1

REVISION OF WHOLE COURSE

2
 GENERAL PHARMACOLOGY
 Pharmacology: The word “PHARMACOLOGY”
is derived from the Greek word “Pharmakos” means Medicine or Drug,
and “Logos” means Knowledge.
The science which deals with Study of Drugs.
 Pharmacokinetics:
 Pharmacodynamics:
 Pharmacognosy:
 Pharmacy:
 Toxicology:
 Therapeutics:
 Posology: Dose:
 Drug, Crude Drug, Pro-Drug, Prototype Drug.

3
 ROUTES OF DRUG ADMINISTRATION

Routes Of
Drug
Administration
Systemic Local

Parenteral
Inhalational
Enteral Parenteral Eye, Ear, Nose
Oral Intra-venous Mucous Membrane
Rectal Intra-muscular Skin, Throat, Mouth,
Sub-lingual. Sub- Urinary bladder
cutaneous Urethra
Intra-arterial Vagina
Intra-articular Intra-articular
Intra-thecal (Knee)
Intra-dermal. Intra-cardiac. 4
 Advantages / Merits
Disadvantages / Demerits
Sublingual route Inhalational route

5
 ABSORPTION OF DRUG
 Definition: Movement of the drug from the site of
administration into blood stream,
ultimately carried to the site of action.
 Non-ionized drugs are non-polar & lipid soluble,
hence easily diffusible and absorbed.
 Ionized drugs are polar & water soluble,
almost non-diffusible and not absorbed.
 Basic Process of Passage of Drug Across Cell Membrane:
Simple or Passive diffusion.
Facilitated diffusion.
Active transport.
Filtration.
 Factors affecting drug absorption:

6
 DISTRIBUTION OF DRUG
 Distribution: Movement of the drug from blood circulation to the
tissue is called distribution of drug.
 Re – Distribution: Movement of the drug from tissue to blood
circulation / to other tissues, is called redistribution of drug.

 Apparent Volume Of Distribution: The volume of fluid into which a

drug appears to be distributed (diluted) is called the Apparent Volume
of Distribution ( Vd ).
 Low Vd indicates that most of the drug is in the vascular compartment.
 High Vd indicates that most of the drug is in the extra vascular
compartment.

7
 BIOTRANSFORMATION OF DRUG

 Biotransformation: The series of chemical alterations of a

drug occur with in the body, by enzymatic activity.
 The metabolism of drug usually tends to convert less polar
(lipid soluble) substances to more polar (water soluble)
compounds.
 Why metabolism occur ?
1). For termination of Pharmacological Effects of drugs.
2). For the Excretion of lipid soluble substances.
 Microsomal, Non – microsomal, Microfloral Enzymes:
 Phase - I Reactions & Phase - II Reactions.
 Factors affecting drug metabolism.8
 Enzyme induction & Enzyme inhibition.
8
 DRUG ELIMINATION, EXCRETION & CLEARANCE

 Drug Elimination: is the irreversible loss of drug from

the body, it occurs by two processes:
1. Metabolism: The metabolism of drug usually tends to
convert less polar ( lipid soluble) substances to more
polar ( water soluble) compounds.
2. Excretion: is the removal of drugs from the body,
either as a metabolite or unchanged drug.

 Drug clearance: is defined as the volume of plasma

cleared of a drug over a specified time period.
 First-order kinetics:
 Zero-order kinetics:

9
 TERMS
 First pass effect / First-pass metabolism / is a drug
metabolism whereby the concentration of a drug is greatly reduced
before it reaches the systemic circulation.
 Bioavailability: The fraction of administered drug that reaches the
systemic circulation in a chemically unchanged form. form
 Half life of drug: Half life ( t ½ ) is the time taken for the drug
concentration to decline by 50% in the body.
 Therapeutic Index (TI) Ratio between the toxic dose (LD/50 )
and the therapeutic dose (ED/50) of a drug.
 Therapeutic window: (or Pharmaceutical window) is a ratio between
minimum effective concentrations (MEC) to the minimum toxic
concentration (MTC).
 Steady State Concentration (Css): when the rate of drug Elimination is
equal to the rate of drug Administration.

10
 DEFINATIONS

 Receptor: A macro molecule or a site on macro

molecule that binds & interacts with specific
substances is called Receptor.
 Ligand: A molecule that attaches selectively to a
particular
receptor is called Ligand.
 Affinity: Ability of a drug to bind the receptor is called
affinity.
 Intrinsic Activity: Ability of a drug to produce
Pharmacological effects, after binding to a receptor is
called Intrinsic activity.
 Tolerance: Failure of responsiveness to the usual dose
of a drug.
11
 DEFINATIONS
 Agonist: A Drug bind with receptor & initiate
Pharmacologic response. Have: High affinity for
receptor & High intrinsic activity.
 Antagonist: A drug binds with receptor but does not
initiate the action (interfere with binding of agonist).
Have: affinity for receptor & No intrinsic activity.
 Partial Agonist: A drug having same affinity for
receptor
as an agonist but less intrinsic activity than the full
agonist is called partial agonist. Partial agonist, in the
presence of full agonist act as
antagonist.
 Reverse / Inverse – Agonist: is an agent that binds to
the same receptor as an agonist but induces a 12
 DEFINATIONS
 Spare Receptors: When a drug produces maximum effect
by binding to some of the available receptors,
the remaining receptors are called Spare Receptors.
 Silent Receptors: If a drug binds to a component that not
shows any response, that component referred as
Silent Receptor. e.g. Drug binding to Albumin.
 Stimulation of Adenylyl cyclase:…Cyclic AMP (cAMP).
 Stimulation of Phospholipase - C: IP3, DAG.
 Potency: It is the concentration (EC50) or dose (ED50) of a
drug required to produce 50% of that drug's maximal effect.
 Efficacy: (Emax) is the maximum effect which can be
expected from the drug.
13
 DEFINATIONS
 Summation: When two or more drugs are given in
combination, resultant effect is the algebraic sum of their
individual actions.
 Synergism: Two or more drugs may work together against
one target, their net effect is greater than the
sum of their individual effects.
 Potentiaion: When one drug has no apparent action by itself
on one system, but it increases the effects of another drug. So
that their combined effect is greater than the sum of the effects
of each drugs used alone.
 Hypersensitivity: If a drug produce its usual effects at
unexpectedly low dosage, the condition is called
hypersensitivity.
 Idiosyncrasy: The unusual & abnormal reaction of an
individual to a drug due to genetic abnormality. 14
 CLASSIFICATION OF SYMPATHOMIMETICS
1. According to Chemical Nature:

 Catecholamines:
Adrenaline, Noradrenaline, Dopamine,
Dobutamine, Isoproterenol, Fenoldopam.

 Non-Catecholamines:
Phenylepherine, Methoxiamine, Medodrine,
Zylometazoline, Oxymetazoline, Ephidrine,
Amphetamine, Methamphatamine, Pemoline,
Phenmetrazine, Methylphenidate, Modafinil .
 CLASSIFICATION OF SYMPATHOMIMETICS
2. According to Receptor Sensitivity:
Alpha 1 Selective: Phenylephrine, Methoxamine, Metaraminol
Alpha 2 Selective: Clonidine, Methyldopa, Guanfacine,
Apraclonidine. Brimonidine Dexmedetomidine, Tizanidine.
Beta 1 Selective: Dobutamine.
Beta 2 Selective: Salbutamol, Terbutaline, Isoetharine,
Ritodrine, Fenoterol, Rimiterol, Salmeterol,
Indacaterol, Olodaterol, Vilanterol.
Beta 3 Selective: Mirabegron.
Beta 1 and Beta 2: Isoproterol, Adrenaline, Orciprenaline.
Alpha and Beta: Adrenaline, Dopamine, Ephedrine.
Amphetamine, Methylamphatamine,
Pseudoephedrine, Droxidopa.
Dopaminergic Agonist: Dopamine, Bromocriptine, Fenoldopam.
Dopamine reuptake inhibitors:. Armodafinil, Modafinil

16
 CLASSIFICATION Of SYMPATHOMIMETICS
3. According to Mode of Action:

Direct acting:
Adrenaline Noradrenaline Indirect acting:
Dopamine
Midodrine
Phenylephrine
Methoxamine
Amphetamine
Clonidine
Xylometazoline
Ritodrine
Oxymetazoline
Methamphetamine
Isoproterenol Dobutamine Modafinil
Phenmetrazine
Methylphenidate
Tyramine
Atomoxetine
Direct & Indirect acting:
Ephedrine
Pseudoephedrine
Phenylpropanolamine
17
 ADRENALINE ( EPINEPHRINE )

Indications:
 Acute bronchial asthma, Allergy e.g. Anaphylactic shock,
As nasal decongestant,
 With local anesthetic for prolong action.
 Applied locally to stop bleeding ( local haemostatic ).
 Glaucoma, to reduce intraocular pressure.
 By intra cardiac injection in cardiac arrest.
 In emergency of hypotension.
Side effects:
 Anxiety, Restlessness, Headache, Tremor, Tachycardia.
 Tissue necrosis (due to vasoconstriction)
 Cardiac dysrhythmias (when used I / V).
Contraindications:
 Coronary disease, Hypertension, Hyperthyroidism.
 Not used at the base of finger, ear-lobe & penis. 18
 INDIRECT ACTING ADRENERGIC AGONIST

AMPHETAMINE:
 Mechanism of Action: Acts by releasing Norepinephrine.
 Indications:
 As a CNS stimulant in narcotic poisoning & in depression.
 To relieve mental and physical fatigue.
 In obesity, to reduce weight
 As a nasal decongestant.
COCAINE:
 Mode of Action: Peripheral sympathomimetic action by

inhibiting reuptake of norepinephrine.

EPHEDRINE:
 Indirect: Releases Noradrenaline,
 Direct : Stimulate α and ß receptors.
19
 CLASSIFICATION OF ALPHA BLOCKERS
(a). Selective α-1 receptor blockers:
Prazosin, Terazosin, Doxazosin, Alfuzosin,Rawolsin, Tamsulosin,
Bunazosin, Indoramin, Urapidine, Silodosin,
Phenoxybenzamine (Irreversible antagonist),
(b). Selective α-2 receptor blockers:Yohimbine,Tolazoline.
(c). Non- Selective α - receptor blockers: Phentolamine.
(D). Mixed antagonists(α & β bockers): Carvedilol, Labetalol.
Indications: Hypertension, Peripheral vascular disease.
Phenoxybenzamine: Pheochromocytoma.
Tamsulosin: Benign prostatic hyperplasia (BPH).
Phentolamine: Local anesthesia,
Adverse effects: First dose phenomenon Orthostatic hypotension & reflex
tachycardia.

20
 CLASSIFICATION OF BETA - BLOCKERS

Selective β1 - blockers: Non-selective β- blockers:

 Atenolol (β1 & β2):
 Acebutolol
 Carteolol, Carvedilol
 Labetalol , Nadolol
 Betaxolol  Penbutolol, Pindolol
 Bisoprolol  Propranolol, Sotalol
 Celiprolol  Oxprenolol, Timolol.
 Esmolol  Levobunolol.
 Metoprolol
 Nebivolol
α & β blockers:
Selective β2 - blockers:  Carvedilol, Labetalol,
 Butoxamine.  Medroxalol,Bucindolol.

21
 BETA-β BLOCKERS
Propranolol
 Cardiac Therapeutic Uses:
Hypertension, Angina pectoris, Myocardial infarction,
Supraventricular tachycardia.
 Extra-Cardiac Therapeutic Uses: Glaucoma, Migraine,
Hyperthyroidism, Cirrhosis.
 Adverse Effects: Arrhythmias, Sexual impairment,
Bronchoconstriction, Decreased glucagon secretion,
Withdrawal syndrome,
Masks the features of hypoglycemia,
Mask the signs of developing hyperthyroidism.
 Contraindications: Bradycardia, Asthma, Diabetes.
Peripheral vascular insufficiency.
Not used with calcium channel blocker (Verapamil).
22
 PARASYMPATHOMIMETIC DRUGS
DIRECT ACTING INDIRECT ACTING
Muscarinic Agoni Reversible Acting:
Acetylcholine Neostigmine,Physostigmine,
Methacholine Pyridostigmine, Edrophonium
Carbachol Tacrine, Donepezil
Bethanechol Galantamine, Rivastigmine.
Cevimeline
Pilocarpine (b) Irreversible Acting:
Muscarine Ecothiophate, Isoflurophate
Parathion, Malathion, Soman,
Oxotremorine. Sarin, Tabun, Diazinon. Paraoxon
Nicotinic Agonists: Maloxon.
Nicotine
Lobeline
Dimethyl phenyl
Piprazinium(DMPP). 23
 PARASYMPATHOMIMETICS
MECHANISM OF ACTION
 Direct acting: Bind & activate muscarinic or nicotinic receptors.
 Indirect-acting: Inhibiting acetylcholinesterase.

24
 PARASYMPATHOMIMETICS
INDICATIONS
 Bethanechol: Atonic bladder, postpartum or postoperative
urinary retention, reflux esophagitis. Antidote for Atropine.
 Carbachol
Car used for Glaucoma.
 Neostigmine: Myasthenia gravis, Paralytic ileus.
Urinary retention, Glaucoma. Antidote for Tubocurarine.
 Physostigmine: Paralytic ileus, Urinary retention, Glaucoma.
Antidote for anti-cholinergic drugs (Atropine) & tricyclic
antidepressants.
 Pyridostigmine: Used in chronic management of
myasthenia gravis. Antidote for Tubocurarine.
 Edrophonium: Used for diagnosis of Myasthenia Gravis.
 Ecothiophate: Eye drops.
 Pralidoxime: Reactivation of Acetyl cholinesterase. 25
 PARASYMPATHOMIMETICS
INDICATIONS
 Treatment of Myasthenia Gravis:
Anticholinesterases: Neostigmine, Pyridostigmine,
Physostigmine, Ambenonium, Edrophonium, Echothiophate.
Steroids & Immunosuppressants: Prednisone, Methotrexate.
Others: Ephedrine, Potassium salts.

 Treatment of Organophosphorus poisoning:

Atropine, Pralidoxime, Diazepam.

26
 ANTI MUSCARINIC AGENTS
CLASSIFICATION
(a) Natural: Atropine, Scopolamine (Hyoscine)
(b) Semi-synthetic & Synthetic:
Quaternary amines: Anisotropine, Clidinium,
Glycopyrrolate, Isoproamide, Mepenzolate,
Methantheline, Methscopolamine, Oxyphenonium,
Propantheline, Tridihexethyl, Trospium.
Tertiary amines: Atropine, Darifenacin, Dicyclomine,
Oxybutanin, Scopolamine Oxyphencyclimine, Propiverine,
Solifenacin,Tolteridone. Fesoterodine, Tropicamide,
Pirenzepine,Homatropine,Aclidinium, Umeclidinium.

