LMR PHARMA CVS , ENDOCRINE & RESPIRATORY SYSTEM , GASTRO

INTESTINAL SYSTEM & AUTACOIDS

CVS PART-1

LOOP AND THIAZIDE DIURETICS

First-line drugs for hypertension:

1. ACEi / ARBs
2. CCBs
3. Thiazide diuretics

Thiazides as antihypertensives:

• Once a day dosing

• Simplified dosing regimens
• Low cost
• Effective in isolated systolic hypertension
• Potentiate all other anti-HTN drugs (except DHPs)
• Low incidence of postural hypotension
• No fluid retention
• No tolerance
• Lesser incidence of hip fracture

Adverse effects of loop diuretics and thiazides:

1. Hypotension
2. Hyponatremia
3. Hypokalemia
4. Metabolic alkalosis
5. Hypomagnesemia
6. Hypocalcemia (Loop)
7. Hypercalcemia (Thiazides)
8. Hyperglycemia
9. Hypertriglyceridemia
10. Hypercholesterolemia
11. Hyperuricemia
12. Ototoxicity (Loop)

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13. Erectile dysfunction and impotence (Thiazides)

OTHER DIURETICS

Indications of acetazolamide:

1. Glaucoma
2. Acute mountain sickness
3. Catamenial epilepsy
4. Periodic paralysis
5. For alkalinization of urine

Osmotic diuretics:

Adverse effects:
1. Hyponatremia – Headache, nausea and vomiting
2. Hypotension and dehydration
3. Hypokalemia
4. Pulmonary edema (due to initial volume overload)
5. Hypersensitivity reactions (rare)
Contraindications:
▪ Congestive heart failure
▪ Pulmonary edema
▪ Acute tubular necrosis
▪ Anuria
▪ Cerebral hemorrhage

DRUGS ACTING ON RAS

All ACE inhibitors are pro-drugs except

• Captopril
• Lisinopril

Common adverse effects of ACEi / ARBs:

1. Hypotension – Postural hypotension (increased in combination with diuretics)

2. Hyperkalemia
3. Metabolic acidosis
4. Hepatotoxicity
5. Glycosuria

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6. Dysguesia
7. Acute renal failure precipitation
8. Teratogenicity
▪ Fetal lung hypoplasia
▪ Oligohydramnios

Adverse effects of ACEi due to inhibition of bradykinin metabolism (not seen with ARBs):
(Mnemonic: DARU)
1. Dry cough
2. Angioedema
3. Rashes
4. Urticaria

OTHER ANTIHYPERTENSIVES

Treatment of β-blocker overdose: Glucagon – 5-20 mg IV

Interaction of β-blocker + Verapamil / Diltiazem:

Additive negative chronotropic and dromotropic effects
↓
Increased bradycardia + precipitation of AV block
Antihypertensives contraindicated in pregnancy: (Mnemonic: Pregnant woman is NOT
supposed to DAANS):
• Diuretics
• ACEi
• ARBs
• Non-selective beta blockers
• Sodium nitroprusside

CVS PART-2

DRUGS FOR HEART FAILURE

Effects of dopamine at various doses:

RANGE (µg/kg/min IV PREDOMINANT
DOSE
infusion) EFFECT ON
Low <2 D1
Intermediate 2-10 β1

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 High > 10 α1
Inotropic dose of dopamine: 2-5 µg/kg/min IV infusion

Treatment of digitalis-induced arrhythmias:

DIGITALIS-INDUCED ARRHYTHMIA TREATMENT

Tachycardia Potassium supplements
AV block Atropine
Supraventricular arrhythmias Propranolol
Ventricular arrhythmias Lignocaine

DRUGS FOR ISCHEMIC HEART DISEASE (ANTI-ANGINALS)

Adverse effects of nitrates:

1. Throbbing headache
2. Flushing
3. Hypotension
4. Reflex tachycardia and palpitations
5. Sweating
6. Tolerance (on long term use)
7. Methemoglobinemia

Potassium channel openers are not first line drugs due to:

1. Salt and water retention

2. Hyperglycemia

TREATMENT OF NON-ST-ELEVATION MYOCARDIAL INFARCTION (NSTEMI) AND ANTI-

ARRHYTHMICS

Treatment of NSTEMI:

1. Anti-ischemic treatment
➢ Nitrates
➢ β-blockers
➢ CCBs
2. Morphine
3. Anti-thrombotic treatment
➢ Anti-platelets
➢ Anticoagulants

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Clinical classification of antiarrhythmics:

Supraventricular and
Supraventricular Ventricular
ventricular
arrhythmias only arrhythmias only
arrhythmias
• Adenosine • Amiodarone • Lidocaine
• Verapamil • β-blockers – • Mexiletene
• Diltiazem Propranolol,
• Digoxin Sotalol, Esmolol
• Dronedarone • Quinidine
• Procainamide
• Disopyramide
• Flecainide
• Propafenone

HYPOLIPIDEMICS

Drug interactions of statins:

1. Increased risk of myopathy seen in combination with –
• Digoxin
• Amiodarone
• Macrolides
• Nicotinic acid
• Fibrates
• Cyclosporine
• Protease inhibitors
• Warfarin
2. Metabolism inhibited by CYP3A4 inhibitors

MOA of newer hypolipidemics:

Drug
1 Lomitapide
2 Torcetrapib
3 Mipomirsen
4 Evolocumab
Target
Microsomal triglyceride transfer protein (MTP or
MTTP)
Cholesteryl ester transfer protein (CETP)
Antisense oligonucleotide against ApoB 100 mRNA
Proprotein convertase subtilin kexin / 9

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CVS PART-3

ANTI-PLATELET AGENTS

Classification of anti-platelet agents:

Group Examples
1 Inhibition of thromboxane Low dose aspirin (< 325 mg/d)
A2 (TXA2) production
2 Inhibition of Dipyridamole
phosphodiesterase (PDE)
enzyme
3 Inhibition of platelet Ticlopidine
adenosine P2Y12 receptors Clopidogrel
Prasugrel
Ticagrelor
Cangrelor
4 Inhibition of platelet Abciximab
GpIIb/IIIa receptors Eptifibatide
Tirofiban
5 Inhibition of thrombin (PAR- Vorapaxar
1) receptors

PARENTERAL ANTICOAGULANTS

Unfractionated heparin (UFH) v/s Low molecular weight heparin (LMWH):

UNFRACTIONATED HEPARIN LOW MOLECULAR WEIGHT

(UFH) HEPARIN (LMWH)
MOA Binds to AT-III Binds to AT-III
↓ ↓
Inhibits both Xa and IIa Inhibits Xa >> IIa
Route IV, s.c. s.c
S/C Bioavailability Better
Plasma and High Negligible
tissue protein
binding

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 UNFRACTIONATED HEPARIN LOW MOLECULAR WEIGHT
(UFH) HEPARIN (LMWH)
Anticoagulant Less predictable More predictable
effect
Routine With aPTT Not required
monitoring
Passage through Absent Present
placenta
Use in pregnancy Safe Unsafe – to be avoided
Elimination Metabolized by heparinase in Excreted unchanged by kidney
plasma
Use in renal Safe Unsafe – avoided
failure
Adverse effects Greater incidence Lesser incidence
Heparin-induced More likely Less likely
thrombo-
cytopenia
Antidote Protamine sulphate Absent

WARFARIN

Genetic testing recommended – to determine optimal dose of warfarin

This is due to genetic polymorphisms (affecting response to warfarin) in –
• Vit K epoxide reductase
• Cytochrome P450 2C9

Monitoring for warfarin with – PT / INR; Normal INR range maintained: 2.0 to 3.0
INR 3.0 to 3.5 in case of –
1. Recurrent thromboembolism
2. Arterial disease
3. Prosthetic heart valves

Fetal warfarin syndrome:

• Growth retardation
• Hypoplasia of
➢ Nose
➢ Eye sockets

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 ➢ Hand bones

Anticoagulation during pregnancy:

GESTATION PERIOD ANTI-COAGULANT

First 12 weeks Heparin (UFH)
12-36 weeks Warfarin
36 weeks – Labour Heparin (UFH)
Post-partum Warfarin

