How The Body Handles Drugs

Question 1

Oral administration

Answer 1

Absorption from the small intestine
Absorption can be variable:
- lipid solubility of drug = straight into blood
- stomach contents eg. tetracycline, milk
- rate of gastric emptying 
- bioavailability 
Absorption:
>tablets>granules>fine particles>solution>absorption in stomach and small intestine
Movement across cell membrane:
-passage through water channels
-endocytosis
-passive diffusion
-facilitated diffusion/active transport

Question 2

Topical administration

Answer 2

Poorly absorbed but minimises risk of overdose

Has a negative effect on the skin eg. skin thinning

Question 3

Transdermal administration

Answer 3

Long acting
Useful when you want to have low levels of drug in system for a long period of time
Adverse skin effects and variable absorption
Drug must be lipid soluble/very potent

Question 4

Rectal administration

Answer 4

Local/systemic effects
Useful for patients who are vomiting/can’t swallow
eg. Diazepam

Question 5

Inhalation

Answer 5

Causes rapid changes in plasma concentration of blood
Local/systemic effects - difficult ensuring drug reaches target or action
eg. Salbutamol

Question 6

Parental routes

Answer 6

Intravenous eg. Heparin
Intramuscular eg. Pre-meds
Intradermal eg. Local anaesthetics
Subcutaneous eg. Insulin
Intrathecal eg. Chemotherapy drugs
Epidural eg. Nerve blockers in labour
-rapid action
- bypasses stomach and liver

Question 7

How are drugs distributed in the body?

Answer 7

If lipid soluble = blood then tissues
Depends on blood flow to the area
Only free/unbound drugs can diffuse across the membrane and have effects

Question 8

How are drugs metabolised (and excreted)?

Answer 8

Most drugs are lipophilic and are re-circulated
Metabolised mainly in the liver by the smooth ER
>liver disease = plasma half life would increase (also happens in kidney, brain, GI tract, plasma, lungs)
Drug is excreted by the body:
lipid soluble drug –> water soluble drug (by enzymes) = can be excreted

Question 9

What are the 2 phases of metabolism

Answer 9

Phase 1:
- modify the chemical structure of the drug
- makes drug slightly more water soluble
- prepares drug for phase 2
- products can be more chemically reactive that parent drug “pharmacological activation” eg. pro-drugs
> prednisone –> prednisolone
>codeine –> morphine
Phase 2:
- ‘conjugate’ drug to large molecules eg. amino acides
- products generally more water soluble, have an increased molecular weight and inactive “pharmacological inactivation”
- enhance excretion

Question 10

Drug interaction

Answer 10

Drug metabolising enzymes can be:
INDUCED eg. by alcohol - induces liver enzymes (increases drug duration)
INHIBITED eg. by fluoxetine, grapefruit juice (decreases drug duration)

Question 11

How are drugs excreted?

Answer 11

Via urine>bile>faeces>lungs>skin
To increase excretion of drug:
- increase blood flow to the kidneys
_ decrease plasma protein binding

Question 12

Therapeutic responses

Answer 12

Time between taking one drug and taking another and avoiding any drug interactions
Large therapeutic window = good
Loading dose: plasma drug concentration increases rapidly to therapeutic window
Too high of a dose = toxic drug levels = side effects
Not enough of a dose = don’t reach therapeutic window
Narrow therapeutic window - constant monitoring