Pharm 2 Flashcards
Cholinergic agonists
Act on ACh sites or with ACh-esterase
Acetylcholinesterase
Enzyme that breaks down acetylcholine.
Prevents overstimulation of cholinergic receptor sites
Bethanechol
Tx of neurogenic bladder in kids over 8
Children and cholinergic agonists
Kids r more at risk for adverse effects. GI upset, diarrhea, increased salivation could cause choking, bowel/bladder control loss,
Tx of myasthenia gravis or reversal of neuromuscular junction blocker effects in kids
Neostigmine and pyridostigmine
Parasympathomimetic
Mimicking effects of PNS-bradycardia, hypotension, pupil constriction, <bladder tone, relax sphincters, & bronchoconstriction
Myasthenia Gravis
Autoimmune disease characterized by antibodies to cholinergic receptor sites. Causes destruction of the receptor sites and decreased response at the neuromuscular junction. Progressive, debilitating, leading to paralysis
Direct-acting cholinergic agonists
Are similar to ACh and react directly with receptor sites as if ACh had stimulated it. These drugs usually stimulate muscarinic receptors W/I the PNS. Used as systemic agents to increase bladder tone, urinary excretion, and GI secretions, and as ophthalmic agents to induce mitosis to relieve intraocular pressure if glaucoma. No systemic absorption usually occurs
Indirect-acting cholinergic agonists
Cause increased stimulation of the ACh receptor sites by reacting with the enzyme acetylcholinesterase and preventing it from from breaking down the ACh
Direct acting cholinergic drugs
Bethanechol (duvoid, urecholine)
Carbachol (miostat)
Cevimeline (evoxac)
Pilocarpine (pilocar)
Cholinergic agonist are usually associated with many undesirable effects
Because their action cannot be limited to a specific site their effects are widespread throughout the body
Used infrequently
Endrophonium
Is used only to dx myasthenia gravis
Therapeutic effects of direct-acting cholinergic agonists
Mimic effects of ACh and parasympathetic stimulation.
Slowed HR, >myocardial contractility, vasodilation, bronchconstriction, <bladder tone, relaxed bladder and GI sphincters, pupil constriction
Uses of Bethanechol=affinity for cholinergic receptors in urinary bladder.
Oral or subQ
Tx of nonobstructive postoperative and postpartum urinary retention.
Neurogenic bladder atony in adults and in kids older than 8.
Dx and Tx of reflux esophagitis in adults. And Tx of infant &kids for esophageal reflux
Carbachol
Available as ophthalmic agent used to induce miosis or pupil constriction to relieve pressure in glaucoma. Used for some eye surgeries
Cevimelind and pilocarpine which bind to muscarinic receptor throughout the system
Used to increase mouth & GI secretions, relieve dry mouth or symptoms of sjogrens
General contraindications of direct cholinergic agonists
Undesirable systemic PNS stimulation. Condition exacerbation
CAD-cardiac suppression, bradycardia, hypotension, vasomotor instability, peptic ulcer, GI block or surgery, asthma, bladder surgery, epilepsy, Parkinson’s
Adverse effects of direct cholinergic agonists
PNS stimulation- hypoTN, bradycardia, heart block, cardiac arrest. GI: N,V,D cramps, salivation,shart. Swallowing w/ cevimeline and pylocarpine, incont
Drug-drug for direct cholinergic agonists
Acetylcholinesterase inhibitors like neostigmine and tacrine. <risk of overstimulation of PNS
Implementation of cholinergic agonist direct acting
Proper ophthalmic admin to >risk of systemic absorption.
Oral drugs on empty stomach >GI problems
Monitor & keep cholinergic block like Atropine
Miosis
Pupillary constriction
Nerve gas
Unlike most indirect acting cholinergic agonists
An indirect acting cholinergic agonist. Irreversibly binds w/acetylcholinesterase. ACh accumulates and death by muscle rigor
Irreversible direct acting cholinergic agonists
Not used therapeutically
Antidote for nerve has=pralidoxime and for Tx of poisoning by organophosphate pesticides
Two categories of reversible indirect acting cholinergic agonists
- used to treat myasthenia gravis
* used to treat AD
Myasthenic crisis vs cholinergic crisis
Myasthenic crisis=drug
Drug diagnosis=endrpphonium inj
Drugs: Indirect acting cholinergic agonist
MG category
Ambenonium (Mytelase)-MG adult
Endrophonium (Reversol)-dx MG crisis rev. paralytic drugs of surgery
Neostigmine (Prostigmin)-Dx & Tx of MG rev. Paralytic drug of surgery
Pyridostigmine (Mestinon)- mgmt of MG. Antidote for nerve gas
Drugs: indirect acting cholinergic agonists
AD category
Donepezil (Aricept)-mgmt AD & severe dementia.
Galantamine (razadyne)-mgmt & delays mild/moderate AD dementia.
Rivastigmine (excelon)-mgmt mi/mod AD Tx dementia of Parkinso
Tacrine (cognex)-4 AD yanked 2012
Alzheimer’s disease
Progressive neural degeneration in cortex=memory loss, >ADL’s,
>ACh producing neurons and their target beurons
Memantine
Tx AD -blocks various receptor sites in brain slows plaque build-up on axons. Slows/delays AD.
Contraindications cautions of indirect acting cholinergic agonists
Anticholinesterase
Pregnancy- induce labor
Usually effects r localized to cortex and neuromuscular jxn, however same cautions about Systemic PNS
Indications for anticholinergic drugs
- > secretions prior to anesthesia
- Tx Parkinson’s by block ACh stim
- restor HR & BP post surgical vagal stim.
