Pharmacology Flashcards
1
Q
Give 3 examples of enteral (oral) routes of administration of drugs
A
Enteric-coated (intestinal absorption e.g. aspirin) Extended release (slower absorption e.g. metformin) Sublingual/Buccal (rapid absorption and avoids first pass metabolism)
2
Q
Give 3 examples of parenteral (systemic circulation) routes of drug administration
A
Intravenous
Intramuscular
Subcutaneous (insulin)
3
Q
When would you use intramuscular administration of a drug?
A
Anti-psychotics
4
Q
Give 3 other examples of drug administration that are not enteral or parenteral
A
Inhalation (oral, nasal)
Topical
Rectal
5
Q
What is Pharmacokinetics
A
The action of drugs in the body including Absorption, Distribution, Metabolism and Excretion
(What the body does to a drug)
6
Q
What are 4 properties to consider regarding the pharmokinetics of a drug
A
Absorption
Distribution
Metabolism
Elimination
ADME
7
Q
Give 4 mechanisms of absorption (e.g. across GI mucosa)
A
Passive diffusion
Facilitated diffusion
Active transport
Endocytosis
8
Q
What variables affect absorption (ADME)
A
pH
Vascularity (e.g. shock reduces SC absorption)
Surface area
Contact time (e.g. with food = slower gastric emptying)
9
Q
Define bioavailability and equation of it
A
Rate and extend to which an administered drug reaches the systemic circulation (e.g. IV=100%)
AUC oral
——————– x100 = Bioavailability
AUC injected
(auc = area under curve (think))
10
Q
What factors influence bioavailability
A
Solubility
Chemical instability (e.g. GI enzyme destruction of insulin)
Effect of Hepatic metabolism on drug (hepatic transformation of drug to inactive metabolites)
11
Q
Define Distribution (Pharmokinetics - ADME)
A
Drug reversibly leaves bloodstream and enters the extracellular fluid and tissues
12
Q
What 4 factors affect distribution (Pharmokinetics - ADME)
A
Blood Flow (e.g. brain>muscles)
Capillary permeability
Plasma protein binding (e.g. albumin)
Tissue protein binding (e.g. cyclophosphamide accumulating in bladder -> cystitis
Lipophilicity (ability to cross cell membranes)
13
Q
Define Metabolism (Pharmokinetics - ADME)
A
Process of elimination, mainly through hepatic, renal and biliary routes
14
Q
What are the 2 rates of metabolism (Pharmokinetics - ADME)
A
First Order - catalysed by enzymes, rate of metabolism directly proportional to drug concentration
Zero Order - enzymes saturated by high drug doses and rate of metabolism is constant
15
Q
Give examples of chemicals of Zero order metabolism
A
Ethanol
Phenytoin
16
Q
Describe the 2 phases of metabolism (Pharmokinetics - ADME)
A
Phase 1:
Polarise lipophilic drugs
Catalysed by Cytochrome P450 system
Reduction/Oxidation/Hydrolysis
Phase 2:
Conjugation
Example - glucuronic acid, polarisation of drugs to be excreted by renal or biliary systems
17
Q
What system catalyses phase 1 metabolism reactions?
A
Cytochrome P450 system
18
Q
What 3 reactions (and corresponding chemical) are Phase 1 reactions NOT done by P450?
A
Alcohol dehydrogenase
Xanthine oxidase
Amine oxidation
19
Q
Name 3 problematic drugs for Cytochrome P450
A
Contraceptive pills
Warfarin
Anti-epileptics
20
Q
Name inducers of cytochrome P450
A
Anti-epileptics (Phenytoin, Carbamazepine) Rifampicin St Johns Wort Chronic Alcohol intake Smokers (CYP1A2)
21
Q
Define absorption in pharmacokinetics
A
The process of transfer from the site of administration into the general or systemic circulation
22
Q
Give examples of routes of administration
A
Oral Intravenous Intra-arterial Intramuscular Subcutaneous Inhalational Topical Sublingual Rectal Intrathecal
23
Q
What is meant by subcutaneous
A
Situated or applied under skin
24
Q
Define intrathecal
A
occurring within or administered into the spinal theca
25
How would you give Diazepam for a fitting child who had no visible veins & jaws clenched tight?
Rectal
26
How would you give Xray dye for looking at coronary blood vessels?
Angiogram
27
How would you give Ondansetron (antiemetic) in a patient having chemo who cant stop vomiting
Intra Venous (IV)
28
How would you give GTN for a patient having an angina attack at home
Sublingual
29
How would you give insulin for a diabetic adult?
Subcutaneous
30
Define sublingual
Situated or applied under the tongue
31
Which 2 routes of drug administration do not cross at least 1 membrane in its passage from the site of administration to general circulation?
Intravenous or Intra arterial
| drugs acts at intracellular sites must also cross the cell membrane
32
Describe 4 methods of passage across cell membranes
Passive diffusion through the lipid layer
Diffusion through pores or ion channels
Carrier mediated processes
Pinocytosis
33
Which of these regarding passive diffusion through the lipid layer is false:
Drugs move down concentration gradient
Need to have a degree of water solubility to cross phospholipid bilayer directly
Need to have degree of lipid solubility to cross phospholipid bilayer directly e.g. steroids
34
What factors are proportional to the rate of diffusion
Concentration gradient
Surface area
Permeability
..of the membrane
35
What factor is inversely proportional to rate of diffusion?
Thickness of membrane
36
Does movement through pores or ion channels happen against or down the concentration gradient
Down conc gradient
37
Give an example of a very small water soluble molecule that can diffuse through pores or ion channels
Lithium
38
What molecule provides energy for active transport or carrier mediated transport
ATP
39
What are the family of carriers called that facilitate cell-mediated transport?
ATP-Binding Cassette (ABC)
40
How many ATP-Binding Cassette (ABC)s are there in humans
49
41
What is the ABC known as MDR1 also called and what is it's function?
MDR1 = Multi Drug Resistance
OR => P-gp
It removes a wide range of drugs from the cytoplasm to extracellular side.
42
How does Verapamil increase extracellular concentration of Chemo drugs?
Inhibits P-gp and so increases the concentration of anti-cancer drugs in the cytoplasm
43
What 2 ways can a molecule be transferred by facilitated transport (by a carrier)
Passive diffusion down concentration gradient
Use of theelectrochemical gradient of a co-transported solute to transport the molecule against the concentration gradient
Neither require ATP
44
What is OAT1, where is it found and what does it secrete?
Organic Anion Transporter
Kidney
Secretes penicillin and uric acid
45
Name a drug that can block OAT1 and what is the effect of this?
Probenicid
Blocks OAT1 causing uric acid to be excreted
(Crystals of uric acid can form in joints to cause gout)
46
What is pinocytosis?
A form of carrier mediated entry into the cytoplasm. It usually involves the uptake of endogenous macro molecules.
(can be involved in uptake of recombinant therapeutic proteins)
47
Name a drug that can be taken up into liposome(s) for pinocytosis
Amphotericin
48
Give an example of a drug that is a weak acid
Aspirin
49
Give an example of a drug that is a weak base
Propranolol
50
Why are ionisable groups of a drug essential for the mechanism of action of most drugs?
As ionic forces are part of the ligand receptor interaction (on cell membrane)
51
How would you describe drugs with ionisable groupsthat exist between charged (ionised) and uncharged forms
Drugs with ionisable groups that exist in equilibrium between..
52
Which of these is false for drug pharmacokinetics:
The extent of ionisation depends on the strength of the ionisable group and the pH of the solution.
Ionised form regarded as the most lipid soluble
Un-ionised form regarded as lipid soluble
Ionised form regarded as most water soluble
53
What is meant by the pKa of a drug?
pH at which half of a substance is ionised and half is unionised
(Dissociation or ionisation constant)
54
Where are weak acids best absorbed?
Stomach
55
Where are weak bases best absorbed?
Intestine
56
What is the effect on urine from an aspirin overdose?
Normally urine has lower pH than plasma so weak acid will be largely un-ionised and will be reabsorbed into plasma.
57
How can you reduce reabsorption of aspirin into plasma?
If alkalinise urine with IV bicarbonate, can reduce reabsorption of aspirin and lead to faster elimination
58
Which of these regarding oral administration is false:
Easiest and most convenient route for many drugs
Large surface area and high blood flow of small intestine can give rapid and complete absorption of oral drugs
The drug will go straight into systemic circulation
There are a number of obstacles for the drug to overcome before it reaches the systemic circulation
59
What factors affect absorption of an orally administered drug?
```
Drug structure
Drug formulation
Gastric emptying (rate of this determines how soon drug taken orally is delivered to small intestine)
First pass metabolism
```
60
What drugs can not be given orally and why
Benzyl penicillin - unstable at low pH
| Insulin - unstable in presence of digestive enzymes
61
What drugs tend to be only partially absorbed and have much of it passed in the faeces?
Highly polarised drugs
62
Why is Olsalazine used to treat Inflammatory Bowel Disease?
Olsalazine not absorbed in small intestine (highly polarised)
This therefore reduces systemic side effects
63
What is required for a drug to be absorbed from the gut without a carrier protein or other?
Lipid solubility
64
What is important for capsulated drugs or tablets?
The capsule or tablet must disintegrate and dissolve to be absorbed.
65
Give an example of modified release drugs formulated to dissolve slowly
Modified release = MR
| Could have a coating that is resistant to acidity of the stomach in Enteric Coating (EC)
66
What can slow gastric emptying rate?
Food
Trauma
Antimuscarinic drugs (e.g. Oxybutinin)
67
Give an example of an antimuscarinic drug
Oxybutinin
68
How could gastric emptying rate be increased?
Gastric surgery
| e.g. gastrectomy or pyloroplasty
69
In First Pass Metabolism, what 4 major metabolic barriers need to be crossed to reach circulation?
Intestinal lumen
Intestinal wall
Liver
Lungs
70
How can drugs be digested in intestinal lumen
Digestive enzymes present that can split peptide, ester and glycosidic bonds
Peptide drugs (insulin) that can be broken down by proteases
Colonic bacteria can hydrolyse or reduce drugs
71
The walls of upper intestine is rich in cellular enzymes - give example
Mono amine oxidases (MAO)
72
How can Efflux transporters such as P-gp limit absorption of drug in gut?
Luminal membrane of enterocytes contains efflux transporters such as P-gp which may limit absorption by transporting drug back into the gut lumen
73
How can 'short gut syndrome' from extensive bowel surgery decrease absorption?
poor oral absorption as little surface left and rapid transit time
74
What circulation delivers blood from gut to liver?
Splanchnic circulation
75
How can you avoid hepatic first pass metabolism
Giving drug to region of gut not drained by splanchnic e.g mouth or rectum ( GTN )
76
How long until an intravenous route takes effect
30-60 seconds (quickest method)
77
What is slowest method of administering a drug?
Ingestion (30-90 mins)
| Transdermal (variable from minutes to hours)
78
What properties are required for a drug to be administered via transcutaneous methods?
Potent, non-irritant drugs.
(Human epidermis effective barrier to water soluble compounds. Limited rate & extent of absorption of lipid soluble drugs.)
79
When would you use Transdermal patches? (give example)
Slow and continued absorption.
E.g. Fentanyl patch 72
Hourly in chronic parin or palliative care
80
When/why would you use subcutaneous or intradermal?
Use for local effect (e.g. local anaesthetic) or to deliberately limit rate of absorption (e.g. long term contraceptive implants)
Small volume can be given; avoids barrier of stratum corneum; small volume can be given
81
What can increase removal of intramuscular administered drug from inject site?
Increase in blood flow or water solubility
82
What is meant by a Depot intramuscular injection?
Incorporating drug into lipophilic formulation which releases drug over days or weeks (e.g Flupenthixol )
83
Give features of intranasal administration
Low level of proteases and drug metabolising enxymes
Good SA
Local or systemic effects
84
What is the effect of cocaine on nose for drug administration
Cocaine is a vasoconstrictor and can get both local and systmic effects
85
Give example of intranasal drug with local effects
Decongestants
86
Give example of intranasal drug with systemic effects
Desmopressin
87
What are pros of inhalational administration
Large SA and blood flow
88
What are cons of inhalational administration
Risks of toxicity to alveoli and delivery of non volatile drugs
89
What drugs can be given inhalational
Volatiles likeGeneral anaesthetics
| Locally acting drugs like bronchodilators (asthma)
90
Are asthma drugs volatile and how are they given
Non-volatile
| Inhalational as aerosol or dry powder
91
Define distribution
The process by which the drug is transferred reversibly from the general circulation to the tissues as the blood concentration increases and then returns from the tissues to the blood when the blood concentration falls.
92
If equilibrium is reached by a drug between 2 sides of a membrane, what happens if a process removes drug from one side
Results in movement across membrane to restore that equilibrium (lipid soluble drugs for passive diffusion)
93
Define absorption
The process of transfer from the site of administration into the general or systemic circulation
94
Describe the distribution of an IV drug after administered
IV drug injection:
High initial plasma concentration and drug may enter well perfused tissue such as brain, liver and lungs
The drug will also continue to enter less well perfused tissues, lowering the plasma concentration.
Concentrations in the highly perfused tissues then decrease.
*Important in terminating some drugs given as a bolus
95
Give an example of terminating a drugs given as a bolus
Thiopental
This produces rapid anaesthesia because of initial high brain concentrations, but is short lived as continued muscle uptake lowers the blood concentration & indirectly the brain concentration
96
What plasma protein is most commonly bound (reversibly) to drugs?
Albumin
97
True or False:
Binding lowers the free concentration of drug and can act as a depot releasing the bound drug when the plasma concentration drops through redistribution or elimination
All true and important
98
Give an example of a drug that can bind irreversibly and therefore cannot reenter the circulation
Cytotoxic chemo with DNA
99
What makes up the blood brain barrier
Tight junctions, smaller number and sized pores in endothelium and astrocytes
100
What do SLC transporters supply the brain with?
Carbohydrates and amino acids
101
Give and example of a drug that uses the SLC transporters
L-Dopa for Parkinsons
102
How are drugs removed from the brain
Diffusion into plasma
Active transport in the choroid plexus
Elimination in the CSF
103
Give an exmaple of a drug that cannot cross the placenta
Heparin
104
Why does the foetus rely on maternal elimination
Foetal liver has low levels of drug metabolising enzymes
105
Give an example of an opiate given during labour which may persist in newborn who has to then eliminate them
Pethidine 7
106
*Define Elimination in pharmacokinetics
The removal of a drugs activity from the body.
May involve METABOLISM (transformation of a drug molecule into a different molecule) and/or EXCRETION (the molecule is expelled in liquid, solid or gaseous 'waste'
107
Describe process/purpose of metabolism
- Necessary for elimination of lipid soluble drugs.
- They are converted into water soluble products that are readily removed in the urine. (If stayed lipid soluble, they would be reabsorbed).
- One or more new compunds are produced which may show differences from the parent drug (e.g. less biological activity)
- 2 phases
108
What are Phase 1 metabolism reactions
Involve the transformation of the drug to a more polar metabolite. This is done by unmasking or adding a functional group (e.g. -OH, -NH2, -SH).
109
*What is the most common Phase 1 reaction?
Oxidations
110
What group of enzymes catalyse Oxidation (phase 1) reactions?
Cytochrome P450
111
What is Cytochrome P450
Superfamily of membrane bound isoenzymes
112
Where is Cytochrome P450 mainly found?
Smooth Endoplasmic Reticulum
| Largely in liver tissue
113
What is effect of smoking and alcohol on P450 enzymes
Can induce P450 enzymes
| More rapid drug metabolism
114
Give example of drug and example of a food that can inhibit P450
Cimetidine
| Grapefruit
115
Give an example of a genetic variation in Cytochrome P450
CYP2D6 deficiency/slow metaboliser 6-10% population
| e.g. for Tamoxifen
116
What reactions are classed as Phase 1 reactions
Reduction
Oxidation
Hydrolysis
117
*Give examples of Phase 1 reactions that do not involve CYTP450
Oxidation ones:
- Ethanol metabolisation - instead by Alcohol Dehydrogenase
- Monoamine oxidase -inactivates Noradrenaline
- Xanthine oxidase - inactivates 6-mercaptopurine
Other:
Some drugs are metabolised in plasma, lung or gut
118
Give example of drug metabolised in plasma (Phase 1, not CTYP450)
Suxamethonium
| Plasma Cholinesterase
119
*Describe Phase 2 reactions
Conjugation
Involves formation of a covalent bond between the drug OR its phase 1 Metabolite
and an endogenous substrate
The resulting products are usually less active and readily excreted by the kidneys
120
Which of these is Phase 1 reaction?
Synthetic reaction
Degradative reaction
Degradative reaction
| Synthetic reaction is phase 2
121
Give examples of molecules that a phase 1 metabolite can be conjugated with in phase 2 reactions
Glucuronic acid
Sulfate
Acetyl or Methyl groups
122
Which of these corresponds to phase 2 reactions:
Mainly microsomal
Microsomal, Mitochondrial and Cytoplasmic
Mitochondrial, Microsomal,
| Cytoplasmic
123
Where do Phase 1 reactions mainly occur
Mainly microsomal
124
Where can phase 2 reactions occur
Microsomal, Mitochondria, Cytoplasm
125
Describe differences between a phase 1 and a phase 2 metabolite
Phase 1 metabolites formed:
Smaller, Polar or Non-polar, Active or Inactive
Phase 2 metabolites:
Larger, Polar, Water Soluble, Inactive
(for excretion)
126
What is excreted as a fluid?
Low molecular weight polar compounds
| Urine, Bile, Sweat, Tears, Breast milk
127
What is excreted as a solid in faecal elimination?
High molecular weight compounds excreted in bile
128
What is excreted as a gas?
Volatiles
129
What is equation to calculate total urine excretion
Total excretion = glomerular filtration + tubular secretion -reabsorption
130
Describe how molecules end up in faecal excretion
High molecular weight molecules are taken up into hepatocytes and eliminated into bile.
Bile passes down gut: Some drug may be reabsorbed and re-enter the hepatic portal vein in Enterohepatic Circulation
131
*Describe the graph seen for a first order reaction (kinetics)
Change in concentration (dC/dt)at any time is proportional to the concentration.
Exponential decline:
A constant fraction of the drug is eliminated per unit of time.
132
Give an example of First Order Kinetics
Drug given via IV is rapidly distributed to the tissues. (exponential decline)
By taking repeat plasma samples, the fall in the plasma concentration with time can be measured.
133
*Describe a zero order reaction (kinetics)
The change in concentration per time(dC/dt) is a fixed amount of drug per time, independent of concentration.
If a system that removes a drug is saturated the rate of removal of the drug is constant and unaffected by an increase in concentration
134
What would a Zero order graph look like?
Concentratrion (y axis) and Time (x axis)
| Constant gradient down (diagonal line going down)
135
Give example of zero order kinetics
Ethanol follows zero order kinetics once alcohol dehydrogenase has been saturated
(However up to this point, it is presumably first order)
136
Give the equation for a zero order kinetics graph
dC/dt = -k where k is reaction rate constant or gradient
units often mg/min
dC/dt = change in concentration per time
137
Give equation for a first order kinetics graph
dC/dt = -kC where k is the reaction constant
dC/dt is change in concentration per time
138
If plotted a logarithm (e.g.lnC) of concentration against time for first order kinetics equation, what would graph look like
Straight line with slope -k and intercept gives concentration at time zero (lnC x o)
(Diagonal straight line going down)
139
*What is half-life
Period of time required for the concentration or amount of drug in the body to be reduced by one-half.
(usually consider the half life of a drug in relation to the amount of the drug in plasma)
140
*What is bioavailability
The fraction of the administered drug that reaches the systemic circulation un–altered (F).
141
What is the bio-availability of IV drugs
1
| as 100% of the drug reaches the circulation
142
Why may oral drugs have a bio-availability of <1
If they are incompletely absorbed or undergo first pass metabolism
143
How would you determine the oral bioavailability of a drug
AUC oral
---------------
AUC IV
AUC = area under the curve
144
What would it mean if a drug has an oral bioavailability of 0.1
The oral dose will need to be 10x IV dose
145
What is meant by the distribution of a drug
Rate and extent of movement of a drug into and out of tissues from blood
146
What determines the distribution of water soluble drugs
Rate of passage across membranes
147
What determines the distribution of lipid soluble drugs
Blood flow to tissues that accumulate drugs
148
Why is the extent of distribution of a drug important clinically
As this determines the total amount of drug that has to be administered to produce a particular plasma concentration
149
*What is equation to measure the apparent volume of distribution (Vd)
Vd = total amount of drug in body (dose)/plasma concentration
(*Remember APPARENT volume)
150
What is the apparent volume of distribution if give 50 mg of drug and find plasma concentration is 1mg/L
Vd= 50mg/1mg/L
=50L
151
What would a low apparent volume of distribution suggest?
Suggests drug may be confined to circulatory volume
152
What would a high apparent volume of distribution suggest?
Suggests drug may be distributed in total body water
153
*What is meant by Clearance
The volume of blood or plasma cleared of drug per unit time
e.g. if 10% of a drug (carried to liver) is cleared at flow rate of 1000ml/min
The clearance would be 100ml/min
154
If 5% of a drug (carried to liver) is cleared at flow rate of 1200ml/min, What is clearance?
60ml/min
155
If drug has a high Vd, would concentration in plasma be higher or lower
Lower plasma conc
156
If a drug has a high Vd and therefore a lower plasma conc, what would this mean for for rate of elimination.
Rate of elimination is inversely proportional to Vd
157
How would you calculate the rate constant of elimination?
k=CL/Vd
k is the rate constant of elimination
CL is clearance
Vd is apparent volume of distribution
158
What would it mean if the clearance of a drug was zero?
The drug would not be removed and plasma concentration would remain at equilibrium indefinitely (AUC would be indefinitely large)
159
How is clearance of IV drug determined?
Clearance is usually determined using the AUC after an IV dose
CL=Dose/AUC for IV drug
160
How is clearance of an oral drug determined?
CL= Dose x F/AUC for oral drug with bioavailability of less than 1
F is bioavailability
/ means or
161
When are repeated drug doses used
To maintain a constant drug concentration in the blood and at the site of action for therapeutic effect
162
*What is Steady state
Css
| It is a balance between drug input and elimination
163
With IV infusion, how long would it take to reach 95% of Css (steady state)
Approx 4-5 half-lives
164
What is effect on time taken to reach Css (steady state) for a drug with a slower elimination
Will take a long time to reach steady state and it will accumulate high plasma concentrations before elimination rate rises to match drug infusion/input
165
Other than a slow elimination rate, what else can delay reaching a steady state
High Vd
| as t1/2 or half life is also dependent on Vd (t1/2 = 0.693xVd/CL )
166
What is equation to calculate half life or t1/2
t1/2 = 0.693Vd/CL
167
How is Css achieved in IV infusion?
Css is achieved when the rate of elimination equals the rate of infusion
168
How would you calculate steady state for IV infusion
Css = Rate of Infusion/CL
169
How would you calculate plasma clearance for IV infusion
CL=rate of infusion/Css
170
How is rate of elimination calculated for IV infusion
Rate of Elimination = CL x Css so at steady state the rate of infusion also equals this
171
By what route is most long term drug administration
Oral route
172
On graph where have intermittent doses, what will be effect on concentration in plasma
Fluctuating
| Peaks and troughs
173
How does rate of absorption affect the profile of oral administration graph?
Rapid rate of absorption - exaggerated peaks
| Slow rate of absorption - flatter peaks
174
How would you correct a (oral) dose for bioavailability?
D x F/t
F is bioavailability
t is time interval between doses
175
Give final equation to calculate Css
Css = (D x F)/(t x CL)
```
Css - steady state
D - dose
F - bioavailability
t - time interval between doses
CL - clearance
```
176
Explain how reach this for steady state:
| Css = (D x F)/(t x CL)
When steady state is reached, the rate of administration is equal to the rate of elimination
which is CL x drug conc between peaks and troughs
Therefore D x F/t = CL x Css
So Css = (D x F)/(t x CL)
177
Using this equation:
Css = (D x F)/(t x CL)
What factors affect plasma steady state?
Dose (D) or time interval between doses (t)
178
*What is a loading dose?
An initial higher dose of a drug that may be given at the beginning of a course of treatment before dropping down to a lower maintenance dose.
179
Why would you use a loading dose?
Shortens the time taken to reach a steady state.
e.g. if a drug has a long half life, it would take a long time to reach a steady state
if takes 4-5 half life to reach steady state and half life is 24 hours, means it would take 4-5 days to reach a steady state
180
How would you calculate Loading Dose?
Loading dose = Css x Vd
181
After you have reached the steady state by giving a loading dose, what would you given to maintain steady state
Maintenance dose
182
How would you calculate maintenance dose to keep steady state
Css = (D x F)/(t x CL)
(Css x t x CL) / F = D
183
In shock, what needs to be done to control BP
Increase BP
| e.g. with Adrenaline
184
In hypertension, what needs to be done to control BP
Lower BP
| e.g. beta blockers
185
What is bradycardia?
Slow heart rate
186
What is tachycardia?
Fast HR
187
Give examples of multiple effects drugs could have
A drug to lower blood pressure will slow the heart
| A drug to relax the airways may raise pressures in the eye
188
What does autonomic NS do?
Conveys all outputs from the CNS to the body, except for skeletal muscular control
189
What does the autonomic NS regulate?
```
Vascular, airway and smooth muscle
Exocrine secretions (sweat)
Control of Heart Rate
Energy metabolism in the liver
Links to immune system
```
190
Give examples of actions of the Parasympathetic division of the autonomic NS
```
Constricts pupils
Stimulates tear glands
Strong stimulation of salivary flow
Slows heart rate
Constricts bronchi
Stimulates digestive juice secretion
Stimulates intestinal motility
Contracts bladder
Stimulates erection
```
191
Give examples of actions of the Sympathetic division of the autonomic NS
```
Dilates pupils
Tear glands moisturise
Inhibit excess salivary secretion
Accelerates heart rate and constricts arterioles
Dilates bronchi
Inhibits stomach motility and secretion
Inhibits pancreas (and adrenals?)
Inhibits intestinal motility
Relaxes bladder
Stimulates ejaculation
```
192
What neurotransmitter acts on adrenergic receptors
Noradrenaline
193
What are two types of adrenergic receptor
Alpha
| Beta
194
What type of receptor would you find in both parasympathetic and sympathetic fibres
nicotinic receptor
| Between pre and post ganglionic fibre
195
What chemical can be given to mimic the effects of the sympathetic NS
Adrenaline
| e.g. in anaphylactic shock
196
Give examples of organs with dual parasympathetic and sympathetic innervation (with opposing roles)
Gut
Bladder
Heart
197
Give examples of parts of body that only have sympathetic innervation
Sweat glands
| Blood vessels
198
Give example of part of body that only has parasympathetic innervation
Bronchial Smooth Muscle
199
What are two main neurotransmitters that can be targeted by therapeutic innervation
Acetylcholine
| Noradrenaline
200
What neurotransmitter is released by post-ganglionic sympathetic fibres and what receptor does this act on
Noradrenaline
| Acts on alpha and beta adrenoreceptors
201
What is only exception to post-ganglionic sympathetic fibres releasing Nad onto adrenoreceptors
Sweat Glands
| Release ACh to stimulate muscarinic receptors
202
What neurotransmitter is released by post-ganglionic parasympathetic fibres and what receptor does this act on
ACh
| muscarinic receptors
203
What neurotransmitter is released by pre-ganglionic sympathetic fibres and what receptor does this act on
ACh
| nicotinic receptors
204
What neurotransmitter is released by pre-ganglionic parasympathetic fibres and what receptor does this act on
ACh
| nicotinic receptors
205
What are NANCs
Non-Adrenergic, Non-Cholinergic Autonomic transmitters
206
What system used NANCs
Enteric NS
| Autonomic NS divisions
207
Give examples of NANCs
Nitric oxide and Vasoactive Intestinal peptide (parasympathetic)
ATP and Neuropeptide Y (sympathetic)
208
What ganglia are stimulated by nicotine
All autonomic ganglia via specific ganglionic nicotinic receptors
activating both parasympathetic and sympathetic NSs
209
*What can activate muscarinic receptors
ACh
Muscarine (from poisonous mushrooms)
these receptors also susceptible to drug targetting
210
What breaks down ACh
Acetylcholinesterases
211
How many muscarinic receptors are there in the human body?
M1-5 (so 5)
212
*Where is M1 (muscarinic receptor) mainly found
Brain
213
Where are M2 receptors (muscarinic) mainly found
Heart
214
What results from activation of M2 receptors
Slows the heart
215
What can be given to block M2 receptors and what is the result of this
Atropine
(e.g. for life-threatening bradycardia and cardiac arrest)
Speeds up heart rate
216
Where are M3 (muscarinic) receptors found?
Glandular and smooth muscle
217
What results from activation of M3 receptors
Bronchoconstriction
Sweating
Salivary gland secretion
218
Where are M4/5 receptors mainly found?
CNS
219
What is Pilocarpine and what is it's function
```
Muscarinic agonist (stimulates)
Stimulates salivation (useful after radiotherapy or in Sjorgens syndrome)
Activates parasympathetic NS
```
220
What can muscarinic agonists be used for in terms of eye disease
Glaucoma
| by facilitating drainage of aqueous humour
221
What is a side effect of muscarinic agonist
Slow the heart
222
Give examples of Muscarinic ANTAgonists
Atropine
| Hyoscine
223
What are uses of muscarinic antagonists like atropine
Prevent bradycardia and BP drop, dry secretions perioperatively
Treat bradycardia induced by excessive doses of beta blockers
Treat bradycardia in cardiac arrest
224
*How is bronchoconstriction treated?
Drugs that block M3 receptor
| Anti-cholinergics or Anti-muscarinics
225
Give an example of a short-acting Anti-cholinergic/anti-muscarinic (e.g. bronchoconstriction)
Ipratropium bromide (Atrovent)
226
Give example of a long-acting anti-cholinergic/anti-muscarinic (e.g. bronchoconstriction)
LAMAs such as Tiotropium, Glycopyrrhonium
227
How can you increase selectivity in treatment of bronchoconstriction?
Choice of drug delivery mechanism e.g. inhalers
| Receptor selectivity e.g. tiotropium relatively selective for M3 receptors
228
What can anti-cholinergic be used for?
Treating bronchoconstriction
| Overactive bladder e.g. Solifenacin
229
How can you open up pupil to allow eye examination
Short acting anticholinergic
230
What can be used to treat irritable bowel syndrome
Mebeverine
| Acts on parasympathetic fibres in intestinal colic and spasm also
231
Why do anticholinergics worsen memory
| Therefore what can be used for dementia treatment
ACh signalling involved in memory
| Acteylcholinesterase inhibitors may be useful for treatment of dementia
232
What can hyoscine be used for
```
Palliative care
Travel sickness (anti-emetic actions)
```
233
What is the major neurotransmitter innervating skeletal muscle
ACh
234
```
True or False:
Botulinum toxin (botox) prevents NAd release
```
False
| prevents ACh release
235
What are uses of botulinum toxin (botox)
Cosmetic
| Anti-spasmodic (inhibiting ACh release to inhibit muscle activity
236
What are uses of nicotinic blockers
induce relaxation in surgery
237
Give example(s) of nicotinic blocker
Pancuronium
| Suxamethonium
238
What happens in myasthenia gravis
Autoimmune destruction of nicotinic ACh receptors which results in muscle weakness
239
What can be given in myasthenia graves to increase signalling?
Anti-acetylcholinesterase
| to increase amount of ACh in the body
240
Add to drug formulary: Suxamethonium
Broken down by acetylcholinesterase and so contraindicated in patients with low level of this enzyme.
Contra-indication of anti-acetylcholinesterase
241
Give side effects of anti-cholinergics
In brain they can worsen memory snd may cause confusion
| Peripherally - can get constipation, drying of the mouth, blurring of vision, worsening of glaucoma
242
Give examples of anti-cholinergics
Tricyclic antidepressants
Some early antihistamines
Some anti-emetics (prochlorperazine)
243
Give examples of cholinergics
Organophosphate insecticides and Nerve gas
244
Give side effects of cholinergics
```
Irreversible acetylcholinesterase inhibitors and so can cause:
Muscle paralysis
Twitching
Salivation
Confusion
```
245
Define catecholamines
Hormones produced by the adrenal glands
246
What are 3 main catecholamines of body
Adrenaline
Noradrenaline
Dopamine
247
What is the precursor of adrenaline and noradrenaline
Dopamine
| noradrenaline -> adrenaline
248
Where can noradrenaline be used in management
Management of shock in the intensive care unit
249
What factors determine the outcome of a signalling pathway
Which receptor
Which cell its on
Which G protein (7 transmembrane GPCR)
250
What are 5 main adrenergic receptors
Alpha 1 and 2
Beta 1 2 and 3
All G-coupled protein receptors
251
*What are effects of alpha 1 agonist
Vasoconsriction
| particularly in skin and splanchnic (abdominal) beds (less so in brain, lungs and heart)
252
What are uses of alpha agonist
Treatment of Septic Shock
| Topical alpha activation in Nasal Decongestion (Xylometazoline)
253
Name an Alpha 2 agonist
Clonidine
| lowers blood pressure
254
Name Alpha Blockers/Antagonists
Doxazosin - blocks alpha 1 to lower blood pressure
Tamsulosin - help treat prostatic hypertrophy, via alpha 1A subtype in prostate
(no useful alpha 2 blockers)
255
*What are effects of Beta 1 agonists
Increase HR and chronotropic effects
| May increase risk of arrhythmias
256
What are effects of Beta 2 agonists and what is use
Muscle relaxation
| Asthma and can delay onset of premature labour
257
Which Beta agonists affect carbohydrate and lipid metabolism
1 and 3
258
What are general side effects of beta agonists
May affect glucose metabolism in liver
| Tachycardia
259
What are Beta 3 agonists used for
Reduce Over-active bladder symptoms
260
Name 2 beta blockers
Propranolol
| Atenolol
261
What adrenergic receptors are blocked by Propranolol
Beta 1 and 2
262
What are effects of Propranolol
Slow Heart rate
Reduce tremor
May cause wheeze
263
What adrenergic receptor is blocked by Atenolol and where are main effects of drug
```
Beta 1 (selective)
Main effects on heart
```
264
How do beta blockers work
Lower blood pressure (by reduction in cardiac output and gradual reduction in central sympathetic outflow activity)
Reduce cardiac work
Treat arrhythmias
265
What are uses of beta blockers
```
Angina
MI prevention
High blood pressure
Anxiety
Arrhythmias
Heart failure
```
266
**Side effects of beta blockers
```
Tiredness
Cold extremities
Bronchoconstriction
Bradycardia
Hypoglycaemia
Cardiac depression
```
267
What are less direct effects of beta blockers
Methyldopa can be used as a last resort antihypertensive - useful in eclampsia or preeclampsia that blocks NAd synthesis
Monoamine oxidase inhibitor (MAOIs) used as antidepressants by preventing NAd breakdown
268
Patient with cardiac disease (angina and occasional atrial fibrillation) - what would you give
Beta 1 blocker e.g. Atenolol
269
What would you give for this patient with:
COPD
Prostatic hypertrophy
Bladder instability
```
COPD (M3 antagonist, B2 agonist) - would hopefully send them home on inhaler
Prostatic hypertrophy (Alpha agonist)
Bladder instability (B3 agonist)
```
270
Patient admitted with pneumonia and septic shock and get wheezy
NAd for septic shock
| Beta agonist for wheezy
271
Patient is penicillin allergy and gets anaphylaxis
Adrenaline
272
Patient has cardiac arrest
Atropine
| for bradycardia
273
What proteins are Alpha-1 adrenoreceptors coupled with?
Gq protein
| Phospholipase C
274
What proteins are Alpha-2 adrenoreceptors coupled with?
Gi (i=inhibit) protein
| in turn inhibits Adenyl cyclase when NAd binds
275
What are effects of alpha-1 adrenoreceptors
Vasoconstriction
Pupil dilation
Bladder contraction
276
What are effects of alpha-2 adrenoreceptors
Presynaptic inhibition of NAd (-ve feedback)
i.e. when blood sugar is low then alpha-2 in pancreas will be stimulated to reduce NAd release, thereby reducing insulin levels being released from the pancreas
277
What proteins are coupled with Beta-adrenoreceptors
All beta-adrenoreceptors use pathway:
Gs protein
Adenyl cyclase
278
What are effects of Beta-1 adrenoreceptor activation
```
Increased FORCE of heart contraction (+ve inotropic effect)
Increased Heart Rate
Increased electrical conduction in heart
Increased RENIN release from kidney
=Increased Blood Pressure
```
279
What are effects of Beta-2 adrenoreceptor activation
Bronchodilation
Vasodilation
Reduced GI motility
280
What are effects of Beta-3 adrenoreceptor activation
Increased lipolysis
| Relaxation of bladder
281
*Define Adverse Drug reaction
Unwanted or harmful reaction following administration of a drug or combination of drugs under normal conditions of use and is suspected to be related to the drug.
282
How much do ADRs cost NHS annually
£466 million
283
How many hospital admissions are caused by ADRs
1 in 20
284
Define a side effect (different to ADR)
An unintended effect of a drug related to its pharmacological properties and can include unexpected benefits of treatment.
285
What is different between each of these:
Side effects
Toxic effects
Hypersusceptibilty effects
```
Side effects (therapeutic range)
Toxic effects (beyond therapeutic range)
Hypersusceptibilty effects (below therapeutic range)
```
286
Give examples of mild ADRs
Nausea
Drowsiness
Itching
Rash
287
Give examples of severe ADRs
Respiratory depression
Neutropenia (low neutrophils)
Catastrophic haemorrhage
Anaphylaxis
288
What % of ADRs occur in hospital inpatients
10-20%
289
What % of ADRs are preventable according to WHO
60%
290
What are social and economic effects of ADRS
Adversely affect patient's quality of life
Cause patients to lose their confidence in drs
Increase costs of patient care
ADRs can mimic disease
291
Give example of primary and secondary ADRs
B-blockers:
Primary adverse effects = Bradycardia and heart block
Secondary pharmacological adverse effect = Bronchospasm
292
What can be used to classify ADRs
ABCDE Rawlins-Thompson
293
What does each letter stand for in ABCDE Rawlins-Thompson
```
Augmented
Bizarre
Chronic
Delayed
End of use
```
294
What is most common type of ADR in Rawlins-Thompson
Type A - Augmented
295
Describe type A adverse drug reaction (Rawlins-Thompson)
Augmented
An extension of the clinical effect
Predictable
Dose-related
Self-limiting
296
Give examples of Type A reactions (Rawlins-Thompson)
Diuretic causing dehydration
Anticoagulant causing bleeding
Drug for hypertension causing hypotension
297
What groups are at increased risk of Type A reaction (Rawlins-Thompson)
Those with renal or hepatic impairment due to elimination difficulties i.e. have high blood plasma levels of the drug for longer
Elderly (above 65) - decreased glomerular filtration and hepatic impairment etc
298
Describe type B adverse drug reaction (Rawlins-Thompson)
Bizarre
Unexpected
Unrelated to dosage and not expected from known pharmacological action
Unpredictable
Mostly immunological mechanisms
Hypersensitivity
Can be seen in drugs that inhibit certain metabolic pathways
Genetically linked
299
Give example of type B ADR (Rawlins-Thompson)
Heparin causing hair loss
300
What groups at at increased risk of type B ADR (Rawlins-Thompson)
Those with predisposing factors such as
| history of allergy, asthmatics and some family history
301
Describe type C ADR (Rawlins-Thompson)
Chronic
Occurs after long term therapy
May not be immediately obvious with new medicines
302
Give example of type C ADR (Rawlins-Thompson)
Diabetes that result from
| Steroids that predispose to hypoglycaemia
303
Describe type D ADR (Rawlins-Thompson)
Delayed
Also occurs after a long period of time (many years) after treatment
Common to see patient having treatment then after 20-30 years they suffer an ADR
304
Give examples of type D ADR (Rawlins-Thompson)
Teratogenesis (congenital malformations in foetus) after taking thalidomide
Neoplasia
305
Describe features of type E ADR (Rawlins-Thompson)
End of use
Relatively long term use (days/weeks)
Withdrawal reactions
Serious complication of stopping related to clinical effect
306
To identify Type A ADR, what would you ask yourself
Augmented
Is it predictable from the mechanism of action?
Does it seem does-related?
307
To identify Type B ADR, what would you ask yourself
Bizarre
| Is there a history of allergy?
308
To identify Type C ADR, what would you ask yourself
Chronic
| Has the patient been using the medication for a long time?
309
To identify Type D ADR, what would you ask yourself
Delayed
| Has the patient uses a drug in the past that could be causing a problem now?
310
*To identify Type E ADR, what would you ask yourself
End of use
| Is the patient withdrawing from a medicine?
311
*In general what makes someone more susceptible to an ADR
```
Age - elderly
Gender - more common in females
Pregnancy - negative effect on baby etc
Disease - liver or renal in particular
Drug interactions
Diet or alcohol intake changes
Genetics
Hypersensitivity
```
312
*What is Type 1 Hypersensitivity
IgE-mediated drug hypersensitivity
| ANAPHYLAXIS
313
*What is Type 2 hypersensitivity
IgG-mediated cytotoxicity
314
*What is Type 3 hypersensitivity
Immune-complex deposition
315
*What is Type 4 hypersensitivity
T-cell mediated
| usually substance containing metals
316
Through what type of hypersensitivity can some drugs cause renal failure?
Type 2
| IgG-mediated cytotoxicity
317
What type of hypersensitivity involves reaction with antibiotics
Type 3 (immune-complex deposition)
318
Briefly describe process of acute anaphylaxis
Prior exposure to antigen (drug)
Virgin B lymphocyte activation to IgE producing plasma cells
IgE become attached to mast cells, expresses cell surface receptors
319
Define idiosyncrasy
Inherent abnormal response to a drug
320
What are causes of idiosyncrasy
Genetic abnormality, enzyme deficiency
| May be due to abnormal receptor activity
321
What is name for an inherent abnormal response to a drug
Idiosyncrasy
322
Describe process of idiosyncrasy from receptor abnormality
Malignant hyperpryrexia (high fever) with general anaesthetics
Sudden huge rise in calcium concentration
Increase in muscle contraction
Increase in metabolic activity
Rise in body temperature
323
Give example of idiosyncrasy as result of enzyme deficinecy
X-linked enzyme deficiency:
Glucose 6 phosphate dehydrogenase (G6PD) enzyme deficiency and give primaquine (drug for malaria).
Primaquine should not be given as leads to haemolytic and haemolytic anaemia.
324
What are most common drugs to have ADRs
```
Antibiotics
Anti-neoplastics
Cardiovascular drugs
Hypoglycaemics
NSAIDs
CNS drugs
```
325
What systems are most likely to be affected by an ADR
```
GI
Renal
Haemorrhagic
Metabolic
Endocrine
Dermatologic
```
326
*Give 6 examples of common ADRs
```
Confusion
Nausea
Balance problems
Diarrhoea
Constipation
Hypotension
```
327
What % of ADRs are avoidable
30-50%
| Inappropriate or Unnecessary medication
328
*What is the MHRA
Medicines and Healthcare products Regulatory Agency
(Government agency) Responsible for approving medicines and devices for use
329
*What is the yellow card scheme
-ADR reporting scheme
Voluntary
-Collects spontaneous reports and suspected adverse drug reactions
-Introduced in 1964 as worlds first ADR reporting scheme
330
What are strengths of Yellow card scheme
- Can work rapidly and is readily accessible.
- *Continual safety monitoring of a product throughout its life span as a therapeutic agent.
