Pharmacology Flashcards
1
Q
Define
- Pharmacodynamics
- Pharmacokinetics
A
- What the drug does to the body
- What the body does to the drug
2
Q
What are the 4 main types of Cellular targets ??
A
- Ion channels (agonist/ antagonist)
{eg. local anaesthetics (works on voltage gated Na+ channels)} - G protein coupled receptors (produce action through 2nd messengers such as cAMP) eg. Adrenoreceptors
- Tyrosine Kinase receptors (eg. Insulin)
- Nuclear receptors (located within nucleus & drug MUST be Lipid soluble) eg. Prednisolone, levothyroxine
3
Q
Types of Antagonists ??
A
Competitive (binds to the same site of the agonist==> prevents agonist from binding)
Non- competitive (Antagonist occupies another site==> this causes conformational change in binding site of agonist)
4
Q
What is Efficacy ??
A
-Maximal effect a drug can produce (intrinsic activity)- represented by ‘y-value’ (Vmax)
increase in y-value= increase Vmax= Increase Efficacy
- Efficacious drugs can have high/low Potency
5
Q
What is Potency ??
A
Amount of drug needed for a given effect - represented by x-value (EC50)
- Left shift= decrease EC50= Increase potency= lower drug needed
- Unrelated to Efficacy ie. Potent drugs can have high or low efficacy
6
Q
What is Zero-order elimination ??
A
“Metabolism INDEPENDENT of conc. of drug”
Rate of elimination is constant regardless of Cp (Constant amount of drug eliminated per unit time)
{Due to Saturation of Met. processes}
- Cp decreases LINEARLY with time
eg- Phenytoin, Ethanol & Aspirin (Salicylates), Heparin
PEA H
7
Q
What is 1st order elimination ??
A
Elimination is directly proportional to Drug conc. (constant amount of drug eliminated per unit time)
- Cp decreases EXPONENTIALLY with time
- Applies to most drugs
8
Q
Give eg. for
- Capacity limited elimination
- Flow limited elimination
A
- Zero-order elimination (PEA H drugs)
- First-order elimination
9
Q
In how many phases are drug eliminated ??
A
Phase 1 & Phase 2 (occurs in LIVER)
- Geriatric pts. lose Phase 1 first
- Slow acetylators ==> decreased rate of metabolism == increase S/E
10
Q
Hallmark of Phase 1 ??
A
- Lipophilic drugs undergo phase 1
- CYP450 predominance
- has 3 steps (REDUCTION, OXIDATION, HYDROLYSIS)
- Leads to the formation of Toxic Metabolites { Slightly polar metabolite (active or inactive) & ROS metabolites}
11
Q
Hallmark of Phase 2 ??
A
- Polar drugs (H2O soluble) undergo phase 2
- 4 steps (METHYLATION, GLUCURONIDATION, ACETYLATION, SULFATION)
- Inactive Metabolites {Very polar, hydrophillic metabolite produced (EXCEPT Acetylated metabolites)}
- Excretion: Serum (urine, sweat), Bile (stools)
12
Q
Name the drugs which act on Serotonin receptors (Agonists & Antagonists)
A
- 5-HTr (+) used in Migraine (ACUTE Rx.) eg. Sumatriptan, Ergotamine [partial (+)]
- 5-HTr (-) used in Migraine (PROPHYLAXIS) eg.- Pizotifen [5-HT2 r (-) used in migraine prophylaxis]
13
Q
Anti-diarrhoeal drug used in Carcinoid synd. ??
A
CYPROHEPTAHDINE [5-HT2 r (-)]
14
Q
MoA of Ondansetron ??
A
5-HT3 r (-) used as Anti-emetic
15
Q
What should we monitor in pts. on Statins ??
A
LFT (Baseline, at 3 months & at 12 months)
16
Q
What should we monitor in pts. on Amiodarone ??
A
LFT, TFT, U&E, CXR - PRIOR to Rx.
LFT & TFT every 6 months
17
Q
What should we monitor in pts. on Digoxin ??
A
ECG, U&E at least 6 hrs. post-dose
18
Q
What should we monitor in pts. on MTX ??
A
FBC, LFT & U&E
- Prior to Rx.
- Weekly until Rx. stabilised
- Every 2 to 3 months after stabilizing
19
Q
What should we monitor in pts. on Azathioprine ??
A
- FBC, LFT before Rx.
- FBC weekly for the 1st 4 wks.
- FBC, LFT every 3 months
20
Q
Lithium Monitoring ??
A
Lithium levels
- T range : 0.4 to 1.0 mmol/l
- 12 hrs. post-dose
- Weekly until stabilized
- 3 monthly after stabilizing
TFT, U&E before Rx. & Every 6 months
21
Q
What should we monitor in pts. on Sodium Valprote ??
A
- LFT, FBC before Rx.
- LFT “PERIODICALLY” during 1st 6 months
22
Q
What should we monitor in pts. on Glitazones ??
A
LFT
- Prior Rx.
- ‘Regularly’ during Rx.
23
Q
For which drugs do we check the Trough levels immediately before Rx.
A
Ciclosporin
Phenytoin (checked before dose ONLY if
- Dose adjustment done
- Suspected TOXICITY
- NON-ADHERENCE detected
24
Q
Which drugs have a narrow Therapeutic Index (TI) ??
