U2.1 Receptor-Based Pharmacology Flashcards
CNS
Central Nervous System: brain & spinal cord
PNS
Peripheral Nervous System: - Nerves that carry messages to and from the CNS.
Two divisions: Somatic & Autonomic
Somatic Nervous System
Voluntary control over skeletal muscles. (component of PNS)
Autonomic Nervous System
Involuntary control over vital functions of the cardiovascular, digestive, respiratory, & genitourinary systems.
Two division: Sympathetic & Parasympathetic
Main activities of Autonomic Nervous System
- Contraction of smooth muscle of the bronchi, blood vessels, GI tract, eye, and GU tract.
- Contraction of cardiac muscle
- Secretions of salivary, sweat, & gastric glands.
Sympathetic Nervous System
“Fight or Flight” Response
• Brain → Increased alertness & readiness
• Cardiovascular → Increased heart rate & blood pressure
• Musculoskeletal → Ready for sudden, intense physical activity
• GI → Liver produces more glucose for energy. Decreases peristalsis.
• Respiratory → Dilation of bronchi, increased respirations.
• Pupils → Dilation, increased vision.
• Integumentary → Warm, increased perspiration.
• GU → Decreased urine formation.
Parasympathetic Nervous System
“Rest & Digest” Response
• GI → Increased secretions, peristalsis.
• Cardiovascular → Decreased HR and BP.
• Respiratory → Constriction of bronchi, decrease in respirations
Acetylcholine (ACh)
Widely distributed in CNS; a major transmitter in ANS
CNS: May be excitatory or inhibitory; controls voluntary skeletal muscle movement
ANS: Activates the parasympathetic nervous system
Clinical significance: Myasthenia gravis, Alzheimer’s disease
Norepinephrine (NE)
Widely distributed in CNS; a major transmitter in ANS
CNS: May be excitatory or inhibitory
ANS: Activates the parasympathetic nervous system
Clinical significance: Depression, memory, panic attacks
Glutamate
CNS - Most common excitatory CNS neurotransmitter
Clinical significance: Memory
Gamma amiobutyric acid (GABA)
CNS - Most common inhibitory CNS neurotransmitter
Clinical significance: Seizure & anxiety disorders
Dopamine
basal ganglia & limbic system - Usually excitatory; locomotion, attention, learning, & reinforcing effects of abused drugs
Clinical significance: Parkinson’s disease; psychoses; motivation, pleasure
Endorphins & Enkephalins
Widely distributed in CNS and PNS - Usually inhibitory, reduction of pain.
Clinical significance: Opiods bind to endorphin receptors.
Serotonin
Common in brainstem, but also found in limbic system - Usually inhibitory.
Clinical significance: Anxiety, bipolar disorders, depression
Why is synaptic conduction highly selective?
- Synapses at different sites employ different transmitters.
- Many transmitters have more than one receptor.
Do most neuropharmacologic agents act by altering axonal transmission or synaptic transmission?
synaptic transmission
synaptic transmission
Synapses occur due to an electrical impulse. There is a release of neurotransmitters (chemical messengers) these cross the synapse to activate receptors.
- Transmitter synthesis
- Transmitter storage:
- Transmitter release
- Receptor binding
- Termination of transmission
General mechanisms of ANS drugs
- Synthesis of the neurotransmitter in the preganglionic neuron
- Prevention of storage of the neurotransmitter in vesicles within the preganglionic nerve.
- Influencing the release of the neurotransmitter from the preganglionic nerve.
- Bind to the neurotransmitter receptor site on the postganglionic nerve.
- Alters termination of transmission by preventing the normal destruction or reuptake of the neurotransmitter.
General mechanisms of CNS drugs
- Activation - stimulates firing of neurons
- Inhibition – suppresses firing of neurons
- Some have both actions
muscarinic receptors
Ach
Parasympathetic targets: organs other than heart
Stimulatory –> smooth muscle and exocrine gland secretion
Inhibitory –> heart rate and force of contraction
nicotinic receptors
Ach
Sympathetic & Parasympathetic
Postganglionic neurons & neuromuscular junctions of skeletal muscle
Stimulatory –> Smooth muscle & gland secretions
Nicotinic M –> Stimulates contraction of skeletal muscle
How is Ach removed from the synaptic cleft?
