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Pharmacology

Sulfonylureas

1st generation
tolbutamide
chlorpropamide

2nd generation

glyburide
glimepiride
glipizide

Mechanism

glucose normally triggers insulin release from pancreatic β cells by increasing intracellular ATP
→ closes K+ channels → depolarization → ↑ Ca2+ influx → insulin release

sulfonylureas mimic action of glucose by closing K+ channels in pancreatic β cells 
→ depolarization → ↑ Ca2+ influx → insulin release

its use results in

↓ glucagon release
↑ insulin sensitivity in muscle and liver

Clinical use

type II DM

stimulates release of endogenous insulin 
cannot be used in type I DM due to complete lack of islet function

Toxicity

first generation

disulfiram-like effects
especially chlorpropamide

second generation

hypoglycemia
weight gain

Propoxyphene

  • A methadone analog.Used orally to relieve mild to moderate pain.
  • A typical opiate, it does not possess anti-inflammatory or antipyretic actions, but has little or no antitussive activity.
  • Cannot be used parenterally because of irritant properties.
  • Has a low addiction potential primarily due to its lack of potency as an opiate.
  • The most common adverse side effects are:• dizziness, drowsiness, and nausea and vomiting. • these effects are more prominent in ambulatory patients.
  • Withdrawal symptoms have occurred in both adults and in neonates following use of the drug by the mother during pregnancy.
  • CNS depression is additive with other CNS depressants.

Cells of the Nervous System 

1-Neurons (Nerve Cells):function units of the nervous system by conducting nerve impulses, highly specialized and amitotic. Each has a cell body (soma), one or more dendrites, and a single axon. 
• Cell Body: it has a nucleus with at least one nucleolus and many of the typical cytoplasmic organelles, but lacks centriolesfor cell division. 

• Dendrites:Dendrites and axons are cytoplasmic extensions (or processes), that project from the cell body. They are sometimes referred to as fibers. Dendrites (afferent processes) increase their surface area to receive signals from other neurons, and transmit impulses to the neuron cell body. 

• Axon: There is only one axon (efferent process) that projects from each cell body.        
It carries impulses away from the cell body.

2-Glial cells: do not conduct nerve impulses, but support, nourish, and protect the neurons. They are mitotic, and far more numerous than neurons. 

Astrocyte: A glialcell that provides support for neurons of the CNS, provides nutrients regulates the chemical composition of the extracellularfluid.

• Oligodendrocyte: A type of glialcell in the CNS that forms myelin sheaths.

• Microglia:The smallest glialcells; act as phagocytes (cleaning up debris) and protect the brain from invading microorganisms.

• Schwann cell:A cell in the PNS that is wrapped around a myelinatedaxon, providing one segment of its myelin sheath.

DIURETICS

Specific Therapeutic Objective

Clinical State(s)

Drug(s) (Class)

Draw fluid from tissue to vascular space reduce tissue edema

Cerebral edema
glaucoma

Mannitol (Osmotic)
Glucose (Osmotic)
Glycerin (Osmotic)

Decrease renal swelling
expand tubular volume

Renal shutdown

Glucose (Osmotic)
Mannitol (Osmotic)

Modest and/or sustained decrease in venous hydrostatic pressure

Congestive heart failure
Hepatic cirrhosis
Udder edema

Hydrochlorothiazide (thiazide)
Chlorothiazide (thiazide)

Aggressive and/or short-term decrease in venous hydrostatic pressure

Congestive heart failure
Hepatic cirrhosis
Udder edema

Furosemide (loop)

Inhibit aldosterone action

Hepatic cirrhosis
Congestive heart failure

triamterene (K+ sparing)
spironolactone (K+ sparing - competitive)

Reduce potassium wasting 2o to other diuretic

Hepatic cirrhosis
Congestive heart failure

triamterene (K+ sparing)
spironolactone (K+ sparing - competitive)

Inhibit ADH action

Inappropriate ADH secretion

lithium (aquaretic)
demeclocycline (aquaretic

Increase calcium secretion

Malignant hypercalcemia

  • Paraneoplastic
  • Hypervitaminosis D

Furosemide (loop)

Reduce urine output

Diabetes insidpidus

Hydrochlorothiazide (thiazide)
Chlorothiazide (thiazide)

Urine alkalinization

Various

Carbonic anhydrase inhibitors

Neurotransmitters can be classified into:
1. Biogenic amines:
ACh, NA, DA, 5-HT, Histamine
2. Amino acids:
Excitatory (glutamate & asparate)
Inhibitory (GABA& glycine)
3. Others:
Adenosine, melatonin

Ciclopirox:Ciclopirox is a synthetic antifungal agent for topical dermatologic use.

Aquaretics
An aquaretic is a class of drug that is used to promote aquaresis, the excretion of water without electrolyte loss.

Lithium, demeclocycline

Mechanism of Action

1.    Block ADH action on distal tubule and collecting duct. Blocking ADH decreases H2O permeability. H2O is not recovered (distal tubule) using osmotic draw of counter-current multiplier so aquaretics reduce water reabsorption (tubule to blood stream). 
2.    Net effect is an increase in free water clearance
 

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