1. A drug is taken up by the transporter and into a vesicle by VMAT. The drug displaces monoamines, which are now displaced into the cytosol. The transporter will now work in the opposite direction and pump the monoamines out of the cytosol. An example of this are amphetamines.

2. Phosphorylation of the transporter. This inhibits the reuptake of monoamines. Examples of this are cocaine and methylphenidates

-indirect acting

-sympathomimetic

-primarily for central use but also has peripheral effects

-different monoamines may be affected by different drugs

-different areas of the brain may be stimulated because of isozymes of transporters. 

-works more for NE and DA than for 5HT

ADD/ADHD:

patients who have short attention span. lack of focus, inability to complete tasks; can be given with alpha 2 agonists to decrease their hyperactivity

-may be involved with the catecholamines in the cortex

narcolepsy:

hyperinsomnia; patients who fall asleep during the day

obesity:

no longer FDA approved

tolerance develops

reduced appeitie

-increased peripheral resistance, hypertension, and reflex bradycardia (or tachycardia because effects on beta 1)

contraction of smooth muscle (alpha 1 stimulation)

-constriction of the bladder sphincter: painful, difficult urination

-Constriction of the GI smooth muscle: reduced GI motility: can lead to spams

-insomnia, headache, reduced appetitie

-hallucinations, aggression, paranoia

-increased wakefullness, alertness, reduced fatigue

-increased respiration

-elevated mood, increased motor/speech activity, euphoria

-tolerance and dependence may develop: withdrawal syndrome not clear; discontinuation after long term use is associated with fatigue and depression

-toxicity: psychotic effects, euphoria, insomnia, anxiety, panic, suicidal tendencies, arrhythmias, angina  

-DEATH: cerebral hemorrhage if overdosed: no evidence of MI or stroke

- since these drugs cause insomnia, it may be best to take these drugs in the morning, so that by the end of the day, the drug wears off and the patient is able to go to bed at night.

-Also, a patient should also start at a lower dose and then taper up to avoid any s/e

-alpha 2 may also be used to help people sleep

-a combination of fenfluramine and phentermine (amphetamine like anorexiant) 

-when fenfluramine is metabolized, it goes to norfenfluramine. This is very potent for 5HT2B because stimulation of this causes proliferation, esp. in the cardiac valves in the interstitial tissue. It can also cause pulmonary hypertension

-ergots can cause stimulation of 5HT2B as well

-amphetamine-like indirect effects and agonist at all the adrenergic receptors: decogestant, broncodilatory, anorexiant, and stimulant effects

-used IV for the reversal of epidural induced hypotension

-alot of natural products had ephedrine at one point, but it is now band because it was related to alot of deaths

-SNRI

-non-stimulant, low abuse potential

-used for ADD/ADHD: takes about 2-4 weeks for onset of action to occur (less effective than amphetamine and methylphenidate)

-increased heart rate, increased blood pressure, irritability, dry mouth, decreased appetitie, nasuea, anorexia

-tiredness in children and teends, waking or insomnia in adults

-reversible liver damage

-risk of suicidal thoughts (black box warning)

Straterra is metabolized by 2D6

-if we look at the AUC, half-life, and Cmax, we can see a 5-10 fold in PM vs EM

-give a lower dose of straterra with fluoxetine because fluoxetine is a 2D6 inhibitor, therefore would cause a large increase in levels of straterra 

-indirect acting sympatholytics

-metirosine works by inhibiting tyrosine hydroxlyase, causing depletion of NE

-reserpine inhibits VMAT causing depletion of NE as well