Chapter 2 Peripheral nervous system drugs - cholinergic antagonists Flashcards
Cholinergic antagonists
- muscarinic blockers, ganglion blockers, and neuromuscular blockers
- @ therapeutic doses – muscarinic antagonists do not bind to nicotinic receptors and neuromuscular lbockers (Nm antagonists) do not bind to muscarinic receptors
- The above 3 all all compettive antgonists which can be overcome by adequate concentrations of cholinergic agonists
Muscarinic antagonists
- prototype antimuscarinic agent is atropine (an alkaloid isolated from atropa belladona [deadly nightshade] + many other plants
- Atropine blocks muscarinic actions of cholinergic agonists
Actions consist of following order as the dose atropine is increased
1) Decreased salivary and bronchial secretions
2) Decreased sweating (sympathetic controlled)
3) Pupil dilation and tachycardia
4) Inhibition of voidng (constriction of sphincter and relaxation of detrusor)
5) Decreased GI motility
6) Decreased GI gastric secretions
- some antipsychotics, antihistamines, antidepressants, and opoids have anticholinergic effects; should be told that dry mouth, tachycardia, and constipation are probable side effects
Belladonna poisoning
- happens w/ ingestion of anticholinergic drugs or plants such as
1) nightshade
2) thorn-apple
3) Jimson weed
4) Stinkweed
5) Devil’s apple ‘
- poisoning can occur with children receiving atropinic eye drops d/t systemic absorption
sx –
* severe antimuscarinic effects
* restlessness
* headache
* rapid + weak pulse
* ataxia
* burning skin
* possibly coma
Children more susceptible
Treated with IV physotigmine; CNS excitement or convulsions may be treated with benzodiazepines
Ganglion blockers
- Ng antagonists
- block nicotinic receptors in both sympathetic and parasympathetic ganglia
- these ganglia are clusters of synpases between the spinal cord and visceral organs
- Ach is NT in all sympathetic and parasympathetic ganglia
- these ganglion blockers reduce effects of whichever system predominant
- For example, an resting individual - parasympathetic dominates all organs except blood vessels and sweat glands (therefore administration to nonstressed individual will shift to sympathetic predominance)
- d/t complexity and unpredictability
— seldom used (hexamethonium and mecamylamine)
— trimethephan (used for HTN crisis)
Atropine
alkaloids
Atropine is used as an antidote in cholinergic poisoning, or organophosphate poisoning, acting by blocking acetylcholine action at muscarinic receptors. Atropine reverses DUMBBeLSS symptoms, which are diarrhea, urination, miosis, bradycardia, bronchoconstriciton, lacrimation, salivation, and sweating. It should be noted that atropine does not block the CNS excitation (the E in DUMBBELSS), and this is mediated by nicotinic receptors, while atropine blocks muscarinic receptors.
M1 receptor
* stomach - less secretion of pepsin and acid
M2
* Heart (low dose) —– bradycardia [CNS mediated]
* Heart (high dose) —– tachycardia
* CNS — decreased memory and concentration (M1 in agonists…?)
* Lungs — bronchodilation, decreased secretion
* **GI tract — decreased motility ** (M3 in agonists)
* Eye —-
1) cycloplegia (paralysis of cillary muscle resulting in loss of visual accomodation [ability of lens to change its refractive power to view the near objects clearly]); this condition causes muscle to contract! => l/t dilation (this muscle is next to the iris which lies above the eye itself)
2) mydriasis – dilation of pupil of the eye
3) increased outflow resistance (blocking canal for humor fluid to leave)
M3
* glands — decreased salivation and sweating
——
clinical use —
* Preanesthetic to prevent respiratory secretions
* tx of parkinsonism (motor syndrome that manifests as rigidity, tremors, and bradykinesia. Parkinsonism is caused by Parkinson’s disease in about eighty percent of cases of parkinsonism) [However, experts have discovered that people with the condition often have a decrease in dopamine that allows acetylcholine to take over. When this occurs, muscles become too “excited,” which leads to symptoms such as jerking movements and tremors.]
