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. 

CENTRAL NERVOUS SYSTEM PHARMACOLOGY

Antipsychotic Drugs

1. Phenothiazines

a. Aliphatic derivatives
(1) Chlorpromaxine
b. Piperidine derivatives
(1) Thioridazine
(2) Mesoridazine
c. Piperazine derivatives
(1) Fluphenazine
(2) Perphenazine
(3) Prochlorperazine
(4) Trifluoperazine

2. Haloperidol resembles the piperazine phenothiazines.

3. Thiothixene resembles the piperazine phenothiazines.

4. Others (e.g., loxapine, pimozide).

5. Newer and more atypical antipsychotic drugs:
a. Clozapine
b. Olanzapine
c. Quetiapine
d. Risperidone
e. Ziprasidone
f. Aripiprazole

Antidepressant Drugs

Drug treatment of depression is based on increasing serotonin (5-HT) or NE (or both) at synapses in selective tracts in the brain. This can be accomplished by different mechanisms.

Treatment takes several weeks to reach full clinical efficacy.

1. Tricyclic antidepressants (TCAs)
a. Amitriptyline
b. Desipramine
c. Doxepin
d. Imipramine
e. Protriptyline

2. Selective serotonin reuptake inhibitors (SSRIs)
a. Fluoxetine
b. Paroxetine
c. Sertraline
d. Fluvoxamine
e. Citalopram

3. Monoamine oxidase inhibitors (MAOIs)
a. Tranylcypromine
b. Phenelzine

4. Miscellaneous antidepressants

a. Bupropion
b. Maprotiline
c. Mirtazapine
d. Trazodone
e. St. John’s Wort

Antimania Drugs

These drugs are used to treat manic-depressive illness.

A. Drugs
1. Lithium
2. Carbamazepine
3. Valproic acid

Sedative Hypnotics

1. Benzodiazepines
2. Barbiturates
3. Zolpidem and zaleplon
4. Chloral hydrate
5. Buspirone
6. Other sedatives (e.g., mephenesin, meprobamate, methocarbamol, carisoprodol, cyclobenzaprine)
7. Baclofen
8. Antihistamines (e.g., diphenhydramine)
9. Ethyl alcohol

Antiepileptic Drugs

Phenytoin
Carbamazepine
Phenobarbital
Primidone
Gabapentin
Valproic acid
Ethosuximide

Anti-Parkinson Drugs

a. L-dopa plus carbidopa (Sinemet).
b. Bromocriptine, pergolide, pramipexole, ropinirole.
c. Benztropine, trihexyphenidyl, biperiden, procyclidine.
d. Diphenhydramine.
e. Amantadine.
f. Tolcapone and entacapone.
g. Selegiline.
 

Antiarrhythmic Drugs

Cardiac Arrhythmias 
Can originate in any part of the conduction system or from atrial or ventricular muscle.
Result from
– Disturbances in electrical impulse formation (automaticity) 
– Conduction (conductivity) 
– Both

MECHANISMS OF ARRHYTHMIA
ARRHYTHMIA – absence of rhythm
DYSRRHYTHMIA – abnormal rhythm

ARRHYTHMIAS result from:
1. Disturbance in Impulse Formation
2. Disturbance in Impulse Conduction
- Block results from severely depressed conduction
- Re-entry or circus movement / daughter impulse

Types of Arrhythmias

• Sinus arrhythmias 
– Usually significant only 
– if they are severe or  prolonged 

• Atrial arrhythmias 
– Most significant in the presence of underlying heart disease
– Serious: atrial fibrillation can lead to the formation of clots in the heart 

• Nodal arrhythmias 
– May involve tachycardia and increased workload of the heart or bradycardia from heart block 

• Ventricular arrhythmias 
– Include premature ventricular contractions (PVCs), ventricular tachycardia, and ventricular fibrillation 

Indications
• To convert atrial fibrillation (AF) or flutter to normal sinus rhythm (NSR) 
• To maintain NSR after conversion from AF or flutter 
• When the ventricular rate is so fast or irregular that cardiac output is impaired
– Decreased cardiac output leads to symptoms of decreased systemic, cerebral, and coronary circulation 
• When dangerous arrhythmias occur and may be fatal if not quickly terminated 
– For example: ventricular tachycardia may cause cardiac arrest 

Mechanism of Action 
• Reduce automaticity (spontaneous depolarization of myocardial cells, including ectopic pacemakers) 
• Slow conduction of electrical impulses through the heart
• Prolong the refractory period of myocardial cells (so they are less likely to be prematurely activated by adjacent cells 
 

Ibuprofen

used to relieve the symptoms of arthritis, primary dysmenorrhoea, fever; and as an analgesic, especially where there is an inflammatory component.

Indications

rheumatoid arthritis, osteoarthritis, juvenile rheumatoid arthritis, primary dysmenorrhoea

fever, relief of acute and/or chronic pain states in which there is an inflammatory component

MOA

inhibition of  cyclooxygenase (COX); thus inhibiting prostaglandin synthesis.

Adverse effects 

Nitrates 
– Headache, hypotension, dizziness, lightheadedness, tachycardia, palpitations 

Beta-adrenergic blocking agents
– hypotension, bradycardia, bronchospasm, congestive heart failure 

Calcium channel blockers 
– hypotension, dizziness, lightheadedness, weakness, peripheral edema, headache, congestive heart failure, pulmonary edema, nausea, and constipation 

Drugs that increase effects of Antianginal drugs 
• Antihypertensive 
• Diuretics 
• Phenothiazine antipsychotic agents
• Cimetidine 
• Digoxin 

Drugs that decrease effects of Antianginal
• Adrenergic drugs - epinephrine 
• Anticholinergic 
• Calcium salts 
• Phenobarbital, Phenytoin

Adjunctive Antianginal Drugs

In addition to antianginal drugs, several other drugs may be used to control risk factors and prevent progression of myocardial ischemia to myocardial infarction and sudden cardiac death.

These may include:
• Aspirin. This drug has become the standard of care because of its antiplatelet (ie, antithrombotic) effects. Recommended doses vary from 81 mg daily to 325 mg daily or every other day; apparently all doses are beneficial in reducing the possibility of myocardial reinfarction, stroke, and death. Clopidogrel 75 mg/day,
Is an acceptable alternative for individuals with aspirin allergy.

• Antilipemics. These drugs may be needed by clients who are unable to lower serum cholesterol levels sufficiently with a low-fat diet. Lovastatin or a related “statin” is often used. The goal is usually to reduce the serum cholesterol level below 200 mg/dL and lowdensitylipoprotein cholesterol to below 
130 mg/dL.

• Antihypertensives. These drugs may be needed for clients with hypertension. Because beta blockers and calcium channel blockers are used to manage hypertension as well as angina, one of these drugs may be effective for both disorders.

OXYMETAZOLINE
 

It is a directly acting sympathomimetic amine used in symptomatic relief in nasal congestion which increases mucosal secretion.

It is used:
- As a nasal decongestant in allergic rhinitis, with or without the addition of antazoline or sodium chromoglycate. 
- As an ocular decongestant in allergic conjunctivitis.

Compounds like naphazoline and xylometazoline are relatively selective α2 agonists, which on topical application produce local vasoconstriction.