NAPLEX: Pharmacy Foundations Part 1: Basic Science Concepts

Parts of the Peripheral Nervous System

1. Somatic (voluntary)

2. Autonomic (involuntary)

-Parasympathetic (Rest and Digest)

-Sympathetic (Fight or Flight)

What is the primary receptor that works in the somatic?

Ach acting on nicotinic receptors

What happens in the parasympathetic nervous system?

Signal --> (Ach/N) --> (Ach/M) --[Most organs, smooth muscle & glands

Sympathetic Pathway through adrenal medulla

Signal --> (Ach/N)(adrenal medulla) ---[EPI/NE

sympathetic NS:

adrenergic receptors

alpha 1 receptor : blood vessels

beta 1: heart

beta 2: lungs

Functions of the parasympathetic nervous system

think acronym

Acetylcholine (bladder & stomach)

"rest and digest"

Increased SLUDD

-Salivation

-Lacrimation

-Urination

-Digestion

-Defecation

Functions of the sympathetic nervous system

Decreased:

Salivation

Urination

Peristalsis

Increased:

Pupil dilation

Glucose production

BP & HR

Bronchodilation

1 heart 2 lungs

Beta 1: heart

Beta 2: lungs

agonist

a substance that combines with a receptor to START reaction.

can be exogenous or endogenous (mimicking an endogenous substrate)

ligand (substrate)

A substance that creates a signal or produces an effect by binding to receptor enzyme or transporter

endogenous

A substrate that is produced by the body (such as a naturally produced substrate)

exogenous

A substance that is produced outside of the body such as a drug or other chemical

Antagonist

Antagonist A substance that reduces or blocks a reaction can be endogenous or exogenous

Induction

Induction When a substance increases the activity of an enzyme

Inhibition

Inhibition When a substance decreases or blocks the activity of an enzyme

Competitive inhibition

Antagonist binds to same active site as the endogenous substrate

Noncompetitive inhibition

Antagonist binds to an allosteric site (not active site)

The active site shape is changed which does not allow endogenous substrate to bind

ach: muscarinic receptor response

agonist and antagonists

increase sludd

decrease sludd

-Salivation

-Lacrimation

-Urination

-Digestion

-Defecation

What happens when acetylcholine or agonists acts on nicotinic receptors?

antagonists?

Increased HR and BP

neuromuscular blockade (paralysis)

what receptors do epi/ne act on?

alpha 1 (peripheral)

alpha 2 (central)

beta 1 (heart)

beta 2 (lungs)

What do alpha 1 receptors do?

-Peripheral

Smooth Muscle vasoconstriction =

Increased BP

What do alpha 2 receptors do?

Central (in brain mostly)

Less NE and Epi release

Decreased BP, HR (decreased sympathetic output = less ne/epi to act on peripheral receptors)

What do beta-1 receptors do?

Increase myocardial contractility, CO & HR

What do beta-2 receptors do?

Smooth muscle relaxation

Bronchodilation

Common Alpha-1 Agonists

-Phenylephrine

-Dopamin (high-dose)

Common Alpha-1 Antagonists

Alpha-1 Blockers

-Doxazosin, tamsulosin

-Phentolamine

Common Alpha-2 Agonists

-Clonidine

-Brimonidine (opthalmic)

decrease bp, hr

Common Alpha-2 Antagonists

-Ergot alkaloids

-Yohimbine

increase bp, hr

Common Beta-1 Agonists

-Dobutamine

-Dopamine (moderate-dose)

