Week 5 General principles- Pharmacology

Question 1

What does ADME stand for ?

Answer 1

Absorption
Distribution
Metabolism
Excretion

Question 2

What are the 4 main molecular drug targets with examples

Answer 2

Receptors:
Proteins or glycoproteins found on the cell surface or within cell

Ion channels:
Ion channels allow ions (Na+, K+, Ca2+, Cl-) to pass through a cell membrane. Ion channels can be ligand-gates or voltage gated
E.g voltage gated sodium channels

Enzymes:
Enzyme proteins that catalyse biochemical reactions. It can inhibit antagonist (antagonists) or enhance (agonists)
e.g COX enzymes inhibited by drugs like Aspirin

Transporters:
Are membrane proteins that moves substances across the membrane such as glucose, ions and neurotransmitters. E.g SERT (serotonin transporter) targeted by SSRI e.g Fluoxetine to increase serotonin

Question 3

Explain selectivity, Affinity, Potency, Efficacy

Answer 3

Selectivity is how the drug with a specific receptor or enzymes.

Affinity: the strength of binding between the drug and its receptor

Potency: amount

Question 4

l

Answer 4

Production of metabolites with less biological activity
- Production of active metabolities (more potent and persist longer than the parent compound(
- Conversion of inactive pro-drugs to active form
-Production of toxic metabolites
- Prodiction of inactive metabolites that are water soluble for excretion via conjugation

Question 5

Discuss ADME throughout different life cycles

Answer 5

Neonates:
Thin and more permeable skin, decrease in gastric acids, lungs lower mucous membranes, dehydration is more common, maturation of hepatic enzymes, body composition (%body water)

Infants:
Upto 1 years, drug absorption, distribution and excretion similar to adults.
- differences in hepatic metabolism (enhanced)

Children:
Weight to body surface can be used for drug calculations, 75% body water compared to adults 50-60%

Elderly:
Increase in chronic illness, medications, age depended decline in hepatic and renal function
-Changes in body composition
-Higher proportion of body fat (Lipid soluble drugs)
-Decreases total body water and lean body mass

Question 6

Explain drug excreations (3)

Answer 6

GFR and tubular secretions facilitates transfer of drugs from blood to urine

GFR: Capillaries allow movement of drugs. most drugs cross this membrane freely expect large size and heparin, plasma bound drugs e.g warfarin cant cross

Active tubular secretions:
Transporter medicated movement drugs from peritubular capillaries to the tubular lumen. most effective mechanism of renal drug elimination

Passive re-absorption:
Lipid soluble drugs are re-absorbed more readily thus excreted poorly, polar drugs remain in the lumen of the tubule and excreted in the urine, degree of ionisation (pH) influences renal excretion

Question 7

Explain drug excreations (3)

Answer 7

GFR and tubular secretions facilitates transfer of drugs from blood to urine

GFR: Capillaries allow movement of drugs. most drugs cross this membrane freely expect large size and heparin, plasma bound drugs e.g warfarin cant cross

Active tubular secretions:
Transporter medicated movement drugs from peritubular capillaries to the tubular lumen. most effective mechanism of renal drug elimination

Passive re-absorption:
Lipid soluble drugs are re-absorbed more readily thus excreted poorly, polar drugs remain in the lumen of the tubule and excreted in the urine, degree of ionisation (pH) influences renal excretio

Question 8

Discuss Cytochrome P450 enzyme

Answer 8

CYP located on the sER (hepatocytes)
variations in P450 enzymes.

Important for drug interactions- inducers and inhibitors of P450 enzymes e,g dietary- Grapefruit juice, brussel sprouts induce drug metabolism
environmental: cigarette smoke induce CYP
Natural remedies: St John’s wort
- It can increase or decrease metabolism of some drugs
-Drug- drug interactions

Question 9

Discuss first pass metabolism

Answer 9

Drugs absorbed from the GIT pass to the liver via hepatic portal vein.

Phase 1 & 2

Phase 1
Oxidation, reduciton of hydrolysis, catabolic, products produced usually more chemically reactive
e.g Acetaminophen, toxic metabolite (NAPQI), introduce a reactive group (hydroxyl group), Largely occur in the liver

Phase 2
Anabolic reactions, conjugation reactions- Glucuronidation, sulfation, acetylations and glutathione conjugation. Usually produces less metabolically active compound.

Conjugated drug molecules is generally more polar or water soluble, increases urinary