to that of the
well recognised agonist.
 4. Antagonist: It prevents the action of an agonist on a receptor, or the subsequent
response, but does not have any effect of its own. Has affinity, but no intrinsic
activity.
5. Partial agonist: It activates a receptor to produce submaximal effect, but antagonises
the action of a full agonist. Have affinity and submaximal intrinsic activity.
6. Ligand (Latin: ligare - to bind): It is a molecule which attaches selectively to
particular receptors or sites.
7. Affinity: It is the ability of the drug to combine with the receptor.
8. Intrinsic activity (efficacy): It is the ability of the drug to activate the receptor
consequent to its occupation of the receptor site.
9. Inverse agonists: have affinity, but intrinsic activity with a minus sign.

COMBINED EFFECT OF DRUGS

When two or more drugs are given simultaneously, or in quick succession, they may be either
indifferent to each other, or exhibit synergism or antagonism.

Synergism (Greek: Syn – together; ergon – work)

When the action of one drug is facilitated or increased by the other, they are said to be
synergistic.

(a) Additive:

Effect of drugs A + B = Effect of drug A + Effect of drug B

Examples of drugs Uses

Aspirin + Paracetamol Analgesic / antipyretic
(Benorylate)
Nitrous oxide + Ether General anaesthetic
Ephedrine + Theophylline Bronchodilator
Sulfadiazine + Sulfamerazine + Antibacterial
Sulfamethazine

(b) Supraadditive (potentiation):

Effect of drug A + B > Effect of drug A + effect of drug B

Drugs Mechanism
Acetylcholine + Physostigmine Inhibition of breakdown
Levodopa + Carbidopa/Benserazide Inhibiton of peripheral metabolism
Adrenaline + Cocaine/Desipramine Inhibition of uptake
Sulfonamide + Trimethoprim Sequential blockade
Captopril + Diuretics Tackling two contributing factors
Tyramine + MAO inhibitors Increasing releasable CA store
Antagonism

When one drug decreases, or inhibits the action of another, they are said to be antagonistic.

Effect of drugs A + B < effect of drug A + effect of drug B

(a) Physical

Charcoal adsorbs alkaloids and can prevent their absorption – used in alkaloidal poisonings.

(b) Chemical: The two drugs react chemically and form an inactive product, e.g.
 KmNO4 oxidises alkaloids – used for gastric lavage in poisoning.
 Tannins + alkaloids – insoluble alkaloidal tannate is formed.
 Nitrates form methaemoglobin, which reacts with cyanide radical.

(c) Physiological/functional: The two drugs have pharmacological effects in opposite

direction, e.g.
 Histamine and adrenaline on bronchial muscles and BP.
 Hydrochlorthiazide and triamterene on urinary K+ excretion.
 Glucagon and insulin on blood sugar level.

TOLERANCE:

1. Natural:

The species/individual is inherently less sensitive to the drug, e.g. rabbits are tolerant to
atropine and black races are tolerant to mydriatics.

2. Acquired:

By repeated use of a drug in an individual who was initially responsive, e.g. tolerance
develops to sedative action of chlorpromazine, but not to its antipsychotic action.

3. Cross-tolerance:

It is the development of tolerance to pharmacologically related drugs, e.g. alcoholics are

relatively tolerant to barbiturates and general anaesthetics.

TACHYPHYLAXIS (Greek: Tachy - fast, phylaxis - protection) is rapid development of

tolerance, usually seen with indirectly acting drugs, e.g. ephedrine, tyramine, nicotine etc.

DRUG RESISTANCE:

It refers to tolerance of microorganisms to inhibitory action of antimicrobials, e.g.

Staphylococci to penicillin.
 ADVERSE DRUG EFFECTS

Any undesirable or unintended consequence of drug administration.

Type A (Augmented or Predictable) reactions

 These are based on pharmacological properties of drug.

 e.g. Side effects, toxic effects and consequences of drug withdrawal.
 More common, dose-related and mostly preventable.

Type B (Bizarre or Unpredictable) reactions

 These are based on peculiarities of the patient.

 e.g. Hypersensitivity and idiosyncrasy
 Non-dose related, more serious and show withdrawal symptoms of the drug.

Universal antidote:

Burned toast + strong tea + milk of magnesia (2:1:1)

Intolerance:

Apperance of characteristic toxic effects of a drug in an individual at therapeutic doses.

Single dose of Induced diseases

Triflupromazine Muscular dystonias
Carbamazepine Ataxia
Chloroquine Vomiting, abdominal pain

Teratogenicity, Mutagenicity and Carcinogenicity:

Teratogenicity

 It refers to capacity of a drug to cause foetal abnormalities when administered to a

pregnant woman.

Drugs can affect the foetus in 3 stages-

(i) Fertilization and implantation- conception to 17 days – failure of pregnancy,

which often goes unnoticed.
(ii) Organogenesis- 18-55 days of gestation – most vulnerable period, deformities are
produced.
(iii) Growth and development- 56th day onwards – developmental and functional
abnormalities can occur.
HUMAN TERATOGENIC DRUGS:

Drug Abnormality
Thalidomide Phocomelia (Seal-like limbs), multiple defects
Anticancer drugs (Methotrexate) Multiple defects, foetal death
Androgens Virilisation; limb, esophageal, cardiac defects
Progestins Virilisation of female foetus
Stilboestrol Vaginal carcinoma in teenage female offspring
Tetracyclines Discolouration of teeth, affects bone growth of foetus
Warfarin Nose, eye and hand defects, growth retardation
Phenytoin Hypoplastic phalanges, cleft lip/palate, microcephaly
Phenobarbitone Various malformations
Carbamazepine Neural tube defects
Valproate sod. Spina bifida
Lithium Foetal goiter, cardiac abnormalities
Antithyroid drugs Foetal goiter and hypothyroidism
Indomethacin/Aspirin Premature closure of ductus arteriosus
Isotretinoin Craniofacial, heart and CNS defects
ACE inhibitors (Captopril) Hypoplasia of organs

Mutagenicity:

 It refers to capacity of a drug to cause genetic defects, e.g. Mefloquine (Antimalarial)

 Ames (Bacterial reversed mutation assay) test related to mutagenicity.

Carcinogenicity:

 It refers to capacity of drug to cause cancer, e.g. Aflatoxin-B

Drug-induced diseases:

These are called iatrogenic (physician-induced) diseases, and are functional disturbances
caused by drugs.

Disease Drug
Peptic ulcer Salicylates and corticosteroids
Parkinsonism Phenothiazines and antipsychotics
Hepatitis Isoniazid (Antitubercular drugs)
Disseminated lupus erythematosus Hydralazine
 CHOLINERGIC SYSTEM AND DRUGS

(PARASYMPATHOMIMETIC)

Prototype: Acetylcholine (ACh)

 ACh synthesized via L-serine

Synthesis, storage and destruction of ACh:

ATP + Acetate + CoA Acetyl CoA Choline ACETYLCHOLINE + CoA

 Hemicholinium blocks choline uptake (Rate limiting step in ACh synthesis).

 Active transport of ACh into synaptic is blocked by Vesamicol.
 Botulinums toxin decreases release of ACh.
 Black Widow spider toxin induces release of ACh.

Differences between the two types of cholinesterases

Acetylcholinesterase (True) Butyrylcholinesterase

(Pseudo)
Distribution All cholinergic sites, RBC, gray matter Plasma, liver, intestine, white
matter
Inhibition More sensitive to physostigmine More sensitive to
organophosphates
Function Termination of ACh action Hydrolysis of ingested esters

Muscarinic receptor:

M1 (↑) M2 (↓) M3 (↑)

Location CNS, gastric glands CVS Visceral smooth mucles
Nature G-Protein coupled G-Protein coupled G-Protein coupled
Mechanism IP3/DAG ↑Ca++ ↓cAMP IP3/DAG ↑Ca++
Agonist Oxotremorine Methacholine Bethanechol
Antagonist Pirenzepine, Methoctramine, Hexahydrosiladifenidol,
Telenzepine Tripitramine Darifenacin
(↑- excitatory; ↓ - inhibitory)

Muscarinic receptors:

Action Receptors
Enhancing locomotion M4
Inhibitory action M2 and M4
Excitatory action M1 , M3 , M5
Therapeutic Uses of Bethanechol:

(acronym : “BBB”)

 Bethanechol stimulates the Bladder and Bowel

Nicotinic receptor:

NM NN
Location Neuromuscular junction Autonomic ganglia, Adrenal medulla
Nature Ligand gated ion channel Ligand gated ion channel
Mechanism Opening of Na+, K+ channels Opening of Na+, K+, Ca2+ channels
Agonists PTMA, Nicotine DMPP, Nicotine
Antagonists Tubocurarine, α-Bungarotoxin Hexamethonium, Trimetaphan
Ganglionic nicotinic receptor agonists: “Cysteine”

CHOLINERGIC AGONISTS
Choline esters (ABCM) Alkaloids (MAP)
Acetylcholine Muscarine
Bathanechol Arecoline
Carbachol Pilocarpine
Methacholine

Adverse reactions of cholinergic agonists:

(acronym : “DUMBELS”)

 Diarrhoea and decreased blood pressure

 Urination
 Miosis
 Bronchoconstriction
 Excitation of skeletal muscle
 Lacrimation
 Salivation and sweating

ANTICHOLINESTERASES

Agents that inhibit cholinesterase and protect ACh from hydrolysis are called
Anticholinesterases.

Reversible
Carbamates Acridine
Physostigmine (Eserine) Tacrine
Neostigmine
Pyridostigmine
Edrophonium
Rivastigmine, Donepezil^
Galantamine^
Irreversible
Organophosphates Carbamates
Sarin$ Carbaryl*
Soman$ Propoxur* (BAYGON)
Tabun$
Diazinon* ^ - Alzheimers disease
Parathion* $ - Nerve gases
Malathion* *- Insecticides
Echothiophate
Dyflos (DFP)
Cholinesterase reactivator: Pralidoxime
“Sarin and Soman (Two girls) Tya (Tabun) Doghi (Diazinon) Pyara hotya (Parathion)
Melya (Malathion) Itka (Echothiopate) Dukh zala (Dyflos)”

FEATURES OF IMPORTANT DRUGS:

(acronym : “LMNO”)

Drug Features
Physostigmine Lipid soluble
Miotic in glaucoma
Natural
Orally absorbed
Edrophonium Short-acting; diagnostic agent for
myasthenia gravis
Neostigmine Water-soluble; drug of choice in
myasthenia gravis
Echothiophate Water-soluble
 ANTICHOLINERGIC DRUGS

(PARASYMPATHOLYTICS)

Prototype: Atropine

“A goes with B”: Atropine used clinically to treat Bradycardia.

Classification:

1. Natural Alkaloids: Atropine (± Hyoscyamine), Hyoscine (l-scopolamine).

(acronym: NA HA)
2. Semisynthetic derivatives: Homatropine (Tropine ester of mandelic acid), Hyoscine
butyl bromide, Ipratropium / Tiotropium bromide (used in COPD).
3. Synthetic compounds:
(a) Mydriatics: Tropicamide, Cyclopentolate
Mydriatics related to “EYE”. Eye is the sensitive organ of our body. So Take
Care (TC) {T-Tropicamide ; C-Cyclopentolate}
(b) Antisecretory-antispasmodics:
(i) Quarternary compounds: Propantheline, Oxyphenonium, Clidinium,
Pipenzolate methylbromide, Isopropamide, Glycopyrrolate.
(ii) Tertiary amines: Dicyclomine, Valethamate, Pirenzepine.
(c) Vasicoselective: Oxybutynin, Flavoxate, Tolterodine.
(d) Anti-Parkinsonian: Trihexyphenidyl (Benzhexol), Procyclidine, Biperiden.

Pharmacological Actions:

Organs Actions
CNS Tachycardia
Eye Mydriasis
Visceral smooth muscles Relaxed (Due to M3 blockade)
Glands ↓ Sweat, Salivary, Lacrimal secretion
Body temperature Rise (Atropine fever)

Comparative features of Atropine and Hyoscine:

Atropine Hyoscine
Source Atropa belladonna, Datura Hyoscyamus niger
stramonium
Alkaloidal ester of tropic Tropine (base) Scopine (base)
acid with
CNS effect Excitatory Depressant
Anticholinergic property More potent on heart, bronchial More potent on eye and
muscles and intestines secretory glands
Duration of action Longer Shorter
Anti-motion sickness ++ +++
FEATURES OF SOME IMPORTANT DRUGS:

Drugs Features
Hyoscine Lie Detector
Varenicline NN receptor partial agonist; used in Smoking cessation
Rimonabant Selective CB1 antagonist
Antismoking + Antiobesity
Drotaverine Non-anticholinergic, antispasmodic drug

NORADRENERGIC DRUGS

(SYMPATHOMIMETIC DRUGS)

Phenylalanine Tyrosine DOPA Dopamine Noradrenaline

Adrenaline

 Adrenaline – Prodrug of “Dipivefrine”

Difference between α and β adrenergic receptors

(acronym: “ABCD”)

 Alpha = Constrict
 Beta = Dilate

Α β
Rank order of potency of Adr > NA > Iso Iso > Adr > NA
agonists
Antagonist Phenoxybenzamine Propranolol
Effector pathway IP3/DAG↑, cAMP↓, K channel ↑ cAMP↑, Ca2+ ↑
+

Differences between β1, β2 and β3 receptors

β1 β2 β3
“You have 1 heart and 2 lungs”. β1 are therefore primarily on heart and β2 primarily on
lungs.
Location Heart, Bronchi, blood Adipose tissue
JG cells in vessels, uterus, liver,
kidney GIT, urinary tract,
eye
Selective agonist Dobutamine, Salbutamol, BRL 37344
Xamoterol terbutaline
Selective antagonist Metoprolol, Butaxolol CGP 20712A (also
Atenolol β1), ICI 118551 (also
β2 )
Potency of NA as agonist Moderate Weak Strong
Differences between α1 and α2 receptors

α1 α2
Location Postjunctional on effector organs Prejunctional on nerve
ending (α2A), also
postjunctional in brain,
pancreatic β-cells and
extrajunctional in certain
blood vessels, platelets
Function Smooth muscle Contraction Inhibition of transmitter
Gland Secretion release, Platelet aggregation,
Gut Relaxation Decreased insulin release,
Liver Glycogenolysis etc.
Heart Arrythmia
Selective agonist Phenylephrine, Methoxamine Clonidine
Selective antagonist Prazosin Yohimbine, Rauwolscine
Effector pathway IP3/DAG ↑, Phospholipase A2 ↑ - PG cAMP ↓, K+ channel, Ca2+
release channel ↓ or ↑, IP3/DAG ↑

Adrenergic Drugs:

1. Directly Acting – Adrenaline, Noradrenaline, Isoprenaline, Phenylephrine,

Methoxamine, Xylometazoline, Salbutamol etc.
2. Indirectly Acting – Tyramine and Amphetamine.
3. Mixed Acting – Ephedrine, Dopamine, Mephentermine

FEATURES OF SOME IMPORTANT DRUGS:

Drugs Features
Dopamine / Dobutamine Used in Cardiogenic / Septic shock
Ephedrine Obtained by Fermentation
Noradrenaline Peripheral neurotransmitter
Amphetamines Used in dope test for athletes

ANTIADRENERGIC DRUGS

(ADRENERGIC RECEPTOR ANTAGONISTS)

These are drugs which antagonize the receptor action of adrenaline and related drugs.

α-Adrenergic blocking drugs:

1. Non-equlibrium type (Non-competitive):

(i) β-Haloalkylamines: Phenoxybenzamine
 2. Equilibrium type (Competitive):
A. Non-selective
(i) Ergot alkaloids: Ergotamine, Ergotoxine
(ii) Hydrogenated ergot alkaloids: Dihydroergotamine (DHE),
Dihydroergotoxine
(iii) Imidazolines: Tolazoline, Phentolamine
(iv) Miscellaneous: Chlorpromazine
B. α1-selective (First dose effect): Prazosin, Terazosin, Doxazosin, Tamsulosin
C. α2-selective: Yohimbine, Rauwolscine

General effects of α-blockers:

The α-blockers abolish the presser action of Adr, which then produces only fall in BP due to
β2-mediated vasodilatation – vasomotor reversal of Dale.

β1-adrenergic blocking drugs

These drugs inhibit adrenergic responses mediated through the β receptors.

First β-blocker – Practolol (Banned due to Occulomucocutaneous syndrome)

Classification:

Non-selective (β1 and β2):

“Tanveer Pinches His Nasal Problem”

 Timolol
 Pindolol
 Hismolol
 Nadolol
 Propranolol

a. Without intrinsic sympathomimetic activity

Propranolol, Sotalol, Timolol
b. With intrinsic sympathomimetic activity
Pindolol
c. With additional α-blocking property
Labetalol, Carvedilol

Cardioselective (β1): Metoprolol, Atenolol, Acebutolol, Bisoprolol, Esmolol, Betaxolol,

Celiprolol, Nebivolol

First generation Second generation Third generation

(older, non-selective) (β1-selective) (α-blocker + β-blocker +
vasodilator)
Propranolol (membrane “A-BEAM” Labetolol
stabilizing) Acebutolol (membrane (S,R) – α-blocker
 stabilizing) (R,R) – β-blocker
Timolol 2:Atenolol – lipid insoluble Carvedilol
Betaxolol
Sotalol – lipid-insoluble 2: (Acebutolol – membrane CeliProlol
stabilizing)
Esmolol
Pindolol 1: Esmolol Nebivolol
Atenolol (lipid insoluble)
1: Bisoprolol
Metoprolol

β1-selective vs. β1-β2 non-selective

 A through N: β1-selective: Acebutalol, Atenolol, Esmolol, Metoprolol

 through Z: β1, β2-non-selective: Pindolol, Propranolol, Timolol

β-blockers:

β-blockers with
Shortest half life Esmolol
Longest half life Nadolol
Highest bioavailability Pindolol
Lowest bioavailability Alprenolol
β1 + β2 + α1 blocker Carvedilol
β1 + β2 + α2 blocker Celiprolol
Release nitric oxide Nebivolol, Celiprolol
(NO)

Propranolol: contraindications for administering the drug Propranolol are given below

(acronym: “ABCDE”)

 Asthma
 Block (heart)
 Cardiac failure
 DM (hypoglycaemic shock)
 Extremities (occlusive arterial disease)
 HISTAMINE AND ANTIHISTAMINICS

HISTAMINE

Histamine – ‘tissue amine’ (Gr: histos - tissue)

Synthesis:

 Histamine is β-imidazolylethylamine.
 Synthesized from the amino acid histidine.

Pharmacological Actions:

Injected intradermally, it elicits triple response characterised by,

 Red spot: due to intense capillary dilatation.

 Wheal: due to exudation of fluid from capillaries and venules.
 Flush/Flare: Redness in the surrounding area due to arteriolar dilatation mediated by
axon reflex.

Distinctive features of histaminergic receptors:

H1 H2 H3
Agonists 2-Methylhistamine 4-Methylhistamine α-Methylhistamine
Betahistine Dimaprit Imetit
Impromidine
Antagonists Mepyramine Cimetidine Thioperamide
Chlorpheniramine Ranitidine Impromidine
Clobenpropit
Receptor type G-protein coupled G-protein coupled G-protein coupled
Effector pathway IP3/DAG cAMP increase cAMP decrease

Distinctive features of antihistaminics:

Antihistaminics Activity
Betahistine Anti-vertigo in patients of Meniere’s disease
Cinnarizine H1-antihistaminic + anticholinergic + anti-5-HT + sedative
+ vasodilator + antivertigo
Fexofenadine Active metabolite of terfenadine (banned due to Torsades
de pointes)
Astemizole Banned due to Torsades de pointes
Loratadine Long-acting
Cetrizine Active metabolite of hydroxyzine
Levocetrizine R(-) enantiomer of cetrizine
Azelastine Dual acting antihistaminic (Bronchodilator)
Ebastine Converted to active metabolite carbastine
Rupatadine PAF antagonist

5-HYDROXYTRYPTAMINE (5-HT, SEROTONIN) & ITS ANTAGONISTS

 5-HT – Triphasic Response

Drugs Affecting 5-HT System

5-HT system Drugs

5-HT precursor Tryptophan hydroxylase
Synthesis inhibitor p-chlorophenylalanine
Uptake inhibitor Tricyclic antidepressants (TCAs)
Storage inhibitor Reserpine
Degradation inhibitor Tranylcypromine, Chlorgyline
Neuronal degeneration 5,6-dihydroxytryptamine

5-HT Agonists and Antagonists

Receptors Agonists Antagonists

Nonselective D-Lysergic acid diethyl -
amide (LSD)
5-HT1A Buspirone (partial) -
5-HT1B/1D Sumatriptan (partial) -
5-HT2 - Ketanserin, Cyproheptadine,
Methylsergide
5-HT 2A/2C Clozapine
5-HT3 2-Methyl 5-HT (selective) Ondansetron, Granisetron,
Tropisetron
5-HT4 Cisapride, Renzapride -
(selective)
5-HT6-7 Clozapine -

Drugs as Antihistaminics:

Antihistaminics Uses
Cyproheptadine Carcinoid and postgastrectomy dumping syndromes
Methylsergide Carcinoid and postgastrectomy dumping syndromes
Ketanserin Antihypertensive, Raynaud’s disease
 DRUG THERAPY OF MIGRAINE

Drug therapy of migraine

Severity Drug therapy
Mild Simple analgesics/NSAIDs (± antiemetic)
Moderate NSAIDs/ergot alkaloids/sumatriptan
Severe Ergot alkaloids/sumatriptan/rizatriptan + prophylaxis:
 Propranolol/β-blockers
 Amitriptyline/TCAs
 Flunarizine/Ca2+ channel blockers
 Valproate/topiramate
 Methylsergide/Cyproheptadine
Longest Acting Triptan – Frovatriptan

PROSTAGLANDINS, LEUKOTRIENES (EICOSANOIDS) AND PLATELET

ACTIVATING FACTOR

PROSTAGLANDIN AND LEUKOTRIENES

Prostaglandins (PGs) and Leukotrienes (LTs) are derivatives of 20 carbon atom

polyunsaturated essential fatty acids.

