thingsilearnedinschooltoday:

Calcium channel blockers: can be either dihydropyridines as in amplodipine, felodipine and nifedipine, or nondihydropyridines, as in verapamil and diltiazem (these last two are commonly used for angina pectoris so they do not apply in this post). They inhibit calcium entry into blood vessels (but nifedipine acts on vascular smooth muscle), thus decreasing blood pressure (calcium stimulates contraction). Side effects include peripheral and facial edema (amlodipine), flushing, headache, dizziness, reflex tachycardia (felodipine) and hypotension. Be sure to monitor HR, BP, and signs of edema.

Alpha blockers: these include prazosin, terazosin, and doxazosin. These prevent stimulation of alpha 1 receptors on arteries, allowing vasodilation to occur thus lowering blood pressure, and decreasing venous return to the heart. They may also be used in heart failure and hyperplasia. Side effects include postural hypotension (lightheaded, dizzy, reflex tachycardia). Make sure that BP is monitored (hypotension is common from first dose).

Direct agents: hydralazine blocks alpha 1 receptors on arteries which decreases peripheral resistance and thus arterial blood pressure. It can be given parenterally for hypertensive crises. Side effects include reflex tachycardia, increased blood volume, systemic lupus erythematosus like symptoms, headache, dizziness, weakness and fatigue. Be sure to monitor HR, reports of palpitation and faintness. The second direct agent is minoxidil which acts on arterioles to cause vasodilation, thus decreasing peripheral resistance and blood pressure. It can be used in severe hypertension (while hydralizine is for essential hypertension), but it can also promote HAIR GROWTH!! Side effects include reflex tachycardia, sodium and water retention, hypertrichosis, pericardial effusion, nausea, headache, fatigue, skin reactions, breast tenderness, glucose intolerance and thrombocytopenia. Be sure to monitor HR and BP.

Central acting alpha 2 agonists: First we have methyldopa which activates these receptors (agonist!!) to inhibit sympathetic outflow, thus causing vasodilation, HENCE lowering BP. Side effects include hemolytic anemia, hepatotoxicity, xerostomia, sexual dysfunction, orthostatic hypotension, many CNS effects like drowsiness, decreased mental acuity, nightmares, and depression. Monitor for antibodies against RBCs using Coomb’s test, assess liver function, and check blood counts. Secondly there is clonidine which selectively activates alpha 2 receptors on the brainstem to reduce sympathetic outflow to blood vessels and the heart, thus decreasing blood pressure. Side effects are similar: CND depression, xerostomia, adverse effects like nightmares. Monitor BP and HR.

Alpha 2 agonists are my favorite counterintuitive mechanism of action. See, alpha 2 receptors are autoreceptors, meaning they aren’t on the neuron after the synapse but are on the presynaptic neuron, and what they do is tell it “hey you’ve released enough norepinephrine there buddy, I think it’s time to take a break.” So, alpha 2 agonists will make the neuron constantly think (pardon my homunculus)  that it’s already fired, thus causing it to release much less norepinephrine, if it releases any at all. Alpha 2 agonists are not only used for hypertension, but also for ADHD, Tourette syndrome/tic disorders, and opioid potentiation. They can also be used in a form of anesthesia, although this is usually only done as veterinary anesthesia (xylazine, for example).

antarki:

There is very little drug related info on this website that does not relate to hur dur drinking, or smoking pot, so I figured I would add a bit of my own personal experience with various substances, across the legal spectrum, in the hopes that maybe someone will find this information helpful.

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Nice article! Never tried racetams myself yet, but am hoping to give it a go soon. Probably gonna wait until I start taking grad school classes and really need the extra cognitive boost.

wanderlustfulmaniac asked: Yea, I don't know what delta and those other things are. Teach me? :x

I’d be glad to! I don’t know how much background you have or don’t have so I’ll try to answer this in the most high-level and least jargony way I can. Feel free to ask more questions if you don’t understand something.

Okay so there are the three main types of opiate receptors. They’re all G-protein coupled receptors (GPCR). What this means is when they’re activated (say, when an opiate or endorphin binds to them), they activate another protein inside the cell, which activates more proteins in a really complicated cascading process. Mu is most important one for classical opiate action (I say classical opiate to mean everything you’d think of as an opiate: morphine, fentanyl, codeine, Vicodin, OxyContin, tramadol, etc). What it does when activated is enhances the release of a neurotransmitter called GABA. GABA acts on the brain similarly to Xanax, alcohol, or Ambien. In particular it activates a kind of receptor called a GABA-A receptor. This isn’t a G-protein coupled receptor, instead it’s an ion channel. What this means is that when GABA binds to the receptor, the neuron’s ion channels open up immediately and the neuron immediately starts signalling. Neurons with GABA-A receptors on them tend to be inhibitory. So this is how morphine and other mu opiates reduce pain, by releasing GABA onto nerve cells responsible for transmitting pain signals. Some endorphins also activate the mu opiate receptor. There’s also a different mu opiate receptor (called MOR1D) which is responsible for itching. This is because it binds to a receptor for gastrin-releasing peptide, a compound that’s responsible for transmitting itch signals.

The other two are a little less well-known. Kappa opiate receptor is what salvinorin A (from Salvia divinorum) binds to. When it’s activated, it activates a compound called phosphodiesterase (this is the same compound that’s inhibited by Viagra, although obviously in a very different set of cells!) which breaks down cyclic adenosine monophosphate, or cAMP. cAMP is important in signalling between neurons, and it has an excititory or activating role. Since kappa opioid receptor activation inhibits cAMP, it has an inhibiting role on neurons. This includes both neurons responsible for pain signalling and neurons involved in perception and cognition (which is why salvia causes hallucinations). Certain kinds of endorphins, called dynorphins, activate this receptor.

The delta opiate receptor is probably the least understood. Most opiates act on it to some degree or other, but there aren’t any commonly used drugs that directly activate only the delta opiate receptor. We don’t have much of a clue how they work, as far as I’m aware. But one thing we do know is, while opiates activating the mu receptor reduce the speed of breathing, opiates activating the delta receptor might actually increase it. They also increase brain-derived neurotrophic factor (BDNF) which is a compound that increases neuron growth. So perhaps delta opiates have a future as smart drugs (nootropics) or antidepressants. Enkephalin is the name of the endorphins that act at this receptor.

There are a few receptors that used to be thought of as opiate receptors but no longer are, either because they don’t respond to endorphins at all or because they are genetically very different from the delta, mu, and kappa receptors. The sigma receptor is poorly understood but seems to play a role in long-term modulation of how neurons behave. Some of its ligands include PCP, methamphetamine, the antidepressant Luvox, cocaine, and most cough suppresants. The opioid growth factor receptor was formerly known as the zeta opiate receptor. It doesn’t have anything to do with neurotransmission at all, but the endorphin Met-enkephalin binds to it, so that’s why it was thought to be an opiate receptor. It actually controls tissue proliferation, including skin proliferation, and is the target of a few anti-wart drugs.