- Tx bradycardia from carotid sinus reflex hyperactivity
- Tx pylorospasm and hyper bowel
- Tx motion sickness
- relax biliary and ureteral colic
- relax blad detrusors/tightsphincters
- control lagh cry in brain injury
- relax uterine hypertonicity
- mgmt of peptic ulcer
- control rhinorhea hay fever
- antidote for cholinergics/mushroom
- ophthalmic mydriasis/cycloplegia
Mydriasis
Relaxation of the pupil
Cycloplegia
Inhibition of lens to accommodate near vision
Fx of atropine and scopolamine
Work by blocking only muscarinic effectors in the PsNS and a few cholinergic receptors in SNS. Those that <sweating. Compete with ACh do not block nicotinic
Flavoxate any trospium
Act specifically on smoot muscle of urinary tract. Tx overactive bladder and bladder spasms.
Ipratropium and tiotropium
Act specifically to >respiratory secretions and cause bronchodilation
Cyclizine and meclizine
Reduce sensitivity of labarynth apparatus
•partially bloc cholinergic chemoreceptor trigger zone
>motion sickness prevent N,V
Hyoscyamine and methscopolomine
Act specifically on receptor in GI tract. Tx peptic ulcer, IBS, GI disorders
Antichoinergics and kids
Used often in kIds, but kids more sensitive to adverse effects constipation, urinary retention, heat int., confusion.
Dycyclomine not for kids!
Anticholinergics in older adults
Extreme caution. Adverse effects increased. Heat intolerance. Confusion, hallucination, psychotic syndromes. Renal imp. Lower dose
African Americans mydriatic effects
Increased dose for dark pigmented eye to achieve mydriatic effect
Anticholinergics contraindicated in conditions that could exacerbate
Glaucoma-poss. Increase in intraocular pressure
Stenosing peptic ulcer, intestinal atony, paralytic ileus, GI block, severe ulcerative colitis, toxic megacolon, prostatic hypertrophy, bladder block, cardiac arrhythmia, tachycardia, myocardial ischemia, kidney/liver imp., MG-low dos sometimes used.
Adverse effects of anticholinergics
Systemic blocking of cholinergic receptors. Adverse effect in one case may be the desired effect I another. Systemic effects dose dependent. CNS effect: blurred vision, pupil dilation, cycloplegia , intraocular pressure. Weaknesses dizziness, insomnia, mental confusion
Atropine toxicity
Poison belladonna, in a variety of other natural products.
Sudden onset of bizarre mental and neurological symptoms.
10.0mg=coma, dillusion, hallucination. Physostigmine antidote.
Drug to drug interactions with antichinergics
Antihistamines, antiparkinsonism’s, MAO inhibitors, &tricyclic antidepressants. Phenothiazines effectiveness decreases and <risk of paralytic ileus
Monitor patients on antichinergics for
Dry mouth, swallowing, constipation, urinary retention, tachycardia, pupil dilation, photophobia, cycloplegia, blurring of vision, heat intolerance >sweatig
Propantheline
Adjunct in Tx of ulcers
Ipratropium
Tx COPD, asthma
Tiotropium
COPD
Scopolamine patch
Tx N, V, Of motion sickness
Caution for pregnant or lactation
Safety of scopolomine patch
Apply to clean/ dry Wear gloves don't touch adhesive Change 3 days Elderly more sensitive Remove for defib/CPR or MRI
Parkinson’s Disease
Loss of dopamine in the substantial nigra of brain
Anticholinergic drugs counter balance the excessive cholinergic activity. Benztropine and diphenhydramine
The don’t mix insulins
Insulin glargine (Lantus) and insulins detemir ( levemir) cannot be mixed in syringe with anything else
Pregnancy/lactation considerations of insulin
Doesn’t cross placenta. Can inhibit good nutrient rich breast milk
Drug to drug interactions w/insulin
MAO inhibitors, beta blockers, salicylates and alcohol decrease glucose levels.
•beta blockers block SNS which hinders ability so see signs of hypoglycemia
Herbal remedy and antidiabetics
Juniper berry, ginseng, garlic, fenugreek, coriander, dandelion root, celery. = hypoglycemia
Sulfonylureas
1st oral agents for type 2 DM.
Stimulate pancreas release insulin
Bind to K+ channel on pancreatic beta cells. May improve insulin binding. <effects of anti diuretic hormone on renal cells. Only work if pt. has Fx beta cells. 1st or 2nd gen
1st generation sulfonylureas
* may be thought to <CVD and death
Chlorpropamide (diabinese) most frequent. Reliable predictable effect
Tolazamide (tolinase) less predictabl
Tolbutamide (Orinase) preferred for pt. w/renal imp. Easily cleared.
Sexing generation sulfonylureas
Glimepiride (amaryl)-less$$$
Glipizide (Glucotrol)
Glyburide (diabeta & micranase, glynase, prestab)
2nd gen sulfonylureas
Adjunct to diet/and/or insulin mgmt of type 2
Excreted urine &bile sfr renal imp
Less interaction w/ pro- bound drug
Long acting
Severe hypoglycemia
<40mg/dL
Short acting insulin
Humalog, novalog, regular
<15 mins. H &N
30-60min
Combo insulin
30-60 min
Then 1-2 hour
Intermediate insulin
NPH and Lente
60-120
Long insulin
PZ1, Lantus, Ultralente
4-8 hours
Short/rapid insulin
Aspart, lispro, glusiline (novolog, humalog, apidra)
Onset: 10-20, 15, 20-30
Lasts: 3.5, 3.5-4.5, <6
Long acting insulin
Glargine (lantus)- 60min, 24+
Detemir (levemir)-60-120min, 24+
Do not mix
