Pharmacology EXAM 2 GVSU

Neuropharmacology

The study of drugs and how they affect the nervous system. They can either excite or depress normal neuronal functions.

Axonal conduction

Not very selective; This process involves an action potential moving along an axon. All axon conductions are the same.

Synaptic transmission

This process is more selective and involves information being carried across neuron gaps to posy synaptic cells- another neuron, muscle cell, or cell within a secretory gland.

Steps in synaptic transmission

1. transmitter synthesis
2. transmitter storage
3. transmitter release
4. receptor binding
5. termination of transmission

Mort and Merv represent?

If a drug has more receptor then it is more selective and desirable.

3 primary functions of the ANS?

Regulates the heart, secretory glands, and smooth muscles.

7 functions of the parasympathetic nervous system?

Bronchoconstriction, empty the bladder, empty the bowel, increase gastric secretions, decrease heart rate, constrict pupils, and focus eyes for near vision.

What four things do PSNS drugs affect?

Digestion of food, excretion of waste, control of vision, and conservation of energy(by decreasing CO).

3 main functions of the sympathetic NS?

1. Regulation of the cardiovascular system- maintains blood flow to the brain, redistributes blood, vasoconstriction.
2. Regulation of body temperature- Regulates BF to the skin, promotes secretion of sweat, induces piloerection when cold.
3. Implementation of "fight or flight"- Increases HR, increases BP, shunts blood away from skin to viscera, dilates bronchi in lungs, dilates pupils, glucogenolysis.

how does the ANS regulate physiological processes? (4 ways)

1. Patterns of innervation and control- innervations of the PSNS and SNS in which effects are opposed, complementary, or one system is effected.
2. Feedback regulation
3. Baroreceptor reflex- to reg BP
4. Autonomic tone

2 sites in which drugs can act?

synapses- area between two neurons
junctions- area between post-synaptic neuron and effector organs.

True or false? Acetylcholine is found at every pre/post synaptic neuron of the PSNS and every pre-synaptic neuron of the SNS?

True

The adrenal medulla of the SNS releases which NT?

Epinephrine

Which NT is released by post synaptic neurons of the SNS when innervating sweat glands? What about other SNS organs?

Ach(sweat glands) and NE(various organs)

Function of Nicotinic N? (located at the adrenal medulla and all ANS ganglia)

Promote ganglia transmission and promotes the release of EPI.

Function of Nicotinic M? (located at neuromuscular junctions)

Promotes skeletal muscle contractions

Function of muscarinic receptors?

Activates almost all target organs of the PSNS- promotes bronchoconstriction, decrease in HR, increases gastric secretions, erection, constricts the pupils, bladder emptying, vasodilation, etc.

Function of alpha 1 receptors?

Vasoconstriction, constriction of radial muscle (leading to mydriasis), ejaculation, and contraction of the bladder neck and prostate.

Function of alpha 2 receptors? (located PRE-SYNAPTICALLY)

Inhibits the release of NE from neurons.

Function of beta 1 receptors?

Heart- Increases conduction velocity at the AV node, increases HR, and the force of contractions.
Kidneys- Renin released to increase BP

Function of beta 2 receptors?

Lungs- bronchodialation
Vasodilatation of heart, lungs, and skeletal muscles.
Glycogenolysis at liver and muscle.
Contraction of skeletal muscle and relaxation of uterine muscles.

Function of dopamine receptors?

Vasodilation at kidneys to improve perfusion.

Life cycle of epinephrine: 4 steps

1. Synthesis of NE in chromaffin cells of the adrenal medulla. (NE is made first and then converted into EPI)
2. EPI is stored in vesicles in the adrenal medulla
3. EPI is then released into the bloodstream where it can then activate all alpha and beta receptors.
4. EPI is terminated via hepatic metabolism

Effects of muscarinic agonists/drug name?

Drug name: bethanechol
Effects: Decreases heart rate, constricts bronchioles, increases GI tone/mobility, relaxes bladder muscles, vasodilation, increased secretions, miosis.
Adverse effects: bradycardia, excessive urination/diarrhea, increased bladder pressure, or bronchoconstriction.

Therapeutic uses for bethanechol?

It is used to treat urinary retention or 'off label' GERD; take one hour before meals or 2hours after meals.

Pilocarpine can be used to treat 2 other health adversities...(Another type of muscarinic agonist)

Glaucoma and xerostomia

Source for muscarinic toxicology?

Mushrooms- treat with antagonists like atropine

Atropine can be found naturally in what 2 plants?

Atropa belladonna and datura stramonium

Pharmacologic effects of atropine?

Increased HR, decreased secretions, decreased GI mobility, relaxes bronchi, mydriasis, mild CNS excitation.

Therapeutic uses for atropine?

Preanesthetic medication, asthma, bradycardia, eye disorders, GI hyper-mobility, etc.

Overactive bladder is treated using?

Anticholinergic drugs

4 major symptoms of OAB?

