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1. AUTONOMIC NERVOUS SYSTEM
SNS PNS
 Thoraco-lumbar outflow Cranio sacral outflow
 T1-L2 c3,c7,c9,c10,s2-s4
 Pupillary dilation(mydriasis) pupillary constriction(miosis)
 Loss of accommodation contraction of ciliary muscles
 Salivation (decreases) salivation (increases)
 Mucous secretion (decreases) mucous secretion (increases)
 Bronchodilation bronchoconstriction
 HR (increases) HR (decreases)
 BP (increases) BP (decreases)
 Peristalsis (decreases) peristalsis (increases)
 Sphincter constriction sphincter relaxation
 Detrusor relaxed (urinary retention) detrusor contracted (micturition)
 Sweating (increases) secretions & excretions are increased
byPMS
 Neurotransmitter-adrenaline/noradrenaline neurotransmitter-acetyl choline
 Ganglia are close to SC ganglia are close to organs
 Vasoconstriction vasodilation
 Ejaculation erection
 In SNS dopamine can be NT of post-ganglionic fibers at renal and mesenteric vasculature
 Ganglion blockers are Nn blockers eg. Hexamethionium,trimethophan,mecalamine
 Ach acts as neurotransmitter at
1. Neuro-muscular junction
2. At all ganglia (SNS & PNS)
3. Parasympathetic post-ganglionic fibres
4. Few sympathetic post-ganglionic fibres (sweat glands)
SYNTHESIS OF ACH:
 Ach is synthesized from acetyl COA and choline within the cholinergic neurons.
 The rate limiting step of ACH synthesis is Choline reuptake.
 HEMICHOLIUM blocks choline reuptakes.
 Vesamicol inhibits the incorporation of Ach into the synaptic vesicles.
 Botulinum inhibits the reuptake of Ach from the synaptic vesicles.
 Cholinesterase Ach E is an enzyme which breaks down Ach into Acetate and choline.
 Anti-cholinesterase/cholinesterase inhibitors increase the level of Ach.
 Anticholinergic drugs block the activity of Ach.
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2. Cholinergic Receptor
a.Nicotinic b.Muscarinic (usually m1-m2)
1. Nn 2.Nm 1.M1 2.M2 3.M3
Ganglions Skeletal muscles Gastric glands Heart Eye
Adrenal medulla GIT
Urinary
bladder
Bronchus
Smooth
muscles
PIRENZEPINE:
 Specific m1 blocker
 Used in treatment of peptic ulcer
CHOLINERGIC DRUGS/PARASYMPATHOMIMETIC DRUGS:
I. Direct acting cholinergic agonists
1. Acetylcholine
2. Pilocarpine
3. Bethanechol
4. Carbachol
5. Methacholine
6. Muscarine
 ACH is not used clinically because it is quick metabolized cholinesterases in the plasma
 Bethanechol has no nicotinic action and is used in the treatment of urinary retention and
postoperative paralytic ileus
 Carbachol has activity both on nicotinic and muscarinic receptor
 Methacholine has maximum activity on myocardium
 Pilocarpine causes pupillary constriction (miosis) and is used in treatment of glaucoma
 Pilocarpine and cevilimine are used for treatment of dry mouth in sjogren patient
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3. II. Indirect acting cholinergic drugs/cholinesterase inhibitors/anti-cholinesterases
a.Reversible
1.lipid soluble 2.water soluble
Physostigmine Neostigmine
Donepezil Pyridostigmine
Gallantamine Edrophonium
Tacrine
PHYSOSTIGMINE NEOSTIGMINE
 Tertiary compound Quaternary compound
 Lipid soluble Water soluble
 Crosses cornea Does not cross cornea
 Crosses BBB(blood-brain-barrier) Does not cross BBB
 Can be used in treatment of glaucoma Cannot be used
 Can be used in treatment of Alzheimer’s diseases Cannot be used
PHYSOSTIGMINE (NATURAL)
 Is a drug of choice for treatment of atropine/belladonna poisoning
EDROPHONIUM
 Is a short acting anti-cholinesterase used in the diagnosis of myasthenia gravis
 Used in “TENSILON TEST”
After edrophonium 1.symtoms improve → myasthenia crisis
2.symtoms worsen → cholinergic crisis
NEOSTIGMINE – acts on both Nn and Nm receptors
Is preferred for treatment of myasthenia. It does not cross BBB.
