cholinergics and histamanergics (dont think i spelled either right)

Anticholinergic: Contraindications

• [...]
  

  • Increased angle closure pressure

• [...] obstruction (e.g. prostatic hyperplasia)
  

  • Prevents contraction 

• [...] obstruction
  

  • Slows motility 

• [...]
  

  • Delays gastric emptying

  • increase ulcer symptoms 

• [...]
  

  • Worsens symptoms 

• Glaucoma, especially angle-closure glaucoma

• Urinary Tract

• GI

• Peptic ulcer disease

• Myasthenia Gravis

Effects of Histamine on Organ Systems 

• CV
  

  • H1→ [...] BP, flushing, sense of warmth, headache, edema 

  • H2→ [...] HR

• dec

• inc

[...]

• MOA:

  • Blocks neural pathways from vestibular apparatus in the inner ear to the emetic center in the brainstem 

• More significant CNS effects than atropine at therapeutic doses (crosses BBB more easily)
  

  • Drowsiness, amnesia, fatigue, dreamless sleep, euphoria 

• Clinical uses:
  

  • Motion sickness (transdermal)

    • must be used prophylactically for best results

  • Postoperative (IM,IV)→for nausea and vomiting 

Scopolamine

Scopolamine

• MOA:

  • Blocks neural pathways from vestibular apparatus in the inner ear to the emetic center in the brainstem 

• [More or less] significant CNS effects than atropine at therapeutic doses ([why?])
  

  • Drowsiness, amnesia, fatigue, dreamless sleep, euphoria 

• Clinical uses:
  

  • Motion sickness (transdermal)

    • must be used prophylactically for best results

  • Postoperative (IM,IV)→for nausea and vomiting 

• More

• crosses BBB more easily

Motion sickness can also be treated by 1st generation H1 antagonist --> Diphenydramine

Scopolamine

• MOA:

  • Blocks neural pathways from vestibular apparatus in the inner ear to the emetic center in the brainstem 

• More significant CNS effects than atropine at therapeutic doses (crosses BBB more easily)
  

  • Drowsiness, amnesia, fatigue, dreamless sleep, euphoria 

• Clinical uses:
  

  • [...] (transdermal)

    • must be used prophylactically for best results

  • Postoperative (IM,IV)→for nausea and vomiting 

Motion sickness

Histamine poisoning from [...]

• Normal concentration is less than 0.1 mg/100 g of fish 

• FDA considers toxic > 50 mg/100 g of fish

• Poorly preserved fish (often tuna, sardines, mackerel)
  

  • Gram negative bacteria thrive

  • Histidine in the fish muscle gets converted to histamine by bacterial enzymes 

Scombroid Syndrome

[...] 

• blurred vision 

• Anticholinergic effect 

cycloplegia

cyclopes has blurred vision 

cycloplegia 

• blurred vision 

• [cholinergic or anticholinergic] effect 

Anticholinergic

cyclopes has blurred vision 

[...]

• Unique antihistamine because it has anti-serotonergic activity

• No longer used for allergies

• Off-label use for treating decreased appetite secondary to chronic disease 

Cyproheptadine

[H1 or H2] antagonists

• Allergy

• cold medicine

• sleep aids

• motion sickness

• antiemetic, etc.

H1

1st and 2nd generation H1 antagonists 

[H1 or H2] antagonists

• Indications:

  • Peptic ulcer disease

  • GERD

  • Ulcer prophylaxis

  • Heartburn 

• Drugs

  • Famotidine

  • Cimetidine

  • Ranitidine

H2

[...]

• dilation of the pupil of the eye

• Anticholinergic effect 

Mydriasis

Mydriasis = dilation 

Mydriasis

• dilation of the pupil of the eye

• [cholinergic or anticholinergic] effect 

Anticholinergic

Mydriasis = dilation 

Anticholinergics: therapeutic uses

• Ophthalmology
  

  • MOA: 

    • causes mydriasis and cycloplegia

  • Indication: 

    • ophthalmoscopic examination of retina

  • Drugs

    • [...]

    • [...]

    • [...] 

