This drug combination contains loperamide hydrochloride, which is used to treat diarrhea. Loperamide works by slowing intestinal movement and fluid secretion to allow more time for water absorption. It is well absorbed from the gastrointestinal tract and has a half-life of around 10-14 hours. Common side effects can include abdominal pain, nausea, and vomiting. Loperamide should be used with caution in patients with liver or kidney disease and is not recommended for children under 2 years old.

1. Drugs for Nasal & Sinus
conditions
Paracetamol + Caffiene + Phenylephrine HCl
+ Chlorpheniramine Maleate
Antihistamines, Decongestants, and
Analgesics (Systemic)

2. Description
• Category  Antihistaminic (H 1-receptor)-decongestant-analgesic
• The formulation contains a clinically proven analgesic-antipyretic Paracetamol along with a decongestant
Phenylephrine and an antihistamine Chlorpheniramine maleate
• Paracetamol produces analgesia by elevation of the pain threshold and antipyretic effect through action on
the hypothalamic heat-regulating center

3. • Antihistaminic (H 1-receptor):
Antihistamines used in the treatment of allergy act by competing with histamine for H 1-receptor sites on
effector cells. They thereby prevent, but do not reverse, responses mediated by histamine alone. The
anticholinergic actions of most antihistamines provide a drying effect on the nasal mucosa
• Decongestant:
Sympathomimetic amines act on alpha-adrenergic receptors in the mucosa of the respiratory tract to produce
vasoconstriction, which temporarily reduces the swelling associated with inflammation of the mucous
membranes lining the nasal passages
• Analgesic:
Acetaminophen or Salicylates: The mechanism of analgesic action has not been fully determined.
Acetaminophen and salicylates may act by inhibiting prostaglandin synthesis in the central nervous system (CNS)
and, through a peripheral action, by blocking pain-impulse generation. The peripheral action may also be due to
inhibition of the synthesis of prostaglandins or to inhibition of the synthesis or actions of other substances that
sensitize pain receptors to mechanical or chemical stimulation. Acetaminophen may act predominantly in the
CNS, whereas salicylates may act predominantly via peripheral actions.
Caffeine: A mild CNS stimulant. Caffeine-induced constriction of cerebral blood vessels may contribute to relief
of headache. Also, preliminary evidence suggests that the addition of caffeine to acetaminophen and/or aspirin
may provide a more rapid onset of action and/or enhanced pain relief with lower doses of analgesics.
Mechanism of Action – General

4. • Paracetamol is equal to aspirin in analgesic and antipyretic effectiveness, and it is unlikely to produce many of
the side effects associated with aspirin and aspirin-containing products
• Sympathomimetic decongestants reduce the nasal congestion due to increased nasal blood flow associated with
colds and influenza. Phenylephrine is sympathomimetic vasoconstrictor that has been used as a decongestant. It
is a relatively selective alpha-adrenoceptor agonist. The majority of the sympathomimetic action is due to direct
stimulation of the adrenoceptors and relatively little is due to an indirect effect via release of noradrenaline. Its
pressor action is weaker than that of noradrenaline but of longer duration. At therapeutic doses, it does not
cause significant stimulation of the central nervous system
• Chlorpheniramine provides prompt relief of itchy-watery eyes, runny nose, sneezing, itching of the nose or
throat due to respiratory allergies
• Caffeine enhances the analgesic activity of Paracetamol and serves to reduce incidence of sedation due to
Chlorpheniramine maleate
• The pharmacokinetics of this combination is well matched and synergistic. All the drugs are well absorbed orally.
Mechanism of Action – Formulation

5. • Relief of nasal and sinus congestion
• Relief of allergic symptoms of the nose or throat due to upper respiratory tract allergies
• Relief of sinus pain and headache
• Adjunct with antibacterials in sinusitis, tonsillitis and otitis media
Indications

