Cholinoceptor blocking drugs Flashcards
What type of drug is atropine? (What receptor does it work on?)
Muscarinic antagonist
M
What type of drug is ipratropium? (What receptor does it work on?)
Muscarinic antagonist
M
What type of drug is benztropine? (What receptor does it work on?)
Muscarinic antagonist
M
What type of drug is hexamethonium? (What receptor does it work on?)
Nicotinic antagonist
Nn, Nm
What type of drug is mecamylamine? (What receptor does it work on?)
Nicotinic antagonist
Nn, Nm
What type of drug is d-tubocuraine? (What receptor does it work on?)
Non-depolarizing neuromuscular blocker
Nm
What type of drug is succinylcholine? (What receptor does it work on?)
Depolarizing neuromuscular blocker
Nm
True or false: atropine blocks only M1 type of muscarinic receptors
False–all muscarinic
What are the pharmacological effects of atropine on secretions?
decreased secretions
What are the pharmacological effects of atropine on the heart?
Tachycardia
What are the pharmacological effects of atropine on bod heat?
Hyperthermia
What are the pharmacological effects of atropine on the urinary tract?
Retention and constipation
What are the pharmacological effects of atropine on the CNS?
Behavioral excitation and hallucinations
True or false: atropine does not affect blood pressure when given alone
True
Atropine is used in the treatment of what?
Peripheral vasodilation caused by choline esters or AChE inhibitors
Acute intoxication of physostigmine is treated with what?
Atropine
Why is atropine given for pericardiocentesis?
Prevents vagal reaction in some procedures
What are the effects of ipratropium (atrovent) on the lungs? What receptors are used here?
Decreases bronchoconstriction
Decreases bronchial secretions
M3
What are the clinical uses for ipratropium (atrovent)?
COPD flares
What is the primary site of action for benztropine (cogentin)?
Muscarinic receptors in the brain
What is the effect of benztropine (cogentin)?
Reestablishes dopaminergic cholinergic balance
What is the clinical use of benztropine?
Parkinson’s disease
What are the two ganglionic blocking agents discussed in class?
hexamethonium
Mecamylamine
What is the effect of hexamethonium/mecamylamine on arterioles?
vasodilation/hypotension
What is the effect of hexamethonium/mecamylamine on veins?
Dilation, decreased CO
What is the effect of hexamethonium/mecamylamine on the heart?
tachycardia
What is the effect of hexamethonium/mecamylamine on iris?
Mydriasis
What is the effect of hexamethonium/mecamylamine on ciliary muscle?
cycloplegia
What is the effect of hexamethonium/mecamylamine on the GI tract?
Decreased tone, and motility
What is the effect of hexamethonium/mecamylamine on the bladder?
urinary retention
What is the effect of hexamethonium/mecamylamine on salivary glands?
Xerostomia
What is the effect of hexamethonium/mecamylamine on sweat glands?
Anhidrosis
How do depolarizing neuromuscular blocking agents like succinylcholine cause paralysis?
Overload the receptors by keeping channel open
How do non-depolarizing neuromuscular blocking agents like D-tubocurarine cause paralysis?
Block Nm receptors
All of the neuromuscular blocking drugs resemble what chemical?
Ach
Do neuromuscular blocking drugs cross the cell membrane?
No–ionized
What are the neuromuscular blocking drugs used for?
Facilitate tracheal intubation
Why don’t the neuromuscular blocking drugs act on the CNS?
Have a quaternary N+
What is the MOA of d-tubocurarine (small doses and large)?
Prevents opening of nicotinic channel
small doses compete with Ach, large doses enter channel pore
What is phase 1 of the MOA of succinylcholine?
Binds to Nm, keeps channel open
What is phase 2 of the MOA of succinylcholine?
end plate is repolarized, but desensitized
What is the clinical use of succinylcholine?
Decreases neuromuscular transmission during anesthesia
What is the last muscle to be affected by succinylcholine?
diaphragm
What are the side effects of neuromuscular blockers?
Hypotension
Hyperkalemia
Hyper or hypokalemia with succinylcholine?
Hyperkalemia
What causes the hyperkalemia seen with succinylcholine?
Massive muscle contraction
What is the order of response to succinylcholine (which types are affected first/last)?
Larger muscles paralyzed first
How does tubocurarine produce hypotension?
Massive histamine release
What is the effect on the eye with succinylcholine?
Increased intraocular pressure
Why is muscle pain a side effect of succinylcholine use?
Large muscular contractions
What is the pathway of catecholamine synthesis? (5)
Y Dopa Dopamine Norepi Epi
In most sympathetic postganglionic pathways, what is the final product/neurotransmitter?
norepinephrine
What happens to norepinephrine in the adrenal medulla?
Converted to epinephrine
What is the rate limiting step in catecholamine synthesis?
Y to dopa by tyrosine hydroxylase
What is the drug that can interfere with catecholamine synthesis?