CHEMISTRY

 PGs are derivatives of prostanoic acid.

 The fatty acid released from membrane lipids is 5,8,11,14-eicosatetraenoic acid
(arachidonic acid).

PROSTAGLANDIN ANALOGUES:

Prostaglandin Drugs
PGE1 Gemeprost, Misoprostol,
Alprostadil
PGE2 Dinoprostone
PGF2 Carboprost, Dinoprost
PGI2 Alpha-prostacycline

PLATELET ACTIVATING FACTOR (PAF):

PAF Drugs
Agonist Edelfosine
Antagonist Ginkgo biloba (Ginkgolide B)
 NONSTEROIDAL ANTIINFLAMMATORY DRUGS AND ANTIPYRETIC-
ANALGESICS

Classification:

A. Non-selective COX inhibitors (traditional NSAIDs)

1. Salicylates: Benorylate (Aspirin + Paracetamol), Aspirin, Diflunisal,
Salicylamide (acronym: “BADS”)
2. Propionic acid derivatives: Ketoprofen, Naproxen, Ibuprofen, Flurbiprofen,
FEnoprofen (acronym: “KNIFE”)
3. Anthranilic acid derivative: Mephenamic acid
4. Aryl-acetic acid derivatives: Diclofenac, Aceclofenac
5. Oxicam derivatives: Piroxicam, Meloxicam, Tenoxicam (acronym: “PMT”)
6. Pyrrolo-pyrrole derivative: Ketorolac
7. Indole derivative: Indomethacin, Sulindac
8. Pyrazolone derivatives: Phenylbutazone, Oxyphenbutazone
B. Preferential COX-2 inhibitors
Nimesulide, Meloxicam, Nabumetone, Etodolac
C. Selective COX-2 inhibitors
Celecoxib, Etoricoxib, Parecoxib
D. Analgesic-antipyretics with poor anti-inflammatory action
1. Paraaminophenol derivative: Paracetamol (Acetaminophen)
2. Pyrazolone derivatives: Metamizole (Dipyrone), Propyphenazone
3. Benzoxazocine derivative: Nefopam

Aspirin (prototype):

 Aspirin is acetylsalicylic acid.

 Chemically salol (phenyl salicylate)

Aspirin: side effects (acronym: “ASPIRIN”)

 Asthma
 Salicylism
 Peptic ulcer / Phosphorylation-oxidation uncoupling / PPH / Platelet disaggregation /
Premature closure of PDA
 Intestinal blood loss
 Reye’s syndrome
 Idiosyncrasy
  Noise (tinnitus)

Pharmacokinetics: Glycine conjugation

 Propionic acid derivatives:

Derivatives Features
Ibuprofen Used in dental surgery pain
Naproxen (Naphtalene ring) Inhibits leucocyte migration
Ketoprofen Inhibit LOX
Flurbiprofen Ocular anti-inflammatory

 Aceclofenac:
- Enhance glycosaminoglycan synthesis.
- Chondroprotective property.

 Piroxicam: Longest acting NSAID.

 Ketorolac: Only NSAID given by IV route.

 Indomethacin:

- Frontal headache (common side effect)

- Use: Barterr’s Syndrome

 Sulindac (Prodrug):

- NSAID having strong oxygen radical scavenging effect

- Chemistry: Sulfur + Indane
- Active metabolite: Reduced sulphide form

 Metamizol (Dipyrone): derivative of amidopyrine

 Meloxicam: COX-2/COX-1 selectivity

 Nabumetone:

- It is a prodrug, and generates an active metabolite (6-MNA).

- All NSAIDs are acidic except Nabumetone.

 Etoricoxib:
Et (Eiffel tower) tallest building, so highest COX-2 selective
- Highest COX-2 selectivity.
 Parecoxib: Prodrug of valdecoxib.

 Paracetamol (acetaminophen):
- Deethylated active metabolite of Phenacetin.
- Inhibits COX-3 (isoenzyme located in dog brain).
- Toxicity: Paracetamol undergoes glutathione conjugation to yield N-acetyl-p-
benzoquinone imine (NAPQI), a highly reactive arylating metabolite of
paracetamol.
- Treatment: N-acetylcysteine, Methionine
- Use: Commonly used as over-the-counter analgesic.

 Nefopam: Anticholinergic + Sympathomimetic

ANTIRHEUMATOID DRUGS

Classification:

A. Disease modifying antirheumatic drugs (DMARDs)

(acronym: “CHAMP”)
1. Cyclosporine
2. Hydroxychloroquine or Chloroquine
3. Auranofin and other gold compounds
4. Methotrexate
5. Penicillamine
B. Biologic response modifiers (BRMs)
1. TNF α inhibitors: Etanercept, Infliximab, Adalimumab
2. IL-1 antagonist: Anakinra
C. Adjuvant drugs: Corticosteroids: Prednisolone and others

 Methotrexate (MTX)
- Dihydrofolate reductase inhibitor
- Immunosuppressant + Antiinflammatory + Anticancer
- DMARD of first choice

 Azathioprine
- Purine antimetabolite
- Converted to 6-mercaptopurine by the enzyme thiopurine methyl transferase

 Sulfasalazine
- Sulfapyridine + 5-aminosalicylic acid (5-ASA)

 Chloroquine and hydroxychloroquine

 - Antimalarial
- ADR: Retinal damage / Corneal opacity

 Leflunomide
- Immunomodulator prodrug
- Mechanism: Inhibits dihydrorotate dehydrogenase
- Teratogenic drug

DRUGS USED IN GOUT

For acute gout

NSAIDs
Colchicine
Corticosteroids
For chronic gout / hyperuricaemia
Uricosurics Synthesis inhibitor
Probenecid Allopurinol (Purine analogue)
Sulfinpyrazone Febuxostat (Non-purine analogue)

 Allopurinol (Pyrazine + Pyrimidine):

- Competitive inhibitor of xanthine oxidase

- Allopurinol Alloxanthine (oxypurine)

DRUGS FOR COUGH AND BRONCHIAL ASTHMA

DRUGS FOR COUGH

Classification:

1. Pharyngeal demulcents: Lozenges, Cough drops, linctuses containing syrup,

glycerine, liquorice.
2. Expectorants (Mucokinetics)
(a) Bronchial secretion enhancers: Sodium or Potassium citrate, Potassium iodide,
Guaiphenesin (Glyceryl guaiacolate), balsam of Tolu, Vasaka, Ammonium chloride.
(b) Mucolytics: Ambroxol, Acetylcysteine, Bromhexine, Carbocisteine (acronym:
“ABC”)
3. Antitussives: (Cough centre suppressants)
(a) Opioids: Codeine, Pholcodeine
(b) Nonopioids: Noscapine, Dextromethorphan, Chlophedianol
(c) Antihistaminics: Chlorpheniramine, Diphenhydramine, Promethazine
4. Adjuvant antitussives
 Bronchodilators: Salbutamol, Terbutaline

Drugs for cough Characteristics

Bromhexine Potent mucolytic and mucokinetic
Codeine Standard antitussive (action blocked by
naloxone)
Noscapine (Narcotine) Used in spasmodic cough
Dextromethorphan d-isomer: antitussive
l-isomer: analgesic

DRUGS FOR BRONCHIAL ASTHMA:

 Bronchial asthma is characterised by hyperresponsiveness of tracheobronchial smooth

muscle to a variety of stimuli, resulting in narrowing of air tubes along with increased
secretion and mucus plugging.
 The virus responsible for Severe Acute Respiratory Syndrome (SARS) is Coronavirus.

Symptoms: Dysponea, wheezing, cough etc.

Causes: Infection, irritants, pollution, exercise, exposure to cold air, psychogenic

Types of asthma:

 Extrinsic asthma: Mostly episodic, less prone to status asthmaticus.

 Intrinsic asthma: More perennial, status asthmaticus common.

Etiology:

- Release of mediators like histamine, protease enzymes, TNFα, PGs, LTs, PAF etc.

Chronic obstructive pulmonary disease (COPD): is a progressive disease with emphysema

(alveolar destruction) and bronchiolar fibrosis.

Classification:

1. Bronchodilators
A. β2 Sympathomimetics (agonists):
(acronym: “SMART”)
 Salmeterol
 Metaproterenol
 Albuterol (Salbutamol)
 Ritodrine
 Terbutaline
B. Methylxanthines: Caffeine, Theophylline, Theobromine, Doxophylline
C. Anticholinergics: Ipratropium bromide, Tiotropium bromide
 2. Leukotriene antagonists (anti-LUKotrienes)
MonteLUKast, ZafirLUKast
3. Mast cell stabilizers
Sodium cromoglycate, Ketotifen
4. Corticosteroids
A. Systemic: Hydrocortisone, Prednisolone and others
B. Inhalational: Beclomethasone dipropionate, Budesonide, Fluticasone propionate,
Flunisolide, Ciclesonide.
5. Anti-IgE antibody
Omalizumab

 SYMPATHOMIMETICS
- Fastest acting bronchodilators when inhaled.

- Adrenergic drugs cause bronchodilatation through β2 receptor stimulation

increased cAMP formation in bronchial muscle cell relaxation.

- β2-agonist misused by sportspersons is Clenbuterol.

Drugs for asthma Characteristics

Salbutamol (Albuterol) Highly selective β2-agonist
Bambuterol Biscarbamate ester prodrug of terbutaline
Salmeterol First long-acting selective β2-agonist used in
nocturnal asthma
Formoterol Round-the-clock bronchodilatation

METHYL XANTHINES

 All Xanthophyllines act on adenosine receptor except Enrophylline.

Drugs Chemistry
Caffeine 1,3,7-Trimethylxanthine
Theophylline 1,3-Dimethylxanthine
Theobromine 3,7-Dimethylxanthine

Note: Theophylline produces Tachycardia; caffeine produces bradycardia

 ANTICHOLINERGICS

- Inhaled ipratropium/tiotropium are the bronchodilators of choice in COPD.

- Nebulized ipratropium + Salbutamol Refractory asthma

- CD4 : CD8 ratio in asthma and COPD, respectively, is 4:1 and 1:4

 LEUKOTRIENE ANTAGONISTS (Cystenyl leukotrienes LT-C4/D4)

Montelukast and Zafirlukast

- Effective in aspirin induced asthma

- ADR: Churg-Strauss syndrome (vasculitis with eosinophilia).
- zAfirlukast: Antagonist of LT

Zileuton

- zIlueton: Inhibitor of 5-LO

- Blocks LTC4/D4 as well as LTB4 synthesis.

 MAST CELL STABILIZERS

Sodium cromoglycate (Cromolyn sod.)

- Synthetic chromone derivative, which inhibits degranulation of mast cells.

Ketotifen

- Dual acting antihistaminic (Bronchodilator + Antihistaminic)

 INHALED STEROIDS
- Inhaled steroids should be the step one treatment for all asthmatic patients.
 ANTERIOR PITUITARY HORMONES
Acidophils are either somatotropes GH; or lactotropes Prolactin

Basophils are gonadotropes FSH and LH; thyrotropes TSH; and corticotrope-
lipotropes ACTH

Pathology:

 Increase in GH Gigantism (Childhood); Acromegaly (Adults)

 Decrease in GH Dwarfism (Children)

Recombinant DNA GH (rhGH) used in Turner’s syndrome.

 GH INHIBITORS

Somatostatin

- 14 amino acid peptides inhibit the secretion of GH, TSH and prolactin.

Octreotide

- Octapeptide surrogate of somatostatin.

Pegvisomant

- Polyethylene glycol complexed mutant GH binds to the GH receptor, but does not
trigger signal transduction.

 PROLACTIN INHIBITORS

Bromocriptine

- Synthetic ergot derivative ergocryptine is a potent dopamine agonist.

- Greater action on D2 receptors; partial agonist/antagonist on D1-receptor.

ADRENOCORTICOTROPIC HORMONE (ACTH, CORTICOTROPIN)

Pathology

Increase in ACTH Cushing’s syndrome Rx Ketoconazole

Decrease in ACTH Addison’s disease Rx Hydrocortisone + Fludrocortisone

 THYROID HORMONES AND THYROID INHIBITORS
Normal weight of thyroid gland – 25 gm

THYROID HORMONE
 The thyroid gland secretes 3 hormones – thyroxine (T4), triiodothyronine (T3) and
calcitonin.
 T3 and T4 produced by thyroid follicles and Calcitonin produced by interfollicular ‘C’
cells.

Chemistry

- Both T4 and T3 are iodine-containing derivatives of thyronine, which is a

condensation product of two molecules of the amino acid tyrosine.
- Thyroxine (T4) – 3,5,3,5-tetraiodothyronine
- T3 – 3,5,3-triiodothyronine

THYROID INHIBITORS

These are drugs used to lower the functional capacity of the hyperactive thyroid glands.

Thyroytoxicosis occurs due to excessive secretion of thyroid hormones. The two main causes
are Graves’ disease (autoimmune disorder) and toxic nodular goiter.

Classification:

1. Inhibit hormone synthesis (Antithyroid drugs)

Propylthiouracil, Methimazole, Carbimazole.
2. Inhibit iodide trapping (Ionic inhibitors)
Thiocyanates (-SCN), Perchlorates (-ClO4), Nitrates (-NO3)
3. Inhibit hormone release
Iodine, Iodides of Na and K, Organic iodide
4. Destroy thyroid tissue
Radioactive iodine (131I, 125I, 123I).

Compounds in groups 1 and 2 are called goitrogens.

 PROPYLTHIOURACIL (PTU):

Mechanism It inhibits PTU:

- Peroxidase / Peripheral deiodination

 - Tyrosine iodination Union (coupling)

 IODINE AND IODIDES

Action – ‘Thyroid constipation’

 RADIOACTIVE IODINE

Radioactive iodine Use

127
I Stable isotope of iodine
131
I Commonly used in medicine (emits X-rays & β-particles)
123
I Rarely used diagnostically
The most common indication is hyperthyroidism due to Graves’ disease or toxic nodular
goitre.

INSULIN, ORAL HYPOGLYCAEMIC DRUGS AND GLUCAGON

Diabetes mellitus (DM): It is a metabolic disorder characterized by hyperglycaemia,

glycosuria, hyperliaemia, negative nitrogen balance and sometimes ketonaemia.

Insulin first discovered by Best and Banting and its chemical structure was first discovered by
Sanger.

Types

 Type I Insulin-dependent diabetes mellitus (IDDM), juvenile onset diabetes mellitus.

 Type II Non-insulin dependent diabetes mellitus (NIDDM), maturity onset diabetes
mellitus.

INSULIN

Insulin

(51 amino acids)

A-chain B-chain

(21 AA) (30 AA)

Insulin is synthesized in the β-cells of pancreatic Islets of Langerhans.

Preproinsulin Proinsulin Insulin

(110 AA) (86 AA) (51 AA)

Types of insulin preparations and insulin analogues:

Insulin preparations are (acronym: “INSULIN”):

Insulin soluble / regular / crystalline, NPH / isophane insulin, Semilente insulin, Ultralente
insulin, Lente insulin, Insulin conjugated with protamine and Zn (PZI), Newer insulins, e.g.
single peak, monocomponent (pure) and human insulin.

Rapid acting
Insulin lispro
Insulin aspart
Insulin glulisine
Short acting
Regular (soluble) insulin
Intermediate acting
Insulin zinc suspension or Lente
Neutral Protamine Hagedorn (NPH) or isophane insulin
Long acting
Protamine zinc insulin (PZI)
Insulin glargine

- Lente insulin is a 7:3 mixture of ultralente (crystalline) and semilente (amorphous)

insulin zinc suspension. Ultralente is long-acting and semilente is short-acting.
- Regular soluble insulin is the ONLY insulin given by i.v. route.
- Insulin lispro is the ONLY insulin prepared by recombinant DNA (rDNA)
technology.
- Drawback of insulin: Given by injection.
- ADR of insulin: Hypoglycaemia

ORAL HYPOGLYCAEMIC DRUGS

These drugs lower blood glucose levels and are effective orally.

Classification:

SULFONYLUREAS
First generation (acronym: “TACT”) Second generation
Tolbutamide (shorter-acting) Glibenclamide (Glyburide)
Acetohexamide Glipizide
Chlorpropamide (longest acting) Gliclazide (Antiplatelet action)
TolButamide (Tolerated Best) Glimepiride (Extrapancreatic action)

BIGUANIDES
Phenformin (banned due to lactic acidosis)
Metformin (lactic acidosis less common)
MEGLITINIDE / D-PHENYL ALANINE ANALOGUES
Repaglinide Nateglinide
THIAZOLIDINEDIONES (acronym: “TPR”)
Thiaglitazone (banned)
Pioglitazone
 Rosiglitazone
α-GLUCOSIDASE INHIBITORS
Acarbose (complex oligosaccharide)
Miglitol (more potent in inhibiting sucrase)
DIPEPTDYL PEPTIDASE-4 (DPP-4) INHIBITORS
Sitagliptin
Vildagliptin
NEWER ANTIDIABETICS
Pramlitinide
Exenatide
Mazindol
Ciclazindol
Guar gum

Mechanism of Action:

Antidiabetics
Thiazolidindiones (e.g. Rosiglitazone)
Sulfonyl ureas (e.g. Tolbutamide)
Mechanism
Increases the tissue sensitivity to insulin
(Peroxisome proliferator-activated receptor
ϒ; PPARϒ)
Increases the sensitivity of β-cells to glucose

CORTICOSTEROIDS

The term ‘corticosteroid’ or ‘corticoid’ includes natural gluco and mineralo corticoids.

Biosynthesis

- The corticoids (both gluco and mineralo) are 21 carbon compounds having a
cyclopentanoperhydro-phenanthrene (steroid) nucleus.
- They are synthesized in the adrenal cortical cells from cholesterol.

5-α-pregnane Trans-anti-trans-anti-trans (All 3 rings are in “chair” confirmation)

5-β-pregnane Cis-anti-trans-anti-trans

Actions

Glucorticoid: Effects on carbohydrate, protein and fat metabolism.

Mineralocorticoid: Effects on Na+, K+ and fluid balance.

Classification:

GLUCOCORTICOIDS
Short acting
Hydrocortisone (cortisol)
Intermediate acting
Prednisolone
 Methyl prednisolone
Triamcinolone
Long acting
Dexamethasone
Betamethasone
Deflazacort
MINERALOCORTICOIDS
Desoxycorticosterone acetate (DOCA)
Fludrocortisone
Aldosterone

Metyrapone Inhibits 11,β-hydroxylase in adrenal cortex and prevents synthesis of

hydrocortisone.

