DOPAMINE

It is an immediate metabolic precursor of noradrenaline. It activates D1 receptors in several vascular beds, which causes vasodilatation. It acts on dopaminergic and other adrenergic receptors (α & β1).

Adverse effects of dopamine include nausea, vomiting, ectopic beats, anginal pain, tachycardia, palpitation and widened QRS.
Contraindications are atrial or ventricular tachyarrhythmias, hyperthyroidism and pheochromocytoma.

Acid-Peptic disorders

This group of diseases include peptic ulcer, gastroesophageal reflux and Zollinger-Ellison syndrome.

Pathophysiology of acid-peptic disorders

Peptic ulcer disease is thought to result from an imbalance between cell– destructive effects of hydrochloric acid and pepsin on the one side, and cell-protective effects of mucus and bicarbonate on the other side. Pepsin is a proteolytic enzyme activated in gastric acid (above pH of 4, pepsin is inactive); also it can digest the stomach wall. A bacterium, Helicobacter pylori, is now accepted to be involved in the pathogenesis of peptic ulcer.

In gastroesophageal reflux the acidic contents of the stomach enter into the oesophagus causing a burning sensation in the region of the heart; hence the common name heartburn or other names such as indigestion and dyspepsia.

However, Zollinger-Ellison syndrome is caused by a tumor of gastrin secreting cells of the pancreas characterized by excessive secretion of gastrin that stimulates gastric acid secretion.

These disorders can be treated by the following classes of drugs:

A. Gastric acid neutralizers (antacids)
B. Gastric acid secretion inhibitors (antisecretory drugs)
C. Mucosal protective agents
D. Drugs that exert antimicrobial action against H.pylori

Class III Potassium Channel Blockers

Prolong effective refractory period by prolonging Action Potential

Treatment: ventricular tachycardia and fibrillation, conversion of atrial fibrillation or flutter to  sinus rhythm, maintenance of sinus rhythm
– Amiodarone (Cordarone) – maintenance of sinus rhythm
– Bretylium (Bretylol) 
– Ibutilide (Corvert) 
– Dofetilide (Tykosyn) 
– Sotalol (Betapace) 

 Amiodarone 
- Has characteristics of sodium channel blockers, beta blockers, and calcium channel blockers 
- Has vasodilating effects and decreases systemic vascular resistance 
- Prolongs conduction in all cardiac tissue 
- Decreases heart rate 
- Decreases contractility of the left ventricles 

Class III - Adverse Effects 
- GI- Nausea vomiting and GI distress 
- CNS- Weakness and dizziness
- CV-Hypotension, CHF, and arrhythmias are common. 
- Amiodarone associated with potentially fatal Hepatic toxicity, ocular abnormalities and serious cardiac arrhythmias. 

Drug – Drug Interactions
These drugs can cause serious toxic effects if combined with digoxin or quinidine. 
 

Classification

1. Natural Alkaloids of Opium

Phenanthrenes -> morphine, codeine, thebaine

Benzylisoquinolines -> papaverine, noscapine

2. Semi-synthetic Derivatives

diacetylmorphine (heroin) hydromorphone, oxymorphone hydrocodone, oxycodone

3. Synthetic Derivatives

phenylpiperidines pethidine, fentanyl, alfentanyl, sufentnyl

benzmorphans pentazocine, phenazocine, cyclazocine

propionanilides methadone

morphinans levorphanol

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.

Monoamine oxidase inhibitors (MAOIs) 

e.g. phenelzine, tranylcypromine, moclobemide

- Belong to first generation antidepressants with TCAs
- Most MAOIs irreversibly inhibit the intraneuronal catabolism of norepinephrine and serotonin by MAO-A and MAO-B
- increase brain levels of noradrenaline and 5-HT
- Moclobemide causes selective, reversible inhibition of MAO-A

DRUG INTERACTIONS

Hypertensive crises similar to cheese reaction with OTC cough/cold preparations containing indirect-sympathomimetics
e.g. ephedrine

- Other antidepressants should not be started at least 2 weeks after stopping MAOIs and vice versa due to risk of serotonin syndrome
- Similar interaction with pethidine

ADVERSE DRUG REACTIONS

- Antimuscarinic side effects (e.g. dry mouth, blurred vision, urinary retention)vision, urinary retention)
- Excessive central stimulation causes tremors, excitement and insomnia
- Postural hypotension
- Increased appetite with weight gain