DRUGS THAT AFFECT NEUROTRANSMISSION

Local anesthetics, tetrodotoxin, 1 saxitoxin2

Action potential propagation (release) Examples

Nerve axons

Action potential propagation (release) SITE

Action potential propagation (release)

ACTION

Block sodium channels = Block conduction = No entrance of Tyrosine from the nerve axons

Na+ is the enzyme responsible for the entrance of tyrosine in the presynaptic region.

a-Methyltyrosine (metyrosine)

Metyrosine inhibits the Tyrosine hydroxylase.

Transmitter synthesis EXAMPLE

Adrenergic nerve terminals and adrenal medulla: cytoplasm

Transmitter synthesis SITE

Transmitter storage

ACTION

Prevents storage, Depletes

Transmitter synthesis

ACTION

Blocks synthesis of catecholamines

Adrenergic terminals: vesicles

Transmitter storage SITE

Reserpine

Transmitter storage EXAMPLE

Tyramine, Amphetamine (both of them are stimulant as they promote the release of neurotransmitters)

Bretylium, Guanetidine / Guanethidine

Transmitter release EXAMPLES

Adrenergic nerve terminals

Adrenergic nerve terminals

Transmitter release SITE

Transmitter release

ACTION

Promote transmitter Release ↑ Norepinephrine

Inhibit release ↓ Norepinephrine

Contraction (urinary retention)

A1

Bladder/sphincter

Ejaculation

A1

Penis, seminal vesicles

Contraction (dilates pupil)

Erects hair

A1

Pupillary dilator muscle Pilomotor smooth muscle

Contraction

A1

Most vascular smooth muscle (innervated)

Increase secretions

A1

Sweat glands (apocrine) stress

Constriction

Increased blood pressure

Increased contractility

A1

Blood vessels

Contraction

A1

Prostate

Inhibition of lipolysis

Lipolysis is the process of obtaining energy from fats.

Triglycerides → hydrolysis →Fatty acids & Glycerol

A2

Fat cells (adipocytes)

Contraction

A2

Some vascular

smooth muscle

Decreased gastrointestinal tone and motility (constipation)

A2

Smooth muscle

Decreased blood pressure (reduced Norepinephrine)

A2

Blood vessels

Inhibition (via the negative feedback mechanism) of transmitter release

A2

Adrenergic and cholinergic nerve terminals

Aggregation

A2

Platelets

Probably multiple (vasoconstriction)

A2

Postsynaptic CNS adrenoceptors

Increases heart rate, force, and rate of contraction

+ Inotropy - force of contraction

+ Chronotropy - rate of contraction

+ Dromotropy - conduction velocity

*Exacerbation of these three will lead to TACHYCARDIA.

Beta 1 agonist is contraindicated to HYPERTENSIVE PATIENTS.

Beta blockers - given to patients with HTN to manage the blood pressure.

B1

Heart

Increased renin secretion

Increased angiotensin

Increased blood pressure

Juxtaglomerular apparatus - special cell in the kidneys. It synthesizes, stores and secrete the enzyme RENIN.

When the Beta 1 receptor is activated, there will be an increase in the production of renin.

Renin - an important enzyme in producing ANGIOTENSIN

B1

Kidney

Renin

an important enzyme in producing ANGIOTENSIN

Activates

Lipolysis

B3 Fat cells

Dilates renal blood vessels

D1 Smooth muscles

Modulates transmitter release

D2 Nerve endings

Promotes smooth muscle relaxation

Bronchodilation

Beta 2 agonist - given to patients with BRONCHIAL ASTHMA.

B2

Respiratory, uterine, and vascular smooth muscle

Promotes potassium uptake (increased potassium influx)

→ DECREASED amount of potassium in the circulatory system

→ HYPOKALEMIA

B2

Skeletal muscle

Activates glycogenolysis

Increased blood sugar

Glycogenolysis - breaking down of glycogen to glucose

B2

Human liver

Decreased gastrointestinal tone and motility (constipation)

B2

Smooth muscle (gastrointestinal tract)

Bronchodilation

B2

Lungs

Relaxation of uterine muscle

B2

Uterus

❖ A1 Epinephrine

❖ A1, A2, B1, B2

Phenylephrine

A1, A2, B1

Norepinephrine

A2

Clonidine, Brimonidine, Naphazoline, Oxymetazoline, Xylometazoline

A1, A2 (partial), B1, B2

Dobutamine

B2 (for asthmatic px)

Fenoterol, Salbutamol, Terbutaline, Salmeterol, Formoterol

Amphetamine

powerful CNS stimulant (stimulates the increase of catecholamines)

Amphetamine

highly addictive; one of the active ingredients of shabu (Methamphetamine)

Ephedrine

It is also a stimulant but not as powerful as amphetamine

Ephedrine

Used to prevent low blood pressure during anesthesia

Blood vessels

Important in controlling PVR (Pulmonary Vascular Resistance) and venous capacitance

Alpha receptors

increase arterial resistance → vasoconstriction → increased BP

B1

↑ or increased Calcium influx → vasodilation ■ Beta 2 receptors = promote smooth muscle relaxation

D1 receptors

vasodilation, natriuresis → mild increase in BP (Blood Pressure)

Pulmonary Vascular Resistance (PVR)

resistance against blood flow from the pulmonary artery to the left atrium

Venous capacitance

degree of active constriction of the vessels which affects the return of blood to the heart, and thus leading to CARDIAC OUTPUT.

Natriuresis

increased secretion of Sodium ion. (↑ levels of sodium ion = ↑ contraction of the heart)

Alpha receptor activation

↑ increased PVR (pulmonary hypertension) and ↓decreased venous capacitance → ↑ total blood flow in the circulatory system

Beta receptor activation

↑ increased cardiac output

Cardiac output (CO)

volume of the blood being pump by the heart

Cardiac Output (CO)

Heart rate (HR) x Stroke Volume (SV)

Radial pupillary dilator of the iris

alpha receptor activation: Mydriasis

Blood vessels of the Upper respiratory tract

alpha receptor activation: decongestant action