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

Celecoxib

is a highly selective COX-2 inhibitor and primarily inhibits this isoform of cyclooxygenase, whereas traditional NSAIDs inhibit both COX-1 and COX-2. Celecoxib is approximately 10-20 times more selective for COX-2 inhibition over COX-1.

Being a sulphonamide can cause skin rash &  hypersensitivity rxn., occasional oedema& HT.

Indication

Osteoarthritis ( 100‐200mg BID ) , rheumatoid  arthritis, dysmenorrhea, acute gouty attacks,  acute musculoskeletal pain. 

Selective serotonin reuptake inhibitors (SSRIs)

e.g. fluoxetine, paroxetine, citalopram, and sertraline
- Most commonly used antidepressant category
- Less likely to cause anticholinergic side effects
- Relatively safest antidepressant group in overdose
- Selectively inhibits reuptake of serotonin(5-HT)

Mode of Action;
- Well absorbed when given orally
- Plasma half-lives of 18-24 h allowing once daily dosagedaily dosage
- Metabolised through CYP450 system and most SSRIs inhibit some CYP isoforms
- Therapeutic effect is delayed for 2-4 weeks

ADVERSE DRUG REACTIONS

- Insomnia, increased anxiety, irritability
- Decreased libido
- Erectile dysfunction, anorgasmia, and ejaculatory delay
- Bleeding disorders
- Withdrawal syndrome

Antihypertensives Drugs

CATEGORIES
I.    Diuretics to reduce blood volume 
Chlorothiazide (Diuril)

II. Drugs that interfere with the Renin-Angiotensin System

A. Converting enzyme inhibitors             Captopril , enalapril, Lisinopril

B. Angiotensin receptor antagonists         Saralasin Losartan 

III. Decrease peripheral vascular resistance and/or cardiac output

A. Directly acting vasodilators
1. calcium channel blockers           Nifedipine , Diltiazem,  amlodipine

2. potassium channel activators     Minoxidil 

3. elevation of cGMP                      Nitroprusside 

4. others                                         Hydralazin e

B. Sympathetic nervous system depressants

1. α-blockers                             Prazosin, phentolamine, phenoxybenzamine

2. β-blockers                             Propranolol ,Metoprolol, atenolol

3. norepinephrine synthesis inhibitors     Metyrosine 

4. norepinephrine storage inhibitors     Reserpine
 
5. transmitter release inhibitors         Guanethidine 

6. centrally acting: decrease 
sympathetic outflow                     Clonidine , methyldopa

Stages of anesthesia

Stage I

Analgesia

Still conscious but drowsy

Stage II

Excitement stage

Loss of consciousness, however, irregular ventilation may be present which affects absorption of inhalation agents.

Reflexes may be exaggerated.

This is a very dangerous stage

Stage III

Surgical anesthesia

Loss of spontaneous movement

Regular, shallow respiration

Relaxation of muscles

Stage IV

Medullary paralysis

Death

Amoxicillin

a moderate-spectrum

β-lactam antibiotic used to treat bacterial infections caused by susceptible

Mode of action Amoxicillin acts by inhibiting the synthesis of bacterial cell walls. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a major component of the cell wall of Gram-positive bacteria. microorganisms. It is usually the drug of choice within the class because it is better absorbed, following oral administration, than other beta-lactam antibiotics. Amoxicillin is susceptible to degradation by  β-lactamase-producing bacteria, and so is often given clavulanic acid.

Microbiology Amoxicillin is a moderate-spectrum antibiotic active against a wide range of Gram-positive, and a limited range of Gram-negative organisms

Susceptible Gram-positive organisms : Streptococcus spp., Diplococcus pneumoniae, non β-lactamase-producing Staphylococcus spp., and Streptococcus faecalis.

Susceptible Gram-negative organisms  Haemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitidis, Escherichia coli, Proteus mirabilis and Salmonella spp.

Resistant organisms Penicillinase producing organisms, particularly penicillinase producing Staphylococcus spp. Penicillinase-producing N. gonorrhoeae and H. influenzae are also resistant

All strains of Pseudomonas spp., Klebsiella spp., Enterobacter spp., indole-positive

Proteus spp., Serratia marcescens, and Citrobacter spp. are resistant.

The incidence of β-lactamase-producing resistant organisms, including E. coli, appears to be increasing.

Amoxicillin and Clavulanic acid Amoxicillin is sometimes combined with clavulanic acid, a β-lactamase inhibitor, to increase the spectrum of action against

Gram-negative organisms, and to overcome bacterial antibiotic resistance mediated through β-lactamase production.