1. Urinary urgency
2. Urinary frequency
3. Nocturia
4. Urge incontinence

Muscarinic Subtypes M1, M2, and M3 are found?

M1-Salivary glands and the CNS
M2- Heart
M3- Bladder, GI, Eyes, Salivary glands

What is the name of the drug that is highly M1 selective? used for OAB

darifenacin

Primarily M3 Selective Antagonists? used for OAB

Oxybutynin

Nonselective anticholinergic drug? used for OAB

tolterodine

Beta 3 agonist drug used to relax the bladder's detrusor muscle and increase urine storage?

mirabegron

cholinesterase inhibitors are drugs that...

Prevent the enzymatic breakdown of Ach; non-selective and has limited therapeutic effects.

Two main reversible cholinesterase inhibitors?

Neostigmine(Contains an ammonium group) and physostigmine(able to cross membranes)

Irreversible cholinesterase inhibitor drug name?

Echothiophate iodide-used in chemical warfare/insecticides

Neostigmine and Physostigmine can cause?

an increase in Ach levels! Bradycardia, bronchial constriction, urinary urgency, increased GI tone/mobility, miosis, increased glandular secretions, INCREASED FORCE OF MUSCLE CONTRACTIONS, etc.

Myastenia Gravis (MG) attacks Nm receptors and can be treated with which cholinesterase inhibitor?

Physostigmine

Signs of a cholinergic crisis?

Diarrhea/diaphoresis, urination, miosis, bradycardia, emesis, lacrimation, and salvation. (DUMBELS)

Neuromuscular blocking agents MOA...

Prevents Ach from activating Nm receptors; causing muscle relaxation(useful before surgery, endotracheal intubation, mechanical ventilation, etc.)

True or false? Neuromuscular blocking agents can cross the BBB

False. They all contain an ammonium ion/positive charge

Two neuromuscular blocking agent classifications?

Competitive(non-depolarizing) and depolarizing

MOA of competitive neuromuscular blocking agents...

The drugs compete with Ach for the Nm receptor binding site, blocking activation; causing muscle relaxation/flaccid paralysis, and hypotension.

Competitive (non-depolarizing) neuromuscular blocking agent drug name...

Pancuronium- rapid onset of paralysis, peaks at 25-45 min, complete recovering after 1 hour.

Depolarizing neuromuscular blocking agents: drug prototype and MOA?

Succinylcholine
MOA: blinds to Nm receptors on the motor end plate and causes a state of constant depolarization, remains bound.
-Ultra-short acting and peaks at 1 minute

Adverse effects of succinylcholine?

Prolonged apnea, malignant hyperthermia (due to muscle rigidity), post-op muscle pain, and hyperkalemia.
DO NOT TAKE WITH ANTIBIOTICS

5 catecholamines (adrenergic agonist)

Epinephrine(alpha and beta), NE(alphas and beta 1), dopamine(a 1, b 1, and dopamine), isoproterenol(betas), and dobutamine(beta 1)

3 noncatecholamines (adrenergic agonists)

albuterol(beta 2), ephedrine(alphas and betas), and phenylephrine(alpha 1)

Alpha 1 agonist activation therapeutic effects:

hemostasis-reduction of blood loss via vasoconstriction
nasal decongestion via mucosal vasoconstriction
delayed absorption of local anestetics
elevation of BP
Mydriasis

True or false? Alpha 1 agonists can cause tissue necrosis if extravasation occurs.

true

Centrally acting Alpha 2 agonist activation therapeutic effects?

Inhibition of NE released->decrease in sympathetic outflow and relief of severe pain

Beta 1 agonist activation therapeutic effects?

Increased force of contractions/AV conduction for those with HF, increased HR during shock, can initiate heart contractions during cardiac arrest.

True or false? Beta 1 activation can cause heart dysrhythmias and angina pectoris?

true!

Therapeutic applications of Beta 2 agonists?

Treating asthma via bronchial dilation and delay of preterm labor by relaxing the uterine smooth muscles.

Adverse effects of beta 2 activation?

Hyperglycemia and a tremor

Which NT is often used to treat anaphylactic shock?

Epinephrine

Therapeutic uses of epinephrine? - ONLY ADMINISTER VIA IV, IM, OR SUBQ

Delays absorption of local anesthetics, hemostasis, can increase BP, can overcome AV heart block, restores cardiac functioning, causes bronchodialation in those with asthma, and treats anaphylactic shock.

Therapeutic uses of norepinephrine? -activates alpha 1/2 and beta 1

Used during hypotensive states and cardiac arrest; good for diabetic patients; administered IV

Isoproterenol therapeutic uses?- activates B 1 and 2

Used to treat an AV heart block, cardiac arrest, and shock!

Dopamine therapeutic effects (dose-dependent)?- only able to activate alpha 1 at high doses

Treats shock-increasing cardiac output and renal perfusion and heart failure-increases heart contractions

Dobutamine therapeutic uses?-activates beta 1 receptors

Treats heart failure, but may cause tachycardia!

