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89 Cards in this Set
- Front
- Back
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What is a drug? |
A substance that modifies activity of living tissue & interferes with normal & abnormal physiology |
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What is physiology? |
Science of how living tissues function |
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What is therapeutics? |
Study of use of pharmacological agents in disease states |
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What is pathology |
Study of how body goes wrong in disease states |
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What is an agonist |
Drugs or naturally occurring substances which can directly cause a measurable response |
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What are the 2 types of an agonist’s measurable response & what do they depend on? |
Excitatory & inhibitory. Responses depend on receptor being activated. |
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What is an agonist’s affinity? |
Binding of agonist (drug) to its receptor |
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What is an agonist’s efficacy? |
Ability of agonist to activate its receptor (i.e elicit a response) Antagonists = no efficacy |
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What does an agonist’s response curve allow to be made? |
Comparisons of EC50 values (the lower the value, the more potent the drug) |
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What is pharmacological antagonism? |
When drugs counteract each other by acting on the same receptor |
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What is an antagonist’s affinity? |
Binding of antagonist (drug) to its receptor |
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What is chemical antagonism? |
When one drug antagonises the action of another by chemically combining with it |
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What is physiological antagonism? |
When 2 drugs counteract each other by producing opposing effects on different receptors |
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Define latrogenicity |
Capacity to produce disease from side effects or inappropriate prescribing of drugs (e.g. anti malarial drug mefloquine (Lariam) associated with neuropsychiatric side effects) |
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What happens during competitive antagonism? |
Control curve parallel shifted to right by increasing concentrations of antagonist (increasing agonist concentration restores the response) |
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What happens during irreversible competitive antagonism? |
Bond between antagonist and receptor is so strong due to covalent bonding (increasing antagonist conc. cant displace agonist |
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What are non competitive antagonists? |
Act at sites other than agonist binding site |
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What is botulism caused by? |
Eating contaminated food, canned or bottled foodstuffs that have been incompletely sterilised |
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3 main symptoms of botulism |
Muscle paralysis Respiratory failure Death |
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What is clostridium botulinum? |
Gram positive Rod shaped Anaerobic Spore forming |
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What is botulinum toxin? |
Temporarily removal of facial wrinkles Severe underarm sweating Cervical dystonia (neck & shoulder pains) Blepharospasm (uncontrollable blinking) Strasismus (misaligned eyes) |
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What is tetrogenicity |
Capacity to produce abnormalities of unborn foetus (e.g Thalidomide, late 1950s) |
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2 types of thalidomide |
(R) Thalidomide (Sedative) (S) Thalidomide (Teratogenic) |
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What should an ideal drug have? |
High potency and high specificity |
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3 ways in which drugs are studied |
In vivo In vitro High throughput screening |
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Function of a-subunit |
Bonds guanine nucleotide GTPase |
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Function of B-subunit |
Stable complex associated with membrane |
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What does aBy mix determine? |
Specificity |
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4 Heterotrimeric G protein families |
Gq (aq) G12 (a12) Gs (as) Gi (ai) |
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2 types of ion channels as drug targets |
Open or closed channel (Verapomil: cardiac Ca+ channel blocker) |
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What are enzymes as drug targets? |
Inhibitors (Ibuprofen: cyclo - oxygenase inhibitor) |
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What is Salbutanol used for? |
(Agonists) Asthma Antagonists - Cimetidine for peptic ulcer |
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6 steps of chemical signalling |
(1) & (2) : Agonist synthesis & release (3) : Transport (4) : Detection by target cell (5) : Physiological response (6) : Signal inactivation & end of response |
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G Protein- coupled receptor (GPCR) |
Affects cell physiology within seconds with long lasting effects Promotes GTP/GDP exchange |
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3 different sub units of Heterotrimeric G proteins |
Stoichiometry : a : b : y (determines specificity) |
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What do G Proteins act as? |
Molecular switches (GDP = OFF) (GTP = ON) |
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Function of By-subunit |
Stable complex associated with membrane |
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Function of Gq |
Activates phospholipase C (an effector) Indirectly increases intracellular Ca2+ Activates protein kinases |
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Function of G12 |
Na+/H+ exchange Indirectly inhibit Ca2+ currents |
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Function of Gs |
Stimulates adenylyl cyclase (an effector) Indirectly activates Ca2+ channels |
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Function of Gi |
Inhibits adenylyl cyclase |
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What does unoccupied GPCR NOT interact with |
It’s G protein |
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What does GPCR activation induce? |
Dissociation of a & By G protein subunits |
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What does activation of G protein NOT involve? |
Phosphorylation of GDP to GTP |
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What are effectors? |
Enzymes that produce intracellular signal molecules (2nd messengers) |
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What does effector Adenylyl cyclase do? |