• Homatropine

• Atropine

• Tropicamide 

Anticholinergics: therapeutic uses

• Cholinergic Poisoning
  

  • Drugs

    • [...]

    • [...] 

• Atropine

• Pralidoxime (2-PAM) 

Sketchy -- paralidoxime (closes lid on toxic spray) 

Anticholinergics: therapeutic uses

• Bardycardia 

  • Atropine 

    • MOA: blocks [which] receptors on the SA nodal pacemaker cells

M2

Anticholinergics: therapeutic uses

• [What's the indication?]
  

  • Ipratropium (metered dose inhaler, nebulizer)

    • Inhaled so there is minimal systemic absorption

    • Blocks ACh in the bronchial smooth muscles→bronchodilation

    • Adverse effects: 

      • xerostomia

      • cough

      • blurred vision

  • Others: 

    • tiotropium

    • aclidinium

    • umeclidinium 

• COPD/asthma

Anticholinergics: therapeutic uses

• COPD/asthma
  

  • [...] (metered dose inhaler, nebulizer)

    • Inhaled so there is minimal systemic absorption

    • Blocks ACh in the bronchial smooth muscles→bronchodilation

    • Adverse effects: 

      • xerostomia

      • cough

      • blurred vision

  • Others: 

    • tiotropium

    • aclidinium

    • umeclidinium 

Ipratropium

Anticholinergics: therapeutic uses

• COPD/asthma
  

  • Ipratropium (metered dose inhaler, nebulizer)

    • Inhaled so [how much systemic absorption is there]

    • Blocks ACh in the bronchial smooth muscles→broncho[dilation or constriction]

    • Adverse effects: 

      • xerostomia

      • cough

      • blurred vision

  • Others: 

    • tiotropium

    • aclidinium

    • umeclidinium 

• there is minimal systemic absorption

• dilation

Anticholinergics: therapeutic uses

• [Indication?]
  

  • Drugs: 

    1. Oxybutynin 

    2. tolterodine

    3. trospium

    4. solifenacin

    5. darifenacin

    6. fesoterodine 

  • MOA: 

    • somewhat targets M3 receptors in bladder to relieve spasms

      • Oral, IV, patch

      • 1/5 the anticholinergic activity of atropine

      • 4 to 10x the antispasmodic activity of atropine

      • No effects at skeletal muscle or autonomic ganglia

      • Adverse effects: 

        • dizziness, drowsiness, xerostomia, constipation

• Overactive bladder

Anticholinergics: therapeutic uses

• Overactive bladder
  

  • Drugs: 

    1. Oxybutynin 

    2. tolterodine

    3. trospium

    4. solifenacin

    5. darifenacin

    6. fesoterodine 

  • MOA: 

    • somewhat targets [...] receptors in bladder to relieve spasms

      • Oral, IV, patch

      • 1/5 the [...] activity of atropine

      • 4 to 10x the [...] activity of atropine

      • No effects at skeletal muscle or autonomic ganglia

      • Adverse effects: 

        • dizziness, drowsiness, xerostomia, constipation

• M3

• anticholinergic

• antispasmodic

Anticholinergics: therapeutic uses

• Overactive bladder
  

  • Drugs: 

    1. [...] 

    2. [...]

    3. [...]

    4. [...]

    5. [...]

    6. [...] 

  • MOA: 

    • somewhat targets M3 receptors in bladder to relieve spasms

      • Oral, IV, patch

      • 1/5 the anticholinergic activity of atropine

      • 4 to 10x the antispasmodic activity of atropine

      • No effects at skeletal muscle or autonomic ganglia

      • Adverse effects: 

        • dizziness, drowsiness, xerostomia, constipation

1. Oxybutynin 

2. tolterodine

3. trospium

4. solifenacin

5. darifenacin

6. fesoterodine 

Anticholinergics: therapeutic uses

• Irritable Bowel Syndrome (IBS) 
  

  • Drugs 

    • [...] 

    • [...]