No cns side effects. It also directly stimulates Nm receptors.
Can be used in the treatment of post-operative paralytic ileus and in urinary retention.
Neostigmine is given for the reversal of skeletal muscle relaxant (after surgeries)
Neostigmine is also used in the treatment of cobra bites (cobra venom curare like activity)
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4. PYRIDOSTIGMINE
It’s an oral long acting form of neostigmine.
Donepezil, Rivastigmine, Galantamine, Tacrine are used in the treatment of alzheimer’s disease.
Tacrine is not commonly used because of the hepatotoxic potential.
IRREVERSIBLE
1.Organophosphate 2 Carbamates
Parathion Propoxur
Malathion Carbaryl (Sevin)
Tabun
Sarin
Echothiophate
 Among irreversible anti-cholinesterases, only Echothiophate is used clinically for
treatment of glaucoma
 All other drugs are poisons
 They are generally used as insecticides
Clinical features of organo-phosphate (OP) poisoning:
 Pin-point pupils (miosis)
 Salivation
 Lacrimation
 Sweating
 Bronchoconstriction
 Diarrhea
 Urination
 Bradycardia
 Hypotension
 Coma & death
 Muscle paralysis
 Rx: airway
Breathing
Circulation
Gastric lavage
 ‘Atropine’ is a specific anti-dote for both OP poisoning & carbamate poisoning
 Cholinesterase enzyme reactivators like pralidoxime are used in treatment of OP
poisoning
 Oxime should be used very early in the treatment before strengthening of
phosphate bond
 Diacetylmonoxime can cross BBB & regenerate ACH E in brain, but pralidoxime
cannot cross BBB.
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5.  Chronic exposure to OP’s leads to the demyelination of axons and neuropathies.
ANTI-CHOLINERGIC DRUGS
A) Nicotinic Antagonist
Nn Antagonist Nm Antagonist
Hexamethonium Vecuronium
Trimethoprim Atracurium
Mecalamine Tubocurarine
B) Muscarnic Antagonist
Specific M1 Specific M3 Non-specific Muscarinic
blocker blocker blocker
1.Pirenzepine 1.Dorefinacin 1.Atropine
2.Telezepine 2.Solefinacin 2.Scopolamine
 Natural= Atropine, hyoscine [scopolamine]
 Semisynthetic :- Ipratropium
 Synthetic
 Mydriatic – tropicamide, cyclopentolate
 Antispasmodic & antisecretory – dicyclomine
Glycopyrrolate
Propantheline
 Central anticholinergic :- Benztropine
Benzhexol
Trihexyphenidyl
 Bladder specific: M3
Darifenacin
Solefenacin
Oxybutynin
Tolterodine
 Atropine is a CNS stimulant
 It has a long duration of action as mydriasis for about 3~5 days (used in children)
 Acting on the heart it produces tachycardia used in treatment of heart blocks (AV
blocks) & bradycardia
 Atropine causes bronchodilation
 ↓ smooth muscle contraction (↓ peristalsis)
 Produces dry mouth , ↓ sweating , produces hyperthermia , produces mydriasis,
cycloplegia, constipation , urinary retention , blurred vision ,
 Contraindications :
1. Narrow angle glaucoma, can precipitate acute congestive glaucoma
(treatment of ACG = i.v mannitol)
2. BPH (benign prostate hyper trophy)
3. C/I in children due to risk of hyperthermia
 Uses :
1. DOC for OP poisoning and carbamate poisoning
2. Given along with neostigmine to produce reversal of skeletal muscle
relaxation. (muscarinic side effects)
3. DOC for early mushroom poisoning due to Inocybe species
Contraindication – mushroom poisoning due to Amanita muscaria
4. Thiotic acid is used for late mushroom poisoning by Amanita phalloides
5. Used in Rx of acute iridocyclitis as it relieves ciliary spasm