A
“Warning These Drugs Are Lethal”
- Warfarin
- Theophilline
- Digoxin
- Anti-epileptics
- Lithium
25
Drugs which INDUCES Cytochrome P450 ??
"Ind. - CRAP2 MNGs2"
- Carbamazepine
- Rifampin
- Alcohol (CHRONIC)
- Phenytoin
- Phenobarbital
- Modafinil
- Nevirapine
- Griseofulvin
- St. John's wort
- Smoking (affects CYPIA2, therefore higher doses of Aminophilline needed)
26
Drugs which INHIBITS Cytochrome P450 ??
2SICK F2(AC)ES ROGQ
- Sodium Valproate
- Sulfonamides
- Isoniazid
- Cimetidine
- Ketoconazole
- Fluconazole
- Alcohol (ACUTE overuse)
- Chloramphenicol
- Ciprofloxacin
- Erythromycin/ Clarithromycin
- SSRIs- Fluoxetine, Sertraline
- Ritonavir
- Omeprezole
- Grapefruit juice
- Quinupristine
27
Give examples of Sulfa drugs and their S/E
"Scary Sulfa Pharm FACTS"
- Sulfonamide ABx.
- Sulfonamides
- Probenecid
- Furosemide
- Acetazolamide
- Celecoxib
- Thiazides
- Sulfonylureas
28
Which drugs are affected by Acetylator status ??
50% of UK population are Hepatic-N-Acetyltransferase deficient.
DHIPS
- Dapsone
- Hydralazine
- Isoniazid
- Procainamide
- Sulfasalazine
29
Through which pathway does Adrenoreceptors work ??
All are G-protein coupled
- Alpha 1: activate Phospholipase C --> IP3 --> DAG
- Alpha 2: Inhibits Adenylate cyclase
- Beta 1, 2, 3: Stimulates adenylate cyclase
30
Give examples of Alpha & Beta r AGONISTS
Alpha 1- PHENYLEPHRINE
Alpha 2- CLONIDINE
Beta 1- DOBUTAMINE
Beta 2- SALBUTAMOL
Beta 3- being developed (stimulates LIPOLYSIS)
31
Give eg. of Alpha & Beta ANTAGONISTS
Alpha 1- DOXAZOSIN
Alpha 1a- TAMSULOSIN (acts mainly on Uro-genital tract)
Non-Selective- PHENOXYBENZAMINE (was previously used in PAD)
Beta 1- ATENELOL
Non-Selective- PROPRANOLOL
32
Which drugs have MIXED alpha & beta ANTAGONISM ??
CARVIDILOL & LABETELOL
33
What is the dose of ADRENALINE in
- Anphylaxis ??
- Cardiac arrest ??
It is a SYMPATHOMIMETIC Amine with both alpha & beta stimulating actions
- 0.5ml 1:1000 (IM)
- 10ml 1:10000 (IV) or 1ml 1:1000 (IV)
34
How to manage accidental injection of Adrenaline ??
Local infiltration of PHENTOLAMINE
35
Beta blocker overdose Rx. ??
Bradycardia - ATROPINE
Resistant cases - GLUCAGON
36
Types of CCBs ??
Acts on Voltage gated Ca2+ channel present in Myocardial cells, Conduction system, Vascular SM
Non-Dihydropyridines ("ND is VD")
- Verapamil
- Diltiazem
Dihydropyridines
- Nifedipine, Amlodipine, Felodipine
37
Difference b/w the 2 types of CCBs ??
BOTH acts on Voltage-gated Ca2+ channels
Non- Dihydropyridines
- acts on both HEART [(-ve) Ionotrophic Verapamil >>>Diltiazem] & Vascular SM
Dihydropyridines
- acts more on Peripheral vascular SM than the heart (so, they do not worsen HF)
38
Imp. S/E of Ergot derived DA r agonists ??
Bromocriptine, Cabergoline, Pergolide
- Pulm., Retroperitoneal, Cardiac FIBROSIS
39
What is Oculogyric Crisis ??
Dystonic reaction to certain drugs/ medical condition
- Restless + Agitated + Involuntary UPWARD deviation of eyes
40
How dose the following occur:
- Mydriasis ??
- Miosis ??
- Alpha 1 r mediated; RADIAL muscle contraction
- M3 r mediated; Sphincter muscle contraction
41
What drugs cause MYDRIASIS ??
- Anti-Cholinergics: Atropine, TCAs, Tropicamide, Scopalamine, Antihistamines
- Sympathomimetics: Indirect (Amphetamines, Cocaine, LSD)
ACL
42
What drugs cause MIOSIS ??
Sympatholytics: Alpha 2 (+), Opioids except Meperidine
Parasympathomimetics: Pilocarpine, Organophospates
43
Hallmark feature of Salicylate poisoning ??
Hyperventilation, TINNITUS, pyrexia, N & V, sweating
Children: Met. Acidosis predominates
44
Rx. of Salicylate poisoning ??
- ABC, Charcoal
- Urinary Alkalinization + IV (NaHCO3)
- Haemodialysis
45
How to differentiate Aspirin poisoning from Cinchonism ??