6. • Antihistamines:
Well absorbed from the gastrointestinal tract after oral administration
• Sympathomimetic amines:
Most sympathomimetic amines (except phenylephrine) are well absorbed from the gastrointestinal tract after
oral administration. Phenylephrine has reduced bioavailability (about 38%) from gastrointestinal tract because
of first pass metabolism by monoamine oxidase in the stomach and liver
• Analgesics:
Acetaminophen: Rapid and almost complete; may be decreased if acetaminophen is taken following a high-
carbohydrate meal.
Salicylates: Generally rapid and complete but may vary according to specific salicylate used and other factors
such as tablet dissolution rate and gastric or intraluminal pH. Food decreases the rate, but not the extent, of
absorption.
Caffeine: Well absorbed from the gastrointestinal tract.
Absorption

7. CONTRAINDICATIONS
The use is contraindicated in patients with:
• Hypersensitivity to any of the ingredients of the formulation
• Severe hypertension
PRECAUTIONS
• In case a hypersensitivity reaction occurs which is rare, formulation should be discontinued
• Formulation contains Paracetamol and therefore should not be used in conjunction with other Paracetamol
containing products
• It should be used with caution in patients with renal or hepatic dysfunction, diabetes mellitus,
hyperthyroidism, cardiovascular problems, epilepsy and closed angle glaucoma
• It is advisable not to drive or operate machinery when on treatment with its use

8. DRUG INTERACTIONS
• Clinically significant drug interactions may occur on concomitant administration of formulation along with
monoamine oxidase inhibitors, tricyclic antidepressants, beta-adrenergic agents, methyldopa, reserpine and
veratrum alkaloids
ADVERSE REACTIONS
• It is generally well tolerated and adverse events are rare
• Hypersensitive individuals may display ephedrine-like reactions such as tachycardia, palpitations, headache,
dizziness and nausea
• Use of sympathomimetics has been associated with fear, anxiety, restlessness, tremor, weakness, dysuria,
insomnia, hallucinations and convulsions
• Chlorpheniramine may cause sedation

9. Drugs for Influenza (flu) and
Cold
Paracetamol + Phenylephrine
hydrochloride + Ascorbic acid

10. Paracetamol is an analgesic (a pain killer) and antipyretic (it reduces body temperature when you have a
fever)
Phenylephrine hydrdochloride is a decongestant which unblocks the nose and sinuses helping breathe more
easily without causing drowsiness
Ascorbic acid (Vitamin C) is a common ingredient of flu and cold products and is included to help replace the
vitamin C which may be lost in the initial stages of flu and colds
Indications
For the relief of the symptoms of influenza (flu) and colds
Mechanism of Action

11. Precautions 
• Formulation may cause dizziness. If affected, do not drive or operate machinery
• In blood vessel disease (such as Raynaud’s Phenomenon)
• Incase of an enlarged prostate
• Pregnancy or breast feeding
• Contraindicated in Patients taking any other Paracetamol-containing products or on any other flu, cold or
decongestant products
• If allergic to paracetamol, phenylephrine hydrochloride or vitamin C
• In patients suffering from severe kidney or liver problems, overactive thyroid, diabetes, high blood pressure
or heart disease, angle closure glaucoma or phaeochromocytoma.
• In patients taking tricyclic antidepressants (e.g. imipramine or amitriptyline) or drugs for heart problems
(including beta-blockers) or you are taking (or have taken within the last two weeks) drugs called monoamine
oxidase inhibitors
Precautions and Contraindications

12. • Allergic reactions which may be severe such as skin rash and itching sometimes with swelling of the
mouth or face or shortness of breath
• Skin rash or peeling or mouth ulcers
• Breathing problems. More likely if you have experienced them before when taking other painkillers such
as ibuprofen and aspirin
• Unexplained bruising or bleeding
• Nausea, sudden weight loss, loss of appetite and yellowing of the eyes and skin
• Nervousness, irritability, restlessness and excitability
• Headache, dizziness or insomnia
• Raised blood pressure or an usually fast pulse rate or a sensation of an unusually fast or irregular
heartbeat
• Nausea, diarrhoea or sickness
• Unexplained bruising or bleeding
Side Effects