Common Beta-1 Antagonists

Beta-1 selective blockers

-metoprolol

decrease contractility, co, hr

Common Beta-2 Agonists

-albuterol

-terbutaline

Common Beta-2 Antagonists

Non-selective blockers

-propranolol

Common Dopamine Agonists

-Levodopa

-Pramipexole

improve parkinsons

Common Dopamine Antagonists

-1st generation antipsychotics

-metoclopramide

worsen parkinsons

Common Serotonin Agonists

-triptans

Common Serotonin Antagonists

-5HT-3 antagonists like ondansetron

-2nd generation antipsychotics

drugs with multiple receptor effects

isoproterenol: b1/b2 agonist

carvedilol: alpa 1, b1/b2 aantagonist

NE: alpha 1, b1

Catecholamine Metabolism

Dopamine ---> NE --- EPI ---> Harmless metabolites

Tryptophan --> 5-HT ---> Harmless metabolites

Acetylcholinesterase

The enzyme that breaks down acetylcholine in the synaptic cleft

Acetylcholinesterase inhibitors

- Donepezil (Aricept, Aricept ODT)

- Rivastigmine (Exelon, Exelon Patch)

- Galantamine (Razadyne, Razadyne ER)

Angiotensin Pathway

Liver released angiotensinogen // Renin is released from the kidney ---> Angiotensin I ---> angiotensin II ---[Aldosterone secretion/Vasoconstriction]

Catechol-O-methyltransferase (COMT)

Breaks down levodopa

COMT inhibitors

Entacapone

Tolcapone

Cyclooxygenase (COX)

Converts arachidonic acid into prostaglandins (inflamation/pain) and thromboxanes (platelet aggregation)

What blocks COX enzymes?

NSAIDS

MAO inhibitors

Phenelzine

Isocarboxazid

Selegiline

Tranylcypromine

Phosphodiesterase

Converts cAMP (smooth muscle relaxant) to AMP

PDE-5 inhibitors

Sildenafil

Vardenafil

Tadalafil

Vitamin K epoxide reductase (VKOR)

Coverts Vitamin K into active form which is used to make Factor II, VII, IX, X

VKORC1 inhibitor

Warfarin

Xanthine Oxidase (XO) Pathway

Hypoxanthine --> Xanthine --> Uric Acid --> Allantoin

Xanthine Oxidase Inhibitors

Allopurinol

Febuxostat

What do MAOi cause?

Build of of 5-HT, NE, EPI

MAOIs used for depression

**SPIT**

Selegiline

Phenelzine

Isocarboxazid

Tranylcypromine

What risks can MAOi's lead to when combined with other drugs that increase NE and Epi?

Hypertensive Crisis (Increased BP, HR, agitation & death)

Common Drugs:

-Bupropion

-SNRIs

-TCAs

-Amphetamines/stimulants

-Linezolid

-Methylene blue

-Tyramine-rich foods

What risks can MAOi's lead to when combined with other drugs that increase 5-HT?

common drugs (lots)

Serotonin Syndrome

(Agitation, Tachycardia, Diaphoresis, Mydriasis, Hyperreflexia, Clonus, Tremor, N/V/D, HTN)

Common Drugs:

-SSRIs

-SNRIs

-TCAs

-Mirtazapine

-Trazodone

-St. John's Wort

-Opioids

-Tramadol

-Antiemetics (ondansetron)

-Buspirone

-Lithium

-Triptans

-Ergotamines (migraine drugs)

-Dextromethorphan (HD)

Drugs with a sulfonamide group

Celecoxib

Sulfamethoxazole

Loop diuretics (bumetanide & furosemide)

Triptans

Thiazide diuretics

Acetazolamide

Sulfonylureas (chlorpropamide, acetohexamide)

What does a beta-lactam look like?

Square with N component and double bonded O fused to another 5 or 6 sided ring

what do nsaids look like?

what does aspirin (salicylate) look like

What compounds contain Iodine?

Levothyroxine

Amiodarone

contains and "i" in the structure

Degradation reactions:

Oxidation hydrolysis photolysis

oxidation

transfer of electrons

drugs with oh on aromatic ring are at risk

protect from light, heat metal ions to extend exp date

hydrolysis

breakdown by water

esters, amides, lactams at risk

protect from moisture

photolysis

breakdown by light

ascrobic acid, nitroprusside, phytonadione at risk

protect from light