CNS c/f- Tinnitus, Deafness, Visual defects are
- Transient in Aspirin poisoning
- Permanent in Quinine toxicity
46
Indication of Haemodialysis in Salicylate poisoning ??
S conc. > 700 mg/L
Met. Acidosis resistant to Rx.
Acute Renal F
Pulm. Edema
Seizures
Coma
47
PCM metabolic pathway ??
Normally PCM conjugates with GLUCORONIC Acid/Sulphate
- Overdose==> Saturated conjugation system==> Oxidation by P450 mixed func. oxidases occurs==> N-Acetyl-B-Benzoquinone produced (toxic metabolite)
Normally, GLUTATHIONE conjugates with NABBq to form MERCAPTURIC Acid (non toxic)
- Glutathione stores run out==> NABBq forms Covalent bond with cell protein==> Denatures, Cell death
This process occurs in HEPATOCYTES & Renal TUBULES
48
What is the King's College Hospital criteria for Liver transplantation ??
Arterial pH < 7.3 (or) ALL of the following
- Prothrombin time > 100 sec.
- Grade III or IV Encephalopathy
- S Cr. > 300 umol/l
49
Indication to start N-Acetyl Cysteine in PCM overdose ??
NAC is the precursor of Glutathione (increases its hepatic production)
- Staggered overdose (all tab. NOT taken within 1 hr.)
- Doubt over time of PCM intake
- Plasma PCM conc. on/above a single Rx. line [100mg at 4 hrs & 15mg at 15hrs]
50
TCA overdose C/F ??
Early- Anti-cholinergic prop. (Dry mouth, MYDRIASIS, agitated, sinus tachycardia, blurred vision)
Arrhythmias
Seizures
Met. Acidosis
Coma
51
ECG changes seen in TCA overdose ??
Sinus Tachycardia
QT interval prolonged
QRS widening
- >100ms: increased risk of SEIZURES
- > 160ms: VENTRICULAR Arrhythmias
52
St. John's Wort ??
similar to SSRI's & also has NE uptake inhibition
- as effective as TCAs in Rx. of Mild-moderate depression
53
OP poisoning
- MoA
- C/F
OPs (-) Acetylcholineesterases==> Upregulates NICOTINIC & MUSCARINIC Cholinergic neurotransmission ==> SLUD c/f
- Salivation
- Lacrimation
- Urination
- Defecation/ Diarrhoea
- Hypotension, Bradycardia
- MIOSIS
54
Rx. of OP poisoning ??
ATROPINE
Pralidoxime (role unclear)
55
Carbon Monoxide poisoning effect on O2 dissociation curve ??
- Left shift & Tissue Hypoxia
- O2 sats. of Hb decreases ==> EARLY Plateau in the curve
56
What are the typical CarboxyHb levels ??
< 3% in Non-Smokers
3 to 10% in Smokers
10 to 30% - Headache, N & V
> 30% - Severe toxicity
57
Indication of Hyperbaric O2 therapy in CO poisoning ??
- CNS signs other than Headacha
- Cardiac Ischaemia
- LoC at any time
- Arrhythmia
- Pregnancy
58
How does Cyanide poisoning occur ??
It is used in Insecticides, Photograph devt. & Metal production
It (-) Cytochrome C Oxidase enzyme ==> cessation of Mitochondrial electron chain transfer
59
C/F & Rx. of Cyanide poisoning ??
BRICK-RED skin, BITTER Almond smell
- Acute: Hypoxia, Hypotension, Headache, Confusion
- Chronic: Ataxia, Peripheral neuropathy, Dermatitis
ABCs
(IV) Hydroxocobalamin, also,
Amyl nitrite (inhaled) + Na nitrite (IV) + Na Thiosulfate (IV)
60
What injury is MC seen with the ingestion of
- Strong Alkali ??
- Strong Acid ??
- Oesophagus (LIQUIFACTIVE Necrosis)
- Gastric (COAGULATIVE Necrosis)
61
CI of use of FLECAINIDE ??
- Post- MI
- STRUCTURAL HEART Disease (eg. HF)
- SAN dysfunction (2nd degree/ greater AV block)
- ATRIAL FLUTTER
62
Indications & S/E of Flecainide ??
AF
SVT a/w Accessory pathway (WPW)
S/E
- Negatively Inotropic
- Bradycardia
- Proarrhythmic
- Oral paraesthesia
- Visual disturbances
63
What is Amiodarone induced Hypothyroidism ??
High Iodine content of Amiodarone causes WOLFF-CHAIKOFF effect (Temporary protective mechanism of the thyroid gland that protects it from excessive iodine level)
- Amiodarone can be continued if desirable
64
What is Amiodarone induced Thyrotoxicosis ??
2 types
- AIT type 1: Excess Iodine induced synthesis of thyroid. Goitre is PRESENT
- AIT type 2: Drug related destructive thyroiditis. Goitre is ABSENT
65
What is the Rx. of
- Amiodarone Induced Thyrotoxicosis type 1 ??
- AIT type 2 ??
- Carbimazole or K+ perchlorate
- AIT type 2:- Corticosteroids
Unlike in AIH, the drug has to be STOPPED IF possible in pts. with AIT
66
What is Digoxin ??
