Ur cooked if u don't learn this

Adrenergic receptors are

GCPR

Adrenergic drugs used for

• hypertension

• shock

• asthma

• angina

Rate limiting step in NE synth

tyrosine to L-dopa

Adrenoreceptor Alpha 1

• vasuclar, geniutourinary, intestinal smooth muscle

• heart

• liver

Ad Alpha 2

• pancreatic B cells

• Platelets

• Nerves

• Vascular smooth muscle

• AUTORECEPTOR

Ad Beta 1

Heart

Ad Beta 2

Smooth and skeletal muscle (LUNGS)

Ad Beta 3

Adipose

Dopamine

regulates movement

Norepipnephrine

• stimulate Alpha1and2, Beta1

• counteract hypotension (INCREASE BP)

• limited use bc of non-selectivity

Epinephrine

• adrenalin

• short duration

• potent stimulant of ALL alpha and beta

• vasoconstrictor

• cardiac stim

NE metabolism

• COMT (post-synaptic)

• MAO (intra neural)

• major metabolite: vanillylmandelic acid

MAOI

• MAO inhibitors

• prevent deamination of catecholamines in presynpatic, tissues

• 2 types (a and b)

NE re-uptake inhibitor

cocaine

increase BP

Indirect Ad agonist

• do not bind receptors

• displace stored catecholamines

• inhibit re-uptake

• Amphetamines, dexthylphenidate, methylphenidate

Alpha-1 Agonist

• increase BP

• phenylephrine

Alpha 2 Agonist

• DECREASE NE (treat hypertension)

• decrease eye secretion

• decrease insulin

• increase platelet aggregation

• clonidine

Beta 1 Agonist

• increase Heart rate, cardiac output

Non-selective B Agonist

Isoproterenol

B2 agonist

• RELAX resipiratory, uterine, GI muscle

• Dobutamine (racemic)

• Levalbuterol

• Albuterol

Alpha 1 Antagonist

• RELAX muscle

• DECREASE BP

• Prazosin

Alpha 2 Antagonist

• INCREASE HR, BP, Insulin

• Yohimbine

Beta 1 Antagonist

• reduce sympathetic heart stim

• LOWER BP

• treat GLAUCOMA

• metoprolol

• acebutolol (PARTIAL AGONIST)

Non-selective Beta Antagonist

• propranolol

Non-selective alpha antagonist

• phenocybenzamine (IRREVERSIBLE)

• phentolamine

Both alpha and beta antagonist

• carvedilol

Cholinergic drugs target

• brain

• neuromuscular junction

• heart, eyes, lungs, genitourinary, GI

rate lim of acetylcholine synth

uptake of choline

Vesamichol

inhibits ACh into vesicle

Lamber-Eaton myasthenic syndreome (LEMS)

• autoantibody

• blocks Ca2+ channel

Botulinum toxin

• blocks vesicle fusion, ACh release

• treat diseases with increase muscle tone

• cosmetically (wrinkles)

• headache/pain

ACh in CNS

• modulation of sleep

• learning/memory

• suppression of pain

• neuronal dev

• immunosuppresion

• epilepsy

Muscarinic

GPCR

Nicotinic

Ligand gated ion channels

2 ACh bind to open ion channel permeable to K+, Na+, Ca2+

M subtypes

5 total

M2: heart

M3: smooth muscle

M1,4,5: CNS

N subtypes

2

Nm: skeletal MUSCLE

Nn: CNS

Risk of cholinergic agents

• depolarizing blockade

• can stimulate AND block receptors

Acetylcholine inhibitors

• bind to AChE and inhibit

• INDIRECT agonist (increase ACh)

• increase transmission, parasympathetic tone, cholinergic activity

• simple alcohols (edrophonium)

• carbomic acid esters: neostigmine, physostigmine

• organophosphates: isoflurophate

Organophosphates

• IRREVERSIBLE AChE inhibitor

• COVALENT bond

• toxic

• treated by ATROPINE, Pralidoxime

• ex. ISOFLUOROPHATE, SARIN gas

PAM

• reactivates AChE

• displace organophosphate

• given BEFORE aging to reverse effect

• DOES NOT ENTER CNS

Muscarinic tox

• V/D

• sweating

• hypersalivation

• miosis

• bronchoconstriction

Nicotinic tox

• confusion, seizure

• respiratory compromise

• depolarizing neuromuscular blockade (paralysis)

Muscarinic agonist

• choline esters: methacholine, carbachol, bethanechol

  • more hydrophilic (charged)

  • low penetration

  • more resistant to hydrolysis

• alkaloids: muscarine, pilocarpine

• treat GLAUCOMA

Why are drugs other than ACh used?

ACh lacks receptor selectivity

undergoes rapid hydrolysis

ACh structure

• quaternary ammonium

  • strongest activity when all 3 are METHYL

• ethylene bridge

  • less activity when larger molecules bound

• ester

  • rule of 5: less activity if molecule is longer

Nicotinic Agonist

• Choline ester: succinulcholine

• HIGH AFFINITY FOR NICOTINIC RECEPTORS

• resistent to hydrolylsis

• induce paralysis by depolarizing bloackage

• antiepileptic

• nicotine is also nicotinic agonist

Muscarinic aNTAGONIST

• PARASYMPATHOLYTIC EFFECT

  • sympathetic response predominates

• Naturally occuring alkaloids (ATROPINE)

• synthetic quaternary ammonium compounds

• also scopolamine

Atropine toxicity

• dose DEPENDENT

• dry mouth, less sweat, tachycardia, urinary retention, blurred eyes, CNS

• treated eith AChe inhibitor

Nicotinic Antagonists

• act as ganglionic blockers (Trimethaphan, Mecamylamine)

• or act as non-depolarizing neuromuscular blockade (somaatic)

• Paralysis

• TUBOCURARE

• adverse: histamine release, lower BP, incraese HR

Excitable cells

• Neuronal

• cardiac

• smooth muscle

• skeletal muscle

• endocrine cells

Local anesthetics block

Na+ channels, inhibit action potential

Phosphodiesterases

• convert cAMP to AMP

Achetylcholineesterase

degrade ACh

Sensory and somatic PNS carry signals to CNS and motor signals from CNS to striated muscle (T/F)

T

Ganglia

relay stations between pre and post

POST ganglionic fivers

NONmyleniated

Symapthetic fivers

thoracic and lumbar

short pre-ganglionic neuron

Parasympathetic fibers

cranial and sacral

long pre-ganglsionic neuron

Nicotinic receptors

• somatic system

• activated by ACh

• first at post ganglionic

Parasympathetic

• muscarinic receptors at organ

Sympathetic

• Adrenergic receptor at