Catalyses the reaction in which ATP is converted into cAMP (requires cleavage of PPi) |
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What does effector Phospholipase C produce? |
IP3 & DAG |
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What are the 3’ & 5’ cyclic phosphate rings? |
High energy bonds |
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When is there an increase in cyclic nucleotide’s tissues? |
Upon stimulation of adenylyl cyclase or guanylyl cyclase |
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Enzymes that destroy cAMP |
Phosphodiesterases |
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What is increased adenylyl cyclase activity accompanied by? |
Increase phosphodiesterase activity |
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What does activated PKA phosphorylate? |
CREB, a transcription factor |
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Define CRE |
cAMP response element [TGACGTCA] Enhancer found in genes regulated by cAMP |
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Define CREB |
Protein recruited to initiate transcription |
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Function of Phospholipase C. |
Cleaves specific membrane phospholipids Produces Phospholipids |
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Target for IP3. |
IP3 Receptor |
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What does IP3 Receptor activation release? |
Intracellular stores of Ca2+ |
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Target for cAMP |
Protein Kinase A |
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Target for DAG. |
Protein Kinase C |
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Target of phosphorylate. |
Proteins on specific serine & threonine residues thus changing their activity and/or localisation |
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What can act as a binary switch? |
Dephosphorylation |
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GPCR Signalling cycle |
1) Unstimulated state 2) Receptor activation by agonist 3) Receptor activation of G Protein (a subunit exchanges GTP for GDP) 4) G protein effector. Interaction & production of second messengers 5) GTPase (a subunit) |
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3 factors which regulate activity & specificity in GPCR Signalling |
Receptor specificity Second messenger pathways Cellular localisation |
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Signal Termination |
GTPase activity of G protein Removal (or degradation) of second messenger Inactivation of receptor for extracellular signal Desensitisation of enzymes involved in producing second messengers Protein kinases & phosphate activities |
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How do second messengers regulate cellular processes? |
Uptake & utilisation of glucose Storage & mobilisation of fat Gene activity Membrane ion channel activity Secretion of cellular products |
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Long term effects: control of cellular fate |
Cell proliferation Differentiation Survival of cells |
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Neuronal function |
Information input Depolarisation Action potential generation & direction of propagation Neurotransmitter release |
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Where do neurotransmitters release signals to? |
Neurons Glands Muscle |
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Neurotransmitters |
CNS-glutamate, GABA, serotonin, dopamine, norandrenaline PNS- norandrenaline & acetylcholine |
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The membrane is more permeable to... |
K+ than Na+ |
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What is the Nernst Equation used to calculate? |
The equilibrium potential (Ex) for an ion knowing the concentrations of the ion (at 37degrees) |
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What is the membrane impermeable to? |
Pr- the Nernst equation does not apply to these ions |
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Leaked Channels |
Opened most of the time E.g K+ leak channels regulate membrane potential E.g Na+ leak channels generate unstable membrane potentials |
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Gated channels |
Closed most of the time, opened upon appropriate activation |
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Voltage activated channels |
Open/close due to changes in membrane potential E.g Na+ , K+ , Ca2+ & Cl- channels |
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Ligand activated channels |
Open/close due to the binding of a chemical (agonist/cAMP/cGMP/H+) |
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3 examples of ligand activated channels |
Nicotinic cholinergic receptor opens when 2 molecules of acetylcholine bind Transient receptor potential channels (TRP channels - also voltage & stretch) Typerpolarisation - activates cyclic nucleotide gated channels |
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Mechanically activated channels |
Open/close due to a mechanical stimulus Sensory receptors that respond to pressure or stretch |
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Result from a net gain of Na+ ions |
The potential dissipates : the charge leaks away from the membrane are diluted down by the bulk of the intracellular fluid of & K+ moves out to restore the resting membrane potential. (areas become depolarised) |
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How does system restore? |
Voltage gated K+ channels & Na+/K+ pump |
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Rising Phase |
Depolarisation Na+ influx via voltage gated Na+ channels Na+ channels inactivate Refractory period: absolute & relative |
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Falling Phase |
Repolarisation K+ efflux via voltage gated K+ channels |
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Propagation along the neuron |
Positive ions move outside the membrane Positive ions enter next segment of axon |
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Transmission across a synapse: transmission in the nervous system |
Membrane potential Local potential Action potential Propagation alone the neuron Transmission across the synapse |
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Sites of Drug Actions |
Local Anaesthetics Anticholinesterase Drugs Potassium channel blockers Neuromuscular Blockers |
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Local Anaesthetics |
Prevent Na+ gated channels from opening Neurotransmission decreased |
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Anticholinesterase Drugs & Potassium Channel Blockers |
Neurotransmission is increased |
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Neuromuscular Blockers |
Compete with acetylcholine D-Tubocurare competitive drug |
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What does Strychnine poisoning lead to & why? |
Tremors Twitching Rigor in face & limbs Convulsions Because Strychnine competes with glycine - an inhibitory neurotransmitter |
