Drugs Flashcards
1
Q
Beta Blockers effects
A
- May block beta-adrenoceptors non-selectively or selectively
- During exercise, or stress, RATE, FORCE and CO are depressed
- Reduced maximal exercise tolerance
- Myocardial O2 requirement falls, thus better oxygenation of the myocardium
- Decrease excessive sympathetic drive and help restore normal sinus rhythm
- Delay conduction through AV node and help restore sinus rhythm
- Increase amount of time spent in the diastole, improving perfusion to left ventricle
2
Q
Beta blockers - Used for
A
Used to treat//
- Arrhythmia
- Angina
- Heart failure (compensated, chronic - start low and go slow)
- Hypertension (no longer first line unless comorbidities are present like angina)
3
Q
Beta Blockers - Side effects
A
- Bronchospasm
- Bradycardia
- Hypoglyceamia
- Fatigue
- Cold extremities (beta 2 adrenoceptor mediated vasodilation in cutaneous vessels is prevented)
4
Q
Propranolol
A
- Non selective beta blocker
5
Q
Atenolol
A
Beta-1 selective beta blocker
6
Q
Bisoprolol
A
Beta-1 selective beta blocker
7
Q
Atropine
A
- Non selective muscarinic ACh receptor antagonist
- Increase in HR
- No effect upon arterial BP
- No effect upon response to exercise
Treatment for//
- Severe bradycardia (following M.I.) + monitoring as given cautiously
- In anti cholinesterase poisoning
8
Q
Digoxin
A
- Cardiac glycoside
- Increases CONTRACTILITY of the heart
- Positive inotrope (also dobutamine)
> blocks SARCOLEMMA ATPase
causes increase of Ca2+ in the cell and that is subsequently stores
Increased calcium induced calcium release
INCREASED CONTRACTILITY
> stimulates vagal activity
slows conduction and prolongs refractory period in AV node and bundle of His
> AV Node
> narrow therapeutic window
1.0 - 2.6 nmol/L
Treatment//
- IV in acute heart failure where CO is insufficient in providing adequate tissue perfusion
- Orally in chronic heart failure
- Heart failure with AF
9
Q
Digoxin - side effects
A
- Narrow therapeutic window
- excessive depression of AV node conduction
- can cause arrythmias
- nausea
- vomiting
- diarrhoea
- disturbance of colour vision
- can be dangerously enhanced in hypokalaemia
10
Q
Organic nitrates
A
- relax all types of smooth muscle
- venorelaxation
- arteriolar dilatation
- Blood is redirected towards ischaemic zone in angina
> In angina - benefit derives from decreased myocardial oxygen requirement via
i) decreased preload
ii) decreased afterload
iii) improved perfusion to the ischaemic zone
11
Q
Arterial Pulse Wave Reflection
A
Blood collides with Y shaped junction of artery bifurcation.
Pressure in the other direction (negative pressure wave going back to the heart) – more work for the heart to do.
Organic nitrates decrease this effect
12
Q
GTN (glyceryltrinitrate)
A
> Short acting
Sublingual (as it has extensive first pass metabolism)
more sustained if transdermal patch
Treatment//
- Angina
- Acute coronary syndrome
Tolerance/adverse effects//
- repeated administration of GTN/organic nitrates can lead to diminished effects
- postural hypotension
- headaches
13
Q
Isosorbide Mononitrate
A
- Organic Nitrate
- longer lasting than GTN
- resistant to first pass metabolism
- orally as prophylaxis fro angina
14
Q
Renin release stimulated by
A
- renal sympathetic nerve activity increased
- renal artery hypotension
- decreased sodium delivery to distal tubules of kidney (decreased glomerular filtration)
15
Q
ACE inhibitor (-prils)
A
Block conversion of angiotensin 1 to angiotensin II (Angiotensin Converting Enzyme)
Inhibit metabolism of bradykinin
Cause venous dilatation
Fall in arterial blood pressure
- produces a dry cough
Treatment//
> Hypertension - reduced TPR and MABP
> Cardiac Failure - decreasing vascular resistance
16
Q
AT1 receptor Blockers (ARBs) (-sartans)
A
ARBs block angiotensin II at AT1 receptors in a competitive manner
indicated when patient cannot cope with dry cough associated with ACEIs
17
Q
Bradykinin
A
Vasodilator
causes blood pressure to fall.
18
Q
What are ARBs and ACEIs contraindicated in?
