GLP-1 analogs

Exenatide

Mechanism

GLP-1 is an incretin released from the small intestine that aids glucose-dependent insulin secretion
basis for drug mechanism is the observation that more insulin secreted with oral glucose load compared to IV 

Exenatide is a GLP-1 agonist

↑ insulin
↓ glucagon release
the class of dipeptidyl peptidase inhibitors ↓ degradation of endogenous GLP-1
e.g.) sitagliptin, -gliptins 
 

Clinical use
type II DM
 

Toxicity
nausea, vomiting
pancreatitis
hypoglycemia
if given with sulfonylureas

Gentamicin

Gentamicin is a aminoglycoside antibiotic, and can treat many different types of bacterial infections, particularly Gram-negative infection.

Gentamicin works by binding to a site on the bacterial ribosome, causing the genetic code to be misread.

Like all aminoglycosides, gentamicin does not pass the gastro-intestinal tract, so it can only be given intravenously or intramuscularly.

Gentamicin can cause deafness or a loss of equilibrioception in genetically susceptible individuals. These individuals have a normally harmless mutation in their DNA, that allows the gentamicin to affect their cells. The cells of the ear are particularly sensitive to this.

Gentamicin can also be highly nephrotoxic, particularly if multiple doses accumulate over a course of treatment. For this reason gentamicin is usually dosed by body weight. Various formulae exist for calculating gentamicin dosage. Also serum levels of gentamicin are monitored during treatment.

E. Coli has shown some resistance to Gentamicin, despite being gram-negative

Serotonin-norepinephrine reuptake inhibitors(SNRIs)

e.g. venlafaxine and duloxetine
- Inhibit the reuptake of both 5-HT and norepinephrine 
- Has a more favourable adverse effect profile than TCAs

Norepinephrine reuptake inhibitor

e.g. bupropion, reboxetine

Monoamine receptor antagonists

e.g. mirtazapine, trazodone, mianserin

Routes of Drug Administration

Intravenous

• No barriers to absorption since drug is put directly into the blood.
• There is a very rapid onset for drugs administered intravenously.  This can be advantagous in emergency situations, but can also be very dangerous.
• This route offers a great deal of control in respect to drug levels in the blood.
• Irritant drugs can be administer by the IV route without risking tissue injury.
• IV drug administration is expensive, inconvenient and more difficult than administration by other routes.
• Other disadvantages include the risk of fluid overload, infection, and embolism.  Some drug formulations are completely unsafe for use intravenously.

Intramuscular:

• Only the capillary wall separates the drug from the blood, so there is not a significant barrier to the drug's absorption.
• The rate of absorption varies with the drug's solubility and the blood flow at the site of injection.
• The IM route is uncomfortable and inconvenient for the patient, and if administered improperly, can lead to tissue or nerve damage.

Subcutaneous

Same characteristics as the IM route.

Oral

• Two barriers to cross: epithelial cells and capillary wall.  To cross the epithelium, drugs have to pass through the cells.

• Highly variable drug absorption influenced by many factors:  pH, drug solubility and stability, food intake, other drugs, etc.
• Easy, convenient, and inexpensive.  Safer than parenteral injection, so that oral administration is generally the preferred route.
• Some drugs would be inactivated by this route
• Inappropriate route for some patients.
• May have some GI discomfort, nausea and vomiting.
• Types of oral meds = tablets, enteric-coated, sustained-release, etc.
• Topical, Inhalational agents, Suppositories

Methyl salicylate

also known as oil of wintergreen, betula oil, methyl ester) is a natural product of many species of plants Structurally, it is methylated salicylic acid It is used as an ingredient in deep heating rubs

Stimulants: 

Amphetamines: amphetamine is a substrate of serotonin and NE uptake transporters so in cytoplasm, it competes for transport into storage vesicles → ↑ [ ] in cytoplasm then excess amines bind to membrane transporter and are transported out of cell

Drugs: 
a.    Dextroamphetamine: psychomotor stimulant (↓ fatigue), short-term weight loss, prevents narcolepsy
b.    Methylphenidate (Ritalin): prevents narcolepsy, treatment for ADD and ADHD
c.    Methamphetamine: psychomotor stimulant, abused widely (cheap, easy to make)

Side effects: 
a.    CNS: euphoria, anxiety, agitation, delirium, paranoia, panic, suicidal/homicidal impulses, psychoses, tolerance (develops rapidly to most CNS effects), physical dependence (not clinically relevant)
b.    CV: headache, chills, arrhythmias and HTN (may be fatal)