  • MOA: 

    • spasmolytic effects on the smooth muscle of GI tract 

    • decreases peristalsis 

• Dicyclomine 

• Hyoscyamine

Just because I'm dying or high, doesn't mean I will poop

Anticholinergics: therapeutic uses

• Irritable Bowel Syndrome (IBS) 
  

  • Drugs 

    • Dicyclomine 

    • Hyoscyamine

  • MOA: 

    • spasmolytic effects on the smooth muscle of GI tract 

    • [increases or decreases] peristalsis 

decreases

Just because I'm dying or high, doesn't mean I will poop

Anticholinergics: therapeutic uses

• Parkinsons 
  

  • Drugs 

    • [...] 

    • [...] 

  • MOA: antagonizes ACh 

• Benztropine 

Anticholinergics: therapeutic uses

• Reduction of Secretions/Drooling 
  

  • Drugs 

    • [...] 

    • [...]

  • MOA: 

    • anticholinergic effects inhibits salivation and secretion

    • causes bronchodilation 

• Glycopyrrolate 

• Atropine

Anticholinergics: therapeutic uses

• [Indication?] 
  

  • Drugs 

    • Glycopyrrolate 

    • Atropine

  • MOA: 

    • anticholinergic effects inhibits salivation and secretion

    • causes bronchodilation 

• Reduction of Secretions/Drooling 

Cholinergic Clinical Uses: Neuromuscular junction

• Myasthenia gravis
  

  • Edrophonium is used as a diagnostic agent; not available in the US

  • [...] and [...] are used for long-term therapy 

Pyridostigmine and neostigmine

H1 antagonists clinical use: Generalized Anxiety

• [...] 
  

  • in adjunct with organic disease states in which anxiety is manifested

• Hydroxyzine 

Histamine

• Mediator of allergic and inflammatory rxns with some role in anaphylactic rxns

• Causes

  • Local vaso[dilation or contraction]

  • release of [...] and [...]

• Chemotactic response via: 

  • neutrophils, eosinophils, basophils, monocytes, and lymphocytes 

• dilation

• C-reactive protein and antibodies

Histamine binds to various receptors throughout the body 

• 4 histamine receptors
  

  • H1 

    • smooth muscle, endothelium, brain 

    • [Important in?]

  • H2 

    • gastric mucosa, cardiac muscle, mast cells, brain

    • [important in?]

  • H3 

    • presynaptic brain, myenteric plexus

    • part of GI nervous system (NT control)

  • H4 

    • CD4+ T cells, eosinophils, neutrophils 

    • immune response regulation

• acute allergic response

• gastric acid secretion

Histamine Receptor Antagonists

• Physiological antagonists
  

  • [What] causes opposite effect of histamine on smooth muscle 

  • used in [...] treatment

• Epinephrine

• anaphylaxis

Histamine release

• Immunologic
  

  • Release (degranulation) occurs when an antigen binds to the IgE Ab on the cell

  • Type I allergic reaction (e.g. hay fever and acute urticaria)

• Chemical and mechanical
  

  • Direct injury to mast cells

  • Causes release of histamine

    • Ex: [...]: causes direct interaction with mast cells and causes a reaction

morphine

Histamine

• Functions as a NT and neuromodulator

• Location
  

  • [...]

  • [...] 

• Mast cells

• Basophils 

Mast cell histamine

• Stored in granules in a bound inactive form

• Most abundant at sites of [...]
  

  • Nose

  • mouth

  • feet

  • blood vessels

  • internal body surfaces 

potential tissue injury

Non-mast cell histamine

• Brain: 

  • neuroendocrine control

  • CV regulation

  • thermal and body weight regulation

  • sleep and arousal

• Fundal cells of the stomach

  • histamine release [stimulates or inhibits] acid production 

stimulates

Toxicity of H1 antagonists 

• [What type of] effects
  

  • Sedation 

  • Dry mouth

  • Blurred vision 

  • Urine retention 

  • GI upset, nausea, constipation 

• Caution in [...]
  