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6.  Scopolamine / hyoscine
 Is a CNS depressant
 Used as a transdermal patch & DOC for treatment of motion sickness
 Produces twilight sleep
 It also produces mild amnesia & is used as lie detector
 Central anticholinergic like benzhexol , benztropine , biperiden are used in drug
induced parkinsonism
 Tropicamide is a short acting mydriatic preferred for refractive error testing in
adults
 Cyclopentolate – for mydriasis and cycloplegia
 Ipratropium and tiotropium –DOC for COPD
 Dilates larger airways
 Also used in asthma
 Pirenzepine and Telenzepine –selective m1 blocker used for peptic ulcer
 Dicyclomine –is an antispasmodic drug used in colicky abdominal pains
 Glycopyrrolate –DOC for ↓ secretions in pre-anesthetic medications
 Propantheline –also as good anti-secretory properties
 Dicyclomine –used in Rx of renal colic
 Tiotropium –C/I in urinary retention
PHENYLALANINE
↓ phenylalanine hydroxylase
TYROSINE
↓ tyrosine hydroxylase
DOPA
↓ DOPA decarboxylase
DOPAMINE
↓ dopamine hydroxylase
NORADRENALINE
↓ methyl transferase
ADRENALINE
 Methyl transferase is present only in adrenal medulla and adrenaline is synthesized
only in adrenal medulla
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7.  COMT –cathechol o methyl transferase
 MAO –mono-amine oxidase
 TCA –tricyclic antidepressant
 MAO is an enzyme which degrades NA within the free pool of the neuron
 COMT is an enzyme which degrades NA in the synapse
 MAO inhibitors and COMT inhibitors ↑ catecholamines [dopamine ,NA]
 Reserpine blocks incorporation of catecholamines into synaptic vesicles
 Guanethidine and bretylium inhibit the release of NA from synaptic vesicle
 Metyrosine inhibits the rate limiting step of catecholamine synthesis by tyrosine
hydroxylase
 Cocaine and TCAs are reuptake blockers and ↑ the NA activity
 Cocaine causes
 Hypertension
 Septal perforation
 Tactile hallucinations ‘COCAINE BUGS’
RECEPTORS OF SNS:
α
α1 α2
Vasoconstriction (↑BP) ↓ Sympathetic activity
Urinary sphincter contraction
Mydriasis (dilatation of pupil)
Ejaculation is by α1 receptors
↑ aq.humor outflow
β
β1 β2 β3
Tachycardia (↑HR) vasodilation lipolysis
↑cardiac output bronchodilation detrusor relaxation
↑ force of contraction uterine relaxation
↑ renin (juxtaglomerular ↑ aqueous humor
cells ) kidney production
↑ tremor
Hypokalemia
Glycogenolysis
Gluconeogenesis
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8. Dopamine receptors:
D1 receptors–on renal vasculature and cause vasodilation of renal vasculature
D2 receptors –are present in the brain
Dopamine receptors are also present on CTZ (vomiting center) chemo trigger zone
Excess d2 receptor ↑ dopamine => nausea and vomiting
ADRENERGIC DRUGS
Direct acting
Catecholamines Non-Catecholamines
Endogenous Exogenous ● xylometazoline
●Dopamine ●Dobutamine ● Clonidine
●Adrenaline ●Fenoldopam ●Phenylephrine
●Noradrenaline ●Isoprenaline ●Salbutamol
●Methoxamine
●Prenaltrenol
Indirect Acting
Reuptake Inhibitors Releasers
●Cocaine ●Amphetamine
●TCA ●Tyramine
Mixed Action
●Ephrine
●Pseudoephrine
→Fenoldopam D1 agonist used in Hypertensive emergencies
→Neuro transmitter agents that is normally released in the SA node of the heart in response to
increase BP is Ach.
●Releaser release NA from free pool
Releasers are Ephedrine, Amphetamine, Tyramine. They show the phenomenon called
Tachyphylaxis.