A
Pregnancy
Bilateral renal stenosis
19
Q
Calcium Antagonists
A
Prevent opening of L-type channels in excitable tissues
Limit increase in calcium concentration
Arteriolar dilatation, reducing TPR and MABP
In nodes - can reduce rate of conduction through the AVN
In ventricular AP - can reduce force of contraction
Ventricular rate in rapid AF reduced by suppression of conduction through AV node
Interact preferentially with L-type calcium channels found
> in the heart
> in smooth muscle
20
Q
What do L-type calcium channels mediate?
A
> UPSTROKE of AP in the nodes
> Phase 2 (plateau phase) of ventricular AP
21
Q
Verapamil
A
- Cardiac L-type selective calcium channel antagonist
used for//
hypertension
atrial flutter
cause coronary vasodilation - so suitable for patients with ANGINA and HYPERTENSION
adverse effects//
heart block in high doses
22
Q
Amlodipine
A
Dihydropyridine - relatively selective for smooth muscle L-type calcium channels
Treatment//
Angina
Adverse Effects//
- ankle oedema
23
Q
Diltiazem
A
Intermediate activity calcium antagonist
24
Q
Calcium Antagonists - adverse effects
A
Hypotension
Dizziness
Flushing
Ankle oedema
due to excessive vasodilation
25
Which calcium antagonist should be avoided in heart failure?
Verapamil - particularly in combination with a beta blocker
26
Potassium Channel Openers
Opening of potassium channel causes hyper polarisation - which switches off L-type Calcium channels
Hyperpolarisation - because more positive charge on outside of cell than inside, so membrane potential is very negative.
27
Minoxidil
Potassium channel opener
Drug of last resort in HYPERTENSION
28
What can minoxidil cause?
Reflex tachycardia (can be prevented by a beta blocker)
Salt and water retention
29
Nicorandil
Potassium channel opener
- Used in angina refractory to other treatments
30
alpha1-adrenoceptor antagonists
- cause vasodilation by blocking vascular alpha-1 adrenoceptors
- ↓MABP
PRAZOSIN and DOXAZOSIN
Benign prostatic hyperplasia
Postural hypotension
31
Diuretics
Act on kidneys to increase the excrete of Na, Cl and H2O
Relaxant effects on vasculature
Thiazide and Loop diuretics
32
Thiazide diuretics
Inhibit NaCl reabsorption in the distal tubule by blocking the Na+/Cl- co-transporter
Cause up to 5% of filtered Na+ to be excreted along with H20 producing a moderate diuresis
33
Loop Diuretics
Inhibit NaCl reabsorption in the thick ascending limb of the loop of Henle by blocking the Na+/K+/2Cl- co-transporter
Cause up to 15-25% of filtered Na+ to be excreted with accompanying H20 producing a strong diuresis
34
What undesirable effect do diuretics have, and how can this be corrected?
Loss of potassium.
corrected by potassium sparing diuretic/ K+ supplements
35
Bendroflumethiazide
Thiazide diuretic
- Mild heart failure
- Hypertension
- Severe resistant oedema (+ loop)
36
Furosemide
Loop diuretic
acute pulmonary oedema IV)
Chronic heart failure
37
In vascular smooth muscle, how does contraction come about?
- GPCR activation promotes release of Calcium from sarcoplasmic reticulum
- Calcium combines with Calmodulin to form Ca2+-calmodulin
- Ca2+-Cal activates Myosin light chain kinase
- MLCK then phosphorylates myosin light chain
- ---> CONTRACTION
38
Relaxation in vascular smooth muscle cells?