  • Sedation more pronounced with combined with alcohol and other CNS depressants 

• Excitation and convulsion in children 

• [...] hypotension (e.g. promethazine)

• Anti-ACh

• elderly

• Postural

[...] disease is characterized by cholinergic deficiency in the cortex and basal forebrain 

• Contributes to cognitive deficits

• Donepezil, galantamine and rivastigmine
  

  • Inhibit acetylcholinesterase

  • Work primarily in the CNS

  • Increase the ACh in the CNS for synaptic transmission 

Alzheimer’s

Alzheimer’s disease is characterized by cholinergic deficiency in the cortex and basal forebrain 

• Contributes to cognitive deficits

• [...], [...] and [...]
  

  • Inhibit acetylcholinesterase

  • Work primarily in the CNS

  • Increase the ACh in the CNS for synaptic transmission 

• Donepezil, galantamine and rivastigmine

Alzheimer’s disease is characterized by cholinergic deficiency in the cortex and basal forebrain 

• Contributes to cognitive deficits

• Donepezil, galantamine and rivastigmine
  

  • [MOA?]

  • Work primarily in the CNS

  • Increase the ACh in the CNS for synaptic transmission 

• Inhibit acetylcholinesterase

Cholinergic Organ System Effects: Cardiovascular

• [increase or decrease] peripheral vascular resistance and [speeds up or slow downs] HR

• Agents are not used clinically for these purposes

• Adverse effects: 

  • [increased or decreased] inotropy, chronotropy, CO, and vascular resistance 

• Decrease

• slows

• decreased

Cholinergic Organ System Effects: Genitourinary 

• [...]

  • treats urinary retention, neurogenic bladder

• [...]

  • post-op bladder distension/urinary retention 

• Bethanechol

• Neostigmine

Cholinergic Organ System Effects: GI

• [Increased or decreased] motility, secretion 

• [Contracts or relaxes] sphincters

• Neostigmine and Bethanechol: 

  • post-op ileus

  • atony of the urinary bladder

• Pilocarpine and Cevimeline

  • dry mouth due to Sjӧgren’s 

• Increased

• Relaxes

Postoperative ileus (POI) may be defined as the impairment of gastrointestinal (GI) motility after intra-abdominal or nonabdominal surgery

Cholinergic Organ System Effects: GI

• Increased motility, secretion 

• Relaxes sphincters

• [...] and [...]: 

  • post-op ileus

  • atony of the urinary bladder

• Pilocarpine and Cevimeline

  • dry mouth due to Sjӧgren’s 

Neostigmine and Bethanechol

Postoperative ileus (POI) may be defined as the impairment of gastrointestinal (GI) motility after intra-abdominal or nonabdominal surgery

Cholinergic Organ System Effects: GI

• Increased motility, secretion 

• Relaxes sphincters

• Neostigmine and Bethanechol: 

  • post-op ileus

  • atony of the urinary bladder

• [...] and [...]

  • dry mouth due to Sjӧgren’s 

• Pilocarpine and Cevimeline

Postoperative ileus (POI) may be defined as the impairment of gastrointestinal (GI) motility after intra-abdominal or nonabdominal surgery

Cholinergic Organ System Effects: Respiratory

• [contraction or dilation] of smooth muscle of the bronchial tree 

• [stimulates or inhibits] secretion

• Avoid in asthma patients 
  

  • Methacholine is occasionally used for bronchial challenge test to help diagnose asthma 

• Contraction

• Stimulates

Cholinergic Organ System Effects: Respiratory

• Contraction of smooth muscle of the bronchial tree 

• Stimulates secretion

• Avoid in asthma patients 
  

  • [...] is occasionally used for bronchial challenge test to help diagnose asthma 

Methacholine

[cholinergic or anticholinergic] effects

Anticholinergic

Acetylcholine binds to the [nicotinic or muscarinic] receptors in the ganglia 

nicotinic

ACh is released via [...] dependent exocytosis 

• Blocked by Botulinum Toxin 

calcium

ACh is released via calcium dependent exocytosis 

• Blocked by [...]

Botulinum Toxin 

ACh synthesized from acetyal coenzyme A and choline 

• Via [which enzyme?]