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9. ●TCA – Imipramine, Amitriptyline, Nortyrptaline
adrenaline acts on →α1,α2,β1,β2
NA (no β2) →α1,α2,β1
isoprenaline→β1,β2
 isoprenaline and atropine are used in treatment of AV blocks
vasoconstriction causes reflex bradycardia
vasodilation causes reflex tachycardia
1. adrenaline uses: DOC for anaphylactic shock
2. Nasal packing for stopping epistaxis
3. Adrenaline can be used for treatment of
 Asthma
 Cardiac arrest
 Dopamine : D1 renal vasodilation , B1→ ↑CO,↑FOC,↑HR
Dopamine acts on,
 D1 receptor at a dose of 1~2 µg/kg/min
 β1 receptors at a dose of 2~10 µg/kg/min
 α1 receptors at a dose of >10 µg/kg/min
dopamine at a dose of 5~10 µg/kg/min is used as DOC for treatment of cardiogenic shock
with renal failure
 noradrenaline : [↑ BP, but ↓HR] can be used in treatment of hypovolemic shock but not
preferred
 fluids + vasodilation’s [as BP is low]
 followed by α1 agonists like
1. methoxamine
2. mephentermine
 Dobutamine : ↑ CO with little action on HR
 Is a selective β1 agonist
 Used for Rx of failing heart on an operation table
 Dobutamine has no action on dopamine receptors
 α1 agonists (selective):
 xylometazoline
 oxymetazoline → nasal decongestants
 naphazoline
 methoxamine
→for hypovolemic shock
 mephentermine
 phenylephrine –nasal decongestant + mydriatic
 phenylephrine is used to produce mydriasis without cycloplegia
 nasal decongestants on prolonged use will produce atrophic rhinitis called as Rhinitis
medicamentosa
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10.  α2 agonists:
 clonidine
 α-methyldopa
 guanfacine
 tizanidine
 clonidine:
 can be used in Rx of HTN but produces ‘rebound HTN’ on withdrawal
 rebound HTN on clonidine withdrawal is treated by giving phentolamine
 clonidine can also be used to control diarrhea in diabetic patients [Rx of diabetic
gastropathy]
 used for prophylaxis of migraine
 also used in management of alcohol and opioid withdrawal
 α –methyldopa:
 DOC for HTN in pregnancy
 It produces Abs and leads to a +ve coombs test
 Tizanidine
 Is used for neuropathic pains and as muscle relaxant
 Apraclonidine and brimonidine are used topically for the Rx of glaucoma
 DOC for HTNsive crisis is sodium nitroprusside
 DOC for HTNsive crisis in pregnancy –hydralazine
 α blockers:
 Non selective αblockers (both α1,α2)
1. Phentolamine (competitive or reversible)
2. Phenoxybenzamine (irreversible or non-competitive)
 Selective α1 blockers
1. Prazosin
2. Terazosin
3. Doxazosin
4. Tamsulosin
 Selective α2 blockers
1. Yohimbine
 “VASOMOTER REVERSAL OF DALE” is shown by adrenaline after pre-treatment with
αblockers like phenoxybenzamine
 Phenoxybenzamine is irreversible ,non-selective αblocker produces vasodilation,
hypotension and reflex tachycardia
 Pre-treatment with phenoxybenzamine is used to prevent hypertensive episodes during
operative manipulations of pheochromocytoma
 Phentolamine is reversible ,non-selective ,αblocker
 It is used for Rx of
1. Rebound HTN after clonidine withdrawal
2. Can be used i.v for hypertensive crisis
3. It is used to treat cheese reaction
4. It is used in Rx of Raynaud’s phenomenon
5. Intracorporeal injection of phentolamine and papaverine is used for
erectile dysfunction
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11. 6. Is used for Dx of pheochromocytoma (rapid fall of BP after his injection =>
pheochromocytoma)
 MAOI causes cheese reaction
 Tyramine is normally present in certain foods and can lead to cheese reaction in patients
taking MAO inhibitors
 Selective αblockers:
 α1a receptors are present on prostatic urethra and eye (iris muscle)
 α1b receptors are present on BVs
 prazosin is a DOC for Rx of HTN with BPH (elderly MALES WITH HTN)
 The major side effect of α1 blockers/ prazosin is 1st dose hypotension or postural
hypotension (c/I in active workers)
 The drug is also used in the Rx of scorpion sting.
 α blockers produce inhibition of ejaculation
 α blockers are the only anti-hypertensive drugs with GOOD LIPID PROFILE.
 Tamsulosin is a selective α1a blocker used in the Rx of isolated BPH.
 Side effect of Tamsulosin – Retrograde ejaculation.
