Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Gastrointestinal > ADME of Medicines > Flashcards

ADME of Medicines Flashcards

1
Q

What are the oral routes of administration of drugs?

What does this mean for their absorption?

A
  • Buccal / sublingual
    • ​Direct absorption into the blood stream.
    • Avoids first pass metabolism.
    • Not ideal surface for absorption.
  • Gastric mucosa
    • ​Enteric coating.
  • Small intestine
    • ​Main site of drug absorption.
    • Large surface area, more neutral pH.
  • Large intestine
    • ​Poor absorption, long transit times.
  • Rectal mucosa
    • ​Direct to systemic circulation.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the 4 ways in which small molecules cross cell membranes?

A
  • Diffusing directly through the lipid.
    • Lipid solubility is highly important.
  • Diffusing through aqueous pores.
    • More likely important for diffusion of gases.
  • Transmembrane carrier protein.
    • E.g. solute carriers.
  • Pinocytosis.
    • Mostly macromolecules, not drugs.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Drugs have physiochemical factors which affect their ionisation.

What does this mean for weak bases and weak acids and their absorption?

A
  • Weak bases
    • ​Ionised in acidic pH
    • Absorbed in the small intestine
    • Possibly ionised in plasma.
  • Weak acids
    • ​Unionised in acidic pH.
    • BUT also absorbed in small intestine.
      • Large surface area.
  • Weak base will accept a proton, weak acid will donate a proton. In an acidic environment, weak acids are less likely to be ionised; in a basic acid weak bases are less likely to be ionised. But, in an acidic environment a weak base will be ionised.
  • This means that in the small intestine, a weak acid will be favourably absorbed (because an unionised drug will move across the membrane more freely), but a weak base in the small intestine will also be absorbed because the SI is specialised for absorption. So, by being ionised a weak base drug is not at a great disadvantage.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the effect of food on drug absorption?

A
  • In general, food tends to slow the rate of gastric emptying.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What direct or indirect effects do antacids and proton pump inhibitors have on absorption?

A

Causes changes in gastric or intestinal pH.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What direct or indirect effects do laxatives and anticholinergics have on absorption?

A

Causes changes in gastrointestinal motility.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What direct or indirect effects do vasodilators have on absorption?

A

Causes changes in gastrointestinal perfusion.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What direct or indirect effects does neomycin have on absorption?

A

Interferes with mucosal function.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What direct or indirect effects do tetracycline, calcium and magnesium have on absorption?

A

Causes chelation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What direct or indirect effects does cholestyramine have on absorption?

A

Causes resin binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What direct or indirect effects does charcoal have on absorption?

A

Causes adsorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

List the factors that affect oral absorption.

A
  • Particle size and formulation
  • GI motility
  • First pass metabolism
    • First pass metabolism by the gut wall or hepatic enzymes.
  • Physicochemical factors
    • Direct drug interactions, dietary factors, varying pH.
  • Splanchnic blood flow
    • Increased flow increases drug absorption.
  • Efflux pumps
    • P-glycoprotein.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

List the parenteral routes by which drugs can be absorbed.

A
  • Subcutaneous
    • Slow absorption due to blood flow.
  • Intramuscular
    • Lipophilic drugs rapidly absorbed
    • Polar drugs via bulk flow and endothelial cell junctions.
    • High MWT or very liphphobic drugs via lymphatics.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What factors affect the rate of onset of drugs which are administered parenterally?

A
  • Extent of capillary perfusion.
  • Drug vehicle.
  • Affected by factors that alter perfusion.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe inhalation as a mode of administration of drug.

A
  • Drug absorbed by the alveolar epithelium and bronchial mucosa.
  • Systemic effects
    • ​Lipid-soluble drugs
      • Volatile / gaseous anaesthetics
    • Drugs of abuse
    • Accidental poisoning
  • Local effects
    • ​Modify structure (ipratropium)
    • Particulate size (salbutamol)
    • Selectivity for receptors (salbutamol)
    • Rapid breakdown in circulation (fluticasone)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe intranasal administration of drugs.

A
  • Easily accessible, rich vascular plexus.
  • Advantages
    • ​Avoids hepatic first pass metabolism.
    • Ease, convenience, safety.
  • Limitations
    • ​Limited drugs suitable.
      • Requires concentrated drug.
17
Q

Describe the use of the topical route for administration of drugs.

A
  • Healthy skin as a barrier
    • Stratified, squamous epithelium
    • Keratinised layer
    • Sebaceous gland secretions
  • Local effects
    • Corticosteroids for eczema (hydrocortisone)
    • Antihistamines for insect bites (mepyramine)
    • Local anaesthetics (EMLA)
  • Systemic effects
    • Transdermal patches (HRT, GTN, nicotine)
    • Accidental poisoning (AChEsterase insecticides)
  • Surface area / volume ratio
18
Q

List the different types of intravascular devices (IVDs).

A
  • Peripheral venous catheters
  • Central venous catheters (CVCs)
    • Peripherally inserted CVCs
    • Skin-tunneled CVCs (e.g. Hickman and Broviac lines)
  • Arterial catheters
19
Q

What are the 3 methods of administering intravenous medications?

A
  1. Continuous infusion
  2. Bolus injection
  3. Intermittent infusion
20
Q

Describe continuous IV infusion.

A
  • Stable drugs
  • Short half life
  • Time dependent effects
  • Needs dedicated IV site
21
Q

Describe bolus injection.

A
  • Rapid response required
  • Incompatibilities
  • Unstable drugs
22
Q

Describe intermittent infusion.