ChAT (choline acetyltransferase)

All autonomic ganglia have [Nicotinic or Muscarinic] receptors

nicotinic

All receptors at the neuromuscular junction are [nicotinic or muscarinic] receptors

nicotinic

All target organs of the parasympathetic nervous system have [nicotinic or muscarinic] receptors

muscarinic

Almost all efferent fibers leaving the CNS are cholinergic. Why? 

• [...] 

Because preganglionic neurons release acetylcholine 

Almost all efferent fibers leaving the CNS are [...] 

cholinergic

Atropine 

• [What type of] antagonist at the muscarinic receptors
  

  • Increasing ACh can overcome atropine

• Clinical Uses
  

  • Bradycardia

  • Salivation/secretion

  • Ophtalmology 

  • Muscarine-containing mushroom poisoning

  • Organophosphate poisoning

Competitive

Atropine 

• Competitive antagonist at the muscarinic receptors
  

  • [How can the effects of atropine be overcome?]

• Clinical Uses
  

  • Bradycardia

  • Salivation/secretion

  • Ophtalmology 

  • Muscarine-containing mushroom poisoning

  • Organophosphate poisoning

• Increasing ACh can overcome atropine

Atropine Effects 

• Eye
  

  • Clinical use → [...] 

• ophthalmologic procedures 

• Causes unopposed sympathetic dilator activity and mydriasis by blocking cholinergic responses on the pupillary sphincter muscle of the iris
  

• Dilation results in photophobia
  

• Because the lens is fixed for far vision, objects up close appear blurred
  

• Clinical use → ophthalmologic procedures 

Cholinergic Clinical Uses:  Neuromuscular Junction

• Reversal of neuromuscular blockade
  

  • NMBs block the nicotinic ACh receptor inducing paralysis 

  • [...] and [...] are used after surgery to reverse neuromuscular blockade 

Neostigmine and pyridostigmine

Cholinergic drugs mimic Ach ([aka?])

cholinomimetics

Cholinergic Drugs

• Direct-acting 
  

  • [how does it work?] 

• Indirect-acting 
  

  • [how does it work?]

• Directly act on ACh receptors 

• Increases ACh through inhibition of acetylcholinesterase

Cholinergic Organ System Effects: Eye

• Direct/indirect agents were used in past to treat glaucoma

• [...] 

  • treats acute angle-closure glaucoma 

  • can lead to blindness

  • MOA

    • contraction of iris and ciliary muscles→aqueous humor outflow 

• Carbachol 

  • used if Pilocarpine is not effective

• Pilocarpine 

pile of carp -- pilocarpine

Cholinergic Organ System Effects: Eye

• Direct/indirect agents were used in past to treat glaucoma

• Pilocarpine 

  • treats acute angle-closure glaucoma 

  • can lead to blindness

  • MOA

    • contraction of iris and ciliary muscles→aqueous humor outflow 

• [...] 

  • used if Pilocarpine is not effective

Carbachol

pile of carp -- pilocarpine

Cholinergic Response

• Cardiovascular

  • [Increase or Decrease] HR and BP 

Decrease

Cholinergic Response

• GI 

  • [increases or decreases] motility

  • [relaxes or contracts] sphincters

  • [stimulates or inhibits] secretion 

• Increases

• relaxes

• stimulates

Cholinergic Response

• Glands 

  • [Increase or decrease] secretions (tears/sweat/salivary)

Increase

Cholinergic Response

• GU 

  • [Relaxes or contracts] sphincters

  • [Relaxes or contracts] bladder wall  

• Relaxes

• Contracts

Cholinergic Response

• Respiratory 

  • Bronchial [constriction or dilation] 

  • [increase or decrease] secretions 

• constriction

• Increase

Cholinergic Response

• Eye -- [contraction or dilation] 

Miosis (contraction of the pupil) 

Direct 

• Esters 
  

  • [Is it structurally related?] to ACh

• Alkaloids 
  

  • [Is it structurally related?] to ACh

  • So [is it metabolized] by acetylcholinesterases

• Structurally related

• Not structurally related

• not metabolized

Effects of Atropine on Organ Systems

• Heart
  

  • High doses cause [tachycardia or bradycardia] by blocking M2 receptors on the SA nodal pacemaker, thereby antagonizing parasympathetic tone of the heart

• Clinical use

  • acute symptomatic [tachycardia or bradycardia]

  • cholinergic poisoning 

• tachycardia

• bradycardia

Effects of Atropine on Organ Systems 

• Respiratory
  

  • Promotes broncho[dilation or constriction]

  • [increases or decreases] secretion

• dilation

• decreases

Inhibits bronchoconstriction caused by histamine, bradykinin, etc. 