13. Theory – General
Drugs

14. Paracetamol is a common analgesic that is used for the relief of fever, headaches, and other minor aches and
pains. It is a major ingredient in numerous cold and flu medications and many prescription analgesics. It is
remarkably safe in standard doses, but, because of its wide availability, deliberate or accidental overdoses are
not uncommon.
Paracetamol and aspirin have similar analgesic properties
In other context it is formulated as 4-hydroxyacetanilide or N-acetyl-p-aminophenol, it is a white odourless substance.
Paracetamol has long been suspected of having a similar mechanism of action to aspirin because of the similarity in structure.
Over 100 years after it was first discovered, we are now learning what the mechanism of action is that makes paracetamol
such an effective and useful medicine. It now appears paracetamol has a highly targeted action in the brain, blocking an
enzyme involved in the transmission of pain.
Paracetamol

15. The production of prostaglandins is part of the body's inflammatory response to injury, and inhibition of prostaglandin
production around the body by blocking the cyclooxygenase enzymes known as COX-1 and COX-2 has long been known to be
the mechanism of action of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen. However,
their action in blocking COX-1 is known to be responsible for also causing the unwanted gastrointestinal side effects
associated with these drugs. Paracetamol has no significant action on COX-1 and COX-2, which left its mode of action a
mystery but did explain its lack of anti-inflammatory action and also, more importantly, its freedom from gastrointestinal side
effects typical of NSAIDs.
Early work had suggested that the fever reducing action of paracetamol was due to activity in the brain while its lack of any
clinically useful anti-inflammatory action was consistent with a lack of prostaglandin inhibition peripherally in the body.
Now, recent research has shown the presence of a new, previously unknown cyclooxygenase enzyme COX-3, found in the
brain and spinal cord, which is selectively inhibited by paracetamol, and is distinct from the two already known
cyclooxygenase enzymes COX-1 and COX-2. It is now believed that this selective inhibition of the enzyme COX-3 in the brain
and spinal cord explains the effectiveness of paracetamol in relieving pain and reducing fever without having unwanted
gastrointestinal side effects.
Chemical Formula C8H9NO2
Molecular Weight 151.17
Metabolism hepatic
Elimination Half Life 1–4 hours
Physical properties
Melting Point 169°C
Density 1.263 g/cm
3
Solubility in water 1.4 g/100 ml (20°C)
also soluble in ethanol

16. However, there are important differences between the effects of aspirin and those of paracetamol.
Prostaglandins participate in the inflammatory response, but paracetamol has no appreciable anti-inflammatory
action. Furthermore, COX also produces thromboxanes, which aid in blood clotting — aspirin reduces blood
clotting, but paracetamol does not. Finally, aspirin and the other NSAIDs commonly have detrimental effects on
the stomach lining, where prostaglandins serve a protective role, but paracetamol is safe.
Indeed, while aspirin acts as an irreversible inhibitor of COX and directly blocks the enzyme's active site,
Boutaud et al. (2002) found that paracetamol indirectly blocks COX, and that this blockade is ineffective in the
presence of peroxides. This might explain why paracetamol is effective in the central nervous system and in
endothelial cells but not in platelets and immune cells which have high levels of peroxides.

18. Pharmacodynamics 
Main mechanism of action: direct competitive antagonist of adenosine receptors - A1 and A2a
Effects on Monoamines:
-Elevates levels of 5-HT in the brain
-Stimulates NE neurons
-Increases rate of DA formation
→However, this may be quickly followed by a decrease
→Yet, injection of caffeine usually increases locomotor activity, an effect supposedly blocked by a DA receptor antagonist
Pharmacokinetics  Absorption through:
Stomach
Small intestine
Large intestine
Effects of caffeine Depends on
Food in the body
Caffeine in the substance
Caffeine

