PHARYNGEAL DEMULCENTS 
Administered in the form of lozenges, cough drops and cough linctus. 
Produce soothing action on throat directly and by increasing the flow of saliva and provide symptomatic relief from dry cough.

EXPECTORANT

Expectorants are the drugs which increase the production of bronchial secretion and reduce its viscosity to facilitate its removal by coughing. 

ANTITUSSIVES

They are central cough suppressants and act centrally to raise the threshold of cough centre and inhibit the cough reflex by suppressing the coordinating cough centre in the medulla oblongata. 

Codeine - it depresses cough centre but is less constipating and abuse liability is low.

Pholcodeine is similar to codeine in efficacy and is longer acting. It has no analgesic or addicting property.

Noscapine is another opium alkaloid of benzylisoquinoline group. It is used as antitussive with no analgesic and drug abuse or drug dependence property. 

Dextromethorphan is a synthetic compound and its dextroisomer is used as antitussive and is as effective as codeine

Pipazethate is another synthetic compound of phenothiazine category used as antitussive with little analgesic and sedative properties.

ANTIHISTAMINICS
They do not act on cough centre but provide relief due to their sedative and anticholinergic action.

BRONCHODILATORS
Bronchodilators are helpful in individuals with cough and bronchoconstriction due to bronchial hyperreactivity. They help by improving the effectiveness of cough in clearing secretions.

Gastric acid secretion inhibitors (antisecretory drugs):

 HCl is secreted by parietal cells of the gastric mucosa which contain receptors for acetylcholine (muscarinic receptors: MR), histamine (H2R), prostaglandins (PGR) and gastrin (GR) that stimulate the production, except PGs which inhibit gastric acid production.
 
Therefore, antagonists of acetylcholine, histamine and gastrin inhibit gastric acid secretion (antisecretory). On the other hand, inhibitors of PGs biosynthesis such as NSAIDs with reduce cytoprotective mechanisms and thus promote gastric mucosal erosion. Also, the last step in gastric acid secretion from parietal cells involve a pump called H+ -K+-ATPase (proton pump). Drugs that block this pump will inhibit gastric acid secretion. Antisecretory drugs include:

1. Anticholinergic agents such as pirenzepine, dicyclomine, atropine.
2. H2-receptors blocking agents such as Cimetidine, Ranitidine, Famotidine, Nizatidine (the pharmacology of these agents has been discussed previously).
3. Gastrin-receptor blockers such as proglumide.
4. Proton pump inhibitors such as omeprazole, lansoprazole.

Major clinical indications of antisecretory drugs:

• Prevention & treatment of peptic ulcer disease.
• Zollinger Ellison syndrome.
• Reflux esophagitis. 

Antimania Drugs

MANIC SYMPTOMSMANIC SYMPTOMS

Elevated  or irritable mood
Increased activity or psychomotor agitation
Reduced need for sleep
Inflated self esteem or grandiosity
Increased or pressure of speech
Flight of ideas

These drugs are used to treat manic-depressive illness.

1. Lithium
2. Carbamazepine
3. Valproic acid

Mechanisms of action

1. Lithium works inside the cell to block conversion of inositol phosphate to inositol.
2. Carbamazepine blocks sodium channels 
3. Valproic acid blocks sodium and calcium channels

PHARMACOKINETICS

Absorbed readily and almost completely from the GI tract; peak concentrations in 1-2 hrs

Lithium toxicity

1. Nausea, diarrhea, convulsions, coma, hyperreflexia, cardiac arrhythmias, hypotension.
2. Thyroid enlargement; increases thyroid stimulating hormone (TSH) secretion; may cause hypothyroidism.
3. Polydipsia, polyuria (lithium inhibits the effect of antidiuretic hormone on the kidney).

Clinical applications concerning lithium 

- Patients must be warned against sodium-restricted diets because sodium restriction leads to greater retention of lithium by the kidney.
- Patients must have regular (e.g., monthly) blood checks because the margin of safety is narrow.

Endocrine Effects – Goitre and hypothyroidism commonly

Cardiac Effects:– ECG changes(common) - T-wave flattening/inversion and appearance of U wavesflattening/inversion and appearance of U waves

Li and Pregnancy -1st Trimester:Cardiovascular anomalies of the newborn, especially Ebstein's malformation
- 3rd Trimester: Neonatal goiter, CNS depression, hypotonia ("floppy baby" syndrome)

Drug–drug interactions of lithium
Diuretics and newer nonsteroidal anti-inflammatory drugs (NSAIDs) reduce lithium excretion and may cause lithium toxicity.