Cardiac gylcoside (Mainly used in RATE Control in AF)
67
MoA of Digoxin ??
- Decrease conduction via AV Node==> Slows VENTRICULAR Rate in AF & Flutter
- Increases myocardial force of contraction via (-) of Na+/K+/ATPase pump
- Stimulates VAGUS nerve
68
What is a hallmark feature about Digoxin toxicity ??
Toxicity is not dependant solely on drug plasma conc. as it can also occur within therapeutic range
Likelihood of toxicity rises progressively from 1.5 to 3 mcg/l
69
Features of Digoxin toxicity ??
Lethargy, N & V, Anorexia
- YELLOW-GREEN Vision, Confusion
- GYNAECOMASTIA
- Arrhythmias (AV block, Bradycardia)
- REVERSE Check/ Tick sign on ECG
70
What are the ppt. factors of Digoxin toxicity ??
- HYPOKALAEMIA (digoxin binds to ATPase pump on the same site as K+) in hypo-K+, Digoxin more easily binds to the ATPase pump==> increased inhibitory effect
- Hypo-Mg2+, Hypoalbuminaemia
- Hyper Ca2+, Hyper Na+
- Acidosis
- Hypothermia, Hypothyroidism
- Increasing age
- Renal failure
- MI
71
Rx. of Digoxin toxicity ??
DIGIBIND
- monitor K+
- correct Arrhythmias
72
What ppt. Lithium toxicity ??
- Dehydration
- Renal Failure
Drugs
- Diuretics (specially THIAZIDES)
- ACEi/ ARBs
- NSAIDs
- Metronidazole
73
Lithium toxicity Rx. ??
Mild to moderate: Vol. resuscitation with NS
Severe: Haemodialysis
74
What are 2 possible types of Penicillin allergies ??
- Intolerance/ Side Effect: eg. Diarrhoea
- Coincidental rash: eg. Amoxicillin in pts. with Infectious Mononucleosis
75
Which Cephalosporins can be used in pts. with H/o Penicillin allergy ??
- Use with Caution: Cefixime, Cefotaxime, Ceftazidime, Ceftriaxone
Avoided are- Cefaclor, Cefadroxil, Cefalexin, Cefradine, Ceftaroline fosamil
76
Types of Penicillins ??
Phenoxymethylpenicillin
Benzyl P
Flucloxacillin
Amoxicillin
Ampicillin
Co-amoxiclav
Co-fluampicil (Magnapen)
Piperacillin with Tazobactam
Ticarcillin with Clavulanate
77
What are the types of Heparin & their MoA ??
Both work by Antithrombin III activation
- Uf-H: forms complex with AT III ==>(-)Thrombin, 9a, 10a, 11a, 12a
- LMWH: forms complex with AT III ==> (-)10a
78
What is HIT ??
Immune mediated Thrombocytopaenia (> 50% decrease in Plts.)
- Antibodies are formed against Plt. factor 4 (PF4) & Heparin ==> these antibodies bind to [PF4-H] complex on Plt. surface ==> activates Platelets [by cross linking with FcyIIA receptors]
79
Risks involved with Aspirin use ??
- NOT used in < 16 yrs (risk of Reye's synd.)
- Exception is KAWASAKI disease - aspirin can be used.
It POTENTIATES the following drugs
- OHAs
- Warfarin
- Steroids
80
MoA of Aspirin ??
Cyclooxygenase- 1 & 2 inhibitor
COX is responsible for syn. of PGs, Prostacyclins, Thromboxane A2 (required for Plt. aggregation)
81
Features of HIT ??
- > 50% fall in plts., Thrombosis, Skin allergy
- NOT developed until 5 to 10 days of Rx.
82
Rx. of Heparin overdose ??
PROTAMINE SULFATE
[this only PARTIALLY reverses the LMWH effect]
83
S/E of Heparin ??
Uf-H : Bleeding, HIT, Hyper-K+, OSTEOPOROSIS
LMWH : Bleeding, Lower risk of HIT & Osteoporosis
84
How is Heparin monitored ??
Uf-H : APTT
LMWH : Anti-Factor 10a
85
Mention indications of Immunoglobulins
- Primary & Secondary immunodeficiency
- ITP, MG, GBS
- Kawasaki disease
- Toxic Epidermal Necrolysis
- Pneumonitis due to CMV post transplantation
- Dermatomyositis
- Chr. Inflam. Demyelinating Polyradiculopathy
86
What are the types of K+ sparing diuretics ??
Epithelial Na+ channel blockers at DCT
- Amiloride
- Triamterene
Aldosterone antagonist (at Collecting duct)
- Spironolactone
- Eplerenone
87
Amiloride indications ??
Weak diuretic given with Thiazide/ Loop diuretics as an alternative to K+ supplementation
88
Indication of Spironolactone ??
- Ascites (secondary to cirrhosis due to hyperaldosteronism, large doses 100 or 200 mg used)
- Heart Failure
- Nephrotic Synd.
- Conn's Synd.
Should be used in caution when ACEi is used (Hyper-K+)
89
Indications of Botox ??