OTHER ORAL ANTICOAGULANTS

Routine monitoring for anticoagulants:

TEST DONE FOR

aPTT Heparin
Argatroban

PT / INR Warfarin

Oral Factor Xa inhibitors:

• Rivaroxaban
• Apixaban
• Edoxaban
• Batrixaban

ENDOCRINE SYSTEM

Drugs for diabetes mellitus – Classification and insulins

Classification of anti-diabetics:

Parenteral Oral
• Insulins • Sulfonylureas
• GLP-1 analogues • Meglitinide analogues
• Pramlintide • Biguanides
• Thiazolidinediones
• α-glucosidase inhibitors
• DPP-IV inhibitors
• SGLT2 inhibitors

Advantages of ultra-short acting insulins over regular insulin:

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1. Faster absorption (due to dissociation of insulin hexamers into monomers) – faster onset
of action – can be given after meals also
2. Shorter duration of action – lesser risk of hypoglycaemia

Drugs for diabetes mellitus – other antidiabetics

Contraindications to metformin:

• Renal failure
• Severe liver disease
• Severe pulmonary disease
• Decompensated CHF
• Chronic alcoholics
• Patients requiring a radiographic contrast administration

Adverse effects of DPP-IV inhibitors:

• Hypotension
• Urinary frequency
• Urinary tract infections – Urosepsis and Pyelonephritis
• Genital mycotic infections
• Ketoacidosis
• Acute kidney injury and renal impairment
• Hyperlipidemia

Corticosteroids, Anti-thyroid drugs and Drugs for SIAD

Adverse effects of systemic corticosteroids:

1. Hypothalamo-pituitary adrenal (HPA) axis suppression (due to negative feedback inhibition

on pituitary ACTH secretion)
2. Cushingoid features – Moon face, buffalo hump, orange-on-sticks appearance,
telangiectasia, etc. (due to lipid redistribution from extremities to trunk)
3. Hyperglycemia (due to increased liver gluconeogenesis)
4. Muscle atrophy and myopathy (due to breakdown of proteins in muscles)
5. Osteoporosis (due to breakdown of proteins in bones)
6. Thinning of skin and easy bruisability (due to breakdown of proteins in skin)
7. Telangiectasiae (due to breakdown of proteins in skin)
8. Hypertension (due to increased synthesis of alpha-1 receptors in the blood vessels)
9. Immune suppression – increased risk of opportunistic infections
10. Increased risk of peptic ulceration

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11. Euphoria and mood disturbances
12. Posterior subcapsular cataract

Steroid-induced osteoporosis generally manifests within – 6 months of therapy

Teratogenicity due to anti-thyroid drugs:

• Fetal goitre
• Fetal hypothyroidism
• Aplasia cutis congenita
• Posterior choanal atresia

Drugs for osteoporosis

Bisphosphonates: MOA:

High affinity for calcium phosphate

↓
Get sequestered at sites of active remodeling
↓
Get released in acid environment of osteoclasts
↓
1. Activate osteoclast apoptosis
2. Disrupt osteoclast cytoskeleton and ruffled border
3. Inhibit osteoclast differentiation through suppression of IL-6
4. Inhibit farnesyl pyrophosphate synthase enzyme (2nd and 3rd gen BPNs) involved in
osteoclast survival

Net effect –

• Reduction in osteoclast activity and number

• Hence, anti-resorptive

Indications:

1. Osteoporosis
➢ Senile osteoporosis
➢ Post-menopausal osteoporosis
➢ Steroid-induced osteoporosis
2. Osteogenesis imperfecta
3. Osteolytic bone mets
4. Paget’s disease of bone
5. Hypercalcemia of malignancy

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Adverse effects:

1. GI symptoms
➢ Heartburn
➢ Esophagitis
➢ Gastritis
➢ Abdominal pain
➢ Diarrhea
2. Osteonecrosis of jaw (rare)
3. Flushing and flu-like symptoms (on IV infusion)
4. Dizziness
5. Nephrotoxicity (zoledronate)

RESPIRATORY SYSTEM

Treatment of acute severe asthma:

1. Nebulized salbutamol (2.5 – 5 mg) + Ipratropium bromide (0.5 mg)

2. Hydrocortisone hemi-succinate (100 mg IV stat followed by 100-200 mg 4-8 hrly as IV
infusion)
3. High flow humidified oxygen inhalation
4. Salbutamol / Terbutaline 0.4 mg IM /s.c. may be added

Preferred bronchodilators:

• For treatment of BA: β agonists

• For treatment of COPD: Inhaled anticholinergics (due to increase in inherent vagal tone in
COPD)

Adverse effects of β agonists:

1. Tremors
2. Tachycardia
3. Tolerance
4. Hypokalemia
5. Hyperglycemia
6. V/Q mismatch

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Adverse effects of theophylline:

Adverse effect Mechanism

Nausea and vomiting PDE4 inhibition
Headache
Gastric discomfort
Diuresis A1 receptor antagonism
Epileptic seizures
Cardiac arrhythmias PDE3 inhibition and A1 receptor antagonism
Behavioural disturbance ??

Drugs affecting theophylline metabolism:

Drugs inducing theophylline Drugs inhibiting theophylline

metabolism metabolism
1. Rifampicin 1. Allopurinol
2. Phenytoin 2. Cimetidine
3. Phenobarbitone 3. Ciprofloxacin
4. Cigarette smoking 4. Erythromycin
5. Alcoholism 5. Zileuton
6. Young age (< 18 years) 6. Zafirlukast
7. Fluvoxamine

GASTROINTESTINAL SYSTEM

Interaction between ranitidine and sucralfate:

• Sucralfate directly binds to ranitidine → Decreases its absorption from GIT.

• Hence, combination to be avoided.

Examples of prokinetic agents:

1. 5-HT4 agonists
➢ Prucalopride
2. D2 antagonists
➢ Metoclopramide
➢ Domperidone
➢ Itopride
3. Motilin receptor agonists

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 ➢ Erythromycin
4. 5-HT3 antagonists
5. Guanylate cyclase C agonists
➢ Linaclotide
➢ Plecanatide

Adverse effects of metoclopramide:

1. Dystonias
2. Parkinsonian features
3. Tardive dyskinesia
4. Oculogyric crisis
5. Galactorrhea
6. Sedation
7. Dizziness
8. Diarrhea

AUTACOIDS – 1 (ANTIHISTAMINES AND DRUGS FOR ERECTILE DYSFUNCTION)

Differences between 1st and 2nd generation antihistamines:

1st gen (conventional)

2nd gen (newer) antihistamines
antihistamines
1 Cross BBB Do not cross BBB
2 Sedating Non-sedating
3 Central anticholinergic action + No central anticholinergic action

Contraindications to PDE5 and PDE6 inhibitors:

1. Coronary artery disease

2. Patients taking nitrates – Increased risk of MI and mortality

Autacoids – 2 (Drugs for gout)

Drugs for acute gout:

1. NSAIDs (DOC) – except Aspirin

2. Colchicine
3. Steroids

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Drugs for maintenance treatment of gout:

CLASS MECHANISM EXAMPLES

1 Xanthine oxidase Reduce synthesis of Allopurinol
inhibitors uric acid Febuxostat
2 Uricosuric agents Increase urinary Probenecid
excretion of uric acid Sulfinpyrazone
Benzbromarone
3 Uricase analogues Enhance metabolism Rasburicase
of uric acid to allantoin Pegloticase

MOA of colchicine:

1. Inhibits release of chemotactic factors from synovial cells – reduced inflammation in the
joints
2. Binds to tubulin and inhibits granulocyte migration into the joint
3. Inhibits mitotic spindle formation and arrests cell division at mitosis
It has NO –
• Analgesic activity
• Anti-inflammatory activity
• Effect on blood urate levels

Autacoids – 3 (Remaining topics in autacoids)

Effects of aspirin at various doses:

DOSE EFFECT OF ASPIRIN

75 – 325 mg/d Anti-platelet
600 – 800 mg/d Analgesic
Antipyretic
2 – 4 g/d Analgesic
Antipyretic
Anti-inflammatory

❑ ❑ ❑

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