PHAR232 exam prep Flashcards
Nicotine can increase blood pressure and heart rate. Given what you know about the autonomic nervous system and the location of receptors within that system, explain how nicotine can accomplish this, being sure to include information on intracellular signalling events. HINT: in one location in the periphery, nAChRs control vesicle mobilisation and therefore you need to remember how vesicles are mobilised
1ST activation of Sympathetic Ganglia
= Activate nAChRs
= Incease Influx of Na+ ions
= depolarization & AP
= Increase in NA alpha 1 and beta 1 Rs
= Activate PLC
= increase IP3 & DAG
= increase Ca2+ from SR
= Increase Ca++
= Constriction of blood vessels
= Increase BP, HR and contraction force
2nd = stimulate nAChRs on Adrenal Glands
- Influx of Na+ - depolarize to threshold = AP
- Open voltage gated Ca2+ channels
- Mobilise ACh vesicles
- Release Adrenalin
- Activate beta-1 receptors in the heart
- Activate adenylate cyclase
= Increase cAMP + PKA - = Increase voltage gated Ca2+ activity
- = Increase Ca2+
- = Increase HR, contraction force
It is well established that the sympathetic nervous system controls sweating and flushing of the skin. However, acetylcholinesterase inhibitors can increase the amount of sweat that is produced. In light of what you know about the autonomic nervous system, explain how this is possible.
= AchE inhibitors = reduced ACh breakdown
= Increased ACh
= Increased SNS
= SNS uses ACh as the NT at the skin, sweat glands and superficial skin
= Increasesd ACh = increase sweating and flushing
= Increases goosebumps
Even if Ach is predominantly associated with PNS **
Organophosphate pesticides are acetylcholinesterase inhibitors. Explain the type of symptoms you would expect from organophosphate pesticide poisoning in a person and the extent to which a muscarinic acetylcholine receptor antagonist would work as an antidote. Using resources available on the web, is there anything else that can be used as an antidote? If so, what is the name of this drug and what is its role in the management of organophosphate pesticide poisoning.
Blocking AChE = Increases ACh
= Significantly Increased PNS
= Shallow breathing,
= Slowed HR
= hypotension, unconsciousness,
= Skin: flushing, heavy sweating
= Increased saliva,
= diarrhoea, incontinence, blurry vision (constricted pupils)
= Muscle twitching
= Tear production
Drug to counteract = atropine
= mAChR antagonist (competitive)
= competitive binding on mAChRs
= Reduced ACh binding
= Reduces PNS overstimulation
You have found a drug that binds to the receptors on the pre-synaptic cell that act as the “eyes” of the synapse (i.e. the autoreceptors). If this drug is able to increase the amount of neurotransmitter released, what must its action be at this receptor? Explain your answer.
- Alpha-2 receptors upon activation, INHIBIT NT release
- = negative feedback mechanism
- Needs to be an antagonist of autoreceptors to INCREASE NT release
Cocaine blocks the neuronal noradrenaline transporter (NET, also known as uptake 1) in the adrenergic synapse. What is the effect on the activity of the noradrenergic synapse in the presence of cocaine? NOTE: please focus on the synapse, not a particular target tissue.
- NET = acts like VACCUUM removing NA
= Cocaine blocks NET (noradrenaline transporter)
= Decreased re-uptake of NA
= NA synaptic cleft accumulation
= Prolonged NA availability
= Increased HR
= Increased SNS
Monoamine oxidase inhibitors are used to treat depression. If you block this enzyme, what happens to signalling at the adrenergic synapse? NOTE: please focus on the synapse, not a particular target tissue.
MOAs = breakdown of NT to metabolites
- MOA inhibitors = Increased MOI
- = decrease breakdown of serotonin, dopamine and NA
- = Increased NT in presynaptic neuron
- = Increased vesicle storage
- = Increase NT availability
- = Increased NT release into synaptic cleft
- = Prolonged NT availability in synaptic cleft
You are involved with a team trying to manage a patient who has been administered a drug that blocks beta-2 adrenergic receptors. Explain the effect of these drugs directly on blood vessels. Speculate on the effect on overall blood pressure if these drugs only acted directly on blood vessels.