- Blepharospasm
- Hemifacial spasms
- Focal spasticity (CP, Stroke)
- Spastic Torticollis
- Severe HYPERHIDROSIS of Axillae
- Achalasia
90
What is Motion Sickness ??
Apparent discrepancy exists b/w VISUALLY perceived movt. & VESTIBULAR systems sense of movt. ==> N & V
Rx.
- HYOSCINE (transdermal patch) most effective
- Non-sedating antihistamines- CYCLIZINE or CINNARAZINE preferred over Sedating type- Promethazine
91
How are Igs formed ??
From a large pool of donors (eg 5000)
IgG molecules with a subclass distribution similar to that of normal blood
Half life- 3 wks
92
How are Monoclonal Antibodies produced ??
Somatic Cell Hybridization
- Fusion of Myeloma cells with SPLEEN cells from mouse which has been immunized with the desired antigen ==> Fused cells aka HYBRIDOMA acts as a factory for producing MC antibodies
- Main limitation: mouse antibodies are immunogenic ==> leads to Human anti-mouse antibody formation ==> which is overcome by a process- HUMANISING (combining the variable region from mouse with constant region from human antibody
93
MoA of
- Infliximab
- Rituximab
- anti-TNF (used in RA, Crohn's)
- anti-CD20 (used in RA & NHL)
94
Features of Hypo-Mg2+ ??
Similar to Hypo-Ca2+
- Paraesthesia
- Tetany
- Seizures
- Arrhythmias
- Decreased PTH==> Hypo-Ca2+
- ECG features similar to Hypo-K+
- Exacerbates Digoxin toxicity
95
What is Cinchonism ??
Quinine toxicity
- Tinnitus + Visual blurring + Flushed & dry skin + Abd. pain
Fatalality
- Short term cause: Arrhythmias, Flash Pulm. oedema
- Long term cause: Renal failure
96
Rx. of Hypo-Mg2+ ??
< 0.4 mmol/L or Tetany, Arrhythmias or Seizures
- IV [Mg2+] replacement (40 mmol/L MgSO4 over 24 hrs)
> 0.4 mmol/L
- Oral Mg2+ salts (10 to 20 mmol/day)
- DIARRHOEA can occur with oral Mg salts
97
Hallmark features of Cinchonism ??
QRS prolonged: due to Na+ blockade
QT prolonged: due to K+ blockade
- Hypoglycaemia (stimulates Insulin synthesis)
- Flash Pulm. Oedema (causes Hypoxia ==> necessitating PPV)
- CNS c/f are PERMANENT but is Transient in Aspirin poisoning
98
Rx. of Cinchonism ??
Largely Supportive
- Fluids, Ionotropes, HCO3, PPV
Quinine cannot be extracted by Extracorporeal method
99
Tell the following for OCTREOTIDE
- MoA ??
- S/E ??
- Long acting SOMATOSTATIN Analogue [normally D cells of pancreas produce this==> (-) release of GH, Glucagon, Insulin]
- GALLSTONES (secondary to biliary stasis)
100
Indication of Octreotide ??
- Acute Rx. of Variceal Bleed
- Acromegaly
- Carcinoid
- Following pancreatic Sx. (prevents complications)
- VIPomas
- Refractory diarrhoea
101
Drugs that exacerbate HF ??
- Pioglitazone (fluid retention)
- Verapamil [(-) Inotrope]
- Flecainide [Class Ic]- (-) Ionotropic & pro-arrhythmic effect
Fluid retention
- NSAID's (except Low dose Aspirin)
- Glucocorticoids (Fluid retention)
102
What drugs should be avoided in Renal Failure pts. ??
- Abx.- Tetracyclines, Nitrofurantoin
- NSAIDs
- Lithium
- Metformin
103
Which drugs have the tendency to accumulate in Chronic Renal Failure pts. ??
- Most Abx. including Penicillins, Cephalosporins, Vancomycin, Gentamycin & Streptomycin
- Digoxin, Atenelol
- MTX
- Sulfonylureas
- Furosemide
- Opioids
104
Drugs Relatively safe in Renal Failure ??
- Abx. ERYTHROMYCIN, RIFAMPICIN
- Diazepam
- Warfarin
105
Which drugs can be cleared with Haemodialysis ??
BLAST
- Barbiturates
- Lithium
- Alcohol (including methanol, ethylene glycol)
- Salicylates
- Theophylline (CHARCOAL haemoperfusion preferred)
106
Drugs which CANNOT be cleared with haemodialysis ??
2BDT
- BZPs
- Beta blockers
- Digoxin
- Dextropropoxyphene (Co-proxamol)
- TCAs
107
Drugs that commonly cause Urticaria ??
"Ur- PAN O"
- Penicillins
- Aspirin
- NSAIDs
- Opiates
108
Drugs that cause Lung Fibrosis ??
- Amiodarone
- Anti-Rheumatoid drugs: MTX, Sulfasalazine
- Cytotoxics: Busulphan, Bleomycin
- Ergot derived DA agoinst: Bromocriptine, Cabergoline, Pergolide
- NITROFURANTOIN
109
Nicorandil (K+ channel opener) S/E ??
- Anal ulceration
- Headache
- Flushing
110
Beta blockers S/E ??
- Bronchospasm (specially in Asthmatics)
- Fatigue
- Cold peripheries
- Sleep disturbance
111
Sulphonylureas S/E ??
- Hypoglycaemia
- Increased appetite & Wt. gain
- SIADH
- Cholestatic liver dysfunc.
112
Name the drugs causing AGRANULOCYTOSIS ??
- Carbimazole, PTU
- Atypical antipsychotics: Clozapine
- Carbamazepine
- Penicillins, Chloramphenicol, Co-trimoxazole
- Mirtazapine (Anti-depressants)
- MTX
113
Name the drugs known to cause Impaired Glucose Tolerance
- Thiazide
- Furosemide (less commonly)
- Steroids
- Tacrolimus, Ciclosporin
- IFN-alpha
- Nicotinic acid
- Antipsychotics
- BETA-BLOCKERS (slight impairment)
114
Drug induced Thrombocytopaenia causes ??
- Quinine
- Abciximab
- NSAIDs
- Furosemide
- Penicillins, Sulfonamide, Rifampicin
- Carbamazepine, Na Valproate
- Heparin
115
Names the drugs causing Urinary Retention
- TCAs: Amitriptyline
- Opioids
- NSAIDs
- Disopyramide
- Anticholinergics
- Antipsychotics, Antihistamines
116
Drugs causing corneal opacities ??
- Amiodarone (also causes Optic neuritis)
- Indomethacin
117
Drugs causing Optic Neuritis
Ethambutol
Amiodarone
Metronidazole
118
S/E of Sildenafil ??
- Blue discolouration of Retina
- Non-arteritic Anterior Ischaemic Neuropathy
119
Drugs causing Retinopathy ??
Chloroquine
Quinine
Sildenafil
120
What is Finasteride ??
5 Alpha-reductase inhibitor
(enzyme which converts Testosterone to DHT)
Used in
- BPH
- Male-pattern baldness
121
S/E of Finasteride ??
- Impotence
- Decreased Libido
- Ejaculation problems
- Gynaecomastia & Breast tenderness
- Decrease PSA levels
122
PDE-V inhibitor MoA ??
Increases cAMP ==> SM relaxation
Used in
- Erectile dysfunction
- Pulm. HTN
123
Mention the following about PDE-5 inhibitor
- CI ??
CI :
- Pts. on NITRATES & related drugs (eg. Nicorandil)
- Recent Stroke, MI (wait for 6 months)
124
Give egs. of PDE-5 inhibitors
Sildenafil (Viagra)
- 1st PDE-5 inhibitor drug
- Short acting (taken 1 hr before sex)
TADALAFIL (Cialis)
- Longer acting than sildenafil
- Can be taken on a regular basis
VARDENAFIL (Levitra)
125
S/E of PDE-5 inhibitors ??
Visual disturbance
- Blue discolouration
- Non-arteretic Anterior Ischaemic Neuropathy
Nasal congestion, Flushing
GI side effects
Priapism
Headache
126
Moa of METFORMIN ??
Acts by AMP-activated Protein Kinase activation
- Increases Insulin Sensitivity
- Decreases Hepatic Gluconeogenesis
- may also Reduce GI absorption of Carbohydrates
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S/E of Metformin ??
- GI upset (Nausea, Anorexia, Diarrhoea)
- Reduced Vit-B12 absorption
- Lactic Acidosis (in Severe liver disease or Renal failure)
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CI for Metformin use ??
Dose reviewed: Cr > 130 umol/l or eGFR < 45 ml/min
Stopped: Cr > 150 umol/l or eGFR < 30 ml/min
Iodine-containing X-ray Contrast media (eg.-Angiography, IVP): Stop Metformin on the day of procedure & for 48hrs thereafter
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Tell the MoA of the following
- Statins
- Ezetimibe
- Nicotinic acid
- Fibrates
- Cholestyramine
- HMG CoA reductase inhibitor
- Decrease Cholesterol absorption from Small Intestine
- Decreases Hepatic VLDL secretion
- PPAR-alpha agonists==> increases LPL expression
- Decreases Bile acid reabsorption in SI ==> Upregulates the amount of Cholesterol converted to BA
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What are Novel Psychoactive Substances (NPS) ??
STIMULANTS (eg- Mephedrone, Benzylpiperazine)
CANNABINOIDS (referred as 'Spice')
HALLUCINOGENS- can be Dissociatives (eg.-Methoxetamine) or Psychedelics
DEPRESSANTS (Opioid/ BZP based)-
OTHER substances
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What are Stimulant Novel Psychoactive Substances ??
Stimulants
- Similar to MDMA, Amphetamines, Cocaine
- Causes Increased Serotonin, DA, Noradrenaline => High/ Euphoria
- Eg.- Mephedrone ('bath salt', M-CAT, 'meow meow') It is a Cathinone & structurally similar to Khat
- Eg.- Benzylpiperazine (Exodus, Legal X, Legal E)
- Swallowed as Pill/Powder (Bombing) or Snorted
- S/E: similar to MDMA/Cocaine + Serotonin syndrome
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What are Cannabinoids NPS ??
- Synthetic Cannabinoid r AGONISTS
- Common name: 'Spice'
- Sprayed on herbal mixture & Smoked
- Also available in Liquid form- used in e-cigarettes
- S/E: similar to Cannabis
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What are Hallucinogenics NPS ??