19. Distribution
• Throughout the body and the brain
• Water soluble
• Crosses blood brain barrier
• Reaches the fetus
• No accumulation within body
Metabolism
The enzyme CYP1A2 is responsible for the metabolism of caffeine in the liver.
One form of the enzyme, produced by the gene variant 1A, metabolizes caffeine rapidly while another form, 1F,
metabolizes it slowly.
Longer/Slower Metabolism if:
 Alcohol
 Asians
 Men
 Newborn
 Liver Damage
 Pregnant
Shorter/Faster Metabolism if:
 Cigarettes
 Caucasians
 Women
 Child

20. Multiple mechanisms of Action
• Adenosine antagonist
- both A1 and A2 sites
• 2nd messenger theory
- Phosphodiesterase inhibition
- cAMP, AMP, intracellular calcium
Doses
50-200 mg
• Sleepy first 5 minutes
• Blood levels peak at 30 min.
• Stimulant effects
300-1000 mg
• Prolonged ability to perform
• Exaggeration of side effects
• Pronounced insomnia
• Nervousness
• Irritability
• Tremor
• Restlessness
1000+ mg
• “Caffeinism”
• All of the above worsen
• GI disturbances
• Cardiac arrhythmias

21. Effects on the Body
•Central Nervous System - stimulant
• Autonomic Nervous System - change in EMG activity
• Cardiovascular System
- heart and blood vessels
- blood platelets
• Gastrointestinal System - cause for ulcers?
• Respiratory - increases blood and air to lungs
• Skeletal Muscles - contraction (contrarily)
• Energy Metabolism
- basal metabolic rate, free fatty acids, oxidation of fats in exercise
• Neurotransmitters
- norepinephrine in CNS, norepinephrine and epinephrine in blood, seratonin
in brain
• Neuroendicrine effects - stress (high doses)

22. Behavioral Effects (w/ 100~200 mg)
• Increases wakefulness, alleviates fatigue, facilitates concentration
• Can also produce: elevated mood, shaky/jittery feeling
• ↑ time to fall asleep,↓ amount and quality of sleep
• ↑ attention/vigilance, ability to sustain performance
• ↑ work capacity/speed,↓ # of errors
Tolerance
• Decreased A2a receptor expression
• Increased A1 receptor expression
• Tolerance to respiratory effects after 8 consecutive days of daily
administration
• Cross-tolerance
• Caffeine tolerance is pharmacodynamic
Fig. 3-d: Percent change on a repeated acquisition test, which
assesses motor learning and memory

23. Symptoms of Withdrawal
The most commonly reported symptoms of withdrawal are:
• Headache
• Fatigue
• Sleeplessness/Drowsiness
• Difficulty Concentrating
• Work Difficulty
• Irritability
• Depression
• Anxiety
• Flu-like symptoms
• Impairment in psychomotor,
vigilance, and cognitive performances

24. Uses
• Treatment of migraine headaches, caused by dilation of blood vessels
• Mixed with ergotamine tartrate (vasoconstrictor)
• Increases the power of aspirin and other painkillers by about 40%
Has also been used to treat:
• Chronic obstructive pulmonary disease
• Asthma
• Breathing problems in newborns
• Overdoses with opioid drugs
Other Positive Effects
• Weight Loss Effects
• Increased Alertness
• Enhanced Concentration
• Enhance Physical Endurance and Delay Fatigue

25. Negative Effects
• Effect on the Heart
• Diuresis
• Gastritis
• Heartburn
• Lower birth weights
• Pregnancy risks
• Panic Attacks
• Jitters
• Anxiety
• Raised Blood Pressure
• Insomnia
Dangerous Combination
• Because of risk of increased blood pressure, caffeine should be
used cautiously by patients who take other drugs that raise bp
• Anti-Depressants that are MAO inhibitors
Marplan, Nardil, and Parnate
• High doses of cold medicine
Phenylpropanolamine
• Adds to the effects of other stimulants
Cocaine, amphetamines, metamphetamines

