Anticholinergics

Question 1

Anticholinergic drugs competitively antagonize the effects of what?

Answer 1

Ach

Question 2

What terms are commonly used interchangeably when blocking the parasympathetic nervous system?

Answer 2

• Antimuscarinic and anticholinergic

- although truly an anticholinergic can have effects at Nicotinic cholinergic sites as well

Question 3

What drug is a naturally occurring alkaloid of the Belladonna plant or synthetic derivatives?

Answer 3

Atropine

Question 4

What drug occurs in Hyoscyamus or “Henbane”?

Answer 4

Scopolamine

Question 5

Antihistamines, antipsychotic and antidepressant drugs may also have what type of effects do to similar structures of anticholinergics?

Answer 5

antimuscarinic effects (anti parasympathetic)

Question 6

How do anticholinergics cause parasympatholytic effects?

Answer 6

Combine reversibly with muscarinic receptors preventing Ach from activating site

Question 7

How can anticholinergics effects be overcome or reversed?

Answer 7

increasing Ach concentration = (muscarinic receptor activation= parasympathetic effects “rest and digest”)

Question 8

Where are the effects of muscarinic receptor M1 activation seen?

Answer 8

CNS and stomach

Question 9

Where are the effects of muscarinic receptor M2 activation seen?

Answer 9

airway smooth muscle, heart, CNS

Question 10

Where are the effects of muscarinic receptor M3 activation seen?

Answer 10

CNS, glands, airway smooth muscle

Question 11

Where are the effects of muscarinic receptor M4 activation seen?

Answer 11

CNS, heart

Question 12

Where are the effects of muscarinic receptor M5 activation seen?

Answer 12

CNS

Question 13

Low dose anticholinergics will inhibit which muscarinic receptor?

Answer 13

M3 receptors (glands-bronchial and salivary)

Question 14

Slightly higher dose anticholinergics will stimulate which muscarinic receptor?

Answer 14

M2 receptors (heart and eye)

Question 15

High dose anticholinergics will inhibit which muscarinic receptor?

Answer 15

M1 cholinergic control of GI motility and secretion and urination,

Question 16

Which anticholinergic drugs will produce CNS effects?

Answer 16

• Mainly scopolamine
• minimal from atropine at normal doses
• none from Glycopyrrolate

Question 17

What are the CNS effects seen with scopolamine and atropine?

Answer 17

-Sedation (usually first, especially with Scopolamine), followed by stimulation, hallucinations
– Amnesia
– Decreases tremor from Parkinson’s (decreased dopaminergic activity, relative excess of cholinergic activity)

Question 18

What is Central Anticholinergic Syndrome (aka postop delirium)?

Answer 18

• Side effects ranging from stupor to excitation and delirium, seizures, coma etc from muscarinic receptor involvement in the brain.
• commonly from atropine toxicity

Question 19

What drugs/compounds can cause Central Anticholinergic Syndrome?

Answer 19

-Any compound with antimuscarinic effects which cross BBB includes:
– Antipsychotic and antidepressant drugs
– Antiparkinson and antihistamines
– Belladonna alkaloids, tertiary amines, certain plants

Question 20

What is the anticholinergic effect seen with the eye?

Answer 20

– Mydriasis
– Cycloplegia
– Reduced lacrimal secretion (dry eyes)

Question 21

What is mydriasis?

Answer 21

blocking action of pupillary constrictor muscle= dilation

Question 22

What is cycloplegia?

Answer 22

weakens contraction of ciliary muscle, lost ability to accommodate

Question 23

What is the anticholinergic effect seen with the cardiovascular system?

Answer 23

Net effect is increased HR, little effect on BP

Question 24

Why is increased HR seen after giving anticholinergic?

Answer 24

• SA node sensitive to muscarinic blockade

- Atria very innervated by PNS via the vagus

Question 25

Low doses of Atropine can cause what?

Answer 25

-Initial bradycardia (may be the result of block of presynaptic fibers which normally limit Ach release in the SA node)

Question 26

Does the parasympathetic nervous system have any innervation on blood vessels?

Answer 26

No but stimulates release of EDRF (endothelium derived relaxing factor)

Question 27

Release of EDRF (endothelium derived relaxing factor) results in what?

Answer 27

coronary dilation

Question 28

At toxic doses (and in some individuals at normal doses) antimuscarinic drugs can cause?

Answer 28

cutaneous vasodilation, especially in the upper body (mechanism is unclear)

Question 29

What is the anticholinergic effect seen with the respiratory system?

Answer 29

– Causes bronchdilation and reduced secretions (not as efficient as Beta stimulants) – Smooth muscle and secretory glands receive vagal stimulation so blocking this results in above

Question 30

What is the anticholinergic effect seen with the GI system?

Answer 30

-Decreased motility and secretions –Antisialagogue= decrease saliva –Less effect on gastric secretions but volume is reduced

Question 31

What is the anticholinergic effect seen with the GU system?

Answer 31

– Relaxes smooth muscle of ureter and bladder wall, slowed voiding (can cause retention) – Useful in treating spasms – No significant uterine effects

Question 32

What is the anticholinergic effect seen with the sweat glands?

Answer 32

– Suppression of thermoregulatory sweating | – Elevated temp only in large doses or in infants (“atropine fever”)

Question 33

What are anticholinergics used for pre-op?

Answer 33

– Antisialagogue – Sedation (rarely) – Protection from vagal response

Question 34

Other uses for anticholinergics include:

Answer 34

- Sedation - Mydriasis for ophthalmology - Treatment of bradycardia - Bronchodilation - Motion sickness

Question 35

What are some situations where anticholinergics are used to treat bradycardia?

Answer 35

– From other drugs (volatile agents, narcotic, beta blocker) – From cardiac pathology – From anticholinesterase agents

Question 36

What anticholinergics can be used for motion sickness?

Answer 36

Scopolamine & Dramamine- (thought to block medulla from over stimulation from vestibular apparatus)

Question 37

What is Ipratropium Atrovent used for?

Answer 37

- bronchodilator | - Also available as nasal spray for allergic rhinitis

Question 38

Where is Ipratropium metabolized and excreted?

Answer 38

Metabolized in liver, excreted in feces

Question 39

Common side effects from Ipratropium (Atrovent)?

Answer 39

cough, headache, dry mouth, palpitations, nausea, etc.

Question 40

What is the structure of atropine and what does this allow for or prevent?

Answer 40

- Tertiary amine | - lipid soluble, allows it to cross BBB

Question 41

Small doses of anticholinergics, most particularly Atropine, may result in what?

Answer 41

decreased heart rate (<0.1mg pediatrics)

Question 42

What the physiology of the bradycardia seen with low doses of atropine?

Answer 42

- Thought to be the result of block of presynaptic inhibitory M1 receptors (from more affinity in low doses) on vagal nerve endings which normally provide negative feedback to stop further ACH release. - The lack of negative feedback mechanism results in more ACH which overcomes the sinoatrial, M2 blockade from the low dose

Question 43

What is the structure of Scopolamine and what does this allow for or prevent?

Answer 43

* Tertiary amine, lipid soluble | * Readily crosses BBB

Question 44

What is the structure of Glycopyrrolate and what does this allow for or prevent?

Answer 44

* Quaternary ammonium | * Does not cross BBB