(c).Many Anti-histaminic, Anti-psychotic, & Anti-depressant

Imipramine, drugs have significant anti-muscarinic effects.
27
 ANTIMUSCARINIC AGENTS
CLASSIFICATION (on the basis of uses):
 Mydriatics: Atropine, Homatropine, Glycopyrrolate,Tropicamide.
 Antispasmodics / Motion Sickness :Scopolamine (Hyoscine).
 Bronchodilators, COPD: Ipratropium, Tiotropium. Aclidinium.
 Act on GIT: Pirenzepine, Telenzepine, Dicyclomine.
 Anti Parkinsonism: Benztropine,
 Involuntary voiding:
voiding Oxybutynin, Trospium, Darifenacin.
 Cholinergic Poisoning: Atropine, Pralidoxime.

28
 ANTIMUSCARINIC AGENTS
Atropine
Indications: Contraindications:
Mydriasis,
Bradycardia Narrow angle glaucoma.
Antipsychotic, Prostatic hyperplasia.
Urinary urgency Peptic ulcer.
Motion sickness CCF with tachycardia.
Traveler’s diarrhea
Biliary or renal colic Adverse Effects: Mydriasis,
Parkinson’s disease Blurred vision, Cycloplegia,
Urinary incontinence Sandy eyes,Tachycardia,
Cholinergic poisoning
Dry mouth, Constipation,
Pre-anesthetic medication
Organophosphorous poisons. Urinary retention,
Elevated body temperature,
Dry skin, Confusion,
Hallucination, Depression
Respiratory and Circulatory
collapse, Death. 29
 NEUROMUSCULAR BLOCKERS
Classification
 Depolarizers: Succinylcholine,
 Nondepolarizer: Tubocurarine, Metocurine, Atracurium, Cisatracurium, Doxacurium,
Mivacurium. Pancuronium, Pipecuronium, Rocuronium, Vecuronium, Gallamine.
 Long acting: Tubocurarine, Metocurine, Pancuronium,
Doxacurium, Pipecuronium.
 Intermediate: Atracurium, Cisatracurium, Rocuronium,
Vecuronium.
 Short-acting: Mivacurium.

Indications: Used as muscle relaxant during surgery or setting of

Fractures, dislocations. Endotracheal Intubation, Tetanus.
Contraindications: Asthma, Myasthenia gravis,
Hypersensitivity, Gallmaine in Pregnancy.

30
 ANTI-HYPERTENSIVE DRUGS

 Diuretics:
 Sympathoplegics:
 Centrally acting sympathoplegics:
 Ganglion blockers:
 Adrenergic neuron blockers:
 Alpha blockers:
 Beta blockers:
 Angiotensin system blockers:
 Calcium channel blockers:
 Direct vasodilators:
31
 ANTI HYPERTENSIVE DRUGS
CENTRALLY ACTING SYMPATHOPLEGIC DRUGS
 Methyldopa: M.O.A: Methyldopa converted to alpha-
methyldopamine and alpha-methyl-norepinephrine (stored in
vesicle of axon). Instead of nor-epinephrine, alpha-methyl-
norepinephrine is released. It stimulate alpha-2 receptors in
brain, inhibit adrenergic outflow.

 Clonidine:Stimulate central presynaptic alpha-2 receptors.

 Reserpine: Deplete of noradrenaline stores in sympathetic

nerve endings and in peripheral tissues resulting in
decrease sympathetic tone in blood vessels.

32
 CALCIUM CHANNEL BLOCKERS
Classification

DIHYDROPYRIDINE NON- DIHYDROPYRIDINE

1st generation: Nifedipine Diphenyl alkyl amines:
2nd generation: Amlodipine
Felodipine, Isradipine, Verapamil

Nicardipine, Nisoldipine, Benzodiazepine:

Diltiazem
Much greater
Nimodipine, affinity .
Clevidipine Significant effect
for Vascular calcium on both
channels than the channel Cardiac & Vascular
in the Heart Smooth muscles
 CALCIUM CHANNEL BLOCKERS
Indications
 Cardiac Indications: Hypertension, hypertrophic
cardiomyopathy, angina pectoris, supraventricular
tachycardia, atrial flutter & fibrillation.
 Extra Cardiac Indications: Raynaud's Phenomenon,
migraine headache, cerebral vasospasm stroke,
premature Labor (Tocolytic).
 Nicardipine / Nimodipine selective for cerebral blood vessels.
 Side Effects: Headache, Flushing and Peripheral Edema more
common with Dihydropyridine.
Bradycardia, heart block and heart failure more
common with Verapamil.
Constipation – more common with Verapamil
34
35
 RENIN - ANGIOTENSIN SYSTEM
BLOCKERS
 Angiotensin Converting  Angiotensin Receptor
Enzyme (ACE) Inhibitors Blockers (ARB)
Captopril Losartan
Lisinopril Valsartan
Enalapril Candesartan
Fosinopril Eprosartan
Moexipril
Irbesartan
Perindopril
Telmisartan
Quinapril
Ramipril Olmesartan
Benazepril
Aldosterone Receptor Blockers:
Trandolapril Spironolactone, Eplerenone

Renin Antagonist : Aliskiren, Beta blockers 36

 Angiotensin Converting Enzyme (ACE) Inhibitors
Mechanism of Action
 ACE Inhibitors: Inhibit the Angiotensin converting enzyme
Peptidyl dipeptidase, that hydrolysis the angiotensin – I to
angiotensin –II. Prevent metabolism of bradykinin.
 ARB: Competitive antagonist to angiotensin – II.
They have high affinity for the AT-1 receptor.
 Clinical Uses: Hypertension, Congestive heart failure,
Left ventricle dysfunction after a myocardial infarction,
Diabetic nephropathy.
 Adverse effects: Sever hypotension, acute renal failure,
hyperkalemia, dry cough, angioedema, altered taste sense,
skin rashes, drug fever.
 Contraindications: Pregnancy, One kidney, Unilateral /
Bilateral renal artery disease. 37
 VASODILATORS
Oral – Vasodilators: Hydralazine, Minoxidil.
Parentral – Vasodilators: Sodium Nitroprusside, Amyl nitrite,
Nitroglycerine, Diazoxide, Fenoldopam.
Hydralazine: Dilates arteriole, but not veins.
Minoxidil: Dilate arterioles, but not veins.
Sodium Nitroprusside: Dilates both arterial and venous vessels.
Fenoldopam: arteriolar direct dilator.
Diazoxide: act on arterioles. Chemically similar to thiazide
diuretics, but has no diuretic activity
Side effect:
Minoxidil: Hypertrichosis (so used for baldness).
Nitroprusside: Accumulation of cyanide (treatment by sodium
thiosulfate). Fenoldopam: increase the intra ocular pressure
Diazoxide: Hyperglycemia (inhibit release of insulin).
. 38
 TREATMENT OF ANGINA PECTORIS

 Nitrates:
 Amyl nitrite (extremely volatile liquid).
 Nitroglycerine (moderately volatile liquid).
 Isosorbide dinitrate (solid).
 Beta blockers: Atenolol, Metoprolol, Propranolol.
 Calcium channel blockers: Diltiazem, Verapamil.
 Anti-platelet drugs: Aspirin, Ticlodipine.
 Newer Anti-anginal drugs: Ranolazine, Trimetazidine,
Allopurinol, Ivabradine, Fasudil.

39
 CCF Congestive Cardiac Failure
Drugs With Positive Inotropic Effects:
 Cardiac Glycosides: Digoxin, Digitoxin, Ouabain.
 Bipyridines / Phosphodiesterase Inhibitors:

Milrinone, Inamrinone, Levosimendan.

 Beta-Adrenergic Agonists: Dobutamine, Dopamine.

Drugs Without Positive Inotropic Effects:

 Diuretics: Thiazide, Frusemide, Spironolactone, Eplerenone.
 Angiotensin antagonists: Captopril, Losartan.
 β-blockers: Bisoprolol, Metoprolol.
 Vasodilators: Nitrates, Hydralazine. Nesiritide, Sacubitril,

Carperitide, Ularitide, Bosentan, Tezosentan, Serelaxin.

 Other Drugs: Cimaglermin, Liraglutide, Empagliflozin.

40
 CCF Congestive Cardiac Failure
 Digitalis: Mechanism of Action:
 Competitively inhibit Na+ / K+/ ATPase (sodium pump)
 Vagal stimulation, slowing S.A node & AV conduction.

 Side Effect: chromatopsia (objects appear yellow).

 Dobutamine: It is selective beta -1 agonist.
 Inamrinone / Milrinone: Inhibit Phosphodiesterase.

41
 Singh-Vaughan Williams Classification
Class Mechanism Action Notes
Can abolish
Na+ channel Change the slope tachyarrhythm
I
blocker of phase 0 ia caused by
reentry circuit.
Can indirectly
↓ heart rate alter K+ and
II β blocker and conduction Ca++
velocity conductance.
↑action
potential
K+ channel duration or Inhibit reentry
III
blocker refractory period tachycardia
(ERP). Delay
repolarization
Ca++ Slowing the rate ↓ conduction
IV channel of rise in phase 4 velocity in 42SA
 Singh-Vaughan Williams Classification
Class Mecha Drugs
ni
IA Na+ Quinidine, Procainamide, Disopyramide.
IB channe Lidocaine, Mexiletine, Tocainide,
lblocke Phenytoin.
r
IC Encainide, Flecainide, Propafenone,
Moricizine.
II β Propanolol, Esmolol, Acebutolol, l –
blocker Sotalol.
III K+ Amiodarone, Dronedarone, Vernakalant,
blocker d ,l -Sotalol, Dofetilide, Ibutilide.
IV Ca Verapamil, Diltiazem.
block
Miscella Adenosine, Digitalis, Magnesium,
 CLASSIFICATION OF DIURETICS

Loop diuretics Thiazide diuretics Potassium

 Furosemide  Hydrochlorothiazide sparing diuretics
 Torsemide  Bendroflumethiazide Spironolactone
 Bumetanide  Chlorothiazide Eplerenone
 Ethacrynic Acid.  Chlorthalidone Amiloride
 Hydroflumethiazide Triamterene.
 Indapamide
Carbonic
 Methyclothiazide
anhydrase Osmotic diuretics
 Metolazone Mannitol
inhibitors
Acetazolamide  Polythiazide Glucose
Dorzolamide  Quinethazone Urea.
Brinzolamide.  Trichlormethiazide.

44
 LOOP DIURETICS
Furosemide, Bumetanide, Torsemide, Ethacrynic
Acid
Mode of action:
 Selectively inhibit the
Na+ / K+ / 2Cl- transport
system in thick ascending limb.
 By inhibiting this transporter,
reduces reabsorption of NaCl.
Indications:
 Acute pulmonary and other edema.
 Acute renal failure, Acute Hypercalcemia, Acute Hyperkalemia.
 Side Effects: Hypotension, Hypovolemia, Hyponatremia.
 Hypokalemia, Hypomagnesemia, Metabolic alkalosis, Hyperuricemia, Allergic
reactions, Ototoxicity reversible.
 Contraindication: hepatic cirrhosis, borderline renal failure, heart failure.
 THIAZIDE DIURETICS
Mode of action:
 Thiazides inhibit NaCl reabsorption
in the distal convoluted tubules by
blocking Na+/Cl- transporter.
 NaCl drag the water for excretion.
Indications:
 Hypertension, Heart failure,
 Nephrolithiasis due to idiopathic hypercalciurea.
 Nephrogenic Diabetes Insipidus (anti-diuretics action).
Side Effects: Hypokalemia, Hyponatremia,
Hyperuricemia, Metabolic alkalosis, Volume depletion,
Hyperglycemia, due to impaired release of insulin.
Atherosclerosis, due to hyperlipidemia, impotence.
 Contraindications: Hepatic cirrhosis, CCF.
 CARBONIC ANHYDRASE INHIBITOR DIURETICS
Acetazolamide, Dorzolamide, Brinzolamide
Mode of action:
 By inhibiting carbonic anhydrase,
decrease the reabsorption
of NaHCO3 in proximal tubule
(45%) causes diuresis.
Indications: Mountain sickness,
 Glaucoma,, Epilepsy, Metabolic alkalosis, CSF leakage,
Hyperphosphatemia.
Side effects: Hyperchloremic Metabolic Acidosis:
 Renal stone formation: (due to phosphaturia & hypercalciurea).
 Renal Potassium Wasting, Drowsiness, Hypersensitivity
reaction: (fever, rashes, nephritis, bone marrow suppression).
 Contraindications: Hepatic cirrhosis.
47
 POTASSIUM SPARING DIURETICS

Spironolactone, Eplerenone Mode of actions:

 Acts as competitive antagonist to Aldosterone receptors and
reduce Na+ reabsorption in the collecting tubules.
Result in:
 Increased sodium Na+ loss.
 increased chloride Cl- loss.
 Decreased potassium K+ loss.
Amiloride, Triamterene Mode of action:
 They directly interfere with Na+ entry through the sodium-
selective ion channels on collecting tubules.
 Inhibit K+ secretion and excretion.

48
 POTASSIUM SPARING DIURETICS
Spironolactone, Eplerenone
Amiloride, Triamterene
Indications:
 Cirrhosis of liver, Cardiac failure,
 Nephrotic syndrome.
 Primary & Secondary Aldosteronism.
Toxicities:
 Hyperkalemia. Hyperchloremic Metabolic Acidosis.
 Kidney Stones.
 Gynecomastia (Spironolactone), Impotence.
 Benign prostatic hyperplasia.
Contraindications:
 Chronic renal failure in fatal hyperkalemia.

49
 AGENTS THAT ENHANCE WATER EXCRETION
Osmotic Diuretics MANNITOL
Mode of action:
Limits the reabsorption of water by osmotic force at proximal

tubule & descending loop of Henle.

Also oppose the action of ADH in collecting tubule.
Thus reducing Na+ and water reabsorption, but eventually

leading to hypernatremia.
Indications: To increase urine volume, Prevent anuria.
Reduction of Intracranial pressure.
Reduction of Intraocular pressure.

Side Effects:
Extra cellular volume expansion, Severe dehydration,
Hyperkalemia, Hyponatremia, Hypernatremia:

Contraindications: Congestive Cardiac Failure.