- cyclic GMP promotes the activation of protein kinase G (PKG)
- PKG activates Myosin light chain PHOSPHATASE
- This dephosphorylates myosin light chain leaving myosin light chain
- RELAXATION
39
Anti-arrhythmic drugs
4 classes, 1 is split into 1a, b and c
Classes I: Ia, Ib, Ic
II
III
IV
40
Class Ia
Block voltage-activated Na+ channel
Slow rise of AP and prolong refractory period
Act on VENTRICLES, ATRIA, AV accessory pathways
Moderate rate of dissociation
41
Class Ib
Block voltage-gated Na+ channel
Prevents premature beats
Act on VENTRICLES
Rapid rate of dissociation
42
Class Ic
Voltage activated Na+ channel
Slow rate of dissociation
Act upon ATRIA, Ventricles and AV accessory pathways
Depress conduction
43
Disopyramide
Class Ia anti-arrhythmic
Moderate rate of block and unblock
Block open channels
If AP frequency is high, moderate dissociation results in insufficient time for blocking and unblocking
Used to prevent recurrent ventricular arryhthmias
44
Lignocaine
Class Ib anti-arrhythmic
rapid block/dissociation
prevents premature beats
45
Flecainide
Class Ic anti-arrhythmic
slow rate of block and unblock
strongly depresses conduction in myocardium and reduces contractility
Prophylaxis of paroxysmal atrial fibrillation
Negative inotropic action - may trigger ventricular arryhthmias
46
Class II
Beta-adrenoceptor antagonist (beta blockers)
Control SVT by suppressing impulse conduction through AV node
Suppress excessive sympathetic drive that may trigger VT
decrease rate of depolarisation in SA and AV nodes
Act on VENTRICLES and AV node
47
Class III
Voltage-activated K+ channels BLOCKERS
Prolong AP duration increasing refractory period
Act upon ATRIA
48
Class IV
Voltage Activated Ca2+ channels
Slow conduction in SA and AV nodes
Act on AV NODE
Decrease force of cardiac contraction
49
Amiodarone
Class III anti-arrhythmic
Potassium channel blocker
Prolongs the AP
Increases refractory period
suppresses reentry
effective against SVT and VT as it has Ia and IV actions and also blocks beta adrenoceptors
Effective when many other drugs have failed
Adverse effects//
- pulmonary fibrosis
- thyroid disorders
- photosensitivity reactions
- peripheral neuropathy
50
Where do class I agents bind?
They preferentially bind to areas of myocardium in which firing frequency is highest.
Channels which are in the OPEN and INACTIVATED states
51
Adenosine
>Activates A1 adenosine receptors coupled to Gi/o
-- opens ACh-sensitive K+ channels
-- Hyperpolarises the AV node briefly, suppressing impulse conduction
-- Used to terminate paroxysmal supraventricular tachycardia caused by re-entry
Acts upon AV node
52
Anticoagulants
>Treatment of venous thrombosis and embolism
- -DVT
- - Prevention of post-op thrombosis
- - patients with artificial valves
Risk of haemorrhage
53
Warfarin
> Anticoagulant
> Competes with vitamin K for binding hepatic vitamin k reductase
> renders factors II, VII, IX and X inactive
> Oral
> Slow onset of action
Disadvantages//
> low therapeutic index
> Effects of warfarin must be monitored regularly
54
LMWHs
```
> Anticoagulant
> Inhibit factor Xa via antithrombin III
> SC
> Elimination is of first order
> Renal excretion - so not used in renal failure
```
55
Enoxaparin
LMWH
Anticoagulant
given SC
not used in renal failure
56
Dalteparin
LMWH
Anticoagulant
Given SC
Not used in renal failure
57
Fondaparinux
LMWH
Anticoagulant
Given SC
Inactivates Xa via antithrombin III
Short duration of action
Not used in renal failure
58
Idrabiotaparinux
LMWH
Anticoagulant
Long duration of action
59
Heparin
Anticoagulant
Inactivates Thrombin (IIa) via antithrombin III
Inactive Xa via antithrombin III
Administered IV or SC
In vitro clotting test required to determine dosage
Zero order elimination
Used in renal failure (is not excreted renally)
60
LMWHs and Heparin - Adverse effects
> Haemorrhage
> Osteoporosis
>Hypoaldosteronism
> Hypersensivity reactions
61
Dabigatran
- what does it directly inhibit?
Orally active inhibitor (anticoagulant)
Direct inhibitor of THROMBIN (IIa)
Convenience of administration
Predictable degree of anticoagulation
Prevent venous thrombosis (hip and knee replacements)
No antidote in case of overdose
62
Rivaroxaban
Orally active inhibitor (anticoagulant)
Directly inhibits Factor Xa
Taken orally - convenient
Predictable degree of anticoagulation
Used to prevent venous thrombosis in hip and knee replacements
No antidote in case of overdose
63
"Antidote" for heparin?
