Doxycycline

Commonly prescribed for infections and to treat acne. treat urinary tract infections, gum disease, and other bacterial infections such as gonorrhea and chlamydia., as a prophylactic treatment for infection by Bacillus anthracis (anthrax). It is also effective against Yersinia pestis and malaria.

Pramlintide -Amylin mimetics

Mechanism
synthetic analogue of human amylin that acts in conjunction with insulin
↓ release of glucagon
delays gastric emptying

Clinical use

type I and II DM

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. 

Effects and Toxic Actions on Organ Systems

1. Local anesthetics (dose dependent) interfere with transmission in any excitable tissue (e.g. CNS and CVS).

2. CNS effects

 a. Central neurons very sensitive.

 b. Excitatory-dizziness, visual and auditory disturbances, apprehension, disorientation and muscle twitching more common with ester type agents.

 c. Depression manifested as slurred speech, drowsiness and unconsciousness more common with amide type agents (e.g. lidocaine).

 d. Higher concentrations of local anesthetic may eventually produce tonic-clonic[grand mal]  convulsions.

 e. Very large doses may produce respiratory depression which can be fatal. Artificial respiration may be life-saving.

 3.CVS effects

 a. Local anesthetics have direct action on the myocardium and peripheral vasculature by closing the sodium channel, thereby limiting the inward flux of sodium ions.

 b. Myocardium usually depressed both in rate and force of contraction. Depression of ectopic pacemakers useful in treating cardiac arrhythmias.

 c. Concentrations employed clinically usually cause vasodilation in area of injection.

 d. Vasoconstrictors such as epinephrine may counteract these effects on myocardium and vasculature.

4.  Local Tissue Responses

 a. Occasionally focal necrosis in skeletal muscle at injection site, decreased cell motility and delayed wound healing.

 b. Tissue hypoxia may be produced by action of excessive amounts of vasoconstrictors.

Distribution

Three major controlling factors:  

Blood Flow to Tissues:  rarely a limiting factor, except in cases of abscesses and tumors.
Exiting the Vascular System:  Occurs at capillary beds.
- Typical Capillary Beds - drugs pass between cells 
- The Blood-Brain Barrier-  Tight junctions here, so drugs must pass through cells.  Must then be lipid soluble, or have transport system.
- Placenta - Does not constitute an absolute barrier to passage of drugs.  Lipid soluble, nonionized compounds readily pass.  
- Protein Binding:  Albumin is most important plasma protein in this respect.  It always remains in the blood stream, so drugs that are highly protein bound are not free to leave the bloodstream.  Restricts the distribution of drugs, and can be source of drug interactions.

Entering Cells:  some drugs must enter cells to reach sites of action.

Neurolept Anesthesia
An antipsychotic agent such as droperidol plus an opiate analgesic agent such as fentanyl or sufentanil. This latter agent is approximately eight to ten times more potent than fentanyl.