ANDROGENS AND DRUGS FOR ERECTILE DYSFUNCTION

Androgens (Male Sex Hormones)

Classification:

1. Anabolic Steroids (Drugs misused by cricketers)

Nandrolone, Oxymetholone, Stanozolol, Methandienone
2. Impeded Androgens
Danazol (Drugs misused by athletes)
3. Antiandrogens
Flutamide and Bicalutamide (nonsteroidal), Cyproterone acetate (steroid)
4. 5-α Reductase Inhibitor (used in benign hypertrophy of prostate)
Finasteride (inhibits type 2 isoenzyme), Dutasteride (inhibits Type 1 & 2)

Drugs Admistered in Erectile Dysfunction

1. Androgens: Testosterone therapy (Parenteral / Transdermal)

2. Phosphodiesterase-5 (PDE-5) inhibitors: Sildenafil, Tadalafil, Vardenafil
3. Papaverine/Phentolamine: induce penile erection (PIPE)
4. Prostaglandin E1: Alprostadil

ESTROGENS, PROGESTINS AND CONTRACEPTIVES

These are substances which can induce estrous in spayed animals.

Classification:

1. Natural estrogens
Estradiol
2. Synthetic estrogens
(i) Steroidal: Ethinylestradiol, Mestranol, Tibolone.
(ii) Nonsteroidal: Diethylstilbesterol (stilbesterol), Hexestrol, Dienestrol.
ANTIESTROGENS

1. Antiestrogens: Clomiphene citrate.

2. Selective estrogen receptor modulators (SERMs): Tamoxifen citrate, Raloxifene,
Ormeloxifene.
3. Selective estrogen receptor down regulators (SERDs): Fulvestrant (pure estrogen
antagonists).
4. Aromatase Inhibitors: Letrozole and Anastrozole (non-steroidal), Exemestane
(steroidal).

Oral Contraceptive Pill (OCP):

Types: Only progestin pill (minipill), Combined pill, Phasic pill and post-coital pill,
Sequential pill.

Mechanism: Ovulation inhibition, Cervical mucus thickening, Prevention of implantation,

Suppression of contraction.

IMPORTANT POINTS TO REMEMBER:

- Levonorgestrel (I-pill) is used under emergency conditions.

- Most commonly used combination: Estrogen + Progesterone

OXYTOCIN AND OTHER DRUGS ACTING ON UTERUS

Uterine Stimulants (Oxytocics, Abortifacients)

These drugs increase uterine motility, especially at term.

Oxytocin Oozes (releases) and PROlactin PROduces milk.

1. Posterior pituitary hormone: Oxytocin (nonapeptide), Desamino oxytocin.

2. Ergot alkaloids: Ergometrine (Ergonovine), Methylergometrine.
3. Prostaglandins: PGE2, PGF2α, 15-methyl PGF2α, Misoprostol.
4. Miscellaneous: Ethacridine, Quinine.

UTERINE RELAXANTS (TOCOLYTICS)

These are drugs that decrease uterine motility. They have been used to delay or postpone
labour, to arrest threatened abortion and in relieving dysmenorrhoea.

Classification:

1. Adrenergic agonists: Ritodrine, Isoxsuprine.

2. Calcium channel blockers: Nifedipine
3. Magnesium sulphate IV
4. Oxytocin antagonist: Atosiban
 5. Miscellaneous drugs: Ethyl alcohol, nitrates, progesterone, general anaesthetics.

DRUGS AFFECTING CALCIUM BALANCE

Influences affecting bone turnover

Increase resorption Decrease resorption
(acronym: “CAPITAL”) (acronym: “MEAT Grows Bone”)
Corticosteroid Mithramycin
Alcohol Estrogen
PGE2 (Prostaglandin) Androgen
IL 1 and 6 (Interleukin) Thiazide
TH (Thyroid hormone) GH
PArathormone Bisphosphonate
Loop diuretic Gallium nitrate
Calcium sensitizer: Pimobendan

Conditions or Diseases causing Hypercalcemia:

(acronym: “CHIMPANZEES”

 Calcium supplementation
 Hyperparathyroidism
 Iatrogenic, caused by thiazide diuretics
 Milk alkali syndrome / Malignancy
 Paget’s disease
 Addison’s disease
 Neoplasm
 Zollinger-ellison syndrome
 Excess vitamin D
 Excess vitamin A
 Sarcoid

Calcitonin

- Calcitonin is the hypocalcaemic hormone produced by parafollicular ‘C’ cells of

thyroid.
- Rise in plasma Ca2+ increases, while fall in plasma Ca2+ decreases calcitonin
release.

Actions (GPCR):

Calcitonin inhibits proximal tubular calcium and phosphate reabsorption by direct action on
kidney.
Uses:

1. Hypercalcaemic states
2. Postmenopausal osteoporosis
3. Paget’s disease

Note: Also administered as nasal formulation

VITAMIN D

Forms of Vitamin D Name

Vitamin D Calciferol
Vitamin D2 Ergocalciferol
Vitamin D3 Cholecalciferol
Active form Calcitriol (vit. D3)
Non-hypercalcaemic analogue Calcipotriol (used in ‘psoriasis’)

Use: Fanconi syndrome (caused due to ‘tetracyclines’)

BISPHOSPHONATES

Analogues of pyrophosphate: carbon atom replacing oxygen in the P-O-P skeleton.

- OsteoBlast Builds bone

- OsteoClast Consumes bone

Classification:

BISPHOSPHONATES
First generation BPNs
Etidronate
Tiludronate
Second generation BPNs
Pamidronate
Alendronate
Ibandronate
Third generation BPNs
Risedronate
Zoledronate

Uses:

1. Osteoporosis: The second and third generation BPNs are effective in preventing and
treating postmenopausal osteoporosis in women, as well as idiopathic and steroid
induced osteoporosis in both, men and women.
2. Paget’s disease
Other drugs for hypercalcaemia:

1. Gallium nitrate: Potent inhibitor of bone resorption; acts by depressing ATP-

dependent proton pump at the membrane of osteoclasts.
2. Mithramycin (Plicamycin): Cytotoxic drug which inhibits bone resorption.
3. Glucorticoids: Prednisolone

SKELETAL MUSCLE RELAXANTS

These are drugs that act peripherally at neuromuscular junction / muscle fibre itself, or
centrally in the cerebrospinal axis, to reduce muscle tone and / or cause paralysis.

PERIPHERALLY ACTING MUSCLE RELAXANTS

I. Neuromuscular blocking agents

A. Non-depolarizing (Competitive) blockers
1. Long-acting: d-Tubocurarine (Fade phenomenon), Pancuronium, Doxacurium,
Pipecuronium
2. Intermediate-acting: Vecuronium, Atracurium, Cisatracurium, Rocuronium,
Rapacuronium.
3. Short-acting: Mivacurium
B. Depolarizing blockers
Succinylcholine (Suxamethonium), Dexamethonium
II. Directly acting agents
Dantrolene sodium, Quinine

CENTRALLY ACTING MUSCLE RELAXANTS

1. Mephenesin congeners: Mephenesin, Carisoprodol, Chlorzoxazone, Chlormezanone,

Methocarbamol.
2. Benzodiazepines: Diazepam and others
3. GABA derivative: Baclofen
4. Central α2 agonist: Tizanidine

Comparative features of central and peripheral muscle relaxants

Centrally acting Peripherally acting

Decrease muscle tone without reducing Cause muscle paralysis, voluntary
voluntary power movements lost
Selectively inhibit polysynaptic reflexes in Block neuromuscular transmission
CNS
Cause some CNS depression No effect on CNS
Given orally, sometimes parenterally Always given IV
Used in chronic spastic conditions, acute Used for short-term purposes (surgical
muscle spasms, tetanus operations)
IMPORTANT POINTS:

Steroidal anaesthetic acting on GABA-A receptor – Alphaxolone

DRUGS ACTING ON PERIPHERAL (SOMATIC) NERVOUS SYSTEM

LOCAL ANAESTHETICS

These are drugs, which upon topical application, or local injection, cause reversible loss of
sensory perception, especially of pain, in a restricted area of the body.

General anaesthesia Local anaesthesia

Site of action CNS Peripheral nerves
Area of body involved Whole body Restricted area
Consciousness Lost Unaltered
Care of vital functions Essential Usually not needed
Physiological trespass High Low
Poor health patient Risky Safer
Use in non-cooperative Possible Not possible
patient
Major surgery Preferred Cannot be used
Minor surgery Not preferred Preferred

Classification:

INJECTABLE ANAESTHETIC
Low potency, short duration
Procaine
Chloroprocaine
Intermediate potency and duration
Lidocaine (Lignocaine)
Prilocaine
Lignocaine + Prilocaine (Eutectic mixture)
High potency, long duration
Tetracaine (Amethocaine)
Bupivacaine
Ropivacaine
Dibucaine (Cinchocaine)
SURFACE ANAESTHETIC
Soluble Insoluble
(acronym: “TLC”) (acronym: “BOB”)
Tetracaine Benzocaine
Lidocaine Oxethazaine
Cocaine (ocular anaesthesia) Butylaminobenzoate (Butamben)
Benoxinate
Chemistry:

Ester-linked LAs Amide-linked LAs

Cocaine Lidocaine
Procaine Bupivacaine
Chloroprocaine Dibucaine
Tetracaine Prilocaine
Benzocaine Ropivacaine
Tropane containing LA – Alpha-eucaine

Trick to remember:

- If the drug contains two ‘i’ it is an ‘amide’.

- If the drug contains one ‘i’ it is an ‘ester’.

Note: “Cocaine is the only local anaesthetic which causes “HYPERTENSION”.

DRUGS ACTING ON CENTRAL NERVOUS SYSTEM (CNS)

GENERAL ANAESTHETICS

General anaesthetics (GAs) are drugs that produce reversible loss of all sensation and
consciousness.

STAGES OF ANAESTHESIA

Stage Type Uses

I Analgesia Labour incisons and minor operations
II Delirium Nil
III Surgical Anaesthesia Most of the surgical operations
1. Surgical Anaesthesia Rolling eyeballs
2. Surgical Anaesthesia Loss of corneal and laryngeal reflexes
3. Surgical Anaesthesia Pupil starts dilating and light reflex is
lost
4. Surgical Anaesthesia Intercostal paralysis, shallow abdominal
respiration, dilated pupil
IV Medullary Paralysis -

CLASSIFICATION

Inhalational
Gas Volatile liquids
Nitrous oxide (acronym: “HIDES”)
Halothane
Isoflurane
Desflurane
Enflurane
Sevoflurane
Intravenous
Inducing agents Slower acting drugs
(acronym: “TEMP”)
Thiopentone sod. Benzodiazepines
Methohexitone sod. Diazepam
Propofol Lorazepam
Etomidate Midazolam
Dissociative anaesthesia
Ketamine
Opioid analgesia
Fentanyl (+ Droperidol)

Nitrous oxide (N2O)

- High MAC (minimum alveolar concentration) – Potent analgesic / Poor

anaesthetic
- Second gas effect and diffusion hypoxia occur with N2O only.

Use: Dental and obstetric analgesia.

Halothane (Fluothane):

- Mechanism: Acts on RyR (Ryanodine receptor).

- Adverse effect: Malignant hyperthermia
- Succinylcholine accentuates the condition and IV Dantrolene used to treat
malignant hyperthermia.

Thiopentone sodium

- Drug of choice: ‘Narcoanalysis’

- Adverse effect: Laryngospasm
- Contraindication: Intermittent porphyria

Propofol

- Pain during injection of propofol is common; can be minimised by combining

with lidocaine.
 - Michael Jackson died due to overdose of Propofol.

Ketamine

- Pharmacologically related to the hallucinogen ‘phencyclidine’ (Angel’s dust).

Isoflurane

- Steal phenomenon occurs with isoflurane.

ETHYL AND METHYL ALCOHOL

Forms of alcohol

Forms Strength
Absolute alcohol 99 % w/w ethanol
Rectified spirit 90 % w/w ethanol
Proof spirit 49.29 % w/w or 57.1 % v/v alcohol

Disulfiram

Mechanism:

- Inhibits aldehyde dehydrogenase

- Inhibits alcohol dehydrogenase
- Inhibits dopamine β-hydroxylase

Use: Aversion technique in chronic alcoholics

SEDATIVE-HYPNOTICS

Sedative: A drug that subdues excitement and calms the subject without inducing sleep,
though drowsiness may be produced.

Hypnotic: A drug that induces and / or maintains sleep, similar to normal arousable sleep.

Sleep

Stage Name
0 Awake
1 Dozing
2 Unequivocal sleep
3 Deep sleep transition
4 Cerebral sleep

Classification:
BARBITURATES
Long acting Short acting Ultra-short acting
Phenobarbitone Butobarbitone Thiopentone
Mephobarbitone Pentobarbitone Methohexitone
Secobarbitone Hexobarbitone
BENZODIAZEPINES
Hypnotic Antianxiety Anticonvulsant
Diazepam Diazepam Diazepam
Flurazepam Chlordiazepoxide Lorazepam
Nitrazepam Oxazepam Clonazepam
Alprazolam Lorazepam Clobazam
Temazepam Alprazolam
Triazolam
NEWER NON-BENZODIAZEPINE HYPNOTICS
Zopiclone, Zolpidem, Zaleplon

BZD classification based on duration of action:

1. Long-acting: Diazepam, Nitrazepam, Flurazepam, Prazepam, Chlordiazepoxide

2. Short-acting: Temazepam, Oxazepam Triazolam, Alprazolam, Lorazepam
(acronym: “TOTAL”)

Mechanism:

Type Mechanism
Barbiturates GABA-mimetic action
Benzodiazepines (BZD) GABA-facilitatory action

BZD-inverse agonists: dimethoxyethyl-carbomethoxy-β-carboline (DMCM)

Note: Lorazepam is the only BZD that undergoes direct glucuronide formation.

Benzodiazepines: Three Members that undergo Extrahepatic metabolism are:

“Outside The Liver”

 Oxazepam
 Temazepam
 Lorazepam

Drugs affecting GABA-receptor gated chloride channel:

Drugs Mechanism
Muscimol GABAA agonist
Bicuculline GABAA antagonist
Baclofen GABAB agonist
Phaclofen GABAB antagonist
NON-BENZODIAZEPINE HYPNOTICS

- Acts on α1 subunit

Drug Basic Ring

Zopiclone Cyclopyrrolone
ZolPIdem Imidazo-pyridine

IMPORTANT POINTS TO REMEMBER:

- Nitrazepam has been shown to increase REM sleep.

- BZDs produce centrally mediated skeletal muscle relaxation.

Melatonin

- N-acetyl-5-methoxy tryptamine
- Principal hormone of the ‘pineal gland’.

Ramelteon: Melatonin receptor agonist

ANTIEPILEPTIC DRUGS

Epilepsy: These are a group of disorders of the CNS, characterized by paroxysmal cerebral
dysrhythmia, manifesting as brief episodes (seizures) of loss of disturbance of consciousness.

Epilepsy is characterised by,

1. Convulsions
2. Seizures
3. Disease of lightening
4. Jackson’s disease

Classification:

1. Barbiturate: Phenobarbitone
2. Deoxybarbiturate: Primidone
3. Hydantoin: Phenytoin, Fosphenytoin
4. Iminostilbene: Carbamazepine, Oxcarbazepine
5. Succinimide: Ethosuximide
6. Aliphatic carboxylic acid: Valproic acid (sodium valproate), Divalproex
7. Benzodiazepines: Diazepam, Lorazepam, Clonazepam, Clobazam
8. Phenyltriazine: Lamotrigine
9. Cyclic GABA analogue: Gabapentin
10. Newer drugs: Vigabatrin, Topiramate, Tiagabine, Zonisamide, Levetiracetam
Choice of antiseizure drugs

Type of seizures Drug of choice

Generalised tonic-clonic / major / grandmal Carbamazepine
Simple partial (cortical focal) Phenytoin
Complex partial (temporal lobe / Carbamazepine, Valproate, Phenytoin
psychomotor)
Absence / minor / petitmal (acronym: “VALET”)
Valproate, Ethosuximide
Myoclonic Valproate
Atonic Valproate
Febrile seizures Diazepam (rectal)
Status epilepticus Diazepam (i.v.)
Lorazepam (i.v.)
Infantile spasms (Hypsarrythmia) Valproate, Clonazepam
Diabetic neuropathy and Post-therapeutic Gabapentin
neuralgia
PTZ induced clonic seizures Ethosuximide
Trigeminal neuralgia Carbamazepine

 Primidone:

Primidone Liver Phenobarbitone + Phenylethyl malonamide (PEMA)

 Phenytoin (Diphenylhydantoin):

(acronym: “PHENYTOIN”)

 Pregnancy
 Hypertrophy of gum / Hirsutism
 Edema
 Neurological
 Yellow discoloured limb
 Thrombosis
 Osteomalacia
 Inhibit insulin
 Neutropenia

- Metabolism: Areneoxide metabolite

Carbamazepine:
- Other uses: Bipolar mood disorder, Antidiuretic action

Oxcarbazepine: ‘Epoxide’ metabolite

Divalproex (Semisodium valproate)

 - Valproic acid : Sodium valproate (1:1)

Antiepileptic + Carbonic anhydrase inhibitor – Topiramate, Zonisamide

Vigabatrin: mechanism Vi-GABA-Tr-In: Via GABA Transferase Inhibition

Nootropic drug – ‘Levetiracetam’

Anti-Epileptic Side Effects:

“ABCDEFGH”

 Ataxia
 Blood dyscrasia
 Cleft lip
 Dupuytrens / Vit. D. deficiency
 Exfoliation of skin and Stevens Johnsons
 Fits
 Gum hypertrophy
 Hirsutism

ANTIPARKINSONIAN DRUGS

Parkinsonism: It is an extrapyramidal motor disorder characeterized by:

(acronym: “RAFT”)

1. Rigidity
2. Akinesia
3. Flat facies
4. Tremor (at rest)

Symptoms of Parkinsonism:

- Degeneration of neurones in the substantia nigra pars compacta (SN-PC)

- Imbalance between dopaminergic (inhibitory) and cholinergic (excitatory) system.

Classification:

(acronym: “SALAD”)

 Selegiline
 Anticholinergics
 Levodopa + Peripheral decarboxylase inhibitor (Carbidopa)
 Amantadine
  Dopamine receptor agonist (Bromocriptine)

I. Drugs affecting brain dopaminergic system

(a) Dopamine precursor: Levodopa (l-dopa)
(b) Peripheral decarboxylase inhibitors: Carbidopa, Benserazide
(c) Dopaminergic agonists:
(i) Ergot derivative: Bromocriptine, Piribedil, Pergolide
(ii) Non-ergot derivatives: Ropinirole, Pramipexole
(d) MAO-B inhibitor: Selegiline
(e) COMT inhibitors: Entacapone, Tolcapone
(f) Dopamine facilitator (releaser): Amantadine
II. Drugs affecting brain cholinergic system
(a) Central anticholinergics: Trihexyphenidyl (Benzhexol), Procyclidine,
Biperiden.
(b) Antihistaminics: Orphenadrine, Promethazine.

Receptors Action
D1 Excitatory
D2 Inhibitory
D3 Inhibitory
D4 Inhibitory
D5 Excitatory

Mechanism of Antiparkinsonian drugs:

Drugs Mechanism
Bromocriptine D2 agonist / D1 partial agonist or antagonist
Ropinirole D2 / D3 agonist
Pramipexole D3 agonist

ANTIPSYCHOTIC DRUGS

(NEUROLEPTICS / MAJOR TRANQUILISERS)

These are drugs having a salutary therapeutic effect in psychoses.

Classification:

(acronym: “BOAT IN POND”)

 Butyrophenones
 Other heterocyclics
 Atypical antipsychotics
 Thioxanthenes
 Phenothiazines
 1. Phenothiazines
(a) Aliphatic side chain: Chlorpromazine, Triflupromazine (CAT)
(b) PiperiDine side chain: ThioriDazine
(c) Piperazine side chain: Trifluoperazine, Fluphenazine, Thioproperazine
2. Butyrophenones: Droperidol, Trifluperidol, Penfluridol, Haloperidol (DTPH)
3. Thioxanthenes: Flupenthixol
4. Other heterocyclics: Pimozide, Loxapine
5. Atypical antipsychotics: Clozapine, Olanzapine, Resperidone (CORE), Quetiapine,
Aripiprazole, Ziprasidone (CROZAQ).

IMPORTANT POINTS TO REMEMBER:

 Neuroleptics, except thioridazine, have potent antiemetic action.

 Common side effects of antipsychotics: Extrapyramidal side effects
 Continous use of antipsychotics leads to Tardive dyskinesia.
 Active metabolite of Quetiapine is Sulfoxide.

ANTIMANIC (MOOD STABILIZING) DRUGS

Lithium Carbonate

Lithium carbonate body Lithium chloride

(less hygroscopic) (more hygroscopic)

Drug Features
Lithium Antimanic
High dose Cause increase in thirst and polyuria
Therapeutic concentration Tremors
Contraindication Sick sinus syndrome

ANTIDEPRESSANT DRUGS

(THYMOLEPTICS)

These are drugs which can elevate mood in depressive illness.

