Pharmacology Flashcards
What is pharmacology?
The study of the effects of drugs
What is pharmacokinetics?
How the body affects drugs
What are pharmacodynamics?
He drug affects the body
What are the different ways the body can affect a drug?
Absorption
Distribution
Metabolism
Excretion
What are receptor ligands?
Anything that acts at a receptor
What is potency?
Meaure of how well a drug works
What is an agonist?
A compound that binds to a receptor and activates it
What is an EC50?
Drug concentration that gives half the maximal response
What does efficacious mean?
More successful in producing a desired result (e.g. Drug A is more efficacious than drug B)- higher Emax
What is a partial agonist?
A drug that binds to and activates a receptor, but is not able to elicit the maximum response produced by full agonists
What does it mean if one drug is more potent than another?
Lower concentrations of it will produce a greater response
What is an antagonist?
Compound that reduce the effect of an agonist
What are the different mechanisms of antagonist action?
Competitive: Compete with agonists to bing to receptors
Non-competitive: Binds near a receptor and prevents activation.
What are cholinergic receptors and what are they activated by?
Involved in signal transduction of the somatic and autonomic nervous system.
Acetylcholine neurotransmitter
What are the cholinergic receptor agonists?
Muscarine
Nicotine
What are cholingeric receptor antagonists?
Atropine
Curare
What does affinity mean?
How well a ligand binds to a receptor
What does efficacy mean?
How well a ligand activates a receptor.
What are the actions of NSAIDs?
Analgesia
Anti-pyretics (reduce fever)
Anti-inflammatory
What are some NSAID examples?
Aspirin
Ibuprofen
How do NSAIDs work?
Inhibit COX (enzyme responsible for the breakdown of arachidonic acid to prostaglandin H2) via competitive inhibition
What are prostaglandins/ their action?
Group of lipids made at sites of tissue damage or infection that control inflammation, blood flow and clotting.
What are the two forms of COX?
COX-1 : Found normally and widely around the body
COX-2: Induced in inflammation
Is aspirin COX selective?
No- Works on COX-1 and 2.
What are examples of ACE inhibitors?
Ramipril, captopril
What is the action of ACE inhibitors?
Anti-hypertensives:
Work by inhibiting ACE so prevent the conversion of Angiotensin 1 to Angiotensin 2, resulting in reduced vasoconstriction and less aldosterone release.
What are B-lactam antibiotics + examples?
Antibiotics that work by inhibiting cell wall biosynthesis of bacterial cell walls by inhibiting enzymes.
E.g. Penicillins, amoxicillin, cephalosporins.
What are CYP450’s used for?
Enzymes required to introduce a hydroxyl group to some drugs to enable them to be excreted from the kidneys.
What are examples of proton pump inhibitors?
Omeprazole, Lansoprazole, Pantoprazole, Rabeprazole
What is the action of proton pump inhibitors?
Act to inhibit acid secretion,
What are the different types of diuretics?
Loop
Thiazide
Potassium sparing
Where do loop diuretics work?
Inhibit sodium-potassium co-transporter in the thick ascending loop of Henle
Where to thiazide diuretics work?
Inhibit sodium reabsorption in the distal convoluted tubule
Where to potassium sparing diuretics work?
Interfere with the sodium-potassium exchange in the distal convoluted tubule.
What is the action of neuronal uptake inhibitors?
Result in increased concentration of neurotransmitter in the synapse by preventing re-uptake
What neurotransmitters are subject to reuptake?
Dopamine
Noradrenaline
Serotonin
GABA
What are SSRI’s?
Selective serotonin reuptake inhibitors
What is the action of cocaine?
Inhibits the reuptake of dopamine
What are some examples of calcium channel blockers?
Amlodipine
Verapamil
Diltiazem
What is the action of calcium channel blockers?
Anti-hypertensives: Block the voltage dependent calcium channels found in cariac and vascular smooth msuscle, resulting in reduced vasoconstriction
How do local anaesthetics work?
By interrupting axonal neurotransmission in sensory nerves
What is a first order drug reaction?
The rate of diffusion is directly proportional to the concentration of the drug
What is a second order drug reaction?
Rate is directly proportional to the square of the concentration of the drug
What is a third order drug reaction?
Rate is directly proportional to the cube of the drug concentration
What is a zero order drug reaction?
The rate of diffusion is unrelated to the concentration of the drug
What is the most commonly used graph in pharmacokinetic theory>
Concentration time curve
How many litres of fluid is in the:
- Plasa
- Interstitium
- Intracellular?