50
 BLOOD – COAGULANTS
Drugs used for bleeding disorders
 Vitamin-K, Plasma fraction, Desmopressin acetate.
 FEIBA (Factor Eight Inhibitor Bypassing Activity),
 Novoseven, Cryoprecipitate.
 Fibrinolytic –Inhibitors: Amino caproic acid.
Tranexamic acid.
 Serine Protease Inhibitors: Aprotinin.
 Activated Protein – C: Drotrecogin alfa.

 Amino Caproic acid: It competitively inhibits plasminogen activation.

 Aprotinin: Inhibit fibrinolysis by free plasmin.
The inhibition of kallikrein inhibits formation of factor XIIa. This
inhibits the intrinsic pathway of coagulation and fibrinolysis.

51
 CLASSIFICATION OF ANTICOAGULANTS
Drugs Used Prevention of Blood Coagulation
1. Indirect Thrombin Inhibitors:
 High -Molecular –Weight Heparin (HMWH) /

Un-Fractionated Heparin (UFH).

 Low-Molecular –weight Heparin (LMWH):
Enoxaparin, Dalteparin, Tinzaparin, Danaparoid.
 Fondaparinux.

2. Direct Thrombin Inhibitors:

 Parenteral Direct Thrombin Inhibitors:

Hirudin, Lepirudin, Bivalirudin, Argatroban.

 Oral Direct Thrombin Inhibitors:
Dabigatran, Melagatran, Ximelagatran.
52
 CLASSIFICATION OF ANTICOAGULANTS
Drugs Used Prevention of Blood Coagulation
3. Oral Anticoagulants: Warfarin, Dicoumarol,
Acenocoumarol, Phenprocoumon, Anisindione .
4. Platelet Aggregation Inhibitors: Aspirin, Ticlopidine,
Clopidogrel, Prasugrel, Dipyridamole, Cilostazol.
Ticagrelor, Vorapaxar, Cangrelor, Abciximab,
Eptifibatide, Tirofiban.
5. Fibrinolytic / Thrombolytic Drugs: Streptokinase,
Urokinase, Alteplase, Reteplase, Tenecteplase,
Anistreplase.
6. Factor Xa – Inhibitors:
Apixaban, Rivaroxaban, Edoxaban, Betrixaban.
53
 ANTICOAGULANTS
Indirect Thrombin Inhibitors HEPARIN
Mechanism of action:
Heparin enhance the Antithrombin’s action, (inactivation of
factor Xa).
Indications:
 Deep Venous Thrombosis (DVT), Pulmonary embolism.
 Prevent clotting in open heart surgery & hemodialysis.
 For primary prophylaxis of thromboembolism after
acute myocardial infraction.
Side Effects: Bleeding, Alopecia, Osteoporosis,
Spontaneous fractures, Mineral corticoid deficiency,
Hypersensitivity reactions (urticaria, anaphylactic ).

Antidote: Protamine Sulphate (by slow I/V).

 ANTICOAGULANTS
Direct Thrombin Inhibitors
 They exert their anticoagulant effect by directly binding
to the active site of thrombin.

 Parenteral Direct Thrombin Inhibitors:

Hirudin, Lepirudin, Bivalirudin, Argatroban.

 Oral Direct Thrombin Inhibitors:

Melagatran, Dabigatran, Ximelagatran.

 Hirudin is irreversible thrombin inhibitor,

obtained from leech saliva.

55
 ORAL ANTICOAGULANTS
WARFARIN
Mechanism of action:
 Warfarin is a vitamin K antagonist in liver.
 Inhibit epoxide reductase.

 Ultimately decreases the synthesis of

vitamin K-dependent clotting factors IIa, VIIa, IXa, Xa.

 Warfarin has no effect on previously formed thrombus .
Antidote: Vitamin K.
Adverse Effect: Bleeding.
 Serious birth defect like abnormal bone formation.
 Rarely, infarction of breast, fatty tissue, intestine, extremities.
 Cutaneous necrosis with reduced activity of protein – C.
 FIBRINOLYTIC / THROMBOLYTIC DRUGS

They activate conversion of plasminogen to plasmin,

that hydrolyzes fibrin and thus dissolve the clot.

 Streptokinase.
 Urokinase.
 Alteplase.
 Reteplase.
 Tenecteplase.
 Anistreplase.
 PLATELET AGGREGATION INHIBITORS

 ASPIRIN
 TICLOPIDINE
 CLOPIDOGREL
 PRASUGREL
 DIPYRIDAMOLE
 CILOSTAZOL
 PLATELET AGGREGATION INHIBITORS

 ASPIRIN: M.O.A: Blocks prostaglandin thromboxane - A2

synthesis, by irreversible acetylation & inhibition of
cyclooxygenase. Result in suppression of platelet aggregation
for life of platelet (7-10 days).
 Ticlopidine, Clopidogrel, Prasugrel, Dopidogrel:
M.O.A: Reduce platelet aggregation by irreversibly blocking the ADP
receptors on Platelets.
Uses To prevent stroke of Transient Ischemic Attack (TIA), or
Thrombotic stroke.
 Approved for unstable angina and acute myocardial infarction in
combination with Aspirin.
 Cilostazol is newer phosphodiesterase inhibitor that promote
vasodilation & inhibition of platelet aggregation.
 Used for Intermittent claudication.
59
 DRUDS USED IN ANAEMIAS
 Oral iron: Ferrous sulphate, Ferrous gluconate.
Ferrous fumarate, Carbonyl iron.

 Parenteral iron: Iron Dextran, Iron Sucrose,

 Sodium Ferric gluconate complex,.
 DRUGS FOR HYPERLIPIDEMIA
 HMG-CoA Reductase Inhibitors: (Statins):
Simvastatin, Lovastatin, Atorvastatin, Fluvastatin,
Rosuvastatin, Pravastatin. Pitavastatin.
 Nicotinic Acid: Niacin.
 Fibric Acid Derivatives (Fibrates):
Gemfibrozil, Fenofibrate, Bezafibrate.
 Bile Acid-Binding Resins: (Resins):
Colestipol, Cholestyramine, Colesevelam.
 Inhibitors Of Intestinal Sterol Absorption: Ezetimibe.
 Inhibition Of Microsomal Triglyceride Transfer Protein:
Lomitapide.
 PCSK9 inhibition: Evolocumab, Alirocumab.
 DRUGS FOR HYPERLIPIDEMIA
STATINS: Competitively Inhibition of HMG-CoA reductase.
( which is used for the first step in cholesterol biosynthesis ).

NIACIN: Strongly inhibits lipolysis in adipose tissue -----

( Lipolysis is primary producer of circulating free fatty acids ).
Toxicity: Pruritus, rashes, dry skin, acanthosis nigricans.

Gemfibrozil, Fenofibrate, Bezafibrate: Decreases plasma

triacylglycerol levels by stimulating lipoprotein-lipase activity.

Colestipol, Cholestyramine, Colesevelam: Resins bind with

bile acids in small intestine, decrease reabsorption of bile acids,
excretion of bile acids in the feces is increased up to tenfold.
Ezetimibe: selectively inhibits intestinal absorption of cholesterol.

62
 CLASSIFICATION OF ANTIHISTAMINE
H - 1 Blockers
First Generation: Second Generation:
 Carbinoxamine, Fexofenadine,
 Diphenhydramine, Loratadine,
Desloratadine,
 Dimenhydrinate, Cetirizine,
 Clemastine.Hydroxyzine, Astemizole,
 Cyclizine, Meclizine, Buclizine, Terfenadine,
 Chlorpheniramine, Azelastine,
Epinastine,
 Brompheniramine,
Levocabastine,
 Promethazine, Hydroxyzine, Levocetirizine,
 Ketotifen, Cyproheptadine, Olopatadine.
 Doxylamine, Phenindamine, Diphenhydramine
 Triprolidine. Promethazine
63
 NSAIDs
 Non-Selective Cox Inhibitors:
Aspirin, Sodium salicylate, Sulfasalazine.
Meclofenamic acid, Mefenamic acid, Flufenamic acid, Ibuprofen, Fenoprofen,
Flurbiprofen, Sulindac, Indomethacin, Phenylbutazone.
Diclofenac, Ketoprofen, Oxaprozin,
Naproxen. Paracetamol, Piroxicam,
Tolmetin. Diflunisal, Ketorolac, Olsalazine, Salsalate,
Nabumetone, Azapropazone. Carprofen, Meclofenamate, Tenoxicam.
 Selective Cox Inhibitors:
Celecoxib, Etodolac, Meloxicam.
(Rofecoxib & Valdecoxib are withdrawal due to side effects).

64
 ASPIRIN
 Mode of Action:
 It is a non- selective inhibitor of both Cox-isoforms.
 Irreversibly inhibit platelet COX (lasts for 8-10 days).
 Main Actions:
 Anti-inflammatory.
 Analgesic.
 Anti-pyretic.
 Anti-rheumatic.
 Anti-thrombotic.
 Anti-gout (Uricosuric).
 Indications: Analgesic, Anti – inflammation, Anti – pyretic,
Anti-gout, Unstable angina, Decreases the Transient Ischemic
Attacks, Coronary artery thrombosis, myocardial infarction,
Dysmenorrhea. Close the ductus arteriosus
 Contraindications: Reye’s syndrome.
65
 DRUGS FOR GOUT
 Allopurinol.
 Colchicine.
 Febuxostat.
 Pegloticase.
 Probenecid (Uricosuric).
 Lesinurad (Uricosuric).
 Sulfinpyrazone (Uricosuric).
 Aspirin, Indomethacin, Diclofenac (NSAIDs).
 Prednisone, Triamcinolone (Glucocorticoid).
 Anakinra, Canakinumab, Rilonacept (Interleukin-inhibitors).
 Losartan (Angiotensin Receptor Blocker),
 Fenofibrate (lipid lowering drug).
66
 ANTI - GOUT DRUGS
 Allopurinol prevents synthesis of uric acid, by
inhibiting the enzyme “xanthine oxidase”,
 Febuxostat : same mechanism.
 Colchicine: It has anti-inflammatory effect.
Inhibits the leukocytes migration and Phagocytosis.
 Probenecid, Lesinurad, Sulfinpyrazone: Inhibit the
reabsorption of uric acid in the proximal tubule.
They are uricosuric agents.
 Pegloticase: catalyzing uric acid to the water-soluble
purine metabolite allantoin.
 Anakinra, Canakinumab, Rilonacept: Interleukin-1 inhibitors.
 Allopurinol Used as an antiprotozoal agent.
 Allopurinol bound to lens, resulting in cataract.
 Probenecid causes Nephrotic – syndrome. 67
 DRUGS FOR MIGRAINE

1. Drugs For Acute Attack:

 Triptans = Almotriptan, Sumatriptan, Naratriptan,
Rizatriptan, Eletriptan, Frovatriptan, Zolmitriptan.
 Ergot derivatives: Ergotamine, Dihydroergotamine.
 NSAIDs: Aspirin.
2. Drugs For Prophylaxis:
 Ergot derivatives: Methysergide.
 Beta-blockers:…. Propranolol.
 Ca++ Blockers:…. Verapamil, Nimodipine.
 Tricyclic Anti-depressants: Amitriptyline, Nortriptyline.
 Sumatriptan: Serotonin agonist, acting at 5-HT1D receptors.
 Ergotamine: Vasoconstriction of cranial arteries.
Gangrene due to over dose.
 DRUGS FOR RHEUMATOID ARTHRITIS (RA)
 NSAIDs: Aspirin, Ibuprofen, Diclofenac & others.
 Corticosteroids: Cortisol, Prednisolone & others.
 Immunosuppressant: Azathioprine, Cyclosporine.
 Disease Modifying Anti-Rheumatic Drugs (DMARD)
(i). Non-Biologic / Synthetic DMARDs: Methotrexate,
Sulfasalazine, Chloroquine, Hydroxychloquine, Gold Salts,
Cyclophosphamide, Mycophenolate mofetil, Leflunomide,
(ii). Biologic DMARDs:
 TNF-alpha blocker: Adalimumab, Certolizumab, Etanercept,
Golimumab, Infliximab.
 T-cell activation inhibitor……Abatacept.
 IL-1 receptor antagonist ……Ankinra.
 IL-6 receptor antagonist…….Tocilizumab.
 Tyrosine kinase inhibitor……Tofacitinib.
 Anti-B lymphocyte antibody...Rituximab.

69
 RHEUMATOID ARTHRITIS (RA)
Immunosuppressant Drugs Azathioprine
 Azathioprine: inhibits purine synthesis.
Purines are needed to produce DNA and RNA.
 Cyclosporine: It is antibiotic.
Inhibits interleukin-1 and -2 production.
Inhibit macrophage T-cell interaction.
T-cell dependent B-cell function is also affected.
 Methotrexate: Inhibition of the enzyme dihydrofolate reductase
 Abatacept: Inhibits the activation of T-cells.
 Sulfasalazine: Suppression of T-cell responses,
Inhibition of B-cell proliferation, Inhibit inflammatory cytokines.
 Adalimumab is fully human IgG1 anti-TNF antibody.
70
 DIABETES MELLITUS (DM)
Mechanism of Action of Insulin
 Insulin bind to receptor and phosphorylase
Tyrosine kinase, Insulin Receptor Substrate (IRS),
Phosphatidylinositol-3 kinase.
 Translocation of glucose transporters (GLUT 4) to
cell membrane, with a result:

Complications of Insulin Therapy:

 Hypoglycemia,
 Insulin antibodies,
 Insulin allergy,
 Lipodystrophy,
 Increased Cancer Risk.
71
 DIABETES MELLITUS (DM)
Rapid Acting Insulin: Lispro, Aspart, Glulisine
 Taken immediately before meal, Very fast & Shorter duration.
 Onset of action 5-15 min, Peak activity 1h, Duration 3-5 h.
Short Acting Insulin Regular Humulin Insulin:
 Peak 2 – 3h, onset in 30 minutes, Duration 5 - 8 hours,
 Used 30-45 minutes before meal.
Intermediate Acting Insulin NPH Humulin Insulin:
 NPH (Neutral Protamine Hagedorn or Isophane).
 Absorption & onset of action is delayed with protamine.
 Onset 2-5 hours, duration 4-12 hours.
Long Acting: Glargine, Detemir:
 Maximum effect after 4-6 hours, for ˃11-24 hours.
Ultra Long Acting: Insulin Degludec:
 DIABETES MELLITUS (DM)
Classification of Oral Hypoglycemic Drugs
1. Drugs That Primarily Stimulate Insulin Release By
Binding To Sulfonylurea Receptor:
 Sulphonylurea: (Insulin secretagogues):
 First generation: Tolbutamide, Chlorpropamide,
Tolazamide, Acetohexamide.
 Second generation: Glyburide, Glipizide, Glimepiride,

Gliclazide.
 Meglitinide: (Insulin secretagogues): Repaglinide.
 D-Phenylalanine Derivatives (Insulin secretagogues):

Nateglinide.
2. Drugs That Affect Absorption Of Glucose:
 Alpha-Glucosidase Inhibitors: Acarbose, Miglitol, Voglibose.

