B: 1-7 Flashcards
M1-R location
Nerve endings
M2-R location
Heart
some nerve endings
I love you! M2
M3-R location
Effector cells
Smooth muscles
Glands
Endothelial cells
a1-R action
Arterial and venous contraction
Mydriasis
Urinary spinchter contraction
a2-R action
Central and peripheral presynaptic inhibition
↓ insulin release
↓ lipolysis and FFA release
↓ Aqueous humor production
B1-R action
↑ SA, AV rate and automaticity
↑ Cardiac contractility
↑ Renin release
B2-R action
Peripheral vasodilation Bronchodilation ↑ Insulin release ↑ Lipolysis and FFA release ↑ Heptaic gluconeogenesis+ Glycogenolysis ↑ Aqueous humor production
B1 effect on the heart SA, AV rate and automaticity=
Positive chronotopic effect
Nicotinic N-R location
ANS ganglia
Adrenal medula
Nicotinic M-R location
Neuromascular end plate
Which factors contribute to the Cholinergic presynaptic inhibatory effect?
a2 M2 Hemicholinium Vasamicol Botulinum toxin
Which factors contribute to the Cholinergic presynaptic stimulatory effect?
M1 B2 AT1 4-Aminopyridine Latrotoxin
Hemicholinium blocks
Choline/Na+ cotransporter
4-Aminopyridine MOA
Inhibitis K+ ch → Depol. → Neutransmittr release
Which factors contribute to the Adrenergic presynaptic inhibatory effect?
a2 M2 H3 Metyrosine Reserpine
Which factors contribute to the Adrenergic presynaptic stimulatory effect?
B2 M1 AT1 4-Aminopyridine Latrotoxin Indirect acting sympathomimetics
Reserpine MOA
Inhibitis VMAT
Metyrosine MOA
Inhibitis Tyrosine hydroxylase
Iris radial muscle are controlled by
Dilated pupil is also called
a1
Mydriasis
Ayi see you 1
Iris circular muscle are controlled by
Constricted pupil is also called
M3
Myosis
Ciliary muscles are innervated by
B- relaxation
M3- contraction
איריס היא אמא לשלושה ילדים
Bladder wall is innervated by
B2- Relax
M3- Contracts
Penis innervation
a- ejaculation
M- erection
Far vision
↓ M3 tone will relax ciliary muscle
Flat lens
Near vision
↑ M3 tone will contract ciliary muscle
Spherical lens
ciliary m contraction > decrease the diameter of the ring of ciliary muscle causing relaxation of the zonule fibers
the lens becomes more spherical, increasing its power to refract light for near visio
Miosis
M3 ↑
How to lower aqueous humor production?
a2 agonist
B2 antagonist
Cholinomimetics
- Choline esters: Acetylcholine, Bethanechol, Carbachol, metacholine
- Alkaloids: Muscarine, Nicotine, pilocarpine
- Synthetic: Vareniciline
- Carbamates: Neo, Pyrido, Riva -stigmine
- Organophosphates: Malathion, Sarin
- Alcohol: Edrophonium, donepezil
Carbachol receptor preferance
M=N
קר בחול אז בוא נשחק יפה ביחד
Bethanechol receptor preferance
M
Pilocarpine receptor preferance
M
Carbachol indications
Glaucoma
Which direct acting cholinomimetic is resistance to acetylcolinesterase?
Carbachol
כל כך קר אז אף אחד לא מתקרב אליו
Carbachol
How to give
Topical
Pilocarpine drug properties
Oral, I.M , topical in eye
Lipd soluble
30min-2h duration of action
activates muscarinic receptor ( increa IP3 + DAG)
may also activate EPSP s via M-R in ganglia
dry mouth is also called
Xerostomia
Pilocarpine indications
Glaucoma
Xerostomia
Incuced sweat test in CF
What is the difference btw. tertiary and quaternary amine?
Tertiary freely cross the BBB
זה יותר קטן אז הוא מצליח לעבור
Which Carbamates are tertiary amine?
Physostigmine
Physostigmine indications
Antidote in case of Atropine overdose
Neostigmine duration of action and indication
2-4 h
MG (treatment)
Non obstructive ileus
Urinary retention
Reversal of N(M) block –> in surgery anesthesia
Pyridostigmine duration of action and indication
4-8 h
MG
Which has a longer duration of action?
