Drugs for Nasal & Sinus conditions

Paracetamol + Caffiene + Phenylephrine HCl+ Chlorpheniramine Maleate

Antihistamines, Decongestants, and Analgesics (Systemic)

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

• 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

• 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

• 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

• 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

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 Paracetamolcontaining 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

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

Drugs for Influenza (flu) and Cold

Paracetamol + Phenylephrine hydrochloride + Ascorbic acid

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

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

• 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

Theory – General Drugs

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 paracetamolsuch 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

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/cm3

Solubility in water 1.4 g/100 ml (20°C)also soluble in ethanol

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.

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:StomachSmall intestineLarge intestine

Effects of caffeine Depends onFood in the bodyCaffeine in the substance

Caffeine

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 AsiansMen Newborn Liver Damage Pregnant

Shorter/Faster Metabolism if:

Cigarettes CaucasiansWomen Child

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

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, seratoninin brain• Neuroendicrine effects - stress (high doses)

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

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

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

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 inhibitorsMarplan, Nardil, and Parnate

• High doses of cold medicinePhenylpropanolamine

• Adds to the effects of other stimulantsCocaine, amphetamines, metamphetamines

Drugs for Diarrhoea Loperamide hydrochloride +

Simethicone

• Loperamide/simethicone is combination medication used to treat diarrhea and gas simultaneously

Loperamide is a μ-opioid receptor agonist that works in the intestinesAlthough it is an opioid, it has no effects on the central nervous systemIt 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 passSimethicone is not absorbed from the gastrointestinal tract so there are no systemic side effects.

Introduction to the combination

PHARMACOLOGICAL ACTIONLoperamide 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.

INDICATIONSIndicated for the control and symptomatic relief of acute and chronic non-specific diarrhoea and its commonly associated symptoms: discomfort, bloating, cramping and flatulenceIt also inhibits peristalsis and slow intestinal transit time in patients with ileostomies, colostomies and other intestinal resections

CONTRA-INDICATIONSIn patients with a known hypersensitivity to any component of this medicineShould not be used in children under 12 years of ageShould 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 antibioticsShould not be used when inhibition of peristalsis is to be avoided and must be discontinued promptly if constipation, abdominal distension or subileus developLoperamide administration may precipitate toxic megacolon in patients with inflammatory bowel disease.The safety of use during pregnancy and lactation has not been established.

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

Anti Vertigo DrugsMeclizine + Caffeine

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

Neurotransmitters – Presence & FunctionsGlutamate-Vestibular nerve fibersAcetylcholine 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

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

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

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-CPSMigraine-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

Anticonvulsant-Barbiturates-Phenytoin-Carbamazepine

Alcohol Salicylates Cinchona alkaloids-quinine Aminoglycosides Alkalyting agents

Common drugs producing vertigo

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

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

• 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

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

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

Vestibular Compensation

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

• 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

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

• 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

• 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

Delayed Compes.- BarbituratesBenzodiazepinesAntihistaminesNeuroleptics

Accelerated compes.- BetahistinesFlunarizineGinkgo-biloba extractCaffeine

Agents affecting Vestibular Compensation

Worldwide trends

US – BenzodiazepinesMeclizine

France – AcetylleucineFlunarazine

India - CinnarizineBetahistine

Vertigo-Pharmacologic treatment

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

PharmacodynamicsMeclizine, 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

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

Introduction to the combination

Mucoactive AgentsAmbroxol Hydrochloride

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

• 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 )

Drugs of Respiratory System

• 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

AmbroxolHydrochloride

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

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