Pharma (copy)

the deepest place in hell.

morphine

stimulate opiate receptors

morphine uses

severe visceral pain
primary neurogenic shock
pain control and sedation
preanesthetic med
pulmonary edema

morphine side effects

pinpoint pupils
urinary retention and constipation

diuretics

increase the volume urine by increasing water and solute excretion

thiazides: hydeochloro-thiazide mechanism

inhibit NA/CL transporter in distal convoluted tubule moderate diuresis

thiazides: hydeochloro-thiazide uses

mild and moderate hyepertension
heart failure
edema
hypercaluria and renal calucim stones
nephrogenic diabetes insipidus

thiazides: hydeochloro-thiazide side effects

hypokalemia
hypercalcemia
hypochoremic alkalosis
hyperglycemia hyperuricemia and hyperlipidemia

Loop diuretics: furosemide mechanism

inhibit na/k/2cl transporter in thick ascending limb of loop of henle

Loop diuretics: furosemide uses

edema: acute pulmonary edema, ascites
severe hyphertension
acute renal failure
hypercalcemia

Loop diuretics: furosemide side effects

hypokalemia
hypercalcemia
hypochoremic alkalosis
hyperglycemia hyperuricemia and hyperlipidemia
hypocalcemia
dehydration = hypotension
ototoxicity

K-+ sparing diuretics: spironolactone, eplerenone mechanism

inhibitors of aldosterone receptor in cortical collecting ducts decreasing Na reabsorption and K secretions

K-+ sparing diuretics uses

with thiazide or loop diuretics
hyperaldosteronism
heart failure
chronic kidney disease
polycystic ovary syndrome

K-+ sparing diuretics side effects

gynecomastia (spironlactone)
metabolic asidosis
hyperkalemia

K-+ sparing diuretics

spironolactone, eplerenone (more for selctive aldosterone receptors with less side effects)

Loop diuretics

furosemide

thiazides

hydeochloro-thiazide

antihypertensive effect diuretic

decrease na body storage= decreasing lung volume= decrease cardiac output.

antihypertensive effect thiazides

direct vasodilating effects

angiotensin converting enzyme inhibitor

captopril

angiotensin converting enzyme inhibitor mechanism

inhibit angiotensin converting enzyme= decrease formation of active angiotension II= mixed VD= decrease remodling of heart = increase bradykinn

angiotensin converting enzyme inhibitor uses

Hypertension, epically high renin
heart failure
diabetic nephropathy
myocardial infarction to decrease infarct size and remodeling of heart

angiotensin converting enzyme inhibitor side effect

dry irritant cough
first dose hypotension
hyperkalemia
contraindicated: 2- 3 trimester of pregnancy
proteinuria
neutropenia
decrease taste and allergic manifestation

angiotension II

Block AT receptors

Calcium Channel Blockers

block voltage dependent L type calcium channels present in heart blood vessels and smooth

calcium channel blockers VERAPAMIL uses

prophylaxis of all types of angina
cardiac arrhythmias

calcium channel blockers VERAPAMIL side effects

Heart failure
bradycardia
heart block
constipation
(not combined with beta blockers)

calcium channel blockers NIFEDINPINE uses

hypertension
preeclampsia of pregnancy
peripheral vascular diseases

calcium channel blockers NIFEDINPINE side effects

hypotension
reflex tachycardia
ankle edema
aggravate angina

Calcium Channel Blockers Verapamil uses

Prophylaxis of ALL Types of Angina
Cardiac Arrhythmias

Calcium Channel Blockers Verapamil side effects

Heart failure
Bradycardia
Heart Block. (not combined with beta blockers)
Constipation

direct vasodilators: marked hypotension

headache, congestion, and flush

direct vasodilators: mark hypotension simulates

baroreceptors
sympathetic system
renin angiotensin aldosterone system

baroreceptors
sympathetic system
renin angiotensin aldosterone system stimulation leads to:

increase heart rate, contractility, o2 needs and increase in na and retension which then increase heart work

increase heart work

leads to angina, myocardial infraction ,and heart failure

leads to angina, myocardial infraction ,and heart failure avoided by

combined direct vasodilators with beta blocker and loop diuretic

direct vasodilators common side effects

Reflex tachycardia (ADD beta-blocker)
Oedema(ADDDiuretic)

direct vasodilators Common uses:

hypertension: →↓TPR
heart failure:→↓ AFTERLOAD &→↓ VR →↓ PRELOAD

mechanism of action of organic nitrate

Release NO → dilate veins (low dose ↓ preload) and arteries (high dose ↓ afterload), dilate epicardial coronary arteries

organic nitrate uses

• Acute angina: sublingual/buccal spray (sit, avoid syncope)

• Long-term prophylaxis: oral slow release, patch, ointment (need 8–10h nitrate-free period to avoid tolerance)

