Pharmacodynamics Flashcards
What are the four main locations that drugs act on?
- Receptors
- On DNA
- Enzymes
- Membranes
What drugs stimulate receptors?
Agonists
What drugs prevent receptor stimulation?
Antagonists
What do receptors do?
They initiate cellular responses
What are receptors?
Proteins in or on cells?
What are the four main types of proteins that receptors are linked to?
- G-protein coupled receptors
- Ion channels
- Gene transcription
- Enzymes
Name a Beta2 adrenoceptor agonist
Salbutamol
Name a Beta2 receptor antagonist
Propanol
Name a H1+2 receptor agonist
Histamine
Name an opiate Mu receptor agonist
Morphine
Name an opiate Mu receptor antagonist
Naloxone
Name a M2 muscarinic agonist
Acetylcholine
Name a M2 muscarinic antagonist
Atropine
How do G protein coupled receptors interact with ion channels?
They cause confirmation changes which allow ion exchange
How to G protein coupled receptors affect enzymes?
They activate or inhibit enzymes which will result in second messengers being produced or inhibited
What are the two types of opioid analgesics?
1 - Morphine based
2 - Synthetic
What are the three main opioid receptors?
Delta, Kappa and Mu
What type of receptors do opioids act on?
G-Protein Coupled Receptors
What occurs after receptor binding of opioids?
- Inhibition of adenylate cyclise -> decreased intracellular cAMP
- Couple to K:Ca ion channels -> inhibition of transmitter release and postsynapse excitability
75% of presynapse receptors for opioids are….?
Mu receptors
By what 3 means do opioid analgesics work?
- Inhibits pain transmission in dorsal horn
- Activates descending pathways in grey matter inhibiting pain transmission (reduced GABA)
- Inhibits nociceptive afferents in tissues
How is pain transmission inhibited at the dorsal horn?
By inhibiting presynaptic afferent impulses
How are the descending pathways activated?
By inhibiting GABA release in periaqueductual grey matter (PAG)
Why does activating the descending pathways inhibit pain?
It inhibits the discharge of the Dorsal Horn
What does the dorsal horn project into?
The Thalamus
What does the thalamus project in to?
The Cortex
Why does respiratory depression occur when morphine is administered?
The activation of Mu receptors reduce the respiratory centres sensitivity to CO2
Why can nausea and vomiting occur when morphines administered?
Activation of the chemoreceptors trigger zone
Why can pupillary constriction occur when morphine is administered?
Activation of the kappa receptors leads to the stimulation of the oculomotor nucleus (parasympathetic NS)
Why is it important to be cautious when administering morphine to someone with asthma?
It can cause histamine release leading to bronchospasm and hypotension
What does tissue damage lead to the production of? Causing activation of nociceptive fibres?
Bradykinins
ATP
H ions
Prostaglandins
What non analgesic effects to kappa opiod receptors have on the body? (3)
Decreased RR
Pupil miosis
Sedation
What non analgesic effects to mu opiod receptors have on the body? (2)
Resp depression (resp centre - medulla oblongata) Euphoria
What is histamine?
An inflammatory mediator
What does IgE production in an allergic reaction lead to?
Mast cell degranulation and histamine release
What are the main effects of H1 receptors? (3)
Vasodilation
Increased cap permeability
Bronchospasm
What are the main effects of H2 receptors? (4)
CNS effects
Gastric acid production
Smooth muscle relaxation
T cell and Cytokine proliferation
What actions does chloraphenamine have? (4)
Anti-allergic
Sedative
Anti-muscarinic
Anti-emetic
What is chloraphenamine?
A potent H1 antihistamine
What are the main two things chloraphenamine reduces?
Urticaria and Bronchoconstriction
What are receptors that regulate gene transcription called?
Nuclear receptors
Where are nuclear receptors located?
The cytosol
Name some glucocorticoids (4)
Oestrogen
Progesterone
Steroid hormones
Thyroid hormones
How are inflammatory mediators produced by glucocorticoids
Glucocorticoid > nuclear receptor > conformation change > binds to DNA > gene expression (transcription, translation and mRNA synthesis > production and release of inflammatory mediators
What are enzymes?
Proteins that catalyse chemical reactions in the body
True or False enzymes have specific binding sites for substrates?
True
What is aspirin?
An enzyme inhibitor
How does aspirin work?
Irreversibly inactivates COX
What does inactivation of COX by aspirin lead to?
Reduction in prostaglandin and thromboxane production
Do most other NSAIDs and COXIBs bind irreversibly or reversibly?
Reversibly
Low doses of aspirin irreversibly block TXA2 formation in platelets… what effect does this have?
It has an antithrombotic effect and helps reduce heart attack risk
What drugs act on non mammalian cell targets? (4)
Anti-virals
Anti-biotics
Anti-parasitics
Anti-fungals
What class of antibiotic is penicillin?
A beta-lactam antibiotic (bacteriocidal)
What do bacteriocidal antibiotics do?
Lead to cell lysis and death
What does penicillin bind to?
Penicillin binding protein (DD-transpeptidase)
What does pencillin binding to a bacterium result in?
Inability to cross link peptidoglycan in cell wall which leads to cell wall degredation, cell lysis and death
Why does penicillin usually have minimal side effects?
As it acts on bacterial proteins (little effect on host) - selective toxicity
What does the ABCDE of adverse drug reactions (ADR) stand for?
Augmented Bizzare Chronic Delayed End of Use
Name an augmented ADR
Decreased RR with morphin (predictable, common, dose dependent)
Name a bizzare ADR
Anaphylaxis (unpredictable, uncommon, cure=stop use)
Name a chronic ADR
Growth retardation with corticosteroid therapy
Name a delayed ADR
Teratogenic drugs (thalidomide)
Name an end of use ADR
Withdrawal from benzodiazipines
How does paracetamol act?
Selectively inhbits COX and weakly inhibits prostaglandins
What are the parasympathetic spinal cord outputs?
Craniosacral
What are the sympathetic spinal cord outputs?
Thoracolumbar
What the two main alpha receptor agonists?
Adrenaline and Noradrenaline
What 3 main effects does beta1 receptor stimulation have on the heart?
changes…
Rate
Force
Contractility
What effect does beta2 receptor stimulation have on the lungs?
Smooth muscle dilation
How does ipatropium bromide function?
It ‘deactivates’ parasympathetic influence stopping bronchial smooth muscle contraction
What kind of antagonist is ipatropium bromide?
A cholinergic antagonist
What do pumps and carriers on cell membranes allow?
A cell to regulate it’s internal environment
List some drugs that act on pumps and carriers
- Diuretics
- Digoxin
- Anaesthetics
What are voltage-operated channels?
Channels in a cell membrane that are activated by electrical membrance changes
How does tetracaine work?
It blocks sodium channels
True or False sodium must ionise and enter the intracellular axon to function?
True
What are chelating agents?
Chemical compounds that react with metal ions to form a stable water soluble complex