A
  • Unstable drugs
  • Long half life
  • Concentration dependent effects
  • Less compatibility concerns
23
Q

What are the complications of IV drug administration?

A
  • Fear / phobia / pain
  • Infection / sepsis
  • Thrombophlebitis
  • Extravasation / infiltration
  • Emboli
  • Anaphylaxis / hypersensitivity
  • Overdose
  • Insufficient mixing
  • Stability of medicines in solution must be considered:
    • Light [total parenteral nutrition (TPN)]
    • Temperature (e.g. insulin, TPN)
    • Concentration (e.g. amiodarone)
    • pH (e.g. midazolam)
    • Interaction of medicines with the syringe or bag
24
Q

Describe extravasation and infiltration with respect to IV cannulation.

A
  • In both - the needle tip has gone into a tissue space.
  • Extravasation is when there is something which is ‘irritant’ but infiltration is just adding volume to the tissue space.
  • They can both be dangerous but extravasation is associated with more tissue damage.
25
Q

List the factors which affect distribution of a drug.

A
  • Cardiac output and blood flow
  • Plasma protein binding
  • Lipid solubility
  • Degree of drug ionisation
  • pH of compartments
  • Capillary permeability
26
Q

What effect does organ perfusion have on distribution of drugs?

A
  • Initial rate of distribution of drugs depends heavily on blood flow.
27
Q

Describe the effect of albumin binding on the distribution of drugs.

A
  • Albumin is a predominate plasma binding protein (40g/L).
  • Lipid-soluble drugs bind non-specifically.
  • Weak acids bind to a specific, saturable site.
28
Q

List the sites of drug metabolism.

A
  • Gut lumen
  • Gut wall
  • Plasma
  • Lungs
  • Kidneys
  • Nerves
  • Liver
29
Q

List the potential results of drug metabolism.

A
  • Pharmacological deactivation
  • Pharmacological activation
  • Type of pharmacological response
  • No change in pharmacological activity
  • Change in drug uptake
  • Change in drug distribution
30
Q

Describe phase 1 and phase 2 of drug metabolism.

A
  • Phase 1 metabolism
    • ​Generally oxidation, reduction or hydrolysis.
      • Introcude / reveal a reactive chemical group.
      • “Functionalisation”.
    • Products are often more reactive
  • Phase 2 metabolism
    • ​Synthetic, conjugative reactions.
    • Hydrophilic, inactive compounds generated (usually).
31
Q

Give examples of oxidations, reductions and hydrolysis reactions in phase 1 metabolism.

A
  • Introduces of unmasks functional group
    • E.g. -OH, -NH2, -SH, -COOH etc.
  • Oxidations
    • ​Mixed-function oxidase system (cytochrome P450)
    • Alcohol dehydrogenase
    • Xanthine oxidase
  • Reductions
    • ​Ketone reduction
    • Anaerobic cytochrome P450 metabolism
  • Hydrolysis
    • ​Ester hydrolysis (e.g. cholinesterases)
    • Amine hydrolysis
32
Q

Describe mixed-function oxidase system (CP450s).

A
  • Microsomal (ER) enzymes
    • ​Liver, kidney, lung, intestine etc.
  • Consists of:
    • ​Cytochrome P450
    • NAPDH-CP450 reductase
    • Lipid
  • Requires:
    • ​Molecular oxygen
    • NAPDH
33
Q

What are the products of phase 2 metabolism?

A
  • Detoxified, water-soluble, easily secreted products.
    • Suitable for excretion in bile or urine.
34
Q

Describe the factors which must be considered with respect to drug metabolism.

A
  • Many enzymes capable of metabolising drugs.
    • Overlapping substrate specificities.
    • Metabolism of endogenous compounds.
  • Potential for competition and saturation.
    • Drugs and endogenous compounds for the same enzyme.
    • Different enzymes for the same substrate.
    • Enzyme can be saturated, conjugate depleted.
  • Issues of variation / induction / inhibition.
    • Inter-individual responses can vary
    • Substantial issue due to broad specificity of enzymes.
35
Q

In what form are drugs excreted from the body?

A
  • Drugs are eliminated either unchanged or as metabolites.
    • In general, hydrophilic drugs eliminated more readily than lipophilic drugs.
  • Possible sources of excretion include:
    • Breath
    • Urine
    • Sailva
    • Faeces
    • Perspiration
    • Milk
    • Bile
    • Hair
  • The kidneys are the most important organs involved in the elimination of drugs and their metabolites.
36
Q

Describe biliary excretion.

A
  • Transfer of drugs from plasma to bile
    • ​Organic cation transporters (OCTs)
    • Organic anion transporters (OATs)
    • P-glycoproteins (P-GP)
  • Concentrated in bile, delivered to intestine
    • ​Hydrophilic drug conjugates (e.g. glucuronides)
    • Hydrolysis of conjugate can occur
      • Reabsorption of liberated drug
      • Enterohepatic circulation
37
Q

Describe enterohepatic circulation.

Which drugs are metabolised via this pathway?

A
  • Oral antibiotics
  • Oral synthetic oestrogens
38
Q

Describe renal excretion of drugs.

A
  • Glomerular filtration
    • ​Filters drugs below 20kDa in molecular weight
    • Not filtered if drug is bound to plasma albumin
  • Tubular secretion
    • ​OATs and OCTs
    • OATs transport against electrochecmical gradient
    • Cleared even if bound to plasma albumin
  • Diffusion across renal tubule
    • ​If tubule is freely permeable, 99% of drug is reabsorbed
      • Lipophilic drugs excreted poorly
      • Polar drugs remain in the lumen
    • Urinary pH?

Gastrointestinal (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions