Pharmacodynamics- Dr. Clark Exam

Referred to as "cranio-sacral"

Parasympathetic system

Important cranial nerve in parasympathetic system

CN X (vagus)

PSNS has _____ pre-ganglion and _______ post-ganglion

Long; short

Referred to as "thoracolumbar system"

sympathetic nervous system

The SNS has ___ preganglionic fibers and ___ postganglionic fibers

Short; long

Which nervous system innervates more (has more extensive branching)?

SNS

Which NS decreases heart rate and cardiac output?

PSNS

Which NS dilates lung bronchioles?

SNS

Which NS stimulates glycogen breakdown and increase in blood glucose?

SNS

Which NS stimulates breakdown of fat and increase in blood fatty acids?

SNS

Which NS increase basal metabolism?

SNS

Which NS increases secretion of HCl & digestive enzymes, increasing gut motility?

PSNS

Which NS decreases secretion and intestinal motility?

SNS

Which NS relaxes urinary sphincter, contracts detrusor muscle, and promotes urination?

PSNS

Which NS constricts the rectal sphincter, relaxes wall muscles, and inhibits defecation?

SNS

Which NS constricts the iris?

PSNS

Which NS adjusts the eye for far vision?

SNS

Which NS promotes erection?

PSNS

Which NS promotes ejaculation?

SNS

Neurotransmitter always released at the pre-ganglia

Acetylcholine

Released at the post-ganglionic neuron in SNS

norepinephrine

Released at the post-ganglionic neuron in PSNS

Acetylcholine

Adrenal medulla produces...

A mixture of epi and NE, but mostly Epi

Synthesis of ACh

Acetyl CoA + Choline —> Acetylcholine + Coenzyme A (acetylation rxn)

Enzyme in synthesis of acetylcholine

CHAT

Release of ACh occurs when an action potential triggers ________ influx

Ca2+

What enzyme causes the breakdown of ACh

Acetylcholinesterase

Precursor for DA, NE, and Epi

Tyrosine

Rate-limiting enzyme in the synthesis of catecholamines

Tyrosine hydroxylase

Catecholamine that is produced in the chromaffin cells of the adrenal medulla, not in sympathetic neurons

Epi

Synthesis of DA, NE, and Epi

1. Tyrosine + Tyrosine hydroxylase

2. Dopa + Dopa decarboxylase

3. Dopamine + dopamine beta-hydroxylase

4. Norepinephrine + PMNT

5. Epinephrine

What is this structure?

What is this structure?

What is this structure?

How does MAO breakdown NE, Epi, and DA?

deamination

How does COMT breakdown NE, Epi, and DA?

O-methylation rxn

Receptors present on the presynaptic terminal and modulate its own release and uptake process

Autoreceptors

Receptors that regulate the synthesis/release of mediators other than its own ligand

Heteroreceptors

2 types of cholinergic receptors

nicotinic and muscarinic

What kind are muscarinic receptors

G-protein coupled

subtypes of muscarinic receptors

M1, M3, and M5- stimulate IP3/DAG pathway

M2 and M4- inhibition of cAMP

M2 also elevates K+ excretion

Which Cholinergic receptor has a slower but more prolonged response

Muscarinic

Which cholinergic receptor operates as a ligand operated channel?

Nicotinic

How do nicotinic receptors work?

2 molecules of Ach binds to receptor, ion channel opens, Na enters, local depolarisation

2 subtypes of nicotinic receptors

Nn (neuronal) and Nm (muscular)

Which Cholinergic receptor has an instantaneous response?

Nicotinic

All adrenergic receptors are

G-protein coupled receptors

Types of alpha receptors

A1: 1A, 1B and 1D - activation of IP3/DAG

A2: 2A, 2B, and 2D - inhibition of cAMP

Also, 2A elevates the K+ conductance

IP3 can elevate intracellular _____ levels

Ca2+

3 types of beta receptors

B1, B2, and B3- activate cAMP

What is the action of all choline esters?

Stimulate muscarinic receptors... activate PSNS

Which choline ester is given orally?

Bethanechol

Which choline ester is given as an inhalant?

Methacholine

Is muscarine used as a drug?

No

Is nicotine used as a drug?

Yes

Where is muscarine found naturally?

In a variety of mushrooms

What are the side effects of mushroom poisoning?

Salivation

Lacrimation

Urination

Defecation

How is mushroom poisoning treated?

Atropine

Where is pilocarpine found naturally?

In the leaves of Pilocarpus plants in S. America

Pilocarpine is very _____ (Lipid/water) soluble and ________________ (can/cannot) enter the CNS

Lipid, can

Only alkaloid agent given therapeutically?

Pilocarpine

What is pilocarpine used for?

glaucoma, emergency lowering of intraocular pressure

Nicotine initially acts as a _____ but in large doses becomes a _____.

Stimulant; blocker

can nicotine cross the blood brain barrier?

Yes, but this can result in convulsions

How do you treat toxicity from irreversible ACHESE inhibitors?

Atropine

FLuids

Oxygen

Oximes

Diazepam

How/Where does pralidoxime work to treat neurotoxicity?

Reactivates AChE at the NMJ to reverse respiratory paralysis

(Pralidoxime is charged so it cannot enter the CNS)

What are the side effects from overactivation of the PSNS?

Diarrhea

Urination

Miosis

Bronchorrhea

Bronchospasm

Emesis

Lacimation

Laxation

Salivation

What agents are short-acting AChE inhibitors?

Alcohols, Edrophonium

Edrophonium is used to diagnose what

myasthenia gravis

What agents are the medium acting AChE inhibitors?

Carbamates, -imine drugs

Most AChE inhibitors are _________________ in action

Intermediate

Physostigmine is used for

treatment of Glaucoma

Neostigmine is used for

MG

Pyridostigmine is used for

myasthenia gravis

What agent was administered prophylactically during the Gulf war?amb

Pyridostigmine

Ambemonium is used for

MG

Demacarium is used for

Glaucoma

What agents are the irreversible AChE inhibitors?

Organophosphates

What agents were used as war gases and pesticides?

Organophosphates

Atropine is used as a Cholinergic ____________________ (agonist/antagonist)

Antagonist (inhibits PSNS)

Relationship between dosage and response to atropine

Low doses- salivary glands are affected

Medium doses- heart and eye

High doses- GI and urinary

Doses that are high enough to decrease GI acid secretion will also affect the salivary glands!

What are the side effects of atropine

Dry mouth

Urinary retention

Constipation

Tachycardia

Overdose with atropine results in total block of ________________________ function

Parasympathetic

signs of atropine toxicity

Dry as a bone, blind as a bat, red as a beet, mad as a hatter

What is used to treat atropine toxicity?

Physostigmine

What is scopolamine used for?

Motion sickness and promote amnesia

Scopolamine is ______ lipid soluble than atropine

More... it has more pronounced effects

Ipratropium is used for

COPD

tiotropoium is used for

COPD

Tiotropium is dosed _______ a day and ipratropium is dosed _____ times a day

Once; four

tropicamide is used for

Mydriasis (eye drops)

Used as a long-acting tropicamide

Cyclopentolate

Benztropine is used for

Parkinson's disease

Trihexyphenidyl is used for

parkinsons disease

Tolterodine is used for

Overactive urinary bladder

fesoterodine is used for

overactive urinary bladder

Oxybutynin is used for

overactive bladder

Trospium is used for

overactive bladder

Darifenacin is used for

overactive bladder

Solifenacin is used for

overactive bladder