Classification:

1. Reversible inhibitors of MAO-A (RIMA)

Moclobemide, Clorgiline (MCA)
 2. Tricyclic antidepressants (TCAs)
(acronym: “TCA”)
 Trimipramine
 Clomipramine
 Amitriptyline
(a) NA + 5-HT reuptake inhibitors
Imipramine, Trimipramine, Clomipramine, Amitriptyline, Doxepin, Dothiepin
(b) Predominantly NA reuptake inhibitors
(acronym: “DNA / RNA”)
 Desipramine / Reboxetine
 Nortriptyline
 Amoxapine
Desipramine, Nortriptyline, Amoxapine, Reboxetine
3. Selective serotonin reuptake inhibitors (SSRIs)
Fluoxetine, Fluvoxamine, Citalopram (S+), Paroxetine, Sertraline (FFCPS)
4. Atypical antidepressants
Monica + Bill Clinton AT TV
Mianserin, Bupropion, Congener of trazodone (Nefazodone), Amineptine,
Trazodone, Tianeptine, Venlafaxine.

MAO INHIBITORS

MAO Inhibitors Drugs

Non-selective (acronym: “PIT”)
Phenelzine, Isocarboxazid,
Tranylcypromine,
MAO-A Moclobemide, Clorgiline
MAO-B Selegiline

Deamination of MAO Inhibitors:

MAO Inhibitors Deaminates

MAO-A 5-HT and NA
MAO-B Phenylethylamine

MAOI Side Effects:

“3Hs”

 Hepatocellular jaundice
 Hyperthermia
 Hypertension

Cheese reaction:
 Reaction Drugs
Causes Tyramine, Dopa
Treatment Phentolamine (IV)

Chemistry:

Drug Chemistry
Amoxapine Tetracyclic
Fluoxetine Bicyclic

IMPORTANT POINTS TO REMEMBER

- Amoxapine – Antipsychotic + Antidepressant

- Escitalopram – S(+) enantiomer of citalopram
- Venlafaxine, Duloxetine – Serotonin and Noradrenaline reuptake inhibitor
(SNRI)
- Mirtazapine – ‘Noradrenergic and specific serotonergic antidepressant’ (NaSSA)
- Bupropion – DA + NA uptake (α1-blocking action)

ANTIANXIETY DRUGS

(MINOR TRANQUILIZERS)

Classifiication:

1. Benzodiazepines: Diazepam, Oxazepam, Chlordiazepoxide, Lorazepam, Alprazolam

2. Azaspirodecanediones: Buspirone, Ispapirone, Gepirone (acronym: “BIG”)
3. Sedative antihistaminic: Hydroxyzine
4. β-blocker: Propranolol

Alprazolam: High potency anxiolytic BZD

Hydroxyzine:

It has following pharmacological activities:

1. Sedative
2. Antihistaminic
3. Antianxiety
4. Antiemetic
5. Antimuscarinic
6. Spasmolytic
 OPIOID ANALGESICS AND ANTAGONISTS

OPIOID ANALGESICS:

A dark brown, resinous material obtained from poppy (Papaver somniferum) capsule. It
contains two types of alkaloids.

Phenanthrene derivatives

Morphine (10% in opium)

Codeine (0.5% in opium)

Thebaine (0.2% in opium) (Nonanalgesic)

Benzoisoquinoline derivatives (Nonanalgesic)

Papaverine (1%)

Narcotine / Noscapine (6%)

Classification of Opioids

1. Natural opium alkaloids: Morphine, Codeine (methyl-morphine)

2. Semisynthetic opiates: Heroin (Diacetylmorphine), Pholcodeine
3. Synthetic opioids: Pethidine (Meperidine), Fentanyl, Methadone,
Dextropropoxyphene, Tramadol.

Pethidine (Meperedine):

Pethidine Hydrolysis Meperidinic acid (major metabolite)

Pethidine Demethylation Norpethidine (minor metabolite)

Dextropropoxyphene: It is marketed only in combination with paracetamol

Receptors Agonist Antagonist

µ (mu) Endorphins β-funaltrexamine
κ (kappa) Dynorphins Norbinaltorphimine
δ (delta) Enkephalins Naltrindole
Note: Endorphins are the brain’s natural pain killers

Actions ascribed to different types of opioid receptors:

µ (mu) κ (kappa) δ (delta)

“MD CARES” Analgesia (spinal κ1) Analgesia (Spinal +
Miosis (supraspinal- κ3) Affective component of
supraspinal)
Dependency Respiratory depression Respiratory depression
(lower ceiling)
Constipation Dysphoria, psychotomimetic Affective behaviour
Analgesia Miosis (lower ceiling) Reinforcing actions
Respiratory depression Sedation Reduced G.I. motility
Euphoria Physical dependence
(nalorphine type)
Sedation Reduced G.I. motility

Complex Action Opioids and Opioid Antagonists

1. Agonist-antagonists (κ analgesics)
Nalorphine, Pentazocine, Butorphanol.
2. Partial/weak µ-agonist + κ-antagonist
Buprenorphine
3. Pure antagonists
Naloxone, Naltrexone, Nalmefene

Chemistry of opioids:

Drug Chemistry
Nalorphine N-allyl-normorphine
Naltrexone N-allylnor-oxymorphone

Derivatives:

Derivatives Drugs
Benzomorphane derivative Pentazocine
Morphinan derivative Levorphenol
Oripavine derivative Buprenorphine

Uses of opioids:

Drugs Uses
Pethidine (Meperidine) Opioid analgesic (in pregnancy)
Methadone Opioid withdrawal (dependence)
Methadone Opioid maintenance

- Butorphanol: ‘Nasal’ formulation

Opioid antagonists:

The Narcotic Antagonists are NAloxone and NAltrexone.

Antagonists Drugs
Drug of choice Naloxone
First opioid antagonist Naltrexone
Pure opioid antagonist Nalmefene
Note: Naloxone is used to treat overdose with all opioids except Buprenorphine.

Endogenous Opioid Peptides:

 Opioid Peptides Derived from Action on receptors
Endorphins Pro-opio-melanocortin (POMC) µ, δ
Dynorphins Prodynorphin µ, κ, δ
Enkephalins Proenkephalins Met-enk: µ, δ
Leu-enk: δ

IMPORTANT POINTS:

Brompton’s mixture = Cocaine + Heroine Treat cancer pain

CNS STIMULANTS

These are drugs whose primary action is to stimulate the CNS overall,, or to improve specific
brain functions.

CNS stimulants mostly produce a generalized action, which may, at high doses, result in
convulsions.

Classification:

1. Convulsants: Strychnine, Picrotoxin, Bicuculline, Pentylenetetrazol (PTZ).

2. Analeptics (Respiratory stimulants): Doxapram, Nikethamide
3. Psychostimulants: Amphetamines, Cocaine, Methylphenidate, Modafinil, Pemoline,
Methylxanthine (Caffeine). (acronym: “CAMP”)

 Picrotoxin:
- Obtained from Anamirta cocculus
- Blocks Cl ion channel non-competitively; acts on picrotoxin sensitive site.

 Bicuculline:
- GABAA antagonist

COGNITION ENHANCERS

(CEREBROACTIVE DRUGS)

These are a heterogenous group of drugs developed for use in dementia and other cerebral
disorders.

Dementia: Refers to acquired global impairment of intellect, memory and personality

(cognitive functions) in the absence of gross clouding of consciousness or motor
involvement.
Alzheimer’s disease: Deposition of β-amyloid protein in the form of senile plaques and is
the most common cause of dementia.

Classification:

1. Cholinergic activators:
Tacrine, Velnacrine, Rivastigmine, Donepezil, Galantamine
2. Glutamate (NMDA) antagonist:
Memantine
3. Miscellaneous cerebroactive drugs:
Piracetam, Pyritinol (Pyrithioxine), Dihydroergotoxine (Codergocrine), Piribedil,
Ginkgo biloba.

IMPORTANT POINTS TO REMEMBER:

- Rivastigmine: Inhibits both AChE and BuChE, but is more selective for the G1
isoform of AChE.
- Galantamine: Direct agonistic action on nicotinic receptors.
- Piracetam: ‘Nootropic’ drug
- Ginkgo biloba: Platelet activating factor (PAF) antagonistic action. Has been
implicated in ‘Cerebral thrombosis’

DRUGS AFFECTING RENIN-ANGIOTENSIN SYSTEM AND PLASMA KININS

Angiotensin Peptide
Angiotensin – I Decapeptide
Angiotensin – II Octapepide
Angiotensin – III Heptapeptide

Actions of Angiotensin:

CVS Smooth Adrenal Kidney CNS Peripheral

muscles cortex symphathetic
structures
Vasoconstriction Contraction Trophic to Promotes Induce Enhances
of visceral the zona Na+/H+ drinking sympathetic
smooth glomerulosa exchange in behaviour activity
muscles PCT and ADH
release
Increases force Enhance Reduces Increases
of myocardial release of renal blood central
contraction aldosterone flow sympathetic
outflow
Induces
hypertrophy,
hyperplasia
Angiotensin receptors:

Selective Angiotensin antagonist Examples of drugs

AT1 Losartan
AT2 PD 123177

ANGIOTENSIN CONVERTING ENZYME INHIBITORS

First ACE inhibitor Teprotide (nonapeptide)

Comparative features of some ACE inhibitors:

ACE inhibitors Chemistry Activity status

Captopril Sulfahydryl dipeptide Active
Enalapril (Prodrug: Carboxyl tripeptide Prodrug
Enalaprilat)
Lisinopril Lysine derivative of enalaprilat Active
(carboxyl)
Fosinopril Phosphinate compound Prodrug
Trandolapril Carboxyl prodrug Prodrug
Ramipril Carboxyl Prodrug
Benazepril Nonsulfhydryl prodrug Prodrug
Note: ACE inhibitor + Endopeptidase inhibitor – Omapatrilate

ACE Inhibitor Side Effects:

(acronym: “CAPTOPRIL”)

 Cough
 Anaphylaxis
 Palpitations
 Taste
 Orthostatic hypotension
 Potassium elevated
 Renal impairment
 Impotence
 Leukocytosis

ANGIOTENSIN ANTAGONISTS

Losartan:

- Competitive antagonist and inverse agonist of A-II

- More selective for AT1 than AT2 receptor

Candesartan:

- Produces largely unsurmountable antagonism

 - Highest affinity for the AT1 receptor

PLASMA KININS (POLYPEPTDES)

Plasma kinins Kallikreins Kininogen

Plasma kinins Chemistry

Bradykinin Nonapeptide
Kallidin Decapeptide

CARDIAC GLYCOSIDES AND DRUGS FOR HEART FAILURE

DIGITALIS:

Mechanism of Action:

- Digitalis increases force of cardiac contraction.

- Inhibits Na+K+ ATPase pump.

Venodilators (primarily decrease preload)

Glyceryl trinitrate
Isosorbide dinitrate
Arteriolar dilators (primarily decrease afterload)
Hydralazine
Minoxidil
Ca2+ channel blockers (Nifedipine)
Pot. Channel openers (Nicorandil)
Mixed dilators (decrease pre- and after load)
ACE inhibitors
AT1 antagonists (ARBs)
Prazosin (α1-blocker)
Amrinone, Milrinone
Nitroprusside

- Ionotropic means Force of contraction

- Chronotropic means Cardiac Rate (HR)
- Dromotropic means conDuctivity
- Lusiotropic means reLaxation (Loose)

Amrinone (Inamrinone)

Most important actions of amrinone:

1. Positive inotropy
2. Direct vasodilatation

- Has been called an Inodilator

Rubidium chloride Diagnosis of myocardial blood flow

ANTIARRHYTHMIC DRUGS

These are drugs used to prevent or treat irregularities of cardiac rhythm.

Classification:

Class Actions Drugs

(acronym: “MBA College” - Membrane stabilizers, Beta blockers, Action potential
widening agents, Calcium channel blockers)
I. Membrane stabilising agents
(Na+ channel blockers)
A. Moderately decrease “Queen Pe Dil Mera”
in dv/dt of 0 phase Quinidine, Procainamide,
Disopyramide, Moricizine
B. Little decrease in “Lo Phir Mein Tera”
dv/dt of 0 phase Lidocaine, Phenytoin,
Mexiletine, Tocainide
C. Marked decrease in Flecainide, Encainide,
dv/dt of 0 phase Propafenone
II. Antiadrenegic agents Propranolol, Esmolol, Sotalol
(β-blockers) (also class III)
III. Agents widening AP Sotalol, Ibutilide, Bretylium,
(prolong repolarization and Amiodarone
ERP)
IV. Calcium channel blockers Verapamil, Diltiazem
Note: Class IA agents also have Class III property; Propranolol has Class I action as well; sotalol and
bretylium have both Class II and Class III actions.

In addition

1. For PSVT (Paroxysmal Supraventricular Tachycardia): Adenosine, Digitalis

2. For AV block: Sympathomimetics – Isoprenaline, etc.
Anticholinergics – Atropine
3. Digitalis is used in AF, AFI and PSVT to control ventricular rate.

Drugs that prolong Q-T interval

(have potential to precipitate Torsades de pointes)
Antiarrythmics Quinidine, Procainamide, Disopyramide,
Propafenone, Amiodarone
Antimicrobials Quinine, Mefloquine, Artemisinin,
Halofantrine, Sparfloxacin, Gatifloxacin
Antihistaminics Terfenadine, Astemizole, Ebastine
Antidepressants Amitryptiline and other tricyclics
Antipsychotics Thioridazine, Risperidone
Prokinetic Cisapride

Amiodarone: action, side effects (6 Ps):

 Prolongs action potential duration

 Photosensitivity
 Pigmentation of skin
 Peripheral neuropathy
 Pulmonary alveolitis and fibrosis
 Peripheral conversion of T4 to T3 is inhibited, giving rise to hypothyroidism

Choice of drugs for Cardiac Arrhythmias:

Arrythmia Drug of choice

PSVT Adenosine
Atrial flutter Digoxin
Atrial fibrillation Digoxin
Ventricular tachycardia Lidocaine
Torsades de pointes Isoprenaline, Magnesium
Wolff-Parkinson-White Amiodarone
syndrome (WPW)
Antidepressant induced Class I C, e.g. Flecainide
arrhythmias

ANTIANGINAL DRUGS

These drugs are those that prevent, abort or terminate attacks of angina pectoris.

Angina pectoris is a pain syndrome due to induction of an adverse oxygen supply / demand
situation in a portion of the myocardium.

A. Classical / Stable angina (common form): Attacks are provoked by exercise, strong
emotions, eating, or coitus; and subside when the increased energy demand is
withdrawn or met.
B. Variant / Prinzmetal’s angina (uncommon form): Attacks occur during rest, or
during sleep, and are unpredictable.

Classification

1. Nitrates
(a) Short-acting: Glyceryl trinitrate (GTN, Nitroglycerine)
(b) Long-acting: Isosorbide dinitrate (short-acting by sublingual route), Isosorbide
mononitrate, Erythrityl tetranitrate, Pentaerythritol tetranitrate
2. β-Blockers: Propranolol, Metoprolol, Atenolol etc. (contraindicated in
variant/prinzmetal angina)
3. Calcium channel blockers
 (a) Phenyl alkylamine: Verapamil
(b) Benzothiazepines: Diltiazem
(c) Dihydropyridines: Nifedipine, Felodipine, Amlodipine, Nitrendipine, Nimodipine,
Lacidipine, Lercanidipine, Benidipine
4. Potassium channel opener: Nicorandil, Pinacidil, Cromakalim
5. Others: Dipyridamole, Trimetazidine, Ranolazine, Oxyphedrine

Clinical classification

A. Used to abort or terminate attack: GTN, Isosorbide dinitrate (sublingually)

B. Used for chronic prophylaxis: All other drugs

NITRATES (GTN as prototype)

Preload reduction

Nitrates dilate veins more than arteries peripheral pooling of blood decreased
venous return, i.e., preload on heart is reduced end diastolic size and pressure are
reduced decreased cardiac work according to Laplace relationship, which describes
the effectiveness of ventricular wall tension as below.

Wall tension = intraventricular pressure  ventricular radius

Afterload reduction

Nitrates also produce some arteriolar dilatation slightly decreasing total peripheral
resistance (t.p.r.), or afterload, on heart.

Mechanism of action

Rapidly denitrated to release the free radical nitric oxide (NO)

Activates cytosolic guanylyl cyclase

Increased cGMP

Causes dephosphorylation of myosin light chain kinase (MLCK)

Interferes with activation of myosin and fails to interact with actin to cause contraction

Relaxation
Pharmacokinetics

- All except isosorbide mononitrate undergo variable first pass metabolism in liver.
- Nitrates are rapidly denitrated by a glutathione reductase and a mitochondrial
aldehyde dehydrogenase.

Adverse effects

- Methemoglobinemia

Tolerance

Cross-tolerance (Nitrates) Rx Dithiothreitol -SH regenerating group

Interactions

Sildenafil  Nitrates Hypotension, Myocardial infarction

Duration of action of nitroglycerine via different routes:

Routes Duration of action

Sublingual 10-30 mins
Buccal 30-300 mins
Oral 2-6 hrs
Ointment 3-8 hrs
Discs Upto 24 hrs

Organic nitrates available for Angina Pectoris

Drug Duration of action

GTN (Nitroglycerine) 10-30 min (sublingual)
Isosorbide dinitrate 20-40 min (sublingual)
2-3 hr (oral)
Isosorbide mononitrate 6-10 hr (oral)
Erythrityl tetranitrate 4-6 hr (oral)
Pentaerythritol tetranitrate 3-12 hr (oral)

CALCIUM CHANNEL BLOCKERS

Drugs Category Chemistry

Verapamil Hydrophilic papaverine Phenyl alkylamine
congener
Nifedipine Lipophilic 1,4-Dihydropyridine
Diltiazem Hydrophilic 1,5-Benzothiazepine

Calcium channels

1. Voltage-sensitive channel
 2. Receptor-operated channel
3. Leak channel

Voltage-sensitive calcium channels

L-type T-type N-type
(Long lasting (Transient current) (Neuronal)
current)
Conductance 25 pS 8 pS 12-20 pS
Activation threshold High Low High
Inactivation rate Slow Fast Medium
Location and  Excitation-  SA node-  Only on neurones
Function contraction pacemaker in CNS,
coupling in activity sympathetic and
cardiac and  ‘T’ current and mysenteric
smooth muscle repetitive spikes plexuses-
 SA, AV node- in thalamic and transmitter
conductivity other neurones release
 Endocrine cells-  Endocrine cells-
hormone release hormone release
 Neurones-  Certain arteries-
trasmitter release constriction
Blocker Nifedipine, Mibefradil, ω-Conotoxin
Diltiazem, Flunarizine (Na+ &
Verapamil, Ca+), Ethosuximide
Mibefradil
Note: Verapamil  β-blockers – additive sinus depression

ANTIHYPERTENSIVE DRUGS

- These are drugs used to lower BP in hypertension.

- The WHO-ISH guidelines have defined blood pressure to be 140 mm Hg systolic
and 90 mm Hg diastolic, though risk appears to increase even above 120/80 mm
Hg.

CLASSIFICATION:

1. Diuretics
Thiazides: Hydrochlorothiazide, Chlorthalidone, Indapamide
High ceiling (Loop): Furosemide
K+ sparing: Spironolactone, Amiloride
2. ACE inhibitors
Prodrugs: Enalapril, Perindopril, Ramipril, Fosinopril etc.
Non-prodrugs: Captopril, Lisinopril
3. Angiotensin (AT1 receptor) blockers
Losartan, Candesartan, Irbesartan, Valsartan, Telmisartan
4. Calcium channel blockers
Phenylalkylamines: Verapamil
Benzothiazepines: Diltiazem
 Dihydropyridines (Phosphosensitive drugs): Nifedipine, Felodipine, Amlodipine,
Nitrendipine, Lacidipine etc.
5. β-adrenergic blockers
Propranolol, Metoprolol, Atenolol etc.
6. β + α adrenergic blockers
Labetalol, Carvedilol
7. α-adrenergic blockers
Prazosin, Terazosin, Doxazosin, Phentolamine, Phenoxybenzamine
8. Central sympatholytics
Imidazoline derivatives: Clonidine, Rilmenidine, Moxonidine
Dopamine precursor: Methyldopa
9. Vasodilators
Arteriolar: Hydralazine, Minoxidil, Diazoxide
Arteriolar + Venous: Sodium Nitroprusside

 High Ceiling (Loop) Diuretics X Aminoglycoside antibiotics : Ototoxicity

 Thiazide diuretics (7-position): Free sulphamoyl group.

