Lecture 6

Question 1

Drug administration routes

Answer 1

Enteral: via the digestive system (slow)

Parenteral: not via the digestive system (faster)

Question 2

Types of enteral methods

Answer 2

• Oral: through the mouth (most convenient)
• Rectal: through the rectum (weak bases)
• Gastric: through the stomach (weak acids)
• Buccal/sublabial: between the lip and gum
• Sublingual: under the tongue (hydrophilic)

Question 3

Types of parenteral methods

Answer 3

• Subcutaneous: under the skin
• Intramuscular: into the muscle
• Intravenous: into the artery (hydrophilic)
• Inhalation: into the lungs
• Transdermal: through the skin (patches)
• Spinal or intracranial: into the spinal cord or brain

Question 4

Drug dosage based on administration routes

Answer 4

With each obstacle eliminated en route to the brain, a drugs dosage can be reduced by a factor of ~10 to induce the same effect.
E.g., orally 1000 ug = inhaled 100 ug = intravenous 10 ug

Question 5

Blood-brain barrier

Answer 5

To be able to act in the brain, the drugs must be transferred from the blood stream to the extracellular fluid

• Only very small uncharged molecules can pass through the blood/brain barrier
• Active transport system for amino acids, glucose and fats.

Question 6

Areas without blood-brain barrier

Answer 6

1. Pineal gland: allows entry of chemicals that affect day-night cycles
2. Pituitary: allows entry to chemicals that influence pituitary hormones
3. Area postrema: allows entry of toxic substances that induce vomiting.

Question 7

How are drugs eliminated by the body?

Answer 7

• Catabolised (broken down)
• Excretion

Question 8

Catabolised drugs

Answer 8

Liver
Kidneys
Intestines

Question 9

Excreted drugs

Answer 9

Urine
Feces
Sweat
Breast milk
Exhaled air

• NB: Drugs that are not excreted can accumulate in the body and become toxic

Question 10

7 ways in which drugs influence the synapse

Answer 10

1. synthesis
2. storage
3. release
4. receptor interaction
5. inactivation
6. reuptake
7. degradation

Question 11

Agonist/antagonist - neurotransmitter

Answer 11

Agonist: substance that mimics or enhances the effects of a neurotransmitter

Antagonist: operates against the effects of the neurotransmitters

Question 12

Psychopharmacology

Answer 12

The study of how drugs effect cellular function in the nervous system of the brain and the neural mechanisms through which they influence behaviour

Question 13

Classifications of psychoactive drugs

Answer 13

1. Psycholeptics: substances that inhibit psychological functions
2. Psychoanaleptics: substances that stimulate psychological functions
3. Psychodyleptics: substances that disorganise psychological functions

Question 14

Types of psycholeptic drugs

Answer 14

• Sedatives and hypnotics (alcohol)
• Anxiolytics (benzodiazepines)
• Antipsychotics (chlorpromazine)
• Mood regulators (lithium)

Question 15

Types of psychanaleptic drugs

Answer 15

• Antidepressants (TCAs, SSRIs)
• Stimulants (cocaine, caffeine)

Question 16

Types of psychodyleptic drugs

Answer 16

• Narcotic analgesics (heroin)
• Hallucinogens (LSD)

Question 17

Sedative-hypnotics & anxiolytics (psycholeptics)

Answer 17

• Act as GABA agonists

Binding of sedative-hypnotic drugs acts like GABA causing increased chloride conductance.
Binding of anti-anxiety drugs enhances binding effects of GABA.
Because of their different actions, these drugs should never be taken together.

Question 18

Antipsychotics (psycholeptics)

Answer 18

• Act as dopamine antagonists.
• Block the dopamine receptor leading to decreased effect of dopamine

Question 19

Antidepressants (psychoanaleptics)

Answer 19

Monoamine oxidase inhibitors

• Inhibit degradation of serotonin (SE = activating)
• Tricyclic antidepressants (1st gen): inhibit reuptake of SE
• Selective serotonin reuptake inhibitors (2nd gen): SSRIs inhibit reuptake more selectively for SE.
• 1st gen typically have more side effects than 2nd gen.

Question 20

Stimulants (psychoanaleptics)

Answer 20

Cocaine

• dopamine agonist
• block reuptake of dopamine

Amphetamine

• norepinephrine + dopamine agonist
• promote release and block reuptake of NE and DA

Question 21

Narcotic analgesics (psychodysleptics)

Answer 21

Highly addictive, affect multiple neurotransmitters and receptors.

Question 22

Hallucinogens (psychodysleptics)

Answer 22

• Nonspecific amplifiers, influenced by intention
• Anandamide endocannabinoid and THC phytocannabinoid act as neuromodulators to inhibit release of glutamate and GABA

Question 23

Disinhibition theory - drug behaviour

Answer 23

Alcohol impairs judgement and (rational) decision making (frontal cortex) but spares (subcortical) instinctual behaviours (aggression, desire).

Question 24

Behavioural myopia (nearsightedness) - drug behaviour

Answer 24

Tendency to respond to a restricted set of immediate and prominent cues while ignoring more remote cues and possible consequences.

Question 25

Learning - drug behaviour

Answer 25

Drug induced behaviour is learned and context dependent, specific to culture, group and setting.

Question 26

Wanting-and-liking theory

Answer 26

With repeated drug use, wanting a drug and liking a drug progress in opposite directions. Wanting is associated with drug cues, e.g., room or social activity. Liking is likely mediated by a small localised set of nuclei controlled by opioid and endocannabinoid systems.

Question 27

Types of drug tolerance

Answer 27

- Metabolic tolerance - Cellular tolerance - Learned tolerance

Question 28

Drug sensitisation

Answer 28

- More likely to develop with intermittent exposure - Linked to conditioning of novel cues

Question 29

Hormones

Answer 29

- Neurotransmitters, chemical messengers. - Mostly produced by glands (endocrine system) - Released to the blood circulation

Question 30

Hormone release

Answer 30

- Regulated by neurohormones released in the brain (hypothalamus) - Gland is stimulated to produce releasing hormone (ACTH by pituitary gland) - Endocrine glands release their own hormones. - Hormone has its effect elsewhere in the body

Question 31

Chemical classes of hormones (2)

Answer 31

Steroid hormones Peptide hormones

Question 32

Steroid hormones

Answer 32

- Testosterone, cortisol - Synthesised from cholesterol in glands - Bind to steroid receptors on the cell membrane or in cell - Can directly influence gene transcription.

Question 33

Peptide hormones

Answer 33

- Insulin, endorphins - Synthesised by cellular DNA - Bind to metabotropic receptors - Indirectly influence cell physiology or gene transcription.

Question 34

Functional groups of hormones (3)

Answer 34

Homeostatic hormones (maintain balance) Gonadal hormones (sex hormones) Glucocorticoids (stress hormones)

Question 35

Homeostatic hormones

Answer 35

Maintain state of internal metabolic balance

Question 36

Gonadal hormones

Answer 36

Testosterone, estrogen. Control reproductive functions and induce gender effects on brain development

Question 37

Glucocorticoids

Answer 37

Cortisol, corticosterone. Secreted in times of stress Fast pathway (seconds) - Hypothalamus - Spinal cord - Adrenal medulla - Epinephrine Slow pathway (minutes-hours) - Hypothalamus (CRH) - Pituitary gland (ACTH) - Bloodstream - Adrenal cortex - Cortisol The bodies response to stress is the same whether the stressor is exciting, sad or frightening.