Pharmacology E2 Flashcards
Two divisions of the ANS
Parasympathetic (medulla and sacral output)
Sympathetic (thoracic and lumbar output)
* outweighs parasympathetic bc of adrenal gland
Adrenal gland
secretes epinephrine into systemic circulation
POTS (Postural Orthostatic Tachycardia Syndrome)
Form of dysautonomia. HR>120 bpm within the first 10 minutes of standing; PositiveTilt Table test
Dysautonomia
disorder of ANS function that involves dysfuction of either the sympathetic or parasympathetic components
Parasympathetic ganglia
located in close to end organs
1st neuron –> long
2nd neuron –> short
Sympathetic ganglia
located closer to CNS and farther from end organs
1st neuron –> short
2nd neuron –> long
Blood-brain-barrier
lipophilic, small, uncharged molecules readily pass through
NT at preganglionic synapse (nicotinic)
ACh
*different receptors than those at NMJ
Responses to parasympathetic innervations
- Pupil constriction
- Bronchi: constriction, inc secretion
- GI tract: inc peristalsis, inc sphincter tone, inc blood flow
- Saliva: copious, liquid
- Heart: dec HR, dec BP
- bladder: dec sphincter tone, stim detrusor muscle (urine void)
Main transmitter that innervates end organs
NE
*exception: sweat glands, skeletal muscle, blood vessels - ACh
Responses to sympathetic innervations
- Pupil dilation
- CNS: drive, alertness
- Liver: glycogenolysis, glucose release
- GI tract: dec peristalsis, inc sphincter tone, dec blood flow
- Saliva: little, viscous
- Heart: inc HR, inc force, inc BP
- fat tissue: lipolysis, FA liberation
- Bladder: inc sphincter tone, relax detrusor muscle (inc urine accommodation)
ACh
50% in SV, 50% free in cytoplasm
- SV release is via Ca/E-requiring exocytosis
^botulinum inhibits, leading to flaccid paralysis - AChase terminates ACh action
- primary receptors for ACh nicotinic (@ganglia and NMJ) or muscarinic (@ end organs)
Bethanechol
Direct Cholinomimetic
Agonist (mAchR)
Causes GI/Bladder contraction, used to treat post-operative “lazy gut syndrome”
Succinylcholine
Direct Cholinomimetic
Agonist (nAchR)
Depolarizing NMJ blocker –> spastic paralysis by continued activation of muscle nAchRs.
(Used pre-operatively).
Carbachol
Direct Cholinomimetic
Agonist (mAchR)
stim miosis (pupil constriction)
tx: glaucoma
Pilocarpine
Direct Cholinomimetic
Agonist (mAchR)
Stim sweat glands
Dx: cystic fibrosis
Atropine
Antagonist (mAchR)
Tx: Achase blocker overdose
(tx: acute spastic paralysis)
Tubocurarine
Antagonist (Ach-nicotinic (NMJ))
Non-depolarizing blocker Pre-op muscle relaxation
a-Bungarotoxin (snake venom)
(Flaccid paralysis)
Trimethaphan
Antagonist (Ach-nicotinic-ganglia)
Tx: malignant hypertension
Pyridostigmine
ACHase inhibitor
Reversible
Does NOT cross BBB
Tx; myasthenia gravis
Physostigmine
ACHase inhibitor
Reversible
Crosses BBB
Tx; myasthenia gravis
Edrophonium
ACHase inhibitor
Short-acting
Does NOT cross BBB
Dx: myasthenia gravis
Parathion
Organophosphate
ACHase inhibitor Irreversible Crosses BBB Used to kill rodents --> rural pediatric poisoning --> looks like flour --> spastic paralysis --> nerve gas (warfare)
Antidote for human poisoning due to organophosphates
Pralidoxime (2-PAM)=regenerates AChase
Myasthenic crisis
Flaccid paralysis (blocked or lack of receptors) due to insufficient tx of myasthenia gravis
IMPROVES w/ short-acting AChase inhibitor (edrophonium)
Cholinergic crisis
Spastic paralysis (excessively stimulated receptors) due to too much ACh (bradycardia and hyper salivation)
WORSENS w/ AChase inhibitor
Tx: atropine (anti-cholinergic med)
Catecholamines
Norepinephrine and epinephrine (noradrenaline and adrenaline)
Catecholamine Synthesis and secretion
- Active TYR uptake pump
- Tyr –> dopa–> dopamine –> NE –> EPI
^tyr hydroxylase=RLS - Active transport of cytoplasmic NE and DO into SV
- NE transport out of vesicles, methylation to EPI in cytoplasm and uptake back into vesicles (adrenal medulla*)
- Release of NE via vesicular exocytosis (Ca, E dep; inhib via Mg)
- NE binding to pre- and post- synaptic receptors
- active reuptake of NE into neurons from synaptic cleft
- catabolism of NE and DO by monoamine oxidases
α-methyl-para-tyrosine
Feedback inhibition from
Epinephrine
Norepinephrine
Dopamine
α-methyl DOPA
Affects adrenergic system
Inhibits synthesis of NE
Target: DOPA decarboxylase
Sympatholytic
Tx of Hypertension (crossed the BBB)
Carbidopa
Affects adrenergic system
Inhibits synthesis
Target: DOPA decarboxylase
Sympathomimetic
Tx of Parkinsonism
(does NOT cross the BBB, prevents DOPA from being decarboxylated in the periphery)
Monoamine-oxidase (MAO)
DA, NE, EPI, serotonin degradation
- MAO inhib: depression tx
“False transmitters” (can displace NE from synaptic vesicles)
Alpha-methyl NE
Tyramine (cheese, metabolized to octopamine)
Avoid when on MAO inhibitor (Displaced NE can diffuse out of presynaptic terminus –> constrict blood vessels –> inc bp –> HYPERTENSIVE CRISIS
Drugs that inhibit catecholamine reuptake
Some antidepressants
- tricyclics (amitriptyline) inhibit NE, 5HT uptake
- SSRIs (fluoxetine) inhibit only 5HT uptake
Do NOT give with clonidine
Why should reuptake inhibitor antidepressants not be taken with presynaptic α2 agonists?
