General pharm – Cholinergic agents (anti-)

a)

If an agent is cholinergic, it will cause DUMBBELSS signs/symptoms –> Diarrhea, Urination, Miosis, Bradycardia, Bronchoconstriction, neuromuscular Excitation, Lacrimation, Salivation, Sweating.

b)

Anti-cholinergic agents block cholinergic receptors directly. They will cause the opposite of DUMBBELSS –> Constipation, Urinary retention, Mydriasis, Tachycardia, Not bronchodilation (β2 agonism, but not M antagonism, will bronchodilate), Skeletal muscle relaxation, Dry eye, Dry mouth, Anhydrosis.

Atropine

• Highest yield anti-muscarinic for USMLE.
• Directly blocks/antagonizes muscarinic receptors.
• 50F + intraoperatively atropine is administered; what effect will this have on the patient’s vital signs? –> answer = ↑ heart rate.
• Parasympathetic activity (i.e., increased endogenous ACh binding to M2 receptors on atria) will normally slow the heart rate, so blocking this activity will increase heart rate.
• Used as first-line Tx for organophosphate poisoning; then use pralidoxime.

Anti-cholinergic.

Benztropine

• Used to treat cogwheel rigidity in Parkinson disease and acute dystonia due to antipsychotic use.
• High-yield drug for USMLE.
• 72M + shuffling gait + unilateral resting tremor + stiff arm muscles; a drug with which type of MOA will improve his muscle stiffness? –> answer = anti-cholinergic (benztropine).
• 40M + Hx of schizophrenia + started on fluphenazine + a few hours later has abnormal eye movements; Tx? –> answer = benztropine. Patient has oculogyric crisis, which is a type of acute dystonia. Torticollis is another type of acute dystonia, which is an abnormally tight and crooked neck.
• Diphenhydramine is a first-generation H1 blocker that has strong anti-cholinergic side-effects and is sometimes the answer if benztropine not listed. USMLE will not list both at the same time.

Anti-cholinergic (anti-muscarinic).

Blocks muscarinic receptors directly.

Benztropine

• Used to treat cogwheel rigidity in Parkinson disease and acute dystonia due to antipsychotic use.
• High-yield drug for USMLE.
• 72M + shuffling gait + unilateral resting tremor + stiff arm muscles; a drug with which type of MOA will improve his muscle stiffness? –> answer = anti-cholinergic (benztropine).
• 40M + Hx of schizophrenia + started on fluphenazine + a few hours later has abnormal eye movements; Tx? –> answer = benztropine. Patient has oculogyric crisis, which is a type of acute dystonia. Torticollis is another type of acute dystonia, which is an abnormally tight and crooked neck.

Diphenhydramine is a first-generation H1 blocker that has strong anti-cholinergic side-effects and is sometimes the answer if benztropine not listed. USMLE will not list both at the same time.

a) Muscarinic receptor antagonists (block M receptors directly)

Ipratropium, tiotropium, or albuterol.

Ipratropium, Tiotropium

• First-line inhaled muscarinic antagonists used for COPD.
• Don’t bronchodilate as much as they merely decrease any degree of bronchoconstriction.
• Albuterol, a β2 agonist, can also be used first-line for COPD.
• 45M + long Hx of smoking + hyper-inflated lungs; next best step in pharmacologic Tx? –> answer = ipratropium, tiotropium, or albuterol. On one of the 2CK IM forms, ipratropium is correct.

Oxybutynin

• Super-HY for USMLE and shows up all over the NBME exams.
• Used for urge incontinence (hyperactive detrusor).
• Don’t confuse with bethanechol, which is a muscarinic agonist used to treat neurogenic (flaccid) bladder.
• 32F + blurry vision + clonus in right foot + leakage of urine; Tx for urinary leakage? –> answer = oxybutynin. (IV methylprednisolone is a steroid used to treat acute flares of multiple sclerosis, but oxybutynin will specifically address the urge incontinence classically seen MS).

a) Anti-cholinergic (anti-muscarinic). Blocks muscarinic receptors directly.

b) Urge incontinence.

Oxybutynin

• Super-HY for USMLE and shows up all over the NBME exams.
• Used for urge incontinence (hyperactive detrusor).
• Don’t confuse with bethanechol, which is a muscarinic agonist used to treat neurogenic (flaccid) bladder.
• 32F + blurry vision + clonus in right foot + leakage of urine; Tx for urinary leakage? –> answer = oxybutynin. (IV methylprednisolone is a steroid used to treat acute flares of multiple sclerosis, but oxybutynin will specifically address the urge incontinence classically seen MS).

a) Scopolamine

b) Anti-cholinergic (anti-muscarinic). Blocks muscarinic receptors directly.

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Scopolamine

• Classic muscarinic antagonist used for motion sickness.
• 42F + going on a whale watch + Hx of motion sickness; an agent with which type of receptor binding will help prevent motion sickness in this patient? –> answer = muscarinic receptor antagonism (scopolamine).

a) Anti-cholinergic (anti-muscarinic). Blocks muscarinic receptors directly.

b) Motion sickness.

a) Anti-cholinergic (anti-muscarinic). Blocks muscarinic receptors directly.

Hyoscyamine 

• Anti-muscarinic used sometimes for irritable bowel syndrome.

Amitriptyline 

• TCA anti-depressant with potent anti-cholinergic side-effects. Also first-line agent for diabetic neuropathic pain.
• 22F + just started on new drug for depression + now is hot, red, dry; which drug was she started on? –> answer = amitriptyline –> “hot, red, dry” is classic combo for anti-muscarinic effects –> anhydrosis (not sweating) means the patient doesn’t dissipate heat well.
• 78M + history of BPH and T2DM + on amitriptyline for neuropathic pain + has suprapubic mass + elevated creatinine; next best step? –> answer = “stop all anti-cholinergic medications” –> amitriptyline is a TCA used first-line for diabetic neuropathic pain –> anti-cholinergic side-effects can cause urinary retention (suprapubic mass = full bladder). After the TCA is stopped, a catheter will need to be inserted (Surg shelf).

a)

• TCAs (mixed serotonin/NE reuptake inhibitors).
• 1st-gen H1 blockers (histamine 1 receptor blockers).
• Anti-psychotics (D2 receptor antagonists).

b)

All cause anti-cholinergic, anti-α1, and anti-H1 side-effects.

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If an agent is cholinergic, it will cause DUMBBELSS signs/symptoms –> Diarrhea, Urination, Miosis, Bradycardia, Bronchoconstriction, neuromuscular Excitation, Lacrimation, Salivation, Sweating.

Anti-cholinergic agents block cholinergic receptors directly. They will cause the opposite of DUMBBELSS –> Constipation, Urinary retention, Mydriasis, Tachycardia, Not bronchodilation (β2 agonism, but not M antagonism, will bronchodilate), Skeletal muscle relaxation, Dry eye, Dry mouth, Anhydrosis.

“Stop anti-cholinergic meds” (frequently how the answer is written on USMLE). In this case, stop the amitriptyline.

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USMLE wants you to know three classes of drugs that cause three different types of side-effects.

Can seem annoying to learn at first, but super-HY and loaded with points on the Steps.

Tricyclic antidepressants (TCAs; e.g., amitriptyline), first-generation H1 blockers (e.g., diphenhydramine, chlorpheniramine), and antipsychotics all cause anti-cholinergic, anti-α1, and anti-H1 side-effects.

Anti-muscarinic –> “opposite of DUMBBELSS.”

Anti-α1 –> orthostatic hypotension / fainting.

Anti-H1 –> sedation.

Benztropine or diphenhydramine.

The latter is a first-gen H1 blocker with potent anticholinergic side-effects.

This patient has acute dystonia, not neuroleptic malignant syndrome. NMS will have fever. USMLE slams students on this.

Rigidity + fever = NMS; but rigidity + no fever = acute dystonia.

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Benztropine

• Used to treat cogwheel rigidity in Parkinson disease and acute dystonia due to antipsychotic use.
• High-yield drug for USMLE.
• 72M + shuffling gait + unilateral resting tremor + stiff arm muscles; a drug with which type of MOA will improve his muscle stiffness? –> answer = anti-cholinergic (benztropine).
• 40M + Hx of schizophrenia + started on fluphenazine + a few hours later has abnormal eye movements; Tx? –> answer = benztropine. Patient has oculogyric crisis, which is a type of acute dystonia. Torticollis is another type of acute dystonia, which is an abnormally tight and crooked neck.
• Diphenhydramine is a first-generation H1 blocker that has strong anti-cholinergic side-effects and is sometimes the answer if benztropine not listed. USMLE will not list both at the same time.

Diphenhydramine, Chlorpheniramine

• First-generation H1 blockers with such strong anticholinergic side-effects that they frequently show up in USMLE Qs as just being anticholinergics straight-up (i.e., no mention of technically being anti-histamines).
• Used to treat acute dystonia with anti-psychotic use if benztropine not listed.
• 44M + schizophrenia + started on aripiprazole + now has diffuse muscle stiffness/rigidity + temperature is 98.6F; treatment? –> answer = benztropine or diphenhydramine. The latter is a first-gen H1 blocker with potent anticholinergic side-effects. This patient has acute dystonia, not neuroleptic malignant syndrome. NMS will have fever. USMLE slams students on this. Rigidity + fever = NMS; but rigidity + no fever = acute dystonia.
• 38F + schizophrenia + started on olanzapine + now neck is crooked and stiff; Tx? –> answer = diphenhydramine.