• IV: acute MI, acute pulmonary edema, refractory HF

organic nitrate side effects

Hypotension, reflex tachycardia, severe throbbing headache, flushing, coronary dependence, tolerance, rebound ischemia/infarction if stopped suddenly

organic nitrate contra

With sildenafil (Viagra) → severe fatal hypotension

Hydralazine moa

Direct Arteriolar - VD. May act through release of NO

Sodium Nitroprusside moa

Nitroprusside → release NO

Minoxidil moa

(Prodrug) Activate K+ Channel

Diazoxide moa

Direct Arteriolar VD. Activates K+ channels

Hydralazine side effects

•Reversible Rheumatoid arthritis & Lupus erythematosus-like syndrome. •Peripheral neuritis

Sodium Nitroprusside se

a. Largedose:Severe Hypotension & Shock.

b. SuddenStop: ReboundHypertension.

Minoxidil side effects

Hypertrichosis (stimulate hair growth).

Diazoxide SE

Hyperglycemia (decrease Insulin release) & Hyperuricemia

Centrally Acting Sympathoplegics

Methyldopa & Clonidine (α₂ agonists) moa

Activate central α₂ receptors → ↓ sympathetic outflow → ↓ TPR & CO → ↓ BP

Methyldopa uses

Hypertension with pregnancy

Clonidine uses

-Hypertension: Mild and moderate hypertension with renal insufficiency-Prophylaxis: migraine headache. -Morphine withdrawal

Centrally Acting Sympathoplegics

Methyldopa & Clonidine (α₂ agonists) side effecs:

-Sedation. Depression Parkinsonism Bradycardia, Postural hypotension

-Don't stop clonidine suddenly→ rebound hypertensive crisis. Treatment by Phentolamine

Neprilysin Inhibitor & BNP Sacubitril (with ARB)

Inhibits neprilysin → ↑ natriuretic peptides → vasodilation, natriuresis, ↓ sympathetic tone, ↓ aldosterone, ↓ BP

Sacubitril

cannot be used alone; it must always be combined with an ARB to block the effect of the excess angiotensin II.

cannot be used with an ACEI, due to an increased risk of angioedema if ACEI and ARNI are used together or within proximit

Neprilysin Inhibitor & BNP: Nesiritide (recombinant BNP) mechanism

Binds natriuretic peptide receptors → natriuresis, diuresis, ↓ preload & afterload

Neprilysin Inhibitor & BNP: Nesiritide (recombinant BNP) Uses

Acute decompensated heart failure

Cardiac Glycosides (Digitalis)

Digoxin Mechanism

Inhibits Na⁺/K⁺ ATPase → ↑ intracellular Ca²⁺ → ↑ contractility; ↑ vagal tone → ↓ AV conduction

Cardiac Glycosides (Digitalis)

Digoxin uses

HF with reduced EF (symptomatic on optimal therapy), atrial fibrillation/flutter (controls ventricular rate)

Cardiac Glycosides (Digitalis)

Digoxin toxicity

GIT: anorexia, nausea, vomiting

Neurological: headache, fatigue, confusion

Gynecomastia

Vision: blurred vision, yellow-green vision

CVS: any arrhythmia possible including: Bradycardia, Heart block, Ventricular extrasystole Ventricular fibrillation.

> 2ng/ml

Bipyridines: Amrinone moa

Inhibit Phosphodiesterase enzyme III

Bipyridines: Amrinone uses

IV short-term in resistant HF

Bipyridines: Amrinone effects

a- Allergy → Fatal Thrombocytopenia & Hepatotoxicity.

b- increase Myocardial O2-consumption →Worsens Angina pectoris.

Antihypertensive Drug Classes First-line

ACEIs, ARBs, Beta-blockers, CCBs, Diuretics

Antihypertensive Drug Classes First-line Antihypertensive Drug Classes First-line

Central α₂ agonists, Vasodilators, Alpha-blockers

Drugs Used for the 1 Treatment of Heart Failure

1 Treatment of Heart Failure-Angiotensine- converting enzyme inhibitors( ACEIs)

2-Angiotensine receptor blocker (ARBs) 3-Aldesterone antagonist

4-beta-blockers

5. Vasodilators

6-Diuretics

7-Neprilysin Inhibitor

8-Hyperpolarization-activated cyclic nucleotide- gated channel blockers

9-Sodium-Glucose Cotransporter-2 Inhibitors

10-Inotrpic agents (Digitalis

Thionamides — Carbimazole / Methimazole / PTU uses

Principal therapy for hyperthyroidism Adjuvant to I¹³¹ while waiting for effect Preparation for surgical treatment (thyroidectomy) Thyroid storm — PTU preferred (inhibits T4 → T3 conversion)

