Lecture 6 Flashcards
Drug administration routes
Enteral: via the digestive system (slow)
Parenteral: not via the digestive system (faster)
Types of enteral methods
- 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)
Types of parenteral methods
- 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
Drug dosage based on administration routes
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
Blood-brain barrier
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.
Areas without blood-brain barrier
- Pineal gland: allows entry of chemicals that affect day-night cycles
- Pituitary: allows entry to chemicals that influence pituitary hormones
- Area postrema: allows entry of toxic substances that induce vomiting.
How are drugs eliminated by the body?
- Catabolised (broken down)
- Excretion
Catabolised drugs
Liver
Kidneys
Intestines
Excreted drugs
Urine
Feces
Sweat
Breast milk
Exhaled air
- NB: Drugs that are not excreted can accumulate in the body and become toxic
7 ways in which drugs influence the synapse
- synthesis
- storage
- release
- receptor interaction
- inactivation
- reuptake
- degradation
Agonist/antagonist - neurotransmitter
Agonist: substance that mimics or enhances the effects of a neurotransmitter
Antagonist: operates against the effects of the neurotransmitters
Psychopharmacology
The study of how drugs effect cellular function in the nervous system of the brain and the neural mechanisms through which they influence behaviour
Classifications of psychoactive drugs
- Psycholeptics: substances that inhibit psychological functions
- Psychoanaleptics: substances that stimulate psychological functions
- Psychodyleptics: substances that disorganise psychological functions
Types of psycholeptic drugs
- Sedatives and hypnotics (alcohol)
- Anxiolytics (benzodiazepines)
- Antipsychotics (chlorpromazine)
- Mood regulators (lithium)
Types of psychanaleptic drugs
- Antidepressants (TCAs, SSRIs)
- Stimulants (cocaine, caffeine)
Types of psychodyleptic drugs
- Narcotic analgesics (heroin)
- Hallucinogens (LSD)
Sedative-hypnotics & anxiolytics (psycholeptics)
- 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.
Antipsychotics (psycholeptics)
- Act as dopamine antagonists.
- Block the dopamine receptor leading to decreased effect of dopamine
Antidepressants (psychoanaleptics)
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.
Stimulants (psychoanaleptics)
Cocaine
- dopamine agonist
- block reuptake of dopamine
Amphetamine
- norepinephrine + dopamine agonist
- promote release and block reuptake of NE and DA
Narcotic analgesics (psychodysleptics)
Highly addictive, affect multiple neurotransmitters and receptors.
Hallucinogens (psychodysleptics)
- Nonspecific amplifiers, influenced by intention
- Anandamide endocannabinoid and THC phytocannabinoid act as neuromodulators to inhibit release of glutamate and GABA
Disinhibition theory - drug behaviour
Alcohol impairs judgement and (rational) decision making (frontal cortex) but spares (subcortical) instinctual behaviours (aggression, desire).
Behavioural myopia (nearsightedness) - drug behaviour
Tendency to respond to a restricted set of immediate and prominent cues while ignoring more remote cues and possible consequences.
Learning - drug behaviour
Drug induced behaviour is learned and context dependent, specific to culture, group and setting.
Wanting-and-liking theory
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.
Types of drug tolerance
- Metabolic tolerance
- Cellular tolerance
- Learned tolerance
Drug sensitisation
- More likely to develop with intermittent exposure
- Linked to conditioning of novel cues
Hormones
- Neurotransmitters, chemical messengers.
- Mostly produced by glands (endocrine system)
- Released to the blood circulation
Hormone release
- 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
Chemical classes of hormones (2)
Steroid hormones
Peptide hormones
Steroid hormones
- Testosterone, cortisol
- Synthesised from cholesterol in glands
- Bind to steroid receptors on the cell membrane or in cell
- Can directly influence gene transcription.
Peptide hormones
- Insulin, endorphins
- Synthesised by cellular DNA
- Bind to metabotropic receptors
- Indirectly influence cell physiology or gene transcription.
Functional groups of hormones (3)
Homeostatic hormones (maintain balance)
Gonadal hormones (sex hormones)
Glucocorticoids (stress hormones)
Homeostatic hormones
Maintain state of internal metabolic balance
Gonadal hormones
Testosterone, estrogen.
Control reproductive functions and induce gender effects on brain development
Glucocorticoids
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.
