PharmacoKinetics Autonomic Nervous System

Absorption and Routes of Administration

Enteral/ Oral

Receiving the medication by mouth (oral) or through other parts of the GI tract (NG tube, PEG).

Absorption and Routes of Administration

Parenteral

Receiving medication through any other routes like intravascular, intramuscular, intrathecal injections, topical applications, inhalation, patch, etc.

Absorption and Routes of Administration

Intravascular (IV)

Direct introduction of the medication to the blood and central circulation

NO absorption needed

Fastest

Ex: pain meds, anesthesia, saline

Factors Affecting Absorption

Medication molecular weight

smaller size, more absorption

Factors Affecting Absorption

Lipophilicity (hydrophobicity)

More lipophilic, less polar, more absorption

Hydrophilicity: more water soluble = reduced absorption rate

Factors Affecting Absorption

Ionization

Less ionized, more absorption

Factors Affecting Absorption

Acidic drugs

Higher absorption in LOWER pH; stomach

Factors Affecting Absorption

Basic drugs

Higher absorption in HIGHER (more alkaline) pH; small intestine

Factors Affecting Absorption

Blood flow (vascularity) to the absorption site

Greater B.F. = Greater absorption

Small intestine has higher vascularity than stomach

Factors Affecting Absorption

Surface area

Greater SA = greater absorption

Microvilli in the intestinal epithelial wall

Factors Affecting Absorption

Transition time

the longer the time of contact with the absorption surface, the higher the absorption

Bioavailability def

The extent to which a drug is absorbed into the systemic circulation

Why is bioavailability always compared to intravascular route?

IV = direct route

Bioavailability: First pass phenomenon

The first-pass effect describes the initial hepatic metabolism of enterally administered medications

Transfer of the drug to the liver through portal vein

Metabolism/ elimination of the drug

Distribution

Albumin bound drug

No effect

Cannot leave the blood to the tissues

Cannot reach the target receptors

Distribution

Free drug

Drug has effect

Active form

Separated from albumin

Distributed to the tissues

Action on target receptors

Distribution

Albumin

Main blood protein

Acts as a reservoir of the drug in the blood

Distribution

Low albumin

More free drug is available to the tissues

Higher effects

Higher risk of toxicity

Dose adjustment is necessary

P-Glycoprotein Pumps

Push medications and their metabolites out

P-Glycoprotein Pump Induction

Increases renal excretion of drugs

Decreases intestinal and gastric absorption of drugs

Decreases BBB penetration of drugs

Decreases meds in tissues

Metabolism

Phase I

Mainly in liver

Cytochrome P-450 isoenzymes: changes chemical structure

Metabolism

Phase II

Mainly in liver

Conjugation: make more polar = lower absorption

Metabolism

CYP-450 Enzymes

Key enzymes in phase I metabolism

May be inhibited or induced by some medications, smoking, alcohol intake

Metabolism

CYP-450 Inductoin

Increases the drug metabolism

Metabolism

CYP-450 Inhibition

Reduces the metabolism

Drug- Drug Interactions:

If drug A is metabolized by CYP-450 to its inactive metabolite

And if drug B is CYP-450 inducer

What happens to serum conc. of drug A?

Drug A gets fully destroyed

Drug B ensures full metabolism of Drug A

Drug- Drug Interactions:

If drug A is metabolized by CYP-450 to its inactive metabolite

And if drug B is CYP-450 inhibitor

What happens to serum conc. of drug A?

Drug B prevents Drug A metabolism/ destruction

Drug Half- Life (t 1/2)

The time needed for the serum concentration of a drug to be reduce by half

The slower the clearance: the longer the t 1/2

Drug Half- Life (t 1/2)

Hepatic insufficiency

Renal insufficiency

Insufficient metabolism = longer t ½

Can lead to toxicity

Drug conc. 10mg

t ½: 4 hours

4 hours after taking med?

8 hours after taking med?

4 hours later: 5mg

8 hours later: 2.5 mg

Neurotransmitters

Sympathetic

• Epinephrine (adrenaline)

• Norepinephrine (noradrenaline)

• Dopamine

Neurotransmitters

Parasympathetic

• Acetyl Choline

  • Serotonin

Adrenergic Receptors

Alpha 1

Vascular system, bladder neck

Hypertension

Agonist: Raises BP

Antagonist: Lowers BP

Adrenergic Receptors

Alpha 2

Everywhere against adrenergic system (?)

Adrenergic Receptors

Beta 1

Heart

Agonist: Raises HR

Antagonist: Lowers HR

Adrenergic Receptors

Beta 2

Lungs and Uterus

Agonist: relaxes lungs (asthma) relaxes uterus (stop contractions/ keep baby longer)

Albuterol

Beta- 2 agonist

Asthma: bronchodilation (relaxes lungs)

Side effect: High HR

Epinephrine

Alpha-1 agonist

Vasoconstriction = increase BP

Metoprolol

Beta-1 antagonist

Decrease HR

side effect: SOB

Diazepam

GABA agonist

CNS depression

Sedation

Ondanseteron

Serotonin blocker

Anti nausea and vomiting

Atropine

Muscarinic receptor blocker (acetyl choline antagonist)

Increase HR

Blocks parasympathetic