26. Drugs for Diarrhoea
Loperamide hydrochloride +
Simethicone

27. • Loperamide/simethicone is combination medication used to treat diarrhea and gas simultaneously
 Loperamide is a μ-opioid receptor agonist that works in the intestines
Although it is an opioid, it has no effects on the central nervous system
It reduces diarrhea by slowing the transit time of contents through the intestinal tract thereby allowing more
water to be reabsorbed from the intestinal lumen
 Simethicone reduces gas by allowing smaller gas bubbles to coalesce into larger bubbles in the intestinal
tract, making them easier to pass
Simethicone is not absorbed from the gastrointestinal tract so there are no systemic side effects.
Introduction to the combination

28. PHARMACOLOGICAL ACTION
Loperamide hydrochloride inhibits hypermotility by direct action on the bowel wall. Its inhibition of peristalsis is the result
of decreasing the activity of both the longitudinal muscles (preparatory and reflex phases) and the circular muscles (reflex
phase).
Loperamide hydrochloride normalises the stool in acute diarrhoea.
Loperamide hydrochloride is incompletely absorbed from the gut, and it is almost completely metabolised in the liver
where it is conjugated and excreted via the bile. Loperamide hydrochloride is mainly eliminated via the faeces.
Simethicone is a nonabsorbable inert surface acting agent with antifoaming properties.
INDICATIONS
Indicated for the control and symptomatic relief of acute and chronic non-specific diarrhoea and its commonly associated
symptoms: discomfort, bloating, cramping and flatulence
It also inhibits peristalsis and slow intestinal transit time in patients with ileostomies, colostomies and other intestinal
resections
CONTRA-INDICATIONS
In patients with a known hypersensitivity to any component of this medicine
Should not be used in children under 12 years of age
Should not be used as the primary therapy, in acute dysentery, which is characterised by blood in stools and high fever.
Should not be used in patients with acute ulcerative colitis or pseudomembranous colitis associated with broad-spectrum
antibiotics
Should not be used when inhibition of peristalsis is to be avoided and must be discontinued promptly if constipation,
abdominal distension or subileus develop
Loperamide administration may precipitate toxic megacolon in patients with inflammatory bowel disease.
The safety of use during pregnancy and lactation has not been established.

29. SIDE-EFFECTS
• Reversible paralytic ileus may occur at a high dose level
• Constipation and or abdominal distension, dry mouth, abdominal pain or discomfort and other gastro-intestinal
disturbances (eg. nausea and vomiting), drowsiness or dizziness and fatigue may occur
• Hypersensitivity reactions such as skin rash and urticaria and less frequent cases of anaphylactic shock and bullous
eruption including Toxic Epidermal Necrolysis
• Other medications may have caused or contributed to some of these cases.
PRECAUTIONS
• In patients with diarrhoea, fluid and electrolyte depletion may occur. In such cases administration of appropriate fluid
and electrolyte replacement (oral rehydration therapy {ORT}) is the most important measure
• Patients with hepatic dysfunction should be monitored closely for signs of central nervous system toxicity because of the
reduced first-pass metabolism

30. Anti Vertigo Drugs
Meclizine + Caffeine

31. Vertigo Definition: Illusion of spinning sensation of self or Surroundings, usually due to disturbance of
vestibular system
Types of Dizziness Patients
Experience
Pathologic Causes
Vertigo Illusion of movement of patients or
Surroundings
Disturbance of peripheral or CNS pathways of
vestibular system
Syncope or
Presyncope
Impending loss of
consciousness
Cerebral perfusion of brain falls below a critical
level
Disequilibrium A sense of imbalance Vestibular, Proprioceptive, Cereballer, Visiual
III defined dizziness Emotional disorders Hyperventilation, Anxiety, Depression,
Conversion reaction
Vertigo

32. Neurotransmitters – Presence & Functions
Glutamate-Vestibular nerve fibers
Acetylcholine muscaranic recepters(m2)- pons & medulla (Excitatory)
GABA-Vestibular neurons (inhibitory)
Histamine-diffusely in vestibular structures.
-H1& H2 receptors- Pre & post synaptically on vestibular cells
MAO, Dopamine, 5-HT, Norepinephrine maintain resting tone of vest nucleus
Vertigo Mechanisms
Mechanism Known :
-Migraine
-Epilepsy
-Meniere’s disease
-Central causes
In most of case- no convincing scientific evidence of cause & mechanism.
Vertigo - Neuroanatomical & Neurochemical
Basis