Thionamides — Carbimazole / Methimazole / PTU uses in pregnancy

1st trimester: Propylthiouracil (PTU) Thereafter: Methimazole

Thionamides — Carbimazole / Methimazole / PTU adverse effects

All: Agranulocytosis (most serious)

Methimazole: Teratogenicity

PTU: Hepatitis

Progestogens Uses

Oral contraception (alone or with estrogen) — MAIN USE Functional uterine bleeding
Dysmenorrhea
Amenorrhea
Endometriosis

Progestogens Side Effects

Weak androgenic actions (some progestogens)
• Edema
• Psychic depression
• Increased cholesterol → atherosclerosis risk

Estrogen Uses

Contraception (with progestogens)
Postmenopausal hormonal therapy (HT) with progestogen
Vaginal estrogen (if only vaginal atrophy)
Primary hypogonadism (ovarian failure)
Premature or surgical menopause

Estrogen Side Effects

Nausea & breast tenderness (most common)
Thromboembolic events & myocardial infarction
Salt & water retention → edema, hypertension, weight gain
Increased blood sugar
Risk of breast & endometrial carcinoma (add progesterone to reduce risk)

Androgens examples

Testosterone propionate — sublingual, IM, or SC

Methyl testosterone — sublingual

Androgens Main Use

Replacement therapy in male primary or secondary hypogonadism (pituitary failure)

Androgens Adverse Effects

Cholestatic jaundice (testosterone)
Masculinization & hirsutism in females
Salt & water retention Precocious puberty in children Premature epiphyseal plate closure in children

Anabolic Steroids Examples

Nandrolone

Methandrostenolone

Anabolic Steroids Clinical Uses

Osteoporosis

General wasting

Acute renal failure

Aplastic anemia

Anabolic Steroids Adverse Effects

Same as androgens (see previous slide)

Calcium Homeostasis: Parathyroid Hormone (PTH)

Increases serum Ca²⁺, decreases serum phosphate

Chronic elevation → depletes bone Ca²⁺ → Osteoporosis

Intermittent exposure → activates osteoblasts > osteoclasts (anabolic)

Calcium Homeostasis: Vitamin D

Increases both serum calcium AND phosphate

Calcium Homeostasis: Vitamin D uses

Uses: Hypocalcemia, rickets, osteomalacia, secondary hyperparathyroidism (renal disease) Topically (1,24-OH Vit D3): Psoriasis — decreases cellular proliferation

Calcium Homeostasis: Calcitonin

Decreases serum Ca²⁺ (when elevated above normal) Given SC injection or nasal spray

Calcium Homeostasis: Calcitonin uses

Hypercalcemia, osteoporosis, Paget's disease, pain relief in osteoporotic fractures

Treatment of Osteoporosis — Non-Pharmacological

Adequate dietary calcium and vitamin D intake

Weight-bearing exercise

Cessation of smoking

Pharmacological options are divided into:

Anti-Resorptive Agents

Anabolic Agents

Monoclonal Antibodies

Anti-Resorptive Agents — Bisphosphonates indications

Prevention and treatment of osteoporosis

Anti-Resorptive Agents — Bisphosphonates example drugs

Alendronate (oral)

IV Ibandronate — once every 3 months (if oral not tolerated)

Zoledronic acid — once yearly IV

Anti-Resorptive Agents — Bisphosphonates adverse effects

Esophagitis and esophageal ulcers

Anti-Resorptive Agents — Bisphosphonates Contraindications

Renal impairment Peptic ulcer disease

SERMs — Raloxifene mechanism

Selective Estrogen Receptor Modulator

SERMs — Raloxifene uses

Prevention AND treatment of postmenopausal osteoporosis (avoids breast & uterine cancer risk vs. estrogen)

SERMs — Raloxifene

Preferred over standard HRT for postmenopausal osteoporosis

Denosumab (anti-RANKL, monoclonal antibody)

Blocks RANKL receptors

Denosumab (anti-RANKL, monoclonal antibody) uses

Postmenopausal osteoporosis with high fracture risk (intolerant/unresponsive to other therapies)

Denosumab (anti-RANKL, monoclonal antibody) route

SC injection every 6 months

Denosumab (anti-RANKL, monoclonal antibody) side effect

Infections, secondary malignancies, hypocalcemia, dermatological reactions

Anabolic Agent — Teriparatide (Recombinant PTH) Mechanism

Recombinant form of parathyroid hormone Intermittent dosing activates osteoblasts > osteoclasts → net bone formation

Anabolic Agent — Teriparatide (Recombinant PTH) Route & Dosing

Subcutaneous injection — once daily

Anabolic Agent — Teriparatide (Recombinant PTH) Indication

Treatment of osteoporosis in patients at HIGH risk of fractures Reserve for high-risk patients (not first-line)