* severe bradycardia
* peptic ulcers
* IBS
* mild diarrhea
* bladder spasms
* enuresis (involuntary urination, especially by children at night)
* bronchospasm (happen when the muscles that line your bronchi (airways in your lungs) tighten. This results in wheezing, coughing, and other symptoms)
adverse effects
* dry mouth
* urinary retention
* tachycardia
* CNS-drive bradycardia (general increase in vagal tone) —- LOW DOSE
* High doses — CNS excitation (irritability, delerium) followed by CNS depression => possibly result in death (low dose – more mild excitabilty)
* Add on to above point — atropine does not necessarily depress CNS, but can stimulate medulla and other higher cerebral centers (potentially extreme confusion, deliriant hallucinations, and excitation especially among the elderly. These latter effects are because atropine is able to cross the blood–brain barrier)
Contraindicated
* closed angle glaucoma
* open angle glaucoma (In open-angle glaucoma, the increase in pressure is often small and slow. In closed-angle glaucoma, the increase is often high and sudden.)
* prostatic hypertophy (can l/t complete urinary retention by not relaxing sphincter or contracting detrusor)
* heart disease
* obstructive bowel disease
* asthma patients (Giving atropine, either systemically or as a nebulised solution, results in bronchodilatation. Inhaled doses of 2.5 mg atropine are associated with adverse effects such as dryness of the mouth, tachycardia, palpitations and blurred vision. With higher inhaled doses, systemic absorption can result in urinary retention (particularly in the elderly), headache and changes in mental status. Atropine is therefore no longer given as a nebulised solution)
frequent dosing needed, secreted via urine
Scopolamine
alkaloid
**MORE POTENT **
* Eye —- (M2)
1) cycloplegia (paralysis of cillary muscle resulting in loss of visual accomodation [ability of lens to change its refractive power to view the near objects clearly]); this condition causes muscle to contract! => l/t dilation (this muscle is next to the iris which lies above the eye itself)
2) mydriasis – dilation of pupil of the eye
3) increased outflow resistance (blocking canal for humor fluid to leave)
- **glands (M3) **— decreased salivation and sweating
Less potent
* Heart (M2) – HR [tachy?]
* Lungs (M2) — brochodilation, decreased secretion
* GI tract (M2) — dec motility
clinical use —
* prevention of motion sickness (Anticholinergic antiemetics are agents that block muscarinic receptors and inhibit cholinergic transmission from the vestibular nuclei [medulla and pons of hindbrain] to the vomiting center [4th ventricle]. Anticholinergic antiemetics are mainly used to prevent or treat motion sickness)
* N/V
* irritable colon syndrome (stops excessive motility)
* mild dysentery
* diverticulitis
adverse effects
* More CNS depression than atropine at low doses; similar to atropine at high doses (CNS excitation [irritability, delirium, etc] => CNS depression => coma)
Contraindicated
* if hypersensitive to belladonna (Its roots, leaves and fruits contain alkaloids: atropine, hyocyamine and scopolamine) or barbiturates
* barbiturates – Barbiturates have a depressant effect on the brain. They increase the activity of gamma aminobutyric acid (GABA), a brain chemical that creates a sedating effect.
They can have short- to long-acting effects. It depends on the specific drug.
Barbiturates are habit-forming. You can develop a tolerance to and dependence on them. This means you need greater amounts to get the same effect. In addition, abruptly stopping this type of medication causes withdrawal symptoms.
Dicylcomine (bentyl)
synthetic-tertiary compound
- nonspecific direct relaxant effect on smooth muscle (has no antimuscarinic activity and thus little effect on gastric acid secretion)
clinical use –
* IBS to decrease bowel motility
adverse effects:
* tachycardia
* headache
* flushing
* drowsiness
* nervousness
* dry mouth
* constipation
* urinary retention
pharmacokinetics
little or no antimuscarinic activity with no effect on gastric acid secretions
CONTRAindicated – in infants < 6 months old
Atropine pneumonic
Atropine is used as an antidote in cholinergic poisoning, or organophosphate poisoning, acting by blocking acetylcholine action at muscarinic receptors. Atropine reverses DUMBBeLSS symptoms, which are diarrhea, urination, miosis, bradycardia, bronchoconstriciton, lacrimation, salivation, and sweating. It should be noted that atropine does not block the CNS excitation (the E in DUMBBELSS), and this is mediated by nicotinic receptors, while atropine blocks muscarinic receptors.
Oxybutynin (ditropan)
syntheitc-tertiary compound
- direct antipasmodic effect on smooth muscle (bladder); no anticholinergic effects
- 1/5 of the anticholinergic effect of atropine with 4-10 times the antispasmodic activity
clinical use — relief of bladder spasm that cause urinary leakage and incontinence
adverse effects:
* tachycardia
* headache (blood brain barrier)
* flushing (Anticholinergics decrease how much you sweat, which can cause your body temperature to rise.)
* drowsiness (CNS depressant)
* nervousness (blood brain b arrier)
* dry mouth
* constipation
* urinary retention
===========
* decreased sweating, decreased lacrimation
* rash (d/t increased temperature)
* mydriasis (dilation of pupil of the eye)
* cycloplegia (dilation d/t paralysis of ciliary muscle)
flavoxate (urispas)
synthetic-tertiary compound
- relaxes smooth muscle of lbadder and also has direct effect on muscle
clinical use —
* symptomatic relief of dysuria (Discomfort when urinating can have causes that aren’t due to underlying disease.)
* urgency
* nocturia (the need for patients to get up at night on a regular basis to urinate)
* suprapubic pain
adverse effect —-
* tachycardia
* headache (blood brain barrier)
* flushing (Anticholinergics decrease how much you sweat, which can cause your body temperature to rise.)
* drowsiness (CNS depressant)
* nervousness (blood brain b arrier)
* dry mouth
* constipation
* urinary retention
===========
* decreased sweating, decreased lacrimation
* rash (d/t increased temperature)
* mydriasis (dilation of pupil of the eye)
* cycloplegia (dilation d/t paralysis of ciliary muscle)
tolterodine (detrol)
synthetic-tertiary compound
- relaxes smooth muscle of bladder and also has direct effect on muscle
clinical use —
* treatment of overactive bladder
adverse effects —
* dry mouth
* constipation
* headache
* dyspepsia
* blurred vision
reduce dose with liver impairment
trihexyphenldyl (artane)
biperiden (akineton)
procyclidine (kemadrin)
benztropine (cogentin)
clidinium bromide
mepenzolate bromide (cantil)
**methoscopolamine (pamine)
syntehtic-tertiary compound
- centrally acting (CNS)
- reduce akinesia (inability to voluntarily move one’s muscles and limbs. It is most commonly associated with advanced Parkinson disease due to the degeneration of dopaminergic neurons), tremor, and rigidity by 20%
- may also reduce drooling
clinical use —
* adjunct tx of parkinsonism
* control of drug-induced extrapyramidal d/o
adverse effects:
* tachycardia
* hypotension
* dry mouth
* disorientation
* constipation
* blurred vision
* urinary retention
* decreased sweating
more selective CNS activity than atropine
Exceptions..
**methoscopolamine action at organ is GI compared the rest!
Glycopyrrolate (robinul)
- centrally acting (CNS)
- reduce akinesia (inability to voluntarily move one’s muscles and limbs. It is most commonly associated with advanced Parkinson disease due to the degeneration of dopaminergic neurons), tremor, and rigidity by 20%
- may also reduce drooling
clinical uses —
1) peptic ulcer
2) IV form => dec salivary and tracheobroncial secretions and
3) to block cardiac inhibitory reflexes during induction of anesthesia and intubation
adverse effects:
* tachycardia
* hypotension
* dry mouth
* disorientation
* constipation
* blurred vision
* urinary retention
* decreased sweating
more selective CNS activity than atropine