Protamine sulfate
64
Anti-platelet Drugs
Treatment of arterial thrombosis
65
Aspirin
> Antiplatelet (main one)
> Irreversibly blocks cyclooxyrgenase (COX) in platelets, preventing TXA2 synthesis
> Inhibits COX in endothelial cells inhibiting production of anti-thrombotic prostaglandin I2
- anti-thrombotic effect
>THROMBOPROPHYLAXIS
> Used in ACUTE MI
66
Clopidogrel
> Antiplatelet drug
> Prodrug requiring hepatic metabolism
> Links to P2Y12 receptor producing irreversible inhibition
> Used when patient is INTOLERANT to aspirin
> Has synergistic effect when combined with aspirin
> Used in Acute MI with ST elevation
67
Tirofiban
> Antiplatelet
> Given IV
> Short term treatment to prevent M.I. in high risk patients WITH angina (+ aspirin and heparin)
68
Fibrinolytics (thrombolytic)
> Opposes coagulation cascade
> Used to reopen occluded arteries in acute M.I. or stroke
> IV administered
> PCI is superior if available
Adverse effects//
haemorrhage
69
Streptokinase
> Fibrinolytic
> May cause allergic reaction
> Extracted from cultures of streptococci
> Reduces mortality in acute M.I.
70
Alteplase (and duteplase)
> FIbrinolytics
> Show selectivity for clots
> No allergic reactions
> IV infusion
71
Haemorrhage caused by fibrinolytics can be controlled by?
Oral TRANEXAMIC ACID - inhibits plasminogen activation
72
Antithrombin III
> ATIII inhibits coagulation
> Neutralises all serine proteases (Xa, IXa etc) in coagulation cascade
> Heparin binds to ATIII, increasing its affinity for clotting factors to greatly increase their inactivation (hence less coagulation)
73
Proton Pump Inhibitors
Irreversible inhibition by covalent modification of the gastric gland parietal cell H+/K+-ATPase (the ‘proton pump’) present in the apical (canalicular) membrane.
Treatment of peptic ulcer disease
Dyspepsia
Eradication of H pylori
74
Omeprazole
PPI
Treatment of peptic ulcer disease
Dyspepsia
Eradication of H pylori
75
Lansoprazole
PPI
76
What is used to eradicate H pylori?
Omeprazole + amoxicillin/ metronidazole/ clarithromycin
77
Side effects of PPIs
Headache, diarrhoea, abdo pain, nausea, fatigue, dizziness
78
What should not be used in peptic ulcer disease?
NSAIDs
79
H2 receptor antagonists
Ranitidine
Competitive antagonism of the H2 receptor located on the basolateral membrane of acid secreting parietal cells of the gastric glands
Reduces gastric acid production
Less effective than PPIs
80
Ranitidine
H2 receptor antagonist
Reduces gastric acid secretion
81
What may histamine receptor antagonists and PPIs disguise?
The symptoms of gastric cancer
82
Anti-motility drugs
Overall effect is constipating
> Treatment of acute diarrhoea
> Symptomatic relief of diarrhoea (IBS)
> Analgesia for acuter, moderate pain (codeine)
83
Loperamide
Anti-motility
84
Do not use anti-motility drugs in...
> Acute ulcerative colitis
> Acute bloody diarrhoea
> Clostridium difficile colitis
85
Bulk forming laxatives
i) Used for constipation and faecal impaction. Viral/bacterial gastritis
ii) Mild chronic diarrhoea
do not use in intestinal obstruction
indigestible polysaccharide
86
Methylcellulose
Bulk forming laxatives
87
Osmotic Laxatives
Water is attracted to the stool, increasing the bulk and stimulating peristalsis
1) Constipation and faecal impaction
2) Bowl prep
3. Hepatic encephalopathy
Do not use in intestinal obstruction
88
Lactulose
Osmotic laxative
89
Macrogols
Osmotic laxative
90
Stimulant laxative
Increase water and electrolyte secretion from the colonic mucosa. Colonic content is increased stimulating peristalsis
1) Constipation (PO)
2) Faecal impaction (suppository)
91
Senna
Stimulant laxative
92
Glycerol suppository
Stimulant laxative
93
Faecal softners
Detergent-like action.
Arachis oil (enema)
Docusate sodium
Increased H2o and electrolyte secretion, increased peristalsis.
94
Dopamine D2 Receptor Antagonist
Antiemetic
Nausea and vomiting associated with neoplastic disease; radiation sickness and drug induced emesis.