73
 DIABETES MELLITUS (DM)
Classification of Oral Hypoglycemic Drugs
3. Drugs That Primarily Lower The Glucose Levels By
Their Actions On The Liver, Muscle, & Adipose Tissue:
 Biguanides (Euglycemic agents):Metformin,
agents): Phenformin.
 Thiazolidinediones (TZDs) ( Euglycemic agents):

Pioglitazone, Rosiglitazone, Troglitazone.

4. Drugs That increase the Incretin Action:
 Glucagon – like Polypeptides-1 (GLP-1) receptor agonists:

Dulaglutide, Exenatide, Liraglutide, Lixisenatide, Semaglutide.

 Dipeptidyl Peptidase-4 (DPP-4) Inhibitors:
Alogliptin, Linagliptin, Saxagliptin, Sitagliptin,Vildagliptin,
Gemigliptin, Teneligliptin,Trelagliptin, Omarigliptin,
Evogliptin, Gosogliptin.
74
 DIABETES MELLITUS (DM)
Classification of Oral Hypoglycemic Drugs
5. Sodium-Glucose Co-Transporter 2 (SGLT-2) Inhibitors:
Dapagliflozin, Canagliflozin, Empagliflozin, Ertugliflozin,
Ipragliflozin.

6. Other Glucose-Lowering Drugs:

 Islet Amyloid Polypepetide Analog:
Analog Pramlintide (injectable).
 Bile Acid Sequestrants: Colesevelam hydrochloride.
 Dopamine Agonist: Bromocriptine.

75
 DIABETES MELLITUS (DM)
Insulin Secretagogues
Sulfonylureas: Tolbutamide, Tolazamide, Glyburide, Glipizide.
i). Increase Insulin release: Binds to 140 – kDa sulfonylurea
receptor, inhibit the efflux of K + ions, results in depolarization.
Depolarization opens the voltage gated Ca ++channel,
results in Ca++ influx & release of preformed insulin.
ii). Reduction of serum Glucagon concentration:
Meglitinide Repaglinide:
 M.O.A: Lower blood glucose levels by blocking

ATP-dependent potassium channels in pancreatic

beta cells, which in turn, stimulates insulin secretion.
D-Phenylalanine Derivatives Nateglinide:
 M.O.A: Releases the insulin very rapidly from β-cells

through closure of the ATP-sensitive K + channel.

76
 DIABETES MELLITUS (DM)
Euglycemic agents
Biguanides Metformin M.O.A: decreases hepatic glucose
production, decreases intestinal absorption of glucose, and improves
insulin sensitivity by increasing peripheral glucose uptake and
utilization.
Indications: Metformin is insulin-sparing agent,
First-line therapy for type-2 DM.
Useful in the prevention of type-2 diabetes in

middle age obese person, but not in older.

Thiazolidinediones (Tzds) Pioglitazone, Rosiglitazone:

M.O.A: depends on the presence of insulin for its action,
decreases insulin resistance in periphery & in liver.
Adverse effects: Anemia, Weight gain, bone fractures in
women, (due to decreased osteoblast formation).

77
 DIABETES MELLITUS (DM)
Alpha Glucosidase Inhibitors Acarbose, Miglitol
M.O.A: Competitive Inhibitors of alpha glucosidase in the
intestinal brush border, thus decreases the absorption of
starch and disaccharides.
 Acarbose alone has effect on alpha-amylase,
 Miglitol has effect on isomaltase, beta-glucosidase.
 Contraindications: Inflammatory bowel disease.

78
 DIABETES MELLITUS (DM)
Incretin – Based Therapies
 Incretins are a group of gastrointestinal hormones
increases the amount of insulin released from the beta
cells after eating.
 The two main candidate molecules that fulfill criteria
for an incretin are Glucagon-like peptide-1(GLP-1) and
Gastric inhibitory peptide (GIP).
 GLP-1 Receptor Agonists: Exenatide, Liraglutide
 Both GLP-1 and GIP are rapidly inactivated by the
enzyme Dipeptidyl peptidase-4 (DPP-4).
 Dipeptidyl Peptidase-4 (DPP-4) Inhibitors:
Sitagliptin, Saxagliptin, Linagliptin
79
 DIABETES MELLITUS (DM)
 Bile Acid Sequestrants: Colesevelam Hydrochloride.
Exact mechanism of action is not known but presumed to
decrease in farnesoid X receptor (FXR) activation.
FXR effects on cholesterol, glucose & bile acid
metabolism. Drug may impair glucose absorption.

 Amylin Analog: Pramlintide.

Injectable antihyperglycemic agent.
Suppress glucagon release via unknown mechanism.

 Sodium Glucose Co-transporter - 2 (SGLT2) Inhibitors:

Dapagliflozin, Canagliflozin, Empagliflozin, Ertugliflozin,
Ipragliflozin. The main approved indication for the use of these
drugs is as third-line therapy for diabetes mellitus.
80
 Synthesis of Thyroid Hormones

 Step 1: Transport of iodide into the thyroid gland, this is called

iodide trapping.
 Step 2: Iodide is oxidized by thyroidals peroxidase to iodine.
 Step 3: Iodine rapidly iodinates tyrosine with in the
thyroglobulin molecule to form mono-iodotyrosine and
di-iodotyrosine. This process is called iodine organification.
 Step 4: Two molecules of di-iodotyrosine combine with in
thyroglobulin molecule to form Tetra-iodothyronine T4.
One molecule of di-iodotyrosine combine with
mono-iodotyrosine to form Tri-iodothyronineT3.
This process is called cuppling.
81
 THYROID HORMONES

 Natural = animal origin. T4, T3.

 Synthetic = Levothyroxine, Liothyronine, Liotrix.
 M.O.A: Activate nuclear receptors leading to increased
formation of RNA and then to protein synthesis.

82
 ANTI-THYROID DRUGS
1. Drugs Preventing Synthesis of Thyroid Hormone:
 Thioamides: Methimazole, Carbimazole, Propylthiouracil.

2. Drugs Inhibiting Iodine Pump:

 Anion Inhibitors: Perchlorate, Pertechnetate, Thiocyanate.

3. Drugs Inhibiting Release of Thyroid hormone:

 Iodides: Lugol solution, Potassium iodide.
4. Radioactive Iodine: 131- I
5. Iodinated Contrast Media: Ipodate.

6. Adjunctive drugs:
 Beta blockers: Metoprolol, Propranolol, Atenolol.
 Calcium blocker: Diltiazem.

7. Amiodarone-Induced Thyrotoxicosis: Glucocorticoids. 83

 ANTI-THYROID DRUGS
1. THIOAMIDES
 THIOAMIDES: M.O.A: The major action is to prevent hormone
synthesis by inhibiting the thyroid peroxidase-catalyzed
reactions and blocking iodine organification.
In addition, they block coupling of the iodotyrosines.
Toxicity: Agranulocytosis (Dangerous).
 Perchlorate, Pertechnatate, Thiocyanate:
M.O.A: Block reuptake of iodide transport mechanism.
Perchlorate may cause Aplastic anemia.
 Lugol solution, Potassium iodide:
M.O.A: Inhibit organification and hormone release.
 Radioactive iodine is also called I-131 or RAI.
destroy the thyroid gland.
84
 ADRENO CORTICOSTEROIDS
Classification
(a) Short to medium acting Glucocorticoids:
Cortisol, Prednisone, Prednisolone,
Methylprednisolone, Meprednisone .

(b) Intermediate acting Glucocorticoids:

Triamcinolone, Paramethasone, Fluprednisolone.

(c) Long acting Glucocorticoids:

Betamethasone, Dexamethasone.

(d) Mineralocorticoids: Aldosterone, Fludrocortisone,

Desoxycorticosterone acetate.
85
 GLUCOCORTICOIDS
Indications / Clinical Pharmacology
 Adrenocortical Insufficiency (Addison’s disease).
 Congenital Adrenal Hyperplasia.
 Diagnosis of Cushing’s Syndrome.
 Stimulation of Lung-Maturation in the Fetus:
 Organ transplant: (Pulse therapy).
 Rheumatic arthritis.
 Allergic reactions: Asthma, Bee sting, Allergic rhinitis,
 Eye disease:........Acute uvitis, Allergic conjunctivitis.
 G.I.T diseases:....Inflammatory bowel disease (IBS).
 Dermatological conditions: Pruritic eczema, psoriasis.
 Intra-articular & Intratendinous use: Painful Osteoarthritis
 Infections:.....................Septicaemia.

86
 GLUCOCORTICOIDS
Toxicity

 Insomnia Growth retardation

 Peptic ulcer
 Weight gain Behavioral changes
 Osteoporosis
 Muscle wasting
Cushing’s syndrome
 Acute psychosis Adrenal suppression
 Thinning of skin
 Hypokalemia Visceral fat deposition
 Glaucoma
 Diabetes Congestive heart failure
 Edema Bacterial & mycotic infection
Benign intracranial
hypertension.

87
 Antagonists Of
ADRENAL CORTICAL AGENTS

Glucocorticoids Antagonist:
 Metyrapone.
 Amino – glutithide.
 Ketoconazole.
 Mitotane.
 Trilostane.
 Mifepristone.

Mineralocorticoid Antagonist:
 Spirenolactone.
 Drospirenone.

88
 GLUCOCORTICOIDS ANTAGONIST

AMINO – GLUTETHIDE:
 Block the conversion of cholesterol to pregninolone & causes

reduction of all active steroid hormones.

 Used with Dexamethasone to reduce estrogen production in

patient with carcinoma of breast (1gm daily).

 Used with Metyrapone to reduce steroid in Cushing’s

syndrome.
KETOCONAZOLE: A anti–fungal imidazole derivative.
 Potent, non–selective inhibitor of adrenal & gonadal steroid

synthesis.
MITOTANE: is a steroidogenesis inhibitor and cytostatic
antineoplastic medication. Used orally for
adrenocortical carcinoma and Cushing's syndrome 89
 OXYTOCICS OXYTOCIN
Mode Of action: Oxytocin acts through G-protein-coupled
receptors, form IP3 & Ca++ second messengers.
Uses:
 Used I/M to elicit milk ejection.
 Used I/V for augmentation of labour.
 Used I/M for control of postpartum hemorrhage (PPH).

Contraindications:
 Significant cephalo-pelvic disproportion.
 Unfavorable fetal positions (transverse lies).
 Fetal distress where delivery is not imminent.
 Prolonged use, uterine inertia /severe toxemia.
 Cord prolapsed or total placenta previa.

Prostaglandins PGE1 PGE2 PGF2

Ergot Alkaloids Ergonovine
90
 TOCOLYTICS

Ritodrine, Salbutamol, Terbutaline, Rimiterol.

Mode of action: Activation of beta-2 receptors results in
stimulation of enzyme adenylyl cyclase, increases cAMP.

Magnesium sulphate (Mgso4): MOA: Ca++ antagonist.

Atosiban: Competitive antagonist of Oxytocin receptor.

 HORMONAL CONTRACEPTION
MECHANISM OF ACTION
(1). Main action is suppression of gonadotropin secretion, there
by inhibiting ovulation.
(2). Development of endometrial atrophy, making the
endometrium unreceptive to implantation.

(3). Production of viscous cervical mucus, that impedes

sperm transport.
2
(4). Effect on secretion & peristalsis within the fallopian tube,
which interferes with ovum & sperm transport.

EMERGENCY / POST COITAL CONTRACEPTIVES:

Conjugated estrogens, Ethinyl estradiol, Diethylstilbestrol,
L-Norgestrel, Norgestrel. Mifepristone.
92
 OPIOID ANALGESICS

 Morphine, Heroin (Diamorphine).

 Hydromorphone, Oxymorphone,
 Methadone, Meperidine,
 Fentanyl, Codeine,
 Levorphanol, Butorphanol,
 Hydrocodone, Oxycodone,
 Pentazocine, Phenazocine.
 Nalbuphine, Buprenorphine,
 Tramadol, Tapentadol.
 Alfentanil, Sufentanil, Remifentanil.
93
 OPIOID ANALGESICS
1. Classification
Strong Agonist:
 Phenanthrrenes: Morphine, Hydromorphone, Oxymorphone,
Heroin (Diamorphine, Diacetylmorphine).
 Phenylheptylamine: Methadone.
 Phenylpiperidine: Fentanyl, Sufentanil, Alfentanil,
Ramifentanil, Meperidine.
 Morphinans: Levorphanols.

Mild to Moderate:
 Phenanthrens: Codeine, Hydrocodone, Oxycodone.
 Phenylheptylamine: Propoxyphene.
 Phenylpiperidine: Diphenoxylate, Difenoxin, Loperamide.

94
 OPIOID ANALGESICS
Classification
 Natural Opium Alkaloids:
Morphine, Codeine, Thebaine.
 Semi-Synthetic:
Diacetyl-morphine, Hydrocodone, Dihydrocodeine,
Oxymorphone.

 Synthetic:
Meperidine (Pethidine), Methadone,
Pentazocine, Phenazocine.

95
 OPIOID ANALGESICS
Mechanism of Action
 Morphine act on its receptors:
ų = Miyo, MOR: қ = Kappa, KOR:
δ = Delta, DOR: σ = Sigma, NOR:
 They are present in CNS and other tissues.
 ų = Miyo, MOR: analgesia, euphoria, sedation,
miosis, respiratory depression, decreased GIT motility,
smooth muscle spasm, nausea, vomiting, feeding,
release of growth & prolactin hormone.
 қ = Kappa, KOR: analgesia, sedation, miosis, diuresis.
 δ = Delta, DOR: analgesia, release of growth hormone.
 σ = Sigma, NOR: learning and memory. 96
 OPIOID ANALGESICS
Mechanism of Action
 1). Opioid analgesics bind to specific receptors
in the brain, which are coupled to inhibitory – G (Gi)
protein & inhibits adenylyl cyclase, result into
inhibition of release of excitatory neurotransmitter
from nerves terminals, which containing
nociceptive stimuli (pain stimuli).
 2). Open K+ channel to inhibit post-synaptic neurons.
 3). Close Ca++ channels on presynaptic neurons
to inhibit release of neurotransmitters from
nociceptive nerves terminals.