Effects of Atropine on Organ Systems

• GU

  • [Constricts or Relaxes] smooth muscle of ureters and bladder wall 

Relaxes

Effects of Atropine on Organ Systems

• GI
  

  • [increased or decreases] tone and motility by blocking the muscarinic receptors in the GI

    • Gastric emptying time is [prolonged or shortened]

• Decreases

• prolonged

Effects of Atropine on Organ Systems

• GI
  

  • [stimulates or inhibits] salivary secretions causing [...]

    • can make swallowing difficult

• Inhibits

• xerostomia

• Clinical use

  • used during pre-anesthesia to inhibit salivation 

Effects of Histamine on Organ Systems 

• Bronchiolar smooth muscle
  

  • H1 → broncho[dilation or constriction] 

constriction 

Effects of Histamine on Organ Systems 

• GI
  

  • H1→ [contraction or dilation] of intestinal smooth muscle

  • H2→ [increased or decreased] secretion of acid from parietal cells 

• contraction

• increased

Effects of Histamine on Organ Systems 

• Skin 

  • [...] 

• Nervous system
  

  • H1 → [...]

• GU
  

  • Histamine induced contractions cause [...] 

• wheel and flare 

• pain and itching

• abortion 

H1 antagonists : clinical use 

• Allergic reactions
  

  • [which drug?]

    • Combined with EPI in anaphylaxis reactions

    • Allergic rhinitis, urticaria, hay fever→ 2nd generation agents preferred for these

  • [...] 
    

    • for Pruritus 

  • MOA: 

    • antagonizes histamine effects on smooth muscle, blood vessels, immune cells 

    • Also blocks muscarinic receptors 

      • 1st generation much more potent than 2nd generation to block these receptors

Hydroxyzine

H1 antagonists : clinical use 

• Allergic reactions
  

  • Diphenhydramine

    • Combined with EPI in anaphylaxis reactions

    • Allergic rhinitis, urticaria, hay fever→ [1st or 2nd] generation agents preferred for these

  • Hydroxyzine 
    

    • for Pruritus 

  • MOA: 

    • antagonizes histamine effects on smooth muscle, blood vessels, immune cells 

    • Also blocks muscarinic receptors 

      • 1st generation much more potent than 2nd generation to block these receptors

2nd

H1 antagonists : clinical use 

• Allergic reactions
  

  • Diphenhydramine

    • Combined with EPI in anaphylaxis reactions

    • Allergic rhinitis, urticaria, hay fever→ 2nd generation agents preferred for these

  • Hydroxyzine 
    

    • for Pruritus 

  • MOA: 

    • antagonizes histamine effects on smooth muscle, blood vessels, immune cells 

    • Also blocks [...] 

      • 1st generation much more potent than 2nd generation to block these receptors

muscarinic receptors 

H1 antagonists : clinical use 

• Allergic reactions
  

  • Diphenhydramine

    • Combined with EPI in anaphylaxis reactions

    • Allergic rhinitis, urticaria, hay fever→ 2nd generation agents preferred for these

  • Hydroxyzine 
    

    • for Pruritus 

  • MOA: 

    • antagonizes histamine effects on smooth muscle, blood vessels, immune cells 

    • Also blocks muscarinic receptors 

      • [1st or 2nd more potent?] to block these receptors

1st generation much more potent than 2nd generation

H1 antagonists : clinical use 

• Nausea and vomiting 
  

  • [...] 