Metyrosine
People who eat fermented cheese cannot take with type of medications? Why?
Ones that interfere with catecholamine breakdown
Tyramine in cheese will increase NE synthesis
What is the drug that inhibits the packaging of dopaminergic neurotransmitters?
Reserpine
Blocking catecholamine synthesis will result in hyper or hypotension?
Hypotension
What is the protein that takes up NE back into the neuron?
Norepinephrine transporter NET
The VAMP protein that releases catecholamines from the nerve terminal is inhibited by what?
Bretylium
What are the two routes of NE breakdown?
Reuptake via NET1
Degradation by catechol-O-methyl transferase
What is the MOA of cocaine/Tricyclic antidepressants?
Inhibits NET1 transporter for dopamine/NE
Why does cocaine cause MI?
Increased NE d/t blockage of NET1
What is the MOA of MAOIs?
Cannot metabolize dopa via mitochondrial monoamine oxidase
What is the main source of peripheral vascular resistance in our bodies?
Arterioles
What is the MOA of alpha 1 receptors?
Gq–phospholipase C, PKC
What is the MOA of beta 1, beta 2 receptors?
Gs–adenylate cyclase, increases cAMP
What is the MOA of alpha 2 receptors?
Gi-inhibits adenylate cyclase, decreases cAMP
What are the two receptors that decrease cAMP?
ALpha 2
M2
What is the autoreceptor on the cholinergic system?
M2
What is the autoreceptor on the adrenergic system?
alpha2
What are the receptors that utilize the Gq protein?
H1 alpha1, V1, M1, M3
What are the receptors that utilize the Gs protein?
Beta 1, Beta2, D1, H2, V2
What are the receptors that utilize the Gi protein?
M2, alpha2, D2
alpha 1 activation in the eye causes what?
contraction
alpha 1 activation in the arterioles causes what?
contraction
alpha 1 activation in the veins causes what?
Contraction
alpha 1 activation in the bladder causes what?
contraction
alpha 1 activation in the male sex organ causes what?
ejaculation (contraction)
alpha 1 activation in the liver causes what?
glycogenolysis
alpha 1 activation in the kidney causes what?
Decreased renin release
alpha 2 activation in the prejunctional nerve terminals causes what?
decrease transmitter release and NE synthesis
alpha 2 activation in the platelets causes what?
aggregation
alpha 2 activation in the pancreas causes what?
Decreased insulin
beta 1 activation on the SA node causes wha?
Increased HR
beta 1 activation on the AV node causes wha?
increased conduction veloicty
beta 1 activation on the atrial and ventricular muscles causes wha?
increased force of contraction
beta 1 activation on the kidney causes wha?
Increased renin release
beta 1 activation on the purkinje fibers causes wha?
Increased automaticity
beta 2 activation on the blood vessels causes what?
vasodilation
beta 2 activation on the uterus causes what?
relaxation
beta 2 activation on the brochioles causes what?
dilation
beta 2 activation on the skeletal muscles causes what?
increased glycogenolysis, contractility
beta 2 activation on the liver causes what?
Increased glycogenolysis
beta 2 activation on the pancreas causes what?
Increased insulin synthesis
D1 activation in the kidney causes what?
Vasodilation–increased GFR
Which has a higher affinitiy for catecholamines: alpha or beta receptors. Why is this significant?
beta
Is the cause for the dose dependent effects seen with catecholamines
What is the only place in the body that NE is converted to epineprhine?
Adrenal medulla
What does MOA-A degrade?
5HT, NE, and tyramine
What does MOA-B degrade?
dopamine
Phospholipase C activates what enzyme through Ca release?
PKC
What are the G coupled receptors for the Nn and Nm?
None–use Na/K channels
What is the adrenergic receptor you would want to activate if you wanted to increase GFR/urianry output?
D1
What are the receptors that you want to block in the eye to reduce aqueous humor production?
Beta 1, beta 2
What is the effect of activating alpha 1 receptor in the eye?
Mydirasis (dilation) d/t radial muscle activation
What is cycloplegia?
Impairment of the ciliar muscle of the eye, not allowing for accomodation
Why don’t you see cycloplegia with use of alpha 1 agonists?
Ciliary muscle does not have an alpha 1 receptor
Why does atropine cause cycloplegia?
Inhibits M on the sphincter muscle
What is the equation for blood pressure?
TPRCO : CO=HRSV
Increasing blood pressure increases baroreceptor discharge to work on what part of the brain? What does this in turn do?
Vasomotor center–Decreases sympathetic tone/decreases vasoconstriction
What is the effect of the vasomotor center on the PANS to decrease blood pressure?
increase vagal tone
What are the three effects of the vasomotor center on the SANS in response to increased BP?
decreased vasoconstriction
Decreased cardiac contraction
Decreased HR
What is the receptor on blood vessels that increaes total peripheral resistance when activated? What happens to the heart rate when this happens?
alpha 1
reflex bradycardia