33. Vertigo
• Benign positional vertigo
• Vestibular neuronitis
• Labyrinthitis
• Meniers.s disease
• Post traumatic vertigo
Common “Peripheral
Vertigo”
• Vestibular portion of 8th nerve
• Vestibular nuclei within brain stem
• Central connections of vestibular nuclei
*Cerebellar Floccules
*Visual sensory connections
*Afferent from joint & tactile receptors
Central Vertigo

34. Peripheral
Short duration
Severe, often paroxysmal
Accompanied by auditory symptoms
Fatiguilibility
Reproducibility inconsistent
Nystagmus
- Unidirectional
- Horizontal-rotatory, Never vertical
- Inhibited by visual fixation
- Nystagmus with Vertigo Fall & past pointing-
towards side of lesion
Central
Chronic/Permanent
Less severe, Continuous S/S of brain stem/
Cerebellum,
Auditory less freq
No fatiguilibility
Reproducibility consistent
Nystagmus
- Uni/bidirectional
- Horizontal-rotatory, vertical
- Not inhibited
- Sometimes only Nystagmus, no vertigo
Veriable

35.  Less common than peripheral & systemic causes.
 Vertiginous symptoms usually less common.
 Additional neurological science usually present.
 Vertigo as a sole manifestation rare.
Central Vertigo-Causes
 Brainstem ischemia & infarction-VBI, infarction in territory of Int.auditory artery (collegen disorder),
subclavian steel phenomenon.
 Demylinating diseases-MS, postinfection demylination
 CP angle tumors.
 Cranial neuropathy(isolated 8th nerv/multiple cranial nerves)-vasculitis, granulomatous dis(sarcoidosis),
maningeal carcinomatosis.
 Intrinsic Brainstem lesions.
 Other posterior fossa lesions- cerebellar infarct, haematoma
 Seizure disorder-CPS
 Migraine-Basilar artery migraine, migranous aura
 Degenerative heridofamilial-SCA-PSP
 Cervical Vertigo-Neck trauma, irradiation to upper cervical sensory roots, CVJ anomalies
Vertigo - Central Vertigo-Characteristics

36.  Anticonvulsant
-Barbiturates
-Phenytoin
-Carbamazepine
 Alcohol
 Salicylates
 Cinchona alkaloids-quinine
 Aminoglycosides
 Alkalyting agents
Common drugs producing vertigo

38. Specific treatment
 Antimigraine drugs
 Antiepileptic drugs
 Salt restriction & diuretics in meniere’s disease
Symptomatic Treatment-Goals
• Elimination of vertigo
• Vestibular supression
• Enhancement/non compromise of process of vestibular compensation
• Reduction of accompanying neurovegetative & psycho affective signs(nausea,vomiting,anxiety)
• Treatment of cause
Vertigo-Treatment

39.  Decrease in asymmetry in vestibular tone
 Decrease in vestibular function in normal & abnormal side both
Vestibular Suppression
Vestibular Suppressants
 Anticholinergics -Homatropine
-Scopolamine(Hyoscine)
 Antihistamines -Diphenhydramine
-Cyclizine
-Dimenhydrinate
-Meclizine
-Hydrocyzine
-Promethazine
-Cinnarizine
-Flunarizine
 Benzodiazepines -Diazepam
-Lorazepam
-Clonazepam

41. • Suppressants reduce activity at intact side and thus hamper recovery by VC
• Not recommended for long term use
• They should be discontinued as soon as possible
Treatment with Vestibular Suppressants

42. Histaminergic Receptors
Role of Histamine
• Histamine is not a major neurotransmitter in the vestibular pathway
• It exerts effect by acting on H1 and H3 receptors present in the brain
• Structure of H1 receptors is similar to Muscaranic receptors
• Drug which blocks H1 receptors will also have an anti-cholinergic effect

43.  Plasticity of the CNS
 Sensory feedback (Vertigo) required for compensation
 2 goals (decrease in vertigo and increase in compensation) often incompatible
Vestibular Compensation

44. Right labyrinth damaged Left Labyrinth normal
Less electrical discharge Normal electrical discharge
Imbalance between two sides- Vertigo
Sensation of unequal inputs from two sides by CNS
Habituation and adaptation to the error
possible ways
Increasing elect. discharge from Decreasing electrical discharge from
damaged labyrinth normal labyrinth
Not possible Cerebellar Clamp or Vestibular shutdown
Vestibular Compensation

45. • Cerebellum through connections with Vestibular nuclei induces reduction in resting electrical discharge-
cerebellum induced vestibular shutdown
• Reduces inequality between electrical discharge between the two sides by lowering electrical discharge of
normal vestibular labyrinth
Advantages
 symptomatic relief of vertigo in acute
case
 At rest, no vertigo
Disadvantage
 reduced vestibular sensitivity
 Inhibited vestibular system fails to react normally to
vestibular assault
 Sudden head movement leads to vertigo
Chronic compensation is essential .
Acute compensation by cerebellar clamp or
vestibular shutdown

46. Normal situation
Right vestibule equal Left vestibule
Right vestibular nuclei Left vestibular nuclei
Vertigo
Right vestibule damaged Left vestibule normal
Less electrical normal electrical
Discharge discharge
Right vestibular nuclei Left vestibular nuclei
Biswas A, Neurotological Diseases IN ‘An Introduction to neurotology”, 1998, 85-7.
Chronic compensation for vertigo

47. • Inhibitory effect of cerebellum on vestibular nuclei is gradually removed and requisite anatomical restructuring
of central vestibular pathways takes place
• Cerebellum monitors afferent ( sensory) and efferent (motor) inputs form the two sides
• Vestibular nuclei on damaged vestibular side gets connected anatomically and functionally to vestibular nuclei
on normal vestibular side.
• Capacity of cerebellum to adapt to the affected or changed vestibular scenario is called plasticity of CNS.
• Whole compensatory mechanism controlled by CNS , mediated by cerebellum. Compensatory mechanism
ineffective if cerebellum malfunctioning, (Cerebellar degeneration)
• If after the above compensatory mechanisms, still errors in vestibular functioning, corrected by other afferent
such as propioceptive and visual system.
• Central compensation initiated and enhanced by head movements- adaptation exercises and vestibular
habituation therapy
Chronic compensation

48. • Adaptation
a phenomenon which helps a patient with persisting peripheral dysfunctional state to regain normal balance.
• Habituation
repeated exposure of the body to “mismatched “ sensory input.
• Compensation
a goal directed process induced by some recognized errors, directed towards its elimination
General Principles
• Decrease centrally sedating or vestibular suppressant drugs
• Exercise must provoke vertigo
• Initiate as early as possible
• Exercise should simulate real life situations
• Maintenance exercises to recurrence of symptoms
Vestibular Rehabilitation

49.  Delayed Compes.- Barbiturates
Benzodiazepines
Antihistamines
Neuroleptics
 Accelerated compes.- Betahistines
Flunarizine
Ginkgo-biloba extract
Caffeine
Agents affecting Vestibular Compensation

50. Worldwide trends
 US – Benzodiazepines
Meclizine
 France – Acetylleucine
Flunarazine
 India - Cinnarizine
Betahistine
Vertigo-Pharmacologic treatment

51. Status  Approved
Description  A histamine H1 antagonist used in the treatment of motion sickness, vertigo, and nausea during
pregnancy and radiation sickness. [PubChem]
Indication  For the prevention and treatment of nausea, vomiting, or dizziness associated with motion
sickness
Pharmacodynamics Meclizine, a piperazine-derivative H1-receptor antagonist similar to buclizine, cyclizine,
and hydroxyzine, is used as an antivertigo/antiemetic agent. Meclizine is used in the management of nausea,
vomiting, and dizziness associated with motion sickness and vertigo in diseases affecting the vestibular
apparatus
MOA  Along with its actions as an antagonist at H1-receptors, meclizine also possesses anticholinergic, central
nervous system depressant, and local anesthetic effects. Meclizine depresses labyrinth excitability and
vestibular stimulation and may affect the medullary chemoreceptor trigger zone
Absorption  Well absorbed
Meclizine hydrochloride

52. Meclizine–Caffeine is an antivertigo medication used to treat nausea, vomiting, and dizziness associated with motion
sickness.
Introduction to the combination

53. Mucoactive Agents
Ambroxol Hydrochloride

54. Mucus
• Mucus is a slippery secretion produced by mucus membranes.
It is a normal protective layering around the airway, eye and
urinary tract
• Mucus is an adhesive gel produced in the airway by
submucosal glands and goblet cells and is principally water Mucous cells on the stomach lining
Introduction
Phlegm
• Phlegm is more related to disease than is mucus. Phlegm is a secretion in the airway during disease
and inflammation. Phlegm usually contains mucus with bacteria, dust
• Once phlegm has been expectorated by a cough it becomes sputum

55. • Cilia are short, hair-like, rhythmically beating organelles on the surface of certain cells
• It moves or expels fluids, abnormal phlegm , dust particles and microbes by their conveyor belt like action
A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from
secretions, irritants, foreign particles and microbes.
Classification:
1. Non Productive cough ( Dry Cough )
2. Productive cough ( Wet cough )

56. Drugs of Respiratory System

57. • It possesses both Expectorant & Mucolytic effects
• It increases bronchial secretion and decreases viscosity to make coughs more productive
• It dilutes the thick mucus in the respiration track and facilitates excretion of it
Indications
• Acute Chronic Bronchitis
• Laryngitis, Pharyngitis, Sinusitis
• Asthmatic Bronchitis ,Cough
• Bronchiectasis
• Chronic Pneumonia
Ambroxol Hydrochloride

58. Ambroxol
Hydrochloride
Expectorant
Increases the bronchial
secretion
Lubricate the
irritated
Respiratory Tract
Increased mucus flow by cilia
through coughing
Mucolytic
Breakdown of Acid
Mucopolysaccharide Fiber
Thinner & Watery
mucus
Mechanism of Action

59. Status  Approved
Description  Ambroxol is a secretolytic agent used in the treatment of respiratory diseases associated with viscid or
excessive mucus. It is the active ingredient of Mucosolvan, Lasolvan or Mucoangin. The substance is a mucoactive drug with
several properties including secretolytic and secretomotoric actions that restore the physiological clearance mechanisms of
the respiratory tract which play an important role in the body’s natural defence mechanisms. It stimulates synthesis and
release of surfactant by type II pneumocytes. Surfactants acts as an anti-glue factor by reducing the adhesion of mucus to
the bronchial wall, in improving its transport and in providing protection against infection and irritating agents
Indication  Ambroxol is indicated as “secretolytic therapy in bronchopulmonary diseases associated with abnormal mucus
secretion and impaired mucus transport. It promotes mucus clearance, facilitates expectoration and eases productive cough,
allowing patients to breathe freely and deeply
MOA  Ambroxol is a mucolytic agent. Excessive Nitric oxide (NO) is associated with inflammatory and some other
disturbances of airways function. NO enhances the activation of soluble guanylate cyclase and cGMP accumulation.
Ambroxol has been shown to inhibit the NO-dependent activation of soluble guanylate cyclase. It is also possible that the
inhibition of NO-dependent activation of soluble guanylate cyclase can suppress the excessive mucus secretion, therefore it
lowers the phlegm viscosity and improves the mucociliary transport of bronchial secretions
Absorption  Rapid and almost complete
Ambroxol Hydrochloride – Drug bank