| What are cholinergic antagonists? | drugs block action of Ach, cholinergic blockers, anticholinergic, parasympatholytics
Divided into Antimuscarinic drugs (M1 selective and non selective) and antinicotinic drugs (ganglion blockers and neuromuscular blockers) |
| How are antimuscarinic anticholinergics? | Block muscarinic receptors causing inhibition of all their functions, block salivary and sweat glands, with little or no effect on neuromuscular junctions/ ganglia, some anti-histamine/antidepressants can have antimuscarinic activity.
Muscarinic receptors are found in autonomic effect organs like heart, smooth muscle, brain, and exocrine glands |
| How is atropine as antimuscarinic drug? | Tertiary amine belladonna alkaloid, high affinity for muscarinic receptors binds competitively prevents acetylcholine from binding.
Acts centrally or peripherally, action for 4 hours except when topic on eye may last for days
Action on eye (persistent mydriasis, unresponsiveness to light, cycloplegia (cannot focus on near vision), in patients with narrow angle glaucoma can lead to increase in intraocular pressure dangerous.
On GI (antispasmodic reduce activity of GI, no effect of HCl production, not effective for healing of peptic ulcer)
On Urinary (reduce hypermotility of bladder, used in enuresis among children but a adrenergics better use)
On CV (Block M2 receptors on SA node cause increase in cardiac rate, don't affect BP)
On secretions (block salivary glands, dries mucosa (xerostomia), sweat and lacrimal glands also affected)
Ophthalmo (mydriatic and cycloplegic effects, replaced by short acting antimuscarinics)
Antispasmodic (relaxes GI and bladder)
Antidote of cholinergic agonists (treats overdoses of cholinesterase inhibitors and mushroom poisoning(
Antisecretory (prior to surgery stop respiratory secretions |
| What are pharmacokinetics and adverse effects of atropine? | Pharmacokinetics (readily absorbed, partially metabolized by liver, eliminated by urine)
Adverse effects (depends on dose, dry mouth, blurred vision, tachycardia and constipaton.
CNS effects (restlessness, confusion, hallucinations, and delirium which may progress to depression, collapse of CV and respiratory system, and death
Low doeses of anticholinesterases may be used to overcome atropin toxicity)
It is generally available as sulfate salt can be admin IV, SC, IM, ophthamic, oral but only in combination with other products
Effects from 0.5 mg (some dryness), 1 mg (accelerated HR and mild pupil dilation), 2 mg (palpitation, dilated pupils, blurring) , 5 mg (difficulty speaking/swallowing, restessness fatigue, dry hot skin), 10 mg (pulse rapid weak, hallicination , delirium, coma) |
| How is scopolamine as antimuscarinic? | Tertiary amine belladonna alkaloid, produces peripheral effects like atropine, greater action on CNS (observed at therapeutic doses).
Actions (anti-motion sickness, unusual blocking of short-term memory, produces sedation but at higher doses excitation, may produce euphoria)
Therapeutic uses (limited prevention of motion sickness, blocking short term memory, prophylactic effect not treating of motion sickness, amnestic action important adjunct drug in anesthetic products) |
| How is ipratropium (bromid) as antimuscarinic? | Inhaled , derivative of atropine, useful in treatment of asthma in patients unable to take adrenergic agonists, benificial also in COPD |
| How are tropicamide and cyclopentolate as antimuscarinics? | Ophthalmic solutions for similar conditions as atropine, duration shorter than atropine, Tropicamide 6 hours, cyclopentolate 24 hours |
| How are ganglion blockers? | Act on nicotinic receptors of parasympathetic and sympathetic autonomic ganglia, no selectivity to parasympathetic or sympathetic and not effective as neuromuscular antagonsits.
Rarely used therapeutic, serve as tools in experimental pharmacology |
| How is nicotine as ganglionic blocker? | It is a component of cigarette smoke, poison with undesirable effects, w/out therapeutic benifit and deleterious to health, highly addicitive.
Causes release of dopamine in brain stimulating nicotinic receptors of Ach, gives people good feeling.
Available as patches, lozenges, gums, other forms. Absorbed and effective in reducing craving for nicotine in people who wish to stop smoking, depending on the dose depolarizes autonomic ganglia, resulting first in stimulation then in paralysis of all ganglia.
Nicotine receptors exist at CNS, participating in stimulant effect of the drug |
| What are the actions of nicotine as ganglionic blocker? | CNS (highly lipid soluble readily crosses BBB, low doses produces euphoria and arousal as well as relaxation.
Improves attention, learning, problem solving, and reaction time.
High doses lead to central respiratory paralysis, it is also an apetite suppressant.)