Plasma= 5 litres Interstitial= 15 L Intracellular= 45 L
What are the 5 ways a drug can move from its site of administration to its target?
Simple diffusion Facilitated diffusion Active transport Through extracellular space (through pores) Non ionic diffusion
What is bioavailability?
The amount of drug taken up as a proportion of the amount administered
What are the different routes of drug administration?
Oral Intramuscular Intravenous Transcutaneous Intrathecal (into CSF) Sublingual Inhalation Topical Rectal
What route of administration has the lowest bioavailability?
Oral
What is the volume of drug distribution?
The total amount of drug in the body divided by concentration of drug in the plasma
Where are proteins/ large molecules active?
In the plasma compartment
Where are water soluble molecules active?
In the plasma and interstitial compartment
Where are lipid soluble molecules active?
In the intracellular fluid
Where is the elimination of a drug from?
The plasma compartment via the renal or hepatic route
What is clearance?
The volume of plasma that can be completely cleared of drug per unit time OR the rate at which plasma drug is eliminated per unit plasma concentration
What is the unit for clearance?
ml/ min
How are drugs cleared?
Either by the kidney or the liver
How can renal clearance be measured?
Rate of appearance in urine divided by plasma concentration
What kind of drugs are eliminated by the kidneys?
Water soluble small molecules
What is the hepatic extraction ratio?
The proportion of drug removed by one passage through the liver
What is phase 1 of hepatic drug metabolism?
Make the drug more hyrophilic so it can be excreted by the kidneys (add hyrdoxyl group)
What enzyme is involved in Phase 1 reactions?
CYP450
What is phase 2 of hepatic drug metabolism?
Glucocordination: Add a glucuronic acid group to make very hydrophobic drugs more hydrophilic
What happens to the drugs once they have been metabolised by the liver?
They enter the bile and then the gut via the cystic duct.
What happens to the phase 2 glucuronides once they enter the gut?
They are metabolised by large bowel flora and can then reenter the blood to have greater effects, before going back to the liver to be re-conjugated and excreted again
What is steady state?
When the infusion dosage= the rate of elimination from the plasma
What is the ideal drug for IV infusion?
One with small volume of distribution so it is easy to reach steady state
One which is broken down by tissue/ plasma enzymes irrespective of liver and renal function
One with low risk of toxicity and easy to determine concentration in plasma
What neurotransmitter is used by the parasympathetic nervous system?
ACh
What neurotransmitter is used by the sympathetic nervous system?
Noradrenaline
What are the side effects of muscarinic agonists?
Diarrhoea Urination Miosis Bradycardia Emesis (vomiting) Lacrimation (tears) Salivation Sweating
What are the different classes of adrenoreceptors?
Alpha-1 Alpha-2 Beta-1 Beta-2 Beta-3
What is the action of alpha-1 adrenoreceptors?
Vasoconstriction
Pupil dilation
Bladder contraction
What is the action of alpha-2 adrenoreceptors?
Presynaptic inhibition of noradrenaline
What is the action of Beta-1 adrenoreceptors?
Increased force of contraction Increased heart rate Increased electrical conduction Increased renin release Increased blood pressure
What is the action of Beta-2 adrenoreceptors?
Bronchodilation
Vasodilation
Reduced GI motility
What is the action of Beta-3 adrenoreceptors?
Increased lipolysis
Relaxation of bladder
What are the 3 components to pain?
Sensory
Emotional
Actual/ potential tssue damage
What are the different classifications of pain?
Acute pain Cancer pain Chronic non-cancer pain Nociceptive pain Neuropathic
What is nociceptive pain?
Pain caused by structural dysfunction (e.g. fracture or IBS)
Where does acute pain arise from>
Nociceptors
What are nociceptors?
Nerve endings of the peripheral nervous system (myelinated A delta fibres and unmyelinated C afferent fibres)
What is the pain pathway?
- Noxious stimulus
- Nociceptors
- Spinal cord via ascending pathway
- Spinal cord modulation
- Thalamus
- Cortical areas + somatosensory cortex + prefrontal cortex
- Pain experience/ memory
What are the different types of noxious stimulus?
Mechanical
Thermal
Chemical
Which nerve fibres transmit pain and what type?
C fibres (unmyelinated): characterised by diffuse, dull pain A delta fibres (myelinated): Localised sharp pain
What is the action of A beta and A alpha fibres?
A-alpha: Carry information related to proprioception
A-Beta: Carry information related to touch
Why does rubbing the site of injury/ Tens machine work to reduce pain?