Benztropine or diphenhydramine.

The latter is a first-gen H1 blocker with potent anticholinergic side-effects.

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Benztropine

• Used to treat cogwheel rigidity in Parkinson disease and acute dystonia due to antipsychotic use.
• High-yield drug for USMLE.
• 72M + shuffling gait + unilateral resting tremor + stiff arm muscles; a drug with which type of MOA will improve his muscle stiffness? –> answer = anti-cholinergic (benztropine).
• 40M + Hx of schizophrenia + started on fluphenazine + a few hours later has abnormal eye movements; Tx? –> answer = benztropine. Patient has oculogyric crisis, which is a type of acute dystonia. Torticollis is another type of acute dystonia, which is an abnormally tight and crooked neck.
• Diphenhydramine is a first-generation H1 blocker that has strong anti-cholinergic side-effects and is sometimes the answer if benztropine not listed. USMLE will not list both at the same time.

Diphenhydramine, Chlorpheniramine

• First-generation H1 blockers with such strong anticholinergic side-effects that they frequently show up in USMLE Qs as just being anticholinergics straight-up (i.e., no mention of technically being anti-histamines).
• Used to treat acute dystonia with anti-psychotic use if benztropine not listed.
• 44M + schizophrenia + started on aripiprazole + now has diffuse muscle stiffness/rigidity + temperature is 98.6F; treatment? –> answer = benztropine or diphenhydramine. The latter is a first-gen H1 blocker with potent anticholinergic side-effects. This patient has acute dystonia, not neuroleptic malignant syndrome. NMS will have fever. USMLE slams students on this. Rigidity + fever = NMS; but rigidity + no fever = acute dystonia.
• 38F + schizophrenia + started on olanzapine + now neck is crooked and stiff; Tx? –> answer = diphenhydramine.

Prochlorperazine

• Antipsychotic med used as an anti-nausea medication.
• Can cause anti-cholinergic, anti-α1, and anti-H1 effects, like the other antipsychotics.
• 50F + just had surgery + has nausea + started on prochlorperazine + faints when she stands up; why? –> answer = “antagonism at α1 receptors” (orthostatic hypotension).

Prochlorperazine

• Antipsychotic med used as an anti-nausea medication.
• The anti-nausea effect comes from the anti-cholinergic side-effects. As discussed above, scopolamine is an anti-cholinergic used for motion sickness (i.e., it prevents nausea). Even though prochlorperazine is an anti-psychotic (D2 antagonist), because its anti-cholinergic effects are so significant, that’s actually a good thing when we want to treat nausea (i.e., it acts like scopolamine).
• Anti-cholinergic, anti-α1, and anti-H1 effects.
• 50F + just had surgery + has nausea + started on prochlorperazine + faints when she stands up; why? –> answer = “antagonism at α1 receptors” (orthostatic hypotension).

a) Tx for organophosphate poisoning.

b) Regenerates active acetylcholinesterase in patients with organophosphate poisoning. Pralidoxime will kick out the phosphate group from the organophosphate that’s bound to and inhibiting the acetylcholinesterase –> regenerates active acetylcholinesterase.

c) Atropine blocks muscarinic receptors directly. This is the answer before pralidoxime. If the USMLE Q lists both answers, choose atropine first.

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Organophosphates act as acetylcholinesterase inhibitors –> cause DUMBBELSS in patient working on fruit farm or who “drank fluid” attempting to commit suicide.

20F + working on fruit farm + has constricted pupils + bradycardia + drooling; what’s the Tx for this patient’s condition? –> answer = atropine, followed by pralidoxime.

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If an agent is cholinergic, it will cause DUMBBELSS signs/symptoms –> Diarrhea, Urination, Miosis, Bradycardia, Bronchoconstriction, neuromuscular Excitation, Lacrimation, Salivation, Sweating.

Anti-cholinergic agents block cholinergic receptors directly. They will cause the opposite of DUMBBELSS –> Constipation, Urinary retention, Mydriasis, Tachycardia, Not bronchodilation (β2 agonism, but not M antagonism, will bronchodilate), Skeletal muscle relaxation, Dry eye, Dry mouth, Anhydrosis.

Jimson weed

• 16M + tactile and/or visual hallucinations + hot, red, dry + chewing on weeds; Dx? –> answer = Jimson weed –> illicit drug used by some teenagers –> weird, but tested on USMLE –> contains atropine compounds.

Contains atropine compounds.

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Jimson weed

• 16M + tactile and/or visual hallucinations + hot, red, dry + chewing on weeds; Dx? –> answer = Jimson weed –> illicit drug used by some teenagers –> weird, but tested on USMLE –> contains atropine compounds.