They are Dissociatives/ Psychedelics
- Dissociatives: Ketamine like effect with sense of not connected to body or time. eg.- Methoxetamine ('mexxy')
- Psychedelics: LSD like effect but NPS version can also be a stimulant
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What are Depressant NPS ??
Either Opioid or BZP based
- Pill/ Powder
- Str. very similar to original drug class, so, S/E are similar
- BZP-NPS: have Longer 1/2 life
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What are Other substances of NPS ??
- Gamma-Hydroxybutyric acid (GHB) & Gamma-Butyrolactone (GBL): 'G', 'Geebs' or 'Liquid Ecstacy'
- GHB: Resp. depressant, when takes with [-OH], potentially life threatening
- Nitrous oxide: 'Hippie crack'
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Cocaine poisoning ?
Alkaloid derived from Coca plant; is a Recreational Stimulant
- MoA: (-) DA, NA & Serotonin uptake
Rx.-
- 1st line: BZPs
- Chest pain: BZPs + GTN
- If MI develops => PCI
- HTN: BZPs + Na-Nitroprusside
Beta-bockers cause unopposed Alpha mediated Coronary vasospasm
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Cocaine S/E ??
CVS
- CA spasm=> M ischaemia or MI
- Both Tachy- & Brady- cardia
- HTN
- QRS widening & QT prolongation
- Aortic dissection
CNS : Seizures, MYDRIASIS, Hypertonia, Hyperreflexia
Psychaitric effecy
- Agitation, Psychosis, Hallucinations
Others
- ISCHAEMIC Colitis (consider if Abd. pain + Rectal bleed)
- Hyperthermia
- Met. Acidosis. - Rhabdomyolysis
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What is Ecstacy poisoning ??
MDMA (3,4 Methylenedioxy-methamphetamine)
- CNS: Agitation, Anxiety, Confusion, ATAXIA
- CVS: Tachycardia, HTN
- HYPO Na+
- Hyperthermia
- Rhabdomyolysis
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Rx. of Ecstacy poisoning ??
SUPPORTIVE
- Dantrolene in hyperthermia
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What are the features of Ethylene glycol toxicity ??
It is a type of alcohol used as a Coolant or Antifreeze
3 Stages
STAGE 1: Similar to [-OH] intoxication; Confusion, Slurred speech, HTN
STAGE 2: Met. Acidosis with High A G & high Osmolar gap; Tachy. & HTN
STAGE 3: Acute Kidney Injury
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Rx. of Antifreeze poisoning ??
FOMEPIZOLE (Alcohol dehydrogenase inhibitor)
Haemodialysis
Ethanol was used in the past (works by competing with Ethylene glycol for enzyme [-OH] dehydrogenase)
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Methanol poisoning features ??
Effects a/w Alcohol (intoxication, N & V, etc.) + Visual problems including blindness (form of Optic neuropathy)
- C/F are due to Formic acid accumulation
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Rx. of Methanol poisoning ??
FOMEPIZOLE (competitive inhibitor of Alcohol dehydrogenase)
Haemadialysis
Co-factor Therapy with FOLINIC ACID to reduce ocular complications
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Rx. of Alcohol drinking problem ??
BZPs for Acute withdrawal
DISULFIRAM :
- Promotes ABSTINENCE [(-OH) intake causes severe reaction due to Acetaldehyde dehydrogenase (-)]
- Even small amount of (-OH) can produce severe symptoms
- CI: IHD, Psychosis
ACAMPROSTATE :
- Reduces CRAVING
- Weak NMDA r antagonist
- Improves Abstinence
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Features of Mercury poisoning ??
Paraesthesia
Visual Field defect
Hearing loss, Tinnitus
Irritability
Somatitis, Bleeding gums
Renal Tubular Acidosis
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What is Ciclosporin ??
Immunosuppressant which decreases Clonal proliferation of T-cells by reducing IL-2 release
MoA: Binds to Cyclophilin => forms a complex =(-)=> Calcineurin (a phosphatase that activates various transcription factors in T cells)
"Non- Myelotoxic drug"
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Indications & S/E of Ciclosporin ??
- Post-Organ transplant
- RA, Psoriasis, UC, Pure Red cell Aplasia
S/E (everything is Increased)
- Nephro- & Hepato- Toxicity
- Fluid retention, HTN
- Hyper K+, Hypertrichosis
- Gingival Hyperplasia
- Tremors
- IGT, Hyperlipidaemia
- Increased susceptibility to severe infections
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Immunosuppressant that is 'Virtually Non-Myelotoxic' ??
Ciclosporin
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Features of Tacrolimus ??
Immunosuppressants commonly used to prevent Transplant rejection
MoA: Binds to FKBP => forms a complex =(-)=> Calcineurin (a phosphatase that activates various transcription factors in T cells) => Decreases clonal proliferation of T- cells by reducing IL-6
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Difference b/w Ciclosporin & Tacrolimus ??
Ciclosporin binds to CYCLOPHILIN
Tacrolimus binds to FKBP
T is more potent than C, so Rejection chances are less
Nephrotoxicity & IGT is more with T than with C
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Indications for Allopurinol therapy in Gout ??