97
 OPIOID ANALGESICS
Morphine
Effects: Analgesia, Euphoria, Sedation, Sleep architecture,
Miosis, Respiratory depression, Cough Suppression,
Nausea & Vomiting, Constipation, hyperthermia / hypothermia,
Truncal rigidity, Tolerance & dependence, Opioid-induced
hyperalgesia, Hypotension and bradycardia, biliary colic,
Decrease uterine tone, Renal functions decreased, Stimulate the
releases of prolactin and growth hormones, decreased libido in
male, dysmenorrhea or amenorrhea, Pruritus.
 Contraindications of Morphine:
Head injury, Hypotension, Emphysema, During delivery,
Bronchial asthma, Impaired hepatic or renal function.
 Opioid Antagonist: Naloxone, Naltrexone, Nalmefene

98
 ALCOHOLS
Management of Alcohol Withdrawal Syndrome

 Thiamine therapy initiated.

 Chlordiazepoxide and Diazepam.
 Naltrexone:
 Acamprosate: Used to treat alcohol dependence.
 Disulfiram: Acts by inhibiting aldehyde dehydrogenase.
Alcohol is metabolized as usual, but acetaldehyde accumulat

99
 SEDATIVE & HYPNOTICS
BENZODIAZEPINES:
 Short Acting: Midazolam, Triazolam, Eszopiclone, Zaleplon,
Zolpidem, Halazepam, Quazepam, Buspirone, Ramelteon.
 Intermediate: Alprazolam, Lorazepam, Oxazepam, Temazepam.
 Long Acting: Chlordiazepoxide, Clorazepate, Diazepam,
Flurazepam, Clonazepam.

BARBITURATES:
 Long Acting: (Onset I h. Duration of action 6-8).
Phenobarbital, Barbitone, Methyl-Phenobarbitone.
 Intermediate & Short Acting: (Onset 15 min. Duration 3-4h.
Amobarbital, Butabarbital, Amobarbital, Secobarbital,
Pentobarbital, Mephobarbital, Pentobarbital.
 Ultra Short Acting: Onset 30 second. Duration 5-10 min.
Thiopental, Methohexital, Hexobarbitone.
100
 SEDATIVE & HYPNOTICS
NON – BARBITURATE SEDATIVES:
 Chlorinated compounds: Chloral hydrate, Chlorobutanol.
 Heterocyclic compounds: Methaqualone, Glutethimide,
Meprobamate.
 Aldehyde group: Paraldehyde.
 Alcohol: Ethyl alcohol.
 Anti-histamines: Cyclizine, Hydroxyzine.
 Melaton receptor agonist: Tasimelteon.
 Orexin receptor antagonist: Suvorexant.

 Newer Drugs For Anxiety:

 Buspirone relieves anxiety without causing marked sedative or euphoric
effects.
 Zolpidem Used for short - term treatment of insomnia.

101
 BENZODIAZEPINES
 Mode of Action: Bind to Benzodiazepine GABA receptors in
CNS, Open the chloride channel, Which leads chloride
conductance, Causes hyperpolarization,
Decrease in the firing rate of neurons.
 Indications: Anxiety, Insomnia, Sedation & amnesia, Epilepsy,
As component of balanced anesthesia,
For control of withdrawal effects, As muscle relaxants.
 Side effects: Drowsiness, Ataxia, Confusion, Dependence,
Sexual function impairment, Withdrawal effects.
 Antagonist: Flumazenil.

102
 BARBITURATES

Mode of Action:
 Bind to molecular component of GABA receptors,
 Increasing the duration of GABA – gated Cl - channels.
 Higher conc: may be GABA-mimetic (directly).
 Also suppress the actions of excitatory neurotransmitters

(Glutamic acid).
Indications: Insomnia & Sedation, Anticonvulsant,
 Surgical anesthesia, Neonatal jaundice, Eclampcia,
 Status Epileticus in children.

Treatment of Barbiturate Poisoning:

Antidotes: Caffeine, Strychnine.
Artificial respiration, Purging of stomach, Hemodialysis,
Alkalinization of the urine.
 ANTIDEPRESSANT DRUGS
 Serotonin Selective Reuptake Inhibitors (SSRIs):
Fluoxetine, Fluvoxamine, Sertraline, Paroxetine, Citalopram.
 Serotonin & Norepinephrine Reuptake Inhibitor (SNRI):
 Serotonin & Norepinephrine Reuptake Inhibitor (SSNRI):
Duloxetine, Venlafaxine, Desvenlafaxine, Milnacipran.
 Tricyclic Antidepressants (TCA):
Amitriptyline, Nortriptyline, Protriptyline, Doxepin,
Imipramine, Desipramine, Clomipramine, Trimipramine.
 5-HT2 Antagonists: Trazodone, Nefazodone.
 Tetracyclic & Unicyclic Anti-depressants:
Bupropion, Mirtazapine, Amoxapine, Vilazodone, Maprotiline.
 Mono-Amine Oxidase Inhibitors: Phenelzine, Isocarboxazid,
Tranylcypromine, Selegiline, Moclobemide. 104
 Selective Serotonin Reuptake Inhibitors (SSRI)
Fluoxetine, Paroxetine, Citalopram,
Escitalopram, Sertraline, Fluvoxamine
Mechanism of action:
 Primary action is allosterically inhibition of Serotonin

Transporter (SERT).
 SSRI have also modest effect on other neurotransmitters.
 SSRI do not bind to histamine, muscarinic & other receptor.

Adverse Effects:
 Decrease sexual function,
 Delayed orgasm,
 Loss of libido,

105
 (i) Selective- Serotonin-Norepinephrine Reuptake
Inhibitors (SSNRI)
Duloxetine, Venlafaxine, Desvenlafaxine, Milnacipran
Mechanism of action:
 Bind & block to both Serotonin (SERT) & (NET)
 Norepinephrine transporters.

Indications:
 Major depression, Generalized anxiety,
 Stress urinary incontinence,
 Pain disorders including neuropathies & fibromyalgia,
 Vasomotor symptoms of menopause,

106
 (ii) Tri-Cyclic –Antidepressants (TCA)
Imipramine, Desipramine, Clomipramine, Doxepin,
Trimipramine, Amitriptyline, Nortriptyline, Protriptyline
Mechanism of action:
 Primarily inhibit 5-HT & Norepinephrine reuptake.
 TCA are potent H-1, Muscarinic & Alpha blockers.

Adverse Effects:
 Common are anti-cholinergic, dry mouth, constipation,

urinary retention, blurred vision, confusion.

 α-blocking causes orthostatic hypotension.
 H-1 antagonism causes weight gain & sedation.

 TCA are class 1-A anti-arrhythmic agents and are

arrhythmogenic at higher doses.
 Sexual effects are common with Clomipramine.
 TCA have a prominent discontinuation syndrome.
107
 (ii) Tri-Cyclic –Antidepressants (TCA)
Imipramine, Desipramine, Clomipramine, Doxepin,
Trimipramine, Amitriptyline, Nortriptyline, Protriptyline

Contraindications:
 Narrow angle glaucoma,
 Prostatic hypertrophy,
 Seizures,
 Over dose can cause life threatening dysrhythmias.

(Treatment = I/V Sodium bicarbonate).

108
 5-HT2 Antagonists
Trazodone, Nefazodone
Mechanism of action:
 Principle action is blocking of 5-HT2 presynaptic receptors, (as
anti-anxiety, anti-psychotic, anti-depressant).
 Inhibiting the reuptake of serotonin, norepinephrine,
and/or dopamine.
 Nefazodone is weak inhibitor of both SERT & NET,
but potent antagonist of 5-HT2A receptors.
 Trazodone is weak but selective inhibitor of SERT,
little effect on NET.
Its primary metabolite is a potent 5-HT2A antagonist.
It has weak to moderate α-blocking property and
modest antagonist of H1-receptor.
109
 Tetracyclic & Unicyclic Anti-depressants
Bupropion, Mirtazapine, Amoxapine, Maprotiline

Mechanism of action:
Bupropion and metabolites are re-uptake inhibitor of

Norepinephrine & Dopamine.( less beneficent).

More significant effect is release of catecholamines.
Mirtazapineis antagonist of α2-autoreceptor and
enhance the release of both NE & 5-HT.
Also antagonist to 5-HT2 , 5-HT3 and H1 receptors.
Amoxapine, Maprotiline in action resemble to TCA,
are potent NET inhibitors, less potent SERT inhibitors
and posses anti-cholinergic properties.
Amoxapine is inhibitor of D2-receptor (anti-psychotic).
110
 ANTI - DEPRESSANTS
Clinical Indications
1. Major Depression (MDD):
2. Anxiety Disorders: SSRI, SNRI
3. Panic Disorders: TCA, SNRI
4. Premenstrual Dysphoria Disorder (PMDD)
5. Eating Disorders: Fluoxetine.
Smoking Cessation: Bupropion.
TCA used for migraine & tension head aches.
TCA used for enuresis in children, diabetic neuropathies.

SSRI, Fluoxetine for urinary stress incontinence.

SSRI delay orgasm, used for premature ejaculation.

SSNRI, Duloxetine used for diabetic neuropathy and

fibromyalgia.
Unicyclic, Bupropion used for treatment of SSRI

sexual adverse effect .

111
 ANTIPSYCHOTIC AGENTS
CLASSIFICATION
 Phenothiazines Derivatives:
Aliphatic compounds: Chlorpromazine, Promazine,
Promethazine.
Piperidine derivatives: Thioridazine, Mesoridazine.
Piperazine derivatives: Prochlorperazine, Trifluoperazine,
Fluphenazine, Perphenazine.

 Thioxanthine Derivatives: Thiothixene.

 Butyrophenone Derivatives: Droperidol, Haloperidol.

 Miscellaneous Structures: Pimozide, Molindone.

112
 ANTIPSYCHOTIC AGENTS
CLASSIFICATION
 2nd Generation Antipsychotic Drugs:
Clozapine, Asenapine, Olanzapine, Quetiapine,
Paliperidone, Risperidone, Sertindole, Ziprasidone,
Zotepine, Brexpiprazole, Cariprazine, Lurasidone,
Aripiprazole, Melperone, Blonanserin, Iloperidone.

 Other drugs: Bitopertin, Sarcosine.

 Newer agents for Bipolar disorders:
Valproic acid, Carbamazipine, Lamotrigin. Gabapentin,
Oxcarbazepine, Topiramate, Aripiprazole,
Chlorpromazine, Olanzapine, Quetiapine, Risperidone,
Ziprasidone, Lithium.
113
 ANTIPSYCHOTIC AGENTS
MECHANISM OF ACTION

 Dopamine receptor blocking activity:

The antipsychotic agents block D2 receptors
to varying degree in the mesolimbic system of brain.

 Serotonin receptor blocking activity:

The newer drugs inhibit serotonin receptors
as well as dopamine receptors.

114
 ANTIPSYCHOTIC AGENTS
INDICATIONS OF CHLORPROMAZINE
1. Psychiatric conditions:
 Psychosis (Schizophrenia).
 Manic episode.
 Tourette’s syndrome
 Anxiety associated with minor emotional disorders.
 As tranquilizer to manage agitated patient.
 Used with narcotic to treat chronic pain.
 2. Non-psychiatric conditions:
 Antiemetic (older drugs except thioridazine).
 Hiccough.
 Pruritus.
 Neurolept - anesthesia (droperidol with fantanyl).

115
 ANTIPSYCHOTIC AGENTS
ADVERSE EFFECTS OF CHLORPROMAZINE
 Parkinsonism.
 Aggravate epilepsy.
 Tardive dyskinesia.
 Extra pyramidal effects.
 Drowsiness & confusion.
 Anticholinergic effects, dry mouth, urinary retention,
loss of accommodation & constipation.
 Postural hypotension due to alpha blocking effects.
 Weight gain.
 Hyper prolactinemia in women resulting in amenorrhea, galactorrhea & infertility.
 Loss of libido, impotence & infertility in men.
 Agranulocytosis, Cholestatic jaundice, Skin eruptions.
 Neuroleptic malignant syndrome:

116
 DRUGS USED FOR EPILEPSY
HISTORY
 1857: Potassium bromide.
 1912: Phenobarbital.
 1938: Phenytoin.
 1938 – 1960:
13 anti-seizure drugs were developed.
Primidone, Carbamazepine.

New anti-seizure drugs:

 1990: Gabapentin, Topiramate, Lamotrigine,
Felbamate, Vigabatrin, Pregabalin, Retigabine,
Tiagabine, Zomisamide, Lacosamide.
117
 DRUGS USED FOR EPILEPSY
Generalized Epilepsy
Tonic-clonic: Phenytoin, Carbamazepine,
Primidone, Phenobarbitone,
Valproic acid, Gabapentin,
Lamotrigine, Topiramate,
Zomisamide, Lacosamide.

Absence: Ethosuximide, Clonazepam,

Lamotrigine, Topiramate.

Myoclonic: Clonazepam, Phenobarbitone,

Valproic acid.
Status Epilepticus: Diazepam, Phenobarbitone.
118
 ANTI-EPILEPTIC DRUGS
Mechanism of Action
 Enhancement of inhibitory (GABAergic) transmission.
 Diminishing of excitatory (Glutamatergic) transmission.
 Modification of ionic conductance.

 Carbamazepine & Phenobarbital generally perceived as

the safest anti-epileptic agent in pregnancy.

119
 ANTI-EPILEPTIC DRUGS
Phenytoin
Mechanism of Action:
The major action of Phenytoin is to block sodium channels.
Inhibit the generation of rapidly repetitive action potential .
Side Effects:
Gingival hyperplasia, Nystagmus, Hirsutism, Hirsutism .
On long-term use:
 Coarsening of facial features, Osteomalacia.

 Low folate level & Megaloblastic anemia.

 Teratogenic effects: “Fetal hydantoin syndrome”

( Cleft palate, Cleft lip, Congenital heart disease ).

Contraindications: Diabetes, Osteomalacia, or softening of bones, Porphyria, Pancytopenia, Decreased blood
platelets.

120
 ANTI-EPILEPTIC DRUGS
Carbamazepine
Mode of action: Like Phenytoin.
 Block sodium channel,
 Inhibit high frequency repetitive firing in neurons,
 Act pre-synaptically to decrease synaptic transmission.

