Pharmacology Flashcards
Define pharmacology
The study of the effects of drugs
Define pharmokinetics
How the body affects the drug
What does MADE stand for (pharmokinetics)
M= metabolism
A= absorption
D= distribution
E= excretion
Define pharmacodynamics
How the drug affects the body
What is a receptor?
A component of a cell that interacts with a specific ligand and initiates a change of biochemical events leading to the ligands observed effects
What are the 2 types of ligands?
Exogenous: eg drugs
Endogenous: eg hormones and neurotransmitters
What are 3 chemical types that interact with receptors?
Neurotransmitters
Autoacids
Hormones
What are 2 examples of a neurotransmitter?
Acetylcholine
Serotonin
What are 2 examples of an autoacid?
Local hormones:
Cytokines
Histamine
What are 2 examples of a hormone?
Testosterone
Hydrocortisone
What are 4 types of receptors?
Ligand gated ion channels
G coupled protein receptors (GPCRs)
Kinase linked receptors
Cytosolic/ nuclear receptors
What is an example of a ligand gated ion channel?
Nicotinic ACh receptor
What are ligand gated ion channels used for?
ACh binding opens pore and allows ions to move into cell and change the cells electric charge distribution
Give an example of a GPCR
Beta adrenoreceptors
What are the largest and most diverse group of membrane receptors in eukaryotes?
GPCRs
What is the function of GPCRs?
On ligand binding, GPCRs catalyse the exchange of GDP to GTP
What are kinases?
Enzymes that catalyze the transfer of phosphate groups between proteins - process is known as phosphorylation
Describe the mechanism of kinase linked receptor activation
Ligand binding causes conformational change
Phosphorylation
Signal transduction
What type of hormones use cytosolic/nuclear receptors?
Steroid hormones
How do nuclear receptors work?
Modify gene transcription
How do zinc fingers aid nuclear receptors?
Recognise discrete regions of DNA
Give 2 examples of a chemical imbalance leading to pathology
Allergy- inc. histamine
Parkinson’s- dec. dopamine
Give 2 examples of receptor imbalance leading to pathology
Myasthenia gravis- loss of nicotinic ACh receptors
Mastocytosis- increased C-kit receptors
What is EC50?
Concentration that gives half the maximal response
Define agonist
Compound that binds to a receptor and activates it
Define antagonist
A compound that binds to a receptor but does not activate it
How is intrinsic activity calculated?
Emax of partial agonist
———————————
Emax of full agonist
Can antagonists activate a receptor?
No
Define ligand
A molecule that binds to another (usually larger) molecule
What does the 2 state model of receptor activation describe?
describes how drugs activate receptors by inducing or supporting a conformational change in the receptor from “off” to “on”.
How does competitive antagonists work?
Reverse effects of agonists by competing with the agonist to bind to a receptor- prevents activation by blocking agonist binding
What effect does adding a competitive antagonist have on a dose response curve?
Curve shifts to the right
-more agonist needed to illicit the same response
How does a non-competitive antagonist work?
Binds near the receptor and prevents activation but doesn’t bind directly so agonist can still bind but not activate it
What effect does adding a non-competitive antagonist have on a dose response curve?
Shifts right and down- agonist can bind but not activate it
What is a partial agonist?
An agonist which is unable to induce maximal activation of a receptor population, regardless of the amount of drug applied
What are the 2 categories of cholinergic receptors?
Nicotinic and muscarine
What the ACh receptor for muscarinics?
mAChR
What is the receptor for nicotinics?
nAChR
What is the antagonist of muscarinic receptors?
Atropine
What is the antagonist of nicotinic receptors?
Curare
What are the agonist and antagonists of histamine receptors?
Histamine = agonist
-contracts ileum and acid secretion
Mepyramine = antagonist
-reversed contraction of ileum, no effect on acid secretion
Define affinity
How well a ligand BINDS to the receptor
Is affinity shown by antagonists or agonists?
Both
Define efficacy
How well a ligand ACTIVATES the receptor
Do agonist or antagonists show efficacy?
Only agonists
Name a drug that will permanently inactivate a receptor
BAAM irreversibly antagonises B-adrenoreceptors
Describe receptor reserve
Some agonists need only a small amount of receptors to be activated to produce the maximum response
Do partial agonists have a receptor reserve?
No- maximal response never seen
What does signal amplification determine?
How powerful the response will be
What determines how powerful a signal amplification is?
The type of tissue the receptor is based on
Describe allosteric modulation
Binding of an allosteric ligand at another site can effect an agonists effect on the receptor
Define Emax
Maximum effect a drug can produce
Define intrinsic activity (IA)
Refers to the ability of a drug-receptor complex to produce a maximum functional response
Describe inverse antagonism
A drug binds to the same receptor as an agonist but induces a response opposite to that of the agonist
Define tolerance
The reduction in a drug (agonist) effect over time
What are 3 causes of receptor desensitisation?
Uncoupled (receptor can interact with G-protein)
Receptor internalised in cell vesicle
Receptor is degraded
How do NSAIDs work?
Inhibit COX which breaks arachidoic acid to PGH2 via competitive inhibition
How do ACE inhibitors work?
Inhibit ACE by preventing angiotensin 1 converting to angiotensin 2 So less bind to receptors
What is the effect of ACE inhibitors?
-Lack of binding to AT1 receptors results in reduced vasoconstriction-> reduced hypertension
-Also reduced aldosterone -> reduced hypertension
What type of drugs are captopril and enalapril?
ACE inhibitors
How do B-lactam antibiotics work?
Inhibit biosynthesis of peptidoglycan bacteria cell walls by inhibiting enzyme activity
What are the 3 types of protein ports?
Uniporters
Symporters
Antiporters
Describe the function of a uniporter
Use energy from ATP to pull molecules in
Describe the function of a symporter
Use the movement in of one molecule to pull in another molecule against a concentration gradient
Describe the function of an antiporter
One substance moves against its gradient, using energy from the second substance (mostly Na+, K+ or H+) moving down its gradient.
What is the suffix for a proton pump inhibitor?
Prazolone
What is the function of a proton pump inhibitor (PPI)?
Inhibit acid secretion and reduce acidity to help with reflux ect
Describe the mechanism of PPIs
Irreversibly inactivate proton pumps of parietal cell causing a reduction in stomach acidity
Describe the function of diuretics
Removes water from the blood to reduce blood volume and therefore blood pressure
How do thiazides work as diuretics?
Inhibit Na+/Cl- co transporter on distal tubule of nephron to increase water loss
How does furosemide act as a diuretic?
Inhibits NKCC2 pump on thick ascending limb of LOH reducing ions in three interstitium
-reduces hyperosmolarity so less water diffuses into the blood causing water loss
What are calcium channel blockers used to treat?
Hypertension
How are calcium channel blockers used to treat hypertension?
Block Ca2+ channels in the cardiac muscle, preventing influx of Ca2+ and therefore preventing vasoconstriction
What is the suffix for general anaesthetics?
Ocaine/caine
How do local anaesthetics work?
Block voltage dependent Na channels preventing depolarisation so the action potential can not be generated- so pain is not transmitted
Which enzyme is responsible for 75% of drug metabolism?
CYPs
What are the 3 phases of pharmacokinetics at the plasma level?
UPTAKE into plasma
DISTRIBUTION from the plasma
ELIMINATION from the plasma
What occurs in a first order reaction?
Rate is directly proportional to the concentration of the drug
What occurs in a second order reaction?
Rate directly proportional to the concentration squared
What occurs in a third order reaction?
Rate directly proportional to the concentration cubed
What occurs in a zero order reaction?
Rate unrelated to the concentration of the drug
What are the 5 ways a drug can move from the site of administration to its target?
- Simple diffusion
- Facilitated diffusion
- Active transport
- Through extracellular spaces
- Non-ionic diffusion
Define bioavailability
Amount of drug taken up as a proportion of the amount administered
What is the ideal bioavailability?
1 or 100%
What 2 routes of administration have the highest bioavailability?
Intravenous and intramuscular
What are some routes of drug administration?
Oral
Intramuscular
Intravenous
Transcutaneous (skin patch)
Intrathecal (into CSF)
Sublingual
Inhalation
Topical
Rectal
What are the 4 barriers a drug passes through?
Intestinal wall
Intestinal lumen
Lungs
Liver
What effect does gastric pH have on aspirin uptake?
Aspirin is ACIDIC
-Raised pH = reduced uptake of aspirin from the stomach and therefore a reduction in bioavailability
Where are proteins and large molecules active?
Plasma compartment
Where are water soluble molecules active?
Plasma and interstitial compartment
Where are lipid soluble molecules active?
Intracellular fluid
How is volume of distribution calculated?
Total amount of drug in body
——————————————
Concentration of drug in plasma
What is volume of distribution?
The volume the drug would occupy if it was distributed through all the compartments as if they were plasma
What drugs and molecules are found in the plasma compartment?
Warfarin
Immunoglobulin
What drugs are found in the interstitial compartment?
Aspirin/NSAIDs
Antibiotics
Muscle relaxants
What drugs are found in the intracellular compartment?
Steroids
Paracetamol
Amiodarone (easily taken up by tissue)
Opioids
Local anaesthetics
What compartment are drugs eliminated from?
Plasma compartment
What are the most common routes of drug elimination?