Adverse effects of Diuretics as antihypertensives:

- Hypokalaemia
- Hyperglycemia
- Hyperuricaemia
- Hypercalcemia

 Indapamide is chemically related to chlorthalidone.

 Chlorthalidone is chemically related to diazoxide.

Calcium channel blockers:

- Calcium channel blockers (CCBs) are widely used as one of the first line
monotherapy options, because of their high efficacy and excellent tolerability.
- Negative inotropic action: Verapamil
- Negative dromotropic action: Diltiazem
- ADR of Dihydropyridines – Ankle swelling

- Nifedipine light Nitrosophenyl pyridine

- Nifedipine UV Nitrophenyl pyridine

 Carvedilol: Antioxidant / free radical scavenging properties

 Prazosin: Dilates both resistance and capacitance vessels (First dose effect)

Clonidine:

- Imidazoline derivative
 - Nasal decongestant
- Biphasic response
- High affinity for α2A receptors
- Adverse effects: Pheochromocytoma (Plasma catecholamine conc. increased)
- Interactions: TCAs and chlorpromazine abolish the antihypertensive effects of
clonidine.
- Other uses: Opioid withdrawal

 Methyldopa: False neurotransmitter

 Hydralazine

- Steal phenomenon occurs with Hydralazine.

 Minoxidil:
- Prodrug converted to an active metabolite by sulphate conjugation.
- Used in alopecia

 Diazoxide: K+ channel opener

 Sodium nitroprusside

- Duration of action: 2-5 min

- Nitroprusside is nonenzymatically converted to NO (and CN) by glutathione.
- Side effects – Lactic acidosis (due to the released cyanide)

DIURETICS

These are drugs which cause a net loss of Na+ and water in urine.

Relation to diuretic action

The relative magnitudes of Na+ reabsorption at different tubular sites are:

Site I: Proximal Tubule (65-70 %)

Site II: Ascending limb of Loop of Henle (20-25 %)

Site III: Cortical diluting segment of Loop of Henle

Site IV: Distal tubule (8-9 %) and collecting duct (1-2 %)

Classification:

1. High efficacy diuretics (Inhibitors of Na+-K+-2Cl co-transport)

Sulphamoyl derivatives
 Furosemide, Bumetanide, Torsemide
2. Medium efficacy diuretics (Inhibitors of Na+-Cl symport)
(a) Benzothiadiazines (Thiazides)
Hydrochlorothiazide, Benzthiazide, Hydroflumethiazide, Clopamide
(b) Thiazide-like (related heterocyclics)
Chlorthalidone, Metolazone, Xipamide, Indapamide
3. Weak or adjunctive diuretics
(a) Carbonic anhydrase inhibitors
Acetazolamide
(b) Potassium sparing diuretics
(i) Aldosterone antagonist: Spironolactone
(ii) Inhibitors of renal epithelial Na+ channel: Triamterene, Amiloride
Osmotic diuretics (used for treating Barbiturate poisoning), e.g. Glycerol, Urea,
Mannitol
(acronym: “GUM”)

Furosemide (Sulfonamide loop diuretic):

Route of administration Onset of action (min.)

Intravenous 2-5
Intramuscular 10-20
Oral 20-40

ANTIDIURETICS

These are drugs that reduce urine volume, particularly in Diabetes Inspidus (DI), which is
their primary indication.

ADH (Antidiuretic hormone): it is an octapeptide secreted by the posterior lobe of the

pituitary gland (neurohypophysis), along with oxytocin.

ADH SECRETION
Enhanced by (PHARMA) Inhibited by (GAP)
PG GABA
Histamine ANP (Atrial Natriuretic Peptide)
ACh Peptide (Endogenous opioids)
neuRopeptide Vasopressin
Morphine
AT II

Classification:

1. Antidiuretic hormone (ADH, Vasopressin): Desmopressin, Lypressin, Terlipressin

2. Thiazide diuretics: Amiloride
3. Miscellaneous: Indomethacin, Chlorpropamide, Carbamazepine.
 HAEMATINICS AND ERYTHROPOIETIN

Haematinics These are substances required for the formation of blood, used in treatment of
anaemias.

IRON

- On entering plasma, it is immediately converted to the ferric form and complexed

with a glycoprotein transferrin (Tf).
- Ferritin and Haemosiderin are storage forms of iron.

FOLIC ACID

- Chemically, it is Pteroyl glutamic acid (PGA), consisting of pteridine +

paraaminobenzoic acid (PABA) + glutamic acid.

ERYTHROPOIETIN (EPOETIN)

- Erythropoietin is a sialoglycoprotein hormone, produced by peritubular cells of

the kidney.

Use:

- Primary indication is chronic renal failure due to low levels of EPO.

- Anaemia in AIDS patients treated with zidovudine.
- Cancer chemotherapy induced anaemia.

Adverse effects: Haematocrit

DRUGS AFFECTING COAGULATION, BLEEDING AND THROMBOSIS

Coagulants

These are substances which promote coagulation, indicated in haemorrhagic conditions.

1. Vitamin K

K1 (from plants, fat-soluble): Phytonadione (Phylloquinone)

K3 (synthetic)

Fat soluble: Menadione, Acetomenaphthone

Water-soluble: Menadione sod. bisulfite, Menadione sod. diphosphate

 2. Miscellaneous
Fibrinogen, Antihaemophilic factor, Desmopressin, Adrenochrome
monosemicarbazone, Rutin, Ethamsylate

VITAMIN K

Chemistry and source

- Vit K has a basic naphthoquinone structure, with or without side chain (R) at
position 3. The side chain in K1 is phytyl, in K2 prenyl, while in K3 there is no side
chain.
- Dietary sources – green leafy vegetables, such as cabbage, spinach; and liver,
chesse etc.

DESMOPRESSIN Increases factor VIII activity.

ANTICOAGULANTS

These are drugs used to reduce the coagulability of blood.

I. Used in vivo
A. Parenteral anticoagulants
Heparin, Heparinoids (Heparan sulphate, Danaparoid, Lepirudin, Ancrod).
B. Oral anticoagulants
(i) Coumarin derivatives: Bishydroxycoumarin (Dicumarol), Warfarin sod.,
Acenocoumarol (Nicoumalone), Ethylbiscoumacetate
(ii) Indandione derivatives: Phenindione
II. Used in vitro
A. Heparin
B. Calcium complexing agents:
Sodium citrate, Sodium oxalate, Sodium edentate.

Comparative features of Heparin and Warfarin

Heparin Warfarin
Chemistry Mucopolysaccharide Coumarin derivative
Source Hog lung, pig intestine Synthetic
Route of admin. Parenteral (IV, SC) Oral
Onset of action Immediate Delayed (1-3 days)
Duration of action 4-6 hrs 3-6 days
Activity In vitro and in vivo In vivo only
Mechanism Blocks action of Factor X and Inhibits synthesis of clotting
thrombin factors
Antagonist Protamine sulphate (obtained Vit K
from sperm of certain fish)
Use To initiate therapy For maintenance
Noise - Saddle noise
Note: For heparin 1 IU is present in 7.7 µg of standard preparation
FIBRINOLYTICS (THROMBOLYTICS)

These are drugs used to lyse thrombi / clot to recanalize occluded blood vessels (mainly
coronary artery).

(acronym: “USA”)

- Urokinase
- Streptokinase
- Alteplase (recombinant tissue plasminogen activator)
- Reteplase
- Tenecteplase

ANTIFIBRINOLYTICS

These are drugs which inhibit plasminogen activation and dissolution of clot.

(acronym: “EAT” OR “TEA”)

 Epsilon amino-caproic acid (EACA) It is an analogue of the amino acid lysine.

 Tranexaemic acid
 Aprotinin It is a polypeptide isolated from bovine tissues with polyvalent serine
protease inhibitory activity.

ANTIPLATELET DRUGS (ANTITHROMBOTIC DRUGS)

These are drugs which interfere with platelet function and are useful in the prophylaxis of
thromboembolic disorders.

Aspirin Clopidogrel

Dipyridamole Abciximab

Ticlopidine (GP IIb/IIIa antagonist)

Common side effect of antiplatelet drugs: Neutropenia

GP IIb/IIIa antagonists:

Platelet (PlaTEAlet) inhibitors are Tirofiban, Eptifibatide, Abciximab

GP IIb/IIIa type Antagonists

Monoclonal antibody Abciximab
Peptide Eptifibatide
Non-peptide Tirofiban

Clopidogrel:

CLOPIdogrel is a drug that prevents CLots, an Oral Platelet Inhibitor (OPI).

 HYPOLIPIDEMIC DRUGS AND PLASMA EXPANDERS

Hypolipidemic Drugs

- These are drugs which lower the levels of lipids and lipoproteins in blood.
- Increased risk of atherosclerosis is associated with increased levels of LDL and
decreased levels of HDL.

Classification:

1. HMG-CoA reductase inhibitors (Statins):

Fluvastatin, Lovastatin, Atorvastatin, Pravastatin, Simvastatin (FLAPS).
2. Bile acid sequestrants (Resins):
Cholestyramine, Colestipol
3. Activate lipoprotein lipase (Fibric acid derivatives):
Clofibrate, Gemfibrozil, Bezafibrate, Fenofibrate
4. Inhibit lipolysis and triglyceride synthesis:
Nicotinic acid (Niacin / Vit. B3)
5. VLDL Secretion inhibitors:
Acipimox
6. Others: Ezetimibe, Gugulipid, Probucol

HMG-CoA REDUCTASE INHIBITORS (STATINS):

 They competitively inhibit conversion of 3-hydroxy-3-methyl glutaryl coenzyme A

(HMG-CoA) to mevalonate (rate limiting step in CH synthesis) by the enzyme HMG-
CoA reductase.

(acronym: “HMG-CoA”)

Side effects: Hepatotoxicity / Myositis / Rhabdomyolysis

Contraindications: Girl during pregnancy / Growing children

Interactions: Coumarin / Cyclosporine

Statins Chemistry (Basic ring)

Simvastatin Naphthyl
Fluvastatin Indole
Atorvastatin Pyrrole
Cerivastatin Pyridine

BILE ACID SEQUESTRANTS (RESINS)

 Cholestyramine (Styrene + Divinyl benzene co-polymer)

FIBRIC ACID DERIVATIVES

 All fibrates are Aryloxamine derivatives.

 This effect is exerted through peroxisome proliferator-activated receptor α (PPARα).

NICOTINIC ACID (NIACIN)

 Wide spectrum hypolipidemic drug.

EZETIMIBE

 Cholesterol absorption inhibitor

PROBUCOL

 Hypocholesterolemic drug
 Antioxidant + lipohilic

DRUGS FOR PEPTIC ULCER

Peptic ulcer occurs in that part of the gastrointestinal tract (GIT), which is exposed to gastric
acid and pepsin, i.e., the stomach and duodenum.

Etiology

 Aggressive – acid, pepsin, bile and H. pylori

 Defensive – gastric mucus and bicarbonate secretion, prostaglandins, nitric oxide,
innate resistance of the mucosal cells.

Types of ulcer:

 Gastric ulcer – Acid secretion is normal or low.

 Duodenal ulcer – Acid secretion is high in half the patients, but normal in the rest.

Classification:

1. Reduction of gastric acid secretion

(a) H2 antihistamines: Cimetidine (Antiandrogenic), Ranitidine, Famotidine (H2
inverse agonist), Roxatidine
(b) Proton pump inhibitors: Pantoprazole, Rabeprazole, Omeprazole, Lansoprazole,
Esomeprazole (acronym: “ROLE”)
(c) Anticholinergics: Pirenzepine (M1), Oxyphenonium, Propantheline (POP)
(d) Prostaglandin analogue: Misoprostol
2. Neutralization of gastric acid (Antacids)
 (a) Systemic (water-soluble): Sodium bicarbonate, Sodium citrate
(b) Nonsystemic (water-insoluble): Magnesium hydroxide, Magnesium trisilicate,
Aluminium hydroxide gel, Magaldrate, Calcium carbonate
3. Ulcer protectives: Sucralfate, Colloidal bismuth subcitrate (CBS)
4. Anti-H. pylori drugs: Tetracycline, Amoxicillin, Clarithromycin, Tinidazole,
Metronidazole (acronym: “TACT”).

Basic ring of Anti-ulcer drugs

Anti-ulcer drugs Basic ring (Chemistry)

Cimetidine Imidazole
Ranitidine Furan
Famotidine Thiazole
Omeprazole (Zoles) Benzimidazoles

PROTON PUMP INHIBITORS

Active metabolite – Sulphenamide

Omeprazole

- Inhibits H+K+ ATPase pump

PROSTAGLANDIN ANALOGUES

- PGE2 and PGI2 are produced in the gastric mucosa.

- Inhibits acid secretion and promoting mucus + HCO3 secretion.
- Cytoprotective action
- Primary use of PG – Prevention and treatment of NSAID-associated
gastrointestinal injury and blood loss.

ANTACIDS

Antacid Action Uses

Magnesium hydroxide Fast-acting Laxative
Aluminium hydroxide Slow-acting Constipation

SUCRALFATE: Basic aluminium salt of sulphated sucrose.

RATIONALE DRUG COMBINATION:

 PPI + tetracycline + CBS + metronidazole

DRUGS FOR EMESIS

Emesis: Vomiting occurs due to stimulation of the emetic (vomiting) centre situated in the
medulla oblongata.
  Acts at chemoreceptor trigger zone (CTZ).

Emetics: These are drugs used to evoke vomiting.

1. Act on CTZ, e.g. Apomorphine

2. Act reflexly and on CTZ, e.g. Ipecacuanha

ANTIEMETICS

These are drugs used to prevent or suppress vomiting.

Classification:

1. Anticholinergics: Hyoscine, Dicyclomine

2. H1-antihistaminics: Promethazine, Diphenhydramine, Dimenhydrinate, Doxylamine,
Cyclizine, Meclozine, Cinnarizine.
3. Neuroleptics (D2-blockers): Chlorpromazine, Prochlorperazine, Haloperidol etc.
4. Prokinetic drugs: Metoclopramide, Domperidone, Cisapride, Mosapride, Tegaserod
5. 5-HT3-antagonists: Ondansetron, Granisetron
6. Adjuvant antiemetics: Dexamethasone, Benzodiazepines, Cannabinoids

Uses:

Antiemetics Uses
Hyoscine Motion sickness
Cyclizine, meclizine Sea sickness
Cinnarizine Anti-vertigo

PROKINETIC DRUGS

These are drugs which promote gastrointestinal transit and speed gastric emptying by
enhancing coordinated propulsive motility.

Metoclopramide

- Chemically related to procainamide.

- Also called as a gastric hurrying agent.

Mechanism of action

- D2 antagonist
- 5-HT4 agonist
- 5-HT3 antagonist

Domperidone

It is a D2 antagonist, chemically related to haloperidol, but pharmacologically related to

metoclopramide.
Cisapride

- Prokinetic drug, lacks D2-receptor antagonism.

- Primary indication – Gastroesophageal reflux disease
- Banned due to Torsades de pointes

Tegaserod

- 5-HT4 agonist
- Drug of choice for Irritable Bowel syndrome

Cannabinoids are GPCR (G-protein-coupled receptors).

Methyl polysiloxane (Dimethyl polysiloxane, Simethicone, Dimethicone)

It is a silicone polymer, a viscous amphiphilic liquid – reduces surface tension and collapses
the froth, thus is a good antifoaming agent.

DRUGS FOR CONSTIPATION AND DIARRHOEA

LAXATIVES These are drugs that promote evacuation of bowels.

(a) Laxatives or aperients: milder action, elimination of soft, but formed, stools.
(b) Purgatives or cathartics: stronger action, resulting in more fluid evacuation.

Drugs in low doses act as laxatives and in larger doses as purgatives.

Classification:

(acronym: “BOSS”)

 Bulk forming
 Osmotic purgatives
 Stimulant purgatives
 Stool softeners

1. Bulk forming
Dietary fibre: Bran, Psyllium (Plantago), Isapghula, Methylcellulose
2. Stool softener
Docusates (DOSS), Liquid paraffin
3. Stimulant purgatives
(a) Diphenylmethanes
Phenolphthalein, Bisacodyl, Sodium picosulfate
(b) Anthraquinones (Emodins)
Senna, Cascara sagrada
 (c) 5-HT4 agonist
Tegaserod
(d) Fixed oil
Castor oil
4. Osmotic purgatives
Magnesium salts: sulphate (Epsom salt), hydroxide (Milk of magnesia)
Sodium salts: sulphate (Glauber’s salt), phosphate
Sod. pot. Tartrate (Rochelle salt)
Lactulose (semisynthetic disaccharide of fructose + lactose)

MECHANISM OF ACTION

All purgatives increase the water content of faeces by:

(a) A hydrophilic or osmotic action, retaining water and electrolytes in the intestinal
lumen.
(b) Acting on intestinal mucosa, decreasing net absorption of water and electrolyte;
intestinal transit is enhanced.
(c) Increasing propulsive activity.

Dietary fibre: bran

Bran bind bile acids and promote their excretion degradation of cholesterol in liver is
enhanced plasma LDL-cholesterol is lowered.

Docusates (Dioctyl sodium sulfosuccinate; DOSS)

Anionic surfactants soften the stools by net water accumulation in the lumen, by the action on
intestinal mucosa.

TREATMENT OF DIARRHOEAS

Diarrhoea is too frequent, often too precipitate passage of poorly formed stools.

Non-specific antidiarrhoeal agents and their indications

Class Drug Use

ABSORBANTS Ispaghula Irritable bowel syndrome
Psyllium (IBS), Ileostomy/colostomy
Methyl cellulose diarrhoea
ANTISECRETORY (acronym: “BAMS = O”) Sulfasalazine/Mesalazine –
Bismuth subsalicylate Ulcerative colitis, IBS
Atropine Traveller’s diarrhoea
Mesalazine Drug-induced diarrhoea
Sulfasalazine Carcinoid, diarrhoea in AIDS
Octreotide Acute secretory diarrhoea
ANTIMOTILITY (acronym: “DLC”) Mild diarrhoea
(Opioids) Diphenoxylate-atropine Idiopathic diarrhoea in AIDS
(also antisecretory) Loperamide After anal surgery,
 Codeine colostomy

 Sulfasalazine (Salicylazosulfapyridine)
- It is a compound of 5-aminosalicylic acid (5-ASA), with sulfapyridine linked
through azo bond.
- Azo bond is split by colonic bacteria.

 Olsalazine
- It consists of two molecules of 5-ASA coupled together by azo bond.

 Racecadotril (Prodrug)

- Racecadotril Thiorphan

- Enkephalinase inhibitor

- Prevents degradation of enkephalins (δ-opioid receptor agonists).

 Loperamide
- Opiate analogue; Anticholinergic property
- Directly interacts with calmodulin (responsible for antidiarrhoeal action).

SULFONAMIDES, COTRIMOXAZOLE AND QUINOLONES

Sulfonamidochrysoidine Sulfanilamide (p-amino benzene sulphonamide)

(Prontosil Red)

Sulfonamide

First sulfa drug: Prontosil rubrum (invented by G. Domagk)

Sulfonamide tragedy: Sulfonamide + Diethylene glycol : Sulfanilamide was dissolved in

diethylene glycol and marketed as an elixir. But diethylene glycol is a deadly poison. So
it lead to many deaths.

Classification:

1. Short-acting (4-8 hr): Sulfadiazine

2. Intermediate-acting (8-12 hr): Sulfamethoxazole
3. Long-acting (7 days): Sulfadoxine, Sulfamethopyrazine
4. Special purpose sulphonamides: Sulfacetamide sod., Mafenide, Silver sulfadiazine,
Sulfasalazine

Mechanism of action:

- Inhibits folic acid synthase (PABA).

 - Pus is rich in PABA.

Sulfonamide Disease Route of administration

Sulfadiazine Meningitis Oral
Sulfamethoxazole (+ Traveller’s diarrhoea Oral
Trimethoprim)
Sulfadoxine, Sulfamethopyrazine P. falciparum resistant malaria Oral
(+ Pyrimethamine)
Sulfacetamide sod. Ophthalmic infections Topical
Silver sulfadiazine, Mafenide Pseudomonas infections Topical
(Burnt surfaces and chronic
ulcers)
Sulfasalazine Ulcerative colitis, Rheumatoid Oral
arthritis

Adverse Effects:

(acronym: “CSK” (Chennai Super Kings))

- Crystalluria
- Stevens-Johnson syndrome
- Kernicterus (in babies)

COTRIMOXAZOLE

- Trimethoprim + Sulfamethoxazole – 1:5

- Inhibits bacterial dihydrofolate reductase (DHFRase)
- Drug of choice in treatment of Traveller’s diarrhoea.

QUINOLONES

Classification:

1. Non-fluorinated quinolone: Nalidixic acid

2. First-generation fluoroquinolones: Norfloxacin, Ofloxacin, Ciprofloxacin,
Pefloxacin
3. Second-generation fluroquinolones: Lomefloxacin, Levofloxacin, Sparfoxacin,
Gatifloxacin, Moxifloxacin (potent).
4. Third-generation fluroquinolones: Gemifloxacin, Prulifloxacin

Mechanism of action:

(acronym: “TOPPLE THE QUEEN”: Quinolone interferes with Topoisomerase II)

 - Inhibit DNA gyrase (enzyme responsible for unwinding & supercoiling of DNA)
- Inhibits Topoisomerase IV enzyme in gram-positive bacteria and Topoisomerase
II enzyme in mammals.

Nalidixic acid:

- It is active against gram-negative bacteria (E. coli, Proteus, Klebsiella, Shigella

etc.) but not Pseudomonas.

Adverse effects:

- Phototoxicity is common (highest with Lomefloxacin).

- ‘Torsades de pointes’ is associated with Gatifloxacin.

ANTIBIOTICS

Mechanism of Antibiotics:

(acronym: “BUY AT 30 AND CELLS AT 50”)

30s inhibitors: Aminoglycosides, Tetracyclines

50s inhibitors: Chloramphenicol, Erythromycin, Lincomycin, cLindamycin, Streptogramins

Antibiotics Mechanism
Penicillin Inhibit ‘transpeptidases’
Tetracyclines Binds to 30S ribosomal unit
Chloramphenicol Binds to 50S ribosomal unit
Aminoglycosides (except Binds to 30S-50S ribosomal unit
Streptomycin)
Streptomycin Binds to 30S ribosomal unit
Macrolides Binds to 50S ribosomal unit, Inhibit
‘translocation’

Sources of Antibiotics:

Drug Source
Penicillin Penicillium notatum (Original)
Penicillium chrysogenum (Present)
Clavulanic acid Streptomyces clavuligerus
Demeclocycline Streptomyces aureofaciens
Oxytetracycline Streptomyces rimosus
Chloramphenicol Streptomyces venezuelae
Streptomycin Streptomyces griseus
Gentamicin Micromonospora purpurea
Kanamycin Streptomyces kanamyceticus
Tobramycin Streptomyces tenebrarius
Sisomicin Micromonospora inyoensis
Neomycin Streptomyces fradiae
Framycetin Streptomyces lavendulae
Erythromycin Streptomyces erythreus

Trick to remember:

If the drug ends with ‘mycin’ then it is obtained from Streptomyces species.

If the drug ends with ‘micin’ then it is obtained from Micromonospora species.

Chemistry of Antibiotics:

Antibiotics Chemistry
Penicillins β-lactam ring fused to thiazolidine ring
Cephalosporins β-lactam ring fused to dihydrothiazine ring
β-lactamase inhibitors (Clavulanic acid) β-lactam ring fused to oxazolidine ring
Tetracyclines Octahydronapthacene
Chloramphenicol Nitrobenzene
Macrolides (Erythromycin) Macrocyclic lactone ring with sugars

BETA-LACTAM ANTIBIOTICS

Penicillins:

Penicillin was discovered by Alexander Fleming (1929), from Pencillium notatum, purified
by FLOREY and CHAIN and commercially extracted from P. chrysogenum.

 Biosynthesized from Cysteine and Valine.

 Penicillin Penicillinase Penicilloic acid

Types of bacteria:

 Gram-positive bacteria: Peptidoglycan (80-90%) + Teichoic acid

 Gram-negative bacteria: Peptidoglycan (5-10%) + Lipoproteins

Classification:

I. Natural Penicillin: e.g. Benzyl penicillin (Penicillin G).

II. Semisynthetic Penicillin

1. Acid-resistant alternative to Penicillin G

e.g. Phenoxymethyl penicillin (Penicillin V).

2. Penicillinase-resistant Penicillins

e.g. Methicillin,

Cloxacillin (Penicillinase + Acid-resistant)

 3. Extended spectrum penicillins

(a) Aminopenicillins: Ampicillin, Becampicillin, Amoxicillin

(b) Carboxypenicillins: Carbenicillin, Ticarcillin

(c) Ureidopenicillins: Piperacilin, Mezlocillin

III. β-lactamase inhibitors: Clavulanic acid, Sulbactam, Tazobactam

 Clavulanic acid is a ‘progressive inhibitor’ or called as ‘suicide’ inhibitor.

CEPHALOSPORINS

Common side effect of Cephalosporins: Anaphylactic shock.

Classification:

First-generation Second-generation Third-generation Fourth-

generation
Parenteral Oral Parenteral Oral Parenteral Oral Parenteral
Cephalothin* Cephalexin Cefuroxime Cefaclor Cefotaxime Cefixime Cefepime
Cefazolin Cephradine Cefoxitin* Cefuroxime Ceftizoxime Cefpodoxime Cefpirome
axetil proxetil
Cefadroxil Ceftriaxone Cefdinir
Ceftazidime Ceftibuten
Cefoperazone

 Cephalexin: Most commonly used cephalosporin

Gram-negative Bacteria that first-generation Cephalosporins are active against:

(acronym: “PEcK”)

 Proteus mirabilis
 Escherichia coli
 Klebsiella

Monobactams: Aztreonam

Carbapenems: Imipenem (always given with ‘Cilastatin’),

Meropenem, Feropenem

TETRACYCLINES (BROAD-SPECTRUM ANTIBIOTICS)

Forms of Tetracycline:

Forms Examples of drugs

 Acidic Epitetracycline
Basic Isotetracycline

Common features of tetracyclines:

Tetracycline Oxytetracyline Demeclocycline Doxycycline Minocycline

Source Semisynthetic S. rimosus S. aureofaciens Semisynthetic Semisynthetic
Potency Low Low Moderate High Highest
Plasma t1/2 6-10 6-10 16-18 18-24 18-24
(hr)
Incidence of High High Intermediate Low Low
diarrhoea
Phototoxcity Low Low Highest High -
Toxicity Antianabolic Tooth Diabetes Renal toxicity Vestibular
effect discoloration inspidus toxicity

Tetracycline: Teratogenicity

TEtracycline is a TEratogen that causes staining of TEeth in the newborns.

Side-effects: Tetracyclines cause various side-effects. They are as below.

(acronym: “KAPIL DeV Toxic”)

 Kidney damage
 Antianabolic reaction
 Phototoxicity
 Intracranial pressure raised
 Liver toxicity
 Diabetes inspidus
 Vestibular toxicity
 Teeth and bone toxicity

CHLORAMPHENICOL

Pharmacokinetics: Glucuronic acid conjugation

Interactions: Chloramphenicol  β-lactams / aminoglycosides. Chloramphenicol can

antagonize the bactericidal action of β-lactams / aminoglycosides on certain bacteria.

AMINOGLYCOSIDE ANTIBIOTICS

(POST-ANTIBIOTIC EFFECT)
Common side effect of Aminoglycoside antibiotics: Nephrotoxicity, Ototoxicity

Systemic Topical
Streptomycin Neomycin
Gentamicin Framycetin
Kanamycin
Tobramycin
Amikacin
Sisomicin
Netilmicin

Derivatives:

Antibiotics Derivatives of
Amikacin Kanamycin
Netilmicin Sisomicin
Azithromycin Erythromycin

Nephrotoxicity / Ototoxicity:

Nephrotoxicity / Ototoxicity Drugs

Lowest nephrotoxicity Streptomycin (Triacidic base)
Lowest ototoxicity Netilmicin
Highest nephrotoxicity Neomycin
Highest ototoxicity Neomycin

OXAZOLIDINONE:

- Linezolid: Antibiotic + MAO inhibitor

- Streptogramins (Quinupristin / Dalfopristin): Combination of two
semisynthetic pristinamycin antibiotics (synergism).
- Mupirocin: Topically used antibiotic
- Fusidic acid: Steroidal antibiotic

POLYPEPTIDE ANTIBIOTICS:

Drug Active against

Polymyxin B Gram-negative bacteria
Colistin Gram-negative bacteria
Bacitracin Gram-positive bacteria
Tyrothricin Gram-positive/negative bacteria

ANTITUBERCULAR DRUGS
Source: Mycobacterium tuberculosis

Common side effect: Hepatitis

Classification:

First Line Drugs (high efficacy and low toxicity)

(acronym: “RESPIration”)

1. Rifampicin
2. Ethambutol
3. Streptomycin
4. Pyrazinamide
5. Isoniazid

Second Line Drugs (low efficacy and high toxicity)

(acronym: “PET”) (acronym: “A ROCK”)

1. Paraaminosalicylic acid (PAS) Newer drugs

2. Ethambutol (Etm) 1. Amikacin
3. Thiacetazone (Thz) 2. Rifabutin
4. Cycloserine (Cys) 3. Ofloxacin
4. Ciprofloxacin,
capreomycin
5. Kanamycin

Mechanism:

Drugs Mechanism (Inhibition)

Isoniazid Mycolic acid synthesis, acts on extracellular / intracellular
TB
Rifampin DNA dependent RNA polymerase
Ethambutol Arabinosyl transferases
Para-amino salicylic acid Bacterial folate synthase

Sources:

Drugs Sources
Rifampin Streptomyces mediterranei
Cycloserine Streptomyces orchidaceous

IMPORTANT POINTS TO REMEMBER:

 - Rifampicin: Semisynthetic derivative of rifamycin B (Ansamycin)
- Rifampicin – Red orange coloration (urine, sweat, tears)
- Pyrazinamide: Good ‘sterilizing activity’
- Nicotinic acid derivatives: Isoniazid, Ethionamide
- Cross tolerance occurs with Isoniazid and Ethionamide.
- Anti T.B. drug which does NOT cause ‘Hepatotoxicity’: Ethambutol
- Isoniazid X Pyridoxine (Vit. B6)

ANTILEPROTIC DRUGS

Source: Mycobacterium leprae

Classification:

1. Sulfone: Dapsone (DDS)

2. Phenazine derivative: Clofazimine
3. Antitubercular drugs: Rifampin, Ethionamide
4. Other antibiotics: Ofloxacin, Minocycline, Clarithromycin

Dapsone (DDS)

- It is diamino diphenyl sulfone (DDS)

- Inhibits PABA

Clofazimine

- Drug of choice: Multidrug therapy of leprosy

- Adverse effect: Reddish-black discolouration of skin

ANTIFUNGAL DRUGS

Classification:

1. Antibiotics
A. Polyenes: Amphotericin B (AMB), Nystatin, Hamycin, Natamycin (Pimaricin)
B. Heterocyclic Benzofuran: Griseofulvin (spindle poison)
2. Antimetabolite: Flucytosine (5-FC)
3. Azoles
A. Imidazoles (topical): Clotrimazole, Econazole, Miconazole, Oxiconazole
(acronym: “CEMO”), Ketoconazole (systemic)
B. Triazoles (systemic): Fluconazole, Itraconazole, Voriconazole (acronym:
“FIV”)
4. Allylamine: Terbinafine, Naftifine (acronym: “ANT”)
5. Other topical agents: Tolnaftate, Undecylenic acid, Benzoic acid, Quiniodochlor,
Ciclopirox olamine, Butenafine, Sod. Thiosulfate.
Mechanism of Antifungals:

Antifungals Mechanism
5-Fluocytosine (5-FC) Inhibits thymidylate synthase
Azoles Inhibits sterol-14-α-demethylase
Terbinafine / Naftifine Inhibits squalene epoxidase
Griseofulvin Inhibits DNA synthesis

Sources of Antifungals:

Drugs Sources
Amphotericin B (AMB) Streptomyces nodosus
Nystatin Streptomyces noursei
Griseofulvin Penicillium griseofulvum

Uses of Antifungals:

Drugs Use
Amphotericin B (AMB) Kala-azar, Gold standard for antifungals
Nystatin Vaginitis
Griseofulvin Dermatophytosis

ANTHELMINTICS

Anthelmintics are drugs that either kill (vermicide), or expel (vermifuge), infesting helminths.

Choice of drugs for Helminthiasis

Worm Drug of choice

Roundworm Mebendazole, Albendazole, Pyrantel
Hookworm Pyrantel, Mebendazole, Albendazole
Threadworm Pyrantel, Mebendazole, Albendazole
Strongyloides infection Ivermectin
Whipworm Mebendazole
Filaria Diethyl carbamazine, Ivermectin
Guineaworm Metronidazole
Tapeworms Praziquantel, Niclosamide
Hydatid disease (Echinococcus Albendazole
infection)
River Blindness Ivermectin

Mechanism of Anthelmintics:

Anthelmintics Mechanism
Mebendazole Selectively inhibits microtubule synthesis (so inhibits
cell division, colchicines like effect); decrease glucose
uptake so depletes glycogen stores and decrease ATP
 Thiabendazole Inhibits fumarate reductase, inhibits microtubule
synthesis
Ivermectin Inhibits GABA mediated neurotransmission in
nematodes and cause immobilisation of parasites
Piperazine Neuromuscular blockade by interaction with nicotinic
receptors causing flaccid paralysis
Pyrantel pamoate Causes spastic paralysis by depolarizing muscles,
inhibits AChE
Oxamniquine Inhibits DNA, RNA and protein synthesis
Praziquantel Increases cell permeability, causes massive loss of
extracellular Ca++ ions concentration

ANTIVIRAL DRUGS

Classification:

1. Anti-Herpes virus
“For herpes, GIVe acyclovir”
Foscarnet, Ganciclovir, Idoxuridine, Vidarabine, Acyclovir
2. Anti-Retrovirus
(a) Nucleoside reverse transcriptase inhibitors (NRTIs):
Zidovudine (AZT), Didanosine, Zalcitabine, Stavudine, Lamivudine, Abacavir
(b) Nucleotide reverse transcriptase inhibitors:
Tenofovir
(c) Non-nucleoside reverse transcriptase inhibitors (NNRTIs):
“NED”: Nevirapine, Efavirenz, Delavirdine
(d) Protease inhibitors (PIs): (“SPRAIN”)
Saquinavir, Ritonavir, Amprenavir, Indinavir, Nelfinavir, Lopinavir

(e) Fusion inhibitors:

EnFUvirtide, Maraviroc
(f) Integrase inhibitor:
Raltegravir
3. Anti-Influenza virus:
Amantadine, Rimantadine, Oseltamivir, Zanamivir
4. Non-selective antiviral drugs:
Ribavirin, Lamivudine, Adefovir dipivoxil, Interferon α

Causative organism Virus

Variola Small pox
Varicella Herpes

Analogues:

Drug Analogue
Idoxuridine Thymidine
Trifluridine Thymidine
Vidarabine Thymidine
Acyclovir Deoxyguanosine
Famciclovir Guanine
Penciclovir Guanine
Zidovudine Thymidine
Didanosine Purine
Stavudine Thymidine
Lamivudine Deoxycytidine
Abacavir Guanosine

Acyclovir:

Acyclovir

Herpes virus specific thymidine kinase

Acyclovir monophosphate

Cellular kinases

Acyclovir triphosphate

Inhibits herpes virus DNA Gets incorporated in viral DNA and

polymerse competitively stops lengthening of DNA strand.

The terminated DNA inhibits DNA

polymerse irreversibly.

 Famciclovir: It is an ester prodrug of a guanine nucleoside analogue penciclovir.

 Abacavir (ABC): Potent ARV drug that acts after conversion to Carbovir triphosphate

 Oseltamivir: Effective against H1N1 virus (H – Haemagglutinin ; N – Neuraminidase)

PROTEASE INHIBITORS

- Aspartate amino acid is present.

- First protease inhibitor – Saquinavir.
- All protease inhibitors are peptides except Tipranivir (non-peptide).

RIBAVIRIN: indications RIBAvirin:

 Respiratory syncytial virus (RSV)

  Influenza B
 Arenaviruses (Lassa, Bolivian etc.)

ANTIMALARIAL DRUGS

Classification:

(acronym: “ABC Quinine TDS MAN”)

1. 4-Aminoquinolines: Chloroquine, Amodiaquine, Piperaquine.

2. 8-Aminoquinolines: Primaquine, Bulaquine
3. Acridine: Mepacrine (Quinacrine, Atabrine)
4. Biguanides: Proguanil (Chloroguanide), Chlorproguanil
5. Cinchona alkaloid: Quinine
6. Quinoline-methanol: Mefloquine
7. Tetracyclines: Tetracycline, Doxycycline
8. Diaminopyrimidines: Pyrimethamine, Trimethoprim
9. Sulfonamides and sulfone: Sulfadoxine, Sulfamethopyrazine, Dapsone
10. Sesquiterpene lactones: Artesunate, Artemether, Arteether
11. Mannich base: Pyronaridine
12. Amino alcohols: Halofantrine, Lumefantrine
13. Naphthoquinone: Atovaquone

CHLOROQUINE:

- Rapidly acting erythrocytic schizontocide

Mechanism:

Haeme Polymerization Hemozoin

(Toxic) (Nontoxic parasite pigment)

Adverse effects: Retinal damage, corneal opacity

Uses:

(acronym: “RED LIP”)

 Rheumatoid arthritis
 Extraintestinal amoebiasis
 Discoid lupus
 Lepromatous leprosy
 Infectious mononucleosis
  Photogenic reaction

QUININE:

Levo-isomer (cinchona) “Antimalarial”

Dextro-isomer (quiniDine) “Antiarrythmic”

PROGUANIL (CHLOROGUANIDE):

- Inhibits the preerythrocytic stage of P. falciparum.

- Inhibit the development of gametes instead of killing.
- Inhibits plasmoidal DHFRase.

- Proguanil Cycloguanil (Triazine derivative)

PYRIMETHAMINE:

- Directly acting inhibitor of plasmoidal DHFRase.

SULFONAMIDE-PYRIMETHAMINE (S/P) COMBINATION:

- Sulfonamide (Sulfadoxine / Sulfamethopyrazine)

- Drug of choice: Toxoplasmosis

PRIMAQUINE:

- Tissue schizonticidal
- Drug of choice: Radical cure of relapsing (vivax) malaria

ARTEMISININ:

- Basic Ring: Endoperoxide bridge

- Use: Oral artemisinins are indicated only for treatment of multidrug-resistant
falciparum malaria.

ANTIAMOEBIC DRUGS

These are drugs useful in infection caused by the protozoa Entamoeba histolytica.

Classification:

1. Tissue amoebicides
(a) For both intestinal and extraintestinal amoebiasis:
Nitroimidazoles: Tinidazole, Nimorazole, Metronidazole, Ornidazole,
Secnidazole, Satranidazole (acronym: “TN MOSS”)
Alkaloids: Emetine, Dihydroemetine
(b) For extraintestinal amoebiasis only: Chloroquine
2. Luminal amoebicides
 (a) Amides: Diloxanide furoate, Nitazoxanide
(b) 8-Hydroxyquinolines: Quiniodochlor (Clioquinol), Diiodohydroxyquin
(Iodoquinol)
(c) Antibiotics: Tetracyclines

METRONIDAZOLE:

- Prototype Nitroimidazole
- Topical use of metronidazole is psoriasis.

Drug of choice:

- Amoebiasis
- Giardiasis
- Trichomonas vaginitis
- Pseudomembranous enetrocolitis
- Ulcerative gingivitis

NITAZOXANIDE:

- Salicylamide congener of the anthelmintic niclosamide.

QUINIODOCHLOR (CLIOQUINOL):

- Prolonged / Repeated use of relatively high doses of quiniodochlor caused a

neuropathic syndrome called subacute myelo-optic neuropathy (SMON).

DRUGS FOR LEISHMANIASIS

- Leishmaniasis is transmitted by the bite of the female sandfly Phlebotomus.

- Visceral leishmaniasis (Kala-azar) caused by Leishmania donovani.
- Mucocutaneous (Dermal) leishmaniasis caused by L. braziliensis and L. tropica.

Classification:

1. Antimonial: Sodium stibogluconate (SSG)

2. Diamidine: Pentamidine
3. Antifungal drugs: Amphotericin B (AMB), Ketoconazole (KTZ)
4. Others: Miltefosine, Paromomycin, Allopurinol

IMPORTANT POINTS TO REMEMBER

- Ketoconazole: Lanosterol inhibits Ergosterol

- Miltefosine: First oral antileishmania drug.

 - Paramomycin: Aminoglycoside antibiotic

ANTICANCER DRUGS

Classification:

A. Drugs acting directly on cells (Cytotoxic drugs)

1. Alkylating agents:
(a) Nitrogen mustards: Mechlorethamine (Mustine HCl), Cyclophosphamide,
Ifosphamide, Chlorambucil, Melphalan
(b) Ethyleneimine: Thio-TEPA
(c) Alkyl sulfonate: Busulfan
(d) Nitrosoureas: Carmustine, Lomustine, Streptozocin
(e) Triazine: Dacarbazine
2. Antimetabolites:
(a) Folate antagonist: Methotrexate (MTX)
(b) Purine anatagonist: 6-Mercaptopurine (6-MP), 6-Thioguanine (6-TG),
Azathioprine, Fludarabine
(c) Pyrimidine anatagonist: 5-Fluorouracil (5-FU), Cytarabine (cytosine
arabinoside)
3. Vinca alkaloids: Vincristine (Oncovin), Vinblastine
4. Taxanes: Paclitaxel, Docetaxel
5. Epipodophyllotoxin: Etoposide
6. Camptothecin analogues: Topotecan, Irinotecan
7. Antibiotics: Actinomycin D (Dactinomycin), Doxorubicin, Daunorubicin
(Rubidomycin), Mitoxantrone, Bleomycin, Mitomycin C
8. Miscellaneous: Hydroxyurea, Procarbazine, L-Asparaginase, Cisplatin, Carboplatin,
Imatinib
B. Drugs altering hormonal milieu
1. Glucocorticoids: Prednisolone and others
2. Estrogens: Fosfestrol, Ethinylestradiol
3. Selective estrogen receptor modulators: Tamoxifen, Toremifene
4. Selective estrogen receptor down regulators: Fulvestrant
5. Aromatase inhibitors: Letrozole, Anastrozole, Exemestane
6. Antiandrogen: Flutamide, Bicalutamide
7. 5-α reductase inhibitor: Finasteride, Dutasteride
8. GnRH analogues: Nafarelin, Triptorelin
9. Progestins: Hydroxyprogesterone acetate etc.

ALKYLATING AGENTS:

- These compounds produce highly reactive carbonium ion intermediates, which

transfer alkyl groups to cellular macromolecules by forming covalent bonds.
- The position 7 of guanine residues in DNA is especially susceptible.
 - Alkylation results in crosslinking / abnormal base pairing / scission of DNA
strand.

Mechlorethamine (Mustine HCl):

- First nitrogen mustard.

- Given only by IV route.

Cyclophosphamide:

Cyclophosphamide 4-hydroxy cyclophosphamide Phosphoramide mustard

(Active metabolite)

To prevent this Cystitis Acrolein Aldophosphamide

MESNA given (Toxicity)

- MESNA: Mercaptoethanol sulfonic acid

- MESNA is a –SH compound that is excreted in urine.

 Thio-TEPA (Highest toxicity): Free radical alkylating agent

 Nitrosoureas: Cross Blood brain barrier (BBB)
Streptozocin (acronym: LOose his Car): Streptozocin, Lomustine, Carmustine
 Dacarbazine: Only anticancer drug inhibiting RNA synthesis (rest all others inhibit
DNA)

ANTIMETABOLITES:

1. Folate antagonist

Methotrexate (MTX)

- Inhibits dihydrofolate reductase (DHFRase)

- Dihydrofolic acid inhibits Tetrahydrofolic acid

(DHFA) (THFA)

- MTX has cell cycle specific action – kills cells in S phase.

- Inhibits DNA, RNA and protein synthesis.

Toxicity:

Low doses Megaloblastic anaemia

High doses Pancytopenia

2. Purine antagonists:

Mercaptopurine (6-MP) and thioguanine (6-TG)

6-MP / 6-TG body Monoribonucleotides

Inosine monophosphate monoribonucleotides Adenine + Guanine (nucleotides)

Azathioprine

- Metabolised by xanthine oxidase.

- Metabolism inhibited by allopurinol.

Pyrimidine antagonists:

Fluorouracil (5-FU)

- 5-Fluorouracil body 5-fluoro-2-deoxyuridine monophosphate inhibits Thymidylate

synthase

- Deoxyuridilic acid thymidylate synthase Deoxythymidilic acid

Cytarabine

- Triphosphate of cytarabine inhibits DNA polymerase.

- Blocks generation of cytidilic acid.

VINCA ALKALOIDS:

- Mitotic inhibitors
- Bind to microtubular protein – tubulin
- Inhibits tubulin polymerisation.

VinBLASTine BLASTS Bone marrow

TAXANES:

- Paclitaxel: It is a complex diterpin taxane obtained from bark of the Western yew
tree
- Mechanism: It enhances tubulin polymerisation.

Topoisomerase inhibitors:

Topoisomerases Inhibitors
Topoisomerase I Camptothecin analogues (Topotecan, Irinotecan)
Topoisomerase II Etoposide, Daunorubicin, Doxorubicin

CAMPTOTHECIN ANALOGUES:
 - Irinotecan: Inhibits AChE (cholinergic effects)

DOXORUBICIN:

- Anthracycline antibiotic
- Obtained from Streptomyces peucetius var. caesius

MISCELLANEOUS CYTOTOXIC DRUGS:

These drugs (except L-asparaginase) have been developed by random synthesis and testing
for antitumor activity.

Hydroxyurea:

- Mechanism: It blocks the conversion of ribonucleotides to deoxyribonucleotides

by inhibiting the enzyme ribonucleoside diphosphate reductase.

Procarbazine:

- Anticancer + Monoamine oxidase (MAO) inhibitor

L-Asparaginase:

- Source: Escherichia coli

- Mechanism: L-Asparaginase degrades L-Aspartic acid

- Causes Haemorrhagic pancreatitis.

- Used in acute Lymphocytic leukemia

Cisplatin:

- Platinum coordination complex

- Site – N7 of guanine residue

Imatinib:

- Mechanism: Inhibit tyrosine protein kinases

- Trick to remember: If the drug ends with ‘tinib’ (e.g. Imatinib, Gefitinib etc.)
then it is a tyrosine protein kinase inhibitor.

GENERAL PRINCIPLES IN CHEMOTHERAPY OF CANCER:

Cell cycle non-specific: Kills resting as well as dividing cells.

Cell cycle specific: Kills only actively dividing cells.

 Phases Examples of drugs
Cell cycle non-specific
Nitrogen mustard, cyclophosphamide, chlorambucil, carmustine, dacarbazine, busulfan, L-
asparaginase, cisplatin, procarbazine, actinomycin D
Cell cycle specific
G1 Vinblastine
S MTX, cytarabine, 6-TG, 6-MP, 5-FU,
hydroxyurea, mitomycin C, doxorubicin,
daunorubiciin
G2 Daunorubicin, bleomycin, etoposide,
topotecan
M (M-TV) Paclitaxel, Docetaxel (Taxanes), Vincristine,
Vinblastine (Vinca alkaloids)

Mechanism:

G1 phase – Pre (nucleic acid) synthesis interval

S phase - Synthesis of DNA occurs

G2 phase - Post-synthetic interval

M phase – Mitosis occurs – two G1 cells are produced, which either directly reenter next
cycle or pass into the non-proliferative (G0) phase

Cytoprotectants used in Anticancer therapy:

Anticancer drugs Cytoprotectants

Cisplatin Amifrostin
Cyclophosphamide / Ifosphamide MESNA (Mercaptoethanol sulfonic acid)
Doxorubicin Dexozasone
Current choice of drugs in malignancy:

Sr. Malignancy First line drugs

No.
1. Epstein-Barr virus Cyclophosphamide
2. Infectious mononucleosis Cyclophosphamide
3. Wagner’s granulomatosis Cyclophosphamide
4. Chronic lymphatic Chlorambucil
leukemia
5. Multiple myeloma Melphalan
6. Ovarian cancer Cisplatin
7. Chronic myeloid leukemia Busulfan
8. Malignant melanoma Dacarbazine
9. Chronic myeloid leukemia Hydroxyurea
10. Acute lymphatic leukemia L-Asparaginase
11. Hodgkin’s disease MOPP combination
(Mechlorethamine,
Oncovin, Procarbazine,
Prednisolone)
12. Ewing’s sarcoma Doxorubicin,
Vincristine,
Actinomycin D,
Cyclophosphamide
13. Wilm’s tumour Actinomycin D,
Vincristine
14. Choriocarcinoma Methotrexate
15. Prostate carcinoma Flutamide/Bicalutamide
16. Breast carcinoma Tamoxifen

IMMUNOSUPRESSANT DRUGS

These are drugs which inhibit cellular or humoral, or both, immune responses. Their major
use is in organ transplant and autoimmune diseases.

Classification:

1. Calcineurin inhibitors (Specific T-cell inhibitors)

Cyclosporine (Ciclosporin), Tacrolimus
2. Antiproliferative drugs (Cytotoxic drugs)
Azathioprine, Cyclophosphamide, Methotrexate, Chlorambucil, Mycophenolate
mofetil (MMF)
3. Glucocorticoids
Prednisolone and others
4. Antibodies
Muromonab CD3, Antithymocyte globulin (Polyclonal antibody), Rho (D) immune
globulin

LIST OF AUTOIMMUNE DISEASES:

1. Rheumatoid arthritis
2. Myasthenia gravis
3. Bronchial asthma
4. Psoriasis
5. Chronic active hepatitis
6. Inflammatory bowel disease
7. Dermatomyositis
 8. Uveitis
9. Pemphigus

Cyclosporine:

- It is a cyclic polypeptide with 11 amino acids, obtained from a fungus.

- Highly selective immunosuppressant.

Mechanism: Selectively inhibits T-lymphocyte proliferation, IL-2 and other cytokine

production and response of T-inducer cells to IL-1.

Cyclosporine Side Effects:

(acronym: “4HRT”)

 Hyperkalemia, hypertension, gum hypertrophy, hirsutism

 Renal toxicity
 Tremors

Tacrolimus:

- Macrolide antibiotic

- Source: Streptomyces tsukubaensis

Mechanism: It binds to a cytoplasmic immunophilin protein labelled ‘FKBP’, inhibition of

helper T-cells.

Sirolimus:

- Also known as Rapamune.

- Source: Streptomyces hygroscopicus

Methotrexate:

- Potent immunosuppressant

- First line drug in autoimmune diseases

Mycophenolate mofetil (MMF):

- Prodrug of mycophenolic acid

- Mechanism: Inhibits inosine monophosphate dehydrogenase

DRUGS BANNED IN INDIA

S. Drug Use Reason for Ban
No.
1. Nimesulide Pain killer Increased risk of liver
toxicity
2. Cisapride Increases motility in the upper Serious cardiac
GIT arrhythmias (Torsade
de pointes)
3. Human placenta Vitiligo, wound dressing, Transit diseases and
prevention of ADR due to pose serious health
radiotherapy, fallopian tube hazards
blockage, female infertility,
scarring, post-phlebitic ulcers,
scars due to acne
4. Phenylpropanolamine Used in cold and cough Due to its potential to
(PPA) remedies cause stroke
5. Sibutramine, R-sibutramine Anti-obesity Heart attacks, cardiac
arrests and stroke
6. Letrozole Ovulation inducer Teratogenic effects
like defective bone
formations, cardiac
stenosis and even
cancer
7. Rofecoxib NSAID (selective COX-2 Cardiac problems
inhibitor)
8. Fenfluramine Adrenergic agent (Pressor Cardiac problems
agent)
9. Cerivastatin Anti-hyperlipidemic Rhabdomyolysis
10. Rosiglitazone Antidiabetic Heart attack

DRUGS OF CHOICE
Disease Drug of choice
Absence Seizures VAlproate (acronym: “VAAS”)
Addison’s disease Hydrocortisone
Alopecia (acronym: “FM DVD”)
Finasteride
Minoxidil
Diazoxide
Valproate
Dutasteride
Alzheimer’s disease Anticholinesterases, e.g. Donepezil
Amoebiasis Metronidazole
Arrythmias: Drug induced Class I C, e.g. Flecainide
Asthma: Acute Salbutamol
Asthma: Aspirin induced Montelukast, Zafirlukast (LTC4 inhibitors)
Attention deficit hyperactive Methylphenidate
disorder
Autoimmune diseases Methotrexate
Bartter’s syndrome Indomethacin
Bed wetting (children) Desmopressin
Bell’s palsy Prednisolone (oral)
Benign hypertrophy of prostate Prazosin
Bipolar depression Lithium carbonate
Bird flu Oseltamivir
Buerger’s disease Prazosin, Phenoxybenzamine
Burkett’s lymphoma Cyclophosphamide
Cancer chemotherapy induced Erythropoietin
anaemia
Cancer chemotherapy induced Thalidomide
cachexia
Cancer chemotherapy induced Aspirin
diarrhoea
Cancer chemotherapy induced Ondansetron
vomiting
Chaga’s disease Primaquine, Puromycin, Nifurtimox
Cheese reaction Phentolamine
Chickenpox Acyclovir
Cholera Tetracyclines
Chronic lymphatic leukemia Chlorambucil
Chronic myeloid leukemia Busulfan
Chronic Obstructive Pulmonary Ipratropium, Tiotropium
Disease (COPD)
Cobra bite Atropine + Neostigmine (i.v.)
Colic pain Morphine
Constipation Bran
Crohn’s disease Tegaserod
Cross tolerance Dithiothreitol (-SH regenerating group)
Cryptorchism Gonadotropins
Cushing’s syndrome: Diagnosis Dexamethasone
Cushing’s syndrome: Treatment Ketoconazole
Cytomegalovirus Ganciclovir
Dermatophytosis Griseofulvin
Diabetes inspidus Desmopressin
Diabetes inspidus: Lithium Amiloride
induced
Diabetes ketoacidosis (Coma) Regular soluble insulin
Diabetes: Type I Insulin
Diabetes: Type II Sulfonyl ureas

Dysmenorrheae Mephenamic acid

Epilepsy Phenobarbitone
Fanconi syndrome Vitamin D (Calciferol)
Febrile seizures Diazepam (rectal)
Filariasis Diethylcarbamazine
Gastroesophageal reflux disease Proton Pump inhibitors (PPIs)
(GERD)
Giardiasis Metronidazole
Gilles de la Tourette’s Haloperidol
syndrome
Gonorrhoea Ceftriaxone
Gout: Acute Indomethacin
Gout: Chronic Allopurinol
Graft rejection reaction Cyclosporine
Graves’ disease Radioactive iodine
Hairy cell leukemia Cladribine
Hepatitis C Interferon + Ribavirin
Herpes simplex Keratitis Idoxuridine
Herpes zoster Valaciclovir
Hodgkin’s disease (acronym: “MOPP”) (Mechlorethamine + Oncovine +
Prednisolone + Procarbazine)
Huntigton’s disease Haloperidol
Hydatid disease Albendazole
Hyperlipidemias Atorvastatin (Statins)
Hyperprolactinemia Bromocriptine, Cabergoline
Hypertension in eclampsia Hydralazine
Hypertension in pregnancy Methyldopa
Hypertension: Cyclosporine Calcium channel blockers (CCBs)
induced
Hypertensive emergencies Sodium nitroprusside
Hypertensive emergencies in Hydralazine
pregnancy
Hypertension: Pulmonary Bosentan (ETA/ETB antagonist)
arterial
Hypothyroidism l-thyroxine
Infantile spasms Diazepam
(Hypsarrythmia)
Influenza virus Amantadine
Jet-lag syndrome Melatonin
Kala-azar Sodium Stibogluconate
Leishmaniasis Sodium Stibogluconate
Lie detector Hyoscine
Malaria Chloroquine
Malaria: Cerebral Quinine
Meniere’s disease Betahistine
Meningitis Ampicillin
Migraine Sumatriptan (Triptans)
Migraine: Prophylaxis Propranolol
Morning sickness Prochlorperazine
Motion sickness Hyoscine
Myasthenia gravis Neostigmine
Myxodema coma l-thyroxine
Narco analysis Thiopentone sod.
Narcolepsy Modafinil
Neuroleptanalgesia Fentanyl + Droperidol (i.v.)
Nocturia (adults) Desmopressin
Nocturnal enuresis Amphetamine
NSAIDs induced ulcer Omeprazole (PPIs)
Obsessive-compulsive disorder Fluoxetine
(OCD)
Open angle glaucoma Beta-blockers
Organic brain syndrome Neuroleptics
Osteoporosis Bisphosphonates
Paget’s disease Bisphosphonates
Parkinsonism Levodopa + Carbidopa
Parkinsonism: Drug induced Trihexyphenidyl
Paroxysmal Supraventricular Adenosine
Tachycardia (PSVT)
Patent Ductus arteriosus Alprostadil
Patent Ductus arteriosus: “Come IN and Close the Door”
Treatment INdomethacin is used to Close PDA
Pheochromocytoma Phentolamine
Phobia Fluoxetine
Plague Tetracyclines
Polyuria in renal DI Indomethacin
Postgastrectomy dumping Cyproheptadine
syndromes
Postpartum haemorrhage Methylergometrine
Raynaud’s disease Nifedipine
Red man syndrome Vancomycin
Renovascular hypertension ACE inhibitors
Respiratory syncytial virus Ribavirin
Restless leg syndrome Ropinirole
Rheumatoid Arthritis Methotrexate
River blindness Ivermectin
Sea sickness Cyclizine
Shock: Anaphylactic Adrenaline
Shock: Cardiogenic/Septic Dobutamine
Shock anaesthesia Ketamine
Sleep-apnoea syndrome Modafinil
Sleeping sickness Suramine (Luminal surface active agent)
Smoking cessation Varenicline, Bupropion
Status epilepticus Diazepam, Lorazepam (IV)
Stokes-Adams syndrome Adrenaline
Superinfection Nystatin
Swine flu (H1N1) Oseltamivir
Syphilis Penicillin G (Benzyl Penicillin)
Toxoplasmosis Sulfonamide + Pyrimethamine
Traveller’s diarrhoea Cotrimoxazole
Trichomoniasis Metronidazole
Trigeminal neuralgia Carbamazepine
Turner’s syndrome Growth hormone
Ulcerative colitis Sulfasalazine
Urinary Tract infection Nitrofurantoin
Vancomycin resistant S.aureus Linezolid
Vasospastic angina Nifedipine
Ventricular tachycardia Lidocaine
Vertigo Cinnarizine
Wagner’s granulomatosis Cyclophosphamide
Whooping cough Erythromycin
Zollinger-Ellison syndrome Omeprazole

DRUG OF CHOICE IN PREGNANCY

Category Drug of choice in pregnancy
Anticoagulant Heparin
Anti-HIV Zidovudine
Antihyperlipidemic Cholestyramine
Anti-inflammatory Paracetamol
Antimalarial Chloroquine
Antithyroid Propylthiouracil
Asthma Steroids
Epilepsy Phenobarbitone
Hypertension Hydralazine, Methyldopa
Opioid analgesic Pethidine