- Acetylcholinesterase (AchE)
2. Pseudocholinesterase
acetylcholinesterase
Enzyme in synaptic cleft, breaks down Ach - some drugs alter levels of AchE
pseudocholinesterase
Found in liver. AKA plasma cholinesterase. Breaks down Ach. Some people have genetically altered levels making them unable to break down certain drugs in the plasma.
Alpha1 receptors
Neurotransmitters: Epi, NE, Dopamine ALL sympathetic target organs EXCEPT heart. - Vasoconstriction - Ejaculation - Contraction of bladder neck & prostate - Constriction of skin, mucous membranes - Pupil dilation
Alpha2 receptors
Neurotransmitters: Epi, NE, Dopamine
Presynaptic adrenergic nerve terminals, NOT in organs.
- Regulates NE release
- Can help reduce transmitter release when too much has accumulated in the synaptic cleft
Beta1 receptors
Neurotransmitters: Epi, NE, Dopamine
Heart
- Increases HR
- Increases force of contraction
- Increases velocity of conduction in AV node
Kidneys
- Renin release (renin promotes synthesis of angiotensin which is a vasoconstrictor)
Beta2 receptors
Neurotransmitter: Epi
ALL sympathetic target organs EXCEPT heart
- Bronchial dilation
- Decreased peristalsis
- Decreased urine production
- Glycogenolysis (increases glucose)
- Enhanced contraction of skeletal muscle
- Vasodilation in heart, lung, skeletal muscle
Dopamine receptors
Neurotransmitter: Dopamine
- Has much more effect in CNS
- Dilates renal blood vessels
- Increased force of cardiac contraction
How is action of NE terminated?
- 50 - 80% taken back into pregang nerve –> repackaged in vesicles for future use
- remainder - destroyed by enzymes: MAO & COMT (in kidneys & liver)
Classification of a drug that stimulates the sympathetic nervous system?
sympathomimetics, adrenergic-agonists
Classification of a drug that stimulates the parasympathetic nervous system?
parasympathomimetics, muscarinic agonists
Classification of a drug that inhibits the sympathetic nervous system?
adrenergic antagonists or blockers
Classification of drugs that inhibit the parasympathetic nervous system?
anticholinergics, parasympatholytics, muscarinic blockers
cholinergic synapses
- Ach
- stimulatory
- distributed in CNS
- motor cortex, basal ganglia
- Parkinson’s, Alzheimer’s, Myasthenia gravis
adrenergic synapses
- NE
- excitatory or inhibitory
- heightens alertness, prominent while awake
- depression, anxiety, panic, memory
dopaminergic synapses
- dopamine
- generally excitatory
- arousal & wakefulness
- basal ganglia, limbic system
- mechanism of cocaine, amphetamines, possibly marijuana
endorphins & enkephalins
- CNS & peripheral nervous system
- hypothalamus, pituitary, limbic, spinal cord
- opioid receptor –> affects pain transmission
gamma aminobutyric acid (GABA) synapses
- distributed in CNS
- most commonly inhibitory
- found t/o brain - basal ganglia, hypothalamus
- seizure, anxiety
glutamate synapses
glutamate receptor subtypes: N-methyl, D-aspartate
- distributed in all areas of brain
- ALWAYS excitatory
- death of neurons in high amounts (can be a cause of toxicity)
- memory
serotonergic synapses
- brainstem & limbic system
- 98% of these are found outside CNS in platelets, mast cells GI tract
- Low levels assoc. with anxiety, impulsivity, suicidal ideation.
- synthesizes melatonin
role of blood brain barrier
- allows for continuous flow of glucose and oxygen
- protects from pathogens or toxins
- capillaries not as porous as in other parts of the body
- form a tight barrier to many substances