- Beta-2 receptor on BV usually = vasodilation
- Blocking Beta-2 receptor = vasoconstriction
- = Increased vascular resistance
- = Increase BP
A young man decides to end his life when his relationship breaks up. He purchases a number of bottles of eye drops containing pilocarpine, a muscarinic agonist normally used to treat glaucoma, and drinks the contents in rapid succession. His friends find him shortly thereafter and take him to the Emergency Department of the local hospital. Provide an overview of the symptoms that he will be experiencing upon arrival at the hospital and explain why they occur.
- Knew muscarinic receptors would slow HR
- To lower HR enough for death
mAChRs activation = Increase PNS
= Decrease HR, contraction force and CO
= Vasodilation
= Increase GI = Increase diarrhoea
= Increased glandular secretions = increased tears, sweating, salivation, flushing
= Increased dizziness
= Hypotension
= Blurred vision (decreased intraocular pressure)
Explanation of Symptoms:
mAChRs = Increase PNS
Pilocarpine = muscarinic agonist, or parasympathomimetic
= Increase mAChRs activity
Overstimulation PNS, leading to what’s sometimes termed a “SLUDGE” syndrome (Salivation, Lacrimation, Urination, Diarrhea, Gastrointestinal cramps, Emesis).
Catechol-O-methyltransferase (COMT) is a metabolic enzyme used by adrenergic neurons. Mutations of these enzymes have been identified in a small subset of people with schizophrenia. You work for a large research lab that is trying to develop COMT inhibitors. Describe the role of this enzyme in adrenergic neurons and the impact on adrenergic signalling if this enzyme were inhibited.
Catechol-O-methyltransferase (COMT) – back up enzyme to destroy NA, serotonin and dopamine
= transfers methyl group to catecholamines
= Primary deactivation and breakdown of NA, 5-HT and DA
COMT inhibition
= Increase catecholamines
= Increased serotonin, NA, DA
= Increase NT availability
= Increased cognition
= Prolonged availability for neurotransmission
Potential side effects:
= Adrenergic R overstimulation
= Increased SNS
= Increased HR, BP
Mutations = changed availability of NTs
Inhibit COMT = increases NA
Clonidine is used in the management of hypertension. Given that it is an agonist and that receptors are associated with vasoconstriction, explain how this drug could reduce blood pressure.
Alpha-2 receptors = autoreceptors = turn off NA release
= Decrease neuronal excitation
Alpha-2 = Auto receptor for the adrenergic system
- Presynaptic Location: α2 autoreceptors
- Inhibition of Release: When activated by NA, α2 auto-receptors inhibit release of NA.
- = negative feedback mechanism,
- = limits NA released into synaptic cleft.
Identify ONE (1) condition or disease or disorder the alpha-1 agonist drug is used to treat AND 1 key side effect.
Nasal congestion
side effect: Hypertension
(A1 = VASOCONSTRICTION)
Identify ONE (1) condition or disease or disorder the alpha-2 agonist drug is used to treat AND 1 key side effect.
Hypertension
side effect: Dry mouth
(A2 = INHIBITS NA
= INCREASED PNS )
Identify ONE (1) condition or disease or disorder the Betea-1 agonist drug is used to treat AND 1 key side effect.
Heart failure (to increase CO)
Side effect: Tachycardia
(beta 1 = increase HR, Increase force of contraction)
Identify ONE (1) condition or disease or disorder the beta-2 agonist drug is used to treat AND 1 key side effect.
Asthma to increase bronchodilation
Side effect: Muscle tremors
Think: beta-2 = 2 lungs = increase SNS = want more air
= bronchodilation
Identify ONE (1) condition or disease or disorder the muscarinic agonist drug is used to treat AND 1 key side effect.
- Glaucoma (to reduce intraocular pressure)
Diarrhoea
(muscarinic = increased PNS)
