Sympathomimetics III: Release and Uptake Blockers Flashcards
What are uptake blockers?
They elevate sympathetic activity by increasing the concentration of NE at the synapse–allows more receptors to be stimulated for a longer period of time; one mechanism is to increase the release of NE from the pre-synaptic terminal or block the reuptake of NE back into the terminal
What is an amphetamine?
amphetamine
dexamphetamine
methamphetamine
phentermine (fastin)
methyphenidate (ritalin)
phenmetrazine (preludin)
What class of drugs were first synthesized in 1920’s?
phenylisopropylamines
What are amphetamines?
treatment of attention deficit disorder
hyperactivity disorder
narcolepsy
weight loss
What are amphetamines known for?
known for their abuse potential
What part of the body do amphetamines stimulate?
they stimulate the CNS- cortical and reticular activating systems to increase: wakefulness, altertness, mood, initiative, confidence, elation, euphoria, and concentration ability
fatigue is decreased
What are the examples of amphetamines?
1) methamphetamines (speed, ice)
2) 2,5- dimethoxy-4 methylamphetamine (DOM, sTP)
3) methyane-dioxyamphetamine (MDA)
4) methylenedioxymethamphetamine (MDMA, ecstasy, XTC)
How are amphetamines given and how does that affect their absorption?
they are well absorbed whether given orally, smoked, sniffed or injected
How do the lack of -OH group impact the function of amphetamines?
they lack hydroxyl goups on the phenyl ring thereby increasing bioavailability and duration of action, as COMT cannot methylate the molecule
What structual part of amphetamines and helps with its action?
the presence of side chains off the alpha and beta carbons prevents metabolism by MAO; long duration of action
How long is the half life of amphetamines compared to catecholamines?
the half-lives of amphetamine are hours compared to minutes of catecholamines
How does the body rid its self of amphetamines?
significant amount of drugs are excreted unchanged in the urine; the compounds are weak bases so acidification of the urine will increase the rate of excretion
What is the mechanism of action of amphetamines?
it is to elevate the synaptic concentrations of the biogenic amines within the SNS and CNS
How do amphetamines work?
they compete with NE, Epi, DA, and 5-HT for binding to the plasma membrane transporters for these neurotransmitters; the amphetamines are substrates for transport into the synaptic terminal
What happens to amphetamines after they enter the nerve terminal?
they can displace the endogenous vesicular and non-vesicular pools of neurotransmitter out of the terminal causing release
How does the release of neurotransmitters from the terminal as a result of amphetamines occur?
the release can occur via the reversal of the transporters and via diffusion through the membranes
What are some other actions of amphetamines at higher doses?
they directly stimulate alpha-receptors and block MAO at higher doses
What do elevation of NE at the synapse lead to?
elevations of NE in the synapse lead to stimulation of alpha-receptors in the vasculature and of beta-1 receptos in the heart
What are the side effects of amphetamines?
irregular heart beat
irritability, nervousness, a false sense of well being, and insomnia
drowsiness, fatigue, and mental depression after the stimulant effects
following withdrawal-mental depression, nausea and vomitting, stomach cramps, trembling, tiredness, and weakness
What are the drug interactions between amphetamines and alkalizers of the urine (antacids, sodium bicarbonate)?
decrease the rate of elmination
What is the drug interaction between inhalation anesthetics and amphetamines?
sensitive to the heart to sympathomimetic agents
What is the drug interaction between anti-depressants and amphetamines?
they potentiate cardiovascular effects (hypetension and reflex bradycardia)
What is the drug interaction between amphetamines and insulin?
increase the risk of hyperglycemia
What is the drug interaction between beta blockers and amphetamines?
unopposed action of amphetamine and alpha-adrenergic receptors resulting in hypertension and reflex bradycardia
What is the contraindication of amphetamines?
- agitation
- arteriosclerosis
- cardiovascular disease
- glaucoma
- hypertension
What are ephedrine and pseudoephedrine?
they are related to amphetamines, found primarily in cold prepartions for nasal congestion (Sudafed) usually combined with other cold remedies ; non-prescription but on shelves anymore!! ask pharmacist
How is ephedrine/ pseudoephedrine assist in weight loss?
OTC preparations containing Ma Hung extract.