    • Combined with vitamin B6 

    • Preferred in pregnancy

• Doxylamine (PO) 

H1 antagonists : clinical use 

• Nausea and vomiting 
  

  • Doxylamine (PO) 

    • Combined with [...]

    • Preferred in pregnancy

vitamin B6

H1 antagonists : clinical use 

• Sleep Aids 
  

  • [...]

  • [...]

• Doxylamine

• Diphenhydramine

H1 antagonists : clinical use 

• [...] and [...] 
  

  • Diphenhydramine

  • dimenhydrinate (Dramamine)

  • promethazine

  • meclizine

  • MOA:

    • Antimuscarinic effects 

      • suppresses vestibular end-organ receptors 

      • inhibits activation of central cholinergic pathway

Motion sickness and Vestibular Disturbances

H1 antagonists : clinical use 

• Motion sickness and Vestibular Disturbances 
  

  • Diphenhydramine

  • dimenhydrinate (Dramamine)

  • promethazine

  • meclizine

  • MOA:

    • [What type of] effects 

      • suppresses vestibular end-organ receptors 

      • inhibits activation of central cholinergic pathway

Antimuscarinic

H1 antagonists : clinical use 

• Motion sickness and Vestibular Disturbances 
  

  • [...]

  • [...]

  • [...]

  • [...]

  • MOA:

    • Antimuscarinic effects 

      • suppresses vestibular end-organ receptors 

      • inhibits activation of central cholinergic pathway

• Diphenhydramine

• dimenhydrinate (Dramamine)

• promethazine

• meclizine

H1 antagonists : clinical use 

• Motion sickness and Vestibular Disturbances 
  

  • Diphenhydramine

  • dimenhydrinate (Dramamine)

  • promethazine

  • meclizine

  • MOA:

    • Antimuscarinic effects 

      • suppresses [...] 

      • inhibits [...]

• vestibular end-organ receptors 

• activation of central cholinergic pathway

  
  

  Dragonfly men prompted me close in

Indirect 

• Effects are like cholinomimetic agonists (direct-acting) 

• Bind to and inhibit acetylcholinesterase 
  

  • Increases ACh levels at [which receptors?]

both muscarinic and nicotinic cholinoceptors

Indirect 

• Reversible 
  

  • Alcohols and carbamates 

  • [Shorter or longer] duration of action (compared to the irreversible agents) 

  • Minutes to hours 

• Irreversible 
  

  • Nerve gases and insecticides (organophosphates) 

  • [Shorter or longer] duration of action due to covalent bonds between phosphorus-enzyme complex

  • Some compounds last >100 hours 

  • Crosses BBB due to to lipophilicity 

  • Reversal agents: atropine

Long

Indirect 

• Reversible 
  

  • Alcohols and carbamates 

  • Shorter duration of action (compared to the irreversible agents) 

  • Minutes to hours 

• Irreversible 
  

  • Nerve gases and insecticides (organophosphates) 

  • Long duration of action due to covalent bonds between phosphorus-enzyme complex

  • Some compounds last >100 hours 

  • [Why can it cross the BBB?] 

  • Reversal agents: atropine

• Crosses BBB due to to lipophilicity 

Why is Physostigmine only reserved for emergency cases??

• [...]

• Physostigmine has a tertiary amine that makes it different from the pyridostigmine and neostigmine which allows it to cross the BBB

[...] is the major neurotransmitter stored in vesicles

Acetylcholine (Ach

• Synthesized from actyl coenzyme A (acetyl CoA) and choline pre-ganglionic nerve terminal 
  

• Released in response to an action potential 
  

• Calcium-dependent exocytosis 
  

• Ach binds to the nicotinic receptors on the postganglionic cell

[...] hydrolyzes Ach 

• Found in high concentrations around neuronal membranes

Acetylcholinesterase

[...] denotes receptors that respond to Ach (muscarinic and nicotinic)

Cholinoceptor

[...] 

• contraction of the pupil

Miosis

[Nicotinic or Muscarinic] acetylcholine receptors

• Cardiac and smooth muscle

• Gland cells

• Nerve terminals

• Sweat glands 

Muscarinic