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Principles of Pharmacology and Therapeutics > Clinical Pharmacology > Flashcards

Clinical Pharmacology Flashcards

1
Q

What do we require of drug therapy in all patients where possible?

A

Effective treatment or prophylaxis
Safe
Easily administered by owner/veterinarian
Good value for money

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2
Q

What do we need to understand before medicating pets?

A

What disease/clinical sign we are treating
Which drug/drugs would be effective and why
What are the potential side effects
What patient conditions might affect drug dose
How is the drug administered to maximum effect

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3
Q

What does a drug need to do to be therapeutically effective?

A

Be absorbed into the blood stream (unless local tx)
Be transported to the site of the body where action is required
Have its action terminated once an effect has been achieved
Be eliminated from the body safely

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4
Q

What are pharmacokinetics?

A

What the body does to the drug

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5
Q

What are pharmacodynamics?

A

What the drug does to the body

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6
Q

What does pharmacokinetics encompass?

A

Absorption
Distribution
Metabolism
Elimination

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7
Q

When do drugs not need to be absorbed into the bloodstream?

A

Oral administration of drugs that act within the intestinal lumen
Drugs used topically for local effect on the skin or mucous membranes

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8
Q

What influences drug absorption into the bloodstream?

A

Ability to cross membranes
Route of administration
Chemical formulation of the drug (particle size/rate of dissolution of a tablet)
Volume of injection

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9
Q

What are the advantages and disadvantages of oral drug administration?

A

Convenient
Many drugs are absorbed effectively
Some drugs are destroyed or altered by gastric acid/intestinal flora but can use coated drugs

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10
Q

Where are oral drugs absorbed?

A

Mainly from the small intestine as there is a large surface area (rate of gastric emptying important)

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11
Q

Why is the oral bio availability of a drug <1?

A

Incomplete absorption
Metabolism in gut/gut wall
First pass metabolism in the liver
Enterohepatic recycling and incomplete resorption after excretion into bile

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12
Q

What is the first pass effect?

A

Drugs given orally must pass through the liver before reaching the systemic circulation
They may be metabolised by the liver which will affect how much drug reaches the circulation

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13
Q

How do you tell how large the first pass metabolism of a drug is?

A

If there is a big difference between the dose given IV and the dose given orally = significant first pass metabolism

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14
Q

What effect does pathology have on first pass metabolism?

A

If there is significant hepatic dysfunction then first pass metabolism will be reduced increasing bio availability
Increased risk of toxicity for drugs with narrow therapeutic index and prolonged duration of effect of drug

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15
Q

How is the volume of distribution of a drug calculated?

A

Total amount of drug/plasma concentration

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16
Q

What are the different body compartments?

A

Total body water (plasma, intracellular, extracellular)
Fat
Bone

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17
Q

How is volume of distribution interpreted?

A

Very low (0.05-01 L/kg) confined to plasma
Low (0.2 L/kg) confined to plasma and interstitial space
Intermediate (0.6 L/kg) enters total body water
High (>1 L/kg) sequestered in tissue

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18
Q

What are some important factors affecting distribution?

A

Blood flow
Protein binding
Membrane permeation
Tissue solubility (water, bone, fat)

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19
Q

What factors can alter blood flow?

A 
Shock
Dehydration
Cardiac failure
Age
Drugs (propanolol)
20
Q

What proteins can drugs bind to?

A

Albumin

Several other serum proteins

21
Q

Where do drugs bind to on the proteins?

A

Inert or non-receptor binding sites

22
Q

What factors can influence drug binding?

A

Decreased serum protein levels may result in increased free drug concentration
Very young and geriatric patients have lower plasma protien

23
Q

How does protein binding affect distribution and elimination?

A

Limits passage from blood into interstitial fluid, milk, placenta and glomerular ultrafiltrate

24
Q

Why does protein binding matter?

A

Toxicity associated with displacement is unusual
Displaced drug is instantly available for distribution, metabolism and excretion
New equilibrium is rapidly attained

25
Q

What are the methods that drugs can use to cross membranes?

A

Aqueous diffusion
Lipid diffusion
Facilitated diffusion
Pinocytosis

26
Q

What does aqueous diffusion depend on?

A

Number and size of pores available

27
Q

Where are there lots of aqueous diffusion pores?

A

Gut, cornea, bladder, most capillary beds

28
Q

Where are there few/no aqueous diffusion pores?

A

Blood-brain, blood-eye, blood-milk, blood-prostate, blood-bronchus

29
Q

What is the process of lipid diffusion?

A

Movement of molecules across cell membranes by solution in the lipids of the membrane
Must be lipid soluble

30
Q

What can metabolism of a drug do?

A

Make drugs more water soluble
Terminate drug action
Activate some drugs
May create toxic metabolites

31
Q

What are the sites of drug metabolism?

A

LIVER

Gut, skin, kidney, lungs

32
Q

What is phase I metabolism?

A

Occurs in endoplasmic reticulum and involves oxidation, hydrolysis and reduction

33
Q

What is phase II metabolism?

A

Occurs in microsomes/cytosol
Involves conjugation of the production of phase I reactions with natural substrates
Involves specific transfer enzymes usually causes detoxification (occasionally hepatotoxicity)
Species may differ markedly

34
Q

What natural substrates are used in phase II metabolism?

A 
Glucuronic acid
Glutathione
Glycine
Sulphate
Acetyl CoA
35
Q

What is phase III metabolism?

A

Active drug transport across cellular membranes rather than enzyme catalysed
Efflux reactions
Influx transporters

36
Q

What factors affect metabolising enzymes?

A

Species, genetics, age, diseases, hormonal status, environmental factors, drug-drug interactions, endogenous compounds, nutritional status

37
Q

How do herbivores differ in drug metabolism?

A

Very efficient metabolic capacity so duration of action may be short
Goats metabolise drugs faster than sheep

38
Q

What are the species difference in cats with NSAIDs?

A

Aspirin has prolonged half life
Carprofen is licensed for once only use
Meloxicam 21 hrs vs 24 hrs

39
Q

Why is paracetamol more toxic to cats?

A 
Limited glucuronidation (major in most species)
Capacity limited sulphation 
Results in oxidation yielding high levels of toxic metabolite
40
Q

How does age affect drug distribution?

A

Greater volume of distribution in paediatric animals
Reduced lean body mass and total body water in geriatric animals
Lower plasma protein in young and old animals

41
Q

How does age affect drug metabolism?

A

Reduced hepatic metabolism in neonates

Reduced hepatic blood flow and reduced hepatocyte mass and function in geriatric animals

42
Q

How does age affect drug elimination?

A

Reduced glomerular and tubular function in neonated and old animals

43
Q

What effects can drugs have on hepatic enzymes?

A

Enzyme induction - increases metabolism potentially reducing drug effect or increase toxicity of metabolite
Enzyme inhibition - increases drug activity and risk of toxicity

44
Q

What drugs can cause enzyme induction?

A 
Phenobarbitone
Carbamazine
Charcoal grilled meat
Cigarette smoke
Dexamthasone
Phenytoin
Primidone
Rifampin
45
Q

What drugs can cause enzyme inhibition?

A 
Cimetidine
Ethanol
Ciprofloxacin
Marbofloxacin
Diltiazem
Chloramphenicol
Imidazoles
46
Q

Does enzyme inhibition really matter?

A

First order - unlikely to saturate pathway

Zero order kinetics - will have a serious effect

47
Q

What are the elimination sites of drugs?

A

KIDNEYS

Bile, skin, GI tract, lungs, saliva, milk

Principles of Pharmacology and Therapeutics (8 decks)

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