presynaptic α2 agonists (clonidine) inhibit catecholamine synthesis and release –> worsening depression
Amitriptyline
Catecholaminomimetic (sympathomimetic)
- TCA
- Blocks reuptake of NE and 5-HT
Tx: Depression
Bupropion
Catecholaminomimetic
- DNRI
- Blocks reuptake of DO and NE
Tx: Depression
Citalopram
Catecholaminomimetic
- SSRI
- Blocks reuptake of 5HT
Tx: Depression
Venlafaxine
Catecholaminomimetic
- SNRI
- Blocks reuptake of 5HT and NE
Tx: Depression
Phenelzine
Catecholaminomimetic (sympathomimetic)
- MAO inhibitor
Tx: depression
Amphetamine
Methylphenidate
Catecholaminomimetic
- stimulant
- NE reuptake inhibitor and weak agonist
Tx: ADHD, obesity
Clonidine
Affects adrenergic system
Presynaptic α2 agonist
Inhibits catecholamine release
Sympatholytic
*don’t give with reuptake inhibitor antidepressants (TCA, SSRIs)
Receptors for NE and EPI
α -Adrenergic receptors: NE higher affinity
β-Adrenergic receptors: EPI higher affinity
β1 - Adrenergic receptors
Heart
Stim: - inc HR, inc contractility, inc metabolism, inc O2 consumption, inc BP
β1 BLOCKERS
- dec HR
- dec contractility
- dec workload
- have anxiolytic action
Tx for HTN and post-MI
Exp. Propanolol (non-selective)
Metoprolol/Atenolol (selective)
Which beta blockers are contraindicated in asthma and why?
Non-selective beta blockers (propranolol) bad for pts w/ pulm disorders bc blocking B2 –> bronchoconstriction
Use selective like metoprolol/atenolol instead
β2 – Adrenergic receptors
Lungs
Stim: Bronchodilation, smc relaxation, inc dilation of blood vessels (brain)
β2 AGONISTS
Used for asthma tx
α1 – Adrenergic receptors
Blood vessels, constriction
α2 - Adrenergic receptors
Brain, on surface of pre-syn membranes
When stim –> suppress NE release –> AUTOINHIBITION
Yohimbine
α2 -Antagonist
tx: erectile dysfunction
Cardiovascular effects of PNS (ACh)
dec HR
dec contractility
dec O2 consumption
dec blood pressure
Norepinephrine
Receptor type, clinical use?
Sympathomimetic
Receptor type: α1>β1
Hypotension
Epinephrine
Receptor type, clinical use?
Sympathomimetic
β>α
Tx: Anaphylaxis
**EpiPen
Isoproterenol
Receptor type, clinical use?
Sympathomimetic
β1=β2
Tx: Cardiac arrest
Albuterol, terbutaline
Receptor type, clinical use?
Sympathomimetics
β2
Tx: Asthma
Dobutamine
Receptor type, clinical use?
Sympathomimetic
β1>β2
Tx: Congestive heart failure
Dopamine
Receptor type, clinical use?
Sympathomimetic
D1=D2>β2>β1>α
Tx: Congestive heart failure
Tx of HTN
CNS, heart, blood vessels
a-methyldopa ↓NE, E
Clonidine ↓NE
Atenelol ↓b1
Labetalol ↓ α1>b1
Propanalol ↓b1 = b2↓
Prazosin ↓α1
Phenoxybenzamine ↓α1 = α2↓
Cholinomimetics (direct-acting)
Bethanechol
Carbachol
Pilocarpine
Succinylcholine
Acetylcholine Receptor Antagonists
Atropine
Tubocurarine
Trimethaphan
AChases
Pyridostigmine Physostigmine Edrophonium Parathion Organophosphate
Catecholaminomimetics
Indirect CNS Stimulants
Amitriptyline Bupropion Citalopram Venlafaxine Phenelzine Amphetamine Methylphenidate
Drugs Affecting the Adrenergic System
α-methyl DOPA Carbi DOPA Clonidine Amitriptyline, amphetamine Phenelzine
Adrenergic Receptor Agonists
Sympathomimetics
Norepinephrine Epinephrine Isoproterenol Albuterol Terbutaline Dobutamine Dopamine
Adrenergic Receptor Antagonists
Sympatholytics
Atenolol Metoprolol Propanolol Labetalol Phentolamine Phenoxybenzamine Prazosin
