The basic principles of neuropharmacology 2

Question 1

Medicine

Answer 1

Practices and procedures used for the prevention, treatment or relief of symptoms of disease or abnormal conditions
Term may also refer to a legal drug used for the same purpose

Question 1

Drug

Answer 1

Any substance (other than food) that is used t prevent, diagnose, treat or relive symptoms of a disease or abnormal condition
- can also affect how the brain and he rest of the body work: e.g changes in mood, awareness, thoughts and feelings or behaviour

Question 2

Psychotropic agents

Answer 2

Drugs that influence behaviour

Question 3

Action of drugs on neural target

Answer 3

• the initial target of a drug determines the cells and circuits on which the drug acts and at the same time the potential efficiency and side effects
• the initial binding of a drug to its target is only the beginning of a signalling cascade that affects the behaviour of cells, neural circuits and animals

Question 4

Pharmacodynamics

Answer 4

• gkr, medicine and power
  Drug of action —> pharmacological effect —> response
• “what a drug does to the body”
• the ability of a drug to produce an effect on an organism is dependent on the underlying mechanisms of drug action
  Affinity, efficiency, concentration-response relationships, spare receptors and amplification

Question 5

Pharmokinetics

Answer 5

• gkr, medicine and movement
  Administration —> circulation —> (brain, kidney, liver) —> clearance
• “what the body does to a drug”
• the time course of a drug in the body

Question 6

Pharmokinetis and bioavailability

Answer 6

Ability of a drug to produce an effect on an organism is dependent on a many of it’s properties (& its mechanism of action) from its stability to its elimination —> its bioavailability

Question 7

Stages of pharmokinetis

Answer 7

1. Route of administration
2. Release/liberation
3. Absorbtion (dosing regiments)
4. Distribution (compartments)
5. Metabolism (metabolite kinetics, clearance)
6. Excretion (clearance)

Question 8

Enteral administration

Answer 8

through intestine
- oral administration —> relatively slow onset if action
- sublingual/buccal/rectal

Question 9

Parenteral administration

Answer 9

Other routes including
- intravenous
- intramuscular
- subcutaneous
- intraperitoneal (into peritoneal-abdominal cavity)
- intracerebroventricular
- intracerebral delivery (into brain parenchyma)

Question 10

Oral bioavailability - absorption

Answer 10

Most of the drug are absorbed within the duodenum/jejunum of the small intestine
- villi increase surface area
- highest concentration of villi on duodenum/jejunum
- lines with epithelial cells
- supportive network of capillaries draining the portal vein

Question 11

Drug absorption processes

Answer 11

• passive diffusion
• convective absorbtion
• active transport
• facilitated transport
• ion pair formation
• pinocytosis

Question 12

Is absorption the disappearance of drug from its site of administration or the appearance of drug in the general circulation?

Answer 12

absorption is the disappearance of drug from its site of administration

Question 13

Drug absorbtion depends on intestinal motility:

Answer 13

• food
• exercise
• disease
• drugs
• time of day

Question 14

Oral bioavailability - first pass metabolism

Answer 14

Most venous outflow from stomach, small & large intestine enters the portal vein en route to the liver
- goes into major body fluids e.g plasma
- metabolism: mainly liver (cytochrome P450 enzymes), prodrugs (in active until metabolised)
- excretion: renal and faecal elimination

Question 15

Bioavailability is affected by binding to plasma proteins:

Answer 15

• many drugs bound to circulating plasma proteins such as albumin
• only free drugs can act as receptor site
• highly protein bound drug: >95% bound

Question 16

> 95 % bound

Answer 16

• thyroxine
• warfarin
• diazepam
• frusemide
• heparin
• imipramine
• amitriptyline

Question 17

> 90% but <95% bound

Answer 17

• glibenclamide
• phenytoin
  -propranolol
• sodium valproate

Question 18

Bioavailability is affected by barriers:

Answer 18

• dependent on no. Of cascades/ no. Of events
• decided at every step wether it will reach the liver
• whether it will cross blood brain barrier
• important to determine doses, how much is actually going to the brain?

Question 19

Getting drug to the brain - bioavailability:

Answer 19

• bioavailability of a drug determines how much administered actually reaches the target
• influences by absorbtion of the drug
• affected by metabolism and secretion
• affected by binding of drug to plasma proteins -> makes the drug unavailable to bind to its target
• ability to penetrate BBB/cell membranes

Question 20

Dose

Answer 20

Amount of drug administered

Question 21

Dosing interval

Answer 21

Time between drug dose and administration

Question 22

Cmax

Answer 22

Peak plasma concentration of drug after administration

Question 23

Tmax

Answer 23

Time to reach Cmax

Question 24

Vol of distribution

Answer 24

Apparent volume in which drug is distributed (relates to drug concentration in plasma to drug amount in the body)

Question 25

Concentration

Answer 25

Amount of drug in a given volume of plasma

Question 26

Elimination half-life

Answer 26

The required concentration of drug to reach half its original value

Question 27

Area under the curve

Answer 27

Integral of the concentration-time curve (After a single dose or in steady state)

Question 28

Clearance

Answer 28

Volume of plasma cleared of the drug per unit of time

Question 29

Fundamentals of Pharmokinetics

Answer 29

Volume of distribution Clearance Elimination half-life