Isoflurane (Forane) MAC 1.3%, Blood/gas solubility ratio 1.4
- Better muscle relaxation than with the other halogenated anesthetic agents.
- Isoflurane markedly potentiates the action of the neuromuscular blocking agents.
- Produces rapid onset and recovery of anesthesia.
- Does not sensitize the heart to catecholamines.
- Produces respiratory depression, but produces less cardiovascular depression
- than does halothane.
- It has an extremely low degree of metabolism and is apparently relatively
- nontoxic.

Topical Anesthetics

Benzocaine

Benzocaine is a derivative of procaine, an ester type local anesthetic, and is poorly soluble in water and is

available only as a topical anesthetic.

-  Localized allergic reactions are sometimes encountered    

-  Overdosing is unlikely as benzocaine is poorly absorbed into the blood, which decreases the likelihood of systemic toxicity.

- The onset of surface anesthesia is rapid requiring less than one minute.

Tetracaine

- Tetracaine is an ester type local anesthetic

-  Topically applied tetracaine as opposed to benzocaine has a prolonged duration of action.

Cocaine

- Cocaine is a ester type anesthetic that is used exclusively as a topical agent.

- Cocaine is unique among topical and injectable anesthetics in that it has vasoconstrictive as well as anesthetic properties. It is used sparingly because of its abuse potential but is still used when hemostasis of mucous membranes is essential.

- Cocaine is generally available in concentrations of 2-10 % solution.

Lidocaine

- Lidocaine is an amide local anesthetic that is available in injectable and topical formulations.

- It is available in gel, viscous solution, ointment and aerosol preparations in concentrations ranging from 2-10 %.

- The onset of anesthesia is slower relative to benzocaine but, the duration is about the same.

- Absorption into the bloodstream is greater than benzocaine providing a greater risk of systemic toxicity.

Organic Nitrates 
Relax smooth muscle in blood vessel
Produces vasodilatation
– Decreases venous pressure and venous return to the heart  Which decreases the cardiac work load and oxygen demand. 
– May have little effect on the coronary arteries CAD causes stiffening and lack of 
–    responsiveness in the coronary arteries 
– Dilate arterioles, lowering peripheral vascular resistance  Reducing the cardiac workload

Main effect related to drop in blood pressure by
– Vasodilation- pools blood in veins and capillaries, decreasing the volume of blood that the heart has to pump around (the preload)
– relaxation of the vessels which decreases the resistance the heart has to pump against (the afterload) 

Indications
- Myocardial ischemia 
– Prevention
– Treatment 

Nitroglycerin (Nitro-Bid)
• Used
– To relive acute angina pectoris 
– Prevent exercise induced angina 
– Decrease frequency and severity of acute anginal episodes

Type 
• Oral - rapidly metabolized in the liver only small amount reaches circulation 
• Sublingual – Transmucosal tablets and sprays 
• Transdermal  – Ointment s 
– Adhesive discs applied to the skin
• IV preparations 

Sublingual Nitroglycerine 
•  Absorbed directly into the systemic circulation,  Acts within 1-3 minutes , Lasts 30-60 min 

Topical Nitroglycerine 
• Absorbed directly into systemic circulation,   Absorption at a slower rate. ,  Longer duration of action 
Ointment - effective for 4-8 hours 
Transdermal disc - effective for 18-24 hours 

Isosorbide dinitrate 
• Reduces frequency and severity of acute anginal episodes
• Sublingual or chewable acts in 2 min. effects last 2-3 hours
• Orally, systemic effects in about 30 minutes and last about 4 hours after oral administration
    
Tolerance to Long-Acting Nitrates 
• Long-acting dosage forms of nitrates may develop tolerance
– Result in episodes of chest pain
– Short acting nitrates less effective 

Prevention of Tolerance 
• Use long-acting forms for approximately 12-16 hours daily during active periods and omit them during inactive periods or sleep 
• Oral or topical should be given every 6 hours X 3 doses allowing a rest period of 6 hours

Isosorbide dinitrate (Isordil, Sorbitrate) is used to reduce the frequency and severity of acute anginal episodes.
When given sublingually or in chewable tablets, it acts in about 2 minutes, and its effects last 2 to 3 hours. When higher doses are given orally, more drug escapes metabolism in the liver and produces systemic effects in approximately 30 minutes. Therapeutic effects last about 4 hours after oral administration

Isosorbide mononitrate (Ismo, Imdur) is the metabolite and active component of isosorbide dinitrate. It is well absorbed after oral administration and almost 100% bioavailable. Unlike other oral nitrates, this drug is not subject to first-pass hepatic metabolism. Onset of action occurs within 1 hour, peak effects occur between 1 and 4 hours, and the elimination half-life is approximately 5 hours. It is used only for prophylaxis of angina; it does not act rapidly enough to relieve acute attacks.