Naisbitt Flashcards

1
Q

How do developments in medchem impact drug discovery?

A

With greater knowledge, drugs can be developed to have higher affinities and hence be more selective - therefore a lower dose can be given with less adverse effects

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2
Q

What’s significant about sulphonamides?

A

1st synthetic antibacterial agents

Effective against a wide range of infections - bar Salmonella

Highly toxic in some patients

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3
Q

What is the MOA of sulphonamides?

A

They inhibit Dihydropteroate synthase - blocking para-aminobenzoic acid - which is responsible for synthesising folic acid.

Folic acid is critical for replication of bacteria - ONLY PATHWAY

Humans can get it through diet

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4
Q

What’s an issue with using sulphonamides clinically?

A

They can form toxic metabolites - resulting in allergic reactions and haematoxicity in some patients.

The hydroxylamine metabolites responsible bind to endogenous proteins - the protein is then attacked by immune system

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5
Q

What is the function of noradrenaline wrt asthma?

A

NA binds to the ß2 receptors and increases bronchodilation

However, NA is not selective, binding to ß1 adrenoreceptors - increasing heart rate.

NA also interacts with alpha receptors in blood vessels

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6
Q

What’s the difference in structure between noradrenaline and salbutamol?

A

Salbutamol has a t-But group stuck on the terminal amine

Also has extra carbon on upper OH group of catechol group

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7
Q

What does enteral and parenteral routes of administration describe?

A

Enteral = GI tract - sublingual, oral & rectal

Parenteral = non- GI tract - injections and inhalers

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8
Q

What factors must be considered when deciding the route of administration of drug?

A

Extent of transport across membranes - adsorption

Transit to site of action - distribution

Compliance - age, physical/mental ability

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9
Q

What is the definition of bioavailability?

A

The proportion of drug that passes into the systemic circulation following the first-pass metabolism

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10
Q

What is meant by first pass metabolism?

A

It is the metabolism of a drug after administration but before reaching the systemic circulation

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11
Q

What can be done if therapeutic failure is observed in a patient?

A

Increase dosage, increase doses per day, alter site of administration, change formulation

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12
Q

What factors affect the distribution of a drug?

A

Bulk flow in blood
Diffusion rate
Partitioning - into fat deposits
Binding to plasma proteins - no pharma effect, non-covalent forces

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13
Q

What’s the benefit of the small intestine with oral administration?

A

V. Large surface area ~ 200m^2

High blood flow ~ 1L/min
- maintains diffusion gradient

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14
Q

What does good absorption require a drug to be?

A

Drug must be water soluble
-so molecules in solution can be absorbed

And lipid soluble
-to pass through cell membranes

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15
Q

Rank the types of formulations in order of best—> worst

A

Solution
Emulsion
Suspension
Capsule
Tablet

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16
Q

What protein is bound to by acidic drugs?

17
Q

What protein is bound to by basic drugs?

A

Beta globin

Acid glycoprotein

18
Q

What’s the issue with drugs binding to plasma proteins or partitioning into fat?

A

These drugs have no pharmacological effect

Toxic build up could also occur in fat deposits - low blood supply so drugs become trapped

19
Q

Most drugs are weak acids and bases and so are often in ionised and unionised forms. Can ionised drugs cross cell membranes?

A

NO, only unionised molecules can cross cell membranes

The degree of ionisation - pH - determines the extent of transfer across cell membranes

20
Q

What is the Henderson-Hasselbach equation?

A

pH = pKa + log [A-]/[HA]

21
Q

What does a large [A-]/[HA] mean in the Henderson-Hasselbach equation?

A

A large value for [A-]/[HA] means that there are many ionised molecules for 1 unionised one.

A [A-]/[HA] of 0.01 means there are 100 unionised molecules for every ionised one

22
Q

What’s the point of metabolising drugs?

A

Since most drugs are lipophilic they cannot be excreted efficiently

Such drugs must be metabolised to more polar products to aid excretion

23
Q

Where is the main site of metabolism in the body? What’s the significance of pro-drugs?

A

In liver cells - usually abolishes a drugs pharmacological action

Pro-drugs are metabolised in the body to BECOME pharmacologically active.

24
Q

What does cytochrome p450 require?

25
Where does Phase 1 CYP450 metabolism occur?
On smooth endoplasmic reticulum of hepatocytes
26
What class of enzymes are responsible for Phase 2 metabolism?
Transferase enzymes - transferring a polar group from a conjugating agent to the Phase 1 metabolite Mainly occurs in the liver
27
What compounds are excreted through the kidney?
Polar compounds - particularly phase 2 conjugates
28
How does the liver excrete drug metabolites?
Process is called biliary excretion - active secretion of drug molecules or their metabolites from hepatocytes into the bile. Favours high MW polar compounds
29
What are the other routes of excretion other than the liver and kidneys?
Lungs - volatile compounds Saliva Sweat Breast milk - think morphine overdose in baby
30
If the drug does not reach its target, what happens?
Nothing, no pharmacological effect is exerted/observed