Indications:
Drug of choice for both Partial & Tonic-clonic Epilepsy.
Bipolar Depression (Manic- depressive illness).
Trigeminal Neuralgia, (Initially marketed for the treatment of
trigeminal neuralgia).
Diabetics Neuropathy.

121
 ANTI-EPILEPTIC DRUGS
Sodium Valproate / Valproic Acid
Mode of Action:
 Blockage of NMDA (N-Methyl D-Aspartate) receptor-mediated excitation.

Indications:
 Absence seizures & Generalized tonic-clonic.
 Drug of choice for Myoclonic.
 Drug of choice for Bipolar disorders.
 Migraine prophylaxis.
Adverse effects:
 Most common nausea, vomiting, abdominal cramps,

heart burn.
 Fine tremors, weight gain, increased appetite, hair loss.
 Hepatotoxicity, Thrombocytopenia.
 Spina bifida in the off-spring of women who took

Valproate during pregnancy.

122
 ANTI-EPILEPTIC DRUGS

 Primidone Metabolized to phenobarbital and

phenyl-ethyl-malon-amide (PEMA), both are active.
Mode of action: Although Primidone is converted to
Phenobarbital, but act like Phenytoin.
 Gabapentin & Pregabalin: Originally planned as a spasmolytic.
Effective against Partial & Tonic-Clonic seizures.
Also used for Neuropathic pain, Post-herpetic neuralgia.
 Topiramate: Used for Partial & Tonic-Clonic seizures in children,
infantile spasm, absence seizures, migraine.

123
 ANTI – PARKINSON DRUGS
Dopamine precursor drug: Levodopa.
Dopamine receptors agonists: Bromocriptine, Apomorphine,
Pramipexole, Ropinirole, Rotigotine,
Pergolide.
Mono Amino Oxidase Inhibitors: Selegiline, Rasagiline,
Safinamide.
Catechol – O – Methyl Transferase Inhibitors:
Tolcapone, Entacapone, Opicapone.
Anticholinergic drugs: Benztropine. Biperidine, Orphenadrine,
Procyclidine, Benzhexol, Belladonna.
Miscellaneous: Antihistamine, Amantadine, Pimavanserin,
Istradefylline, Isradipine, Deferiprone,
Exenatide. Co-enzyme Q10. 124
 CARBIDOPA

 Carbidopa is a Dopa - decarboxylase Inhibitor.

 It diminishes the metabolism of the Levodopa
in GIT & peripheral tissues.
 Thus it increase the availability of Levodopa to CNS, &
Lowers the dose of Levodopa.

Therapeutic uses:
 Carbidopa in combination with Levodopa

(25:100, 25:250) is a potent drug regimen to treat

Parkinson’s disease.

125
 ANTI – PARKINSON DRUGS
Levodopa
Adverse Effects:
 Brown coloration to saliva, urine, vaginal discharge.

Contraindications: Psychotic patients,

Close angle glaucoma, Active peptic ulcer,
Cardiac patient, Melanoma.
Bromocriptine:
Bromocriptine, act on D2 receptor,
also used for Hyper prolactinoma,
amenorrhea, infertility, acromegaly,
Neuroleptic malignant syndrome,
stops milk production in men & women.
Adverse effects: Erythromelalgia, (red, tender, painful, swollen
feet & hand)
126
 GENERAL ANAESTHTICS
Pre – Anesthetic Medications
 Benzodiazepines: Diazepam: to subside worry & tension.
 Analgesic: Celecoxib: for smooth induction & pain.

 Anti-cholinergic: Atropine: prevent bronchial secretion,

vagal inhibition & cardiac arrest.
 Anti-emetics: Ondansetron: prevent nausea & vomiting.
 Antihistamine: Cyclizine: to prevent bronchial secretion.

 Antacid / H2 Blocker: Famotidine: reduce gastric acidity.

127
 GENERAL ANAESTHTICS
Classification
(i). Inhalational (ii). Intravenous
Volatile liquids: Barbiturates: Methohexital,
Diethyl ether, Thiopental sodium.
Ethyl chloride, Benzodiazepines:
Halothane, Isoflurane, Lorazepam, Diazepam.
Enflurane, Sevoflurane, Opioids: Fentanyl, Morphine
Desflurane.
 Ketamine.
Gases:  Propofol.
Nitrous oxide,  Etomidate.
Cyclopropane.

(iii). Rectal anesthetic: Tribromoethanol, Thiopental.

128
GENERAL ANAESTHTICS
Inhaled Anesthetics

129
 GENERAL ANAESTHTICS
Halothane
Merits / Advantages:
 Non-inflammable, non-explosive.
 Not irritant to respiratory passage.
 Not unpleasant for induction, has fruity odor.
 Potent & rapid smooth induction & rapid recovery.
 Inhibit pharyngeal & laryngeal reflexes.
 There is no stage of excitement.
 Not stimulates bronchial secretion.
 Produces hypotension so blood loss is reduced.
 Potentiates tubocurarine for muscle relaxation.
130
 GENERAL ANAESTHTICS
Halothane
Demerits / Disadvantages:
 Very low margin of safety.
 Poor muscle relaxation.
 Poor analgesics, ( so used with nitrous oxide).
 Expensive.
 Hepatotoxic.
 Depress respiration.
 Can raise intracranial pressure.
 Can decreases uterine contraction.
 Can cause malignant hyperthermia.
 Produces hypotension & Bradycardia.
 Sensitizes myocardium to adrenaline,
thus causing cardiac dysrhythmias.
131
 GENERAL ANAESTHTICS
Nitrous Oxide
Merits / Advantages:
 Non irritant to respiratory tract.
 Neither inflammable, nor explosive.
 Smooth & rapid induction and recovery.
 Used as adjuvant to more potent anesthetics.
 Powerful analgesic used in labor & burns dressing.
 Least hepato toxic.
 Least cardiac depressant.
 Does not cause respiratory depression.

132
 GENERAL ANAESTHTICS
Nitrous Oxide
Demerits / Disadvantages:
 Not a potent anesthetics by itself, used with others.
 Inadequate muscle relaxant.
 Because it moves very rapidly into & out of the body,
air pockets may expand in abdomen, in pleura
(causing pneumothorax), lungs & skull.
 Does not relax uterine (smooth) muscle.
 Post-operative nausea vomiting & hypoxia.
 Produces hypertension which antagonize the
hypotensive effect of Halothane,
when these two drugs are combined.
133
 GENERAL ANAESTHTICS
Ketamine
Merits / Advantages:
 Short acting, non barbiturate anesthetics that
causes dissociative anesthetics in which
patient remain awake but drowsy, immobile & not feel pain.
 Very good analgesic.
 Used in children & young adult for short procedures
(painful procedures such as dressing of burns).
 Highly lipophilic drug, rapidly distributed in brain, than
redistributed into highly vascular organs.

134
 GENERAL ANAESTHTICS
Ketamine
Demerits / Disadvantages:
 Causes postoperative hallucination,
colorful dreams during induction & recovery.
 Can cause nystagmus, involuntary movements.
 Increase cerebral blood flow, oxygen consumption &
intracranial pressure ( not suitable for neurosurgery).
 Heart rate, arterial BP & cardiac output are increased (within
2- 4 minutes), then decline to normal (10-20 minutes).
 Decreases the respiratory rate slightly for 2-3 min.

135
 LOCAL ANESTHETICS ( L.A )
Classification
Amides L.A:
Esters L.A:
• Lidocaine (medium)
• Cocaine • Mepivacaine (medium)
(medium) • Articaine (fast & medium)

• Procaine (short) • Prilocaine (medium)

• Tetracaine (Long) • Etidocaine (Long)

• Benzocaine (surface) • Bupivacaine (Long)

• Chloroprocaine. • Levobupivacaine (Long)

• Ropivacaine (Long)

Amide L.A has two i in their names.

136
 LOCAL ANESTHETICS ( L.A )
Mechanism of Action
 Local anesthetics bind and block directly to the
intracellular voltage-gated sodium channels.
 They block nerve conduction by reducing the
influx of sodium ions into nerve cytoplasm,
there-by inhibiting the depolarization of nerve.
Order of sensory function block:
1. Pain
2. Cold
3. Warmth
4. Touch
5. Deep pressure
6. Motor.
Recovery in reverse order.
137
 ANTI MICROBIALS

Antimicrobials:
Agents which have lethal or inhibitory effects on the
microorganisms, without damaging the host tissue. (eg,
Claithromycin).

Antibiotics:
They are low molecular weight, natural chemicals,
produced by one microorganism that inhibit the
growth or to kill other microorganisms (eg, Penicillin).

138
 ANTI MICROBIALS

Bacteriostatic drugs:
These drugs arrest the multiplication of bacteria.
They only inhibit the growth of cells, ultimately
elimination of the organisms is dependent
upon host’s phagocytic activity.(Erythromycin).

Bactericidal drugs:
These drugs directly
kill the bacteria.
They only kill the cells
those are actively
growing.(Rifampin).
139
 ANTI MICROBIALS
Spectrum of Activity
Narrow spectrum: Antimicrobials acting only on a single or a
limited group of gram-positives microorganisms (Macrolides).
Moderate spectrum: effective against gram positive and
gram negatives, (Penicillin).
Broad spectrum: effective against
a wide range of organisms,
(Gemifloxacin).
Extend spectrum: effective against
a wide range of organisms,
including Klebsiella, Enterobacter,
Pseudomonas. (Mezlocillin).
Anti-mycobacterial: act on Mycobacteria Tuberculosis
(Isoniazid).
140
 ANTI MICROBIALS
Mechanism Of Actions

141
 ANTI MICROBIALS
Ways Of Drug Resistant
Antibiotic resistance is often plasmid-borne,
which means that resistance can be readily
transferred from one organism to another.

Mechanisms of antibiotic resistance

 Altered receptors for the drug.

 Decreased entry into the cell.

 Antibiotic degrading enzymes.

 Antibiotic altering enzymes.

 Antibiotic efflux pump.

142
 BETA-LACTAM ANTIBIOTICS
PENICILLIN
 Penicillin is antibiotic, discovered by
Sir Alexander Fleming.

143
 PENICILLIN
Role of Penicillinase

O
S
CH3
R C NH CH CH C
CH3
O C N CH COOH

Site of Penicillinase action

Breakage of the  lactam ring.

144
 BETA-LACTAM ANTIBIOTICS
PENICILLIN

 β- Lactam ring can be enzymatically cleaved by

“ Bacterial-β-Lactamase (Pencillinase)”.
 Resulting product “Penicilloic acid”, lacks
antibacterial activity.

145
 BETA-LACTAM ANTIBIOTICS
PENICILLIN
 Natural Penicillin: Penicillin-G, Penicillin-V.
 Semi Synthetic Penicillin:
 Anti-staphylococcal (synthetic):
Oxacillin, Cloxacillin, Dicloxacillin, Methicillin, Nafcillin.
 Anti-pseudomonal Penicillin (synthetic) /
(Extend – Spectrum Penicillin):
• Amino penicillins: Ampicillin, Amoxicillin, Bacampicillin.
• Carboxy penicillins: Carbenicillin, Ticarcillin.
• Ureidopenicillin: Piperacillin, Azlocillin, Mezlocillin.

 Long Acting Penicillin (synthetic):

Benzathine Penicillin, Procaine Penicillin.

146
 BETA-LACTAM ANTIBIOTICS
Mechanism Of Penicillin
1. Inactivation of Penicillin Binding Proteins (PBP):
PBP present on the bacterial cell membrane,
involved in synthesis of cell wall.
2. Inhibition of Transpeptidase:
Penicillin inhibit the transpeptidase, thus hindering the
formation of cross links, which is essential for cell wall
integrity.
3. Production of Autolysins:
Many bacteria (Gram positive cocci) produce degradative
enzymes (autolysins). That participate in normal
remodeling of bacterial cell wall.
In the presence of Penicillin (means absence of cell wall
synthesis), degradation action of autolysins proceeds.
147
 BETA-LACTAMASE INHIBITORS
Sulbactam, Clavulanic, Tazobactam

 Beta-lactamases are enzymes that break open the beta-

lactam ring in beta-lactam antibiotics through hydrolysis
which renders the antibiotic inactive.

 Beta-lactamase inhibitors such as sulbactam,

tazobactam & clavulanate are compounds that
irreversibly bind to & inhibit beta-lactamase enzymes.
 Ampicillin with Sulbactam
 Ticarcillin with Clavulanic
 Pipracillin with Tazobactam.

148
 SIDE EFFECTS OF PENICILLIN

 Allergic or hypersensitivity reactions: Skin rash, Itching,

difficulty in breathing, anaphylactic shock.
 Allergic to Penicillin also have allergy to Cephalosporin.
 Eosinophilia, Hemolytic anemia.
 Diarrhea, Vomiting, Nephritis, Neurotoxicity,
 Vaginal itching & discharge,
 White patches in the mouth or on the tongue.
 Nafcillin associated with neutropenia,
 Oxacillin can cause hepatitis,
 Methicillin causes Interstitial nephritis.
149
 Β - LACTAM ANTIBIOTIC
CEPHALOSPORINS
 They are antibiotics, chemically related to penicillins,
derived from “Cephalosporin-C”.
 Cephalosporin-C” was isolated by:
Guy Newton & Edward Abraham.

150
 Β - LACTAM ANTIBIOTIC
CEPHALOSPORINS
Chemistry:
 Nucleus consists of a ẞ-lactum ring, fused to
Dihydrothiazine ring (7-aminocephalosporanic acid) bears
a close resemblance to 6-aminopencillanic acid.

151
 Β - LACTAM ANTIBIOTIC
CLASSIFICATION OF CEPHALOSPORINS
 First- generation : (Narrow Spectrum) Cefazolin,
Cefadroxil, Cephalexin, Cephalothin, Cephapirin, Cephradine.
 Second - generation: (Intermediate spectrum) Cefaclor,
Cefamandole, Cefonicid, Cefuroxime, Cefprozil, Loracarbef,
Ceforanide, Cefoxitin, Cefmetazole, Cefotetan, Cephamyci
 Third - Generation: (Broad Spectrum): Cefoperazone,
Cefotaxime, Ceftazidime, Ceftriaxone, Ceftizoxime, Cefixime,
Cefpodoxime proxetil, Cefdinir, Cefditoren pivoxil, Ceftibuten,
Moxalactam.
 Fourth - Generation: (Broad Spectrum) Cefepime, Cefpirome.
 Fifth - generation cephalosporins: (Extended Spectrum)
Ceftaroline, Ceftobiprole.
152
 OTHER BETA-LACTAM DRUGS
CELL WALL or CELL MEMBRANE ACTIVE AGENTS

 Monobactans: Aztreonam.
 Carbapenems: Doripenem, Ertapenem, Imipenem,
Mepropenem.
 Glycopeptide Antibiotics: Vancomycin, Teicoplanin,
Dalbavancin,Telavancin, Oritavancin .

 Other Cell-wall Or Membrane Inhibitors:

Daptomycin, fosfomycin, bacitracin, cycloserine.

153
 PROTEIN SYNTHESIS INHIBITORS

 AMINOGLYCOSIDES
 TRETRACYCLINES
 CHLORAMPHENICAL
 MACROLIDES

154
 AMINOGLYCOSIDES
Classification
On The Bases Of Their Side Effects
1. Causing Cochlear Nerve Damage:
Amikacin, Neomycin, Kanamycin, Netilmicin.

2. Causing Vestibular Nerve Damage:

Gentamicin, Tobramycin, Streptomycin.

3. Causing Nephrotoxicity:
Gentamicin, Tobramycin, Neomycin.

4. Which Are Not Given Parenterally:

Neomycin.
155
 AMINOGLYCOSIDES
Side Effects
 All Aminoglycosides are ototoxic & nephrotoxic.
Loop diuretics can potentiate nephrotoxicity.
 Cochlear nerve damage:
tinnitus & hearing loss.
 Vestibular damage:
ataxia & vertigo.
 Allergic reactions on
topical use of neomycin & gent:
 Curare-like neuromuscular blockade .

156
 TETRACYCLINES

 Tetracyclines are a large family of antibiotics with a

common activity & basic structure ( four fused rings ).
 Short-Acting:
Chlortetracycline
Oxytetracycline
Tetracycline
 Intermediate Acting:
Demeclocycline
Methacycline
 Long Acting:
Doxycycline, Minocycline, Tigecycline.
Omadacycline, Eravacycline.
157
 TETRACYCLINES
Side Effects
 Hypersensitivity reactions (drug fever, rashes) un-common.
 Nausea, vomiting, diarrhea, Super infections.
 Dizziness, vertigo.
 Photosensitivity (Demeclocycline) induce sensitivity to sunlight
in fair-skinned persons.
 Yeast infection in female genital (vaginal itching & discharge).
 Causes discoloration of the teeth & enamel dysplasia in the
growing children.
 Bone deformity.
 Growth inhibition.
 Kidney toxicity.
 Liver Toxicity, (especially in pregnant women).
158
 CHLORAMPHENICOL
Adverse Effects
 Gastrointestinal disturbance.
 Oral & vaginal candidacies.
 Bone marrow depression leads to Aplastic anemia.
 Idiosyncratic reaction, irreversible, can be fatal.
 Gray baby syndrome:
Neonates have low capacity to glucuronidate the
antibiotic & have undeveloped renal function,
so decreased ability to degrade & excrete the drug,
which accumulates and causes Gray baby syndrome.
(vomiting, hypothermia, gray color, cyanosis,
depressed breathing, cardiovascular collapse & death).

159
 MACROLIDES
Erythromycin, Clarithromycin, Azithromycin, Ketolides,
Telithromycin, Fidaxomicin
 Erythromycin is prototype drug was obtained in 1952
from Streptomyces erythreus.
 Clarithromycin, Azithromycin, Ketolides & Telithromycin are
semisynthetic.

 Mechanism of Action: Inhibition of bacterial protein synthesis

via binding to 50-S ribosomal RNA.

 Erythromycin:
 Drug of choice for corynebacterial infection (Diphtheria).

160
 ANTIFOLATE DRUGS

Sulphonamides:
 Oral-Nonabsorbable: Sulphasalazine.
 Topically used: Sulfacetamide, Mafenide acetate.

 Oral short acting: Sulfacytine, Sulfisoxazole,

Sulfamethizole.
 Oral intermediate acting: Sulfadiazine, Sulfamethoxazole,
Sulfapyridine, Trimethoprim,
 Oral long acting: Sulfadoxine.

 Aminopyrimidine: Pyrimethamine.
 Trimethoxybenzyl pyrimidine: Trimethoprim.
161
 ANTIFOLATE DRUGS
SULFONAMIDES

 Mechanism of Action:
 By inhibiting the enzyme,
Dihydropteroate synthase,
Sulfonamides competitively inhibit
the incorporation of PABA into
folic acid, thereby preventing the
synthesis of folic acid.
 There will be no formation of
Purines & DNA.

162
 ANTIFOLATE DRUGS
SULFONAMIDES
Adverse Reactions: Sulfonamides provoke hemolytic
reactions in patients with glucose -6-phosphste
dehydrogenase deficiency.

 Fever,  Urticaria,
 Arthritis,  Skin rashes,
 Nausea,  Photosensitivity,
 Vomiting,  Herpetic Stomatitis,
 Diarrhea,  Polyarteritis nodosa,
 Psychosis,  Exfoliative dermatitis,
 Conjunctivitis.  Steven-Johnson syndrome.

163
 ANTIFOLATE DRUGS
TRIMETHOPRIM

Mechanism of Action:
 Trimethoprim selectively inhibits
bacterial Dihydrofolic reductase,
(which converts Dihydrofolic acid
to Tetrahydrofolic acid).

 That inhibit the formation

of Folic acid (bacterial DNA).

164
 DNA GYRASE INHIBITORS
FLUOROQUINOLONES
 First Generation: Nalidixic acid, Cinoxacin.
 Second Generation: Ciprofloxacin, Norfloxacin, Enoxacin,
Lomefloxacin, Levofloxacin, Ofloxacin, Pefloxacin.
 Third Generatiom: Gemifloxacin, Moxifloxacin, Sparfloxacin.
 Fourth Generation: Delafloxacin.

 Mechanism of action: Quinolones block bacterial DNA

synthesis by inhibiting bacterial topoisomerase II (DNA gyrase)

and topoisomerase IV.

165
 Blood Schizonticides
Gametocides Chloroquine, Amodiaquine Tissue / Liver
Schizonticides
Primaquine, Mefloquine, Proguanil
Chloroquine, Pyrimethamine, Quinine,
Primaquine
Quinine. Halofantrine, Artemether,
Lumefantrine ,Piperaquine.

166
 Suppressive:
 Falciparum with Chloroquine, Quinine, Artesunate.
 Resistant falciparum with Mefloquine, Halofantrine.
 Vivax & ovale with Primaquine.
 Radical Curative: Complete elimination of malaria
parasites from the body. No single available agent can
reliably effect a radical cure.
 Prophylactic: Drugs for prevention of Malaria in travelers: eg:
Chloroquine, Mefloquine, Malarone, Doxycycline, Primaquine,
Tafenoquine.

167
 The antimalarials that can be used in pregnancy:
Chloroquine, Amodiaquine, Quinine, Azithromycin,
Sulfadoxine-pyrimethamine, Mefloquine,
Dapsone - chlorproguanil, Artemisinin derivatives,
Atovaquone-proguanil (Malarone), Lumefantrine.
 Antimalarial drugs that should not be used in pregnancy:
Halofantrine, Doxycycline, Primaquine.

168
 BLOOD SCHIZONTICIDE
Chloroquine
Mode of action:
 Chloroquine acts by concentrating in parasite food vacuoles,
 Prevent the conversion of heme into hemozoin.
 Free heme then lyses membrane & leads to parasite death.

169
 BLOOD SCHIZONTICIDE
Chloroquine
Clinical uses:
 Treatment & Chemoprophylaxis of malaria.
 Non-Malarial Indications:
 Amoebic liver abscess: Chloroquine
 Rheumatoid arthritis, high doses.
 Systemic lupus erythematosus (SLE).
Contraindications:
 Psoriasis, Porphyria,
 Retinal & visual field abnormalities or myopathy.
 Used with caution with liver disease, hematological or

neurological disorders.

170
 BLOOD SCHIZONTICIDE
Quinine & Quinidine
 Quinine is alkaloid derived from the bark of Cinchona
tree (1820).
 Mechanism of action: Unknown.
 Clinical uses: Both drugs are drugs of choice for
falciparum malaria, even during pregnancy.
 Adverse Effects: Tinnitus, headache, dizziness.
 Visual disturbance (cinchonism), Auditory abnormalities.
 Hemolysis, leucopenia, agranulocytosis, thrombocytopenia.
 Black water fever rare ( hemolysis, hemoglobin urea ).

171
 BACTERIAL CELL WALL

Gram positive Gram negative Mycobacteria

Lipid bilayer cell Surrounded by two

Membrane covered membranes. Outer Thick mycolate-
by a Porous membrane contains rich outer covering,
Peptidoglycan Lipopolysaccharid works
layer. (LPS) and porins. as exceptionally
efficient barrier.
 DRUGS USED FOR TUBERCULOSIS
 First-Line Agents:  Second-Line Agents:
Isoniazid: 300 mg/day  Streptomycin
 Amikacin
Rifampin: 600 mg/day  Amino Salicylic Acid
Pyrazinamide:25 mg/kg/day  Capreomycin
Ethambutol:15-25 mg/kg/day  Ciprofloxacin
 Clofazimine
 Cycloserine
 Ethionamide
 Levofloxacin
 Linezolid
 Rifabutin
 Rifapentine
 Bedaquiline
173
 FIRST LINE DRUGS FOR TUBERCULOSIS
ISONIAZID (INH)

Mechanism of Action:
 Isoniazid inhibit synthesis of “ mycolic acid ”.
Adverse effects:
 Fever, Skin rashes,
 Systemic Lupus Erythematosus.
 Hepatitis is most common.
 Peripheral neuropathy (due to pyridoxine deficiency).
 Pyridoxine (Vit:B ), 25 – 50 mg/d, is recommended .
6

174
 FIRST LINE DRUGS FOR TUBERCULOSIS
RIFAMPIN
 Mechanism of Action: Rifampin binds to B-subunit of
bacterial DNA-dependent RNA polymerase and
there by inhibit RNA synthesis.
 Side effects:
 Gives harmless orange color to urine, sweat, tears &
contact lenses.
 May cause jaundice and hepatitis.
 FIRST LINE DRUGS FOR TUBERCULOSIS
ETHAMBUTOL
 M.O.A: Inhibits mycobacterial arabinosyl transferase.

 Side effects:
Most common serious event is
retrobulbar neuritis, result in loss of
visual acuity &
red-green color blindness.

 PYRAZINAMIDE:
 Mechanism of action: is unknown.
 Adverse effects: Hepatotoxicity, Nausea, Vomiting,
Hyperuricemia.

176
 SECOND LINE DRUGS FOR TUBERCULOSIS

 STREPTOMYCIN: It is Aminoglycoside antibiotic.

 M.O.A: Protein synthesis inhibitor.

Adverse effects: Ototoxicity, Vertigo, Hearing loss,

Nephrotoxicity,

 ETHIONAMIDE: M.O.A: Chemically related to Isoniazid & also

block the synthesis of mycolic acids.

 CYCLOSERINE: M.O.A: Inhibitor to cell wall synthesis.

 CAPREOMYCIN: Protein synthesis inhibitor.
 Side Effects: It causes nephrotoxicity, ototoxicity, tinnitus,

deafness and vestibular disturbance

 AMEBIASIS

 Amebiasis is a infection with Entamoeba histolytica.

 E. histolytica usually lives as a harmless commensal
in the human bowel, as asymptomatic amebiasis.
 The parasite subsets on debris and not on the tissues
of its host.
 This organism can cause:
 Asymptomatic colitis,
 Severe intestinal infection (dysentery),
 Liver abscess, and
 Other extra intestinal infections.

178
 CLASSIFICATION OF ANTI-AMEBIASIS DRUGS

1. Luminal Amebicides: (drugs for intestinal amebiasis):

Diloxanide furoate, Paromomycin,
Halogeneted hydroxyquinolines.

2. Systemic Amebicides: ( drugs for extraintestinal

amebiasis): Chloroquine, Tetracycline.

3. Mixed Amebicides:
Amebicides (drugs used for both intestinal &
extra intestinal amebiasis): Metronidazole, Tinidazole,
Emetine, Dehydroemetine.

179
CLASSIFICATION OF ANTI-AMEBIASIS DRUGS

Clinical Setting Drug of Choice Alternative Drugs

Asymptomatic Diloxanide furoate /
intestinal Iodoquinol, or
infection Paromomycin.
Mild / moderate Metronidazole, or Tetracycline, or
intestinal Tinidazole, or Erythromycin.
infection Luminal agent.
Severe Metronidazole, or Tetracycline, or
intestinal Tinidazole, or Dehydroemetine/
infection Luminal agent. Emetine.
Hepatic Metronidazole, or Dehydroemetine,
abscess & Tinidazole, or or Emetine, or
other intestinal Luminal agent. Chloroquine.
diseases 180
 ANTI-AMEBIASIS
METRONIDAZOLE & TINIDAZOLE
M.O.A: The Metronidazole is reduced in E. Histolytica.
Reduced Metronidazole metabolite react with the
bacterial DNA, with a lethal effect.
Clinical Uses: Amebiasis, Giardiasis, Trichomoniasis.
Side effects:
 Common: Marked nausea, anorexia, abdominal pain,

and metallic test in the mouth.

 Rare: Pancreatitis, muscular weakness, encephalopathy.
 Metronidazole has a disulfiram-like effect.

 Emetine: M.O.A: It inhibit protein synthesis in trophozoites.

 Chloroquine: is anti-malarial drug, also used in combination
of metronidazole & diloxanide furoate to treat amebic liver
abscess. 181
 ANTI-FUNGAL AGENTS
Classification
 POLYENES : Amphotericin-B, Nystatin, Natamycin, Filipin,
 AZOLES:

Imidazoles: Miconazole, Econazole, Ketoconazole,

Clotrimazole, Befonazole, Butoconazole,
Fenticonazole, Isoconazole, Oxiconazole,
Sertaconazole, Sulconazole, Tioconazole.
Triazoles: Fluconazole, Itraconazole,Isavuconazole,
Posaconazole, Voriconazole, Terconazole.
 PYRIMIDINES: Flucytosine.
 ALLYLAMINES: Terbenafine, Amorolfine, Butenafine.
 ECHINOCANDINS: Anidulafungin, Caspofungin, Micafungin.
 OTHERS: Griseofulvin, Gention violet, Haloprogin,
182
 ANTI-FUNGAL AGENTS
Classification
Systemic drugs for systemic infections (oral or parenteral):
 Amphotericin B, Flucytocine,
 Azoles (Ketoconazole, Fluconazole, Itraconazole)

Oral drugs for mucocutaneous infections:

 Grisofulvin, Terbenafine.

Topical drugs for mucocutaneous infections:

 Azoles (Clotrimazole, Miconazole, Ketoconazole)
 Nystatin.
 AMPHOTERICIN -B
 Mechanism of Action: Bind to ergosterol (sterol) in cell
membrane, & alter the permeability of cell, by forming pores
in the cell membrane.
 Pores allows the leakage of intracellular ions (K+ & Ca++),
altering fungal cell metabolism, leading to fungal cell death.

 Adverse Effects: Anemia due to reduced erythropoietin

production.
 Nystatin is polyene macrolide, like Amphotericin-B,
 Has same pore forming mechanism of action.
 ANTI -FUNGAL
AZOLES:
 Mechanism of Action Reduction of ergosterol synthesis by acting on fungal

cytochrome P-450 and inhibition of14 α demethylase (no conversion of

Lanosterol to Ergosterol).
 Side Effects: Most common adverse effect is minor GIT upset.
upset
 Ketoconazole can cause Impotance, Decrease Libido,

Menstrual irregularities.
 Itraconazole Not affect mammalian steroid synthesis.

TERBINAFINE:
 M.O.A: Interfere with ergosterole biosynthesis.
 Also inhibit the fungal enzyme squlene epoxidase.
 This leads to accumulation of the sterol squalene,
which is toxic to organism.
 ANTI -FUNGAL

GRISEOFULVIN
Mode of action: Deposited in newly forming skin where it
binds to keratin, protecting the skin from new infection.
 Bind with mitotic spindles, inhibit fungal growth.

FLUCYTOSINE
Mode of action:
 (5-Fc) taken up by fungal cells, via permease.
 Converted into 5-Fluorouracil (5-Fu), then into
5-Fluro deoxy–Uridine–Mono–Phosphate (F-dUMP)
and Fluro Uridine–Tri–Phosphate (F-UTP).
 They inhibit DNA & RNA synthesis respectively.

186
187
 ANTHELMINTHICS

 Albendazole
 Mebendazole
 Ivermectin
 Pyrantel,
 Piperazine.
 Thiabendazole.
 Praziquantel
 Niclosamide
 Metrifonate
 Metrifonate
 Oxamniquine
 Diethyl-carbamazine
188
 ANTHELMINTHICS
Helminths Common Drug of Choice Alternative
name Drugs
NEMATODES (INTESTINAL)
Ascaris Roundworm Albendazole Pyrantel,
lumbricoides Mebendazole Piperazine.
Ancylostoma Hookworm Albendazole Pyrantel,
duodenale Mebendazole Thiabendazole.
Enterobius Pinworm Albendazole Pyrantel,
vermicularis Mebendazole Piperazine.
Trichuris Whipworm Mebendazole Albendazole
trichura Thiabendazole.
Strongyloides Threadworm Ivermectin
stercoralis
Trichinella Pork Albendazole Mebendazole.
spiralis Roundworm
189
 ANTHELMINTHICS

Helminths Common name Drug of Alternative

Choice Drugs
NEMATODES (SOMATIC)
Wuchereria Lymphatic Diethyl- Ivermectin.
bancrofti filarial worm carbamazine
Onchocerca Oculodermal Ivermectin Diethyl-
volvulus filarial carbamazine.
Onchocerca Oculodermal Ivermectin Diethyl-
loa loa filarial carbamazine.
Dracuncula Guinea worm Metronidazole Mebendazole.
medinensis

190
 ANTHELMINTHICS
Helminths Common Drug of Alternative
name Choice Drugs
CESTODES
Tinia saginata Beef Praziquantel Niclosamide
Tapeworm
Tenia solium Pork Praziquantel Niclosamide
Tapeworm
Cysticerca Larva of Albendazole Praziquantel
cellulosae T. Solium
Diphyllobothrium Fish Praziquantel Niclosamide
latum Tapeworm
Hymenolepsis Dwarf Praziquantel Niclosamide
nova Tapeworm
Echinococcus Hydatid Albendazole Mebendazole
granulosus Larva
191
 COMMON FORMS OF HELMINTHIASIS &
DRUGS USED IN THEIR TREATMENT
Helminths Common name Drug of Choice Alternative
TREMATODES
Schistosoma Blood flukes Praziquantel Metrifonate
hematobium
S . mansoni Blood flukes Praziquantel Oxamniquine
S . japonicum Blood flukes Praziquantel

FLUKES
Fasciola Liver fluke Praziquantel Niclosamide
hepaticus
Clonorchis Chinese liver Praziquantel Niclosamide
sinensis fluke
F . busci Giant intest: Praziquantel Niclosamide
fluke
Paragonimus Lung fluke Praziquantel Niclosamide
westermani 192
 CLASSIFICATION OF ANTI-VIRAL DRUGS

1. Agents for Herpes Simplex Virus (HSV) &

Varicella Zoster Virus (VZV):
Acyclovir, Famciclovir, Valacyclovir, Penciclovir,
Ganciclovir, Docosanol, Trifluridine, Foscarent .

2. Agents for Cytomegalo Virus (CMV):

Ganciclovir, Valganciclovir, Foscarent, Cidofovir.

3. Agents for Hepatitis Virus: Interferon Alfa,

Hep-B: Adifovir Dipivoxil, Entecavir, Lamivudine,
Telbivudine, Tenofovir. Hep-C: Ribavirin.
4. Agents for Influenza Virus:
Amantadine, Rimantadine, Oseltamivir, Zanamivir.
193
 CLASSIFICATION OF ANTI-VIRAL DRUGS

5. Agents for Retroviral Viruses:

(a) Nucleoside Reverse Transcriptase Inhibitors (NRTI):
Abacavir, Didanosine, Emtricitabine, Lamivudine,
Stavudine, Tenofovir, Zalcitabine, Zidivudine.
(b) Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI):
Delavirdine, Efavirenz, Etravirine, Nevirapine.
(c) Protease Inhibitors (PI): Atazanvir, Darunavir, Fosamprenavir,
Indinavir, Lopinavir, Nelfinavir, Ritonavir, Saquinavir,
Tipranavir.
(d) Entry Inhibitors: Enfuvirtide, Maraviroc.

(e) Integrase Inhibitors: Raltegravir.

194
 CLASSIFICATION OF ANTI - VIRAL DRUGS

Agents to for Herpes Simplex Virus (HSV) &

Varicella-Zoster Virus (VZV) Infections:
 Genital herpes: Acyclovir, Famciclovir, Valacyclovir.
 Orolabial herpes: Acyclovir, Famciclovir, Valacyclovir,
Docosanol, Penciclovir.
 Herpes proctitis: Acyclovir.
 Herpetic keratoconjunctivitis: Ganciclovir, Trifluridine.

 Varicella infection: Acyclovir, Valacyclovir.

 Zoster infection: Acyclovir, Valacyclovir, Famciclovir.
 Acyclovir-resistant HSV or VZV Infection: Foscarnet,

Vidarabine.

195
 CLASSIFICATION OF ANTI - VIRAL DRUGS

Anti-Retroviral Agents:
 Abacavir, Atazanavir, Bictegravir, Darunavir,
Delavirdine, Didanosine, Dolutegravir, Doravirine,
Efavirenz, Elvitegravir, Emtricitabine, Enfuvirtide,
Etravirine, Fosamprenavir, Ibalizumab, Indinavir,
Lamivudine, Lopinavir/Ritonavir, Maraviroc,
Nelfinavir, Nevirapine, Raltegravir, Rilpivirine,
Ritonavir, Stavudine, Zidovudine, Tipranavir,
Tenofovir alafenamide (TAF),
Tenofovir disoproxil fumarate.

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 CLASSIFICATION OF ANTI - VIRAL DRUGS

Hepatitis – B:
 Entecavir, Tenofovir alafenamide fumarate,
 Tenofovir disoproxil, Pegylated interferon alfa-2a,
 Adefovir dipivoxil, Lamivudine, Telbivudine.

 Hepatitis – C:
 Regimen -1: Paritaprevir 150 mg/ Ritonavir 100 mg/
Ombitasvir 25mg once daily +
Dasabuvir 250 mg bid + weight- based
Ribavirin × 12 weeks.

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 CLASSIFICATION OF ANTI - VIRAL DRUGS

Cytomegaloviral Retinitis (CMV retinitis): Valganciclovir,

Cidofovir, Trifluridine, Ganciclovir, Letermovir, Foscarnet.
Anti-Influenza Agents: Baloxavir Marboxil, Oseltamivir,
Zanamivir, Peramivir, Amantadine, Rimantadine.

Coronavirus Disease (COVID-19): Remdesivir, Dexamethasone.

Nirmatrelvir, Ritonavir, Molnpiravir (NET).

Drugs for Respiratory Virus Infections: Amantadine, Ribavirin,

Palivizumab.
Drugs for HIV Infections: Zidovudine (AZT),
Didanosine (ddl), Zalcitabine (ddC), Saquinavir.

Drugs for External Genital and Perianal Warts: Imiquimod.

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 CLASSIFICATION OF ANTI- CANCER DRUGS

1. ALKYLATING AGENTS:
 Nitrogen mustards: Cyclophosphamide, Melphalan,
Chlorambucil, Mechlorethamine.
 Nitrosoureas: ………...Carmustine, Lomustine,
Bendamustine.
 Alkyl sulfonates: ……. Busulfan.
 Platinum complex: ….Cisplatin, Carboplatin, Oxaliplatin.
 Triazines:……………..Dacarbazine, Temozolomide.

 Hylhydrazine:……….. Procarbazine
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 CLASSIFICATION OF ANTI-CANCER DRUGS

2. ANTIMETABOLITES:
 Anti-Folate: Methotrexate, Pemetrexed, Pralatrexate.
 Fluoropyrimidine: 5-Fluorouracil, Capecitabine, TAS-102.
 Deoxycytidine analogs: Cytarabine, Gemcitabine.
 Purine antagonists: Mercaptopurine, Thioguanine.

3. PLANT ALKALOIDS:
 Vinca Alkaloid: Vinblastine, Vincristine,
 Taxanes & other Anti-microtubules: Paclitaxel, Docetaxel,
Cabazitaxel, Abraxane, Ixabepilone, Eribulin.
 Epipodophyllotoxins: Etoposide, Teniposide.
 Camptothecins: Topotecan, Irinotecan,
Liposomal Irinotecan.
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 CLASSIFICATION OF ANTI-CANCER DRUGS

4. ANTI-TUMOR ANTIBIOTICS:
 Anthracyclines: Doxorubicin, Daunorubicin, Idarubicin,
Epirubicin, Mitoxantrone.
 Mitomycin: ………….Mitomycin.
 Bleomycin: …………Bleomycin.
 Actinomycin: ……….Dactinomycin.

5. HORMONES:
 Glucocorticoids:…….Prednisolone.
 Androgens: ………....Testosterone.
 Estrogens: ………….Diethylstillbestrol.
 Progestins: …………Hydroxyprogesterone.
 Antiestrogens: ……..Tamoxifen.
 Antiandrogens: …….Flutamide.
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 CLASSIFICATION OF ANTI-CANCER DRUGS

6. MISCELLANEOUS ANTI-CANCER DRUGS:

Imatinib & Other Tyrosine Kinase Inhibitors:

Imatinib, Dastinib, Nilotinib, Bosutinib, Ponatinib,

Erlotinib, Afatinib, Osimertinib.

Growth Factor Receptor Inhibitors:

Cetuximab, Panitumumab, Nacitumumab.

 Bevacizumab, Ziv-Aflibercept, Ramucirumab.

 Sorafenib, Sunitinib, Pazopanib.
 CLINICAL PHARMACOLOGY
 Acute Childhood Leukemia: Corticisteroids, methotrexate, 6-
mercaptopurine, cyclophosphamide, vincristine, daunorubicin
and asparginase.
 Acute Adult Leukemia: Cytarabine, Doxorubicin, Daunorubicin.
 Chronic Myelogenous Leukemia: Imatinib, Dasatinib, Busulfan..
 Chronic Lymphocytic Leukemia: Chlorambucil,
cyclophosphamide, prednisone, vincristine, Rituximab.
 Hodgkin’s Lymphoma: Mechlorethamine, vincristine,
Procarbazine prednisone, doxorubicin, bleomycin, vinblastine,
 Non-Hodgkin’s Lymphoma: doxorubicin, cyclophosphamide,
vincristine and prednisone.
 Multiple Myeloma: Melphalan , prednisone , dexamethasone ,
bortezomib, Thalidomide.
 CLINICAL PHARMACOLOGY
 Breast Cancer – Stage I & II : Cyclophosphamide,
Methotrexate, fluorouracil, fluorouracil, doxorubicin and
cyclophosphamide.
 Breast Cancer – Stage III & IV: tamoxifen, doxorubicin,
mitoxantrone, docetaxel, paclitaxel, paclitaxel, ixabepilone.
Navelbine, capecitabine, gemcitabine, cyclophosphamide,
methotrexate, cisplatin.
 Prostate Cancer: flutamide, bicalutamide, nilutamide,
Abiraterone, Mitoxantrone, prednisone and estramustine
 Ovarian Cancers: cisplatin and cyclophosphamide, paclitaxel,
carboplatin plus paclitaxel , doxorubicin .
 Testicular Cancers: Etoposide and bleomycin, cisplatin,
 CLINICAL PHARMACOLOGY

 Colorectal cancer : Oxaliplatin, capecitabine,

capecitabine, Oxaliplatin, irinotecan. bevacizumab,
ramucirumab, cetuximab, panitumumab, regorafenib .
 Gastroesophageal cancers: Cisplatin, Gemcitabine,
 Hepatocellular cancer: sorafinib.
 Non-small cell lung cancer: paclitaxel and vinorelbine,
bevacimub with carboplatin & paclitaxel.
 Small-cell lung cancer: cisplatin, Etoposide, cisplatin,
irinotecan. Topotecan.
 Malignant Melanoma: Dacarbazine, temozoloamide, cisplatin
 Brain Cancers: Carmustine, Lomustine, Procarbazine
vincristine, Temozolomide, bevacizumab .
 PRACTICAL SIDE

 Observe the effects of drugs (Atropine, Adrenaline)

Rabbit’s eye:
 Color of Conjunctiva.
 Conjunctival reflex.
 Corneal reflex.
 Light reflex.
 Size of pupil.

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 PRACTICAL SIDE

 Prepare and dispense 30 ml of Carminative mixture.

 Prepare and dispense 30 ml of Castor oil emulsion.
 Prepare and dispense 10 gram of Sulfur ointment.
 Abbreviations.
 Prescription writing:

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