ADVERSE DRUG REACTIONS

Side effects Drug
Agranulocytosis (acronym: “PACTS”)
Phenylbutazone
Aminopyrine, Amodioquine
Chloramphenicol, Chlorpromazine, Clozapine, Colchicine
(4Cs)
Thiouracil
Sulfonamides
Anorgasmia Selective serotonin reuptake inhibitors (SSRIs)
Alopecia (acronym: “ALOPECIA”)
Antithyroid
Lithium
OC withdrawal
Phenytoin
Ethionamide
Cytotoxics
Interferon
Anticoagulants and Albendazole
Black water fever Quinine
Bone marrow depression Vinblastine
Cardiotoxicity Doxorubicin
Cheese reaction Tyramine, Dopa
Churg-Strauss syndrome Montelukast, Zafirlukast
Cinchonism Qunidine
Constipation Iron/Morphine
Corneal opacities (acronym: “MICD”)
Mepacrine
Indomethacin
Chloroquine
Vit. D
Cross tolerance Nitrates
Crystalluria (acronym: “MUMBAI CST (MM CST)”)
Methenamine
Methotrexate
Ciprofloxacin
Sulfonamides
Thiabendazole
Cystitis Cyclophosphamide, Ifosfamide
Discoloration of teeth Tetracycline
Disulfiram-like reaction Cefoperazone, Metronidazole, Procarbazine, Propafenone,
Mebendazole, Chlorpropamide, Nitrofurantoin
Dry cough ACE inhibitors
Dyspepsia Probenecid
Extrapyramidal side effects Antipsychotics
Fancony syndrome Epitetracycline
Gray baby syndrome Chloramphenicol
Gray man syndrome Amiodarone
Gum hypertrophy Phenytoin
Gynaecomastia (acronym: “MTV DISCO”)
Methyldopa / Metronidazole
TCAs
Verapamil
Digoxin
Isoniazid
Spironolactone
Cimetidine
Oestrogens
Hepatotoxicity Anti-T.B (except Ethambutol)
Hepatic necrosis (acronym: “HAVe”)
Halothane
Acetaminophen
Valproic acid
Hirsutism Phenytoin
Hyperkalaemia Spironolactone
Intermittent porphyria Thiopentone sod.
Jarisch-Herxheimer reaction Penicillin G (Benzyl penicillin)
Kernicterus Sulfonamides
Lactic acidosis Phenformin, Sodium nitroprusside
Laryngospasm Thiopentone sod.
Lupus (acronym: “HIP”)
Hydralazine
Isoniazid
Procainamide
Malignant hyperthermia Halothane
Megaloblastic anemia (acronym: “MAPLE”)
Methotrexate
AZT (Zidovudine)
Phenytoin
Liver disease
Ethanol
Mickey Finn syndrome Alcohol + Chloral hydrate (IV)
Monday morning headache / Glyceryl trinitrate (Nitroglycerine)
Monday disease
Nephrotoxicity (acronym: “ABCS”)
Amphotericin B, Cyclosporine, Streptomycin
Neurotoxicity Vincristine
Neutropenia Ticlopidine, Clopidogrel
On-Off effect Levodopa
Optical neuritis Ethambutol
Ototoxicity Streptomycin
Peripheral neuritis Isoniazid
Pheochromocytoma Clonidine
Phocomelia (Seal-like limbs) Thalidomide
Pulmonary edema (acronym: “PONS”)
Phenothiazines
Opioids / Organophosphates
Nitrous oxide
Salicylates
Pulmonary fibrosis (acronym: “BB MAN”)
Busulfan
Bleomycin
Methotrexate
Amiodarone
Nitrofurantoin
RAynaud’s disease (acronym: “BEAR”)
Bleomycin, β-blockers, Ergot
Red man syndrome Vancomycin
Respiratory depression (acronym: “STOP breathing”)
Sedatives and hypnotics
Trimethoprim
Opiates
Polymyxins
Restless leg syndrome Levodopa
Retinal damage/Corneal Chloroquine
opacity
Reye’s syndrome Aspirin
Rhabdomyolysis Statins
Serotonin syndrome SSRIs + MAOIs
Skin pigmentation Clofazimine
Subacute myelo-optic Quiniodochlor (Clioquinol)
neuropathy (SMON).
Somnolence Cetrizine
St. Antony’s fire Ergot
Steven-Johnson syndrome (acronym: “LESS”)
Lamotrigine, Ethosuximide, Sulfonamides, Stevens-Johnson,
Thiacetazone, Carbamazepine, Nevirapine, Amprenavir,
Allopurinol, Bisacodyl, Phenylbutazone, Fluconazole,
Itrocanozole
Stocking and glove Paclitaxel
neuropathy
Superinfection Penicillin G, Tetracycline
Tardive dyskinesia Antipsychotics
Thrombophlebitis Diazepam
Nephrolithiasis Triamterene
Turner’s syndrome Growth hormone
Virilization Androgen

PHOSPHODIESTERASE INHIBITORS (PDEs)

Inhibitors Drugs
Non-selective PDE Theophylline, Papaverine
PDE-1 Vinpocetin (in vinca)

PDE-3 Amrinone, Milrinone, Cilostazole

PDE-4 Roflumilast, Drotaverine, Rolipram
PDE-5 Sildenafil, Tadalafil, Vardenafil

DIFFERENT TYPES OF INHIBITION

Types of inhibition Examples of drugs
Semi-irreversible Carbachol
Pseudoirreversible Rivastigmine, Methotrexate

RECEPTORS
Receptors Synonym Time of response Examples
Ligand-gated ion Ionotropic receptor Milliseconds GABA, Glutamate,
channel 5HT3 receptor,
Nicotinic receptor
G-Protein Coupled Metabotropic/7- Seconds Neuropeptide,
receptor (GPCR) transmembrane spanning Opiate, 5HT,
heptahelical receptor Dopamine,
Muscarinic receptor
Enzyme linked Kinase receptor Minutes Insulin, Growth
 factor, Imatinib
Nuclear Nucleic acid receptor Hours Steroids, TSH,
Vitamins

MECHANISM
Mechanism Type of drugs
IP3 / DAG Pathway H1, M1, M3, 5-HT2, Vasopressin, Oxytocin, Bradykinin (B2
receptor), Angiotensin, Thromboxane, Leukotriene
Increase in cAMP B-receptor, H2, D1, Follicle Stimulating Hormone (FSH),
Leutinizing Hormone (LH), Adrenocorticotropic Hormone
(ACTH), Thyroid Stimulating Hormone (TSH), A2
(adenosine), Glucagon (hormone of fuel mobilization)
Decrease in cAMP M2, D2, 5-HT1, GABA-B, Opioid (µ, δ), A1
Increase in Ca++ ion channel β-receptor
Decrease in Ca++ ion channel D2, GABA-B, Opioid (κ)

ANTIDOTES
Drug/Poisoning Antidote / Antagonist
Aldosterone Spironolactone
Barbiturates Bemegride / Pentylenetetrazole
Belladonna (Atropine) Physostigmine
Benzodiazepines (BZDs) Flumazenil.
Bradykinin Icatibant (Bant – Bradykinin antagonists)
Calcium channel blockers Calcium gluconate
CarbamATes Atropine
Cyanide Nitrates
Endotheline converting enzyme Phosphoramidon
Fibrinolytics (acronym: “EAT” OR “TEA”)
Epsilon amino-caproic acid (EACA), Aprotinin,
Tranexamic acid
Glucorticoid Mifepristone (Antiprogestin)
Glutamate Ketamine
HePaRINE PRotamINE sulphate (obtained from sperm of certain
fish)
Hypnotic Pentylenetetrazole (PTZ)
Iron Desferrioxamine (parenterally)
Deferipone (orally)
Lead Calcium disodium EDTA, Dimercaptosuccinic acid
(succimer)
Levodopa / Isoniazid Pyridoxine (Vit. B6)
Mercury / Arsenic (acronym: “MAD”)
Dimercaprol
Methotrexate Folinic acid (N5 formyl THFA, citrovorum factor),
 Thymidine, I.V. calcium leucovorin
Methyl alcohol/Ethylene glycol Fomepizole (4-methyl pyrazole)
Mushroom poisoning: Early Atropine
Mushroom poisoning: Late Thioctic acid
Opioids (Morphine) Naloxone
Organophosphate Pralidoxime (Cholinesterase reactivator)
Oxytocin Atosiban
Paracetamol N-acetylcysteine, Methionine
Pentylenetetrazole (PTZ) Ethosuximide
Picrotoxin Diazepam
Tricyclic antidepressants (TCAs) Sodium bicarbonate
Valproic acid Carnitine
Warfarin Vitamin K
Wilson’s disease (copper) d-Penicillamine
Menke’s disease is due to deficiency of Copper
β-blockers Glucagon, Adrenaline

MONOCLONAL ANTIBODIES
Monoclonal antibodies Uses
Abciximab Anti-platelet
Alemtuzumab B-cell chronic lymphocytic leukemia
Gefitinib Tyrosine kinase activity/Non-small cell lung cancer
Gemtuzumab Acute myelogenous leukemia
Ibritumomab Rituximab-failed non-hodgkin’s lymphoma
Infiximab Rheumatoid arthritis/Crohn’s disease
Muromonab/Daclizumab/Basiliximab Allograft rejection reaction
Omalizumab Anti-IgE antibody/treatment of asthma
Palivizumab Respiratory syncytial virus
Rituximab (Mab Thera) Non-hodgkin’s lymphoma/Follicular-type
lymphoma
Transtuzumab (Herceptin) Metastatic breast cancer

pH
Parts of body pH
Skin 5.6
Blood 7.4
Saliva 6.8
Tissue / EVF 6.4
Tissue culture medium 5.7
Mouth 7.1
Stomach 1.5
Duodenum 4.0
Large intestine 6.9

BASIC HETEROCYCLIC RINGS

Sr. Heterocyclic ring Drug Name
No.
1. Aziridine Thio-TEPA

2. 1,2,3,4-Tetrazole Cefamandole,
Cefazolin

3. 1,2,5-Thiadiazole Timolol

4. 1,3,4-Thiadiazole Acetazolamide,
Cefazolin,
Sulphamethizole

5. Oxazolidine Paramethadione

6. Isoxazole Cloxacillin,
Isocarboxazide,
Sulfisoxazole

7. Oxazole Sulfamethoxazole

8. Isoxazolidine Cycloserine

9. Thiazole Thiabendazole,
Thiamine

10. Imidazole Azathioprine,

Histamine,
Pilocarpine,
Tolazoline

11. 2-Imidazoline Phenytoin

12. Imidazoline Nitrofurantoin,

Clonidine

13. Pyrazolidine Phenylbutazone,

Sulfinpyrazone
14. Pyrrole Pyrantel pamoate,
Atorvastatin

15. Furan Nitrofurantoin,

Prazosin,
Doxazosin,
Furosemide

16. Thiophene Cefoxitin

17. Morpholine Timolol,

Pramoxine,
Moclobemide

18. Pyrimidine Pyrimethamine,

Trimethoprim,
Sulfadiazine

19. Pyrazine Pyrazinamide,

Amiloride,
Sulfalene

20. Piperazine Prochlorperazine,

Fluphenazine,
Piperazine citrate,
Prazosin

21. Pyridine Nicotine,

Iproniazid,
Isoniazid

22. 1,4-Dihydropyridine Nifedipine,

Amlodipine,
Nicardipine,
Lacidipine,
Felodipine

23. Piperidine Thioridazine,

Meperidine,
Haloperidol

24. Purine Caffeine,

Theophylline,
Theobromine

25. Indole Indomethacin,

Reserpine,
Vincristine,
Vinblastine
26. Isoindoline Chlorthalidone

27. Catechol Adrenaline,

Noradrenaline

28. Pteridine Methotrexate,

Triamterene

29. Phthalazine Hydralazine

30. Benzimidazole Thiabendazole,

Albendazole,
Omeprazole
31. Quinazoline Methaqualone,
Prazosin

32. 1,2-Benzothiazine Piroxicam

33. 2H-Benzopyran Warfarin,

Dicoumarol

34. Benzofuran Griseofulvin

35. Quinoline Quinine,

Quinidine,
Chloroquine,
Primaquine

36. Isoquinoline Narcotine

Papaverine

37. 3H-1,4-Benzodiazepine Chlordizepoxide

38. 2H-1,4-Benzodizepine Diazepam,

Oxazepam (other BZDs)

39. 2H-1,5-Benzodiazepine Clobazam

40. Dibenzodiazepine Clozapine

41. Dibenz (b,f) (1,4) oxazepine Loxapine

42. Dibenzazepine Carbamazepine

43. Dibenzoxepin Doxepin

Dothiepin

44. 1,5-Benzothiazepine Diltiazem

45. Phenoxazine Dactinomycin

46. Phenothiazine Chlorpromazine,

Promethazine

47. Xanthene Propantheline

48. Thioxanthene Thiothixene,

Chlorprothixene

49. Acridine Quinacrine,

Tacrine,
Mepacrine

50. Anthracene Mithramycin,

Mitomycin

51. Anthracycline Doxorubicin

52. Phenanthrene Morphine,

Codeine,
Heroine

53. Cyclopentanoperhydro- All steroids

phenanthrene

IMPORTANT DRUG SYNTHESIS FOR GPAT

Sr. Drug Starting material Synthesis
No.
1. Acetazolamide 5-amino-2-mercapto-1,3,4- 5-amino-2-mercapto-1,3,4-
thiadiazole thiadiazole
2. Allopurinol Cyanoacetamide Cyanoacetamide + Formamide
HCl
3. Amodioquine Paracetamol Paracetamol + 7-chloro-4-amino
quinoline + Diethyl amine
4. Ascorbic acid Ribose Ribose
(Vit. C)
5. Aspirin Salicylic acid Salicylic acid + acetic anhydride
6. Atenolol Phenoxy acetamide Phenoxy acetamide +
Epichlorhydrine +
Isopropylamine
7. Benzocaine p-nitrotoluene p-nitrotoluene + Ethanol
8. Biotin (Vit. B7) Bisbenzyl succinic acid Bisbenzyl succinic acid
9. Bupivacaine α-picoline α-picoline + 2,6-dimethyl aniline
10. Chlorambucil Phenylbutyric acid Phenylbutyric acid +
Dichloroethyl amine
11. Chloramphenicol p-nitrobenzoic acid p-nitrobenzoic acid + 1,3-
 Propandiol
12. Chlorophenesin p-chlorophenol p-chlorophenol + p-
chloropropan-2,3-diol
13. Chloroquine 7-chloro-4-amino 7-chloro-4-amino quinoline + 1-
quinoline methyl-butyl + Diethyl amine
14. Chlorotrianisene Anisole Anisole + p-methoxy benzyl
chloride + Olefin
15. Chlorpheniramine p-chlorobenzyl chloride p-chlorobenzyl chloride +
Pyridine HCl + Copper chloride
16. Chlorpromazine 2-chloro phenothiazine 2-chloro phenothiazine + n-
propane + diethylamine
17. Chlorthalidone 3-amino-4- 3-amino-4-chlorobenzophenone-
chlorobenzophenone-2- 2-carboxylic acid + Diazonium
carboxylic acid chloride
18. Ciprofloxacin Cyclopropylamine Cyclopropylamine + 6-
fluoroquinoline + Piperazine
19. Clofazimine N-(4-chlorophenyl)-o- N-(4-chlorophenyl)-o-phenylene
phenylene diamine diamine
20. Clotrimazole Triphenylcyanide Triphenylcyanide + Imidazole
21. Cortisone Sigmasterol Sigmasterol
22. Cyclizine, Benzhydryl chloride Benzhydryl chloride + N-methyl-
Meclizine, Buclizine piperazine
23. Cyclophosphamide 1,3-oxophosphorine 1,3-oxophosphorine +
Dichloroethylamine
24. Cyproheptadine Phthalic anhydride Phthalic anhydride + Phenyl
acetic acid + 4-chloro-1-methyl
piperidine
25. Dapsone p-chloronitrobenzene p-chloronitrobenzene
26. Diazepam (other 2-amino-5-chloro 2-amino-5-chloro benzophenone
BZDs) benzophenone + Hydroxyl amine + Ethanol +
Chloroacetylchloride + Acetic
acid
27. Dienestrol p-hydroxy propiophenone p-hydroxy propiophenone +
Dienestrol dibenzoate + Ethanol
28. Diethyl carbamazine Piperazine Piperazine + Diethyl carbamoyl
chloride
29. Diethyl stilbesterol Desoxyanisoin Desoxyanisoin
30. Ethacrynic acid 2,3-dichloro phenoxy 2,3-dichloro phenoxy acetic acid
acetic acid
31. Ethambutol 2-amino-1-butanol 2-amino-1-butanol +
1,2-dichloroethane + NaOH
32. Ethinyl estradiol Estrone Estrone
33. Ethosuximide Butanone Butanone + Ethyl cyanoacetate
34. Guanethidine Perhydroazocine Perhydroazocine +
Chloroacetonitrile
35. Haloperidol p-chlorobenzophenone p-chlorobenzophenone + Butyric
chloride + Piperidine + Benzoyl
chloride
36. Ibuprofen Isobutylbenzyl chloride Isobutylbenzyl chloride +
 Propionic acid
37. Imipramine 10,11-Dihydro-5-H 10,11-dihydro-5-H dibenz,[b-f]
dibenz,[b-f] azepine azepine
38. Indomethacin p-anisidine p-anisidine + Indole acetic acid +
Benzoyl chloride
39. Isoniazid γ-picoline γ-picoline + 4-pyridine
carboxamide + Hydrazine
40. Isoxsuprine 4-hydroxy norepinephrine 4-hydroxy norepinephrine
41. Ketoconazole 2,4-dichlorophenyl 2,4-dichlorophenyl bromide +
bromide Glycerine
42. Lignocaine 2,6-xylidine 2,6-xylidine + Methanol +
Diethylamine
43. L-Thyroxine L-Tyrosine L-Tyrosine
44. Mebendazole 4-chloro benzophenone 4-chloro benzophenone + 5-
methyl thiouronium
45. Melphalan L-phenyl alanine L-phenyl alanine
46. Mephenamic acid o-chlorobenzoic acid o-chlorobenzoic acid + 2,3-
xylidine
47. Mepyramine Benzyl chloride Benzyl chloride + p-methoxy
benzyl chloride
48. Methotrexate 2-methyl pteridine 2-methyl pteridine + PABA +
glutamic acid
49. Metronidazole 2-methyl-5-nitroimidazole 2-methyl-5-nitroimidazole +
ethylene chlorhydrin
50. Nalidixic acid 2-methyl pyridine 2-methyl pyridine +
Diethylethoxymethylmalonate +
Ethyl iodide
51. Naproxen Naphthyl chloride Naphthyl chloride + Isopropyl
amine
52. Nicotine β-picoline β-picoline
53. Nifedipine o-nitro benzaldehyde o-nitro benzaldehyde + Methyl
acetoacetate + Ammonia
54. Nitrazepam 2-amino-5-nitro 2-amino-5-nitro benzophenone +
benzophenone Dioxane + Ammonia
55. Nitrofurantoin 1-amino hydantoin 1-amino hydantoin + 5-nitro-2-
furaldehyde
56. Norepinephrine / Catechol Catechol + α-Haloacetophenone
Epinephrine /
Isoprenaline
57. p-aminosalicylic 4-nitro-2-amino toluene 4-nitro-2-amino toluene
acid (PAS)
58. Pantothenic acid Formaldehyde Formaldehyde +
(Vit. B5) Isobutyraldehyde
59. Paracetamol p-amino phenol p-amino phenol + Acetic
anhydride
60. Phenobarbitone Benzyl chloride Benzyl chloride + Diethyloxalate
+ Sodium ethoxide
61. Phenoxybenzamine Phenol Phenol + Propylene oxide
62. Phenylbutazone Butamalonyl chloride Butamalonyl chloride
63. Phenytoin Benzophenone Benzophenone + potassium
cyanide
64. Pralidoxime α-picoline α-picoline
65. Primidone Phenylethylmalonamide Phenylethylmalonamide +
Formamide
66. Procainamide p-nitro benzyl chloride p-nitro benzyl chloride + Diethyl
amino ethylamine
67. Progesterone Diosgenin Diosgenin
68. Propranolol α-naphthol α-naphthol + Epichlorhydrine +
Isopropylamine
69. Pyrimethamine Ethyl propionate Ethyl propionate + p-
chlorophenylacetonitrile +
Isoamyl alcohol + Guanidine
70. Retinol (Vit. A) β-ionone β-ionone + Methyl vinyl lactone
71. Riboflavine D-ribose 3,4-dimethylaniline
72. Salbutamol 4-hydroxy-3-hydroxy ethyl 4-hydroxy-3-hydroxy ethyl
benzaldehyde benzaldehyde + Tertiary butyl
cyanate + Acetic acid
73. Spironolactone Eplerenone Eplerenone
74. Sulfacetamide Sulfanilamide Sulfanilamide + Acetic anhydride
75. Sulfalene 4-acetamido benzene 4-acetamido benzene sulfonyl
sulfonyl chloride chloride + 3-amino-2-methoxy
pyrazine
76. Sulfamethoxazole 3-amino-5-methyl- 3-amino-5-methyl-isoxazole + 4-
isoxazole acetamido benzene sulfonyl
chloride
77. Terfenadine Azacyclanol Azacyclanol + 4-(tertiary butyl-4-
chlorobutyrophenone)
78. Testosterone Sarsapogenin Sarsapogenin
79. Thiotepa Aziridine Aziridine + Trichloro phosphine
sulphide
80. Timolol 1,2,5-thiadiazole 3,4-dichloro-1,2,5-thiadiazole +
Morpholine
81. Tolbutamide p-toluene sulphonamide p-toluene sulphonamide + n-
butane
82. Triamterene 1,4,7-triamino pteridine 1,4,7-triamino pteridine
83. Trimethoprim 2,4-diamino pyrimidine 2,4-diamino pyrimidine + 3,4,5-
trimethoxy benzyl chloride