Pyridostigmine
Neostigmine
Pyridostigmine
Rivastigmine properties as a drug
Lipid soluble
Cross CNS
Given as transdermal patch
Rivastigmine indications
Alzheimer’s disease
Edrophonium indications
Diagnosis of MG Tensilon test (MB Vs. Cholinergic crisis)
cholinergic crisis gets worse
MG= antibodies against postsynaptic acetylcholine receptor.
AchE inhibitiors poisoning
DUMBBLES
Diarrhea Urination Miosis Bradycardia Bronchoconstriction Excitation Lacrimation Secretion
Excesp for AchE inhibitor, what else will you give to a MG patient?
Selective muscarinic antagonist to control muscarinic side effects like GI
Non selective muscarinic antagonists
Atropine Butyl-scopolamine Scopolamine Cyclopentolate Procyclidine
Modest selectivity to M3 muscarinic antagonist
Solifenacin
What is the difference btw. Ipratropium to Tiotropium?
Ipratropium: Non selective. Shorter action
Tiotropium: M3 selective. Longer action
Duration of action of Atropine?
2-4 h
Mydriasis effect for even 8 days ( >72hr)
Atropine indications
- Opthalmology (mydriasis, cycloplegia) >72 hr
- Antidote for ChE inhibitors toxicity
Anti-diarrheal
Anti-spasmodic
Anti-secretery
Bradyarrhythmias
Cyclopentolate indications
topical Opthalmology to produce mydriasis and cycloplegia
Cyclo-round like the eyes
Scopolamine molecule features
Indications
Lipid soluble, can enter the CNS
Motion sickness
Transdermal patch
Suck it up! its only water
Butyl-scopolamine molecule features
Indications
No CNS entry
Pain from GI/GU spasmodic activity (Like menstrual cramps)
Buty female period
Procyclidine
administration
molecule features
Indications
Lipid soluble, enter CNS
Oral, perenteral
Parkinson disease
Extrapyramidal disorders
Whcih Muscarinic antagonists can treat Parkinson
Procyclidine
Solifenacin
Oxybutynin
molecule features
Indications
Oral, ransdermal patch
Bladder spasms
Urinary incontinence
כי הם ספציפיים לאמ3
Solifenacin (m3 selective)
Oxybutynin (non selective antimuscarinic)
Ipratropium
Tiotropium
Indications
Bronchodilator for asthma/COPD
Which is M3 selective?
Ipratropium
Tiotropium
Tiotropium
Adverse effects of Muscarinic antagonists?
↓ Secretion Mydriasis, cyclpolegia Glaucoma exxacerbation Tachycardia CNS effects Urinary retention Constipation
Chemical antagonist for organophosphate
Pralidoxime
Epinephrine is produced by
Exclusively by the medulla of the adrenal gland
NE is produced by
Medulla of the adrenal gland
Sympathetic NS
Epinephrine low dose
B1, B2 stimulation mainly:
HR, SV, CO, pulse pressure ↑
TPR, BP ↓
Bronchodilation
Epinephrine high dose
a1 stimulation mainly:
TPR, BP ↑
Reflex bradycardia
Epi indications
Cardiac arrest Heart block Anaphylactic shock Hypotensive emergency Adjucent to local anesthetics (↓ local blood flow)
Epi side effects
HTN Arrhythmias Stroke MI Pulmonary edema
NE receptor preferance
a1, a2, B1
NE indications
Cardiac arrest Heart block Hypotensive emergency Adjucent to local anesthetics (↓ local blood flow) Shock
NE- What type of shock is it used in?
Cardiogenic
Neurogenuc
Septic
NE side effects
Vasospasms Tissue necrosis HTN Arrhythmias MI
Dopamine dose dependent effect
Low dose: D1 → renal perfusion ↑
Medium: B1 stimulation → cardiac ↑
High: Acts like Epi (Loses selectivity)
Dopamine indications
Shock (with renal failure)
Dopamine side effects
Arrhythmias
Isoprenaline receptor preferance
B1 = B2
Isoprenaline indications
Cardiac arrest
Complete heart block
Acute asthma attack
Dobutamine receptror preferance
B1 > B2»_space;> a1
Dobutamine indications
Cardiogenic shock
Acute heart failure
Cardiac stimulation in cardiac stress test
a agonists
+
Which a?
Phenylephrine: a1 Oxymetazoline: Local a1, systemic a2 Clonidine: a2, I2 Rilmenidine: a2, I2 Methyldopa: a2
POC RM
a2 agonists
Oxymetazoline (also a1)
Clonidine
Rilmenidine
Methydopa
a1 agonists
Phenylephrine
Oxymetazoline- locally
Special feature of Phenylephrine
Not inactivated by COMT → longer duration of action compared to catecholamines
Phenylephrine duration of action
15-60 min
Phenylephrine indications
Opthalmologic (mydriasis)
Decongestant
Hypotension (TPR, mean BP↑)
Phenylephrine side effects
Reflex bradycardia HTN Stroke MI Ischemic necrosis of mucus memb.
Oxymetazoline indications
Topical decongestant
Oxymetazoline side effects
When given systemically due to a2 activation (Hypotension)
Clonidine receptor preferance
a2
I2
Clonidine drug features
Molecule?
How to give?
Imidazole derivative
Oral, Treansdermal patch
Clonidine indications
Antyhypertensive
ADHD
Turettes syndrome
Alcohol withdrawal syndrome
Clonidine side effects
Sedation
Dry mouth
Severe rebound HTN when sudddenly stopped
Drug induced lupus
Which are the a2, I2 agonists?
Clonidine
Rilmenidine
Rilmenidine indications
Antihypertensive
Rilmenidine side effects
Milder compared to Clonidine
Pure a1 agonist
Phenyephrine
Pure a2 agonist
Methyldopa
(Brimonidine, : a2-selective agonists appear to
reduce synthesis of aqueous humor
Tizanidine: an imidazoline related to clonidine reinforces presynaptic inhibition in
the spinal cord
Methyldopa drug features
Prodrug: Transported into the brian and converted to methyl-NE
Methyldopa indications
Antihypertensive
Methyldopa side effects
Sedation
Induces hemolytic antibodies
Drug induced lupus
Which release inducing agent do you know?
Tyramine
Ephedrine
Amphetamine
TEA
Ephedrine indications
- narcolepsy,
- idiopathic postural hypotension,
- enuresis = involuntary urination
Stimulant Appetite suppressant Concentration aid Decongestant Hypotension associated woth anaesthesia Less addictive than Amphetamines
Non selective a-R antagonists
Phentolamine: Competitive
antagonist at a
receptors
Phenoxybenzamine: Irreversible (covalent}
binding to a receptors
How to give Phentolamine?
What is the duration of action?
Oral: 20-40 min
Parenterally: 2-4 h
What is the difference btw. Phentolamine and Phenoxybenzamine?
Phenoxybenzamine binds the a-R irreversibely
Phentolamine indications
Pre-operative management of Pheochromocytoma
Antidote in case of acute HTN due to a agonist overdose
Phentolamine side effects
Orthostatic hypotension with subsequent reflex tachycardia
a1 selective antagonists
Prazosin
Doxazosin
Tamsulosin (approved for only BPH bcz partially selective)
Prazosin
Tamsulosin
Doxazosin
How to give? Duration of action?
Oral
prazosin : 8hr
Doxazosin., tamsulosin : 12-24 hrs
Prazosin
Tamsulosin
Doxazosin
Indications
HTN
BPH
Prazosin for PTSD
Prazosin
Tamsulosin
Doxazosin
Side effects
Orthostatic hypotension
Which drug is a1 antagonist and weak a2 agonist?
Urapidil
Urapidil receptor preferance
a1 antagonist
a2 weak agonist
5-HT weak agonist
B antagonist
Urapidil indications
HTN
Hypertensice crisis
BPH
Carvedilol receptor preferance
B1, B2, a1 antagonist
Which drugs are B1, B2, a1 antagonist
Carvedilol
Labetalol
Carvedilol
Labetalol
How to give?
Duration of action?
Oral, IV
5 h
Carvedilol indications
Congestive HF
**Reduces mortality!
Special feature of Carvedilol?
Reduces mortality in Congestive HF patients