Phenylephrine therapeutic uses?-Non catecholamine that activates alpha 1 receptors (Administered orally, IV, nasal or topical)

decreases nasal congestion, vasoconstriction, dilates pupils, and delays anesthetic absorption.

Albuterol therapeutic uses

Treating asthma because it only activates BETA 2 receptors!

Ephedrine therapeutic uses? (activates alpha and betas)

Asthma, shock, and anesthetic induced hypotension.

Why is ephedrine considered a mixed drug?

Ephedrine can activate alpha and beta receptors indirectly or directly!

Non-selective alpha antagonists? (2)

Phenoxybenzamine
Phentolamine

Selective alpha antagonists? (6)

Prazosin, terazosin, doxazosin, tamulosin, alfuzosin, and silodosin

Therapeutic implications of alpha 1 blockers?

Decrease BP, reverse toxicity from alpha agonists, benign prostatic hyperplasia, pheochromocytoma, and Raynaud's disease(to prevent vasoconstriction).

Adverse effects of alpha 1 antagonists?

Orthostatic hypotension, reflex tachycardia, nasal congestion, inhibition of ejaculation.

Adverse effects of alpha 2 blockage?- by blocking alpha 2 more NE is released

Reflex tachycardia

Therapeutic uses for prazosin?

Hypertension and BPH; vasodialates arterioles and veins/relaxes smooth muscles of the bladder neck

Therapeutic uses for terazosin and doxazosin?

HTN and BPH-same as prazosin

Tamsulosin therapeutic uses?

BPH ONLY! Very selective for alpha 1 in the bladder region! Warning: May cause headache and a prolonged QT interval

alfuzosin therapeutic uses?

BPH; blockage of vascular alpha 1 receptors is weak- may also prolong the QT interval

silodosin therapeutic uses?

BPH ONLY! can reduce semen lost during orgasms

Phentolamine therapeutic uses?-non selective alpha antagonist (competitive)

Blocks both alpha 1 and 2 receptors competitively, used to treat and diagnose pheochromocytoma, prevent tissue necrosis after extravasation of drugs that vasoconstrict, and reversal of soft tissue anesthesia

Phenoxybenzamine therapeutic uses?- non selective alpha antagonist (non-competitive)

NON COMPETITIVE alpha receptor antagonist and only approved to treat pheochromocytoma with LONG lasting effects!

What are the three classes of beta antagonists?

1st generation- non selective
2nd generation- cardioselective and block beta 1 only
3rd generation- with vasodilation properties

True or false? Therapeutic applications of beta blockers are due almost entirely to blockade of beta 1 receptors.

True

Pharmacological effects of propranolol?

Propranolol is a 1st generation, non selective beta blocker.
By blocking beta 1 and beta 2- HR decreases, contractions decrease, the release of RENIN is inhibited, and with beta 2 blockage bronchoconstriction, vasoconstriction, and a decrease in glycogenolysis occurs.

Therapeutic uses for propranolol? -VERY LIPID SOLUBLE

HTN, angina pectoris, myocardial infraction, prevention of migraines, and "stage fright"

Which channel blockers can interact with propranolol?

Calcium channel blockers!

What type of drug is Metoprolol?

2nd generation, Cardioselective beta blocker!

Therapeutic uses for metoprolol?

Treat HTN, angina pectoris, HF, and MI
Adversities: bradycardia, low CO, rebound cardiac excitation, etc.

3rd generation beta blockers include...

carvedilol, labetalol, and nebivolol

Which two 3rd generation beta blockers promote vasodialation by blocking beta 1/2 and alpha 1 receptors?

carvedilol and labetalol

Which beta-blocker promotes vasodilation by causing a release in NO from the vascular epithelium?-3rd generation

nebivolol

two groups of indirect-acting antiadrenergic agents

Centrally-acting alpha 2 agonists and adrenergic neuron-blocking agents

Three drugs that are centrally acting indirect anti-adrenergic agents:

Chlonidine, guanfacine, and methyldopa/methyldopate

Adrenergic neuron blocking agents(within neuron):

Reserpine

Therapeutic uses of clonidine

Approved for HTN, severe pain, and ADHD; selective activation of alpha 2 receptors in the CNS/decreases sympathetic outflow to BV/bradycardia/minimal orthostatic hypotension

therapeutic uses of guanfacine

HTN and ADHD

Methyldopa(by mouth) and methyldopate(IV)

HTN and safe for pregnant mothers

Two ways that adrenergic neuron-blocking agents can act?

1. Causes displacement of NE in the nerve terminal;NE is exposed to destruction by MAO
2. Suppresses the synthesis by blocking uptake of dopamine into presynaptic vesicles.

Therapeutic uses of reserpine

HTN and psychotic states

Other Muscarinic Antagonists

Scopolamine, ipratropium bromide, dicyclomine, glycopyrrolate, and atropine/cyclopentolate/tropicamide