It works by (-) Xanthine oxidase
ULT is indicated in
- >= 2 attacks in 12 months
- Tophi
- Renal disease
- Uric acid renal stones
- Prophylaxis if on Cytotoxics or Diuretics
- Lesch-Nyhan synd. (taken for rest of life)
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S/E of Allopurinols ??
Dermatological S/E are more
- SCAR: Severe Cutaneous Adverse Reaction
- DRESS: Drug Reactions with Eosinophilia & Systemic symptoms
- SJS
Chinese/ Korean/ Thai people are at increased risk
Pts. at high risk of SCAR should be screened for HLA-B 580 I allele
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Interaction of Allopurinol with Azathioprine ??
Azathioprine is metabolized into active compound- 6-Mercaptopurine
- Xanthine oxidase oxidises 6-MCP to 6-Thiouric acid
- Allopurinol can lead to HIGH levels of 6-MCP
- So, reduced dose (eg.-25%) must be used
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Interaction of Allopurinol with
- Cyclophosphamide ??
- Theophylline ??
- Reduces renal clearance => Marrow toxicity
- Increases plasma conc. of Theophylline by (-) its breakdown
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Name the following about COCPs-
- Increased risk of which Cancers ??
- Reduced risk of which Cancers ??
- Increase: Breast & Cervical cancer
- Increase: VTE, STIs (no protection), Stroke & IHD (specially in Smokers)
- Reduced: Ovarian, Endometrial & Colorectal cancer
- Also reduces the risk of Ovarian cyst, Benign breast disease & Acne vulgaris
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How is CIs of COCPs guided ??
UK Medical Eligibility Criteria (UKMEC)
- 1 : No restriction for COCPs use
- 2 : Advantage >> Disadvantage
- 3 : Disadvantage >> Advantage
- 4 : Unacceptable health risks
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What are the UKMEC 3 conditions of COCPs use ??
- >35yrs + Smokes <15 cigarettes/ day
- BMI > 35 kg/m2
- FHx of VTE in 1st degree relatives who are < 45yrs old
- Controlled HTN
- Immobility (eg. uses wheel chair)
- Carrier of BRCA 1/2 mutation
- Current Gallbladder disease
- DM dx. > 20yrs ago is classified as UKMEC 3 or 4 depending on severity
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How are COCPs takes ??
- IF started within first 5 days of cycle, NO need for extra contraception
- IF started at other point in cycle, extra contraception (eg Condoms) used for first 7 days
- Should be taken at SAME time daily
Methods
- Conventional: Taken for 21 days then stopped for 7 days for breakthrough bleed
- Tricycling: 3 packs of 21 pills are taken continuously after which 4- 7 days break is taken
Sex during Pill-free period is safe only if next pack is started ON Time
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What are the UKMEC 4 conditions of COCPs use ??
- > 35yrs + Smokes >15 cigarettes/day
- Migraine with aura
- H/o VTE or Thrombogenic mutation
- H/o Stroke/ MI
- Breastfeeding < 6 wks post-partum
- Uncontrolled HTN
- Current Breast Cancer
- Maj. Sx. with prolonged immobilization
- (+)ve APL antibodies (eg.- SLE)
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Precautions for COCPs ??
Enzyme inducing drugs & Abx. like Rifampicin
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S/E of Tamoxifen ??
- MENSTRUAL disturbance: Vaginal bleed, Amenorrhoea
- Hot flushes
- VTE
- ENDOMETRIAL Cancer
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POPs Disadvantages ??
Irregular periods (MC S/E)
- May not have periods/ Irregular light periods
- No protection against STIs
- Increased incidence of Functional Ovarian Cysts
- S/E: Breast tenderness, Wt. gain, Acne & Headaches (these c/f usually subside in 1st few months)
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POPs advantages ??
ADVANTAGES
- Highly effective & Does't interfere with Sex
- Reversible upon stopping
- Can be used while Breastfeeding
- Can be used in places where COCPs are CI eg.- Smokers >35yrs & Women with H/o VTE
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Which SERM carries a lower risk of Endometrial Ca ??
RALOXIFENE- a Pure Oestrogen receptor antagonist
156
What is Tamoxifen ??
Selective Oestrogen Receptor Modulator (SERM)
- Oestrogen receptor ANTAGOnist
- Used in Oestrogen receptor (+)ve Breast Ca
- Used for 5 years after tumour removal
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What is TRASTUZUMAB ??
aka HERCEPTIN is a Monoclonal antibody directed against HER2/Neu receptor
- Used mainly in Metastatic Breast Ca
S/E
- Flu-like c/f & Diarrhoea (MC)
- Cardiotoxicity: more common when Anthracyclines have been used; do an 2D-Echo before starting Rx.
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Which factor drives use of Telaprevir in Hep C ??
Hep. C genotype
- Genotype 1 has the lowest success rates with respect to viral clearance
- So, Telaprevir & Bocaprevir (NS3/4A Serine Protease inhibitor) are used as initial therapy with genotype 1
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Causes of Gingival Hyperplasia ??
Phenytoin
Ciclosporin
CCBs (specially Nifedipine)
AML
- Myelomonocytic types
- Monocytic types
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