 Β agonists:-
 Non selective β1,β2 agonists –isoprenaline
-isoproterenol
 Selective β1 agonist –dobutamine
–prenaltrenol
 Selective β2 agonist –salbutamol
–formoterol
–salmeterol
–terbutaline
–isoxsuprine
–ritodrine
–formoterol
Selective β3 agonist- mirabegron
 Isoprenaline & Isoproterenol –partial AV blocks
 Dobutamine –Rx of failing heart on operation table
 Mirabegron is used in Rx of urge incontinence
 Salbutamol –DOC for acute asthma
 Not used for prophylaxis of asthma
 Prolonged use can cause ‘Receptor desensitization’
 Side –effects: hyperglycemia, tremors
 Salmeterol - Is an oral long acting β2 agonist
 preferred in ‘Nocturnal asthma’
 Terbutaline , Isoxsuprine , Ritodrine –uterine relaxants (tocolytic agents)
 Used in Rx of premature labor
 DOC for ‘Status asthmaticus’ –i.v hydrocortisone
 DOC for acute asthma -salbutamol
 DOC for prophylaxis of asthma –inhalational steroids
 DOC for nocturnal asthma –salmeterol
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12.  Β blockers:-
 Non-selective β blockers :
1. Propranolol
2. Timolol
3. Pindolol
4. Oxprenolol
5. Alprenolol
 Cardioselective (β1 blockers) :
1. Nebivolol (most cardioselective)
2. Betaxolol
3. Bisoprolol
4. Acebutolol
5. Esmolol
6. Atenolol
7. Metoprolol
8. Celiprolol
 β-blockers with intrinsic sympathomimetic activity:
1. cetiprolol
2. oxprenolol
3. pindolol
4. alprenolol
5. acebutolol
 β-blockers with membrane stabilizing activity:
1. propranolol
2. metoprolol
3. labetalol
4. acebutolol
5. pindolol
 The ultra short acting β-blockers : Esmolol
 The longest acting β-blockers : nadolol
 Maximum membrane stabilizing activity is seen with Propanolol
 DOC for propanol toxicity : Glucagon i.v
 Propranolol : (non-selective β-blockers)
 It is highly lipid soluble non-selective β-blocker undergoes 1st pass metabolism
 Has maximum membrane stabilizing activity
 Used in
1. Essential HTN
2. Renin induced HTN
3. Classical angina (prophylaxis) and C/I in variant angina
4. Life long post MI
5. Hypertrophic obstructive cardiomyopathy (HOCM)
6. Chronic CHF
7. Symptomatic Rx of thyrotoxicosis
8. Provides symptomatic relief in anxiety associated with short term
stressful situations
9. Rx of essential tremors
10. Preferred drug for prophylaxis of migraine
11. Rx of Akathesia
12. In Rx of pheochromocytoma after α-blocker (phenoxybenzamine )
 Alcohol and opioid withdrawal
 Life long post MI drugs = β-blockers and ACEI
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13.  HOCM Drugs –Propanolol and verapamil
 Thyrotoxicosis –sweating , ↑HR , tremors
 Anxiety =diazepam , lorazepam (sedative)
=buspirone (non-sedative anxiolytic)
=propranolol (immediate symptomatic control)
 Cerebellar disorders –
 Half sided headache (DOC) sumatriptan (acute attack)
Photophobia Migraine
Nausea and vomiting (recurrent ) Propanolol
 Akathesia (motor restlessness ) –side effect of anti psychotic Rx
 Contraindications of propanolol :
1. In bronchial asthma
2. Diabetes
3. Peripheral vascular diseases
4. Better avoid in elderly as they produce drowsiness
5. Better avoid in pregnancy
6. Avoided with Verapamil
Digoxin (causes bradycardia)
Quinidine (anti arrthymic drug)
7. Avoided in depression (β-blockers stops NA activators)
8. Hyperlipidemia
9. Acute CHF
 Esmolol :
DOC for atrial fibrillation
 Timolol and betaxolol :
Used in Rx of glaucoma (↓ AH production)
 Sotalol :
Has additional k⁺ blocking activity
Has both class II and class III anti arrhythmic properties
Drugs used in Glaucoma
 Topical PGF2α analogues like latanoprost, bimatoprost given OD at night are
DOC for acute open angle glaucoma. They increase uveoscleral outflow
 β-blockers like timolol decreases aqueous production and are second line drugs
for open angle glaucoma
 Sympathetomimetics like epinephrine, α2 agonist like apraclonidine and
brimonidine decrease aq.humor and are third line drugs for open angle
glaucoma
 Carbonic anhydrase inhibitors like acetazolamide(systemic) decrease aq.humor
production and are used in Acute closed angle and Open angle glaucoma
 Topical miotics like Pilocarpine, Physostigmine, Echothiophate increase
trabecular aqueous outflow and can be used in acute closed angle and open
angle glaucoma
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