MED ORG LEC - 04 ANS Drugs

Sympathetic

• Fight or Flight

• Activated during stressed states

• It uses catecholamines (Dopamine, Norepinephrine, Epinephrine)

Parasympathetic

• Rest and Digest

• Housekeeping

• Responsible for homeostasis

• It uses Acetylcholine (ACh)

Short, Long

Sympathetic

_____ Preganglionic neuron

_____ Postganglionic neuron

Long, Short

Parasympathetic

_____ Preganglionic neuron

_____ Postganglionic neuron

CNS, GI

Predominant Location of M1 Receptor

Wakefulness, Memory, HCl production

The effect when M1 receptor is activated

Heart

Predominant Location of M2 Receptor

Negative Chronotropy (Slow heart rate)

The effect when M2 receptor is activated

Smooth Muscle, Glands

Predominant Location of M3 Receptor

Increased GIT movement, Secretions (tears, sweat, saliva), Miosis (pupil constriction), Bronchoconstriction, Bladder contraction

The effect when M3 receptor is activated

Autonomic Ganglia, Brain

Predominant Location of Nn Receptor

Brain excitation; Firing of ACh

The effect when Nn receptor is activated

Neuromuscular Junctions

Predominant Location of Nm Receptor

Skeletal muscle contraction

The effect when Nm receptor is activated

Acyoxyl Group

• Don’t remove the oxygen

• Terminal methyl can only be replaced by isosteres (for DoA improvement)

Ethyl Group

• Addition of beta-methyl imposes muscarinic selectivity and higher DoA

• Don’t do anything drastic! (ex. lengthening or shortening of length)

Quaternary Ammonium Group

• Don’t do anything! (ex. replace methyl groups, remove methyl groups, remove the positive charge, replace nitrogen)

Bethanecol

• The only oral agent used for urination of patients post-operation

• For resumal of urination post-operation

Indirect Agonists

• SAR is indistinct since the drugs lie in many farfetched chemical classes

• They are instead classified by chemical class (and resulting DoA):

  • Aminoalcohol (short-acting; reversible)

  • Carbamate (intermediate-acting; reversible)

  • Organophosphates (long-acting; irreversible)

-stigmine

Ending suffix of Carbamate

DUMBBELLS

Abbreviation for Adverse Effects

Diarrhea

D in DUMBBELLS

Urination

U in DUMBBELLS

Miosis

M in DUMBBELLS

Bradycardia (Slow Heart Rate)

B in DUMBBELLS

Bronchoconstriction

B in DUMBBELLS

Emesis (Vomiting)

E in DUMBBELLS

Lacrimation (Tears)

L in DUMBBELLS

Lethargy (Sluggish)

L in DUMBBELLS

Sweating

S in DUMBBELLS

Atropine Toxicity

“Alice in Wonderland” effects

Blind as a Bat

Cyclopegia (excessive loss of accommodation)

Dry as a Bone

Reduces secretions in mouth and eye (sandy eyes, dry mouth)

Red as a Beet

Flushing due to vasodilation

Hot as a Hare

Hyperthemia that can lead to atropine fever in children

Mad as a Hatter

Confusion

Pralidoxime/2-PAM

• “Cholinesterase regenerator”

• Binds to organophosphate-inactivated AchE

• Used for poisoning

• Other Option:

  • Atropine

-curiums and -curoniums

Prefix for Non-Depolarizing Nicotinic Antagonists/Neuromuscular Blockers

Vanillylmandelic Acid VMA()

Major metabolite from NE and E

Homovanillic Acid (HVA)

Major metabolite from DA

Blood Vessels: Vasoconstriction

Eyes: Mydriasis

Bladder: Urinary retention

Organ Effects of α1 Adrenergic Agonists?

Blood Vessels: Vasodilation

Eyes: Miosis

Bladder: Urinary relaxation

(opposite of α1)

Organ Effects of α2 Adrenergic Agonists?

Heart: (+) Chronotropy/Inotropy (increased HR)

Organ Effects of β1 (1 heart) Adrenergic Agonists?

Lungs: Bronchodilation

Uterus: Uterine relaxation

Skeletal Muscle: Contraction and K+ influx

Organ Effects of β2 (2 lungs) Adrenergic Agonists?

Lipolysis (fat breakdown or metabolism)

Organ Effects of β3 Adrenergic Agonists?

Kidney: Renal vasodilation

Organ Effects of D1 Adrenergic Agonists?

-zolines

Prefix of Imidazolines

-nidine

Prefix of Guanidines

-zosin

Prefix for Alpha-1 Blockers

-olol

Prefix of Beta Blockers

Nonselective Beta-Blocker Antiadrenergics

• Nadolol

• Sotalol

• Timolol

• Propanolol/Penbutolol

Cardioselective Beta-Blocker Antiadrenergics

• Bisoprolol/Betaxolol

• Esmolol

• Atenolol/Acebutolol

• Metoprolol

Glaucoma

Building up intraocular (eye) pressure due to excessive fluid

Myasthenia Gravis

Autoimmune condition leading to muscle weakness via destruction of Nm receptors

Urinary Incontinence

Inability to control urination

Shock

Excess drop of blood pressure

Reuptake

Return of neurotransmitters to the neurons they came from

Blood-Brain Barrier (BBB)

Thick lipid barrier separating the bloodstream from the CNS

Centrally

Penetrates BBB, and may lead to mental or psychotropic effects

Heart Failure

Inability of heart to pump blood, usually via weakened contractions

Cardiogenic Shock

Specific shock where the problem is the heart contraction (especially from myocardial infarction)

Tocolytic

Drug that prevents contractions in premature labor

Pheochromocytoma

Adrenal tumors releasing excess NE and causing adrenergic excess (especially HTN)

Benign Prostatic Hyperplasia

Noncancerous enlargement of prostate, causing pain by blocking urination

Orthostatic Hypotension

Drop is blood pressure by sudden change of posture

ex. standing quickly from sleep

First-dose phenomenon

Orthostatic hypotension from first intake of quinazolines