If A-Beta fibres are stimulated at the same time as A delta or C fibres, the pain signal is halted and doesn’t reach the brain
What excitatory neurotransmitter is responsible for pain?
Glutamate
What are the basis of pharmacological treatments for pain?
Reducing glutamate and therefore excitation of nerve
Enhancing inhibitory neurotransmitters (GABA, Noradrenaline, Serotonin)
What neurotransmitter is the main CNS inhibitory transitter?
GABA
What is chronic pain>
Persistent pain for longer than 3-6 months
What does noxious mean?
Harmful or poisonous
How many patients do adverse drug reactions occur in?
10-20% of hospital patients
What are the different types of adverse drug reaction?
Augmented Bizarre Chronic Delayed End of use
What are augmented ADR’s?
Commonest type. An exaggeration of the clinical effect. Predictable and dose related
What are some examples of augmented ADR’s
Diuretic causing dehydration
Anticoagulant causing bleeding
Anti-hypertensive causing hypotension
What patients are more at risk of augmented drug reactions and why?
Elderly- have decreased glomerular filtration
Those with renal or hepatic impairment: elimination difficulties
What are type B drug reactions?
Bizarre;
Unexpected/ unpredictable and unrelated to dosage.
May be history of allerfy
What is an example of a chronic drug reaction?
Long term steroids predisposing to hypoglycaemia which may result in diabetes
What is an example of a delayed drug reaction?
Teratogenesis (congenital malformations) after taking thalidomide
Neoplasia
What is an end of use ADR?
Withdrawal reactions after stopping a relatively long-term used drugs
What are the different types of hypersensitivity and how can drugs cause ADR’s with each type?
T1=IgE mediated drug hypersensitivity (Anaphylaxis)
T2= IgG-mediated cytotoxicity (some drugs can cause renal failure)
T3= Immune complex deposition ( reacts with antibiotics)
T4= T-cel mediated (usually substance containing metals)
What are the different types of drug interactions?
Synergy
Antagonism
What is synergy?
Where the actions of 2 drugs combine
What are the risk factors for drug interactions?
Polypharmacy
Old age
Genetics (fast/ slow metabolism)
Hepatic or renal disease
What are the risk factors for a drug having a drug interaction?
Narrow therapeutic index
Steep dose/ response curve
Saturable metabolism
What are the pharmacokinetic mechanisms of drug interaction?
Absorption
Distribution
Metabolism
Excretion
What are the ways drug interactions can affect absorption of drugs?
Motility changes Acidity changes Solubility Non-absorbed complex formation Direct action on enterocytes
How can drug interactions affect the distribution of certain drugs?
Protein binging affects drugs concentration in plasma and therefore reduces its distribution
How can drug interactions affect the metabolism of drugs?
CY450 metabolises many drugs: Inhibition or induction.
What effect can grapefuit have on certain drugs?
Can increase their uptake (increased bioavailability)
How can drug interactions affect the excretion of drugs?
Renal excretion is pH dependant. Therefore drugs that change the pH can affect the excretion of other drugs.
What are the pharmacodynamic mechanisms of drug interaction?
Receptor based: Agonists Partial agonists Antagonists Signal transduction Physiological system- drugs that affect different receptors in the same system.
What is required for a prescription?
Patient name Dose Route Frequency Duration Total no. tablets Drug name Date & signature
What is the oral bioavailability of morphine?
50%
0 in 10% of population
What is given to reverse a morphine overdose?
Naloxone- antagonist
What percentage of the dose of morphine should you give if giving IM or IV instead of orally?
50%
e.g. 5mg instead of 10mg
What is the main side effect of opioid use?
Respiratory depression
addiction
What are the two systemic routes of drug administration?
Enteral
Par-enteral
What does enteral mean?
Through the GI tract
What are the enteral routes of drug administration?
Oral (PO)
Rectal (PR)
Sublingual
What are the par-enteral routes of drug administration?
IV IM SC Inhalation (can be systemic or local) Transdermal
What are the local routes of drug administration?
Topical Intranasal Eye drops Inhalation Transdermal
What will an inducer do?
Increase Cytochrome P450 and speed up the metabolism of other drufs, may result in sub-therapeutic dose
What will an inhibitor do?
Decrease CP450 activity reducing the metabolism of other drugs which may result in toxicity
What happens in a paracetamol overdose?
The Phase II metabolic pathways become saturated, and more paracetamol is shunted to the CPY450 system to produce NAPQI which is toxic.