```
Prochlorperazine
Droperidol
Trifluoperazine
Chlorpromazine
Haloperidol
Levomepromazine
```
95
Prokinetic drugs
Metoclopramide (antiemetic, GORD, migraine)
DOMPERIDONE (does not cross the BBB)
Increase gastric peristalsis
Increase LOS tone
Block D2 receptors in CTZ
96
5HT3-receptor antagonists
-SETRONS
Granisetron
Ondansetron
Palonosetron
Block 5HT3 receptors in the GI tract and CNS
Chemotherapy induced N&V
Radiation induced emesis
Post-op N&V
97
H1 Antihistamine
Promethazine
Cyclizine
Cinnarizine
Block H1 receptors in vestibular nuclei and NTS (nucleus tracts solitarius)
Additional anti-muscarinic effect
Useful in motion sickness, morning sickness, post op N&V
98
Anticholinergics
Hyosine
Dycyclomine
Block muscarinic receptors in vestibular nuclei, NTS and vomiting centre
Motion sickness
99
Predominant receptors in vomiting centre?
Muscarininc M1 & 3
5HT3
H1
100
Predominatn receptos in CTZ?
Dopamine (D2)
5ht3
Opioid H1
outside BBB
more permeable to circulating substances
101
Receptors in vestibular nuclei?
Muscarinic
| Histamine type 1
102
Adjuvant antiemetics
Role in Chemo-indcued nausea and vomiting
103
NK1 (neurokinin 1) receptor antagonist ( adjuvant antiemetics)
Aprepitant
| Antagonism of substance P
104
Corticosteroids as adjuvant antiemetics
Dexamethasone
| Methylprednisolone
105
Benzodiazepines
Lorazepam
Diazepam
Sedative, anti-anxiety, amnesia-inducing
Unpleasant memories of chemo. These drugs bring about a state of forgetfulness so they have fewer memories and do not want to vomit pre-chemo.
106
Cannabinoids
Nabilone
Dronabinol
sedation, hallucinogenic
107
Drugs for IBD
> Aminosalicylates
> Glucocorticoids
> Immunosuppressants
> Biological agents
108
Aminosalicylates
Long term maintenance of remission of IBD
More useful in UC
109
Sulfasalazine***
Aminosalicylate
5-ASA
reduces inflammation by inhibiting COX and LOX
Folic acid supplementation
110
Mesalazine
aminosalicylate
111
Olsalazine
Aminosalicyalate
112
Balsalaside
Aminosalicylate
113
IBD- glucocorticoids
Anti-inflammatory
For acute UC and Crohn's
Prednisolone, Budesonide
Hydrocortisone
for acute flare ups
114
Immunosuppressants in IBD
For disease that is unresponsive to corticosteroids
inhibit t lymphocyte function
Azathioprine***
Ciclosporin]
6 mercaptopurine
Methotrexate
115
Biological agents in IBD
Monoclonal antibodies
Restricted to severe IBD
Block action of TNF alpha (except vedolizumab)
Infliximab
Adalimumab
any "-mab"
116
What is C diff colitis treated with?
Metronidazole
| Vancomycin
117
Opioid Drugs in GI
Constipating effect.
```
Decreased peristalsis
increased segmentation
increased fluid absorption
constriction of pyloric, ileocaecal and anal sphincters
increased tone of large intestine
```
118
Loperamide
Opioid
| one of the main ones
119
Diphenoxylate
Opioid
Overdose produces disturbing side effects - nausea, headache, weakness, blurred vision.
120
Codeine
Opioid
121
Ursodeoxycholic Acid
May be used to dissolve non-calcified cholesterol gall stones
122
Bile salt resins
Prevent reabsorption of cholesterol and lower plasma cholesterol
123
Morphine
Opioid analgesic
Constricts the sphincter of oddi
Buprenorphine and pethidine are alternatives
124
Atropine, or GTN
Biliary spasm relief
125
Chemo Induced N&V Triple Therapy
5HT3 receptor antagonist
Dexamethazone
Aprepitant
126
Post-op nausea & vomiting
5HT3 receptor antagonist
Droperidol
Cyclizine
Dexamethazone
127
Pregnancy Associated N&V
caused by?
Caused by Human Chorionic Gonadotropin (placenta)
Change in diet
Use of ginger and pyridoxine
Wrist acupressure
128
Hyperemesis Gravidarum
Intractable vomiting from pregnancy
1st line - Antihistamine
2nd line - Prochlorperazine, Metoclopramide
129
When to use immunosuppressants in IBD?
For disease that is unresponsive to corticosteroids