Renal or hepatic
Define clearance (2 definitions)
- The volume of plasma that can be completely cleared of drug per unit of time
- The rate at which plasma drug is eliminated per unit plasma concentration
What are the units of clearance?
Mils minute-1 (ml/min)
How is renal clearance calculated?
Rate of appearance in urine
—————————————
Plasma concentration
What is the adult renal blood flow?
18% of cardiac output = 1L/min
What is the adult plasma flow?
60% of blood flow = 600 mls/min
What is the adult glomelular filtration rate?
12% of renal blood flow = around 130 mils/min
How are drugs administered enterally?
Oral
Rectal suppository
How are drugs administered parentrerally?
Subcutaneous
IM
IV
Sublingual
Inhaler
Define potency
The relative strength of the drug
- lower dose needed to initiate a response
Define therapeutic range
Upper and lower bounds of safe doses of a drug
What occurs in phase 1 of drug metabolism?
Non-conjugation
- increases hydrophilicity via enzymes like CYP450
What occurs in phase 2 of drug metabolism?
Conjugation
- Adds functional group to MASSIVELY increase hydrophilicity
Define specificity in terms of pharmacology
Acts on a certain target
Define selectivity in terms of pharmacology
Acts on subtype of target
What organ contributes to most of the drug excretion in the body?
Kidneys
What hormones act at a parasympathetic neurotransmitter?
Presynaptic = ACh (n)
Postsynaptic = ACh (m)
What hormones act at a sympathetic neurotransmitter?
Presynaptic= ACh (n)
Postsynaptic = NAd
What hormones act on a skeletal muscle motor neuron?
ACh at NMJ (n)
Motor neuron -> NMJ
Where are M1 receptors found?
Brain
Where are M2 receptors found?
Heart
Where are m3 receptors found?
Lungs
Which cholinergic receptors are usually Presynaptic?
Nicotinic
Which cholinergic receptors are usually Postsynaptic?
Muscarinic
What are the consequences of overstimulation of ACh?
SLUDGE
-salivation
-lacrimation
-urination
-defacation
-GI distress
-emesis
Where are alpha adrenoreceptors found?
Vessels and sphincters
What is an example of an alpha adrenoreceptor blocker/antagonist?
Tamulosin
Doxazosin
What are alpha adrenoreceptor blockers/anatagonists used to treat?
Hypertension
Benign prostatic Hypertrophy
What is the effect of beta1 adrenoreceptor agonists?
Act on HEART
-increase inotropy (force) and chronotropy (rate) of cardiac contraction
Give an example of a beta1 adrenoreceptor agonist
Dobutamine
What is an example of a beta1 receptor antagonist?
Beta blocker
-propanalol
-bisoprolol
-metoprolol
What are beta1 receptor antagonists used to treat?
AF
Angina
Heart attack
Angina
What are beta1 receptor agonists used to treat?
Cardiogenic shock
Severe heart failure
Where are beta2 adrenoreceptors found?
Lungs (remember 2 = 2 lungs)
What is an example of a beta2 receptor agonist?
SABAs (salbutamol)
What are beta2 agonists used to treat?
Asthma
COPD
Define hepatic extraction ratio
The proportion of drug removed by one passage through the liver
How does cytochrome P450 oxidise substances?
Adds haem group Fe2+
Name 2 cytochrome P450 inhibitors
Amiodarone
Cimetidine
What are cytochrome P450 inhibitors used for?
Makes drugs last longer- they are not eliminated as fast
What percentage of liver function must be lost before drug metabolism is affected?
70%
What are the effects of alpha1 adrenoreceptors?
Vasoconstriction
Pupil dilation
Bladder contraction
What are the effects of alpha2 adrenoreceptors?
Reduce insulin secretion
-found in the pancreas
-stimulated to reduce noradrenaline release
What are the effects of beta3 adrenoreceptors?
Increased lipolysis
Releases bladder
What is an example of a beta 3 agonist?
Mirabergon
When are beta blockers contraindicated and why?
Asthmatics
- They will likely be on beta-2 antagonists anyway
Define pain
Unpleasant sensory and emotional experience associated with actual or potential tissue damage
What are the 3 components of pain?
Sensory
Emotional
Actual/potential tissue damage
What are 3 positive aspects of pain?
Warning of tissue damage
Immobilisation for healing
Protects species- memories of pain
What are 3 physiological effects of pain?
Increased heart rate
Inc blood pressure
Inc respiratory rate
What is nociceptive pain?
Inflammatory chemicals reach nerves to stimulate pain
Define neuropathic pain
Nerve is directly injured- pain originates in nervous system
Define chronic pain
Ongoing persistent pain greater than 3-6 months
Define adverse drug reaction
A response to a drug which is noxious and unintended
What is the oral bioavailability of opiates?
50%
What are the 6 types of ADR?