How is ephedrine/pseudoephedrine and bronchodilator?
usually combined with theophylline
What mechanism of action ephedrine/pseudoephedrine?
release NE withc activates alpha and beta-1 receptors
ephedrine can also stimulate beta-2 receptores directly while pseudoephedrine has little beta-2 action; by now you should know the organ effects
What are the side effects ephedrine and pseudoephedrine?
nervousness or restlessness
trouble sleeping
pounding heartbeat
increase in blood pressue
what are the contraindications ephedrine/pseudoephedrine?
angina
arrhythmia
coronary insufficiency
hypertension
What is cocaine?
its a local anesthetic, most often in dentistry
How many people have used cocaine?
more than 20 million americans have used cocaine in their life time; around 20% of those are regular users and 25% of those will become addicted (1 miliion)
How does cocaine imact the intranasal?
cocaine HCl is water soluble and can readily diffuse through the mucous membrane of the nose; it rapidly enter the CNS followed by redistribution to other tissues
How does cocaine impact the body when it is smoked or given by IV?
cocaine base is heated to an aerosol of particles and vapor is then inhaled directly into the lungs where it enters the bloodstream; cocaine rapidly enters the brain and then is rapidly redistributed, creating the drive for more
How is cocaine broken down?
it is metabolized by hepatic and plasma cholinesterases
What will speed up the elimination of cocaine?
acidification of the urine will speed elimination; cocaine and its metabolites are detectable for 3-4 days in the urine
How does cocaine work?
it binds to the dopamine, NE, and 5-HT transporters thereby blocking uptake and elevating NT levels in the synapse (similar to the amphetamines)
it is not a substrate and does not enter the terminal to elicit the release of the neurotramitters; it will lead to depletion of the terminal
What are the side effects of cocaine?
coronary vasoconstriction and myocardial sensitization
arrhythmias
ischemia/stroke
infaracts
endothelial injury-thromus formation
myocarditis and dilated cardiomyopathy
numerous CNS side effects to learn later
What are the drug interactions of cocaine with inhalation anesthetics?
increased risk of ventricular fibrillation and arrhythmia
What are drug interactions of levo and methyldopa and cocaine?
cardiac arrhythmia
What are drug interaction between cocain and post-ganglionic blockers of hypertension?
decreases effect, hypertensive effects
What is the drug interaction between cocaine and beta blockers?
mutual inhibition of effects as well as unopposed alpha action
What is the drug interaction between cocaine and cholinesterase inhibitors?
potentiation of cocaine’s effects
What is the drug interaction between TCA’s and cocaine?
potentiation of cardiocascular effects
What is the drug interaction between MAO inhibitors and cocaine?
potentiate cardiovascular effects of both drugs
What is the drug interaction between sympathomimetics and cocaine?
potentiate CNS and cardiovascular problems
What is tyramine?
it is not used pharmacologically but it is a produce of tyrosine breakdown in the liver and found in various fermented food; its interaction with MAO inhibitors makes it necessary to understand
What happens to tyramine levels as it broken down by MAO?
significant levels are not attained in normal individuals as tyramine is broken down by MAO; however if MAO is inhibited, the levels of tyramine become significantly elevated.
What is the mechanism of action of tyramine?
tyramine can enter the presynaptic terminal via uptake by the NE transporter and then into vesicle via the vesicular transporter; oncre inside the vesicle it is converted to octopamine by dopamine-B-hydroxylase ( the enzyme that converts dopamine to NE).
What happens to octopamine after it is released?
displaces NE from the vesicle where it is released; octopamine does not stimulate the adrenergic receptors
What is tyramines interactions with MAO inhibitors?
chronic MAO inhibitor use without ingestion of exogenous tyramine leads to a buildup of octopamine in vesicles of sympathetic neurons; when the SNS in activated and vesicules release their contents there is less NE release into the synapse
What happens after less NE is relesed into the synapse?
this results in a failure to fully activate adrenergic receptors, epecially alpha-1 receptors on the vasculature, which leads to an overall decrease in blood pressure (orthostatic hypotension)
What will happen to someone on chronic MAO inhibitor therapy?
ingest tyramine a different result is seen, remember the first effect of tyramine is to cause release; thus when tyramine is ingested a large amount of amine is released cause adrenergic receptor stimulation and since MAO is inhibited degradation is prevented
Which foods have high levels of tyramine and must be avoid in patients on chronic MAO therapy?
cheese
yeast
pickled fish
wine