Peripheral effects as ganglionic blockade (stimulates sympathetic, adrenal medulla and parasympathetic, increase BP and HR, so harmful in HTN pt, induce vasoconstriction decrease coronary blood flow, affecting patients with angina, increase peristalsis, secretions by parasympathetic ganglia
Higher doses BP falls, activity of GI and bladder ceases due to block of parasympathetic_ |
| How is Mecamylamine as ganglionic blockade? | Produces competitive nicotinic blockade of ganglia, selective on sympathetic ganglion.
Hypotensive effect due to reduced sympathetic tone, vasodilation, reduced CO.
Duration of action 10 hours after a single admin, used to lower BP in emergencies |
| What are neuromuscular blocking antinicotinic drugs? | Block cholinergic transmission between motor nerve endings and nicotinic receptors of skeletal muscles, structural analogues of Ach
Either anatognists (non-depolarizing) or agonists (depolarizing) at receptors, clinically useful for producing complete muscle relaxation, without having higher anesthetic doses, also useful in facilitating intubation |
| How are competitive (non depolarizing) blockers? | Curare (d-Tubocurarine) was first drug capable of blocking neuromuscular junction.
D-d-Tubocurarine is a prototype agent in this class, naturally occurring mono-quaternary alkaloids, largely replaced by other agents due to side effects (allergisant), increased safety of anesthesia, less anesthetic required for muscle relaxation so patients recover quickly and completely after surgery. |
| How is mechanism of action of competitive non depolarizing blockers | At low doses (Prevent Ach binding, prevent depolarization of muscle membrane inhibit muscle contraction.
Can be overcome by increasing concentration of Ach in synaptic cleft (admin anticholinesterases))
At high doses (Block ion channels at end plate, lead to weakening of neuromuscular transmission, reduces anticholinesterase action reverse actions of non depolarizing muscle relaxants) |
| What are actions and therapeutic uses of non-depolarizing blcokers? | 1-Benzylisoquinolinium compounds (Curare, Mivacurium, Atracurium release histamine lead to fall in BP, flushing and bronchoconstriction)
Used as adjuvant of anesthesia to relax skeletal muscles, facilitate intubation in surgery, orally ineffective due to quaternary amines, penetrate membranes poorly can't cross BBB, many not metabolized excreted unchanged in urine Curare and miva.
Atracurium degraded in plasma by ester hydrolysis, releases histamine provokes seizures.
Cisatracurium same as atra but less likely to get effects)
2-Aminosteroid drugs (Vecuronium and Recuronium deacetylated in liver, clearance may be prolonged in pt with hepatic disease, excreted unchanged in bile, choice depends on onset of action and duration of muscle relaxation |
| How are drug interactions in non depolarizing blockers? | Anticholinesterases (overcome action of nondepolarizing blockers, but with increased dosage they can cause depolarizing block as a result of elevated Ach concentrations at end-plate membrane)
Aminoglycoside Abx (Gentamycin, inhibit Ach release competing with Ca ions, synergize with curare and other competitive blockers enhancing blockade)
Ca Channel Blockers (increase block in curare) |
| How is mechanism of action of depolarizing agents (Succinylcholine)? | attaches to the nicotinic receptor and acts like acetylcholine to depolarize the junction
Unlike acetylcholine, which is instantly destroyed by acetylcholinesterase, the depolarizing agent persists at high concentrations in the synaptic cleft, remaining attached to the receptor for a relatively longer time and providing a constant stimulation of the receptor.
The depolarizing agent first causes the opening of the sodium channel associated with the nicotinic receptors, which results in depolarization of the receptor (Phase I)
This leads to a transient twitching of the muscle (fasciculations).
Continued binding of the depolarizing agent renders the receptor incapable of transmitting further impulses
With time, continuous depolarization gives way to gradual repolarization as the sodium channel closes or is blocked.
This causes a resistance to depolarization (Phase II) and a flaccid paralysis.
In flaccid paralysis, muscles lose their tone and reflexes, leading to a lack of voluntary movement and a soft or flabby appearance (molle) in the affected limbs |
| What are actions and therapeutic uses of Succinylcholine? | Short-lasting muscle fasiculation and few minutes of paralysis, no ganglionic block unless high doses, weak histamine-release action, duration of action is short, due to rapid breaking by plasma cholinesterase.
If they get into neuroskeletal junction they cannot be degraded so they bind to nicotinic receptors and redistribution to plasma is necessary for metabolism
Note that genetics may increase or decrease plasma cholinesterase levels
It is useful in rapid endotracheal intubation required during anethesia. |
| How are pharmacokinetics of succinylcholine? | Injected IV, breif action (minutes) result from redistribution and rapid hydrolysis by plasma cholinesterase, given by continuous infusion |
| What are adverse effects of succinylcholione? | Apnea (if deficient in plasma cholinesterase lead to prolonged apnea due to paralysis of diaphragm)
Hyperkalemia
Hyperthermia |