A- augmented
B- bizarre
C- chronic
D- delayed
E- end of use
F- failure
What is the most common type of ADR?
Type A- augmented
80%
What are the qualities of a type A ADR?
Predictable
Dose related
Self-limited
What is the morbidity and mortality like for type A ADRs?
Low mortality high morbidity
What is an example of a type A ADR?
Diuretic causes dehydration
Anticoagulant causes bleeding
Hypertension drug causing hypotension
What are the qualities of a type B ADR?
Unexpected
Unrelated to dose
Unpredictable
Mostly immunological eg hypersensitivity
What is the morbidity and mortality like for type B ADRs?
Low morbidity high mortality
What is an example of a type B ADR?
Penicillin causes anaphylaxis
Heparin causes hair loss
What are the qualities of a type C ADR?
Occurs after long term therapy
May not be immediately obvious after starting new medication
Define idiosyncrasy?
Inherent abnormal response to a drug
What is an example of a type C ADR?
Steroids predispose to hypoglycaemia -> diabetes
What are the qualities of a type D ADR?
Effects not visible until a long time after taking the medication due to prolonged exposure
What is an example of a type D ADR?
Tardive dyskinesia due to antipsychotics
What are the qualities of a type E ADR?
Long term use
Withdrawal reaction
Serious complications associated with stopping
What would a predictable dose related ADR likely to be?
Type A
What would a ADR with history of allergy be likely to be?
Type B
What would an ADR when the patient has been taking the drug for a long time be likely to be?
Type C
What would an ADR when a patient had been using the drug and is having problems later on be likely to be?
Type D
What would an ADR associated with withdrawal be likely to be?
Type E
What is an example of a type E ADR?
Opiate withdrawal
What factors increase susceptibility to an ADR?
Old age
Female sex
Drug interactions
Drug or diet changes
Genes
Describe a type 1 hypersensitivity reaction
IgE mediated
Describe a type 2 hypersensitivity reaction
IgG mediated cytotoxicity
Describe a type 3 hypersensitivity reaction
Immune-complex deposition
- reaction with antibiotics
Describe a type 4 hypersensitivity reaction
T cell mediated
Describe the qualities of a type F ADR
Common
Dose related
Often caused by drug interactions
What is an example of a type F ADR?
Failure of oral contraceptives with enzyme inducers
How are ADRs managed?
- Continue drug and manage ADR
- Reduce drug dose
- Stop the drug (type B)
What are the markers of a type A ADR?
Serum concentration
What are the markers of a type B ADR?
Tryptase (released by mast cells)
Urine methylhistamine (breakdown product of histamine)
How are ADRs reported?
Yellow card scheme
When should ADRs be reported?
All suspected ADRs for new medications
All ADRs in children
Fatal, life threatening, disabling, incapacitating or prolonged hospitalisation
Define synergy
The actions of 2 drugs combine
Define drug antagonism
One drug blocks the action of another
What are the patient risk factors for drug interactions?
Poly pharmacy
Old age
Genetics
Hepatic disease
Renal disease
What are the drug risk factors for drug interactions?
Narrow therapeutic index
Steep dose/response curve
Saturable metabolism
What are the factors that affect absorption?
Motility
Acidity
Solubility
Non-absorbed complex formation
Direct action on erythrocytes
What are factors that affect distribution?
Protein binding
What is renal excretion dependent on?
Urine pH
What are 4 drugs that are weak acids?
Aspirin
Ibuprofen
Paracetamol
Warfarin
What are 4 drugs that are weak bases?
Amphetamine
Atropine
Propranolol
Salbutamol
What is required for a prescription?
Diagnosis
Drug treatment
Indications and contraindications
What information is required on a prescription sheet?
Patient name
Dose
Route
Frequency
Duration
Total number of tablets
Drug name
Date and signature
When and why are oral fluids discontinued before surgery?
For 2 hours before
-risk of aspiration under anaesthesia
Which drugs should be discontinued prior to surgery?
ACE inhibitors
Warfarin (bridge to heparin)
Diabetes drugs
What type of drug is morphine?
Receptor agonist
What are some naturally occurring opioids?
Morphine
Codeine
What are some simple chemical modified opioids?
Diamorphine (heroin)
Oxycodone
What are some synthetic opioids?
Pethidine
Fentanyl
How should oral opioid dose be adapted if given parentally?
Halved
What is an opioid antagonist?
Naloxone
What are the side effects of opioids?
Respiratory depression
Sedation
Nausea and vomiting
Itching
Immune suppression
What is the first line response to opioid induced respiratory depression?
Administer naloxone IV
-400 micro grams/ ml
What percentage of paracetamol is metabolised in phase 1 and phase 2 reactions?
Phase 1= 5%
Phase 2 = 95%