- Fairly cheap to operate
- Acts as ‘early warning system’ for identification of previously unrecognised reactions
- Provides information about factors which predispose patients to ADRs
- Allows comparisons of ADR ‘profiles’ between products within same therapeutic class
331
What are weaknesses of yellow card scheme
- *Not all ADRs are reported (only 10% of serious reactions reported)
- Cannot provide an estimate of risk as true number of cases is underestimated and total number of patients exposed is unknown
- Relies on ADR being recognised
- May be stimulated by promotion or publicity
- Reporting high for newly marketed drugs and falls off over time
332
What is meant by the Black Triangle with regards to a drug
Indicates a medicine is undergoing 'additional monitoring'
333
Why are ADR reporting rates low?
Ignorance - not sure how to report
Diffidence - I may appear foolish about reporting a suspected ADR
Fear - may expose myself to legal liability by reporting ADR
Lethargy - too busy to report ADRs
Guilt - I am reluctant to admit I may have caused harm
Ambition - I would rather collect cases and publish them
Complacency - only safe drugs are marketed
334
What are reasons to report ADRs
Important for patient safety
To identify ADRs not identified in clinical trials
To identify new ADRs asap
To compare drugs in the same therapeutic class
To identify ADRs in 'at risk' groups
335
Whats meant by a serious reaction
```
Reaction that..
..is fatal
is life threatening
is disabling or incapacitating
results in hospitalisation
prolongs hospitalisation
```
336
Who can report on a Yellow card
```
Patients
Doctors
Dentists
Coroners
Pharmacists
Nurses (incl midwives and health visitors)
Radiographers
Optometrists
```
337
What pieces of information are needed on Yellow Card
```
Suspected drug(s)
Suspected reaction(s)
Patient details
Reporter details
Additional useful information
```
338
True or False:
| All suspected ADRs for new medicines should be reported
True
339
True or False:
| All ADRs in children should be reported
True
340
What is mast cell degranulation
Cross-linking of IgE receptors releasing acute inflammatory mediators
341
What acute inflammatory mediators are released in mast cell degranulation
Histamine
Thromboxanes, prostaglandins
Tumour Necrosis Factor (TNF)
342
*Describe non-immune anaphylaxis
(Anaphylactoid reactions)
Not caused by IgE antibodies
Due to direct mast cell degranulation
Some drugs are recognised to cause this
No prior exposure
Clinically identical to immune anaphylaxis
343
**Describe the main features of anaphylaxis
```
Exposure to drug, immediate rapid onset
Rash with characteristic blotches
Swelling of lips, face, oedema, central cyanosis (go blue/purple)
Wheeze
Hypotension (anaphylactic shock)
Cardiac arrest
```
344
*Give an alternative presentation of anaphylaxis
Cardiorespiratpry arrest
| No skin changes
345
*Describe management of anaphylaxis
```
Commence basic life support (A airway, B breathing, C circulation)
Specific treatment:
-STOP DRUG if Infusion
-Adrenaline
-IV Anti-histmine
-IV Hydrocortisone (100 to 200mg)
```
346
What are effects of adrenaline (given in management of anaphylaxis)
Vasoconstriction
Bronchodilation
Increased cardiac output
347
What is needed to get drugs circulating if cardiac arrest?
Cardiac massage
348
True or False:
| IV hydrocortisone is likely to cause harm in excess
False
| Iv hydrocortisone unlikely to cause harm in excess so can’t really give too much
349
What dosage of adrenaline is given in management of anaphylaxis
Adrenaline 1mg (10mls of 1:10,000 (IV)), 1ml IV increments
350
Give an example and dose of IV anti-histamine used for management of anaphylaxis
Chlorphenamine (10mg)
351
Give medicine risk factors for drug hypersensitivity
- Protein or polysaccharide based macro molecules e.g. penicillin
- Mono-clonal antibodies (proteins) can cause reactions
352
Give host risk factors for drug hypersensitivity
More common in females compared to males
| Immunosupression
353
Give genetic risk factors for drug hypersensitivity
Certain HLA groups (gene that encodes major histocompatibility complex MHC)
354
*Is Type A ADR a form of allergy
IgE mediated but NO
However some people can be more sensitive to Augmented hypersensitivity e.g. more likely to develop hypotension with anti-hypertensives
355
If suspect ADR, what is procedure
Elicit a full medication history and previous reactions
Check useful sources to find if ADR is described e.g. BNF, eMC, Medicine Information Centres and MHRA
Identify markers
356
What are markers that can be identified for Type A ADR
serum concentration - plasma monitoring
357
What are markers that can be identified for Type B ADR
Tryptase - only released from mast cells
| Urine Methylhistamine - breakdown product of histamine
358
What is the best test to confirm allergy based ADR
Tryptase test
359
If a patient has an ADR, what can be done to prevent further ADR in patient
Continue drug but manage the ADR by other means
Reduce dose of the drug
Stop the drug
360
*Describe management specific to Type A ADRs
Dose-related
May respond to dose-reduction or temporary withdrawal
Severe reactions may require active treatment
361
*Describe management specific to Type B ADRs
Not usually dose-related
SHOULD USUALLY WITHDRAW THE MEDICINE IMMEDIATELY
Give supportive treatment if reaction is severe (e.g. anaphylaxis)
362
*How would you report an ADR
MHRA Yellow-card scheme
363
True or False:
| All suspected ADRs for new medicines should be reported
True
364
True or False:
| All ADRs in children should be reported
True
365
What is difference between Pharmacodynamics and pharmacokinetics
Pharmacodynamics - effect drug has on body
| Pharmacokinetics - what body does with the drug
366
*Pharmacodynamics: what is a summative reaction
Effect of 2 drugs added together
| 1 + 1 = 2
367
*Pharmacodynamics: what is a synergistic reaction
1 + 1 > 2
| Sum of drugs greater than what expect when individually add them together
368
Give examples of synergistic reaction
Clavulanic acid and Amoxil to make Augmentin
| Paracetamol and Codeine to increase analgesic effect
369
*Pharmacodynamics: what is Antagonism
1 + 1 = 0
370
Give example of antagonism (Pharmacodynamics)
Morphine and Naloxone
371
*Pharmacodynamics: what is potentiation
1 + 1 = 1 + 1.5
| Drug A makes Drug B more powerful, but Drug B is not made more powerful by Drug A
372
Give example of Potentiation
Probenicid then Penicillin (increased penicillin in blood)
